chapter 1

PHYSICAL CHEMISTRY

Thermodynamic and Energetics Process

yy Thermodynamics: The study of interconversion of heat The path by which the system changes from one state to
and other forms of energy is called thermodynamics. another is called process.
yy System: A specific portion of the universe which is
under thermodynamic study is called a system.
yy Surroundings: The portion of the universe other than Difference between isothermal process and
that selected for the purpose of thermodynamic study is adiabatic process
called the surroundings.

Types of Thermodynamic Systems Isothermal Process Adiabatic Process

Open system 1. In an isothermal pro- In an adiabatic process,
A system that can exchange matter as well as energy with its cess, temperature of temperature of the
surroundings is called an open system. the system remains system changes.
constant.
Closed system 2. In this process, the In this process, the sys-
A system that can exchange only energy but not matter with system exchanges tem does not exchange
its surroundings is called a closed system. heat with the sur- heat with the surround-
roundings. ings.
Isolated system 3. Total internal en- Total internal energy ΔE
A system that can exchange neither energy nor matter with ergy of the system of the system changes.
its surroundings is called an isolated system. remains constant (ΔE
= 0).

Properties of Thermodynamics System 4. Total heat con- Total heat content of

Intensive properties tent of the system the system remains
changes (ΔH ≠ 0). constant (ΔH = 0).
The properties which do not depend on the total quantity of
matter present in the system, are called intensive properties. 5. In this process, the In this process, the
Example: Temperature, pressure, density. system is not ther- system is thermally
mally isolated. isolated.
Extensive properties 6. This process can be This process cannot be
The properties which depend on the total quantity of mat- made reversible. made reversible.
ter present in the system, are called extensive properties.
Example: amount of heat, volume, weight. 7. In this process, Q = In this process, W = ΔE
W as ΔE = 0. as ΔQ = 0
Thermodynamic equilibrium
A system is said to be in thermodynamic equilibrium, if its
macroscopic (measurable) properties such as temperature, Isobaric process
pressure and composition do not undergo any change with The process which takes place at a constant pressure is
time. called an isobaric process.
3.4  Chapter 1

Isochoric process Work done in vacuum

The process which takes place at a constant volume is called As P = 0, W = 0 i.e., when a gas expands in vacuum, no
an isochoric process. work is done.

Cyclic process Work done in a cyclic process

The process involving a series of operations which finally As ΔV = 0, W = 0 i.e., work done in a cyclic process is
bring the system back to its original state is called a cyclic always zero.
process. yy Expression for maximum work obtained in an isothermal
reversible expansion of an ideal gas
Difference between reversible process and
irreversible process V2
Wm = 2.303 nRT log 10
V1
Reversible Process Irreversible Process
P2
1. The process whose The process whose Wm = 2.303 nRT log
P1
direction can be re- direction cannot be
versed at any stage by reversed by an in-
where Wmax = Maximum work done
an infinitesimal increase finitesimal increase in
in the opposing force the opposing force is n = Number of moles
is called a reversible called an irreversible
process. process. R = Gas constant

2. Such a process is not Such a process is T = Temperature in kelvin

spontaneous, takes spontaneous and V1 = Initial volume
place infinitesimally takes finite time for
slowly and takes infinite completion. V2 = Final volume
time for completion. P1 = Initial pressure
3. In this process, the The thermodynamic P2 = Final pressure
thermodynamic equilibri- equilibrium is at-
um is always maintained tained only when the
between the system and process is completed. Laws of Thermodynamics
the surroundings.
First law of thermodynamics (law of
4. The opposing force is The opposing force is conservation of energy)
infinitesimally less than significantly smaller
the driving force. than the driving force. This law suggests that energy can be transferred from one
system to another in many forms. Also, it cannot be created
5. It is an ideal or hypo- It is a practical or real or destroyed. Thus, the total amount of energy available in
thetical process. force. the Universe is constant.
6. Maximum work can be Work derived from such Einstein’s famous equation (written below) describes
derived from such a a process is always less the relationship between energy and matter:
process. than maximum work.
E = mc2

Expression for the work obtained in an isothermal In the equation above, energy (E) is equal to matter
and irreversible process (against constant pressure) (m) times the square of a constant (c).
Einstein suggested that energy and matter are inter-
W = P (V2 – V1) = PΔV
changeable.
where W = Work done
P = Pressure Second law of thermodynamics
V1 = Initial volume Heat cannot be transfered from a colder to a hotter body. As
a result of this fact of thermodynamics, natural processes
V2 = Final volume
that involve energy transfer must have one direction, and all
ΔV = Change in volume natural processes are irreversible.
 Physical Chemistry  3.5

This law also predicts that the entropy of an isolated c. It is not possible for any machine to produce work
system always increases with time. Entropy is the measure without consuming energy. Such a machine is called a
of the disorder or randomness of energy and matter in a perpetual motion machine.
system. Because of the second law of thermodynamics, d. The total energy of the universe remains constant.
both energy and matter in the Universe are becoming less
useful with the passage of time. Expression for first law of thermodynamics
Q = ΔE + W or Q = ΔE + PΔV
Third law of thermodynamics where Q = Amount of heat absorbed
The third law of thermodynamics states that if all the
ΔE = Change in the internal energy
thermal motion of molecules (kinetic energy) could be
removed, a state called absolute zero would occur. Abso- W = Work done
lute zero results in a temperature of 0 Kelvin or –273.15°
a. For isothermal process, temperature (T) remains
Celsius.
constant.
Absolute Zero = 0 Kelvin = –273.15° Celsius ΔE = 0
The Universe will attain absolute zero when all energy ΔQ = PΔV
and matter is randomly distributed across space. The cur-
b. For isochoric process, volume (V) remains constant.
rent temperature of empty space in the Universe is about
2.7 Kelvin. ΔV = 0
ΔQ = ΔE
First law of thermodynamics c. For isobaric process, pressure (P) remains constant.
It can be stated in any one of the following forms:
ΔQ = ΔE + PΔV
a. Energy can neither be created nor destroyed; however, d. For adiabatic process, heat is neither absorbed not lost.
it may be converted from one form into another.
b. Whenever energy in one form disappears, an equivalent ΔQ = 0
amount of energy in another form appears. ΔE = PΔV

Note
If heat flows into a system or the surroundings to do work on it, the internal energy increases and the sign of q or w
is positive.
   Conversely, heat flowing out of the system or work done by the system will be at the expense of the internal energy,
and will therefore be negative

Internal energy or intrinsic energy (E) Expression for change in enthalpy (ΔH):
The sum of all forms of energy associated with the matter ΔH = ΔE + PΔV
present in a system is called internal energy or intrinsic For an isochoric process, volume remains constant.
energy of the system. The absolute or actual value of the
internal energy cannot be determined but the change in the ΔV = 0
internal energy (ΔE) can be measured. ΔHv = ΔE
ΔE = E2 – E1 For an isobaric process, pressure remains constant.
The change in the internal energy of in a process is in-
dependent of the path taken and depends only on the initial ΔHp = ΔE + PΔV
and final states of the system. Hence, it is a state function.
Thermochemistry
Enthalpy of a system (H)
The branch of chemistry which deals with the quantitative
The total heat content a system is called enthalpy of the system. study of the heat changes associated with chemical reactions
H = E + PV is called thermochemistry.
3.6  Chapter 1

Heat of reaction (ΔH)  dq   ∆H 

Cp =   = 
The quantity of heat absorbed or evolved (enthalpy change)  dt  p  ∆T  p
during the complete transformation of the reactants into the
products as shown in the corresponding thermo chemical
equation, at constant temperature and pressure, is called the Molar heat capacity at constant volume (Cv)
heat of reaction. The quantity of heat required to raise the temperature of one
ΔH = ΔH (products) – ΔH (reactants) mole of a gas by one degree kelvin at constant volume is
Example: C (s) + O2 (g) –→ CO2 (g); ΔH = 393.6 kJ called molar heat capacity at constant volume.

 dq  ∆E
Relationship between heats of reaction at constant Cp =   =
pressure (ΔH) and at constant volume (ΔE)  dt  v ∆T

ΔH = ΔE = PΔV or Relationship between Cp and Cv (Mayer’s Relationship)

ΔH = ΔE + ΔnRT or Cp – Cv = R
Qp = Qv + ΔnRT i.e., Cp > Cv

Heat of formation (ΔHf) Kirchhoff’s equation

The quantity of heat absorbed or evolved when one mole of Expression showing the effect of temperature on the heat of
a compound is formed from its constituent elements, with reaction at constant pressure:
every substance being in its standard physical state is called
∆H 2 − ∆H1
heat of formation. = ∆C p
T2 − T1
Heat of neutralization (ΔHn) Where
The quantity of heat liberated when one gram equivalent of an ΔCp = (Cp of products) – (Cp of reactants)
acid is completely neutralized by one gram equivalent of a base
in a very dilute solution is called the heat of neutralization. ΔH1 = Heat of reaction at temperature T1
ΔH2 = Heat of reaction at temperature T2
Heat of combustion (ΔHc)
The quantity of heat evolved when one mole of a compound Hess’s law of constant heat summation
is completely oxidised to its stable oxidation products, with The total enthalpy change accompanying a chemical reac-
every substance being in its standard physical state, is called tion is always constant (at constant pressure or constant
heat of combustion. volume) and is independent of the number of steps and the
path taken to complete the reaction.
Heat of solution (ΔHs)
i.e., ΔH = ΔH1 + ΔH2 + ΔH3 + …….
The quantity of heat absorbed or evolved when one mole
of a compound dissolves completely in a large excess of a
solvent so that further dilution of the solution produces no KINETICS OF A REACTION
heat change, under standard conditions, is called the heat of
solution of the compound in that solvent.
Molecularity
Molecularity is the number of molecules involved in form-
Example – KCl (s) + Water (Excess) → KCl (aq) + 18.4KJ
ing the product. For example, N2O5 → 2NO2 + ½ O2 is a
slow unimolecular reaction and ½ o2 + ½ o2 → o2 is a fast
Molar Heat Capacity bimolecular reaction.
The quantity of heat required to raise the temperature of
one mole of a substance through one degree kelvin is called
molar heat capacity of the substance. Order of Reaction
Consider the reaction:
Molar heat capacity at constant pressure (Cp)
A+B C+D
The quantity of heat required to raise the temperature of one
mole of a substance through one degree kelvin at constant The rate of the reaction is proportional to the con-
pressure is called molar heat capacity at constant pressure. centration of A to the power of x, [A]X and also the rate
 Physical Chemistry  3.7

may be proportional to the concentration of B to the power First Order Reaction

of y, [B]y. When the reaction rate depends on the first power of con-
The overall equation is, Rate = k [A]x [B]y centration of a single reactant, it is considered to be first
The overall order of reaction is x + y order.
Rate Constant Examples are
A rate constant is a proportionality constant that appears in
yy Absorption, distribution, elimination rates.
a rate law. For example, k is the rate constant in the rate law
yy Microbial death kinetics.
d[A]/dt = k[A].
Rate constants are independent of concentration but Thus the rate of reaction is directly proportional to the
depend on other factors, most notably temperature. concentration of reacting substance and can be expressed
as follows:
Zero Order Reaction Rate of concentration decrease
yy When the reaction rate is independent of concentration −dCx
= = KCx..................................(3)
of the reacting substance, it depends on the zero power dt
of the reactant and therefore is zero order reaction.
If concentration of reactant X is ‘a’ at the beginning
yy In this type of reaction, the limiting factor is something
of reaction when t = 0, and if amount that has reacted after
other than concentration, for example, solubility or
time t is denoted by x, then amount of X remaining at time
absorption of light in certain photochemical reactions.
t will be (a–x).
Rate of concentration decrease Therefore equation (3) can be rewritten as:
−dCx dCx
= = K..................................(1) = K (a − x )
dt dt
dCx
= = − Kdt ..............................(4)
− − − − − − − − − −(4)
(a − x)

SLOPE = K
Integrating equation (4) between time limit 0 to t
a − x dCX t
∫ ∫
Concentration

= − K dt
z dt 0

ln (a – x) –ln a = –Kt
log (a – x) – log a = –kt/2.303
Time log (a – x) = log a – Kt/2.303............................(5)

Figure 1.1 Rate of Concentration Decrease Equation (5) is like y = mx + c (linear relationship)
If first order law is obeyed, then a graph of log (a – x)
Integrating the equation yields X = Kt + constant v/s time t will give straight line with slope of –K/2.303 and
...………… (2) an intercept of log a at t = 0.
A plot of X vs time results in straight line with slope
equal to K. The value of K indicates the amount of drug that
is degraded per unit time, and intercept of line at time zero
is equal to constant in equation (2). SLOPE = –K
2.303
The unit of K is conc time–1, with typical units of mole
L–1 s–1. Log (a – x)
Half-life is given by equation t1/2 = Co/2k.
Examples: Vitamin A acetates to anhydrous vitamin A.
Photolysis of cefotaxime.
Loss in colour of multi sulpha product.
Time
Intravenous infusion.
 Drug released from transdermal drug
delivery systems. Figure 1.2 First Order Reaction
3.8  Chapter 1

Rearranging equation (5) we have ln Co/C = kt

2.303 ln 500 units per ml/C = kt
K= log (a / a − x ).............................(6)
− − − − − − − − − − − ( 6) ln 500 units per ml/C = 0.0693 × 7 = 0.483
t
500/C = Anti ln (0.483) = 1.62
Unit of K for first order is time–1 i.e., SI unit is (sec)–1 C = 308 units per ml
because K is inversely proportional to t.
The half-life, t1/2, of a drug is the time required for 50% Question 2 A penicillin solution has a half life of 21
of drug to degrade and can be calculated as follows: days. How long it will take for the potency to drop to 90%
2.303 C 2.303 100 of the initial potency?
t1 = log 0 = log
2
k C k 50 Ans. K = 0.693/t1/2
2.303 0.693 K= 0.693/21 =0.033 Days–1
= log 2 =
k k ln Co/C = kt
0.693 ln 100 %/90% = 0.033 × t
Therefore, t 1 = .................................(7)
k t = 3.2 days
2

Question 3 A penicillin solution has an initial potency

Shelf life of 125 mg/5 ml. After one month in refrigerator, the potency
It is the time required to reduce the concentration of the is found to be 100 mg/5 ml. What is the half life of penicil-
reactant to 90% of its initial concentration. The t10% value lin under these conditions?
can be calculated as
Ans. ln Co/C = kt
2.303 100 0.104
t10% = log = ln 125 mg per 5 ml/100 mg per 5 ml = k × 30
k 90 k days
0.104
t10% = .................................(8) k = 0.0074 days–1
k
t1/2 = 0.693/k
or t10% = 0.152 t 1 t1/2 = 0.693/0.0074 = 94 Days
2

Pseudo–Zero Order Reaction

Number Initial concentra- Completeness
In solid state, many drugs decompose by pseudo zero order
of half life tion remaining of process
elapsed
i.e., reaction between drug and moisture in solid dosage
form. The system behaves like suspensions and because of
0 100 0% the presence of excess solid drug; the first order rate actually
becomes pseudo zero order. Equation for it is similar to zero
1 50 50 %
order except K is replaced by K’.
2 25 75 % Example: Suspension degradation follows pseudo zero
3 12.5 87.5 % order reaction.

4 6.25 93.75 %
Pseudo-First Order Reaction
5 3.13 96.87 % Here, a second order or bimolecular reaction is made to
behave like first order. This is found in the case in which
6 1.56 98.44 %
one reacting material is present in great excess or is main-
7 0.78 99.22 % tained at constant concentration as compared with other
substance. Here reaction rate is determined by one reactant
Question 1 Penicillin solution containing 500 units per ml even though two are present.
has a half life of 10 days. What will the concentration be 7 days? Examples:
Ans. K = 0.693/t1/2 yy Decomposition of ascorbic acid tablet.
K = 0.693/10 = 0.0693 Days–1 yy Aspirin hydrolysis.
 Physical Chemistry  3.9

Summary of Parameters
Order Integrate rate equation t1/2 Linear Graph
of reaction
Ordinate Abscissa Slope Intercept

0 X = Kt = a/2K X t K 0

1 log (a/a–x) = Kt/2.303 = 0.693/K log (a–x) t –K/2.303 log a

2 (a = b) X/a (a–x) = Kt = 1/aK 1/a–x t K 1/a

Unit of order of reaction yy With help of K at different temperature we can predict

T10%
Order of reaction Unit of K t 10% = 0.105/k (for first order only)
Zero M L–1Sec–1 t 10% = C0/10*k (for zero order only)
First Sec–1

Second M–1Sec–1 Kinetic theory of Gases and

Solution chemistry
Half-life determination method Kinetic Theory Assumptions About Ideal
yy The relationship in general between half-life of a Gases
reaction in which the concentrations of all reactants are There is no such thing as an ideal gas, of course, but many
identical, is gases behave approximately as if they were ideal at ordinary
t1/2 ∞ 1/an–1 working temperatures and pressures.
Where n is the order of reaction. The assumptions are:
Determination of t10% by Arrhenius equation yy Gases are made up of molecules which are in constant
random motion in straight lines.
yy Temperature influences rate and order of reaction. So
yy The molecules behave as rigid spheres.
the shelf life of product can be obtained under exagger-
yy Pressure is due to collisions between the molecules and
ated condition.
the walls of the container.
yy It is said that for every 10°C rise, rate of reaction
yy All collisions, both between the molecules them-
increases by 2–3 times.
selves, and between the molecules and the walls of the
yy For this, Arrhenius equation is used i.e., K = Ae-εa/RT
container, are perfectly elastic. (That means that there
where A =frequency factor, is no loss of kinetic energy during the collision.)
R =gas constant, yy The temperature of the gas is proportional to the aver-
age kinetic energy of the molecules.
K =rate constant,
εa =energy of activation Now, two key assumptions, because these are the two
εa most important ways in which real gases differ from ideal
Therefore, log K = log A − gases:
2.303RT
yy There are no (or entirely negligible) intermolecular
yy Graph of log K v/s 1/T gives straight line with slope
forces between the gas molecules.
εa
and intercepts at t = 0. yy The volume occupied by the molecules themselves
2.303R is entirely negligible relative to the volume of the
yy εa represents energy required by a molecule to react
container.
and undergo reaction. The higher is the value of εa,
higher is the dependency on temperature. The ideal gas equation is:
yy Rate constant at different temperature can be obtained by pV = nRT
εa(T 2 − T1) Pressure, p: Pressure is measured in Pascal, Pa, some-
log( K 2 / K1) =
R (T2 * T1) times expressed as Newton per square metre, N m–2.
3.10  Chapter 1

Volume, V–SI unit of volume is the cubic metre, m3 Charles’ Law

Number of moles, n For a fixed mass of gas at constant pressure, the volume
mass(g) is directly proportional to the kelvin temperature i.e., V =
pV = × RT constant × T
mass of 1 mole(g)
That means, for example, that if you double the kelvin
The gas constant, R–The SI value for R is temperature from, say to 300 K to 600 K, at constant pressure,
8.311 J K–1 mol–1. the volume of a fixed mass of the gas will double as well.
The temperature, T–The temperature has to be in Kelvin.
Colligative Properties
Molar volume at STP Colligative properties are a subset of the intensive properties
1 mole of any gas occupies 22.4 dm3 at STP (standard of a system and can only be applied to solutions. It depends
temperature and pressure, taken as 0°C and 1 atmosphere only on the ratio of the number of particles of solute and
pressure). solvent in the solution, not the identity of the solute.
The molar volume of an ideal gas is therefore 22.4 dm3 1. Vapour Pressure Depression
at STP. 2. Boiling Point Elevation
The van der Waals Equation for Real Gases 3. Freezing Point Depression
 4. Osmotic Pressure
an 2 
 p +  ( V − nb) = nRT
 V2  Ideal Solutions
An ideal solution is the one in which the molecules attract one
yy The measured pressure is less than the ideal pressure
another with equal forces irrespective of their nature. Thus, a
for a real gas. van der Waal has added a term to com-
solution composed of two components A and B will be an ideal
pensate for that.
one if the forces between A and A, B and B should be the same.
yy In the volume term, van der Waal has subtracted the
An ideal solution possesses the following characteristics:
value nb to allow for the space taken up by the mol-
ecules themselves. (i) Volume change of mixing should be zero.
yy a and b are constants for any particular gas, but they ΔVmix = 0; Vsolvent + Vsolute = Vsolution
vary from gas to gas to allow for the different intermo-
(ii) Heat change on mixing should be zero.
lecular forces, and molecular sizes.
ΔHmix = 0 (Heat is neither absorbed nor evolved).
Boyle’s Law (iii) There should be no chemical reaction between the
For a fixed mass of gas at constant temperature, the volume solvent and the solute.
is inversely proportional to the pressure i.e., pV = constant (iv) Solute molecules should be not dissociate or associate
That means that, for example, if you double the pres- in the ideal solution.
sure, you will halve the volume. If you increase the pressure (v) Ideal solutions must obey Raoult’s law at all concen-
10 times, the volume will decrease 10 times. trations.

Comparison between ideal and non-ideal solutions

Ideal solutions Non-ideal solutions

Positive deviation from Raoult’s law Negative deviation from Raoult’s law

1. Obey Raoult’s law at every 1. Do not obey Raoult’s law. 1. Do not obey Raoult’s law.
range of concentration.

2. ΔHmix = 0; It is neither evolved 2. ΔHmix> 0. Endothermic dissolution; 2. ΔHmix< 0. Exothermic dissolution;

nor absorbed during dissolu- heat is absorbed. heat is evolved.
tion.

3. ΔVmix = 0; total volume of 3. ΔVmix > 0. Volume is increased 3. ΔVmix < 0. Volume is decreased dur-
solution is equal to sum of after dissolution. ing dissolution.
volumes of the components.
 Physical Chemistry  3.11

Ideal solutions Non-ideal solutions

Positive deviation from Raoult’s law Negative deviation from Raoult’s law

4. P = pA + pB = pA XA + pB XB 0 0
4. pA > pA XA; pB > pB XB
0 0
4. pA < pA0XA; pB < pB0XB
i.e., pA = ∴ pA + pB > pA0XA + pB0XB ∴ pA + pB < pA0XA + pB0XB

5. A—A, A—B, B—B interactions 5. A—B attractive force should be 5. A—B attractive force should be
should be same, i.e., ‘A’ and ‘B’ weaker than A—A and B—B at- greater than A—A and B—B at-
are identical in shape, size and tractive forces. ‘A’ and ‘B’ have dif- tractive forces. ‘A’ and ‘B’ have
character. ferent shape, size and character. different shape, size and character.

6. Escaping tendency of ‘A’ and 6. ‘A’ and ‘B’ escape easily showing 6. Escaping tendency of both compo-
‘B’ should be same in pure higher vapour pressure than the nents ‘A’ and ‘B’ is lowered show-
liquids and in the solution. expected value. ing lower vapour pressure than
expected ideally.

Examples: Examples: Examples:

dilute solutions; acetone + ethanol acetone + aniline;
benzene + toluene: acetone + CS2; acetone + chloroform;
n-hexane + n-heptane; water + methanol; CH3OH + CH3COOH;
chlorobenzene + bromobenzene; water + ethanol; H2O + HNO3;
n-butyl chloride + n-butyl bro- CCl4 + toluene; Choloroform + diethyl ether,
mide. CCl4 + CHCl3; water + HCl;
acetone + benzene; acetic acid + pyridine;
CCl4 + CH3OH; Chloroform + benzene.
Cyclohexane + ethanol

Raoult’s Law Let a mixture (solution) be prepared by mixing nA

According to this law, the partial pressure of any volatile moles of liquid A and nB moles of liquid B. Let pA and
constituent of a solution at a constant temperature is equal pB be the partial pressures of two constituents A and B in
to the vapour pressure of pure constituent multiplied by the solution and pA0 and pB0 the vapour pressures in pure state
mole fraction of that constituent in the solution. respectively.

Ideal solution Positive deviation Negative deviation

Total Vapour pre

pA P = pA + p B ssu
pA r pA
To
e

tal
Vap
our p
PA

pB pB ressure pB
=

Vapour pressure
Vapour pressure
Vapour pressure

pA
XA

XB
pB
= Ideal
PB
Id
ea
l
XA = 1 Mole fraction XA = 0 XA = 1 Mole fraction XA = 1 Mole fraction
XB = 1 XA = 0
XB = 0 XB = 1 XB = 0 XB = 0 XB = 1
XA = 0

Figure 1.3 Raoult’s Law

3.12  Chapter 1

Thus, according to Raoult’s law, stopped by applying external pressure equal to osmotic
pA = nA/nA+nB pA0 = mole fraction of pressure on solution. If external pressure greater than osmotic
pressure is applied, the flow of solvent molecules can be
A × pA0 = XApA0
made to proceed from solution towards pure solvent, i.e.,
pB = nB/nA+nB pA0 in reverse direction of the ordinary osmosis. This type of
= mole fraction of B × pB0 osmosis is termed reverse osmosis. Reverse osmosis is used
= XBpB0 for the desalination of sea water for getting fresh drinking
water.
If the total pressure be P, then
P = pA + pB Van’t Hoff Theory of Dilute Solutions
= nA/nA+nB pA0 + nB/nA+nB pA0 Van’t Hoff realized that an analogy exists between gases and
= XAPA + XBPB 0 0 solutions, provided, osmotic pressure of solutions is used in
place of ordinary gas pressure. He showed that for dilute
Ideal solutions obey Raoult’s law at every range of solutions of non-electrolysis, the following laws hold good.
concentration. Non-ideal solutions do not obey Raoult’s
law. They show either positive or negative deviation from Boyle-Van’t Hoff law
Raoult’s law.
The osmotic pressure (P or α) of a solution is directly pro-
Relation between Dalton’s law and Raoult’s portional to its concentration (C) when the temperature is
kept constant. The concentration of the solution containing
law
one gram mole in V litres is equal to 1/V (C = 1/V)
The composition of the vapour in equilibrium with the
solution can be calculated by applying Dalton’s law of Thus P ∝ C (when temperature is constant)
partial pressures. Let the mole fractions of vapours A and or P ∝ 1/V
B be YA and YB respectively. Let PA and PB be the partial or PV = constant
pressures of vapours A and B respectively and total pres-
or πV = constant
sure P.
pA = YAP .. (i) Van’t Hoff presumed that the osmotic pressure is
due to the bombardment of solute molecules against the
pB = YBP .. (ii) semipermeable membrane as the gas pressure is due to
pA = XAPA  0
.. (iii) hits recorded by gas molecules against the walls of its
container.
pB = XBPB0 .. (iv)

Equating (i) and (iii) Pressure-temperature law

YA = XAPA
P 0 (Gay-Lussac-Van’t Hoff Law)
Concentration remaining same; the osmotic pressure of
or YA = XAPA0/P = pA/P
a dilute solution is directly proportional to its absolute
Similarly, equation (iii) and (iv) temperature (T), i.e.,

YB = XBPB0/P = pB/P P∝T

or P/T = constant or μ/T constant
Thus, in case of ideal solution the vapour phase is
richer with more volatile components i.e., the one having Combining the two laws, i.e., when concentration and
relatively greater vapour pressure. temperature both are changing, the osmotic pressure will
be given by:
Reverse Osmosis P ∝ CT
When a solution is separated from pure water by a semiper- or P = kCT
meable membrane, water moves towards solution on account
or P = k.1/V.T (since C = 1/V)
of osmosis. This process continues till osmotic pressure
becomes equal to hydrostatic pressure or osmosis can be or PV = ST or πV = ST
 Physical Chemistry  3.13

S is called molar solution constant. The Henry’s law constant “k” is different for every gas,
Here V is the volume of solution containing one temperature and solvent. The units on “k” depend on the
gram mole of the solute. The value of 5 comes out to units used for concentration and pressure.
0.082 lit atm K−1 mol−1 which is in agreement with the The value for k is the same for the same temperature,
value of R, the molar gas constant. In case the solution gas and solvent. This means the concentration to pressure
contains n gram moles in V litres, the general equation ratio is the same when pressures change. The following
would become equation can be used to relate pressure and concentration
changes.
PV = nST or πV = ST
C1 C2
=
Third law P1 P2
Equimolecular solutions of different solutes exert equal
osmotic pressure under identical conditions of tem- Osmolarity
perature. Such solutions which have the same osmotic
yy It is a colligative property.
pressure are termed isotonic or iso-osmotic. When two
Colligative property means when a non-volatile solute
isotonic solutions are separated by a semipermeable
is dissolved in a solvent, the resulting property of solution
membrane, no flow of solvent molecules is observed on
is independent of the nature of solute but is determined
either side.
by the concentration of solute particle.
The law is similar to Avogadro’s hypothesis. It can be
yy Osmoles: Number of osmotically active particles in
stated as, “Equal volumes of dilute solutions of different
solution.
solutes, having the same temperature and osmotic pressure,
yy Osmolarity: Osmoles or milliosmoles per liter of
contain equal number of molecules.”
solution.
For solution I, PV = n1ST yy Osmolality: Osmoles or milliosmoles per kg of
For solution II, PV = n2ST solvent.
yy Iso-osmotic: When two different solutions separated by
Thus, n1 must be equal to n2 when P, V and T are semipermiable membrane have same osmotic pressure,
same. they are called as isoosmotic.
This led van’t Hoff to suggest that a solute in dissolved yy Isotonic: When two different solutions separated by
state (i.e., in solution) behaves as a gas and the osmotic biological membrane have same osmotic pressure, they
pressure of the solution is equal to the pressure which the are called as isotonic.
solute would exert if it were a gas at the same temperature
and occupying the same volume as that of the solution. This
statement is known as van’t Hoff. METHODS OF EXPRESSING THE
CONCENTRATION OF A SOLUTION
Henry’s Law (i) Mass percentage or % by mass
The solubility of a gas in a liquid depends on temperature, It is defined as the amount of solute in grams present
the partial pressure of the gas over the liquid, the nature of in 100 grams of the solution.
the solvent and the nature of the gas. The most common Mass percentage = Mass of solute/Mass of solution
solvent is water. × 100
Gas solubility is always limited by the equilibrium = Mass of solute/Mass of solute
between the gas and a saturated solution of the gas. The +Mass of solvent × 100
dissolved gas will always follow Henry’s law. = Mass of solute/Volume of solution
The concentration of dissolved gas depends on the × Density of solution × 100
partial pressure of the gas. The partial pressure controls the   The ratio Mass of solute/Mass of solvent is termed
number of gas molecule collisions with the surface of the as mass fraction.
solution. If the partial pressure is doubled, the number of
collisions with the surface will double. The increased number   Thus, Mass percentage of solute = Mass fraction × 100
of collisions produce more dissolved gas.   10% solution of sugar means that 10 grams of sugar
is present in 100 grams of the solution, i.e., 10 grams of
Pgas = kC at constant T. sugar has been dissolved in 90 grams of water.
3.14  Chapter 1

(ii) Per cent by volume Concentration of solution = Mass of solute in

It is defined as the volume of solute in mL present in grams/Volume of the
100 mL solution. solution litres
  Per cent of solute by volume = Volume of solute/
=
Mass of solute in
Volume of solution × 100
grams/Volume of the
(iii) Per cent mass by volume
solution in mL × 100
It is defined as the mass of solute present in 100 mL of
solution. Concentration in grams per litre is also termed as
Per cent of solute mass by volume = Mass of strength of the solution. Let wg of the present in V litre
solute/Volume of solution × 100 of solution, then
(iv) Strength or concentration (Grams per litre)
It is defined as the amount of the solute in grams present Strength or concentration of the solution = w/V
in one litre of the solution. gL–1

Note
V is not the volume of the solvent. V is actually the final volume after dissolving a definite quantity of solute in the
solvent.

(v) Parts per million (ppm) In a binary solution,

When the solute is present in trace quantities, it is Mole fraction of solute + Mole fraction of solvent = 1
convenient to express the concentration in parts per Let n moles of solute (A) and N moles of solvent (B)
million (ppm). It is defined as the quantity of the solute be present in a solution.
in grams present in 106 grams of the solution.
Mole fraction of solute = n/N + n = XA
ppm = Mass of solute/Mass of solute × 106 Mole fraction of solvent = N/N + n = XB
Atmospheric pollution in cities is also expressed in Thus, XA + XB = 1
ppm by volume. It refers to the volume of the pollutant Mole fraction is independent of temperature of the
in 106 untis of volume. 10 ppm of SO2 in air means 10 solution.
mL of SO2 is present in 106 mL of air.
(vii) Molality
(vi) Mole fraction
It is defined as the number of the moles of the solute
Components A B C present in 1 kg of the solvent. It is denoted by m.
Mass (in grams) W1 w2 w3 Molality (m) = Number of moles of solute/Number of
Molecular mass m1 m2 m3 kilo/grams of the solvent
No. of g moles w1 w2 w3 Let wA grams of the solute of molecular mass mA be
___ _________________ present in wB grams of the solvent, then
m1 m2 m3
Molality (m) = wA/mA× wB × 1000
Total number of g moles = w1/m1 + w2/m2 + w3/m3
Thus, Mole fraction of A – w1/m1/w1/m1 + w2/m2 + Relation between mole fraction and molality
w3/m3 = fA
XA = n/N + n and XB = N/N + n
Mole fraction of B = w2/m2/w1/m1 + w2/m2 + w3/m3 = fB XA/XB = n/N = Moles of solute/Moles of
Mole fraction of C = w3/m3/w1/m1 + w2/m2 + w3/m3 = fC solvent = wA/mB/wB× mA
The sum of mole fractions of a solution is equal to 1, XA×1000/XB × mB = wA×1000/wB × mA = m
i.e., fA + fB + fC = 1. or XA×1000/ (1 – XA) = m
 Physical Chemistry  3.15

Note
(i) 
Molality is the most convenient method to express the concentration because it involves the mass of liquids rather
than their volumes. It is also independent of the variation in temperature.
Molality and solubity are related by the following relation:
(ii) 
Molality = Solubility×10/Molecular mass of the solute
[Solubility = Mass of solute in grams/Mass of solvent in grams × 100]

(viii) Molarity (Molar concentration) The unit of molarity is mol litre−1 or mol dm−3. d = density
It is defined as the number of moles of the solute per of solution in g/mL
litre or per dm3 of the solution, i.e.,
mA = molecular mass of solute.
Molarity (M) = Number of moles of solutes/Number
of litres of solution Molarity of dilution
or Molarity × number of litres of sol. = Number of
Before dilution After dilution
moles of sol.
M1V1 = M2V2
Let wA g of the solute of molecular mass mA be dis-
solved in V litre of solution. Molarity of mixing Let there be three samples of solu-
Molarity of the solution = wA/mA×V tion (containing same solvent and solute) with their mo-
larity M1, M2, M3 and volumes V1, V2, V3 respectively.
or Molarity × mA = wA/V Strength of the solution These solutions are mixed; molarity of mixed solution
may be given as:
If V is taken in mL (cm3), then
M1V1 + M2V2 + M3V3 = MR(V1 + V2 + V3)
Molarity of the solution = wA/mA × V × 1000
where MR = resultant molarity
M = x × d × 10/mA V1 + V2 + V3 = resultant molarity

Note
Molarity is dependent on volume; therefore, it depends on temperature.
1 M Molar solution, i.e., molarity is 1
0.5 M or M/2 Semimolar
0.1 M or M/10 Decimolar
0.01 M or M/100 Centimolar
0.001 M or M/1000 Millimolar

Normality It is defined as the number of gram equiva- Normality × Equivalent mass

lents of solute present per litre of solution. It is denoted – wA/V
by ‘N’. = Strength of the solution g/L.
Normality (N) = Number of gram equivalents of
solute/Number of litres of the Relationship between normality and molarity
solution Normality = n × Molarity
or Normality × Number of llitres Formality
of the solution It is the number of formula mass in grams present per litre of
= Number of gram equivalents of solution. In case formula mass is equal to molecular mass,
the solute formality is equal to molarity. Like molarity and normality,
the formality is also dependent on temperature. It is used for
Let wA gram of the solute of equivalent mass EA be
ionic compounds in which there is no existence of molecule.
present in V litres of the solution, then,
Mole of ionic compounds is called formole and molarity as
Normality = wA/EA/V = wA/EA×V formality.
3.16  Chapter 1

Electrochemistry Degree of Ionization It is the extent of dissociation of

The study of the inter-relation between chemical reactions an electrolyte.
and electrical energy is called electrochemistry. There are Strong electrolyte An electrolyte that ionizes complete-
two types of cells that can be used for a chemical reaction ly in a solution is called a strong electrolyte.
to take place:
Weak electrolyte An electrolyte that ionizes partially
in solution is called a weak electrolyte.
Electrochemical Cell
The device which is used to convert chemical energy into Cell constant It is the ratio l/A for a conductivity cell
electrical energy at the expense of spontaneous oxidation where l is the distance between the electrodes and A is the
reduction reaction is called an electrochemical cell. Example: area of the electrode.
Daniel cell. 1
Cell constant = =K×R
A
Electrolytic Cell = Specific conductivity × Resistance
The device which is used to bring about a non-spontaneous
chemical reaction using electrical energy is called an elec- Battery It is a combination of two or more galvanic cells
trolytic cell. Example: Electrolysis of fused sodium chloride. electrically connected to work together to produce electric
energy.
Basic Terminology Electrolysis
Specific conductivity (K) It is the conductivity of 1 The process of decomposition of an electrolyte by the
cubic-centimeter of a solution. passage of an electric current through its aqueous solution
or fused mass is called electrolysis. Example: Electrolysis
Equivalent conductivity It is the conductivity of a so- of sodium chloride.
lution containing 1 equivalent of the solute between two
parallel electrodes separated by 1 cm. Electrolysis of fused sodium chloride
The electrolytic cell consists of 2 electrodes of platinum or
1000 K
λ eq = S cm2 equivalent −1 graphite. Fused sodium chloride dissociates to form sodium
N cations and chloride anions. The sodium ions are discharged
at the cathode as sodium atoms (metallic sodium). The chlo-
Molar conductivity It is the conductivity of a solution
ride ions are discharged at the anode as molecular chlorine.
containing 1 mole of a solute between two parallel electrodes
separated by 1 cm. Reaction at cathode:
2Na+ + 2e– → 2Na (Reduction)
1000 K
λm = S cm2 mol −1 Reaction at anode:
N
2Cl– → 2Cl + 2e– (Oxidation)
Kohlrausch’s law It states that the molar conductivity at
2Cl → Cl2 (g)
infinite dilution of an electrolyte is equal to the sum of the
molar conductivities at infinite dilution of the ions produced Faraday’s laws of electrolysis
by the electrolyte.
Faraday’s first law of electrolysis
λ ∞m = v + λ ∞+ + V − λ ∞ The amount (weight) of any substance deposited or liberated
or dissolved at an electrode is directly proportional to the
Ohm’s law It states that the strength of an electric cur- quantity of electricity passed through the electrolyte.
rent is directly proportional to the potential difference and W = ZΔQ.
inversely proportional to the resistance of the circuit.
Hence,W = Z it
V = IR W = Zit
V is potential difference in volts where, i = current (ampere)
I is current in ampere t = time in seconds
R is resistance in ohms Z = electrochemical equivalent
 Physical Chemistry  3.17

Faraday’s Second Law of Electrolysis At anode (oxidation electrode)

The amounts (weights) of different substances deposited Zn (s) »Zn (aq)2+ + 2e– (oxidation half cell reaction)
or dissolved by passing the same quantity of electricity
At cathode (reduction electrode):
through different electrolytes, connected in series are
directly proportional to their equivalent weights. + e−
Cu (2aq ) + 2 → Cu ( s )

WA E A (reduction half cell reaction)

=
WB E B Total reaction
+ 2+
where WB = wt. of substance A Zn ( s ) + CU (2aq ) → Zn ( aq ) + Cu ( s ) (Redox reaction)

WA = wt. of substance B The e.m.f. of the Daniel cell is about 1.1 volt.
EA = equivalent of A
Salt bridge
EB = equivalent of B
It is an inverted U-shaped glass tube filled with a saturated
Faraday solution of KCl or KNO3 or NH4NO3< in agar-agar gel. The
Quantity of electricity passed in order to deposit or dissolve ends of the glass tube are plugged with glass wool. The two
or liberate one gram equivalent (one equivalent) of a sub- ends of the salt bridge are immersed in the solution of the
stance during electrolysis is called one Faraday (F). two half cells.

1 Faraday = 96, 500 coulombs Functions of the salt bridge

E = 96, 500 × Z or yy It connects the two half cells.
E = F × Z where, yy It prevents mixing of two electrolytes.
yy It minimizes the liquid junction potential between the
E = chemical equivalent two electrolytes.
Z = electrochemical equivalent yy It maintains electrical contact between the two
F = 96, 500 coulombs electrolytes.
yy It maintains electrical neutrality in the cells.
Electrochemical equivalent (Z)
The weight (amount) of the element deposited or liber- Conventions used for representing the voltaic cells
ated at the electrode when one coulomb of electricity is yy Negative electrode (zinc electrode in the voltaic cell) is
passed through the electrolyte is called the electrochemical written on the left hand side.
equivalent. yy Positive electrode (copper electrode in the voltaic cell)
W = ZQ is written on the right hand side.
yy The vertical single line is drawn between the electrode
Z = W/Q kg/coulomb and the electrolyte.
Electrochemical cell Electrochemical cells are cells in yy A vertical double line is between two electrolytes
which chemical energy is converted into electrical energy. that indicate indirect contact of the two electrolytic
Electrical energy is made available at the expense of solutions.
spontaneous oxidation reduction reaction taking place yy Concentration of the activities of the two solutes are
within the cell. written in brackets like (C1), (C2), or (a1), (a2).

Example Daniel cell with a salt bridge. In case of a gas electrode, the gas is shown along with
The cell consists of two beakers–one containing copper an inert electrode, used on the left hand side.
sulphate solution and a copper rod that acts as a positive
electrode and the other beaker contains zinc sulphate Standard Calomel Electrode (SCE)
solution with a zinc rod that acts as a negative electrode. A The electrode consists of a broad glass tube with a side tube.
metallic wire is used to connect the two electrodes. The two The broad glass tube consists of pure Hg at the bottom,
solutions are connected with a salt bridge. covered with a saturated paste of Hg2Cl2 and Hg. The tube
Cell representation: Zn | Zn (+aq+ ) || Cu (+aq+ ) | Cu ⊕ is then covered with saturated KCl. Electrical contact with
Hg is made by a platinum wire sealed in the glass tube. The
Cell reaction: side tube is immersed in the desired solution.
3.18  Chapter 1

Electrode potential depends upon concentration of KCl Standard oxidation potential (Eoxd)
solution. The electric potential developed between an electrode and
Pt, Hg (l) | Hg2 Cl2 (s) | KCl (aq) (a = x) the surrounding electrolyte due to the oxidation process
when a metal is dipped into an electrolyte containing the
At 298K, oxidation potentials are:
same metal ions at 1 M concentration at 298 K is called
(a) Sat. KCl: – 0.242V standard oxidation potential.
(b) 1N KCl or 1M KCl: – 0.280V Standard reduction potential (Ered)
(c) 0.1 N KCl or 1M KCl: – 0.334V
The electric potential developed between an electrode and
Oxidation: 2Hg (l) + 2Cl– (aq) Hg2Cl2 (s) + 2e– the surrounding electrolyte due to the reduction process
Reduction: Hg2Cl2 (s) + 2e– 2Hg (l) + 2Cl– (aq) when a metal is dipped into an electrolyte containing the
same metal ions at 1M concentration at 298 K is called the
Advantages of standard calomel electrode standard reduction potential.
yy It is very handy, compact and easy to transport.
yy Its potential can remain constant and it can easily be EMF of the Cell
reproduced. The potential difference, which is responsible for the flow of
It is easy to construct and maintain. current from an electrode of higher potential to the electrode
of lower potential is called the electromotive force (e.m.f.) or
Measurement of electrode potential the effective voltage of the cell and expressed in volts.
The electrode potential of a single electrode can be mea-
sured by combining it with a reference electrode to form a E cell = E oxd (anode) – E oxd (cathode)
cell. The e.m.f. of the cell is measured with a potentiometer. Ecell = E oxd (anode) + E red (cathode)

Concept of electrode potential EMF Series

When an electrode is dipped in its solution containing It may be defined as the series of elements in which elements
its ions, there are two opposing processes taking place– are arranged in the decreasing order of their standard oxidation
electronation and de-electronation. This is known as Nernst potential as compared to the standard hydrogen electrode.
theory of electronation and de-electronation. Also, called as electromotive series or electro-chemical series.
Nernst equation for single electrode potential Li → K → Ba → Ca → Na → Mg → Al →
Mn → Zn → Cr → Fe → Cd → Ni → Sn →
E = E° − 2.303RT
nF log 10  M (naq+ )  Pb → H2 (SRP = 0)

Single electrode potential SRP is Negative

The difference in potentials between the electrode and the → Cu → I2 → Hg → Ag → Br2 → Cl2 → Pt →
surrounding solution at equilibrium in a half cell is called Au → F2
single electrode potential or half cell potential. SRP is Positive

Note
yy Metals having positive SRP will make cathode and positive SRP will make anode during electrolysis.
yy Negative SRP (Standard reduction potential) metals will preferentially reduced first.

Acid-Base and Ionic Equilibrium Arrhenius Theory of Acids and Bases

Introduction Acid is a substance that releases H+ ions (proton) in aqueous
solution.
Acids are substances which are sour in taste and turn blue
litmus to red. e.g., HCl (aq) ⇌ H+ (aq) + Cl– (aq)
Bases are bitter in taste, soapy to touch and turn red
litmus to blue. H2SO4 (aq) ⇌ H+ (aq) + HSO4– (aq)
 Physical Chemistry  3.19

Base furnishes hydroxide ions (OH-) when dissolved Ionization

in water.
Ionization: Formation of ions from substances which
e.g., NaOH (aq) ⇌ Na+ (aq) + OH–(aq) are not in the ionic state.
Ca (OH)2 (aq) ⇌Ca+2 (aq) + 2OH– (aq) Dissociation: Formation of free ions capable of carrying
electric current.
Limitations of Arrhenius theory
Degree of dissociation (α)
yy The theory defines acids and bases in terms of their
aqueous solutions rather than on the basis of the sub- The fraction of total number of molecules of an electrolyte,
stances themselves. which undergoes dissociation at equilibrium, is called
yy It considers substances like HCl as acid only in water degree of dissociation.
and not in non-aqueous solvents.
yy The theory does not explain basic nature of substances Dissociation constant for a weak acid and
like pyridine, NH3, etc., which do not have OH– ions in weak base
their structure. Weak acid Ka is the ratio of concentration of cation (H+) and
yy The theory does not explain amphoteric behaviour of anion (A–) at equilibrium with concentration of undissoci-
compounds like Zn (OH)2. ated acid at equilibrium.
It does not explain acidic nature of salts like FeCl3 and HA ⇌ H+ + A–
basic nature of ammonia.
[H + ][A − ]
Ka =
Lowry-Bronsted Theory HA
Acid substances which donate hydrogen ions (H+). Weak base Kb is the ratio of product of concentration
Example HCl, H2SO4, CH3COOH. of cation and the anion (OH–) formed at equilibrium and
concentration of undissociated base at equilibrium.
Base substances which accept protons (H+) are called
bases. BOH ⇌ B+ + OH–
Example NH3, H2O, OH–. [B+ ][OH − ]
Kb =
[BOH]
Conjugate acid-base pair
Pair of acid and base which differ only by a proton. Acid
donates proton to form a base, while base accepts the pro-
Ostwald’s Dilution Law
ton. Thus, an acid loses a proton to form a conjugate base The degree of dissociation of a given weak electrolyte is
and a base accepts to form a conjugate acid. inversely proportional to the square root of concentration
of solution or directly proportional to the square root of
Examples dilution.
1. Cl– is a conjugate base of HCl.
K
2. H3O+ is a conjugate acid of a base H2O. α= KV =
C
Water is amphoteric according to Lowry and
Bronsted theory. It functions as acid as well as base where C = 
concentration or moles of an
depending upon the nature of substance dissolved in it. electrolyte
V = dilution
Lewis Acid-based Theory For a weak base kb = α 2C
Acid is a substance which can accept a lone pair of electrons.
Kb
Example H+, AlCl3, BF3. α=
C
Base substance which can donate a lone pair of electrons. 1
or α=
Example Cl–, H2O, OH–. C
3.20  Chapter 1

Ionic product of water c. Gravimetric analysis:

The product of the ionic concentration of hydrogen ions and yy Precipitate obtained is washed with solution of
hydroxide ions in pure water or in any aqueous solution is strong electrolyte having common ion with precipi-
called ionic product of water. It is constant at any given tem- tated solid.
perature. At 298K it is 1.0 × 10–14. yy Solubility of precipitate decreases.
Ionic product of water is yy Minor losses due to dissolution are avoided.
yy Example, BaSO4 washed with dilute H2SO4
Kw = [H+] [OH–]
yy BaSO4 Ba+2+ SO42–
Hydrogen ion concentration pH scale yy H2SO4 >> 2H+ + SO42–
pH The negative logarithm, to the base 10, of the hydrogen
ion concentration is known as the pH of a solution. Solubility product
The product of the ionic concentration of the ions of a
1 sparingly soluble electrolyte present in its saturated solution
− log[H + ] = log10 = pH
H+ at a given temperature is called a solubility product of the
electrolyte.
pOH = The negative logarithm, to the base 10, of the For a salt,
hydroxyl ion concentration is known as pOH of a solu-
tion. AB A+ + B– Ksp = [A+] [B–]

 1  AB2 A2+ + 2B– Ksp = [A2+] [B–]2

− log[OH − ] = log10   = pOH
 OH  A2B 2A+ + B2– Ksp = [A+]2 [B2–].
Relation Between pH and pOH Applications
[H+] [OH–] = Kw = 10–14 at 298 K In qualitative analysis:
yy Group II metal cations (Hg+2, Cu+2, Bi+3, Ph+2, etc.) are
pH + pOH = pKw = 14 at 298 K precipitated as sulphides by passing H2S in presence
of HCl.
Common ion effect
yy Group III B metal cations (Co+2, Mn+2, etc.) are precipi-
The suppression of the degree of dissociation of a weak tated by passing H2S in presence of NH4OH.
electrolyte by the addition of a strong electrolyte having yy Group III A cations (Al+3, Cr+3, Fe+2, Fe+3) are
an ion in common with the weak electrolyte is called the precipitated in the form of their hydroxides using
common ion effect. NH4OH.
Applications Prediction of precipitation
a. Purification of NaCl: For a salt, when ionic product exceeds solubility product,
yy Addition of HCl, Cl– is a common ion. precipitation occurs.
yy Concentration of Cl– ions increases.
yy Suppresses solubility of NaCl and it precipitates. Buffer solutions
yy NaCl Na+ + Cl– A buffer solution is the one whose pH does not change on
yy HCl H+ + Cl– dilution or on adding a small quantity of acid or base on
yy Precipitation takes place when ionic product > solubility storage.
product. Acidic buffer solutions It is a solution containing weak
b. Salting out of soap: acid and its salt with a strong base. It is used to obtain pH
lower than 7.
yy Saturated solution of NaCl is added to soap solution.
yy Concentration of Na ions increases. Basic buffer solutions It is a solution having weak base
yy Due to common ion Na+, solubility of soap decreases. and its salt with a strong acid.
yy Results in precipitation of soap. Preparation of acidic buffer solution It is pre-
yy RCOONa RCOO– + Na+ pared by adding a weak acid to a solution of its salt with
yy NaCl Na + Cl–
+
a strong base.
 Physical Chemistry  3.21

Preparation of basic buffer solution It is prepared Applications of buffer solution

by adding a weak base to a solution of its salt with a yy pH of human blood is maintained constant at 7.35 – 7.45.
strong acid. yy pH is maintained at certain level for enzymatic
Properties reaction.
yy Helps in preparation of antibiotics, alcohols by fer-
yy pH does not change on dilution.
yy pH does not alter on storage. mentation.
yy Number of food and pharmaceutical samples pre-
yy Addition of small quantity of acid or alkali does not
served.
change pH.
yy Used in qualitative and quantitative analysis.
Buffer action yy pH of soil is maintained using phosphate buffer.
a. Acidic Buffer: The salt in the acidic buffer dissoci- Hydrolysis of salt
ates completely and gives common ions. The weak
acid dissociates feebly. The reaction in which the anions or the cations or both of a
salt react with water to produce acidity or basicity is called
Example: (CH3COOH + CH3COONa) hydrolysis.
CH3COOH CH3COO– + H+ (incomplete) Degree of hydrolysis (h)
The fraction of total number of moles of the salt which have
CH3COONa CH3COO– + Na+ (complete)
undergone hydrolysis at equilibrium is called the degree of
yy Addition of acid, hydrogen ions from acid and ace- hydrolysis of the electrolyte.
tate ions combine to form weak acetic acid. Hence, Hydrolysis constant (kh)
pH does not change.
The equilibrium constant of the hydrolysis equilibrium of a
H+ + CH3COO– >> CH3COOH salt is called hydrolysis constant of the salt.
Salts of strong acid and strong base do not undergo
yy Addition of base, OH ions react with acid pro- hydrolysis.
ducing anions and water. Hence concentration
of H+ and OH– does not change and pH is not Degree of hydrolysis of strong acid and weak Base
altered. kh
Kh = h2C or h = h = Degree of hydrolysis
CH3COOH + OH >> CH3COO + H2O
– – C
C = Concentration, mol dm3
b. Basic Buffer: The weak base of the buffer dissociates
feebly but the salt dissociates completely. Kh = Hydrolysis constant

Example: (NH4OH + NH4Cl) Weak acid–strong base

NH4OH NH4+ + OH– (incomplete) kh

Kh = h2C or h = h = Degree of hydrolysis
C
NH4Cl >> NH4+ + Cl– (Complete)
C = Concentration, mol dm3
yy When small quantity of acid is added, hydrogen
Kh = Hydrolysis constant
ions from acid combine with base producing
corresponding cations and water; addition of acid Weak acid–weak base
does not change the pH of the buffer.
Kh = h2
H+ + NH4OH >> NH4+ + H2O
h = Kh
yy When small quantity of base is added, OH– ions
combine with NH4+ ions to form NH4OH.Hence, Relation between hydrolysis constant, dissociation
H+ or OH– concentration does not change, pH does constant of acid and ionic product of water
not change. Kw
For weak acid–strong base: K h =
OH + NH4 >> NH4OH.
– +
Ka
3.22  Chapter 1

Kw Ka and Kb = dissociation constant for an acid

For strong acid–weak base: K h = and base respectively.
Kb
Radioactivity
Kw The phenomenon of spontaneous disintegration of unstable
For weak acid–weak base: K h =
Ka × K b nuclei of certain heavy elements with the emission of some
radioactive radiation is called radioactivity.
where Kw = ionic product of water It is not affected by external factors like temperature,
pressure, catalyst and the state of existence, i.e., whether it
Kh = hydrolysis constant is an element or in a combined state.
Characteristics of α, β and γ rays
a-rays b-rays γ-rays

Charge and mass (+2) charge and 4 a.m.u. (–1) charge and Chargeless and zero mass
mass Mass slightly greater than electron

Origin 4
2
He nucleus Electron Electromagnetic radiation

Velocity 1/10th to 1/100th the 99% of the velocity of light Same as the velocity of
velocity of light light

Penetrating Poor; can hardly pass through Greater than a rays; can pass Very high; can pass through
power 0.02 cm thick Al sheet. through 0.2 cm thick Al sheet. 100 cm thick Al sheet.

Ionizing power High Lower than a-rays Very low

Deflection in an Towards the negative plate Towards the positive plate No deflection
electric field

Types of Nuclear Reactions Artificial transmutation

i. Natural radioactivity The process of conversion of a stable isotope of one element
ii. Artificial transmutation into a stable isotope of another element by bombarding it
iii. Artificial radioactivity with suitable high energy (nuclear) particles is called artifi-
iv. Nuclear fission cial transmutation.
v. Nuclear fusion 14 4 17 1
7 N + 2 He → 8 O + 1H
Natural radioactivity ( target ) ( projectile ) ( product / recoil nucleus ) ( emission )

The spontaneous emission of radiation from the nuclei of

heavy elements is called natural radioactivity. Nuclear forces (exchange force)
i. The strong attractive forces which exist between the
Artificial radioactivity protons and neutrons present in the nucleus of an atom
The phenomenon of conversion of a stable nucleus (non- are called nuclear forces. They are (p – n), (p – p) and
radioactive) into an unstable radioactive nucleus by artificial (n – n) forces.
disintegration is called artificial radioactivity. ii. They are short range forces operating in the range of
10-15. They are also called exchanged forces.
10 4 13 * 1
5B + 2 He → 7 N + 0n (Bombardment) iii. The origin of nuclear forces was explained by Japnese
boron α − particle nitrogen neutron scientist Yukawa in 1935.
iv. It is 1040 times stronger than gravitational force
13 * 13 0
7N → 6C + +1 e (Radioactivity) and 102 times stronger than the electromagnetic
carbon position force.
 Physical Chemistry  3.23

The nuclear force is due to the constant exchange iii. During γ-emission, A and Z remain the same.
of mesons (Pions Π+ or Π– or Π0) between protons and
Disintegration law
neutrons. Pions are most unstable particles (Very short
life span). The number of atoms disintegrated per unit time is a con-
stant fraction of the total number of the atoms present at
Mass defect (Δ m) that instant.
The difference between the total mass of the nucleons
(protons and neutrons) present in the nucleus of an atom Decay or disintegration constant (l)
and the actual mass of the nucleus is called the mass defect The fraction of the total number of atoms (nuclei) undergo-
of the nucleus. ing radioactive disintegration per unit time is called decay
Δ m = [ZmH + (A – Z)mn] – Mnucleus or disintegration constant of the element.
Where mH = mass of an atom of hydrogen −d N / N
isotope 11 H λ=
dt
M = mass of nucleus
2.303 N 
Or λ= Log  0  ,
Binding energy (BE) t  Nt 
The amount of energy required to break the nucleus of an
atom into its constituent nucleons is called binding energy where N0 = total number of radioactive atoms initially
of the nucleus. present (t = 0).
B.E. = Δ m × 931 MeV Nt = total number of radioactive atoms present at
time t.
Total B.E ∆m × 931 Mev
B.E. per nucleon = = Half-life period (t1/2)
Mass number( A ) A
The time required for the disintegration of a radioactive ele-
Binding energy affects the stability of the nucleus. ment to reduce to half of the original amount is called half-
life period.
Soddy’s group displacement law
i. When an element emits α-particle, t1/2 =
0.693/λ
A A −4 0 Radioisotopes
ZX → Z−2 Y + −1 e
The naturally unstable elements which spontaneously
ii. When an element emits β-particle, emit some radiations like beta-particles, protons, neutrons,
A A 0
gamma-rays, etc., are called as radioisotopes.
ZX → Z + 1Y + −1e Radio isotope dating was developed by W. F. Libby.

Uses of radioisotopes

C14 (Beta emmiter) Age of archaeological material, to study photosynthesis in plant

Na24 To study blood circulation

I131 To diagnose and treat thyroid disorder

P32 To treat leukemia, to study plant metabolism and usefulness of

phosphorous fertilizers

Co60 To treat certain type of cancers

Ca40 To find out uptake of calcium by plant from soil

Ni60 To stop growth of cancer cell

3.24  Chapter 1

Multiple Choice Questions

1. When there are no external forces, the shape of a liquid (a) Hydrogen can give an electropositive ion by losing
drop is determined by its electrons
(a) Surface tension of the liquid (b) Hydrogen can form an electronegative ion by gain-
(b) Density of liquid ing another electron
(c) Viscosity of liquid (c) Hydrogen can combine with some other elements
by means of covalency
(d) Temperature of air only
(d)   Hydrogen can enter into a coordinate linkage with
2. Choose the wrong statement from the following. other atoms
(a) Small droplets of a liquid are spherical due to surface 8. The Phase rule is applicable to ____________
tension
(a) Homogenous system
(b) Oil rises through the wick due to capillarity
(b) Reversible system
(c) In drinking the cold drinks through a straw, we use
(c) Irreversible system
the phenomenon of capillarity
(d) Heterogeneous system whether physical or
(d) Gum is used to stick two surfaces. In this process chemical
we use the property of adhesion
9. A dilatometer is an apparatus used to measure
3. When the angle of contact between a solid and a liquid
is 90°, then (a) Transition temperature
(a) Cohesive force > Adhesive force (b) Triple point
(b) Cohesive force < Adhesive force (c) Eutectic point
(c) Cohesive force = Adhesive force (d) All of these
(d) Cohesive force >> Adhesive force 10. The nature of bonding between Al and chlorine in
AlCl3 is
4. Rain drops are spherical in shape because of
(a) Electrovalent
(a) Surface tension
(b) Covalent
(b) Capillary
(c) Covalent with polar character
(c) Downward motion
(d) Coordinate covalent
(d) Acceleration due to gravity
5. Ammonia has a net dipole moment while boron trifluo- 11. Pick out the molecule which has zero dipole moment
ride has zero dipole moment because (a) NH3 (b) H2O
(a) Fluorides is more electronegative (c) BCl3 (d) SO2
(b) Fluorides is more electronegative 12. “Equal volume of all gases at the same temperature
(c) Boron trifluoride is pyramidal in shape while NH3 and pressure contains equal number of molecules” is a
is planar statement of ____________
(d) NH3 is pyramidal in shape while BF3 is planar (a) Combined Gas Law
6. The SO4 consists of a central sulphur atom with four (b) Charle’s Law
equivalent oxygen atoms. What should be the inter- (c) Boyle’s Law
nal O-S-O bond angle be (d) Avogadro’s Law
(a) 6° (b) 9° 13. The entropy is measured in ____________
(c) 109.5° (d) 117 (a) Cal K–1 mol–1 (b) JK–1 mol–1
7. Which of the following statements is incorrect? (c) Entropy unit (d) All of above
 Physical Chemistry  3.25

14. Mixing of two or more gases is a ____________ (c) 1 M HCl and 0.2 M H2SO4
(a) Spontaneous Process (d) 0.05 M HCl and 0.1 M H2SO4
(b) Non-spontaneous Process 22. Which of the following includes all the aims of
(c) Reversible Process kinetics?
(d) None of these (i) To measure the rate of reaction
15. The free energy function (G) is defined as (ii) To be able to predict the rate of a reaction
(iii) To be able to establish the mechanism by which
(a) G = H + TS
reaction occurs
(b) G = TS – H
(iv) To be able to control a reaction
(c) G = H – TS
(a) i , ii and iii (b) i and ii
(d) None of these
(c) i and iii (d) i, ii, iii and iv
16. The Second Law of Thermodynamics stated that
23. For first order reaction the rate constant K, has the
(a) It is impossible to take heat from a hotter reser- unit(s)
voir and convert it completely into work by a cy-
(a) 1 mol–1 (b) Time–1
clic process without transferring a part of heat to a
cooler reservoir. (c) (Mol/L) –1
(d) Time.mol L–1
(b) It is impossible to transfer heat from a body at a 24. Thermodynamics is applicable for ____________
lower temperature to one at higher temperature (a) Microscopic system
(c) The efficiency of heat engine in always less (b) Macroscopic system
than 1 (c) Heterogenous system
(d) All of above (d) Homogenous system
17. The unit in which surface tension is measured is: 25. A system in which no thermal energy pass into or out
(a) Dyne.cm (b) Dyne.cm–1 of the system is called ____________
(c) Dyne .cm
1
(d) Dyne1.cm1 (a) Adiabatic System (b) Open System
(c) Closed System (d) Reversible System
18. The reciprocal of viscosity is called ____________
26. An alfa particle is ____________
(a) Surface tension
(b) Frictional resistance (a) An electron
(c) Fluidity (b) One neutron and one proton
(c) Two protons and two neutrons
(d) None of these
(d) An X-ray emission
19. A crystalline solid does not have one of the following
27. In a Geiger Muller counter, one count is directly due to
properties:
____________
(a) Anisotropy
(a) A secondary electron
(b) Sharp melting point
(b) A primary electron
(c) Isotropy
(c) Many electron and ions
(d) Definite and regular geometry (d) A beta particle
20. 36 g of glucose (molecular mass – 180) is present in 28. Following is an example of extensive properties
500 g of water,the molality of the solution is __________
(a) 0.2 (b) 0.4 (p) Mass
(c) 0.8 (d) 1.0 (q) Pressure
21. The molarities of 0.1N HCl and 0.1 N H2SO4 is respec- (r) Temprature
tively: (s) Volume
(a) 0.1M HCl and 0.05 M H2SO4 (a) (p) and (q) (b) (p) and (r)
(b) 0.05 M HCl and 0.1 M H2SO4 (c) (q) and (r) (d) (p) and (s)
3.26  Chapter 1

29. Following all are the examples of endothermic process, 30. At a triple point ____________
except one (a) Both the temperature and pressure are fixed
(a) Melting of solid salts (b) Only temperature is fixed
(b) Evaporation of water (c) Only pressure is fixed
(c) Producing sugar by photosynthesis (d) Sometimes temperature and sometime pressure
(d) Mixing of water with calcium chloride are fixed

Answer Keys
1. (a) 2. (c) 3. (c) 4. (a) 5. (d) 6. (c) 7. (d) 8. (d) 9. (a) 10. (c)
11. (c) 12. (d) 13. (d) 14. (a) 15. (c) 16. (d) 17. (b) 18. (c) 19. (c) 20. (b)
21. (a) 22. (d) 23. (b) 24. (b) 25. (a) 26. (c) 27. (c) 28. (d) 29. (d) 30. (a)
 chapter 2
Organic Chemistry

Atomic Structure yy The atomic weight: The average weighted mass of

its atoms
Structure of an Atom yy Molecular weight: The sum of the atomic weights of all
yy An atom consists of negatively charged electrons, posi- the atoms in the molecule.
tively charged protons, and neutral neutrons.
yy Atomic number: numbers of protons in its nucleus Distribution of electrons in an atom
(E.g., 6C, 7N, 8O) yy The atomic orbital closer to the nucleus has the lowest
yy Mass number: the sum of number of protons and neu- energy.
trons in a atom (E.g., 126C, 147N) yy Degenerate orbital's have the same energy.

Characteristics of protons, neutrons and Distribution of electrons in first four shells

electrons
First Sec- Third Fourth
Protons Electrons Neutrons shell ond shell shell
shell
Charge Unit posi- Unit negative Charge less
tive Atomic orbitals s s, p s, p, d s, p, d, f

Mass Nearly the 1/1837th Very close No. of atomic 1 1, 3 1, 3, 5 1, 3,

same as the the mass of to the mass orbitals 5, 7
mass of H2 proton or H2 of H2 atom
atom atom. Maximum no of 2 8 18 32
electrons
Symbol P  +11 H
1
+1
1
–1
e 1
0
n

Electronic configuration of some smallest

yy Isotopes have the same atomic number but different
elements
mass numbers (E.g., 126C, 136C, 146C)
yy Isobars Isobars are atoms of different elements At- Atom- 1S 2S 2Px 2Py 2Pz 3S
having the same atomic mass but different atomic oms ic no.
number.
H 1 ↑
Isotopes are chemically same and physically differ-
ent. But the converse is true in isobars. That is, isobars are He 2 ↑↓
elements which are chemically different but physically same. Li 3 ↑↓ ↑
Since their number of electrons is different, their chemi-
cal properties are different. Examples of isobars are Fe58 Be 4 ↑↓ ↑↓
and Ni58. B 5 ↑↓ ↑↓ ↑
yy Isotones ↑↓ ↑↓ ↑ ↑
C 6
 Isotones are elements having the same number of
neutrons. Examples of isotones are Chlorine-37 N 7 ↑↓ ↑↓ ↑ ↑ ↑
and Potassium-39. Both have 20 neutrons in their
O 8 ↑↓ ↑↓ ↑↓ ↑ ↑
nuclei.
3.28  Chapter 2

E.g.,
At- Atom- 1S 2S 2Px 2Py 2Pz 3S
oms ic no. H F
F 9 ↑↓ ↑↓ ↑↓ ↑↓ ↑ H N B F
Ne 10 ↑↓ ↑↓ ↑↓ ↑↓ ↑↓ H F

Na 11 ↑↓ ↑↓ ↑↓ ↑↓ ↑↓ ↑
Electronegativity of an atom
yy It depends upon Atomic number and atomic radius of
Rules for determining electronic
an atom.
configuration yy Any atom having more atomic number and lower atom-
The Aufbau principle Electrons occupy the orbital ic radius is more electronegative than other atom.
with the lowest energy orbital first.
E.g., 105B-1S and 2S orbital first filled than one electrons IA IIA IB IIB IIIA IVA VA VIA VIIA

go with 2Px orbitals H

2.1
The Pauli exclusion principle Only two electrons can

increasing electronegativity
Li Be B C N O F
occupy one atomic orbital and the two electrons have op- 1.0 1.5 2.0 2.5 3.0 3.5 4.0
Na Mg Al Si P S Cl
posite spin. 0.9 1.2 1.5 1.8 2.1 2.5 3.0
K Ca Br
Hund’s rule Electrons will occupy empty degenerated 0.8 1.0 2.8
I
orbitals before pairing up in the same orbital. increasing electronegativity
2.5

Bonding and Hybridization Figure 2.1 Electronegativity of an atom

Bond
Polar bond
In a molecule, the atoms are held together by a strong force
A polar bond has a negative end and a positive end (E.g.,
of attraction to form a bond. The force of attraction may be
C+δ—Cl-δ).
due to oppositely charged ions or due to orbital overlap.
Non-polar bond A bond which is made up by same
Types of bonds charged atom is known as non-polar bond. ( H-H, C-C)
Three different types of bonds are formed depending on the Dipole moment It depends upon:
electropositive or electronegative character of atoms involved. 1. Molecule having more than one dipole
2. If centre of negatively charged does not concide with
a. Electropositive element + electronegative element =
centre of positively charged.
Ionic Bond
b. Electropositive element + Electropositive element = Dipole moment (D) = µ = e x d
Metallic bond
Where, e is magnitude of the charge on the atom mea-
c. Electronegative element + electronegative element =
sured in e.s.u (electron spin unit), d is distance between the
Covalent bond
two charges (in cm), µ is dipole moment of molecule
Ionic compounds are formed when an electropositive ele- (Debye unit)
ment transfers electron (s) to an electronegative element or Formal charge = number of valence electrons–(number
transfer of valance shell electron. of lone pair electrons +1/2 number of bonding electrons
E.g., Na+ and Cl–, In which Na+ having one electron in its
Molecular Orbital (MO)
outer orital while Cl– having 7 electon in its outer shell so, Na+
donate its valance shell electron to Cl– to complete the Octet. yy Bonding MO–In-phase overlap forms a bonding MO
yy Anti-bonding MO–Out-of-phase overlap forms an anti-
Covalent Compound:
bonding MO.
Mutual sharing of electrons: non-polar covalent bond (e.g., H2) yy Sigma bond (s) is formed by end-on overlap of two p
Co-ordinate covalent Bond: orbitals
It is a bond formed due to transfer of electron pair from one yy Pi (π) bond is formed due to side by side overlapping
atom to other. of two p orbital.
 O rganic Chemistry  3.29

node

σ* antibonding molecular orbital

Energy

1s atomic 1s atomic
orbital orbital

σ bonding molecular orbital

Figure 2.2 Molecular Orbital

Octet rule F
During bond formation, the atoms gain, lose or share F B
electrons so that the outermost or valence shell of an atom
F
has eight electrons as in inert gases.
Some elements having low-energy d-orbitals also form
Electronic Theory exceptions to the “octet rule”, in that, more than eight
Put forth by Kossel and Lewis in 1916. The main postulates electrons are accommodated around the central atom. The
are central atom in most of these compounds will be bonded
yy Valence shell electrons take part in bond formation. to highly electronegative elements such as fluorine, oxygen
yy Inert gases have stable outermost configuration. and chlorine.
yy Elements tend to acquire inert gas configuration by A surprising element in this group is the inert gas, xe-
gaining or losing electrons. On this basis, Ionic and non. If xenon is exposed to fluorine gas in the presence of
Covalent bonds are explained. light for several weeks, it can form XeF2, a colourless crys-
talline solid.
a. Ionic Bond: Bonds formed by gaining or losing elec-
trons in which the ions formed are held together by
electrostatic force of attraction. Hybridization of Atomic Orbitals and the
Shape of Molecules
Limitations of octet rule The valence shell electron-pair repulsion model
(VESPR) was devised to account for these molecular
yy It fails to explain formation of compounds with incom-
shapes. In this model, atoms and pairs of electrons will be
plete and expanded octets.
arranged to minimize the repulsion of these atoms and pairs
yy It fails to explain about nature of forces responsible for
of electrons.
the combination of atoms.
yy It does not explain energy, stability and reactivity of
molecule. Postulates of the valence bond theory
yy It does not explain geometry and shape of different 1. Covalent bond is formed by overlapping of atomic
molecules. orbitals and hence energy of the system decreases.
2. Atomic orbitals of two atoms having unpaired elec-
Exceptions to the octet rule trons overlap to form a covalent bond.
Elements in groups IA, IIA and IIIA do not follow the octet 3. Electrons in overlapping orbitals should have opposite
rule. spins and in the process, spins are neutralized.
Electron-dot formula for BF3, the boron will not have 4. Overlapping of orbitals causes increase in electron
eight electrons. density in the region where overlapping occurs.
3.30  Chapter 2

5. Overlapping orbitals should have comparable energies. Types of Hybridization

6. The bond formed has directional character and the yy Sp3-Hybridization: Mixing and recasting of’s’ orbitals
strength of the bond is directly proportional to the with three ‘p’ orbital of same atom forming four identi-
extent of overlap. cal orbitals tetrahedrally arranged in space.
7. Number of unpaired electrons which an atom possess- yy Sp2-Hybridization: One’s’ and two ‘p’ orbitals of the
es determines number of bonds formed, and hence its same atom mix and form three identical orbitals trigo-
valency. nally arranged in space.
The number of these new hybrid orbitals must be equal yy Sp-Hybridization: One’s’ and one ‘p’ orbital of the
to the numbers of atoms and non-bonded electron pairs sur- same atom mix and form two identical orbitals diagonally
rounding the central atom. arranged in space.

Examples:
Hybridization In the case of methane, the three 2p orbitals of the carbon
Definition The process of mixing and recasting to atom are combined with its 2s orbital to form four new
form same number of equivalent orbitals with maximum orbitals called “sp3” hybrid orbitals. The name is simply a
symmetry and definite orientation in space is called tally of all the orbitals that were blended together to form
hybridization. these new hybrid orbitals. Four hybrid orbitals were required
since there are four atoms attached to the central carbon
atom. These new orbitals will have energy slightly above
Hybridization involves the following steps the 2s orbital and below the 2p orbitals as shown in the
1. Formation of Excited State: Paired electrons jump following illustration. Notice that no change occurs with the
to higher energy levels to create, if necessary, more 1s orbital.
number of half-filled orbitals.
Examples: 2p
hybridization
sp3
2s
Ground state E
configuration of carbon
1s 2 2s2 2p 2 1s 1s

These hybrid orbitals have 75 per cent p-character and

Excited state 25 per cent s-character which gives them a shape that is short-
1s 2 2s1 2p3 er and fatter than a p-orbital. The new shape looks a little like

sp3-hybridization
1s2 Four sp3 hybrid orbitals

2. Mixing and Recasting of Atomic Orbitals: Orbitals

of valence shell mix to form new set of atomic orbitals
having same energy. The new orbitals then formed are
called hybrid orbitals. A stick and wedge drawing of methane shows the tetra-
3. Orientation of Hybrid Orbitals in Space: Hybrid hedral angles... (The wedge is coming out of the paper and
orbitals are then arranged symmetrically in available the dashed line is going behind the paper. The solid lines are
space. in the plane of the paper.)
H
Need for the concept of hybridization H
yy To explain valencies of element. C
H
yy To explain equivalence of bonds.
yy To explain geometry of molecule. H
 O rganic Chemistry  3.31

In the case of ammonia, the three 2p orbitals of the 2p 2p

nitrogen atom are combined with the 2s orbital to form hybridization
sp2
four sp3 hybrid orbitals. The non-bonded electron pair will 2s
occupy a hybrid orbital. E

2p
hybridization
sp3 1s 1s
2s
E In the following stick model, the empty p orbital is
shown as the probability area—one end shaded blue and the
other is white—there are no electrons in this orbital.
1s 1s

A stick and wedge drawing of ammonia showing the

non-bonding electrons in a probability area for the hybrid F
orbital. F B
H F

H
N In the beryllium dichloride Molecule since only two
H groups are attached to beryllium, we only will have two hybrid
orbitals. In this case, the 2s orbital is combined with only
In the case of water, the three 2p orbitals of the one of the 2p orbitals to yield two sp hybrid orbitals. The
oxygen atom are combined with the 2s orbital to form four two hybrid orbitals will be arranged as far apart as possible
sp3 hybrid orbitals. The two non-bonded electron pairs will from each other with the result being a linear arrangement.
occupy hybrid orbitals. The two un-hybridized p-orbitals stay in their respective po-
sitions (at right angles to each other) and perpendicular to
2p the linear molecule.
hybridization
sp2
2s 2p 2p
hybridization
E sp2
2s
E
1s 1s

A stick and wedge drawing of water showing the non- 1s 1s

bonding electron pairs in probability areas for the hybrid
orbital. In the following stick model, the empty p orbitals are
shown as the probability areas—one green and one blue.

H
O
Cl Be Cl
H

In the boron tri-fluoride molecule, only three groups

are arranged around the central boron atom. In this case, the Hybridization involving d-orbitals
2s orbital is combined with only two of the 2p orbitals (since Some 3rd row and larger elements can accommodate more
we only need three hybrid orbitals for the three groups— than eight electrons around the central atom. These atoms will
thinking of groups as atoms and non-bonding pairs) form- also be hybridized and have very specific arrangements of
ing three hybrid orbitals called sp2 hybrid orbitals. The other the attached groups in space. The two types of hybridization
p-orbital remains un-hybridized and is at right angles to the involved with d orbitals are sp3d and sp3d2.
trigonal planar arrangement of the hybrid orbitals. The trigo- The groups will be arranged in a trigonal bipyramidal
nal planar arrangement has bond angles of 120o. arrangement with sp3d hybridization...bond angles will be
3.32  Chapter 2

120o in the plane with two groups arranged vertically above

Five Groups...sp3d 5 groups = sp3d hybridization
and below this plane. 120 and 90 degree bond angles
trigonal bipyramidal electron-
pair geometry

There will be an octahedral arrangement with sp3d2

hybridization...all bond angles are at 90o.
Six Groups...sp3d2 6 groups = sp3d hybridization
90 degree bond angles
octahe dral electron-pair
geometry

Non-bonded electron pairs are always placed where

they will have the most space...in the trigonal plane for sp3d
hybridization.
If there are six groups (Remember to count non-bonding
electron pairs as groups.) it will have sp3d2 hybridization. If In the molecule C2H4, ethene, both carbon atoms will
it has five groups, it will have sp3d hybridization. Examples be sp2 hybridized and have one unpaired electron in a non-
are SF6, PF5, SF4, ClF3, XeF2. hybridized p orbital.
Number of Description and 3-Dimensional 2p
2p
Groups Attached Shape hybridization
to a Central Atom sp2
2s
Two Groups...sp 2 groups = sp hybridization E
180 degree bond angle
linear electron-pair geometry
1s 1s

These p-orbitals will undergo parallel overlap and form

one pi bond with bean-shaped probability areas above and be-
low the plane of the six atoms. This pair of bean-shaped prob-
Three Groups... 3 groups = sp2 hybridization ability areas constitutes one pi-bond and the pair of electrons in
sp2 120 degree bond angles this bond can be found in either bean-shaped area.
trigonal planar electron-pair
geometry
H C C H H H
C C
H H H H

In H2C2 (acetylene), both carbon atoms will be sp hy-

Four Groups...sp 3
4 groups = sp hybridization
3 bridized and have one electron in each of two unhybridized
109.5 degree bond angles p orbitals.
tetrahedral electron-pair geom-
2p 2p
etry hybridization
sp
2s
E

1s 1s
 O rganic Chemistry  3.33

These p orbitals will undergo parallel overlap to form overlap in the region directly between the two carbon atoms
two pi-bonds at right angles to each other. where the sigma bond is formed.

Sigma Bond Pi (π) bond

Linear overlap along Lateral overlap perpendic-
H C C H H C C H inter-nuclear axis ular to inter-nuclear axis.
Maximum overlap occurs. Extent of overlap is less.
Bond is rotationally Not rotationally symmetri-
symmetrical along cal.
inter-nuclear axis.
Type of Hybrid sp3 sp2 sp
Stronger than Pi-bond. Weaker than a sigma bond.
Atomic orbitals used s, p, s, p, s, p
p, p p
Hybridization Summary
Number of hybrid or- 4 3 2
bitals formed SP Hybridization SP2 Hybridization SP3 Hybridiza-
Number of atoms 4 3 2 tion
bonded to the C Occurs in Occurs in Occurs in
Number of sigma bonds 4 3 2 triple bond com- double bond single bond
pounds (E.g., compounds compounds
Number of left over p 0 1 2 Acetylene) (E.g., Ethylene) (E.g., Methane)
orbitals
S-character-50% S-character-33% S-charac-
Number of pi bonds 0 1 2 ter-25%

Bonding pattern | \ =C= Linear shape Trigonal Shape Tetrahedral

–C– C= or shape
| / C-Triple bond
Bond angle:180° Bond an- Bond angle:
gle:120° Meth-
Sigma Bonds ane:109.5°
Water: 105°
This particular kind of covalent bond in which electrons are
Ammonia: 107°
shared between atoms is called a sigma bond.
The sigma-bond is defined as the linear overlap of Bond dissociation energy The amount energy is con-
atomic orbitals (hybrids except for hydrogen) in which two sumed or liberated when a bond is formed or broken is
electrons are directly between the two bonded nuclei. called bond dissociation energy.
The distinguishing feature of a sigma bond (or sigma
Intramolecular forces A force applicable within the
bonding orbital) is that the overlap region lies directly
molecules is known as intramolecular force.
between the two nuclei.
yy Repulsive forces Applicable on same charged mol-
Pi Bonds ecule.
yy Attractive Forces Applicable on opposite charged
Pi bonds involve the electrons in the leftover p orbital (un-
molecule.
hybridized) for each carbon atom. Those p orbitals are the
Intramolecular forces A force applicable between two
electron clouds or orbitals that are shown going up above
molecules is known as inter molecular force.
and below each carbon atom.
Pi-bonds are defined as the parallel overlap of p-orbitals. 1. Dipole–Dipole interaction: Attraction of positive
A double bond has one sigma-bond and one pi-bond. A end of one dipole with negative end of other dipole is
triple bond thus consists of a sigma-bond and two pi-bonds known as dipole–dipole interaction.
with the pi-bonds in different planes.
Notice that the overlapping occurs in two places, + - + -
above and below the sigma bond. The pi bond does not
3.34  Chapter 2

2. Hydrogen Bonding: H atom serves as a bridge According to Saytzeff's rule, a is more substituted
between two most electro negative atom is known as alkene which is more stable and easily formed.
H-bonding.
Intermolecular H-bonding: It is a bond formed Markonikov’s Rule
between two molecules.
When an acidic reagent is added to –C=C-than the positive
E.g., Water molecule
portion of reagent goes to the side of double bond or triple
H H bond contain more H.
H-Bond formed due
O to weak electrostatic attraction H+ +
H H CH3 CH2 CH2 CH2
O 1° CARBOCATION
CH3 CH2 CH CH2
Intermolecular H-bonding It is a bond formed +
CH3 CH2 CH CH3
within a molecule. 2° CARBOCATION
E.g., Salicylic acid
yy So according to the rule, 2° carbocation can easily
3. Van der Waals force It is a force applicable to non-
formed compared to 1° carbocation.
polar molecule.
Reactive Intermediate in Organic Chemistry
Hofmann Rule
Carbocation/Carbenium ion Carbon having positive
When 4° ammonium hydroxide is strongly heated (≤125°C) charge is known as Carbocation.
it decomposes to yield a 3° amine, water and alkene is
known as Hofmann elimination or β-elimination.
+ C + General structure
Me3N—CH2—CH2—CH3 –→ of carbocation
Me3N + CH2 == CH = CH3+ H2O
It states that in case of alternative β-hydrogen in the Stability of Carbocation 3° > 2° > 1° > Methylcation
charged substrate (4° ammonium); the least substituted R H H H
alkene is predominantly formed.
R C + > R C + >H C + > H C +
Saytzeff Rule
De-hydro halogenation of secondary-and tertiary-alkyl halides R R R H
proceeds by the preferential removal of the hydrogen from 3° 2° 1° Methylcation
the carbon that has the smallest number of hydrogens.
yy Because of 3° Carbocation can easily form so it is more
Or stable than 2° and 1°.
The elimination in which produce more stable alkene yy 3° Carbocation directly attached with three partially
(highly substituted) is preferred. electron donating alkyl group. So it will increase the
H H H stability of Carbocation.
1. CH3 CH3 CH 3
–HBr H Effect of electron donating/withdrawing
H Br group on carbocation
CH3
OH–
A
H H H EDG
C+ -OH
2. CH3 H CH3 CH2 CH CH2
–HBr -NH2
H Br H B
EDG donate the electron to cationic carbon and increase
the stablity of it.
OH–
 O rganic Chemistry  3.35

yy pπ-dπ bonding: filled p orbital of O atom overlaps

EWG with empty d orbital of sulphur/phosphorus.
C+ -NO 2
-CHO Ylides
-SO 3H It may be defined as compound in which +ve charged atom
EDG withdraws the electron and destabilizes carboca- from group 15/16 (Sulphur/Phosphorus) of periodic table is
tion, decrease its stability. directly connected to the carbon carrying unshared pair of
Classical Carbocation: +ve charge located on one car- electrons due to pπ-dπ bonding.
bon atom/delocalized by resonance involving unshared pair
of electrons/or double or triple bonds in allylic position. + _
R 3P=CR 2 R 3P - CR 2
Non-classical Carbocation: +ve charge is delocalized
by double or triple bonds that is not in allylic position is Phosphorous Ylides
known as non-classical carbocation.
Carbene Carbon having open sextet is known as carbene
Classical Carbocation
or divalent carbon is known as carbene.
R
C + Carbene are very reactive species.
R C
C R Double bond and cationic _
carbon is in allylic position Unshared pair of es.
R _
Non classical carbocation R C R

H General Structure of carbene

+
In carbene, these two electrons are paired or unpaired.
Double bond and cationic Singlet carbene: Two non-bonding electrons are in
carbon is not in allylic position paired, present in SP2 hybridized orbitals.

Carbanions: It contains an unshared pair of electrons or

negative charge is known as carbanion. Therefore it acts as
base/nucleophile.
Singlet carbene Triplet carbene
R electrons are in paired electrons are not in paired
R C _ General Structure
Triplet carbine: Electrons are unpaired one electron pres-
of carbanion
R ent in SP2 hybridized orbitals and other presents in vacant
unhybridized p-orbital.
Stability of Carbanions: 1° > 2° > 3°
Nitren Nitrogen analogus of carbene is known as Nitrene.
H H R
R C _ _ > R C _ Unshared pair of –eS.
>R C _
R R R R N_
1º 2º 3º General Structure of Nitrene

Free Radicals: Carbon having single electron is known

Effect of electron donating/withdrawing as free radicals
group on carbanion
Stability of free radicals: 3° > 2° > 1° > Methyl radicals
Stability of carbanion increase by
yy When carbanion carbon conjugated with –C=O, –C=N etc. R H H
yy Carbanion increases its stability with an increase in the
R C > R C > H C
amount of s character at carbanion carbon.
yy Carbanion is stabilized by sulphur/phosphorus atom R R R
due to pπ-dπ bonding 3º 2º 1º
3.36  Chapter 2

Nitrenium Ion: Nitrogen analogus of carbocation is Br

known as Nitrenium ion.
CH 3 -CH 2 -CH 2 -CH 2 -Br CH 3 -CH-CH 2 -CH 3
_
N+ 1-Bromo butane (C4H9Br) 2-Bromo butane (C 4H9Br)

3. Functional Isomers: Structures having a similar

General Structure of Nitrenium Ion molecular formula but differ in functional group are
known as functional isomer.
Stereochemistry
CH 3 -CH 2 -OH CH 3 -O-CH 3
Stereochemistry is the study of the three dimensional shape
Ethanol (C 2H6 O) Dimethyl ether (C 2 H6 O)
of molecules and the effects of shape upon the properties of
molecules. 4. Metamerism: Unequal distribution of carbon chain
yy Isomers are compounds that have the same molecu- on either side of functional group is known as
lar formulas but different structural arrangements of Metamerism.
atoms. CH3 -CH2 -O-CH 2 -CH3
CH3 -O-CH2 -CH 2-CH3
They fall into two categories: Constitutional isomers Methyl propyl ether (C4 H10 O) Diethyl ether (C4 H10O)
and stereo isomers.
yy Constitutional isomers are isomers that have different 5. Tautomerism: The existence of two or more chemical
atomic connectivity. compounds that are capable of facile interconversion
   Examples of constitutional isomers include butane is known as Tautomerism.
and isobutane (both have the molecular formula C4H10, O OH
but different structures and ethanol and dimethyl ether
(both have the formula C2H6O, but again the two differ H3C C CH3 H3C C CH 2
structurally. Keto Enol
yy Stereo isomers are isomers whose constituent atoms
are connected in the same sequence, but in different Optical isomer (d and l)
spatial patterns. Optically active compound: A compound which ro-
A molecule can have more than one stereogenic carbon. tates the plane polarized light is known as optically ac-
The number of stereoisomers can be determined by the 2n tive compound.
rule, where n equals the number of stereogenic carbons. yy Chiral compounds are optically active; they rotate the
Thus, if one stereogenic carbon is present, there are two plane of polarized light.
possible stereoisomers; with two stereogenic carbons, there yy Achiral compounds do not rotate the plane of polarized
are four possible stereoisomers. light. They are optically inactive.
Stereo isomers can be further subdivided into: enantio- yy If the compound rotates the plane polarized light to the
mers and diastereomers. right side, then it known as Dextrorotatory compound.
[d or (+)].
Structural Isomers yy If the compound rotates the plane polarized light to
left side, then it known as laevorotatory compound.
1. Chain Isomers: Structures having a similar molecular
[l or (–)].
formula but differ in arrangement of carbon chain are
known as chain isomer. ‡‡ Ordinary light is converted into plane polar-
ized light by Nicol prism (Polarizer), and
CH3 it is made up of calcite crystals or crystalline
CaCO3.
CH 3 -CH 2 -CH 2 -CH 3 CH3 -CH-CH3
‡‡ Light Source: D-line Sodium lamp at λ = 5830 A0
n-Butane (C4H10 ) Iso butane (C4H10 ) yy A polarizer measures the degree of optical rotation of
a compound
2. Positional Isomers: Structures having a similar molec-
ular formula but differ in position of functional group T α
are known as positional isomers. [α] λ =
1xc
 O rganic Chemistry  3.37

yy T is the temp in °C yy c is the concentration in grams per mL

yy l is the wavelength
yy a is the measured rotation in degrees Each optically active compound has a characteristic
yy l is the path length in decimeters specific rotation.

the plane of polarization

has been rotated
direction of light propagation

light normal polarizer plane-polarizer sample tube plane-polarized

source light light containing a light
chiral compound
(Polarimeter-to measure optical activity)
Figure 2.3 Polarimeter-to measure optical activity

Optical Purity = Observed Specific rotation/Specific yy Orient the lowest priority (4) away from you
rotation of pure enantiomer yy Clockwise = R configuration, Counterclockwise = S
Enantiomer Excess = Excess of a single aTl = specific configuration
rotation enantiomer/Entire mixture
Racemic mixture, which contains an equal amount Cahn-Ingold-Prelog (CIP system)–R/S Notation
(equi-molar mixture) of the two enantiomers, is optically
The Cahn-Ingold-Prelog R/S rules are used for naming
inactive
enantiomers and diastereomers.
Absolute configuration (R, S system) 1. Identify the chiral centres (most commonly an sp3 C
with 4 different groups attached)
yy Rank the groups (atoms) bonded to the chirality center
2. Assign the priority to each group (high = 1, low = 4)
based on atomic number of the atom attached to the
this has the highest priority
chiral center (remember the first point of difference
rule)
3. Position the lowest priority group away from you as if
you were looking along the C-(4) s bond.
4. For the other 3 groups, determine the direction of high
to low priority (1 to 3)
this has the lowest priority 5. If this is clockwise, then the center is R. (Latin: rectus
= right)
clockwise = R configuration
6. If this is counter clockwise, then it is S. (Latin: sinister
= left)
Example: Chlorofluoroiodomethane
The chirality center is easy to spot, and the four at-
tached groups are I, Br, F and H listed in priority order,
highest to to lowest.

Figure 2.4 Absolute configuration (R, S system)

3.38  Chapter 2

1 Naming from the Fischer projection

I 1. Rank the groups (or atom) that are bonded to the
asymmetric carbon and draw an arrow with the high-
est priority to the lowest priority.
H Cl 2
F Cl

3 CH3CH2CH2 CH2CH3

So this is the R enantiomer. H

Sub-rules 2. If the lowest priority is on a horizontal bond, the nam-
yy Isotopes: H vs D? Since isotopes have identical atom- ing is opposite to the direction of the arrow.
ic numbers, the mass number is used to discriminate CH 3
them, so D > H.
yy Same atom attached? By moving out one unit at a H OH
time, locate the first point of difference and apply CH 2CH 2CH 3
rules there. S-2-Pentanol

3. The arrow can go from group 1 to 2, passing group 4,

Naming from the perspective formula but not group 3.
1. Rank the groups bonded to the asymmetric carbon. COOH
Br
H CH3
C OH
CH3CH2 H S-Lactic acid
CH3
4. A Fischer projection can only be rotated 180° in the
plane of the paper to yield the same molecule.
2. If the group (or atom) with the lowest priority is bond-
ed by hatched wedge.
Relative configuration (D/L configuration)
Br
D-Glyceraldehyde
C
H CHO
CH3CH2
CH3 H OH
3. If necessary, rotate the molecule so that the low- CH2OH
est priority group (or atom) is bonded by a hatched
wedge.
CH3CH2 CH3CH2 -OH group is right side to CH2OH So,
D-Glyceraldehyde is relative
switch CH3
C C Configuration
H and H Br H
Br
H CH3 L-Glyceraldehyde
CHO
4. You can draw group 1 to group 2, passing group 4, but
never 3. HO H
1 1 CH2OH
OH OH
L-Glyceraldehyde
C C
H4 H4 -OH group is left side to CH2OH
CH3CH2 CH2CH2Br CH3CH2 CH2CH2Br So, L-Glyceraldehyde is relative
3 2 3 2 Configuration
(R)-1-bromo-3-pentanol
 O rganic Chemistry  3.39

yy Relative configuration has been seen in protein, carbo-

1
hydrate and alkaloids. 1
Geometrical isomer A type of isomer which restricts
the rotation around –C=C–is known as geometrical isomer. OHC CN

X Condition for existance of C C

A
geometrical H CH3
C C
if A = B & X = Y
B Y

CH 2 cl C 6 H5 Z isomer because two

H3 C H3 C
prior group are on
C C C C Same side
H3 C H H3 C C 6 H5
A B Enantiomer and Diastereomer
In structure A and B, one carbon is attached with two simi- Enantiomer The stereoisomer of compounds which are
lar groups so there is no possibility to exist geometrical isomer. non-superimposable mirror image of each other are known
as enantiomers.
Cis-Trans system
H yy Enantiomers are often referred as a optical isomer.
H3C CH 3 H3C yy Chirality is necessary and sufficient condition for
C C C existence of an enantiomer.
C
H CH3 yy Non-superimposabilty on its mirror image is necessary
H H
Cis isomer Trans Isomer and sufficient condition for existence of enantiomerism.
yy It is also a necessary but not sufficient condition for
yy Cis means two similar groups are on same side.
optical activity.
yy Trans means two similar groups are on opposite
yy E.g., Racemic mixture is optically inactive.
direction.
yy All enantiomer have similar physical property
yy Trans isomer is more stable than Cis isomer due to
(exception is specific rotation) while different chemical
steric hindrance is more with cis isomer because two
property.
bulky groups are in same side.
yy Trans isomer having Dipole moment µ = 0 CH3 CH3 CH3 CH 3

E/Z system: In alkenes, if carbon is attached with four H Br Br H Br H H Br

different groups than it will be nomenclatured by E/Z
system.
H Cl Cl H H Cl Cl H
yy E means Entegegen-Opposite side
yy Z means Zusammen-Same side
CH3 CH3 CH 3 CH 3
1 A B C D
yy A and B and C and D are pair of enantiomer
H3 C Br yy While A and C, A and D, B and C and B and D are pair
C C of diastereomer.
Cl H Diastereomer: The stereoisomer of compound which
are not mirror image of each other are known as diaste-
1 reomers.
yy All diastereomers have similar chemical property and
E isomer because two
different physical property.
prior group are on
yy Diastereomer is possible if the molecule is having two
opposite side
or more than two chiral centre.
3.40  Chapter 2

Meso compounds: These are the ones which are super- Epimer When two diastereomers differ in the stereochem-
imposable on their mirror image even though they contain istry at only one stereocentre then these are epimers of each
chiral carbon. Because it has a plane of symmetry in its other.
structure, so it is optically inactive.
yy E.g., Glucose and galactose are epimer at C-4
CH 3 CH3 yy Glucose and mannose are epimer at C-2
Plane of Anomer If diastereomers differ in their configuration at
H Br Br H symmetry C-1 (anomeric carbon), then these are called anomers.

Cl CH2OH
H Cl H
O
H OH
H
Anomeric
CH 3 CH3 carbon
OH OH H H
A B

Erythro/Threo H OH
Erythro: If two similar groups are on the same side of
carbon chain. yy β-anomer: If –OH group is in upward direction to ano-
meric carbon.
Threo: If two similar groups are on the opposite side of yy α-anomer: If –OH group is in downward direction to
carbon chain. anomeric carbon.
COOH COOH
Conformation Different three dimensional arrange-
ments of atoms results due to free rotation about C-C single
H OH OH H bond, this is known as conformation.

Conformation in ethane
H OH OH H
H H
H
COOH COOH H
H
A B
D-Erythro L-Erythro

H
COOH COOH H H H H H
H
H OH OH H Staggered Eclipsed

Staggered forms are more stable than eclipsed because

OH H H OH all atoms are arranged opposite to each other so it reduces
steric hindrance among them.
Anti It is a type of staggered conformation dihedral angle
COOH COOH between two bulky groups is 180°.
C D Gauche: It is a type of staggered conformation dihedral
L-Threo D-Threo angle between two bulky groups is 60°.
 O rganic Chemistry  3.41

Note
Conformation In Cyclohexane: Stability order
Chair conformation > Twist boat conformation > boat conformation >half chair conformation

yy Chair conformation: It is most stable because all H in which a pre-existing chiral center influences the reactivity of a
atoms are in staggered form. reaction center elsewhere in the same molecule.
yy Twist-boat conformation: Where it twists, two H atoms A diastereoselective reaction is the one in which one dia-
are at staggered position. stereomer is formed in preference to another (or in which a sub-
yy Boat form: All H-atoms are at eclipsed form. set of all possible diastereomers dominates the product mixture),
yy Half-Chair form: Because at one end of ring are planar. establishing a preferred relative stereochemistry. In this case, ei-
ther two or more chiral centers are formed at once such that one
Bredt’s Rule: In bridgehead bicyclic compound, double
relative stereochemistry is favoured, or a pre-existing chiral cen-
bond at the bridgehead position are impossible in small system.
ter (which needs not be optically pure) biases the stereochemical
outcome during the creation of another. The degree of relative
Double bond at selectivity is measured by the diastereomeric excess.
H bridgehead position Stereoconvergence can be considered an opposite of
OH are not possible stereoselectivity, when the reaction of two different stereo-
isomers yields a single product stereoisomer.
H
Examples
An example of modest stereoselectivity is the dehydrohalo-
Correct product
genation of 2-iodo-butane which yields 60% trans-2-butene
and 20% cis-2-butene. Since alkene geometric isomers
Stereoselectivity are also classified as diastereomers, this reaction would also
Any chemical reaction that yields predominantly, one ste- be called diastereoselective.
reoisomer, out of several stereoisomer possibilities is said
to be a stereoselective reaction. tBuOK
+ +
It is the property of a chemical reaction in which a single DMSO
60% trans 20% cis 20%
reactant forms an unequal mixture of stereoisomers during the – HI
non-stereospecific creation of a new stereocenter or during the
non-stereospecific transformation of a pre-existing one. The addition of formic acid to norbornene is also
The selectivity arises from the differences in steric stereospecific because the exo isomer is formed exclusive-
effects and electronic effects in the mechanistic pathways ly without any of the endo isomer.
leading to the different products. Stereoselectivity can vary
in degree but it can never be total since the activation
HCO2H
energy difference between the two pathways is finite. How-
O H
ever, in favourable cases, the minor stereoisomer may not be reflux
detectable by the analytic methods used.
An enantioselective reaction is the one in which one enan- H O
exo
tiomer is formed in preference to the other, in a reaction that cre-
ates an optically active product from an achiral starting material, Cram’s rule predicts the major diastereomer resulting
using either a chiral catalyst, an enzyme or a chiral reagent. The from the diastereoselective nucleophilic addition to a car-
degree of selectivity is measured by the enantiomeric excess. An bonyl group next to a chiral center. The chiral center need not
important variant is kinetic resolution, in which a pre-existing be optically pure, as the relative stereochemistry will be the
chiral center undergoes reaction with a chiral catalyst, an en- same for both enantiomers. In the example below, the (S)-al-
zyme or a chiral reagent such that one enantiomer reacts faster dehyde reacts with a thiazole to form the (S, S) diastereomer
than the other and leaves behind the less reactive enantiomer, or but only a small amount of the (S, R) diastereomer.
3.42  Chapter 2

S Stereospecificity
Si Stereospecificity is the property of a reaction mechanism
N that leads to different stereoisomeric reaction products from
O N – BOC
different stereoisomeric reactants, or which operates on
only one (or a subset) of the stereoisomers.
CH2Cl2 , –20°C In contrast, stereoselectivity is the property of a reac-
tant mixture where a non-stereospecific mechanism allows
(S) O 92% anti for the formation of multiple products, but where one (or a
subset) of the products is favoured by factors, such as steric
O N – BOC access, that are independent of the mechanism.
S A stereospecific mechanism specifies the stereochemical
outcome of a given reactant, whereas a stereoselective reac-
tion selects products from those made available by the same,
HO N non-specific mechanism acting on a given reactant. Given a
(S, S) single, stereoisomerically pure starting material, a stereospe-
cific mechanism will give 100% of a particular stereoisomer
The sharpless epoxidation is an example of an enanti-
(or no reaction), although loss of stereochemical integrity can
oselective process, in which an achiral allylic alcohol substrate
easily occur through competing mechanisms with different
is transformed into an optically active epoxyalcohol. In the
stereochemical outcomes. A stereoselective process will nor-
case of chiral allylic alcohols, kinetic resolution results.
mally give multiple products even if only one mechanism is
Another example is sharpless asymmetric dihydroxylation.
operating on an isomerically pure starting material.
In the example below, the achiral alkene yields only one of
possible four stereoisomers. Examples
Nucleophilic substitution at sp3 centres can proceed by the
K2OsO4, 2H2O cat.
stereospecific SN2 mechanism, causing only inversion, or by
(DHQD)2PHAL cat. the non-specific SN1 mechanism, the outcome of which can
K3Fe(CN)6, MeSO2NH2 show a modest selectivity for inversion, depending on the
OH
K2CO3 reactants and the reaction conditions to which the mecha-
OH
nism does not refer. The choice of mechanism adopted by
t-BuOH/ H2O a particular reactant combination depends on other factors
(steric access to the reaction centre in the substrate, nucleo-
(R, R) phile, solvent, temperature).
98% ee
Stereospecificity in substitution reactions
With a stereogenic center next to the carbocation, the
substitution can be stereoselective in intra and intermolecular Nu– X
reactions. In the reaction depicted below, the nucleophile
X Nu C
(furan) can approach the carbocation formed from the least X Y
slow
shielded side away from the bulky t-butyl group resulting in C L fast +Z
high facial diastereoselectivity: Y C+ X
Z C Nu
Y Z Y
OH +L
HBF4 ⊕ Z
Ph CH2Cl2 , –78°C Ph SN1 mechanism non-stereospecific

X X X
δ– δ+
Nu– C L Nu C δ–
Nu C
O L +L
Y Z
Y Z Z
O
Ph SN2 mechanism stereospecific

For example, tertiary centres react almost exclusively

d.r. = 98/2 by the SN1 mechanism whereas primary centres (except
 O rganic Chemistry  3.43

neopentyl centres) react almost exclusively by the SN2 Important Organic Reactions Mechanism
mechanism. When a nucleophilic substitution results in
1. SN1 mechanism
incomplete inversion, it is because of a competition between
the two mechanisms, which often occurs at secondary SN1 indicates a substitution, nucleophilic, unimolecular
centres, or because of double inversion (as when iodide is reaction,
the nucleophile). Rate = k[R–X] follows first order kinetics
The addition of carbenes to alkenes is stereospecific in
that the geometry of the alkene is preserved in the product. This implies that the rate determining step of the mech-
For example, dibromocarbene and cis-2-butene yield cis-2, anism depends on the decomposition of a single molecular
3-dimethyl-1, 1-dibromocyclopropane, whereas the trans species.
isomer exclusively yields the trans cyclopropane. Step-1 Generation of carbocation, slow step, rate determin-
Br Br ing step.
H 3C CH3 CHBr3 , t-BuOK
H3C CH3 R R
– 10 :: – 24ºC
H H
H H R C X R C + + X–
Br Br R R
H 3C H
CHBr3 , t-BuOK
H3C H
– 10 :: – 24ºC Step-2 Rapid attack of nucleophile on carbocationic carbon.
H CH3
H CH3
R R
This addition remains stereospecific even if the starting
R C+ + – OH R C OH
alkene is not isomerically pure, as the products stereochem-
istry will match the reactants.
R R
The disrotatory ring closing reaction of conjugated
trienes is stereospecific in that isomeric reactants will –OH
give isomeric products. For example, trans, cis, trans-2,
4, 6-octatriene gives cis-dimethylcyclohexadiene, whereas H H H H
the trans, cis, cis reactant isomer gives the trans product
H C X HO C X HO C H
and the trans, trans, trans reactant isomer does not react in
this manner. H
H H
CH3
H 3C CH3
PENTAVALENT TRANSITION
H STATE
H H =
H
H H
trans-cis-trans
This pathway is a concerted process (single step) as
CH3 shown by the following reaction coordinate diagrams,
CH3 where there is simultaneous attack of the nucleophile and
displacement of the leaving group.
H
H Reactivity order 3° >2°>1° alkyl halides
CH3 CH3 Stereochemitry Inversion plus partial racemization
HOMO
H Solvent Polar protic solvent increases the rate of SN1
CH3 reaction because it increases the rate of ionization of the
cis H alkyl halide.
3.44  Chapter 2

2. SN2 mechanism The more stable the carbocation is, the easier it is to form,
SN2 indicates a substitution, nucleophilic, bimolecular and the faster the E1 reaction will be carried out.
reaction, described by the expression This E1 mechanistic pathway is most common with:

Rate = k [Nu][R–X]. It follows second order kinetics. yy Good leaving groups

yy Stable carbocations
Reactivity order 10 >20 >30 alkyl halides yy Weak bases
Stereochemitry Total inversion of configuration 5. E2 mechanism
Halides Nucleophilicity in protic solvent: F < Cl <Br E2 indicates an elimination, bimolecular reaction, where
< I, because nucleophile is solvated. rate = k [B][R-LG]. This implies that the rate determining
Halides Nucleophilicity in Aprotic solvent: F > Cl step involves an interaction between these two species, the
>Br > I, because nucleophile is not solvated. base and the organic substrate.

3. E1 mechanism B: H C C LG B–H C=C LG

E1 indicates an elimination, unimolecular reaction,
This pathway is a concerted process with the following
Where rate = k [R–LG]. characteristics:
Simultaneous removal of the proton, H+, by the base, loss
This implies that the rate determining step of the mech-
of the leaving group, LG, and formation of the double-bond.
anism depends on the decomposition of a single molecular
species. Reactivity Rate of reaction increase as more branched
Overall, this pathway is a multi-step process with the alkene is formed.
following two critical steps: Orientation of E2 mechanism follows Saytzeff’s rule.
Step-1: Loss of the leaving group, LG, to generate a carbo-
cation intermediate. 6. Electrophilic addition reactions
yy It is an important class of reactions that allow the inter
conversion of C=C and C≡C into a range of important
H C C LG H C C LG functional groups.
yy Addition reaction is the reverse of elimination
yy An electrophile, Y+, is an electron deficient species that
Step-2: Loss of a proton, H+, from the carbocation to form
will react with an electron rich species (the C=C).
the –C=C–bond.
yy The following pointers may aid your understanding of
these reactions:
yy Intermediate is carbocation, so rearrangement takes
B: H C C B–H C=C place
Reactivity
Reactivity order (CH3)3C → (CH3)2CH → CH3CH2 → yy Electron withdrawing group at “–C=C–”decrease reac-
CH3– tion because intermediate is carbocation.
yy Electron donating group at “–C=C–”increase reaction
4. Orientation of E1 mechanism follows because Intermediate is carbocation so EDG stabilize
Saytzeff’s rule carocation.
yy Orientation of electrophilic addition reactions follows
Selectivity E1 reactions usually favours the more stable Markonikov’s rule.
alkene as the major product: more highly substituted and yy If the two new σ bonds form at the same time from the
trans → cis- same species, then syn-addition is observed.
In an E1 reaction, the rate determining step is the loss yy If the two new σ bonds form at different times from
of the leaving group to form the intermediate carbocation. different species, then anti-addition is observed.
 O rganic Chemistry  3.45

Step-1 Addition of electrophile toward alkene H

Y Y
B
Slow CH W H Y CH2 CH W
R C C R+Y R C C R CH2

Carbocation Rate
Determining step
Y H
Step-2 Addition of nucleophile to carbocation
CH2 CH W
Y W Y
Fast W = Electron withdrawing groups like –CHO, –COOR,
R C C R W R C C R
–COOH, –NO2

7. Nucleophilic addition reactions 8. Mechanism of addition to –C=X

In nucleophilic addition reactions, first, attack of nucleo- (X=hetero atom) multiple bond
phile takes place then addition of electrophile takes place. (Electrophilic addition to –C=O and Nucleophilic addition
to –C=O)
Step-1 Attack of nucleophile towards alkene It is concerned with addition to –C=O, –C=N, –C=S,
W –C≡N, so these all are stronger and polar bonds hence only
Slow – ionic mechanism can operate. No free radical mechanism can
R C C R W– R C C R operate.
In this reaction, nucleophile always goes with carbon
Carboanion Rate atom and electrophile always goes with hetero atom.
Determining step

Step-2 Addition of electrophile to carbanion Nucleophillic addition reaction

Step-1 Addition of nucleophile to –C=O
W Y W
Fast
R C C R Y R C C R O–
O
The following pointers may aid your understanding of Y– A C B (Slow, RDS)
these reactions: A B
yy Intermediate is carbanion, so rearrangement cannot Y
take place.
Step-2 Addition of electrophile to O (Hetero atom)
Reactivity
yy Electron withdrawing group at “–C=C–”increases OH
O–
reaction rate because the intermediate is carbanion, so
it will stabilize carbanion. A C B H A C B (Fast Step)
yy Electron donating group at “–C=C–”decreases reac- Y
Y
tion rate because intermediate is carboanion so EDG
increases the electron density and destabilizes the
carbanion. Electrophillic addition reaction
yy Orientation of nucleophilic addition reactions follows Step-1 Addition of electrophile to O (Hetero atom)
Micheal addition rule:
O OH
yy Attack of nucleophile to the “–C=C–” bond occurs in
such a way that it attacks the side away from carbon H+ A C B (Fast, Step)
A B
having electron withdrawing group.
3.46  Chapter 2

Step-2 Addition of nucleophile Since cyclo octatetraene is non-planar, it is not aromatic,

OH and it undergoes addition reactions just like those of other
OH alkenes.
A C B Y– A C B (Slow, RDS)
H
Y H Br
Br2
In both the mechanisms, the rate limiting step is the H Br
attack of nucleophile reactivity. H
cyclooctatetraene addition product
yy Electron donating groups (A/B): Decrease the reaction
rate, nucleophile cannot attack on carbonyl carbon because (3) A molecule must be completely conjugated:
electron density at carbonyl carbon (–C=O) is increased.
yy Electron withdrawing groups (A/B): Increase the reac- A completely conjugated ring
tion rate, nucleophile can easily attack on carbonyl A completely conjugated ring
carbon because the electron density at carbonyl carbon
(–C=O) is decreased so –C=O becomes more positive.
yy Steric hindrance near –C=O group also decrease the
reactivity.
benzene
yy Aryl group or π bond in conjugation with –C=O also a p orbital on every C
benzene
decrease the reactivity by releasing electron through a p orbitalaromatic
on every C
resonance. aromatic
These rings are not completely conjugated.
Criteria for Aromaticity—Hückel’s Rule These rings are not completely conjugated.
Four structural criteria must be satisfied for a compound to
be aromatic. no p orbitals no p orbital
(1) A molecule must be cyclic: no p orbitals no p orbital
1,3-cyclohexadiene 1,3,5-cycloheptatriene
not aromatic
1,3-cyclohexadiene not aromatic
1,3,5-cycloheptatriene
Cyclic compound cyclic compound
not aromatic not aromatic

(4) A molecule must satisfy Hückel’s rule, and contain a

no overlap particular number of π electrons.
Hückel’s rule:
benzene 1,3,5-hexatriene
Every p orbital overlaps There can be no overlap yy An aromatic compound must contain 4n+2π
with two neighboring between the p orbitals on electrons (n = 0, 1, 2, 3 and so forth).
p orbiotals. the two terminal C’s.
yy Cyclic, planner and completely conjugated com-
aromatic not aromatic pounds that contain 4n π electrons are especially
To be aromatic, each p orbital must overlap with p unstable, and are said to be anti aromatic.
orbitals on adjacent atoms. Benzene is aromatic and especially stable because it
(2) A molecule must be planar: contains 6 p electrons. Cyclobutadiene is antiaromatic and
All adjacent p orbitals must be aligned so that the p especially unstable because it contains 4 p electrons.
electron density can be delocalized.
Benzene Cyclobutadiene
An aromatic compound An antiaromatic compound

Adjacent p orbitals
cannot overlap.
cyclooctatetraene a tub-shaped, Electrons cannot 4n + 2 = 4(1) + 2 = 4n = 4(1) =
not aromatic eight-membered ring delocalize. 6 π electrons aromatic 4 π electrons antiaromatic
 O rganic Chemistry  3.47

Note that Hückel’s rule refers to the number of p 2. Anti-aromatic—A cyclic, planar, completely conju-
electrons, not the number of atoms in a particular ring. gated compound with 4np electrons.

Where The no of π electrons that obey the 3. Not aromatic (nonaromatic)—A compound that lacks
n huckel’s rule one (or more) of the following requirements for aroma-
ticity: being cyclic, planar, and completely conjugated.
0 2 yy An aromatic compound is more stable than a
1 6 similar acyclic compound having the same num-
ber of π electrons. Benzene is more stable than
2 10 1,3,5-hexatriene.
3 14 yy An antiaromatic compound less stable than an acyclic
4 18 compound having the same number of π electrons.
Cyclobutadiene is less stable than 1,3-butadiene.
Considering aromaticity, a compound can be classi- yy A compound that is not aromatic is similar in stability
fied in one of three ways: to an acyclic compound having the same number of
1. Aromatic—A cyclic, planar, completely conjugated π electrons. 1,3-Cyclohexadiene is similar in stabil-
compound with 4n + 2 p electrons. ity to cis,cis-2-4-hexadiene, so it is not aromatic.

o ar omatic

and and and

benzene 1,3,5-hexatriene cyclobutadiene 1,3,-butadiene 1,3-cyclohexadiene cis,cis-2,4-

hexadiene
more stable less stable
aromatic a tiar omatic similar stability

Annulene: Thus, the ring puckers to relieve this strain.

yy To name an annulene, indicate the number of atoms in yy Since [10]-annulene is not planar, the 10 p electrons
the ring in brackets and add the word annulene can’t delocalize over the entire ring and it is notaromatic.
[10]-Annulene fits The molecule puckers to
Hückel’s rule, but it’s keep these H’s further
not planer. away from each other.

[10]-annulene
[14]-annulene [18]-annulene 10 π electrons
4n + 2 = 4(3) + 2 = 4n + 2 = 4(4) + 2 = not aromatic 3-D representation
14 π electrons 18 π electrons
aromatic aromatic
yy Two or more six-membered rings with alternating
double and single bonds can be fused together to form
yy [10]-Annulene has 10 p electrons, which satisfies polycyclic aromatic hydrocarbons (PAHs).
Hückel's rule, but a planar molecule would place the yy There are two different ways to join three rings together,
two H atoms inside the ring too close to each other. forming anthracene and phenanthrene.
3.48  Chapter 2

Annulenes:
Monocyclic, completely conjugated polyenes. According to
the HMO, the 4n + 2 = 2,6,10,14…π-electron annulenes are
aromatic, while the 4n = 4,8,12,16…π-electron annulenes
are anti-aromatic (paratropic compound: a presence of para-
naphthalene anthracene phenanthrene magnetic ring current).
10 π electrons 1 π electrons 1 π electrons
yy As the number of fused rings increases, the number of
resonance structures increases. Naphthalene is a hybrid
of three resonance structures whereas benzene is a
hybrid of two.
Duet Quartet Sextet Octet
Three resonance structures for naphthalene
(aromatic) (anti-aromatic, (aromatic) (anti-aromatic,
diradical) diradical)

Note
yy That according to the Huckel rule, the first pair of π-electrons goes to the π-orbital of the lowest energy. After that the
bonding orbitals are degenerate and occur in pairs of equal energy. According to the Hund’s rule, these orbitals are filled
first with unpaired π- electrons (diradical structure), and then paired (sextet structure). The degeneracy may be removed
by a distortion of a molecule and the resulting loss of symmetry.

1.33 Å

1.567 Å H
H H
1.346 Å        1.462 Å   
[8]annulene H H
[4]annulene [6]annulene nonaromatic H
antiaromatic aromatic distorted
[16]annulene
π 2 × 2 (anti) 1×4+2 4 × 2 (anti) nonaromatic [18]annulene
(non-planar) aromatic (NMR)

7.6 δ 4 × 4 (anti)     4×4+2

H H
H 0.0 δ
H
X
[10]annulene (ZEZZE) [12]annulene
3 isomers - all non- non-aromatic [14]annulene
aromatic (non planar) (non-planar) aromatic (NMR) X=CH2, O, NH are planarized
    and are aromatic
2×4+2 4 × 3 (anti) 3×4+2
 O rganic Chemistry  3.49

Aromaticity in charged rings Huckel orbital array Mobius orbital array

Aromatic systems with two π-electrons:
Aromatic: 4n+2 Aromatic: 4n
⊕ ⊕ ⊕
Antiaromatic: 4n Antiaromatic: 4n+2
2+
+
Homoaromaticity:
Four π-electrons are generally unstable
Homoaromatic systems are that contain conjugated
(anti-aromatic).
delocalized systems that bypass one of the atoms (satu-
.. rated), or alternatively, that have a saturated atom (usually
O

..
..
Et2N COOEt Et2N carbon) interrupting the π-system.
OEt
H H

EtOOC NEt2 EtOOC NEt2

⊕ ⊕
+
R R H
H
Fe(CO)3 Fe(CO)3
Fused ring systems:
I ⊕
Numerous completely conjugated hydrocarbons can be
derived from annulenes. These fused annulenes may be rep-
Six π-electron systems; aromatic and stable: resented by several resonance structures.

For example
− − − Naphthalene: 3 resonance structures may be drawn (without
..

..

−
..

      .. considering Dewar forms).

+ The 1,2 bond has more of C=C character than 2,3 C/C
+ bond.
+ ++
   + 1 1 1
2 2 2
Eight π-electron systems: anti-aromatic and
unstable: 3 3 3
4 4 4
Ten π-electron systems: may be aromatic
Bond order (length) 1.724 (1.36 Å)
[10]annulene –non-aromatic due to its deviation from
planarity (NMR:all hydrogens are of the alkene type).
Two isomers (ZZZZZ, ZEZZE) were prepared. Recent 1.603 (1.415 Å)
calculations suggest that the last one, EZZZZ may be
aromatic.
We observe so called “partial bond fixation”, which is
H
.. typical for the reactivity of fused annulenes. In the case of
. .N naphthalene, we observe that 1,2-bond reacts more like a
2− − double bond: epoxidation, ozonolysis, etc. Note also that the
major resonance contributor is the structure with a double
bond at the ring fusion, the first structure.
Examples of other aromatic systems:
Super large systems: Several interesting cases:
“Normal” annulenes are aromatic according to the Huckel’s Acenaphthylene: the additional C=C has very much char-
rule (4n+2). The presence of the Mobius twist and resulting acter of the regular C=C (does not contribute significantly
phase discontinuity of the atomic orbitals would cause the to the delocalization energy).
reversal of the aromaticity/antiaromaticity rules. Azulene: the bond between two cycles has enhanced C-C
3.50  Chapter 2

character. Aromaticity is believed to be caused by the dipolar 3. Homoaromatic species (vide supra): Another example
structure (+ –) composed of the cyclopentadiene anion and that is reasonably stabile is the cyclobutenium cation,
the cycloheptatriene cation (both aromatic). In agreement is which is explained by the formation of the homoaro-
the large dipole moment of azulene (0.8D). matic acyclopropenium carbocation loop.

1.396 Å HOSO2F
1.466 Å +
1.383 1.406 Å SbF5-SO2CIF
1.381 Å
1.403 Å OAc −75°C
1.386 1.424 Å 1.501 Å
  1.399
2. Fullerenes (Bucky balls and bowels)
Fullerenes are spherical conjugated polyenes that display
− + − + aromatic properties. These recently discovered forms
   of carbon are related to bowl-shaped aromatic hydro-
carbons whose parent is the bowl-shaped hydrocarbon
corannulene. If aromatic systems are constructed of a
− + two-dimensional array of fused six-membered rings,
a planar aromatic system results that upon its ultimate
extension is called graphite. On the other hand, if the
Similarly to azulene, there are bicyclic aromates, that aromatic system is constructed five- and six-membered
may be stabilized by their dipolar forms. Interestingly, they rings where every fivemembered ring is isolated from
do not have to be fused. Such compounds too have large other five-membered rings by circles of six-membered
dipoles rings, then a curved aromatic surface results. Upon ultimate
Conjugated heterocyclic compounds are in many cases extension, this pattern of construction results in carbon
isoelectric with the aromatic nanotubes and fullerenes.
Example: Corannulene compared with coronene.
Other aromatic compounds
1. Mesoionic compounds: their structure cannot be
explained/described by Lewis structures that do not
involve a charge separation. Most of them are five-
membered heterocycles. Example: sydnones
Coronene        Corannulene
R′ R′ .. R′ ..
O ⊕
.O. .O.
..

..

⊕
R N + = R N ⊕ R N
..

..

O O O
..

N .N. .N.
..

2. The dianion of squaric acid (squarate) and the corre-

sponding five-membered species.

O OH O O O O
Buckyball
−2H+ C60
O OH O O O O m/e = 720
Fullerene
 O rganiC Chemistry  3.51

note
y That even though corannulene is not planar, it can be view as being composed of concentric aromatic rings, the
inner ring bearing a negative charge and the outer one a positive charge.

Aromatic carbocyclic compounds 1 1

2 2

resonance resonance resonance

contributor contributor hybrid
Benzene Napthalene Antharacene Resonance contributors are imaginary, but the reso-
nance hybrid is real.

rules for drawing resonance contributors

y Only electrons move.
y Only p electrons and lone-pair electrons move.
y The total number of electrons in the molecule does not
Phenanthrene Chrysene change.
y The numbers of paired and unpaired electrons do not
change.
Aromatic heterocyclic compounds
The electrons can be moved in one of the following
N S O O N S ways
y Move π electrons toward a positive charge or toward
N N N
a π bond.
Pyrrole Thiophene Furan Oxazole Pyrazole Thiazole
y Move lone-pair electrons toward a π bond.
N N N N N y Move a single nonbonding electron toward a π bond.
N
N N
N
N General mechanism for electrophilic aromatic
Pyridine Pyrimidine Pyrazine Pyridazine Triazine substitution of benzene
EAS mechanism/SE2 mechanism
Anti-aromatic A compound is anti-aromatic if it is a pla-
nar, cyclic compound with an uninterrupted ring of π cloud, Step-1 Generation of Arenium ion
but it contains even number of pairs of π electrons. H
H Y H Y H Y

relative stabilities Y

Electrophile
H Y

Arenium Ion

Step-2 Loss of Proton

Benzene Y
H Y
y A planar molecule has six identical carbon–carbon bonds.
y Each π electron is shared by all six carbons. Fast
y The π electrons are delocalized. –H
3.52  Chapter 2

Step 1: It is a slow step and hence a rate yy Electron donation increases reactivity towards electro-
determining step philic substitution and decreases acidity.
yy Intermediate is arenium ion or benzonium ion or whel-
and intermediates OH OH OH OH
yy Reactivity of EAS
yy EDG on benzene ring increases the reactivity towards
electrophillic aromatic substitution.
yy EWG on benzene ring decreases the reactivity towards
electrophillic aromatic substitution. e.g., of reactivity order
2+ 12 � OCH3 CH3 Cl

pKa = 10.20 pKa = 10.19 pKa = 9.95 pKa

! !

yy Electron withdrawal decreases reactivity towards Orientation

electrophilic substitution and increases acidity Why EDG are o/p directing?

CH3 CH3 CH3

Y Y Y
H H H
ortho

most stable

CH3 CH3 CH3 CH3

meta
+ Y+
Y Y Y
toluene H H H

CH3 CH3 CH3

para

H Y H Y H Y
most stable

In the above example, methyl group of toluene acts as a group is attached so it stabilizes the positive charge. This
partially electron donating group, so in the above example, happens with only o/p isomer, it is not seen in m isomer that
the positive charge genaration is on carbon where methyl is why all activating group are o/p directing group.
 O rganic Chemistry  3.53

Why EWG are m-directing?

+ + +
NH3 NH3 NH3
Y Y Y
ortho + H H H

+ +
least stable
+ + +
+
NH3 NH3 NH3 NH3

+ +
meta
+ Y+ Y Y Y
H H H
+
protonated
+ + +
aniline NH3 NH3 NH3

para
+
+ +

H Y H Y H Y
least stable

In the above example (4° Ammonium group) on ring es the positive charge because it wihdraws the electron.
acts as an electron withdrawing group, so in the above This happens with only o/p isomer, it is not seen in m
example, the positive charge genaration is on carbon isomer, that is why all deactivating group are m-directing
where 4° Ammonium group is attached, so it destabiliz- group.

List of electron donating and withdrawing groups

Activating Substituents Most activating

(EDG)    
-NH2
-NHR Strongly activating
-NR2
-OH
-OR      Ortho-Para
          Directing
-NHCOR Moderately activating
-OCOR

     
-R Weakly activating

Ar
-CH=CH2
3.54  Chapter 2

Standard of comparision -H
Deactivating Substituents    
(EWG) -F
-Cl Weakly deactivating
-Br
-I
    
-CHO Moderately deactivating
-COR       Meta
      Directing
-COOR
-COOH
-COCl
    Strongly
-CN deactivating
-SO3H
-NO2
-NR3+

The substituent already attached to the benzene ring

X Y X Y Y
determines the location of the new substituent.
X X X X fast
–
:
Y + X–

+ Y+ or or N NO2
+ NO2
Y –
O O–
Y
ortho isomer meta isomer para isomer
Step 1 Intermediate is carbanion generation or meisenheimer
All activating substituents and the weakly deactivating
complex formation.
halogens are ortho–para directors.
All substituents that are more deactivating than halo- Step 2 is loss of leaving group (X-‑) to stabilize carbanion.
gens are meta directors.
yy Any substituent that donates electrons inductively is an Reactivity
ortho–para directors. The electron-withdrawing substituents at ortho or para to
yy All substituents that donate electrons by resonance are the site of nucleophile attack increase the SN Ar reaction,
ortho–para directors. while electron withdrawing substituents decrease the SN Ar
Nucleophillic Aromatic Substitution Reaction (Bimo- reaction.
lecular displacement mechanism or SN Ar mechanism)
General mechanism for nucleophilic aromatic Benzyne mechanism or aryne mechanism or
substitution benzyne mechanism
It requires strong basic condition.
X X Y X Y
Cl Cl
slow –
+ Y– H
–
+ –:NH2 + NH3
NO2 NO2 N
O
– O
 O rganic Chemistry  3.55

Y yy The overall reaction is an insertion of oxygen atom be-

* tween carbonyl carbon and the adjacent carbon in ketone.
yy Commonly used solvents are glacial acetic acid and
+ Cl– +X
chloroform.
benzyne
NO2 2. Pinacole-pinacolone rearrangements
The acid catalysed rearrangements of vic. diols (1, 2-diols)
to ketone or aldehyde with elimination of water is known as
NH2 NH2 pinacol-pinacolone rearrangement.
– H – NH2 – Me Me Me O
+ :NH2
H+(Dil.H2SO4)
Me C C Me Me C C Me

– OH OH Me
:NH2 X–
Pinacol Pinacolone
benzyne
– Mechanism of pinacole-pinacolone rearrangements
NH2 NH2
H – NH2 –
+ :NH2 ⊕
HO OH HO OH2
⊕
H

Rearrangements H3C CH3 H3C CH3

H3C CH3 H3C CH3
1. Baeyer-villiger rearrangements
pinacol
yy Baeyer-Villiger rearrangements is an example of the
migration of a group from carbon to electron deficient HO HO ⊕ CH3 O CH3
⊕
oxygen. ⊕ CH3 O CH3 -H CH3
-H2O C
yy The reaction involves oxidation of ketones to esters
H2O H3C
by treatment with paracids such as per benzoic acid, H3C CH3 H 3C CH3 H 3C CH3
pertrifluoroacetic acid etc. pinacalone

O O
3. Beckmann rearrangement
CF3 COOOH + CF3COOH The acid catalysed conversion of ketoxime to N-substituted
R R' R OR' amides is known as Beckmann rearrangement.
KETONE ESTER The reaction is catalysed by acidic reagents such as
H2SO4, SOCl2, P2O5, PCl5, C6H5, SO2Cl.
Cyclic ketone is converted into the lactone with ring
The reaction involves migration of group from carbon
expansion.
to nitrogen.
O O
R OH
H+
CF3 COOOH C N RCONHR1
O
Or
R1
Ketoxime
R1 CONHR
Cyclopentanone Substituted amides
Lactone
3.56  Chapter 2

Mechanism of beckmann rearrangement Application

Synthesis of citric acid, furillic acid.
⊕
OH ⊕ Mechanism of benzillic acid rearrangement
OH2 R′ N C R
N N
H
⊕
H 2O H2O OH–
O O– O–
⊕ HO
R R HO O
R′ N C R R
R′ R R′ R 1 R 2 R
O O R3
⊕ #
OH2 ⊕ OH OH O
-H HO O
R′ R′ R′ R
R H +H
R R R O
N N N
H O O O H
H 3O +
O–H O– O–H H–O O–
The migration of group depends not on migration H–O
aptitude but upon the orientation of the group in relation R R6 R R5 R R 4
H
to –OH group. It is found that the migration group is always O
anti to –OH group. Thus the reaction is stereospecific. H

Application 5. Hofmann rearrangement or Hofmann

Synthesis of isoquinoline and lactams. bromamide reaction
The reaction involves the conversion of an amide to a
4. Benzillic acid rearrangement primary amine (1°) with one carbon less, by the action of
The addition of a strong base to a carbonyl group results alkaline hypohalite (NaOH solution + Br2 or Cl2).
in the formation of an anion. The reversal of the anionic
charge may cause removing of attached group W. RCONH 2 + Br2 + 4 NaOH → RNH 2 + 2 NaBr + Na 2 CO + 2 H 2 O

e.g., Bromine is mostly used in this reaction and the inter-

_ mediate is N-bromamide.
W W O
C O C
Mechanism of Hofmann rearrangement
_
-OH OH O O O
Br2
NaOH
O R NH2 NaOH R NHBr R N–Br
C
H
OH –Br
–
N H 2O N OH – CO2
R C R R–NH2
In 1, 2-diketone the group W may migrate to the adjacent O
electron-deficient carbonyl carbon, forming α-hydroxy acid. O
_
O O O O Application
NaOH Synthesis of amino acid, β-amino pyridine from nicotin-
C6H5 C C C6H5 C6H5 C C amide, urea to hydrazine
OH
C6H5 Some important terminology
Benzil
OH O (a) Cheletropic reaction A retrocycloaddition in which
a small molecule such as CO or SO2 is lost.
C6H5 C C _
ONa+ (b) Concerted reaction Any reaction in which all bond
breaking and bond making occurs in a single step.
C6H5
Sodium salt of
(c) Cycloaddition reaction Any addition reaction that
Benzillic acid results in the formation of a new ring.
 O rganic Chemistry  3.57

(d) Electrocyclic reaction An intramolecular reaction Conrotatory means rotate the bond in same direction.
of a single conjugated pi electron system in which a ring is Disrotatory means rotate the bond in opposite direction.
formed or broken. The electrocyclic reaction is completely stereospecific
and stereo selective.
(e) HOMO Highest Occupied Molecular Orbital. The
highest energy molecular orbital that bears an electron pair.
Woodword–Hoffmann Rules for
(f) LUMO Lowest (energy) Unoccupied Molecular Orbital.
Electrocyclic Reaction
(g) Pericyclic reaction Any reaction that occurs by a
concerted shift of electrons in a cyclic transition state. No of pi electron Types of cleavage Motion

(h) Sigmatropic reaction Any pericyclic reaction in 4n+2 Thermal Disrotatory

which the σ bond at one end of the molecule is broken while
4n+2 Photochemical Conrotatory
a new σ bond is formed at the other end.
4n Thermal Conrotatory
(i) Woodward-Hoffmann rules Orbital combination
rules that define the number of atoms and orbitals involved 4n Photochemical Disrotatory
in pericyclic reactions.
Cycloaddition Reaction Any addition reaction that re-
Pericyclic reaction Any reaction that occurs by a sults in the formation of a new ring. Or two unsaturated
concerted shift of electrons in a cyclic transition state. compounds combine to form a cyclic compound.
Types of pericyclic reactions:
yy Electrocyclic reaction (4+2) Cycloaddition reaction:
yy Cycloaddtion reaction
yy Sigmatropic reaction +
Electrocyclic reaction Under the influence of light/heat,
a conjugated polyene can undergo isomerization to form a Diene Dienophile Adduct
cyclic compound with a single bond between the terminal
carbon of the original conjugated system.
A[2 +2] Cycloaddition Reaction
Or
An intramolecular reaction of a single conjugated
electron system in which a ring is formed or broken.
+ no reaction
E.g., 1, 3, 5 hexatriene to 1, 3 cyclohexadiene

hv
The reverse process can also take place. +
Cyclobutane to 1, 3 cyclobutadiene

Woodword–Hoffmann Rules for

Cycloaddition Reaction
I+j Thermal Cleavage Photochemical
cleavage
Conrotatory
Bonding A C 4n Supra, Antra Supara, Supara
Antra, Supra Antara, antara
A
B C D 4n + 2 Supra, Supra Supra, Antra
D Antara, Antara Antra, Supra
B
3.58  Chapter 2

Name Reaction O O R OH
Aldol
1. Aldol Condensation R′ R R′
R Addition
The two mole aldehyde/ketone with α-hydrogen undergoes R′
self condensation on heating with dilute base to give β-hydroxy O R
aldehydes/ketone is called aldol (aldehyde and alcohol).This −H2O
R R′
reaction is known as aldol condensation reaction, which later ∆
on dehydration to give α, β unsaturated carbonyl compound. R′
Various basic reagents like dilute sodium hydroxide, Reaction Mechanism
aqueous alkali carbonate and alkali metal alkoxide can
The base abstract the acidic proton (α-H) to generate
be used.
resonance stabilized carbanion intermediate and generated
The aldol condensation can be applicable on two identi-
carbanion attack on carbonyl carbon of another mole of
cal/different aldehyde or ketone or an aldehyde and ketone.
aldehyde/ketone which leads to form alkoxide anion. The
latter then takes up a proton to form β-hydroxy aldehydes/
ketone, which later on dehydration to give α, β unsaturated
carbonyl compound.

O O O R OH O

R R′ R R′ R R′ R R′
−H2O
H H H R′ R′
−OH O Beta hydroxy Alfa-Beta
ketone unsaturated
R R′
compound
H H
Step-1

2. Arndt Eistert Reaction

The reaction involves the increase the length of carbon chain by one methylene group in carboxylic acid is known as Arndt
Eistert Reaction.
R-COOH RCH2COOH
RCOOH SOCl2 RCOCl 2CH2N2 RCH2COOH
RCOCHN2 Ag2O RCH=C=O H2O
Carboxylic Acid Carboxylic
Diazoketone ketone
Acid Chloride –CH3Cl, –N2 Acid

Steps of Reaction O−
yy Carboxylic acid converts into the acid chloride by thionyl
O R Cl
chloride. + H2C− N+ N
yy The acid chloride reacts with diazomethane to give H
R Cl N+ N
diazoketone. H
yy The diazoketone catalysed by Ag2O in presence of
water split off nitrogen and rearrange to give ketene in-
termediate.(Other than Ag2O, reacto
yy The ketene then reacts with water, alcohol and amine
O O
to form a higher homologue of carboxylic acid, ester N−
and amide. R N+ R
Reaction Mechanism H
H N+ N
The diazomethane is acylated by the acid chloride to give a H
An α-diazoketone
diazoketone.
 O rganic Chemistry  3.59

The generated diazoketone is rearranged to a ketene. This is called Wolff-rearrangement.

O
Ag+, ∆ or hν Ag+
O N−
R : R CH C O
N+ −N2 Wolff rearrangement
R
H
H
A carbene A ketene

Silver salts like PhCO2Ag, Ag2O along with heat or The ketene is immediately attacked by an appropriate
light catalyze the Wolff rearrangement. Where the configu- nucleophile in the solution.
ration of ‘R’ group during Wolff rearrangement is retained.

H – OH OH A carboxylic acid
R
O
R1 – OH OR1 An ester
R CH C O R
Ketene O
R1 – NH2 NHR1
R An amide

3. Baeyer–Villiger Rearrangement Reaction Mechanism

It is an organic reaction in which a ketone is oxidized to an Initially the peroxy group is added to the carbonyl carbon
ester by treatment with peroxy acids or hydrogen peroxide. It to give a Criegee like intermediate. Then one of the group
is an example of reaction in which migration of alkyl group attached to carbonyl carbon is migrated on to the electron
from carbon to electron deficient oxygen. deficient oxygen atom in a concerted step, which is the rate
determining step.
O O H
RCO3H R1 O H O R″ O
R R1 R O O
solvent O R″
Ketone ester R R′ O R O
R′
O
The reagents can be used in Baeyer villiger oxidation
include: Criegee like intermediate

yy Metachloroperbenzoic acid (MCPBA),

yy Peroxyacetic acid (PAA),
O R″ O
yy Peroxytrifluoroacetic acid (TFPAA)
+ R′
yy Hydrogen peroxide/BF3, R O
OH
yy Caro’s acid buffered with disodium hydrogen phos-
phate The substituents which can stabilize the positive charge
yy Sodium percarbonate (Na2CO3.1.5H2O2), can migrate readily. The migratory aptitude of various
yy Magnesium salt of monoperoxyphthalic acid (MMPP), substituents is approximately:
yy Potassium peroxomonosulphate (potassium caroate) 3o-alkyl > cyclohexyl > 2o- alkyl > benzyl > aryl >
supported on hydrated silica also known as “reincarnated 1 - alkyl > methyl
o

caro’s acid”. The electron withdrawing groups (-I groups) on peroxy

yy Baeyer villager monooxygenase (an enzyme abbreviated acids enhance the rate of the reaction.
as BVMO). As the rearrangement is a concerted process, the con-
3.60  Chapter 2

figuration of the migrating chiral substituent is retained. Reaction Mechanism

Reactive or strained ketones react with peroxy benzoic Ist Step: Reversible nucleophillic attack occurs at carbonyl
acid to form lactones. carbon (–C=O).
O IInd Step: It is a rate determining step in which migration of
O O phenyl ring to carbonyl carbon occurs. (Migration of Ar to
mCPBA, NaHCO3 Carbonyl carbon).
CH2Cl
low yield
−
/O\ HO O
−OH
CF3CO3H, CH2Cl2
Na2HPO4 O
O \O/ \O/
O
70%
magnesium
O monoperphthalate O
hexahydrate
C6H13 (MMPP) O 95%

C6H13
COOH COO−
O− OH
4. Benzilic Acid Rearrangement
The benzilic acid rearrangement is the rearrangement
reaction of benzil with potassium hydroxide to benzilic acid.
5. The Claisen Condensation
The addition of strong base to carbonyl carbon (–C=O) of di
ketone results in formation of an anion and react with acid it The Claisen condensation is a carbon–carbon bond form-
will convert to carboxylic acid. ing reaction that occurs between two esters or one ester
and another carbonyl compound in the presence of a strong
base, (C2H5ONa-Sodium ethoxide) resulting in a β-keto ester
or a β-diketone. This reaction is totally differ to Claisen
O KOH (aq.) rearrangement.
HO
MeOH, reflux OK
O O
NaOR′ −
O O
:

RCH2 C OR′ RCH C OR′

ester enolate
Benzil Potassium salt of O
benzilic acid
RCH2 C OR′
HCl O O

R′O− + OR′ C CH C RCH2

R
β-ketoester
HO
OH
Reaction Mechanism (Nucleophilic Acyl Substitution)
O Step-1: In reaction mechanism the ethoxide act as a
nucleophiles and abstract the acidic proton on methyl group
Benzilic acid of ester and generate a carbanion.
 O rganic Chemistry  3.61

Step-2: Generated carbanion attack on carbonyl carbon For aldehydes with a hydrogen atom alpha to the
of another molecule of ester to generate anion and finally carbonyl, i.e. R2CHCHO, the preferred reaction is an aldol
removal of ethoxy to form a β-keto ester and ethanol. condensation, originating from deprotonation of this
tp hydrogen. This reaction restricts the scope of the Cannizzaro
OEt− reaction.
O O
Abstract of proton Reaction Mechanism
H3C OEt H2C OEt The cannizzaro reaction is initiated by the nucleophilic
arban on narat on attack of a hydroxide ion to the carbonyl carbon of an
Step 2 aldehyde molecule by giving a hydrate anion. This hydrate
anion can be de-protonated to give dianion in a strongly al-
O O O O−
kaline medium.
H2C OEt H3C OEt EtO OEt
CH3 O O− O−
HO− OH−
R R H R H
H OH O−
O O
Hydrate anoin Dianoin
EtO CH3
Hydride (H–) is transferred either from the mono an-
The Claisen condensation is the ester analogue of ionic species or dianionic species onto the carbonyl carbon
the condensation. The most commonly the base would be of another aldehyde molecule. The strong electron donating
the alkoxide, R’O- The reaction involves an ester enolate effect of O– groups facilitates the hydride transfer and drives
reacting with another molecule of the ester. In this reac- the reaction further. This is the rate determining step of the
tion enolates are act as a good nucleophiles and the ester reaction.
carbonyl C are act as a electrophilic. The products of these
reactions are β-ketoesters which are important, useful O− O O O−
synthetic intermediates. R H + R R + R H
6. The Cannizzaro Reaction OH H OH H
The base-induced disproportionation reaction of aldehydes
without α-hydrogens in presence to furnish an alcohol and a Under acidic workup it is converted into carboxylic
carboxylic acid is called Cannizzaro reaction. One molecule acid and alcohol.
of aldehyde is reduced to the corresponding alcohol, while
O− O O O−
a second one is oxidized to the carboxylic acid. The oxida-
tion product is a salt of a carboxylic acid and the reduction R H + R R + R H
product is an alcohol. O− H O− H
2 C6H5CHO + KOH → C6H5CH2OH + C6H5CO2K
acidic workup
O
O OH
O O− H
H R + R H
H OH H
OH
Some examples of cannizaro reaction:
HO− Formaldehyde is disproportionated to formic acid and
OH methyl alcohol in strong alkali.
+ NaOH
O 2 HCHO HCOO−Na+ + CH3OH

OH Benzaldehyde can be converted to benzoic acid and

benzyl alcohol.
3.62  Chapter 2

CHO COO−K+ CH2OH hydrocarbon.

KOH O
+ H H
MeOH Zn (Hg)
R R′ HCl, ∆ R R′
Furfural gives furoic acid and furfuryl alcohol in presence
of strong alkali. Reaction Mechanism
The reduction takes place at the surface of the zinc catalyst.
CHO COOH CH2OH
In this reaction, alcohols are not postulated as intermediates,
1) 33% NaOH + because subjection of the corresponding alcohols to these
2) H3O+ same reaction conditions does not lead to alkanes. In the
O O O
mechanism two time carbanions are generated and accept
the proton and converted into alkane.
7. Crossed Cannizzaro Reaction
When a mixture of formaldehyde and a non enolizable alde- 9. Curtius Rearrangement
hyde is treated with a strong base, the later is preferentially The Curtius Rearrangement involves decomposition of acid
reduced to alcohol while formaldehyde is oxidized to formic azides (R-CON3) to isocyanates (R-N=C=O) and nitrogen
acid. This variant is known as crossed cannizzaro reaction. (N2) in inert solvents like benzene and chloroform is known
E.g. Benzyl alcohol and formic acid are obtained when as the Curtius rearrangement.
a mixture of benzaldehyde and formaldehyde is treated with
alkali. O
∆
CHO R N O
+ HCHO R N3 −N2
1) 33% NaOH 2) H3O+ Acid Azides Isocynate

CH2OH The reaction is a preparative method for isocyanates,

+ HCOOH
ureas, amides, and amines.
The reaction including subsequent reaction with water
which leads to amines - is named the Curtius Reaction. This
The reason may be: the initial nucleophilic addition of
reaction is similar to the Schmidt Reaction with acids, dif-
hydroxide anion is faster on formaldehyde as there are no
fering in that the acyl azide in the present case is prepared
electron donating groups on it. The preferential oxidation
from the acyl halide and an azide salt.
of formaldehyde in crossed Cannizzaro reactions may be
utilized in the quantitative reduction of some aldehydes. O
∆ H2O
R N O R NH2
8. Clemmensen Reduction R N3 −N2 −CO2
The carbonyl groups of aldehydes and ketone (mainly)
undergo reduction to methylene groups with amalgamated Mechanism of the Curtius Rearrangement
zinc and concentrated HCl acid is known as Clemmensen Preparation of azides: Acid azides are commonly prepared
reduction. The Clemmensen Reduction allows the deoxygen- by treating hydrazides in cold, aqueous solution with nitrous
ation of aldehydes or ketones, to produce the corresponding acid.

H⊕ ⊕ Zn .Θ. 2H⊕
..

⊕
R C O R C OH R C OH R C OH

R R R R

H H H H
⊕ −H2O Zn H⊕
..

⊕
R C OH2 R C R C Θ R C H
..

−Zn+2
R R R R
 O rganic Chemistry  3.63

Decomposition to Isocynate and Nitrogen O

O
H H tautomerization R
O R N O N OH
− ∆ H
+ R N O
R N N=N −N2 carbamic acid

Reaction with water to isocynate intermediate generate

the unstable carbamic acid derivative which will undergo O
spontaneous decarboxylation to amine derivative: −
R H H2N−R
N OH 2 R−NH2
H −CO2

O Na+ O O
+ − + − + − + −
R Cl N=N=N −NaCl R N=N=N R N−N=N
−

From Isocyanates intermediate we can synthesize Mechanism of the Diels-Alder Reaction

various amine as well as alkyl substituted urea derivative. Y Y
∆
O +
R
R′OH N OR′
O
∆ H
R N O Stereoselectivity
R N3 −N2
O yy The Diels-Alder reaction is stereospecific with respect
RNH2
R to both the diene and the dienophile.
N NHR yy Addition is syn on both components (bonds form from
H
same species at the same time)
10. Diels-Alder Reaction yy This is illustrated by the examples below:
yy a cis-dienophile gives cis-substituents in the product
It is a type of cyclo addition reaction in which 1,4-addition of
an alkene to conjugated diene to form an adduct of six mem- CO2Me CO2Me
bered ring. The double/triple bond containing group is known
as dienophile. So it is a reaction between diene and dieno-
CO2Me CO2Me
phile to get adduct (product). The reaction initiated thermally
or by lewis acid catalyst with or without the use of solvents. yy a trans-dienophile gives trans-substituents in the product.
Y Y CO2Me CO2Me
∆
+

MeO2C CO2Me
Y Y
∆ yy If the diene substituents have the same stereochemistry
+
(here they are both E), then both end up on the same
face of the product
The [4+2]-cycloaddition of a conjugated diene and
a dienophile (an alkene or alkyne), an electrocyclic re- CO2Me CO2Me
action that involves the 4 π-electrons of the diene and 2
π-electrons of the dienophile. The driving force of the reac-
tion is the formation of new σ-bonds, which are energeti- CO2Me
CO2Me
cally more stable than the π-bonds.
3.64  Chapter 2

yy If the diene substituents have opposite stereochemistry 12. Friedel–Crafts Alkylation

(here one is E and one Z), then they end up on opposite The reaction involves the alkylation of an aromatic ring
faces of the product with an alkyl halide using a strong Lewis acid catalyst. With
anhydrous ferric chloride as a catalyst, the alkyl group
CO2Me CO2Me attaches at the former site of the chloride ion.
Reaction Mechanism
CO2Me Step-1: Formation of carbocation by the reaction between
CO2Me
Alkyl halide and FeCl3.
Srep-2: Electrophilic aromatic substitution reaction takes
11. Friedel-Crafts Acylation
place.
Friedel–Crafts acylation involves the acylation of an ar-
omatic ring with an Acyl chloride halide using a strong R Cl + FeCl3 R+ + FeCl4−
Lewis acid catalyst (AlCl3). This electrophilic aromatic sub- Cl
stitution allows the synthesis of monoacylated products −
from the reaction between arenes and acyl chlorides or Cl Fe Cl
anhydrides.
R+ R H Cl R
O O
Cat
+ −HCl
X R −HX +
R catalyst regenerated
X = Cl or RCOO
Limitations of Friedel-Crafts Alkylation
Reaction Mechanism Carbocation Rearrangement: Only certain alkyl benzenes
Step-1: Formation of electrophile (Acylium Ion) can be made due to the tendency of cations to rearrange.
Step-2: Electrophilic Aromatic substitution reaction-In Compound Limitations: Friedel-Crafts fails when used
which benzene ring’s pi electron act as a neucleophile and with compounds such as nitrobenzene and other strong
attack on acylium ion (electrophile). deactivating systems.
.. ⊕
Polyalkylation: Products of Friedel-Crafts are even more
O O O reactive than starting material. Alkyl groups produced in
.. ⊕ AlCl3 Friedel-Crafts Alkylation are electron-donating substituents
Cl AlCl3 Cl meaning that the products are more susceptible to electro-
acylium philic attack than what we began with.
ion
⊕
Cl 13. Fries Rearrangement
O O O
H The reaction of an aryl ester with a Lewis acid catalyst fol-
−HCl lowed by an aqueous acid to give phenols is known as Fries
rearrangement.
⊕
O

Summary of Limitations of Friedel-Crafts Acylations: O CH3 OH O OH

yy Acylation can only be used to give ketones. This is 1. catalyst:
because HCOCl decomposes to CO and HCl under the AlCl3 CH3
+
reaction conditions. 2. aq. HCl
yy Deactivated benzenes are not reactive to Friedel-Crafts
conditions, the benzene needs to be as or more reactive
than a mono-halobenzene CH3 O
yy The Lewis acid catalyst AlCl3 often complexes to aryl
Reaction Mechanism
amines making them very unreactive.
yy Amines and alcohols can give competing N or O acyla- The reaction is catalyzed by Brønsted or Lewis acids such
tions rather than the require ring acylation as HF, AlCl3, BF3, TiCl4 or SnCl4. The acids are used in
 O rganic Chemistry  3.65

excess of the stoichiometric amount, especially the Lewis molecule is also possible: After hydrolysis, the product
acids, since they form complexes with both the starting is liberated.
materials and products The reaction is ortho,para-selective so that, for
The complex can dissociate to form an acylium example, the site of acylation can be regulated by the
ion. Depending on the solvent, an ion pair can form, choice of temperature. Only sterically unhindered arenes
and the ionic species can react with each other within are suitable substrates, since substituents will interfere
the solvent cage. However, reaction with a more distant with this reaction.

Cl
Cl
Cl OH O
Al + Cl
Al Cl Cl
Cl R
O O
..
..

..
Cl Al
>370K
O R O R Cl O O OH
+
R
RT

R O

Photo-Fries Rearrangement with deactivating substituents on the aromatic group.

Photo-Fries rearrangement exists that involves free radi- Because the yields are low this procedure is not used in
cal reaction mechanism. This reaction is also pos-sible commercial production.

O R O− O O OH
hν − O
+
− R
−

R O

14. Gabriel Synthesis O O

The Gabriel synthesis is named for the German chemist 1. KOH
Siegmund Gabriel. Traditionally, it is a chemical reaction 2. R−X NH
N H R−NH2 +
that convert primary alkyl halides into primary amines 3. NH2NH2 NH
using potassium phthalimide The Gabriel reaction has
since been generalized to include the alkylation of sul- O O
fonamides and imides, followed by deprotection to obtain Pthalimide
amines. The utility of the method is based on the fact that
the alkylation of ammonia is an unselective and inefficient Reaction Mechanism
route to amines in the laboratory The conjugate base of Step-1: Reaction between Pthalimide and Potassium Hy-
ammonia, sodium amide (NaNH2), is more basic than it is droxide removes the N-H proton giving an imide ion, a good
nucleophilic nucleophile to get potassium phthalimide
3.66  Chapter 2

−
O O O O

KOH −
NH N K+ N K+ N K+
−H2O
−
O O O O

Step-2: Attack of imide ion to alkyl halide (Nucleophilic substitution by the imide ion on the alkyl halide generates an
intermediate, N-alkyl phthalimide)
−
O R O O O
X
−
R R R′
R′ + +
N K+ N N N
−KX
R′ R′ R
−
O O O O

Step-3: Clavage by base and hydrazine(Hydrolysis or hydrazinolysis liberates a primary alkyl amine)

3/
O O Na+ 2 Br2 + P PBr3

R R
2 NaOH O−
N + H2N O O
O− 3 + PBr3 3 + H3PO3
R′ R R R
OH Br
O O Na+
O
An acyl bromide can readily exist in the enol form, and
H2NNH2 R this tautomer is rapidly brominated at the α-carbon. The
NH
+ H2N monobrominated compound is much less nucleophilic,
NH so the reaction stops at this stage. This acyl intermediate
R
compound can undergo bromide exchange with unreacted
O carboxylic acid via the anhydride, which allows the cata-
lytic cycle to continue until the conversion is complete.
15. Hell-Volhard-Zelinsky Reaction O PBr3 O OH
Treatment with bromine and a catalytic amount of phospho- R R R
rus leads to the selective α-bromination of carboxylic acids. OH Br Br
O O
Br
R R
P (cat) Br OH
R COOH + Br2 R COOH + HBr
−H3PO3 Br Br

Reaction Mechanism 16. Hofmann Rearrangement

Phosphorus reacts with bromine to give phosphorus tribro- It is organic reaction which convert of a primary amide to
mide, and in the first step this converts the carboxylic acid a primary amine with one carbon atom loss by using of
into an acyl bromide. sodium bromamide (NaOBr) prepared by NaOH and Br2.
 O rganic Chemistry  3.67

Process, and should not be confused with the Hofmann

O Br2 O H2O elimination.
R C R NH2
R NH2 NaOH N −CO2 Reaction Mechanism
Step-1: N-Bromination takes place.
The reaction is named after its discoverer: August Step-2: Formation of Nitrene.
Wilhelm von Hofmann. This reaction is also some- Step-3: Formation of Isocynate intermediate.
times called the Hofmann degradation or the Harmon Step-4: Decarboxylation to yield a 10 amine.

Na⊕ Na Na⊕
⊕
O NaOH O Br Br O OH O
−H2O −NaBr H −H2O
R NH2 R NH R N R N

Br Br

−NaBr

.. O
O H2O. . ..
N C O R N

..
⊕ −
H N OH R

OH isocyanate enitrène
R
(6e-)
H O OH
H R NH2
HN O −CO2

R
acide
carbamique

Application O O O Base like O R′

+ pyridine
yy Aliphatic and Aromatic amides are converted into R R′ HO OH piperidine HO R
aliphatic and aromatic amines, respectively.
yy In the preparations of Anthranilic Acid from Phthalimide Reaction Mechanism
yy Nicotinic acid is converted into 3-Amino pyridine. The initial stage is base catalysed aldol condensation with
subsequent dehydration and decarboxylation yield α, β
17. Knoevenagel Reaction unsaturated carbonyl compound.
The reaction starts with the base catalysed methylene
The condensation of aldehyde/ketone with the compounds proton abstraction from dicarboxylic acid group and generate
having active methylene group in the presence of basic carbanion, the generated carbanion attack on the carbonyl
catalyst to give α, β unsaturated carbonyl compound is called carbon of aldehyde and ketone to β hydroxy formation and
Knoevenagel Reaction.The basic catalyst may be ammonia then subsequently dehydration and decarboxylation yield α,
and its derivative like pyridine or piperidine. β unsaturated carbonyl compound.
3.68  Chapter 2

O O O O Mannich reactions. The reactions are usually carried out in

base
aqueous or alcoholic solutions.
HO OH HO OH
− Reaction Mechanism
H H H
R R′ Step-1: The reaction starts with the formation of an iminium
Base ion from the amine and the formaldehyde.
base abstract O R1
acidic proton attack of carbanionic
carbon to carbonyl H .N.
HO H R1
group of aldehyde/ketone H H
+H+ ⊕ R2 ⊕
O HO N
H H H H R2
O O
R′ O −H+
−CO2 HO OH
H2O H R
⊕ 1 R1
HO H R
1
−H2O H −H2O H
HO R R +H+
. .N . .N N⊕
HO R′
H H H
R2 R2 R2
18. Mannich Reaction
Step-2: The compound with the carbonyl functional group
The Mannich reaction is the aminoalkylation reaction,
(in this case a ketone) can tautomerize to the enol form,
involving the condensation of an enolizable carbonyl com-
after which it can attack the iminium ion.
pound (α-CH acidic compound) with a nonenolizable alde-
⊕
hyde (like formaldehyde) and ammonia; or a primary or a O OH OH
secondary amine to furnish a β-aminocarbonyl compound, +H+ −H+
also known as Mannich base. The Mannich reaction is also R3 R4 R3 R4 R3 R4
considered a condensation reaction. The Mannich reaction
H H H H H
is an example of nucleophilic addition of an amine to a ⊕
carbonyl group followed by dehydration to the Schiff base. OH OH H H
The Schiff base is an electrophile which reacts in the second H
R1 R1
step in a electrophilic addition with a compound containing R3 R4 + N⊕ R3 N
an acidic proton. Instead of formaldehyde, other aliphatic or H R2 H R4
H R2
aromatic aldehydes or ketones can be employed.
−H+
R
R H R
N H + C O + HC O H H
R H R O −H2O R1
R3 N
H R H R4
R R2
R
N C C
R 19. Michael Reaction/Michael Addition
O
H R It is the nucleophilic addition of a carbanion or another nucleo-
The amine used may be ammonia or 1 or 2 aliphatic
o o phile to an α,β-unsaturated carbonyl compound. It belongs
amine. Mostly dimethyl amine is used. The aromatic amines to the larger class of conjugate additions. This is one of the
do not undergo Mannish reaction. 30 amine can not give this most useful methods for the mild formation of C–C bonds.
reaction positive because of lacking of proton. The reaction It is also known as conjugate addition type of reaction.
is usually carried out with the hydrochloride salt of amine. Michael Donors: The Michael donors contain active –
This salt exists in equilibrium with the free amine and proton. CH2 (methylene) group or –CH group. The acidic nature of
Hence the acidic conditions are maintained in Mannich methylene group is enhanced by the electron withdrawing
reaction. The Eschenmoser’s salt, [(CH3)2N=CH2]+I- is groups (EWG) like: keto, cyano, nitro, carboxylic acid
used as a source of formaldehyde and dimethyl amine for derivatice etc.
 O rganic Chemistry  3.69

N O however, and also esters; nitriles; sulfones; and compounds

CN COOEt with activated double bonds can act as Michael acceptors.
EtOOC O C
Vinyl ketones, alkyl acrylates, acrylo nitrile, fumarates etc.,
R
are some examples.
EtOOC EtO C COOEt
O Reaction: In michael addition reaction carbanion
N EtOOC always add to the α,β-unsaturated position of the α,β-
Michael donors Michael acceptors unsaturated carbonyl compound it is known as Michael
addition rule.
Michael Acceptors: Not only α,β-unsaturated ketones,

O O
1. base O
C O C
R′ CR2 H R′ CR2 CH2 CH2 C R
2. H2C CH C R

Reaction Mechanism nucleophilic addition type process with the electrons being
Step 1: In first step of the mechanism, an acid-base reac- pushed through to the electronegative O, giving an interme-
tion. Hydroxide anion act as a base and removes the acidic diate enolate.
α-hydrogen giving the reactive enolate. Step 3: In this step, an acid-base reaction. The enolate
Step 2: In this step, the carbanionic carbon attacks the deprotonates a water molecule recreating hydroxide and the
conjugated ketone at the electrophilic alkene (C=C) in a more favourable carbonyl group.

.. .. −
O O
..
..
..
..

HOH O O

..
..
..
..
.. ..
CH2 CH2 H CH3 CH2
H CH3 CH2 CH2 CH C CH3
. .− H2C C
HO ..
..

.. O H .. H
..
H3C O
..

O O
..
..
..
..

CH3 CH2 CH2 CH2 C CH3

. .−
HO
..

..

20. Oxymercuration/Demercuration on the least substituted carbon kicking off the mercury.
In oxymercuration reaction addition of mercury and Oxymercuration - Demercuration Mechanism follows
hydroxyl group to alkene takes place whie in demercuration, Markovnikov’s Regioselectivity. Markovnikov’s Regiose-
it is the process which involves the removal of mercury using lectivity is the process in which the OH group is attached to
Sodium Hydroboride. of the hydrogens (a hydride) of Boro- the most substituted carbon and the H is attach to the least
hydride will do a backside displacement (SN2 type reaction) substituted carbon.

Oxymercuration/Demercuration Reaction
HgOAc
H H H2O H H NaBH4, NaOH, H2O H H
C C + Hg(OAc)2 C C C C
H3C H H3C H H3C H
OH OH H
3.70  Chapter 2

Reaction Mechanism
Mechanism of Oxymercuration/Demercuration
+
HgOAc

..
HgOAc
H H + H +
H H H
C C + HgOAc C C C C ..
H3C H H3C H H3C H O H

..
HgOAc H
H H
C C HgOAc H H HgOAc
H3C + H H H H H H H
OH C C B C C C C
..

H3C H H3C H H3C H

H .. OH H H OH H OH H
O H
..

21. Reimer-Tiemann Reaction Attack of ring’s electron to dichlorocarbene to form banzal

Formylation of phenol with chloroform in alkaline solution chloride,which later on hydrolysed in presence of alkali to
is known as Reimer-Tiemann reaction.The chemical reaction produce salicylaldehyde.
used for the ortho-formylation of phenols. .−. −
O O O
..

− + CHCl2
OH ONa H H
−
aq + CCl2 CCl2
..

CHCl2
CHCl3 + NaOH

NaOH
Intermediate
− −
O O
NaOH CHO CH(OH)2
−H2O

− +
OH ONa

CHO CHO 22. Vilsmeier-Haack Reaction

H+
The Vilsmeier-Haack reaction is an organic reaction involves
convenient methods for formylation of electron rich aromatic
Salicyldehyde ring to an aryl aldehyde using DMF, an acid chloride, and
aqueous work-up.
Reaction Mechanism Reaction Mechanism
Reimer Tiemenn reaction is an electrophilic substitution The mechanism begins with the reaction of DMF with
reaction. The first step is generation of electrophile (Dichloro the acid chloride to form an iminium salt known as the
carbene). Dichlorocarbene contains a sextet of electrons “Vilsmeier reagent”.
and thus is a strong electrophile. The electron rich aromatic ring then attacks the iminium
ion with loss of aromaticity. A deprotonation step restores
− − −
CHCl3 + OH H2O + CCl3 : CCl2 + Cl aromaticity, which is followed by the release of a chloride
Dichloro carbene ion to form another iminium intermediate. Aqueous work-up
(electrophile) then leads to the aryl aldehyde.
 O rganic Chemistry  3.71

O Cl O
O Me +
P
P N H −
Cl Cl O Cl Me2N
Cl P Cl
Me H Cl
O O Cl
Cl H
Me Me + +
N H N H

Me Me −
Cl Iminium salt
Vilsmeier reagent
H H
O
H + + H
Me2N Cl Me2N Cl Me2NH O H H O

−H+ −Cl− −H+

+ Me2NH
+H2O

23. Wolff-Kishner Reduction O H H

Condensation of the carbonyl compound with hydrazine NH2NH2 . NaOH
forms the hydrazone, and treatment with base induces
−H2O
the reduction of the carbon coupled with oxidation of the
hydrazine to gaseous nitrogen, to yield the corresponding Reaction Mechanism
alkane. The wolff Kishner reduction yield aldehydes and In the mechanism, hydrazine molecule act as a neucleo-
ketones to alkanes. phile and attack on carbonyl carbon of ketone and by loosing

N
−

O N H
−

−OH
H2NNH2
−H2O −H2O

− −
N N
− −
−

N H N H
−
C
− H2O
− −OH

− −−
N N
−
−

N H N
H H
−OH −N2
−H2O
H H H
−
C
− H2O
− −OH
3.72  Chapter 2

of water molecule convert in to imine function group. In sub- Wittig reactions are most commonly used to couple
sequent steps by loosing of two mole water and nitrogen mol- aldehydes and ketones to singly substituted phosphine
ecule via carbanion intermediate it will generate alkane. ylides. With simple ylides this results in almost exclusively
the Z-alkene product.
24. Wittig Reaction
Ylides: It may be defined as the group 15 and 16 of periodic
It is a reaction of an aldehyde or ketone with a triphenyl
table having positive charge directly attached to carbon con-
phosphonium ylide (often called a Wittig reagent) to give an
taining negative charge (extra unshared pair of electron) due
alkene and triphenylphosphine oxide (Ph3PO). The reaction
to pπ-dπ bonding is known as ylides.
also known as Wittig Olefination.

R1 Ph3 P+ R1 R3
C O + C− R3 C C + Ph3P O
R2 R4 R2 R4
Aldehyde/ Phosphorous Alkene Triphenyl
Ketone Ylide Phosphene

Reaction Mechanism: Nucleophilic Addition then Than the extra electron on oxygen atom attack on
Elimination electrodeficient phosphorous atom to form a four-membered
In the mechanism the first step is an addition of the phos- cyclic intermediate, an oxaphosphetane.
phorous ylide to the carbonyl icarbon of Aldehyde/ketone The four membered ring clave (due to ring strain) to
lead to the zwitterionic intermediate betaine. form stable alkene and stable tri phenyl phosphene.

H
+ +
PH3P H PH3P R1
+ −
O H
PH3P R2 Betain Like
R1 − Intermediate
R1 H R2 − R2
H O O

1 2 3 4

PH3P R1
H R1 H
+ Ph3PO
H R2 O R2

7 6 5

25. Wurtz Reaction R–X + 2Na + R–X

Dry Ether
R–R + 2NaX
In this reaction, two alkyl halide molecules are coupled
in presence of sodium metal (Na) in anhydrous ether or Reaction Mechanism
Tetrahydrofuran to form a new carbon carbon bond and thus R X + 2Na R−Na+ + NaX
by giving a symmetrical alkane. The Wurtz reaction must
be performed under anhydrous conditions because the alkyl R−Na+ + R X R R + NaX
free radical formed.
 O rganic Chemistry  3.73

26. Williamson Method Table 2.1B Common Suffix used for Hetero Compounds
In the reaction sodium methoxide act as a base and it is pro- Ring Suffixes for fully Suffixes for fully
ceeds via an SN2 mechanism, in which an alkoxide ion attack size unsaturated saturated
on the alkyl group of alkyl halide and displaces a halogen ion. compounds compounds
CH3–ONa+ + CH3Cl CH3OCH3 + NaCl With N Without With N Without
This method cannot be used with tertiary alkyl halides N N
due to the steric hindrance, SN2 mechanism is not operated. 3 -irine -irene Iridine -irane
An SN1 mechanism is likewise unfavored, because as the
3° carbon attempts to become a carbocation, the hydrogens 4 -ete -ete Etidine -etane
on the adjacent carbons become acidic. Under these
5 -ole -ole Olidine -olane
conditions, the alkoxide ion begins to show less nucleophilic
character and, correspondingly, more basic character. This 6 -ine -in - -ane
basic character leads to an acid-base reaction, which results
in the generation of an elimination product (an alkene). 7 -epine -epin - -epane

8 -ocine ocin -ocane

Nomenclature of Hetrocyclic Compounds
Table 2.1A Prefix for Hetero Atoms Heterocyclic Chemistry: Structure and
Hetero atom Valence Prefix Property
Heterocyclic compounds are organic compounds that
O 2 Oxa contain a ring structure containing atoms in addition
N 3 Aza to carbon, such as sulfur, oxygen or nitrogen, as the het-
eroatom.
S 2 Thia Carbocyclic compounds are organic compounds that
contain ring system made up entirely of carbon atoms.
Se 2 Selena
p-Excessive heterocyclic system have an e– -
Te 2 Tellura
donating heteroatom
P 3 Phospha a heteroatom donates a pair of p-electrons to the p-system
(pyrrole, thiophene, furan)
As 3 Arsa
Five member ring containing O, NH, S are p-Excessive
Si 4 Sila system because of in ring system total six electron are dis-
tributed in only five atom so each atom having a more than
Ge 4 Germa one electron that’s why it is p-Excessive heterocyclic system.

E.g. Pyrrole

H
Pyrrole
more favorable charge- more favorable charge-
separated form separated form
..

..

.. ⊕ ⊕ .. ⊕ ⊕
..

..

N N N .S. .S. .S.

H H H
1 2 3 1 2 3
preference: 2 > 3
3.74  Chapter 2

p-Deficient heterocyclic have an e– - accepting atom is more compare to carbon so electron density is more
heteroatom eg. N or N+ at N atom so each carbon has less one electron that’s why it
Six member ring system has N atom is an example of p- is p-Deficient heterocyclic system.
Deficient heterocyclic system due to electronegativity of N
E.g. Pyridine

.N.
⊕ sites with decreased
= electronic density
.. ⊕ ..
N
.N. .N. .N.

E⊕ E⊕

N
Reactivity order towards electrophilic aromatic sub- yy All are aromatic: Thus, 6p electrons
stitution reaction in pyrrole, pyridine and benzene. yy Sp2 hybridised and planar
yy Lone pair electrons on hetero atom is in p-orbital so it
yy Towards SEAR reaction: Pyrrole > Benzene > Pyridine
is overlaps with the carbon p-orbital
yy Thus, electrophilic aromatic substitution is easy.
Heterocyclic Compounds and Benzene: yy Nucleophilic Substitution is Difficult
A Comparison
yy Both are aromatic because it obeys 4n + 2 p e Hückel’s Pyrrole
rule. H H
4 3
yy Delocalization gives rise to resonance resulting in
stability of compounds, benzene is more stable than 5 2
H .. H
heterocyclic compounds. N N N
yy Both undergo electrophilic as well as nucleophilic H H
1
substitution. H
yy Reactions are regioselective.
Structure of Pyrrole
Five member heterocyclic ring system contains one yy It having a 6p electrons, conjugated system and delo-
hetero atom; Pyrrole, Furan and Thiophene calization of p electron takes place.
yy Overlapping p orbital.
yy In pyrrole, each of the 4-C contribute 1p electron and
N S O the sp2hybdridised nitrogen contributes 2 e that’s why
Thiophene Furan obey the 4n + 2 p e Hückel’s rule.
H yy Lone pair electrons on nitrogen atom are in p-orbital so
Pyrrole it is overlaps with the carbon p-orbital.
yy Electron movement thus results in resonance.
All rings have following characteristics; yy Lone pair on N a part of aromatic sextet.

⊕ ⊕ ⊕
N N N N N+ R.H
H H H H H

Delocalization of electron in pyrrole ring

 O rganic Chemistry  3.75

Basicity and Reactvity of Pyrrole amines. Weakly basic but has greater aromatic char-
yy Lone pair on N-atom is part of aromatic sextet, acter
therefore, less available for bonding with acids. Thus ‡‡ Electron pair NOT available to act as base
Pyrrole - less basic, less Nucleophilic than aliphatic ‡‡ Protonation would destroy aromaticity
Electrophilic aromatic substitution reaction in pyrrole

⊕
E E E −H+
⊕
.Y. H .Y. H Y H .Y. E
3
⊕

2 + Ε⊕
H H E
.Y. E E
Resonance Stabilization of
−H+
⊕ 2-Substitution Intermediate
.Y. Y .Y. is greater than that of the
⊕
3-Substitution Intermediate

In pyrrole, Electrophilic aromatic substitution reaction yy It undergoes Substitution reaction rather than addition
occurs at C-2 position because of it having more no of resonat- reaction.
ing structure compare to attack of electrophile at C-3 of pyrrole yy The molecule has a dipole moment as the e– - distribution
ring, and the positive charge in accommodate in three atom is uneven.
rather than two atom, if attack of electrophile occur at C-3. yy The C-C bond lengths > the C-N bond lengths.
Same like pyrrole in furan and thiophene EAS reaction
takes place on C-2. Basicity of Pyridine
yy Pyridine is more basic than pyrrole because of Kb of
Other Properties of Pyrrole
pyridine is 2.3 × 10–9 and Kb of pyridine is 2.5 × 10–14.
Pyrrole having more boiling point than furan and thiophene, yy Pyridine has more Kb value than pyrrole, so more basic.
because of in pyrrole structure inter molecular hydrogen yy Another reason to more basicity of pyridine is, in pyr-
bonding takes place due to the N-H group in ring system. role the lone pair on N atom is involved in aromaticity
Due to intermolecular H-bonding pyrrole has more b.p than while in pyridine it is not a case.
furan and thiophene.
Electrophilic Aromatic Substitution Reaction in
or or Pyridine
O O S S yy Pyridine is highly deactivating ring because of p-Deficient
+ +
heterocyclic system.
Pyrrole and Furan Is Least Aromatic Than Thiophene yy EAS reaction is least readily than benzene, because of
N is more electronegative than C and is a net acceptor
Because of electronegativity of sulphur in less than O and N
of p-density and so makes the p-cloud less available.
containing heterocycles (Furan and Pyrrole) so it can easily
yy In other words, N deactivates the ring, especially in
delocalized electron in ring system that’s why thiophene is
positions 2 and 4.
more aromatic than pyrrole and furan.
yy So electrophilic aromatic substitution (EAS) reaction
Six Member Heterocyclic System: Pyridine occur at C-3 position.
yy Aromatic yy In the below figure it is clearly shown that in pyridine
yy Pyridine replaces the CH of benzene by a N atom (and the positive charge is generate at C-2 and C-4 that’s
a pair of electrons) why EAS reaction is not possible on it so EAS reaction
yy Flat planner molecule with bond angle 1200 (SP2 Hybrid- is possible on C-3 only because there is no any positive
ization )with similar resonance stabilization energy charge generate on C-3.
yy Lone pair of electrons not involved in aromaticity like yy Nucleophilic Aromatic Substitution reaction occurs at
pyrrole C-2 and C-4 , because of positive charge is generate at
3.76  Chapter 2

C-2 and C-4 so neucleophile can easily attack on elec- Electrophilic Aromatic Substitution in Indole
tron deficient center.
Site with increased electron density
⊕ δ+

⇒
δ+ δ+
⊕ ⊕ δ−
..
.N. .N. .N. .N. N

..
..
Fused Heterocycles N N N
⊕ ⊕
eg. Indole, Benzofuran and Benzothiophene
H H H
Indole
H
E
H E⊕ E⊕
N ⊕ ⊕
N E N N
H
Indole H H H

yy It is a fusion of benzene and pyrrole ring it is also

Quinoline and Isoquinoline
known as banzopyrrole.
yy Aromatic because cyclic conjugated, planar 5 4 5 4

yy Aromatic due to 10 p-electrons and obey Huckel’s rule 6 3 6 3

(8p-electrons from the double bond and 2p-electrons 7 2 7 N2

from the hetero atom) lone pair of e from N delocalizes 8
N 8 1
1
to give the aromatic character.
Quinoline Isoquinoline
yy Benzene part of indole is non-reactive.
yy Electrophilic aromatic substitution occurs at the yy It is also known as benzopyridine: due to fusion of one
3-position because of more canonical structures are benzene and one pyridine ring
form if attack occur at C-3 position compare to attack yy Aromatic because cyclic conjugated, planar
of electrophile at C-2. yy Aromatic due to 10 p-electrons and obey Huckel’s
yy Analogous compounds derived by fusion of a benzene rule.
ring to a pyrrole, furan or thiophene nucleus called yy Electrophilic aromatic substitution occurs at the benzene
indole, benzofuran and benzothiophene. ring giving a mixture of substitution products – C-5 and
yy For all analogues: Rings numbered in a way that it gives C-8
lowest possible number to the heteroatom yy Nucleophilic aromatic substitution occurs at the pyridine
ring giving substitution at C-2 and C-4 for quinoline
4 3
and C-1 for isoquinoline
5
yy Electrophilic subsitution in quinoline and isoquinoline:
.. 2
.. ..
6 N1 O. . S. . explanation
7 H yy Attack at C5 and C8; Compare two scenarios: attack at
indole en o n en o io ene C5 and C6

⊕
5-Attack E E H E H E H
⊕
⊕

N N N N
H⊕ H⊕ ⊕ H⊕ H⊕

These are more stable

 O rganic Chemistry  3.77

6-Attack
⊕
E E E E
H ⊕ H H

N⊕ N⊕ ⊕ N ⊕ N
⊕
H H H H

Particularly unstable-+ive charge on +ive C

Carbon atom and N-atom both
having positive charge so highly unstable

Intermediates for substitution at C-5 and C-8 more reso- Replacing a CH group in the pyrrole ring with a
nance stabilized than attack at C-6 because if we look at the nitrogen atom can give rise to two compounds: pyrazole
structure than both C and N atoms having positive charge on it. and imdazole.
Nucleophilic substitution reaction occurs at C-2 and Only one nitrogen atom can contribute two electrons to
C-4 position same like pyridine. the aromatic sextet. It is the nitrogen with the hydrogen and
yy Explain by looking at the anionic intermediates it is described as pyrrole-like nitrogen. While the second
yy Hydride can be displaced at the 2- and 4- positions nitrogen (2nd position) which has no hydrogen is described as
yy Stable intermediate from attack at position 2- and 4-, pyridine-like.
negative charge on nitrogen atom The lone pair on pyrrole-like nitrogen is delocalized round
R R the ring while that on the pyridine-like nitrogen is localized in
sp2 orbital on nitrogen. Thus these compounds have properties
intermediate between those of pyrrole and pyridine.
Nu Nu
N N H Physical Properties of Imidazole and Pyrazole
Solubility
Purines and Pyrimidines yy Imidazole and pyrazole are water soluble solids and
H insoluble in aprotic solvent.
yy They have very much higher boiling point:256 and
N N 187 °C respectively, this difference is due to imidazole
N
has an extensive hydrogen bonding than pyrazole thus
N N imidazole molecules can exist as oligommers, conse-
N
Pyrimidine P rine quently more energy is required to break these bonds to
bring the molecules from one phase to another.
yy Most important heterocyclic ring system from biological yy On the other hand pyrazole molecules can form dimers
point of view, nucleic acids only thus lesser energy is required to break these
yy Pyrimidine: Contains 2 pyridine-like N in a 6-membered molecules.
aromatic system yy N-subsituted imidazole and pyrazole have lower boiling
yy Purine: Contains 4 N in a fused ring system, 3 of these N and melting points than the unsubstituted compounds
are basic and pyridine-like with their l.p. e in sp2 orbitals due to inability to form H-bonds.
in the plane of the ring while remaining 1 N is nonbasic
and pyrrole-like with l.p. e as part of aromatic p e system. Basicity
Imidazole is a stronger base than pyrazole or pyridine and
Diazole: Pyrazole and Imidazole
of course pyrrole. Thus imidazole and pyrazole are more
N stabilized than pyrrole in acidic medium.
N
N N Basicity order: Imidazole > Pyrazole > Pyridine >
Pyrrole
H H
Pyrazole Imidazole This can be explained as follows:
3.78  Chapter 2

Pyrrole is not basic because the lone pair on the only nitrogen is needed to complete the aromatic pi system and
protonation if occurs at all occurs at carbon rather than on nitrogen and the resulting cation is not aromatic.

H this lone pair is in a

.. H A + p orbital contributing
N N H
N N H to the 6π electrons
H in the aromatic ring
H H
pyrrole
aromatic pyrrole nonaromatic cation

Both of imidazole and pyrazole have two nitrogen than imidazoles. This difference is due to the fact that the
atoms and on protonation the positive charge can be delocal- positive charge in pyarzolium ion is less delocalized than in
ized over them. However, pyrazoles are much weaker bases the imidazolium ion.

this lone pair is in a

this lone pair is in an sp2 p orbital contributing
orbital and is not involved N N H to the 6π electrons N NH HN ⊕ NH
with the aromaticity of the ring. in the aromatic ring
Protonation occurs here imidazole imidazolium
the aromaticity of imidazole

Effect of substitution on basicity electrophilic aromatic substitution due to the inductive

yy Generally E.D.G groups on the ring increase the basicity electron-withdrawing effect of the second heteroatom.
while E.W.G. decrease it. yy However, they are more reactive than pyridine due to
yy N-methyl imidazole is more basic than imidazole itself. delocalization of the lone pair of electrons on the N-
yy However, N-methylpyrazole is less basic than pyrazole atom make the C- atoms bear negative charges while
which can be attributed to steric hindrance effect which in pyridine the N- atom exerts inductive electron with-
cause difficulty in accessing the lone pair of electron drawing effect only.
by the proton. yy The orientation in pyrazole, is at the 4-position due to
yy Imidazoles unsubstituted in the 1-position are weak acids. the deactivation effect of the pyridine-like nitrogen
Its acidity is greater than that pyrrole and equals that yy The orientation in imidazole, is at 5-position, due to the
of pyrazole. additional N-atom deactivates its vicinal positions
yy Diazoles are less reactive than 5-membered heterocy- yy However, if the position 5 is occupied the electrophiles
cles with one heteroatom (pyrrole and its analogs) in will be directed to 4-position.

Multiple Choice Questions

1. Which of the following intermediates has a positive (a) Carbocation (b) Carbanion
charge? (c) Carbene (d) Nitrene
(a) Carbocation (b) Carbanion
(c) Carbene 4. Which of the following groups comes under EDG?
(d) Nitrene
(a) Nitro (b) Chloro
2. Which of the following intermediates has a negative
charge? (c) Amino (d) Aldehyde
(a) Carbocation (b) Carbanion 5. Which of the following groups comes under EWG?
(c) Carbene (d) Nitrene
(a) Nitro (b) Methyl
3. Which of the following is a nitrogen analog of carbene? (c) Amino (d) Anilide
 O rganic Chemistry  3.79

6. Which of the following rules is not used to determine 16. In which of the following structures, geometrical isomer
the electronic configuration? is not possible?
(a) Pauli’s (b) Saytzeff (a) Ethene (b) Propene
(c) Hund’s (d) Aufbau (c) 2-Pentene (d) a and b
7. All statements are correct for SN-1 reaction, except 17. Find out the absolute configuration of following
(a) Follows first-order kinetic structure:
(b) Rearrangement is possible 1. 1. CH2COOH1. 2COOH
1. CH 2. Cl2. 2. Cl
2. 2COOH
CH 3.
3.
Cl 3. COOH
3. COOHCOOH
(c) Inversion of configuration takes place
(d) Two-step reaction I CN
I I
CN CN I Br
I I
Br OHC
Br CHOHC
OHC 3COOH CH3COOH
CH3COOH
H H H H H H H H H
8. All statements are correct for SN-2 reaction, except
(a) Follows second-order kinetic (a) 1-S,2-R,3-S (b) 1-S,2-R,3-S
(b) Rearrangement is possible (c) 1-R,2-R,3-S (d) 1-S,2-S,3-S
(c) Inversion of configuration takes place 18. How many isomers are present in the structure of glucose?
(d) Single step reaction
(a) 12 (b) 16
9. All statements are correct for E-2 reaction, except (c) 10 (d) 4
(a) Follows first-order kinetic
19. Which form is more stable in conformation of n-butane?
(b) Reactivity order is 3° > 2° > 1°
(c) Always β-hydrogen abstracted (a) Skew staggered
(d) Single-step reaction (b) Skew eclipsed
(c) Totally staggered (anti)
10. Orientation of elimination reaction follows …
(d) Fully eclipsed
(a) Markoniov’s rule (b) Saytzeff rule
20. All statements are correct for enantiomer, except
(c) Micheal addition (d) Hoffmann rule
(a) It must be a chiral
11. Orientation of addition reaction follows …
(b) Not superimposable on its mirror image
(a) Markoniov’s rule (c) Gives optical activity
(b) Saytzeff rule (d) All enantiomer are optically active
(c) Micheal addition
21. Which of the following bonds is the weakest bond?
(d) a and c
(a) Coordinate bond
12. In polar aprotic solvent the nucleophilicity of (b) Covalent bond
halides is
(c) Van der Walls’ force
(a) F– > Cl– > Br– > I– (d) H-Bond
(b) F– < Cl– < Br– < I
22. Compound A is highly volatile and insoluble in water
(c) F– = Cl– = Br– = I–
so bonding in A is
(d) None of the above
(a) Coordinate bond (b) Ionic bond
13. In polar protic solvent the basicity of halides is (c) Covalent bond (d) Polar covalent bond
(a) F– > Cl– > Br– > I– 23. Which substance has a dipole moment?
(b) F– < Cl– < Br– < I– (a) CCl4 (b) CH2Cl2
(c) F– = Cl– = Br– = I– (c) C2Cl2 (d) C2Cl4
(d) None of the above
24. Which form is more stable in conformation of
14. Which of the following is a polar aprotic solvent? cyclohexane?
(a) DMF (b) Etahanol (a) Chair (b) Boat
(c) Water (d) All (c) Twist boat (d) Half chair
15. Which of the following is a polar protic solvent? 25. Which of the following has a zero dipole moment?
(a) Acetic acid (b) Etahanol (a) CO (b) SO2
(c) Water (d) All (c) SO3 (d) H2O
3.80  Chapter 2

26. Mixture of amino acid can be separated by 34. The separation of racemic mixture into the pure enan-
(a) Sublimation (b) Chromatography tiomer is
(c) Distillation (d) None (a) Racemization
27. Spraying reagent used in detection of amino acid is (b) Resolution
(c) Isomerization
(a) Iodine solution (b) Benedict reagent
(d) All of the above
(c) Molisch reagent (d) Ninhydrin reagent
28. C3H6 + H2 = C3H8 The above reaction is an example of? 35. A meso compound
(a) Substitution (b) Addition (a) Is an achiral molecule that contains chirality centre
(c) Polymerization (d) Esterification (b) Contains plane of symmetry
(c) Is optically inactive
29. The number of optically active isomers of tartaric
(d) Is characterized by all of these
acid is
(a) 2 (b) 3 36. D and L are a pair of _____________ configuration.
(c) 4 (d) 5 (a) Relative (b) Absolute
30. The chiral carbon in the following compound has (c) Cis-trans (d) None of above
_____________ configuration 37. R and S are a pair of _____________ configuration.
CHO (a) Relative (b) Absolute
CH2CH3 CH2CH2CH3 (c) E-Z (d) None of above
H 38. d and l are a pair of _____________ configuration.
(a) R (b) S (a) Relative (b) Absolute
(c) a and b (d) None (c) E-Z (d) Optical isomer
31. Which types of conformation are shown by A and B? 39. A bond in which atoms share a pair of electrons is
(a) Ionic bond
(b) Covalent bond
(c) Electrovalent bond
(d) Binary compound bond
A B 40. Which statement best explains why carbon tetrachloride
(a) A is eclipsed and B is staggered (CCl4) is non-polar?
(b) B is eclipsed and A is staggered (a) Each carbon chloride bond is polar
(c) Both are in staggered form (b) Carbon and chlorine are both nonmetals
(d) Both are in eclipsed form (c) Carbon tetrachloride is an organic compound
32. Tautomerism is not exhibited by (d) The carbon tetrachloride molecule is symmetrical.
41. ________ is a heterocyclic compound with three-
O CH = NOH O O
membered ring.
(a) Furans (b) Pyrroles
(a) () () ()
(c) Ethylene oxide (d) Cyclo propane
O O 42. _____________ is a heterocyclic compound with
O five-membered ring.
33. The term atropiisomerism is used for isomers (a) Aziridine (b) Azoletine
(c) Azole (d) Azoline
(a) That can be interconverted by rotation about single
bonds 43. 1,2-postion with six member heterocyclic contain two
(b) That are geometrical isomers nitrogen atom is called
(c) That are optical isomers (a) Pyrimidine (b) Pyridine
(d) That are enantiomers (c) Pyrazine (d) Pyridazine
 O rganic Chemistry  3.81

44. 1,3-postion with six member heterocyclic contain two 54. The oxidation of ethyl alcohol results in the forma-
nitrogen atom is called tion of
(a) Pyrimidine (b) Pyridine (a) Formic acid (b) Propyl alcohol
(c) Pyrazine (d) Piperazine (c) Acetic acid (d) Acetone
45. A gas whose molecule is monatomic is 55. The process by which heated iodine crystals form a
vapour without passing through the liquid state is
(a) Oxygen (b) Helium
(c) Nitrogen (d) Chlorine (a) Evaporation (b) Sublimation
(c) Condensation (d) Distillation
46. A molecule of ethane is similar to a molecule of meth-
ane in that they both have the same 56. Which compound is a trihydroxy alcohol?
(a) Structural formula (a) Ethylene glycol (b) Glycerol
(b) Molecular formula (c) Butanol (d) Isopropyl alcohol
(c) Number of carbon atoms 57. Trichloromethane is another name for
(d) Number of hydrogen atoms (a) Methyl chloride
47. A reaction between an acid and an alcohol produces an (b) Chloroform
ester and (c) Carbon tetrachloride
(a) Carbon dioxide (b) Water (d) Freon
(c) Glycerol (d) Ethanol 58. The general formula RCOOR’ represents a(n)
48. Removal of hydrogen from alkene produces a/an (a) Ester (b) Ketone
(a) Alcohol (b) Alkane (c) Aldehyde (d) Ether
(c) Alkyne (d) Protein 59. Diels Alder comes under _____________ reaction
49. Secondary alcohols (a) Cycloaddition
(a) Have two hydroxy groups on the carbon chain (b) Electrocyclic
(b) Have a –OH group bonded to a carbon that is (c) Sigmatropic
bonded to two other carbon atoms. (d) All of above
(c) Have hydroxy groups at both ends of the carbon chain 60. Which of the following is/are pericyclic reaction?
(d) Have a hydroxy group on the last carbon of the (a) Cycloaddition
hydrocarbon chain. (b) Electrocyclic
50. Substances having the same molecular formulas but (c) Sigmatropic
different structural formulas are known as (d) All of above
(a) Dimers (b) Isomers
61. As per Woodward–Hoffman rules for electrocyclic
(c) Polymers (d) Allotropes reaction, for 4n system under thermal condition rotation
51. The carbon-carbon bond length in benzene is direction for bonding is _____________
(a) Longer than a double bond (a) Conrotation (b) Disrotation
(b) Shorter than a single bond (c) a and b (d) None of the above
(c) Both a and b
62. As per Woodward–Hoffman rules for electrocyclic
(d) Neither a nor b reaction, for 4n system under photochemical condition
52. A compound has the empirical formula CH2O and rotation direction for bonding is _____________
the molecular mass is 180 grams per mole. What is (a) Conrotation (b) Disrotation
its molecular formula? (c) a and b (d) None of above
(a) CH8O10 (b) C12H4O2
63. As per Woodward–Hoffman rules for electrocyclic
(c) C6H12O6 (d) C12H24O12 reaction, for 4n + 2 system under photochemical con-
53. The highest electronegativity atom from following is dition rotation direction for bonding is ____________
(a) Fluorine (b) Neon (a) Conrotation (b) Disrotation
(c) Lithium (d) Cesium (c) a and b (d) None of above
3.82  Chapter 2

64. Anchimeric assistance is associated with __________ 73. SN1 reaction fast with
(a) Neighbouring group mechanism (a) 1° Alkyl halide (b) 2° Alkyl halide
(b) SN2 mechanism (c) 3° Alkyl halide (d) All
(c) SN1 mechanism 74. Which of the following reagent is used in oppenauer
(d) Elimination mechanism oxidation?
65. Which of the following is a homogeneous catalyst? (a) Aluminiun t-butoxide
(a) Nickel (b) Platinum (b) Liithium aluminium hydride
(c) Palladium (d) Wilkinson catalyst (c) Sodium borohydride
(d) Sodium hydroxide
65. In branching at α and β position of alkyl halide follow-
ing sentence is true. 75. Which of the following is a correct formula of Grignard
(a) Rate of SN1 and SN2 reaction is increased reagent?
(b) Rate of SN1 reaction is increased (a) RMgX (b) RMg2X
(c) Rate of SN2 reaction is increased (c) RMgX2 (d) All
(d) None of the above 76. Bond angle in case of SP2 hybridization is _________
66. Betain Shape intermediate is generated in __________ (a) 120 (b) 180
reaction (c) 90 (d) 109.5
(a) Wittig (b) Aldol 77. Shape in case of SP3 hybridization is __________
(c) Hofmann (d) None of the above (a) Tetragonal (b) Trigonal
67. Dichloro carbene as an intermediate is generated in (c) Linear (d) Octagonal
_____________ reaction 78. Bond angle in case of water molecule is _________
(a) Wittig (b) Aldol (a) 105 (b) 120
(c) Hofmann (d) Reimer Tiemann (c) 107 (d) 109.5
68. In Hoffmann rearrangement 79. Hybridization is case of water molecule is _________
(a) Nitrene is an intermediate (a) SP2 (b) SP3
(b) Nucleophillic rearrangement of alkyl group takes (c) SP and SP3 (d) SP
place
(c) Products have one carbon less compared to starting 80. Bond angle in case of ammonia molecule is ________
material (a) 105 (b) 120
(d) All are true (c) 107 (d) 109.5
69. Correct thing in case of crossed aldol condensation is 81. All statements are true in case of electronegativity,
__________ except
(a) Both aldehyde/ketone have an α hydrogen (a) From downward to upward in periodic table elec-
(b) Only one aldehyde/ketone has an α hydrogen tronegativity is increased
(c) It does not have α hydrogen (b) From right to left to periodic table electronegativity is
(d) All of the above increased
70. Which of the following is an oxidizing reagent? (c) From left to right in periodic table electronegativity
is increased
(a) KMnO4 (b) Concentrated HNO3
(d) From upward to downward in periodic table elec-
(c) H2O2 (d) All
tronegativity is decreased
71. Which of the following is a reducing reagent? 82. Which of the following is a correct order of electro-
(a) H2/Ni (b) Fe/HCl negativity?
(c) NaBH3 (d) All (a) F > O > N > C (b) F > Cl > Br > I
72. SN2 reaction fast with (c) F > O > N > S (d) All of the above
(a) 1° Alkyl halide (b) 2° Alkyl halide 83. Dipole moment of molecule is measured in ________
(c) 3° Alkyl halide (d) All unit.
 O rganic Chemistry  3.83

(a) Debye (b) Dyne/Cm (a) Heat of hydrogenation and combustion are lower
(c) Dyne (d) Poise than expected value
84. Following have zero dipole moment except (b) Benzene undergoes addition reaction rather than
substitution reaction
(a) H2 (b) CH4
(c) All C=C in benzene have an intermediate bond
(c) CCl4 (d) CH3Cl
length between C–C and C=C
85. Which of the following is not inter molecular forces? (d) Benzene follows Huckel’s rule
(a) Repulsion and attraction 94. Which of the following is ortho-para directing group?
(b) Dipole–dipole interaction
(a) Nitro (b) Ester
(c) Van der Waals forces (c) Methyl (d) 4° ammonium compound
(d) H-bonding
95. Which of the following is a meta directing group?
86. Bredt’s rule is applicable for __________
(a) Chloro
(a) Aliphatic system
(b) Cyno
(b) Heterocyclic system
(c) Anilide
(c) Bridgehead bicyclic system
(d) Alkoxy
(d) Spirocyclic system
96. Which of the following is not aromatic?
87. Cahn Ingold and prologue rule is used for determining
(a) Cyclopentadiene anion
________
(b) Cyclopentadine
(a) The R and S configuration (c) Anthracene
(b) The D and L configuration (d) Napthalene
(c) The Cis and Trans configuration
(d) The E and Z configuration 97. The migration of a group from carbon to electron-
deficient oxygen is an example of _____________
88. Which of the following is an example of cyclic ether? reaction.
(a) Oxiran (b) Epoxide (a) Baeyer–Villiger rearrangements
(c) Cyclobutane (d) a and b (b) Pinacole–Pinacolone rearrangements
89. The nomenclature of geometrical isomer is done by (c) Beckmann rearrangement
(a) E and Z configuration (d) Benzillic acid rearrangement
(b) Cis- and trans configuration 98. The acid catalysed conversion of ketoxime to
(c) All of the above N-substituted amides is known as ___________
(d) None (a) Baeyer–Villiger rearrangements
90. Which of the following is a type of structural isomer? (b) Pinacole–Pinacolone rearrangements
(a) Tautomerism (c) Beckmann rearrangement
(b) Metamerism (d) Benzillic acid rearrangement
(c) Functional isomerism 99. Which reaction involves migration of group from car-
(d) All of the above bon to nitrogen?
91. Higher ring strain is associated with (a) Baeyer–Villiger rearrangements
(a) Cyclopropane (b) Cyclobutane (b) Pinacole–Pinacolone rearrangements
(c) Cyclopentane (d) Cyclohexane (c) Beckmann rearrangement
92. Staggered and eclipsed is a type of (d) Benzillic acid rearrangement
(a) Conformational isomer 100. Which reaction involves the conversion of an amide to
(b) Geometrical isomer a primary amine (1°) with one carbon less?
(c) Enantiomer (a) Baeyer–Villiger rearrangements
(d) Optical isomer (b) Pinacole–Pinacolone rearrangements
93. Which of the following statement is not correct for (c) Beckmann rearrangement
benzene? (d) Hofmann rearrangement
3.84  Chapter 2

101. Hexane and 3-methylpentane are examples of: (a) Hinsberg’s test (b) Carboline test
(a) Enantiomers (c) Osazone test (d) Hydroxylamine test
(b) Stereoisomers 111. “Only two electrons can occupy any atomic orbital”
(c) Diastereomers Which principle is this?
(d) Constitutional isomers (a) Aufbau’s principle
102. A reaction between an acid and an alcohol produces an (b) Pauli’s principle
ester and? (c) Hund’s principle
(a) Water (b) Carbon dioxide (d) None of the above
(c) Ethanol (d) Oxygen 112. The compound that is not a Lewis acid is:
103. The quantity of heat evolved when one molecule of (a) BF3 (b) AICI3
hydrogen is burned to carbon dioxide and water is called (c) BeCI2 (d) SnCl4
(a) Heat of sublimation
113. Which aldehyde undergoes Cannizzaro reaction?
(b) Enthalpy
(c) Heat of combustion (a) Acetaldehyde (b) Benzaldehyde
(d) Entropy (c) Formaldehyde (d) Propionaldehyde

104. Which of the following reagent is used for diazotization? 114. What is the degree of unsaturation of compound with
formula C3H6O2?
(a) NaNO2 + dilute HCI
(b) KNO3 + H2SO4 (a) 0 (b) 3
(c) NaNO2 + K2SO4 (c) 1 (d) 2
(d) NaNO3 + Dilute HCI 115. In nitration of the aromatic compounds the nitrating
105. What is the bond angle in SP hybridization? species is
(a) 109.5 (b) 120 (a) NO– (b) NO+2
(c) 180 (d) 119.5 (c) NO3 (d) NO
106. Which of the following is not having dipole moment? 116. The pyrolysis of alkanes present in petroleum is known
(a) Methyl chloride (b) Water as?
(c) Ammonia (d) Methane (a) Thermal cracking
(b) Cracking
107. When you treat phenol with dilute HNO3 at 20°C, you
(c) Combustion
will get _____________
(d) None of the above
(a) Orthonitro phenol
(b) Paranitro phenol 117. Bayer’s reagent is?
(c) Mixture of ortho and para nitro phenol (a) KMnO4 (b) K2Cr2O7
(d) Meta nitro phenol (c) NaNO2 + HCl (d) HNO3 15: 2Cr2O7
108. What is the reactivity order of SN2 reaction? 118. Which of the following would not be a reasonable neu-
(a) Primary > secondary > tertiary cleophile in a SN2 reaction?
(b) Secondary > primary > tertiary (a) NH3 (b) NC–
(c) Tertiary > secondary > primary (c) H2O (d) HO–
(d) Tertiary > secondary > primary > methane 119. How many isomers does above compound will have?
109. What is the reactivity order of El reaction? H
(a) Primary > secondary > tertiary > methane H3C COOH
(b) Secondary > primary > tertiary
(c) Primary > secondary > tertiary
(d) Tertiary > secondary > primary
110. Which test is used to differentiate primary, secondary
and tertiary amines? CH3
 O rganic Chemistry  3.85

(a) 4 (b) 1 123. What is the total number of pi bonds found in the fol-
(c) 3 (d) 2 lowing compound?
120. Different arrangements of atoms that can be converted
into one another by rotation about single bonds are?
H
(a) Enantiomer (b) Diastereomer NO2
(c) Conformations (d) Configuration
(a) 1
121. Dipole movement between two atoms is mainly
(b) 2
(a) Because of sharing of bonding electron pairs not equal
(c) 3
(b) Due to steric hindrance
(d) 4
(c) Because of change in polyhedral bonds
(d) None of the above 124. Which of the functional groups on the following mol-
ecule are susceptible to nucleophilic attack?
122. Which Newman projection shows the most stable con-
formation of the following compound? Br b O
(a) H (b) H
(a) H (b) H a c
Br H H H
Br H H H
(a) a
Cl Br Cl Br (b) b
Cl Br Cl Br (c) c
H Br
H Br
(d) a and c
(c) H Br (d) H 125. Each member of the alkane series differs from the
(c) H Br (d) H preceding member by one additional carbon atom
H Br and
H Br
(a) 1 hydrogen atom
H Br (b) 2 hydrogen atoms
HCl Br
Br Cl Br
(c) 3 hydrogen atoms
Cl Br Cl Br
H (d) 4 hydrogen atoms
H

Answer Keys
1. (a) 2. (b) 3. (d) 4. (c) 5. (a) 6. (b) 7. (c) 8. (b) 9. (a) 10. (b)
11. (a) 12. (a) 13. (a) 14. (a) 15. (d) 16. (d) 17. (d) 18. (b) 19. (c) 20. (d)
21. (c) 22. (c) 23. (b) 24. (a) 25. (c) 26. (b) 27. (d) 28. (b) 29. (a) 30. (a)
31. (b) 32. (a) 33. (a) 34. (b) 35. (d) 36. (a) 37. (b) 38. (d) 39. (b) 40. (d)
41. (c) 42. (c) 43. (d) 44. (a) 45. (b) 46. (d) 47. (b) 48. (c) 49. (b) 50. (b)
51. (c) 52. (c) 53. (a) 54. (c) 55. (b) 56. (b) 57. (b) 58. (a) 59. (a) 60. (d)
61. (a) 62. (b) 63. (a) 64. (a) 65. (d) 66. (b) 67. (a) 68. (d) 69. (b) 70. (d)
71. (b) 72. (a) 73. (c) 74. (a) 75. (a) 76. (a) 77. (a) 78. (a) 79. (b) 80. (c)
81. (b) 82. (d) 83. (a) 84. (d) 85. (a) 86. (c) 87. (a) 88. (a) 89. (d) 90. (c)
91. (d) 92. (a) 93. (b) 94. (c) 95. (b) 96. (b) 97. (a) 98. (c) 99. (c) 100. (d)
101. (d) 102. (a) 103. (c) 104. (a) 105. (c) 106. (d) 107. (c) 108. (a) 109. (d) 110. (a)
111. (b) 112. (c) 113. (b) 114. (c) 115. (b) 116. (b) 117. (a) 118. (c) 119. (b) 120. (c)
121. (a) 122. (a) 123. (c) 124. (d) 125. (b)
 chapter 3
Analytical Chemistry

Pharmaceutical Analysis UV-Visible Spectroscopy (Electronic

Electromagnetic Radiation Spectroscopy)
Electromagnetic (EM) radiation is a periodically changing Basic principle Valence shell electronic transition.
or oscillating electric field propagating in a certain direction Graph Plotted between absorbance and wavelength.
with a magnetic field oscillating at the same frequency but
perpendicular to the electric field.
EM radiation may be considered as a travelling wave
or as a stream of massless elementary particles, often called
photons. Antibonding σ∗
n σ* σ σ*
Characteristics of wave Antibonding π∗
Energy

n π* π π*
yy Wavelength λ (the length of one wave) e e Non-bonding η
‡‡ Expressed in nm/ A°/µm n σ*
yy Frequency ν (the number of waves per unit time) e Bonding π
‡‡ Expressed in cycle per second (cps)/Hertz/Fresnel
‡‡ V = c/λ = c * wave number
e Bonding σ
yy Wave number k (the number of waves per unit length)
‡‡ Wave number =1/λ
‡‡ Expressed in cm-1 or Kaiser Energy value order for transition
Max-Plank Equation n → π* < n → σ* < π → π * < σ → σ*
E = h v = h c/λ Transition probablity
Where E is energy of photon 1. Allowed–extinction coefficient value 104 or greater
ν is frequency of EM radiation = c/λ hence v is inversly 2. Forbidden–extinction coefficient value 102 or less
proportional to λ
h is Plank constant (6.6 × 10–27 erg-sec) Absorption band
c is velocity of light 1. K band–due to π → π* transition
λ is wavelength of EM radiation 2. R band–due to n → π* transition

Cut-off wavelength Above which solvent behaves as transparent

Methanol 210 nm Hexane 199 nm Water 190 Diethyl ether 205 nm

nm

Ethanol 207 nm Benzene 280 nm Heptane 200 nm THF 220 nm

Chloroform 247 nm Carbon tetrachloride 257 nm Acetone 331 nm Dichloromethane 233 nm

 Analytical Chemistry  3.87

Instrumentation 2. Provides narrow effective bandwidth with increased

1. Sources (UV and visible) output.
2. Wavelength selector (monochromator)
3. Sample containers Construction of monochromator
4. Detector 1. Entrance slit
5. Signal processor and readout 2. Collimating mirror (Provide parallel beam of radiation
to prism or grating)
Monochromator Reference Detector 3. Diffracting grating
Ratio Output 4. Focussing mirror
Sample Detector
5. Exit slit

yy Most widely used radiation source in UV deuterium Basically, monochromator converts polychromatic
discharge lamp and in visible tungsten halogen lamp. light (EM radiation of more than one wavelength) into
yy Most widely used detector in UV-visible spectroscopy monochromatic light (EM radiation of single wavelength).
is PMT (photo multiplier tube).
Interferometer
Instead of filtering or dispersing the EM radiation, it si-
multaneously allows source radiation of all wavelengths to
reach detector.
Dynode Construction of interferometer
1. Fixed mirror
2. Moving mirror
Grill
3. Beam splitter (Transmit half of the radiation to fixed
Anode Incident mirror and half of the radiation (which are reflected)
radiation to movable mirror). It is a semi reflecting device and
Photoemissive made up of silicon or germanium coated on metal
cathode halide plate.
Isobestic point common point to every absorption curve
Figure 3.1 UV-Visible Spectroscopy
which is obtained in the spectrum of compound taken at
Wavelength selector different pH.
yy It should provide narrow band of radiation and maxi-
mum throughput. IR Spectroscopy
yy Wavelength isolation can be done using filter, mono-
Basic principle Vibrational level changes
chromator and interferometer.
Graph Plotted between % transmittance and wave number.
Filter A wavelength selector that uses either absorption,
or constructive and destructive interference to control range
of selected wavelength. Selection rule in IR
A. Absorption Filter Narrow effective bandwidth 30 to Only those compounds are IR active which show change in
250 nm and Maximum throughput 10%. dipole moment upon interaction with IR radiation.
B. Interference Filter Narrow effective bandwidth 10 Fundamental frequency of Vibration γ = 1/2π * (K/µ)1/2
to 20 nm and Maximum throughput 40%.
Region Wavelength Wavenumber
Monochromator range (Micron) range (cm–1)
A wavelength selector that uses diffraction grating or
Near/Harmonic/Over- 0.78–2.5 12800–4000
prism, and that allows continuous variation of nominal tone
wavelength.
Middle/Fundamental 2.5–50 4000–200
Advantages of monochromator over filter
1. It provide continuous variation of nominal wavelength. Far/Rotational 50–1000 200–10
3.88  Chapter 3

Bending Change in angle between two bonds. There are Sampling techniques
four types of bends: 1. Mull technique
yy Rocking Nujol (mineral oil) is a mixture of paraffin hydrocarbons. To
yy Scissoring avoid Nujols band in spectrum sometimes hexachlorobuta-
yy Wagging diene or chlorofluorocarbon oil is added.
yy Twisting 2. Pressed pellet/KBr
KBr is used 100 times to sample quantity. This technique
Bending vibrations can be used for quantitative analysis.
Near Near Near
Far
NMR Spectroscopy
Basic principle Nuclear spin changes.
In-plane In-plane Out-of-plane Out-of-plane Nuclear-zeeman effect Splitting of nuclei spin state in
rocking scissoring wagging twisting applied external magnetic field.
Stretching vibrations
Energy levels for a nucleus with spin quantum
number 1/2

Applied
No field magnetic field 1
Symmetric Asymmetric m= −
Energy 2
Figure 3.2 Types of Bending and Stretching Vibrations 0

1
Factors affecting vibration frequency m= +
2
1. Nature of bond present
2. Masses of atoms Larmor equation It is fundamental equation of NMR
3. Force constant of bond spectroscopy.
4. Electronic effect
5. Bond angle W (Angular Precessional Frequency) = γ H
6. Hydrogen bonding 2πv = γ H
7. Symmetry of molecule
Precessional frequency (v) = γ/2π
Type of degree of Linear Non-linear where H = Applied magnetic field
freedom γ = 
Magnogyretic ratio or Gyro-
Transitional 3 3 magnetic ratio = 2πµ/hI

Rotational 2 3 where h is Plank constant and I is Spin Quantum Number.

µ is Magnetic moment of spinning nuclei.
Vibrational 3N-5 3N-6 Magnetic moment = γ * Spin angular moment (h/2π *
Total 3N 3N spin quantum number I)
Note only those Nuclei show NMR absorption signal
having spin quantum number (I) greater or equals to ½.
Finger print region
1. 8 µ to 16 µ or 1500 cm–1 to 500 cm–1 1. If the number of neutrons and the number of protons
2. Absorption is unique and complex. are both even, then the nucleus has no spin.
2. If the number of neutrons plus the number of pro-
Fermi resonance tons is odd, then the nucleus has a half-integer spin
Energy of harmonic or overtone region coincides with (i.e., 1/2, 3/2, 5/2)
fundamental mode of vibration. Instead of one band, two 3. If the number of neutrons and the number of protons
bands of almost equal intensity results. It is normally observed are both odd, then the nucleus has an integer spin
in carbonyl compounds. (i.e., 1, 2, 3)
 Analytical Chemistry  3.89

Element H1 H2 C12 C13 N14 O16 O17 P31 Cl35 F19

Spin quantum number (I) 1/2 1 0 1/2 1 0 5/2 1/2 3/2 1/2

No. of spin states (2I + 1) 2 3 1 2 3 1 6 2 4 2

Nucleus Spin (I) Natural Abundance/% Magnetogyric Ratio (γ) /107 kg–1·s·A Relative Frequency (ν) /MHz
1
H 1/2 99.985 26.752196 100.00
2
H 1 0.015 4.106625 15.35
13
C 1/2 1.10 6.72828 25.15
15
N 1/2 0.366 –2.712621 10.14
17
O 5/2 0.037 –3.62808 13.56
19
F 1/2 100.0 25.18147 94.13
29
Si 1/2 4.67 –5.319 19.88
31
P 1/2 100.0 10.8394 40.52
119
Sn 1/2 8.58 –10.0318 37.27

Population Densities of Nuclear Ideally, Relaxation rates to be fast–but not too fast. If
Spin States the relaxation rate is fast, then saturation is reduced. If the
relaxation rate is too fast, line-broadening in the resultant
Saturation of signal If population densities of upper
NMR spectrum is observed.
and lower spin states becomes exactly equals then we
There are two major relaxation processes:
observe no net signal. This is called saturation of signal.
Saturation of signal can be achieved by intense RF signal. yy Spin-lattice (longitudinal) relaxation
Saturation should be avoided in during NMR experiment. yy Spin-spin (transverse) relaxation

Boltzmann distribution Spin-lattice-relaxation

In the presence of an external magnetic field, different Nuclei in an NMR experiment are in a sample. The sample
mI nuclear spin states have different energies. At thermal in which the nuclei are held is called the lattice. Nuclei in
equilibrium, they will also have different populations the lattice are in vibrational and rotational motion, which
according to the Boltzmann equation creates a complex magnetic field. The magnetic field caused
by motion of nuclei within the lattice is called the lattice
N high field. This lattice field has many components. Some of these
= e− ∆ / k⁄
N low components will be equal in frequency and phase to the
1 Larmor frequency of the nuclei of interest. These compo-
=
e − ∆ / k⁄ nents of the lattice field can interact with nuclei in the higher
energy state, and cause them to lose energy (returning to the
where Nhigh and Nlow are the populations of the upper lower state). The energy that a nucleus loses increases the
and lower states respectively, ΔE = Ehigh – Elow is the energy amount of vibration and rotation within the lattice (resulting
difference between the two states, k is the Boltzmann con- in a tiny rise in the temperature of the sample).
stant, and T is the absolute temperature.
Spin-spin-relaxation
Relaxation Processes Spin-spin relaxation describes the interaction between
It is the process by which nuclei undergo (return back) from neighbouring nuclei with identical precessional frequencies
higher energy state to the lower state. but differing magnetic quantum states. In this situation, the
3.90  Chapter 3

nuclei can exchange quantum states; a nucleus in the lower ‡‡ Chemical shift equivalent protons-Nuclei having
energy level will be excited, while the excited nucleus re- identical chemical shift.
laxes to the lower energy state. There is no net change in the ‡‡ Magnetically equivalent protons-Nuclei having
populations of the energy states, but the average lifetime of identical coupling constant.
a nucleus in the excited state will decrease. This can result
in line-broadening. NMR instrumentation
Chemical shift It is a dimensionless quantity and does 1. Magnet-To provide magnetic field
not depends on applied external field. It is expressed in
parts per million (ppm). RF (60-MHz)
oscillator
δ = Frequency shift (In Hz) X 106/Operating frequency (MHz) RF detector Recorder

Reference for measurement of chemical shift

TMS (tetra methyl silane) is used as reference in proton
NMR. Because
1. TMS has 12 equivalent protons N S
~1.41 T ± a
2. Chemically inert and very low B.P. few ppm
3. Miscible with all organic substances
4. Electron negativity of silicon is very low so shield- Variable
magnetic
ing of protons in TMS are most shielded compared to
field
other organic compounds.
Figure 3.3 NMR instrumentation
TMS is not soluble in aqueous solution hence 2,2
dimethyl-2-2-silapentane-5-sulphonate. 2. Sweep generator–To vary the field strength.
There are two methods, one is field sweep another is
Shift reagent These are paramagnetic substances used
frequency sweep method.
to spread the NMR absorption pattern without increasing
3. Rf transmitter–To provide Rf radiation for NMR
the magnetic field strength.
phenomenon
Example-Lanthanide Fluorinated β-di ketones 4. Rf receiver
Splitting of signal
yy The multiplicity of a multiplet is given by the number of Magnet
equivalent protons in neighbouring atoms plus one, Earlier, NMR magnets were iron core permanent or elec-
i.e., the n + 1 rule tromagnets producing magnetic fields of less than 1.5 T.
yy Equivalent nuclei do not interact with each other. Today, most NMR magnets are of the superconducting
type. Superconducting NMR magnets range in field strength
Type of Multiplet Relative Inten- No. of Vicinal from approximately 6 to 23.5 T.
sity Protons A superconducting magnet has an electromagnet made
of superconducting wire. Superconducting wire has a re-
Doublet 1:1 1 sistance approximately equal to zero when it is cooled to
Triplet 1:2:1 2 a temperature close to absolute zero (–273.15° C or 0 K)
by immersing it in liquid helium. Once current is caused to
Quartet 1:3:3:1 3 flow in the coil, it will continue to flow for as long as the coil
is kept at liquid helium temperatures.
Quintet (Pentet) 1:4:6:4:1 4
The superconducting elements of the wire are made of
Sextet 1:5:10:10:5:1 5 (NbTaTi)3Sn. This material is brittle and therefore is embedded
in copper for strength. The Cu has a high resistance compared
Coupling constant (J) to the superconductor which is carrying the current.
This wire is wound into a multi-turn solenoid or coil.
yy Distance of centre of peaks in a given multiplet. It is
The coil of wire is kept at a temperature of 4.2K or less by
expressed in Hz or cycle per second.
immersing it in liquid helium. The coil and liquid helium
yy Normal range 0–20. Ratio of J for trans to cis alkene is
are kept in a large dewar. This dewar is typically surrounded
approximately 2.
 Analytical Chemistry  3.91

by a liquid nitrogen (77.4K) dewar, which acts as a thermal of the molecule OR if they interchange by a rapid process
buffer between the room temperature air (293K) and the (rapid with respect to the NMR timescale).
liquid helium. If a pair of nuclei can be interchanged by rotation about
There is a vacuum region followed by a liquid nitrogen an axis of symmetry of the molecule, then they are chemically
reservoir. The vacuum region is filled with several layers of equivalent and are called homotopic. E.g., the pair of protons
a reflective mylar film. The function of the mylar is to reflect in dichloromethane are chemically equivalent.
thermal photons, and thus diminish heat from entering the If a pair of nuclei can be interchanged by an improper
magnet. rotational symmetry operation of the molecule, then they
are chemically equivalent and are called enantiotopic. E.g.,
Shim Coils pair of protons attached to the alpha-Carbon in glycine amino
The purpose of shim coils on a spectrometer is to correct acid (they are not chemically equivalent if glycine is part of
minor spatial inhomogeneities in the Bo magnetic field. a polypeptide chain).
These inhomogeneities could be caused by the magnet design, If a pair of geminal protons (CH2) cannot be interchanged
materials in the probe, and variations in the thickness of through a symmetry operation of the molecule, then these
the sample tube, sample permeability, and ferromagnetic protons are diastereotopic and are not chemically equivalent.
materials around the magnet. A shim coil is designed to E.g., the b-methylene protons of amino acids where the
create a small magnetic field which will oppose and cancel methylene group is attached to chiral Cα atom.
out an inhomogeneity in the Bo magnetic field. Chemical shift equivalence by rapid interconversion
Shim Coil function: by passing the appropriate amount of structures may occur due to rapid rotation about bonds
of current through each coil, a homogeneous Bo magnetic or due the rapid chemical changes such as keto-enol
field can be achieved. tautomerism.

Sample Probe Magnetic Equivalence

The sample probe is the name given to that part of the (Spin Coupling Equivalence)
spectrometer which accepts the sample, sends RF energy If in a set of chemically equivalent nuclei, each member of
into the sample, and detects the signal emanating from the the set has exactly the same interaction (J-coupling) to ev-
sample. It contains the RF coil, sample spinner, temperature ery other magnetically active nucleus in the molecule, then
controlling circuitry, and gradient coils. the nuclei are also magnetically equivalent. E.g., the pair of
The purpose of the sample spinner is to rotate the NMR protons in dichloromethane are chemically as well as mag-
sample tube about its axis. In doing so, each spin in the netically equivalent.
sample located at a given position along the Z axis and radius A set of nuclei that are magnetically equivalent will also
from the Z axis, will experience the average magnetic field be chemically equivalent; however, chemical equivalence
in the circle defined by this Z and radius. The net effect is a does not guarantee magnetic equivalence. e.g., the two
narrower spectral linewidth. protons ortho to hydroxy group in tyrosine are chemically
equivalent but they are not magnetically equivalent.
RF Coils
RF coils create the B1 field which rotates the net magneti- Nuclear Overhauser Effect (NOE)
zation in a pulse sequence. They also detect the transverse Nuclear Overhauser Effect (NOE) is the transfer of nuclear
magnetization as it precesses in the XY plane. spin polarization from one nuclear spin population to another
Most RF coils on NMR spectrometers are of the saddle via cross-relaxation.
coil design and act as the transmitter of the B1 field and When a proton is saturated or inverted, spatially-close
receiver of RF energy from the sample. You may find one or protons may experience an intensity enhancement, which
more RF coils in a probe. is termed the Nuclear Overhauser Effect (NOE). The NOE
is unique among NMR methods because it does not
Chemical Shift Equivalence depend upon through-bond J couplings but depends only on
If a set of nuclei exists in identical environments, they are the spatial proximity between protons. In other words, the
expected to have the same chemical shift. Such nuclei are strength of the NOE gives information on how close two
called chemical shift equivalent or chemically equivalent. protons are. For small molecules, an NOE may be observed
Pair of nuclei in a molecule is chemically equivalent if between protons that are up to 4Å apart, while the upper
they are interchangeable through any symmetry operation limit for large molecules is about 5Å.
3.92  Chapter 3

The NOE differs from the application of spin-spin Mass Spectroscopy

coupling in that the NOE occurs through space, not through
Basic principle
chemical bonds. Thus, atoms that are in close proximity to
each other can give a NOE, whereas spin coupling is observed Molecules are bombarded with high energetic electron
only when the atoms are connected by 2-3 chemical bonds. beam, positive ion fragments are sorted out depending upon
The inter-atomic distances derived from the observed NOE their m/z ratio. (No EM radiation used)
can often help to confirm a precise molecular conformation, Graph Plotted between Relative Abundance and m/z.
i.e., the three-dimensional structure of a molecule.
Mass Spectrometer Sorting out mechanism
Magic Angle NMR
Conventional MS Energy and momentum
In nuclear magnetic resonance, magic angle spinning
(MAS) is a technique often used to perform experiments in Time of Flight (TOF) MS Energy and Velocity
solid-state NMR spectroscopy.
By spinning the sample (usually at a frequency of 1 to 70 FT-MS Momentum and Velocity
kHz) at the magic angle θm (ca. 54.74°, where cos2θm=1/3)
with respect to the direction of the magnetic field, the normally Ionization mode in MS
broad lines become narrower, increasing the resolution for A. Gas Phase
better identification and analysis of the spectrum.
1. Electron impact ionization (Unimolecular)–Tungsten
In any condensed phase, a nuclear spin experiences a
filament (50–80 ev) used as electron source.
great number of interactions. The main three interactions
2. Chemical mode (Bi molecular)–Methane (mostly
(dipolar, chemical shift anisotropy, quadrupolar) often lead
used gas), Isobutane, Ammonia and inert gases
to very broad and featureless lines. However, these three
(He, N2 Ar2).
interactions in solids are time-dependent and can be averaged
by MAS. B. Desorption/Condensed Phase
1. Field desorption or Laser desorption
Shielding 2. Plasma desorption or californium fission fragments
All atoms in a molecule are surrounded by electrons that 3. FAB (Fast Atom Bombardment)–Solvent used is Glyc-
occupy  core and valence orbitals. The permanent magnetic erol
field β0 induces a current in the surrounding electrons,
 Argon gas ionized Ar+. ions are accelerated
which in turn generates an induced magnetic field βind .                    
According to Lenz’s Law, the induced field is proportional
Accelerated Ar molecule  Again strike to
to the permanent magnetic field but is opposite in direc-
argon gas (Ar)
tion.
In general, the amount of shielding is proportional    
to the local electron density, i.e., higher electron density Strike to sample dissolved in polar solvent E.g.,

causes more shielding and results a lower Larmor frequency. Glycerol
However, it is possible for some chemical groups with cir-    
cular п electron systems, most notably aromatic rings and
Fragmentation of sample result.
triple bonds, to cause induce chemical shifts which are not
the same for all orientations in space, a phenomenon known 4. Electron Spray Ionization (ESI)
as chemical shift anisotropy. Sorting out system or sector analyser
1. Magnetic Sector Analyser
H
m/z =H2 r2/2 V
C
B0 Where, H is magnetic field strength
H H r is ion tranjectory
C V is applied Voltage
Bind H Bind 2. TOF analyser
Ions are allowed to travel in a field free path, each ion
figure 3.4 Shielding
will take different time to travel a particular distance
 Analytical Chemistry  3.93

depending upon their m/z ratio. This time is known as (c) relative low abundance and broader peak
time of flight.
3. Quadruple analyser Maclafferty rearrangement
Both TOF and Quadruple analysers are used in inter- Migration of γ-hydrogen followed by β bond cleavage and
facing with GC. elimination of ethylene or substituted ethylene neutral
Detector system in MS Electron multiplier tube molecule.
Types of peak in MS
Instrumentation of Mass spectrometer
1. Molecular ion or Parent peak–Comes at molecular 1. Sample inlet system
weight of compound. Peaks at M+1 and M+2 are due 2. Molecular leak–It is pin-hole restriction (0.01 to 0.05
to isotopic abundance. mm diameter) and made up of gold foil. It is used for
Relative intensity ratio for Br and Cl form and
metering the sample to ionization chamber.
M+2 are 1:1 and 1:3 respectively. 3. Ionization Chamber
2. Base Peak 4. Ion separation (Sector analyser)
(a) It is considered as 100% 5. Ion collector (Detector)
(b) Most abundant peak
Recorder 5 separated galvanometers can be used to
3. Metastable peak
record simultaneously, the peaks for fragment ions and
M+ (Origional ion) N+ (daughter ion) parent ions.
+ Z (Neutral molecule)
Meta stable peak M* = (N+)2/M+ Nitrogen Rule It states that organic compound having:

(a) arise due to decomposition of ions in field free 1. an even integral molecular weight must contains either
path none or even number of nitrogen atoms.
(b) appears as weak, diffuse (humped shape) and at 2. odd molecular weight must contain odd number of
non-integral mass nitrogen atoms.

Note
yy Operation of Mass spectrometer requires a collision free path for ions to prevent arching due to high voltage and to
avoid recombination of fragmented ions.
yy For this, Vacuum Systems are used.
yy Vacuum in 1. Ionization Source (10–5 to 10–6 torr) 2. Sector Analyser (10–6 to 10–7 torr)

Luminescence Triplet state One set of electron spins is unpaired.

Luminescence is the emission of light by a substance. It occurs
when an electron returns to the electronic ground state from
an excited state and loses its excess energy as a photon.
Luminescence spectroscopy is a collective name given
to three related spectroscopic techniques. They are:
yy Molecular fluorescence spectroscopy
yy Molecular phosphorescence spectroscopy
yy Chemiluminescence spectroscopy ground
singlet state
excited
singlet state
excited
triplet state
spins is unpaired
Fluorescence and phosphorescence
(photoluminescence) Figure 3.5 Triple Set
The electronic states of most organic molecules can be
divided into singlet states and triplet states. Fluorescence
Singlet state All electrons in the molecule are spin- Absorption of UV radiation by a molecule excites it from a
paired vibrational level in the electronic ground state to one of the
3.94  Chapter 3

many vibrational levels in the electronic excited state. This Jablonski Diagram (Relaxation
excited state is usually the first excited singlet state. Mechanism for Excited State
A molecule in a high vibrational level of the excited
Molecules)
state will quickly fall to the lowest vibrational level of this
state by losing energy to other molecules through collision. Once a molecule has absorbed energy in the form of electro-
magnetic radiation, there are a number of routes by which it
Lowest excited
singlet state can return to ground state (the statistically most common en-
Lowest excited
Ground triplet state ergy state for room temperature chemical species). The follow-
electronic state ing graphic, termed a Jablonski diagram, shows a few of these
processes.
6 1 4 5
Energy

excited vibrational states

Sn (excited rolational states not shown)
4
A = photon absorption
2 3 F = fluorescence (emission)
4 4 S2 P = phosphorescence
IC S = singlet state
Processes involving photons T = triplet state
Radiationless transitions IC = internal conversion
S1
ISC = intersystem crossing
1. Absorption
2. Fluorescence Energy T2
ISC
3. Phosphorescence IC
4. Virbrational relaxation
A F T1
5. Intersystem crossing
6. Internal conversion P
S0
Figure 3.6 Possible physical process following electronic ground state
absorption of a photon by a molecule

Phosphorescence Figure 3.7 Jablonski Diagram

A molecule in the excited triplet state may not always use in-
If the photon emission occurs between states of the
tersystem crossing to return to the ground state. It could lose
same spin state, (e.g., S1 ---> S0) this is termed fluorescence.
energy by emission of a photon. A triplet/ singlet transition
If the spin state of the initial and final energy levels are
is much less probable than a singlet/singlet transition. The
different (e.g., T1 --> S0), the emission (loss of energy) is
lifetime of the excited triplet state can be up to 10 seconds,
called phosphorescence.
in comparison with 10-5 s to 10-8 s average lifetime of an ex-
cited singlet state. Emission from triplet/singlet transitions Since fluorescence is statistically much more likely
can continue after initial irradiation. Internal conversion and than phosphorescence for most molecules, the lifetimes of
other radiationless transfers of energy compete so success- fluorescent states are very short (1 × 10–5 to 10–8 seconds)
fully with phosphorescence that it is usually seen only at low and phosphorescence somewhat longer (1 × 10–4 seconds to
temperatures or in highly viscous media. minutes or even hours).
Three non-radiative deactivation processes are also
Chemiluminescence significant here: internal conversion (IC), intersystem
Chemiluminescence occurs when a chemical reaction pro- crossing (ISC) and vibrational relaxation.
duces an electronically excited species which emits a photon Internal conversion is the radiation less transition be-
in order to reach the ground state. These sort of reactions can tween energy states of the same spin state (compare with
be encountered in biological systems; the effect is then known fluorescence-a radiative process).
as bioluminescence. The number of chemical reactions which Intersystem crossing is a radiationless transition between
produce chemiluminescence is small. A good example of che- different spin states (compare to phosphorescence).
miluminescence is the determination of nitric oxide: Vibrational relaxation, the most common of the three—
NO + O3 → NO2* + O2 for most molecules, occurs very quickly (<1 × 10–12 seconds)
NO2* → NO2 + hv (l = 600–2800 nm) and is enhanced by physical contact of an excited molecule
 Analytical Chemistry  3.95

with other particles with which energy, in the form of vibra- Factor affecting fluorescence and phosphorescence
tions and rotations, can be transferred through collisions. 1. Nature of molecule
This means that most excited state molecules never emit any 2. Nature of substitutents
energy because in liquid samples the solvent or, in gas phase a.  Substituents that delocalize the π electrons
samples, other gas phase molecules that are present “steal” such as –NH2, –OH, –OR etc., enhance the fluo-
the energy before other deactivation processes can occur. rescence.
b. Substituents which withdraw electrons such as
Fluorescence (fluorimetry) and –NO2, –Cl, –Br etc., quench the fluorescence.
phosphorescence (phosphorimetry) 3. Rigidity of molecule
4. Viscosity
Absorption followed by emission i.e., λemitted > λincident 5. Temperature
6. pH
Fluorescence Phosphorescence
Average life time of Average life time for X-ray Diffraction
electron in excited state phosphorescence ranges
Basic principle Inner shell electron transition
is 10–5–10–8 sec. Decay from 10–4 –104 sec. Phos-
rapidly after excitation phorescence may continue Kα line (transition from shell L to Shell K)
source is removed. for sometime after remov- Kβ line (transition from shell M to Shell K)
ing excitation source. Kγ line (transition from shell N to Shell K)
No change in spin state Change in spin state Target material used Co, Ni, Cu, Mn, Mo etc.
Excited singlet state Excited triplet state
(Multiplicity = 1) (Multiplicity = 3) Brag's equation
nλ = 2d sinθ
Where
n = order of diffraction
Ground state (Multiplic- Ground state (Multiplic-
d = lattice spacing or inter planner distance
ity=1) ity=1)
θ = angle between direction of incident beam and that
Fluorescence spectrum is Not a mirror image because of diffracted beam
a mirror image excited triplet energy levels
lies lower than correspond-
ing excited singlet level

Note
Diffraction from crystal is only possible when λ is equal to or less than d.

Detectors
Nephelometry Turbidimetry
1. Photographic film method
2. Counter method 2. Most suitable for di- 2. Most suitable for
(a) Geiger-muller tube lute suspension concentrated suspen-
(b) Proportional counter sion
(c) Scintillation detector 3. Similar to fluorimetry 3. S imilar to colorimetry
(d) Solid state semiconductor because both measure because both
scattered radiations measure transmitted
Nephelometry Turbidimetry but elastic scattering radiations but light
in fluorimetry while intensity decreased
1. Intensity of scattered 1. Intensity of transmit- non-elastic scattering by scattering in
light measured as a ted light measured as a in nephelometry. turbidimetry while
function of concentra- function of concentra- by absorption in
tion of dispersed phase tion of dispersed phase colorimetry.
3.96  Chapter 3

Flame Photometry (Flame Emission 4. Electrode system:

Spectroscopy) a.  Indicator/Working electrode–DME (dropping
mercury electrode)
1. Mainly used for Alkali metal like Li, Na, K and Alkali
b. Reference electrode–Large mercury pool
earth metals like Mg, Ca, Ba, Sr.
2. Principle Supporting Electrolyte
Nebulization (breakdown of liquid into smaller a. It neither reacts with material under investigation
droplets) → Evaporation → Atomization in Flame → nor with DME. It has higher discharge potential
Excitation followed by Emission compared to material under investigation.
b. Quantity of supporting electrolyte taken as 100
Electro Analytical Methods times to material.
c. It carries almost all the current of the solution and
1. Conductometry
raise the conductivity of the solution, thus suppress
Conductivity cell the migration current.
1. Made up of Pyrex glass and Quartz 5. Ilkovic equation Id = 607 n CD1/2 m2/3 t1/6
2. Two platinum electrode system: To avoid polarization, Id =  Diffusion current = Limiting current–residual
Pt electrodes are coated with Pt black (Chloro platinic current
acid and lead acetate mixture). D = diffusion coefficient
3. Cell constant (x=specific conductivity/observed conduc- C = concentration
tivity) is determined using N/50 KCl. m = flow rate of mercury from DME
Specific conductance t = drop time
yy Conductivity offered by 1 ml or cm3 solution. 6. Half wave potential (E1/2)
yy It is the reciprocal of specific resistance (ρ). It has unit Potential corresponding to point of inflexion of polar
ohm-1 cm-1 or mho cm-1 graphic wave. It is a characteristic of nature of reacting
material.
К = 1/ρ = 1/R * L/A 7. Polar graphic Maxima-Developed due to streaming
= Conductance * cell constant (L/A) movement of diffusion layer at interface.
8. Maxima suppressor
πeq = К (Specific conductance) * V (dilution)
Gelatin (0.002–0.01 %) and triton-x-100 (0.02–0.01
K decreases but there is much greater increment in V %) are used as maxima suppressor.
hence overall equivalent conductance increases. Special Note
2. Potentiometry 1. Salt Bridge–It is made up of inert, hot, concentrated,
aqueous solution of KCl, KNO3, NH4NO3 in gelatine
Nernst equation or agar-agar solution. Only those salts can be used in
E = E0-RT/nF loge (P)/(R) preparation of Salt bridge formation which have equal
cations and anions mobility.
Where E = electrode potential of the cell 2. Saturated KCl solution mostly used compared to molar
E0 = standard electrode potential or decimolar solution in the preparation of reference
n = No. of electron consumed in 1 mol oxidation electrodes because it minimize the liquid-liquid junction
or reduction of electro active species potential.
(P), (R) = product and reactant concentration
Chromatography
3. Polargraphy Chromatography terms
1. Polarogram–Graph between current and applied yy Analytical chromatography is used to determine the
voltage existence and possibly also the concentration of analyte
2. Polarograph–Apparatus used for polarography (s) in a sample.
3. Residual/Charging/Capacitance current = Faradic yy Preparative chromatography is used to purify suffi-
current (due to impurity) + Condenser current (due to cient quantities of a substance for further use, rather
supporting electrolyte) than analysis.
 Analytical Chemistry  3.97

yy A bonded phase is a stationary phase that is covalently Distribution of analytes between phases
bonded to the support particles or to the inside wall of The distribution of analytes between phases can often be
the column tubing. described quite simply. An analyte is in equilibrium between
yy A chromatogram is the visual output of the chromato- the two phases;
graph. In the case of an optimal separation, different
peaks or patterns on the chromatogram correspond to Amobile Astationary
different components of the separated mixture. The equilibrium constant, K, is termed the partition
yy A chromatograph is an equipment that enables a coefficient; defined as the molar concentration of analyte in
sophisticated separation e.g., gas chromatographic or the stationary phase divided by the molar concentration of
liquid chromatographic separation. the analyte in the mobile phase.
yy Chromatography is a physical method of separation The time between sample injection and an analyte peak
in which the components to be separated are distrib- reaching a detector at the end of the column is termed the
uted between two phases, one of which is stationary retention time (tR). Each analyte in a sample will have a
(stationary phase) while the other (the mobile phase) different retention time. The time taken for the mobile
moves in a definite direction. phase to pass through the column is called tM.
yy The eluate is the mobile phase leaving the column.
yy The eluent is the solvent that will carry the analyte. tR
yy An eluotropic series is a list of solvents ranked according

Detector singal
to their eluting power.
tM
Chromatogram development technique
1. Frontal analysis–A large volume of sample mixture
is continuously passed through the column. Most weak- Time
ly retained component of the mixture emerges first.
Figure 3.8 Distribution of analyses between phases
2. Displacement analysis–Sample mixture is dissolved
in large volume of solvent and applied to the top of the A term called the retention factor, k ′, is often used to
column. Mobile phase containing displacement agent describe the migration rate of an analyte on a column. You
is passed through the column. may also find it called the capacity factor. The retention fac-
3. Elution Analysis–Most widely used technique. It can tor for analyte A is defined as;
be used for quantitative applications.
A. Isocratic elution (Solvent composition or strength k'A = tR – tM/tM
is not changed during column development)
tR and tM are easily obtained from a chromatogram.
B. Gradient elution (Solvent composition or strength
When an analytes retention factor is less than one, elution
is changed during column development).It is also
is so fast that accurate determination of the retention time is
known as solvent programming.
very difficult. High retention factors (greater than 20) mean
that elution takes a very long time. Ideally, the retention factor
Introduction
for an analyte is between one and five.
Chromatography involves a sample (or sample extract) being We define a quantity called the selectivity factor, α, which
dissolved in a mobile phase (which may be a gas, a liquid describes the separation of two species (A and B) on the column;
or a supercritical fluid). The mobile phase is then forced
through an immobile, immiscible stationary phase. α = k'B/k'A
The phases are chosen such that components of the When calculating the selectivity factor, species A elutes
sample have differing solubilities in each phase. A com- faster than species B. The selectivity factor is always greater
ponent which is quite soluble in the stationary phase will than one.
take longer to travel through it than a component which is
not very soluble in the stationary phase but very soluble in Band broadening and column efficiency
the mobile phase. To obtain optimal separations, sharp, symmetrical chromato-
As a result of these differences in mobilities, sample graphic peaks must be obtained. This means that band
components will become separated from each other as they broadening must be limited. It is also beneficial to measure
travel through the stationary phase. the efficiency of the column.
3.98  Chapter 3

Theoretical plate model of chromatography HETP = A + B/u + C u

The plate model supposes that the chromatographic column Where u is the average velocity of the mobile phase.
is contains a large number of separate layers, called theoret- A, B, and C are factors which contribute to band broadening.
ical plates. Separate equilibrations of the sample between
the stationary and mobile phase occur in these “plates”. The A. Eddy diffusion
analyte moves down the column by transfer of equilibrated
The mobile phase moves through the column which is
mobile phase from one plate to the next.
packed with stationary phase. Solute molecules will take
different paths through the stationary phase at random. This
The column will cause broadening of the solute band, because different
paths are of different lengths.

B. Longitudinal diffusion
Theoretical
plate The concentration of analyte is less at the edges of the band
than at the center. Analyte diffuses out from the center to the
Figure 3.9 Theoretical plate model of chromatography edges. This causes band broadening. If the velocity of the
mobile phase is high then the analyte spends less time on the
It is important to remember that the plates do not column, which decreases the effects of longitudinal diffusion.
really exist; they are a figment of the imagination that help
us understand the processes at work in the column. They also C. Resistance to mass transfer
serve as a way of measuring column efficiency, either by stat-
The analyte takes a certain amount of time to equilibrate
ing the number of theoretical plates in a column, N (the more
between the stationary and mobile phase. If the velocity of
plates the better), or by stating the plate height; the Height
the mobile phase is high, and the analyte has a strong affin-
Equivalent to a Theoretical Plate (the smaller the better).
ity for the stationary phase, then the analyte in the mobile
If the length of the column is L, then the HETP is
phase will move ahead of the analyte in the stationary phase.
HETP = L/N The band of analyte is broadened. The higher the velocity of
mobile phase, the worse the broadening becomes.
The number of theoretical plates that a real column
possesses can be found by examining a chromatographic Van Deemter plots
peak after elution;
A plot of plate height vs average linear velocity of mobile
phase.
5.5t R2
N=
w12/ 2 A typical Van Deemter plot

where w1/2 is the peak width at half-height.

As can be seen from this equation, columns behave as Optimum velocity
Plate height

if they have different numbers of plates for different solutes

in a mixture.
Minimum plate
Rate theory of chromatography height

A more realistic description of the processes at work inside

Mobile phase velocity
a column takes account of the time taken for the solute to
equilibrate between the stationary and mobile phase (unlike Figure 3.10 Van Deemter plots
the plate model, which assumes that equilibration is infinitely
fast). The resulting band shape of a chromatographic peak is Such plots are of considerable use in determining the
therefore affected by the rate of elution. It is also affected by optimum mobile phase flow rate.
the different paths available to solute molecules as they travel
Resolution
between particles of stationary phase. If we consider the vari-
ous mechanisms which contribute to band broadening, we ar- Although the selectivity factor, R, describes the separation of
rive at the Van Deemter equation for plate height; band centres, it does not take into account peak widths.
 Analytical Chemistry  3.99

Another measure of how well species have been separated Instead, to increase the number of plates, the height
is provided by measurement of the resolution. The resolution equivalent to a theoretical plate can be reduced by reducing
of two species, A and B, is defined as the size of the stationary phase particles.
2 [ (t R ) B − (t R ) A ] It is often found that by controlling the capacity
R= factor, k′, separations can be greatly improved. This can be
W A + WB achieved by changing the temperature (in Gas Chromatog-
Baseline resolution is achieved when R = 1.5 raphy) or the composition of the mobile phase (in Liquid
It is useful to relate the resolution to the number of Chromatography).
plates in the column, the selectivity factor and the retention The selectivity factor, α, can also be manipulated to
factors of the two solutes; improve separations. When α is close to unity, optimising
k′ and increasing N is not sufficient to give good separa-
N  – − 1  1 + K B′  tion in a reasonable time. In these cases, k′ is optimised
R=    K ′ 
4  –  B
first, and then R is increased by one of the following
procedures:
To obtain high resolution, the three terms must be
maximized. 1. Changing mobile phase composition
An increase in N, the number of theoretical plates, 2. Changing column temperature
By lengthening the column leads to an increase in 3. Changing composition of stationary phase
retention time 4. Using special chemical effects (such as incorporating
By increasing band broadening—which may not be a species which complexes with one of the solutes into
desirable. the stationary phase)

Note
Column chromatography is used to separate and purify components of a mixture.

TLC and GC are usually used only to analyse mixtures: Instrumentation

to determine the number of components and to see if a
Gas chromatography Specifically, gas-liquid chroma-
desired component is present.
tography–involves a sample being vaporized and injected
TLC is often used to determine the “ideal solvent system”
onto the head of the chromatographic column. The sam-
for a column chromatography or flash chromatography.
ple is transported through the column by the flow of inert,
The ideal system is the one that moves the desired com-
gaseous mobile phase. The column itself contains a liquid
ponent of the mixture to a TLC Rf of 0.25–0.35 and will
stationary phase which is adsorbed onto the surface of an
separate this component from its nearest neighbour by dif-
inert solid.
ference in TLC Rf values of at least 0.20. Therefore, a mix-
ture is analysed by TLC to determine the ideal solvent (s)
for a flash chromatography procedure. Injector
Flow port
Controller
Gas Chromatography
Principle Adsorption (GSC) or partition (GLC) Recorder
Main requirement Thermal stability and volatile na-
ture of compound.
Detector
Column
Derivatization in GC
1. To improve thermal stability of compound (polar com-
pound to non-polar compound). Column oven
2. To introduce a detector oriented tag in molecule.
3. For purposeful adjustment of volatility. Figure 3.11 Gas Chromatography
3.100  Chapter 3

Most common stationary phases The injector can be used in one of the two modes; split
1. Separation of mixture of polar compounds or splitless. The injector contains a heated chamber containing
a glass liner into which the sample is injected through the
Carbowax 20M (polyethylene glycol) septum. The carrier gas enters the chamber and can leave by
2. Separation of mixtures of non-polar compounds three routes (when the injector is in split mode). The sample
vapourises to form a mixture of carrier gas, vapourized
OV101 or SE-30 (polymer of methylsilicone) solvent and vapourised solutes. A proportion of this mix-
3. Methylester of fatty acids ture passes onto the column, but most exits through the
split outlet. The septum purge outlet prevents septum bleed
DEGS (diethylene glycol succinate) components from entering the column.

Columns
Instrumental Components
There are two general types of column, packed and capillary
Carrier gas (also known as open tubular).
The carrier gas must be chemically inert. Commonly used Packed columns contain a finely divided, inert, solid
gases include nitrogen, helium, argon, and carbon dioxide. support material (commonly based on diatomaceous earth)
The choice of carrier gas often depends upon the type of coated with liquid stationary phase. Most packed columns are
detector used. 1.5–10m in length and have an internal diameter of 2–4mm.
Capillary columns have an internal diameter of a few
Sample injection port tenths of a millimeter. They can be of one of the two types:
The most common injection method is where a micro sy- wall-coated open tubular (WCOT) or support-coated open
ringe is used to inject sample through a rubber septum into a tubular (SCOT).
flash vaporizer port at the head of the column. The tempera- Wall-coated columns consist of a capillary tube whose
ture of the sample port is usually about 50°C higher than the walls are coated with liquid stationary phase.
boiling point of the least volatile component of the sample. In support-coated columns, the inner wall of the capillary
For packed columns, sample size ranges from tenths of is lined with a thin layer of support material such as diato-
a microliter up to 20 microliter. maceous earth, onto which the stationary phase has been
Capillary columns, on the other hand, need much less adsorbed. SCOT columns are generally less efficient than
sample, typically around 10–3 microliter. For capillary GC, WCOT columns. Both types of capillary column are more
split/splitless injection is used. efficient than packed columns.
A new type of WCOT column was devised–the Fused
Silica Open Tubular (FSOT) column;
The split/splitless injector
Cross section of a Fused Silica Open Tubular Column
Rubber septum
Septum purge Polyimide coating
outlet Fused silica tube
Carrier gas Chemically bonded
inlet stationary phase

Split cutlet
Heated Figure 3.13 Cross section of a Fused Silica Open
metal block
Tubular Column
Vapourisation
Glass liner chamber These have much thinner walls than the glass capillary col-
umns, and are given strength by the polyimide coating. These
Column columns are flexible and can be wound into coils. They have the
advantages of physical strength, flexibility and low reactivity.
Column temperature
For precise work, column temperature must be controlled
to within tenths of a degree. The optimum column tempera-
ture is depends upon the boiling point of the sample. As
Figure 3.12 Capillary columns a rule of thumb, a temperature slightly above the average
 Analytical Chemistry  3.101

boiling point of the sample results in an elution time of a specific detector responds to a single chemical compound.
2–30 minutes. Minimal temperatures give good resolution, Detectors can also be grouped into concentration
but increase elution times. If a sample has a wide boiling dependant detectors and mass flow dependant detectors.
range, then temperature programming can be useful. The The signal from a concentration dependant detector is related
column temperature is increased (either continuously or in to the concentration of solute in the detector, and does not
steps) as separation proceeds. usually destroy the sampled dilution of with make-up gas
will lower the detectors response. Mass flow dependant
Detectors detectors usually destroy the sample, and the signal is related
A non-selective detector responds to all compounds except to the rate at which solute molecules enter the detector. The
the carrier gas, a selective detector responds to a range of response of a mass flow dependant detector is unaffected by
compounds with a common physical or chemical property and make-up gas.

Detector Type Support gases Selectivity Detectability Dynamic

range

Flame ionization Mass flow Hydrogen and Most organic com- 100 pg 107
(FID) air pounds

Thermal Concentration Reference Universal 1 ng 107

conductivity
(TCD)

Electron capture Concentration Make-up Halides, nitrates, nitriles, 50 fg 105

(ECD) peroxides, anhydrides,
organometallics

Nitrogen- Mass flow Hydrogen and Nitrogen, phosphorus 10 pg 106

phosphorus air

Flame photomet- Mass flow Hydrogen and Sulphur, phosphorus, tin, 100 pg 103
ric (FPD) air possibly boron, arsenic, germani-
oxygen um, selenium, chromium

Photoionization Concentration Make-up Aliphatics, aromatics, ke- 2 pg 107

(PID) tones, esters, aldehydes,
amines, heterocyclics,
organosulphurs, some
organometallics

Hall electrolytic Mass flow Hydrogen, Halide, nitrogen,

conductivity oxygen nitrosamine, sulphur

Flame Ionization Detector

The effluent from the column is mixed with hydro-
gen and air, and ignited. Organic compounds burning in
the flame produce ions and electrons which can conduct
Collector electricity through the flame. A large electrical potential is
Flame electrode applied at the burner tip, and a collector electrode is located
+300V
ignition above the flame. The current resulting from the pyrolysis of
coil Polarizing
voltage any organic compounds is measured. FIDs are mass sensi-
tive rather than concentration sensitive; this gives the advan-
tage that changes in mobile phase flow rate do not affect the
Air Hydrogen detector’s response. The FID is a useful general detector for
Column the analysis of organic compounds; it has high sensitivity, a
large linear response range, and low noise. It is also robust
Figure 3.14 Flame Ionization Detector and easy to use, but unfortunately, it destroys the sample.
3.102  Chapter 3

Thermal conductivity detector 4. Analytical Column

Principal When a compound elutes, the thermal conduc- yy Made up of stainless steel or fused silica
tivity of the gaseous mixture of carrier gas and compound yy Particle size below 5 µm
gas is lowered, and the filament in the sample column yy Mostly used silica gel as stationary phase.
becomes hotter than the other control column. (NP-HPLC)
Its resistance increases, and this imbalance between yy Mostly used bonded phase silica gel as stationary
control and sample filament resistances is measured by a phase. (RP-HPLC)
simple gadget and a signal is recorded. E.g., RP 18 (ODS), RP 8, RP 2
yy Type of material used for column packing
(a) Totally porous
Electron capture detector
(b) Superficially porous/pellicular type
For pesticide analysis (picogram).3H or 63Ni which emits b 5. Detector
particles. Accept electrons of carrier gas. A. UV-Visible spectrometer–(Most widely used)
Ionization: N2 (Nitrogen carrier gas) + b (e) = N2+ + 2e (a) Fixed wavelength (254 nm)
(b) Diode array detector
These N2+ establish a “base line” B. Refractive Index Detector
X (F, Cl and Br) containing sample + b (e) → X
– Temperature sensitive detector and cannot be
–
used in case of gradient elution method.
Ion recombination: X + N2+ = X + N2 C. Fluorescent Detector
The “base line” will decrease and this decrease consti- D. Conductrometric Detector
tutes the signal. Insecticides, pesticides, vinyl chloride, and
fluorocarbons. Ion Exchange Chromatography
Principle
HPLC Ionic compounds of solute are selectively separated by
Derivatization in HPLC forming temporary electrostatic chemical bond with counter
1. To improve sensitivity of the method such as formation ion of stationary phase.
of fluorescent derivative of amino acids. Resin......SO3H + Na+ Resin.....SO3Na + H+
2. To improve resolution by adding functional group
Resin......N (CH3)3OH + Cl–  Resin..... N (CH3)3
that enhances interaction of solute with stationary
Cl + OH–
phase.
Instrumentation Cation exchanger
1. Pump Strong – ..... SO3H Weak – ..... COOH
a. Pneumatic pump
b. Reciprocating pump Anion exchanger
Pressure up to 6000 psi but most of the analytical work
done in 400 to 1500 psi. Strong – ..... NR3Cl Weak – ..... NR2H
2. Sample Injector
a. Micro litre syringe Stationary phase
b. Rotary valve Polymeric Matrix e.g., Styrene (Vinyl benzene)-Divinyl
c. Loop Injector Benzene (DVB) Copolymer
3. Precolumn/Guard/Support column Divinyl Benzene is added to cross-link the chains
yy It is similar to analytical column but differs in formed from Styrene polymerization and gives a three-
particle size (30–50 µ) from analytical column dimensional bead structure.
(Size below 5µ).
yy Function Size Exclusion Chromatography
(a) Prevents dissolution of silica gel (Column Bleed-
ing) by previously saturating the mobile phase. Principle Molecular sieve basis i.e., larger molecule
(b) Removes irreversibly, adsorption of particulate unable to fit into pores are eluted first while small molecules
matter. enters into pores and are eluted later.
 Analytical Chemistry  3.103

Two types Super critical fluid chromatography

1. Gel Filtration-S.P. used are cross-linked carbohydrates Supercritical point is a point at which a gas cannot be
(Soft gel) Liquified no matter how high is the pressure. The resulting
E.g., Sephadex (Cross linked dextran), Agarose liquid has density, viscosity and diffusivity characteristics
(Sepharose), Polyacrylamide (Bio-gel) midway between gaseous and liquid states.
2. Gel Permeation-S.P. used are semi-rigid or rigid gel The most commonly used mobile phase, carbon dioxide
E.g., Cross-linked polystyrene, Alkylated Dextran, has a critical temperature of 31 degree C at 73 atm pressure.
Controlled porosity Glass beads
Thin layer chromatography (TLC)
Principle may be adsorption, partition, ion exchange or
Chiral Chromatography
molecular sieve depending upon the stationary phase used.
Principle
Separation of particular isomer from enantionmeric mixture Paper Chromatography
involves formation of Diastereomers.
Principle Partition
Methods Stationary phase Bound water in pores of cellulose fil-
1. Chiral Stationary Phase ter paper act as S.P.
e.g., Naphthyl Alanine, Naphthyl Leucine, Dinitro
Rf Value = distance travelled by solute/distance
benzoyl phenyl glycine, β-Cyclodextrin
travelled by Solvent front
2. Chiral mobile phase
Rf Value cannot be greater than 1.
Affinity chromatography
Derivatization in TLC
1. Affinity ligand is immobilized by covalent attachment
with inert support E.g., Silica or polysaccharide matrix. Compound class Derivatizing Agent
Affinity ligands selectively adsorb a single molecular
General Iodine Vapor
species which is complementary to it, from a mixture of
solute. General Sulphuric acid (50%)
2. Adsorption is reversible and non-covalent.
Acids Bromo cresol green
3. It exploit lock and key binding.
4. It is specially used for purification and separation of Aldehyde and Ketones 2, 4-dinitro phenyl hydrazine
biological macromolecules.
Amines and amino acids Ninhydrin
Analyte Affinity ligand Alkaloids Mercuric nitrate
Enzyme Coenzyme or inhibitor Barbiturates Diphenylcarbazone
Antigen Antibody Lipids Bromo thymol blue
Lectin Carbohydrate Steroids Antimony trichloride
Hormone Carrier Carbohydrate Aniline Phthalate

Important Table: Pharmaceutical Analysis

Spectral Region Frequency (Hertz) Wavelength Wave number (cm–1) Special Phenomenon

Gamma Rays 3 × 1018 – 3 ×1020 – – Nuclear reaction and Mossbau-

er spectroscopy

X Rays 3 × 1016 – 3 × 1018 0.01–2 nm – Inner shell electron transition

Vacuum or Far UV 1.5 × 1015 – 3 × 1016 2nm–200 nm – Ionization of atoms or molecule

3.104  Chapter 3

Spectral Region Frequency (Hertz) Wavelength Wave number (cm–1) Special Phenomenon

UV 8 × 1014 – 1.5 ×1015 200–400 nm 50, 000–25, 000 Outer or valence shell electron
transition

Visible 4 × 1014 – 4 × 1014 400–800 nm 25, 000–12, 500 Outer or valence shell electron
transition

IR 1012 – 4 × 1014 0.8 µm–1 mm 12, 500–20 Molecular vibration

Micro wave 1010 – 1012 1 mm–30 cm – Molecular rotation

Radio wave 106 – 1010 10 m–2000 m – Nuclear spin change

Spectroscopy Sample Window or Sample cell Spectroscopy Radiation Source Detector

UV Quartz or Fused silica UV 1. H ydrogen 1. B arrier layer

discharge cell (Photo
Visible Glass or plastic lamp Voltaic Cell)
2. Deuterium 2. Photo Emissive
IR Metal halide salts e.g., NaCl, KBr, discharge Cell
CsBr (for Non-Aqueous samples) lamp 3. Photo Multipli-
LiF, CaF2 (For Aqueous samples) 3. Xenon arc er Tube (PMT)
lamp 4. Silicon Diode
ATR-IR (Attenuated Silicon, Germanium, Sapphire 5. Charge coupled
total Reflectance) (single crystal of Al2O3) device (CCD)
6. Photo Diode
NMR Cylindrical Glass Tube
Array

Visible Tungsten Same as UV

halogen lamp
Detector Composition Principle
IR 1. N ernst glower 1. B olometer
Bolometer Pt strip in Evacu- Resistance operates at 2. Themocouple
ated vessel change 1500 degree C or Thermopile
(Rod of fused 3. Thermister
Thermocouple Two dissimilar Voltage or EMF or sintered 4. Golay cell
and metals e.g., Change at mixture of 5. Pyroelectric
Thermopile Bismuth and junction rare earth 6. Semiconductor
Antimony oxide e.g., 7. Photo
Zirconium, conductivity
Thermister Oxide of Mn, Co, Resistance Ytterbium, detector
Ni change Erbium or
Thorium)
Goley cell Xenon gas Membrane 2. Globar source
(Pneumatic) displacement operates at
or Expansion 1300°C (Rod
of gas of Silicon
carbide)
Pyroelectric Non-centrosym- Electric 3. Nichrome
metric crystal polarization wire or coil
below its Curie producing
point. TGS (Tri current NMR Radio Frequency Radio Frequency
glycine sulphate) Oscillator or Receiver or Phase
used as medium Generator Sensitive Detector
 Analytical Chemistry  3.105

Spectroscopy Radiation Source Detector Bathochromic shift Shift towards longer wave-
(Red Shift) length or lower energy
Fluorescence 1. Mercury PMT (Photo
and Phos- vapour Lamp Multiplier Tube) λmax The wavelength at maximum
phorescence 2. Xenon Arc absorption
lamp

Type of Potentio- Indicator Reference Elec- Electrode System Construction

meric Titration Electrode trode
Standard Hydro- It is a primary reference electrode.
Acid-base Glass Calomel (Hg/Hg- gen electrode It consists of Pt electrode immersed
(Neutralization) electrode Cl2) or Ag/AgCl (SHE) in a solution whose hydrogen ion
2
activity is 1.0 and in which H2 gas is
Complexometric Mercury- Calomel (Hg/Hg- bubbled at 1 atm Pressure.
or Chelometric Mercury (II) 2
Cl2) or Ag/AgCl
electrode Calomel ( (Hg/ Solid mercury surrounded with
Hg2Cl2) electrode Hg, Hg2Cl2 Paste and kept in satu-
Precipitation Silver Calomel (Hg/Hg- rated solution of KCl.
Electrode 2
Cl2) or Ag/AgCl
Ag/AgCl elec- Silver wire is coated with thin
Redox Pt elec- Calomel (Hg/Hg- trode film of silver chloride and kept in
trode 2
Cl2) or Ag/AgCl saturated solution of KCl.

Glass electrode Most widely used H+ ion sensitive

Electro-Analytical Basic principle electrode used in pH metre.
Method Calibration of pH metre carried
Conductometry Conductance V/S volume of out in following buffers 7.0, 4.0,
Titrant added 10.0 (sequence order). It is made
up of 22%Na2O, 6%CaO, and
Potentiometry Potential V/S volume of Titrant 72% SiO2.
added (No current flow i.e., I = 0)

Amperometry Current V/S volume of Titrant

added (V=Constant) Woodward Fieser Rule for conjugated Diene, triene
systems
Polargraphy Current V/S Applied Potential
Parent Values Homoannular conjugated 253 nm
diene
Bathochromic shift Shift towards longer wave-
Heteroannular conjugated 214 nm
(Red Shift) length or lower energy
diene
Hypsochromic shift Shift towards shorter wave- Acyclic conjugated diene 217 nm
(Blue Shift) length or higher energy Acyclic triene 245 nm

Hyper chromic shift Increase in intensity Increment Each alkyl substituent or + 5 nm

Ring residue
Hypo chromic shift Decrease in intensity Exocyclic double bond + 5 nm
Double bond extending + 30 nm
Auxochrome A group which extend the conju- conjugation
gation of a chromophore by shar-
ing of non-bonding electrons. Auxo- -Cl, -Br + 5 nm
chromes -OH/-OR/-SH + 6 nm
Chromophore Structural unit responsible for -SR + 30 nm
absorption -NR2 + 60 nm
The molar absorption at λmax -OCOCH3 + 0 nm
max
3.106  Chapter 3

Important Terminology Question: Calculate λ max

of following examples of
1. Homoannular Diene: It is a cyclic diene having conju- Dienes.
gated double bond in the same ring.
For example, H3C CH3
CH 3
yy Parent value for homoannular diene = 253 nm
yy Two alkyl substituents = 2 × 5 = 10 nm
yy Two ring residue = 2 × 5 = 10 nm
H3C yy Total calculated λ max = 253 + 10 + 10 = 273 nm
2. Heteroannular diene: It is a cyclic diene in which double
bonds in conjugation are present in different rings.
For example,

yy Parent value for heteroannular diene = 214 nm

yy Two alkyl substituents = 2 × 5 = 10 nm
3. Endocyclic double bond: A double bond present in a yy Three ring residue = 3 × 5 = 15 nm
ring as shown in the example. yy One exocyclic double bond = 5 nm
4. Exocyclic double bond: A double bond in which one yy Total calculated λ max = 214 + 10 + 15 + 5 = 244 nm
of the double bond is a part of a ring system shown in
ring B.

exocyclic double bond Extending

conjugation

Homoannular
diene

Extending
Endocyclic double bond conjugation

Ring A has one endocyclic yy Parent Value for homoannular diene = 253 nm
and one exocyclic double yy Four ring residue = 4 × 5 = 20 nm
A B bond. yy Two exocyclic double bond = 10 nm
Ring B has only one endocyclic yy Two double bond extanding conjugation = 2 × 30 = 60 nm
double bond yy Total calculated λ max = 253 + 20 + 10 + 60 = 343 nm

Woodward Fieser Rule for α, b-unsaturated carbonyl compounds

Parent O 215 nm

H3C R

R = H (Aldehyde) 207 nm
Values X = OH, OR (Acid or Ester) 193 nm
X = alkyl (Ketone) or six membered ring 215 nm

Increment Homoannular conjugated diene + 39 nm

Exocyclic double bond + 5 nm
Double bond extending conjugation + 30 nm
 Analytical Chemistry  3.107

Woodward Fieser Rule for α, b-unsaturated carbonyl compounds

Auxochromes Alkyl group or α β γ Δ/higher

ring residue +10 nm +12 nm +18 nm + 18 nm

–Cl +15 nm +12 nm +12 nm + 12 nm

–OH 35 nm + 30 nm + 30 nm + 50 nm
–SR – 85 nm – –
–NH2 – 95 nm –
–OCOCH3 + 6 nm + 6nm + 6 nm + 6 nm
–Br + 25 nm + 30 nm +18 nm +31 nm
–OR + 35 nm + 30 nm +18 nm +31 nm

Examples: yy Total calculated λ max = 215 + 10 + 12 = 237 nm

CH3
O
Beta carbon
Alfa carbon O
yy Parent value for α, β uusaturated 6 membered cyclic
yy Parent value for α, β uusaturated acyclic compound = compound = 215 nm
215 nm yy One alkyl substituent on α carbon = 10 nm
yy One alkyl substituents on α carbon = 10 nm yy Two ring residue on β carbon = 2 × 12 = 24 nm
yy One alkyl substituents on β carbon = 12 nm yy One exocyclic double bond = 5
yy Total calculated λ max = 215 + 10 + 12 = 237 nm yy Total calculated λ max = 215 + 10 + 24 + 5 = 254 nm
O
O

Woodward Fieser Rule for Acyl Benzene derivatives

yy Parent value for α, β uusaturated 6 membered cyclic
compound = 215 nm X= Alkyl 246 nm
yy One ring residue on α carbon = 10nm
Parent Value X= H 250 nm
yy Two ring residue on β carbon = 2 ×12 =24 nm
yy Double bond exocyclic to two (both) ring = 2 × 5 = X= OH/OR 230 nm
10 nm
yy Total calculated λ max = 215 + 10 + 24 + 10 = 259 nm
Auxochromes
Ortho Meta Para
Alkyl +3nm +3nm +10nm
O
OH/OR +7nm +7nm +25nm
O Cl 0nm 0nm +10nm

yy Parent value for α, β uusaturated 6 membered cyclic Br +2nm +2nm +15nm

compound = 215 nm NH2 +13nm +13nm +58nm
yy One alkyl substituent on α carbon = 10 nm
NHOCOCH3 +20nm +20nm +45nm
yy One ring residue on β carbon = 12 nm
3.108  Chapter 3

Examples:
SRM Parameter checked

O CH3 Potassium iodide Stray Light in UV/Visible

Didymium or Holomium Wavelength in UV/Vis-

Oxide ible

Polystyrene Film Wavelength in IR

Beer-Lambert Law
Br

yy Parent value for acyl benzene (Ketone) derivative = 246 nm

yy -Br atom at para position = 15 nm
yy Total calculated λ max = 246 + 15 = 261 nm
Io
It
O OH

Br Br

It states that the proportion of the light absorbed

by the solute in a homogenous, transparent medi-
um is independent of the intensity of the incident
OH light and proportional to the number of absorbing
molecules and path length.
yy Parent value for aromatic carboxylic acid derivative =
230 nm A = ЄCl = log (IO/It) = log 1/T = – log T = 2 – log % T
yy -Br atom at two ortho position = 2 × 2 = 4 nm
yy -OH group at para position = 25 A directly proportional to path length (Lambert law)
yy Total calculated λ max = 230 + 04 + 25 = 259 nm A directly proportional to concentration (Beer’s law)

Where A = Absorbance
Karl Fisher Titration (Coulometric end point Є = molar absorptivity/molar extinction coef-
detection) ficient
• It determines water content (moister content) in
pharmaceuticals. C = concentration (mol per litre)
• Reagent consists of mixture of anhydrous metha- l = path length
nol, anhydrous pyridine, and iodine and sulphur T = Transmittance = It/IO
dioxide.
• End point detection-presence of water causes con-
If concentration is taken in g per litre, then the for-
version of iodine to iodide through its reduction
mula becomes
by sulphur dioxide.
• Sodium tartarate dihydrate is used in standardiza- A = aCl
tion of Karl-Fisher reagent. a = absorptivity or extinction coefficient

Standard reference materials used in calibration of

When molecular weight of absorbing molecule is not
spectroscopic instrument
known, the A1cm1% is used to compare absorption
SRM Parameter checked intensity instead of Є.

Potassium dichromate Absorbance in UV/Visible A1cm1% = A/Cl

Quartz cuvett Path length in UV/Visible Where C = concentration (gm per 100 ml)
Toluene in Hexane Resolution in UV/Visible Thus Є = (A1cm1% × mol.wt)/10
 Analytical Chemistry  3.109

Proton (H1) NMR V/S Carbon (C13) NMR Flame Temperature in Kelvin (K)

1. Gyro magnetic (Magnogyretic) Ratio for proton Fuel Oxidant

NMR is 4 times than carbon-13 NMR.
Air Nitrous Oxide (N2O) Oxygen (O2)
2. Proton NMR provide information of periphery while
C-NMR about Backbone. Acetylene 2400 K 3200K 3400K

3. C
 hemical shift normal range for Proton NMR Hydrogen 2300K 2900K 2900 K
(0–10) while for C-NMR (0–200).
Propane 2200K 3000K 3100K
4. P
 roton NMR spectrum is more complex than
C-NMR because homo (H1-H1) as well as hetero Normal Phase Chromatography (NPC)
(H1-H2) nuclear coupling are possible in PMR but in      Stationary Phase (S.P.) Polar
C-NMR hetero nuclear coupling is not possible due
     Mobile Phase (M.P.) Non-Polar
to spin quantum number of C12 is zero and prob-
ability of homo nuclear coupling is very low due Elution Order-Alkane → Olefins → Aromatics →
to natural isotopic abundance of C13 is only 1.1%. Organic halides → Sulfide → Ether → nitro compounds
5. PMR is more sensitive than C13-NMR. → Ester/Aldehyde/Ketone → Alcohol/Amines → Sulfone
→ Sulfoxide → Amides → Carboxylic Acids
Information from PMR Non-polar compound will elute first and most polar will
elute last in the NPC.
Number of Signals Different sets of equivalent
protons in molecule Reverse Phase Chromatography (RPC)
     Stationary Phase (S.P.) Non-Polar
Intensity of Signal Relative number of protons of      Mobile Phase (M.P.) Polar
different kinds
Eluotropic Series–Increasing order of Solvent Polarity
Splitting or Multi- Environment of proton with
plicity of Signal respect to neighbouring proton Hexane/Pentane < Petroleum ether < Cyclo Hexane
< Xylene <Toluene < Diethyl ether < Chloroform
Area of Peak Number of absorbing protons
< Dichloromethane < THF < Acetone <Dioxane <
giving rise to a signal
Acetonitrile < Methanol <Water

List of important Chemical Shift Values (δ)

Protons on Protons on unsaturated Protons on Saturated CH3, CH2, Saturated CH3, CH2,
unsaturated carbons carbons e.g., Benzene, unsaturated carbons and CH protons next CH protons not next
next to oxygen e.g., Aromatic Hydrocarbons e.g., Alkenes to oxygen e.g., CH3O, to oxygen
Aldehyde CH2O

10.5 8.5 6.5 4.5 3.0 0.0

Large Chemical Shift Sm a ll

L ow (Down F ield ) Field H igh (Up F ield )

H igh Frequency L ow

De Shielded Shielding Shielded

Figure 3.16
3.110  Chapter 3

1. System Suitability Parameters for HPLC Method development

Parameters Acceptance criteria

Capacity factor The peak should be well resolved from other peaks.

Resolution (Rs) Rs > 2 between the peak of interest

Tailing factor (T) T is less than or equal to Two.

Theoretical plate (N) In general should be greater than 2000

2. Analytical method validation parameters

Specificity Specificity is the ability to assess unequivocally the analyte in the presence of components
which may be expected to be present. Typically these might include impurities, degradants,
matrix, etc.

The specificity of the method is determined by comparing the spectra (for UV) and chro-
matogram (for RP-HPLC) of the standard and sample solutions of analyte and both are
spectra/chromatogram are overlap.

Precision (n=6) Repeatability(n=6): Repeatability expresses the precision under the same operating
conditions over a short interval of time.

Reproducibility: Reproducibility expresses the precision between laboratories

Intermediate precision (n=3): Intermediate precision expresses within-laboratories variations:

different days, different analysts, different equipment, etc.
The intermediate precision of the method was confirmed by intraday (variation of results
within the same day) and interday (variation of results between days) analysis. The
intraday and interday precision of the proposed methods were performed by analyzing the
corresponding responses three times on the same day for intraday precision and over a
period of three days for inter day with three different concentrations of standard tertiary
mixture solutions.

LOD (Limit of The detection limit of an individual analytical procedure is the lowest amount of
Detection) analyte in a sample which can be detected but not necessarily quantitated as an exact
Value.

LOQ (Limit of The quantitation limit of an individual analytical procedure is the lowest amount of
Quantification) analyte in a sample which can be quantitatively determined with suitable precision and
accuracy. The quantitation limit is a parameter of quantitative assays for low levels of
compounds in sample matrices, and is used particularly for the determination of impurities
and/or degradation products.

The LOD and LOQ can be determine as per following

LOD = 3.3 σ / S and LOQ = 10 σ / S
Where, σ = standard deviation of y intercept of calibration curve (n = 6)
S = slope of a regression equation.

Linearity (n=6) The linearity of an analytical procedure is its ability (within a given range) to obtain test
results which are directly proportional to the concentration (amount) of analyte in the
sample.
Linearity is checked by diluting standard stock solution at six different concentrations and
correlation coefficients (r2) is greater than 0.995.
 Analytical Chemistry  3.111

Range The range of an analytical procedure is the interval between the upper and lower
concentration (amounts) of analyte in the sample (including these concentrations) for
which it has been demonstrated that the analytical procedure has a suitable level of
precision, accuracy and linearity.

Accuracy (n=3) The accuracy of an analytical procedure expresses the closeness of agreement between the
value which is accepted either as a conventional true value or an accepted reference value
and the value found. This is sometimes termed trueness.
The accuracy of the method will be carried out at three levels 80, 100 and 120 % of the
working concentration of sample. This procedure was repeated for three times for each
concentration.

Robustness(n=3) The robustness of an analytical procedure is a measure of its capacity to remain unaffected
by small, but deliberate variations in method parameters and provides an indication of its
reliability during normal usage.
Robustness of the method will be determined by changes in following parameters.

· pH ± 0.2
· Flow rate ± 10 %
· Wavelength ± 2 nm
· Change in mobile phase ratio ± 2 %
*For all validation parameters, % RSD value should not be more than 2.

3. List of Indicator used in different titration methods

Titration Indicators

Complexometric Murexide, solochrome black, Patton and Reedder’s indicator, Calcon or solochrome
dark blue, Xylenol orange, bromopyrogallol, thymolphthalexone, methylthymol
blue, zincon, variamine blue
Precipitation Eosin , fluorescin, Rose Bengal, tartrazine, alizarin red S, rhodamine 6G,
Phenosafranine
Nonaqueous Crystal violet, methyl red, 1- napthol benzein, oracet blue
Aqueous Methyl orange, phenolphthalein, methyl red, thymol phthalein, methyl yellow,
neutral red, congo red etc.

4. List of ICH Guidelines

Quality Guidelines

Q1A - Q1F: Stability

· Q1A(R2)Stability Testing of New Drug Substances and Products

· Q1BStability Testing : Photostability Testing of New Drug Substances and Products

· Q1A(R2)Stability Testing of New Drug Substances and Products

· Q1BStability Testing : Photostability Testing of New Drug Substances and Products

· Q1A(R2)Stability Testing of New Drug Substances and Products

· Q1BStability Testing : Photostability Testing of New Drug Substances and Products

3.112  Chapter 3

Q2(R1): Validation of Analytical Procedures: Text and Methodology

Q3A - Q3D: Impurities

· Q3A(R2)Impurities in New Drug Substances

· Q3B(R2)Impurities in New Drug Products

· Q3C(R5)Impurities: Guideline for Residual Solvents

· Q3DGuideline for Elemental Impurities

· Q3d Training Implementation of Guideline for Elemental Impurities

Q4 - Q4B: Pharmacopoeias

· Q4Pharmacopoeias

· Q4APharmacopoeial Harmonisation

· Q4BEvaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions

Q5A - Q5E: Quality of Biotechnological Products

· Q5A(R1)Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal
Origin

· Q5BAnalysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein Products

· Q5CStability Testing of Biotechnological/Biological Products

· Q5DDerivation and Characterisation of Cell Substrates Used for Production of Biotechnological/

Biological Products

· Q5EComparability of Biotechnological/Biological Products Subject to Changes in their Manufacturing

Process

Q6A- Q6B: Specifications

· Q6ASpecifications : Test Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances

· Q6BSpecifications : Test Procedures and Acceptance Criteria for Biotechnological/Biological Products

Q7 : Good Manufacturing Practice

Q8 : Pharmaceutical Development

Q9 : Quality Risk Management

Q10: Pharmaceutical Quality System

Q11: Development and Manufacture of Drug Substances

Q12: Lifecycle Management

 Analytical Chemistry  3.113

Safety Guidelines

S1A - S1C: Carcinogenicity Studies

· S1Rodent Carcinogenicity Studies for Human Pharmaceuticals

· S1ANeed for Carcinogenicity Studies of Pharmaceuticals

· S1BTesting for Carcinogenicity of Pharmaceuticals

· S1C(R2)Dose Selection for Carcinogenicity Studies of Pharmaceuticals

S2: Genotoxicity Studies

S3A - S3B: Toxicokinetics and Pharmacokinetics

· S3ANote for Guidance on Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies

· S3A Q&AsQuestions and Answers: Note for Guidance on Toxicokinetics: The Assessment of Systemic
Exposure - Focus on Microsampling

· S3BPharmacokinetics: Guidance for Repeated Dose Tissue Distribution Studies

S4: Toxicity Testing

S5: Reproductive Toxicology

S6: Biotechnological Products

S7A - S7B: Pharmacology Studies

· S7ASafety Pharmacology Studies for Human Pharmaceuticals

· S7BThe Non-Clinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval
Prolongation) by Human Pharmaceuticals

S8: Immunotoxicology Studies

S9: Nonclinical Evaluation for Anticancer Pharmaceuticals

S10: Photosafety Evaluation

S11: Nonclinical Safety Testing

Efficacy Guidelines

E1: Clinical Safety for Drugs used in Long-Term Treatment

E2A - E2F: Pharmacovigilance

· E2A:Clinical Safety Data Management: Definitions and Standards for Expedited Reporting

· E2B(R3):Clinical Safety Data Management: Data Elements for Transmission of Individual Case Safety
Reports
3.114  Chapter 3

· E2B(R3): Implementation: Electronic Transmission of Individual Case Safety Reports

· E2C(R2):Periodic Benefit-Risk Evaluation Report

· E2C(R2:) Questions & Answers: Periodic Benefit-Risk Evaluation Report

· E2D:Post-Approval Safety Data Management: Definitions and Standards for Expedited Reporting

· E2E:Pharmacovigilance Planning

· E2F:Development Safety Update Report

E3: Clinical Study Reports

E4: Dose-Response Studies

E5: Ethnic Factors

E6: Good Clinical Practice

E7: Clinical Trials in Geriatric Population

E8: General Considerations for Clinical Trials

E9: Statistical Principles for Clinical Trials

E10: Choice of Control Group in Clinical Trials

E11: Clinical Trials in Pediatric Population

E12: Clinical Evaluation by Therapeutic Category

E14: Clinical Evaluation of QT

E15: Definitions in Pharmacogenetics / Pharmacogenomics

E16: Qualification of Genomic Biomarkers

E17: Multi-Regional Clinical Trials

E18: Genomic Sampling

Multidisciplinary Guidelines

M1: MedDRA Terminology

M2: Electronic Standards

M3: Nonclinical Safety Studies

M4: Common Technical Document

M5: Data Elements and Standards for Drug Dictionaries

M6: Gene Therapy

M7: Genotoxic Impurities

M8: Electronic Common Technical Document (eCTD)

 Analytical Chemistry  3.115

Fourier transform (F.T.) concept

It is a mathematical operation which converts Time Domain Spectra into Frequency Domain Spectra.

Cosine Interferogram FT IR Frequency Domain Spectra

Free Induction DecaySignal FT NMR Frequency Domain Spectra

Time domain trace Frequency domain trace

Stationary
mirror

Time

Beam splitter

Source Movable
mirror

Sample
position

Detector

Advantage of FT of high frequency signals to measurable ones.

1. Fellgett or Multiplex–Increase in S/N ratio Radiation source is He-Ne laser lamp.
2. Jacquinot–Increased energy throughput Laser beam positioning It tells about Sampling Inter-
3. High resolution val time.
4. High sensitivity
Zero position referencing (White light system) It
Michelson interferometer indicates starting point of data sampling for each scan.
It acts as modulating device. Modulation means conversion

Stretching Vibrational Frequencies (cm–1)

C-X
O-H C-C, C-N (Triple bond)
Transparent C=N C-O
C-H X=C=Y C=O
Region C=C C-N
N-H X, Y=C, O, N, S
C-C

4000 2500 2000 1800 1650 1550 500

Alkane – -C-Hstretch (3000 cm–1) -C-Hbend (1440, 1375 cm–1)

(-C-C-) Isopropyl (1375 cm–1) t-Butyl (1375 cm–1)
Alkene – C-Hbend in Cis alkene (700 cm–1) Trans alkene (970cm–1)
(-C=C-)
Alkynes – C-H in triple bonded carbon atom (3300 cm–1)
C triple bond C ( 2150 cm–1)
3.116  Chapter 3

Aromatics – C-Hbend in O-disubstituted 750, 690 cm–1

m-disubstituted 690, 780 cm–1
p-disubstituted 800–850 cm–1
Alcohols – O-H stretching at 3500–3700 cm–1 (without hydrogen bonding)
3200–3500 cm–1 (hydrogen bonding)
C-O stretching at 1100–1300 cm–1
Carbonyl and
Acid derivatives – C=Ostretch order
 Anhydride I band (1810 cm–1) > Acid Halide (1800 cm–1) > Anhydride II band (1760 cm–1) > Esters (1735 cm–1) >
Aldehydes (1725 cm–1) > Ketones (1715 cm–1) > Carboxylic Acid (1710 cm–1) > Amides (1690 cm–1)
Aldehyde can be differentiated from Ketone due to presence of doublet of C-Hstretch at 2750 cm-1 and 2850 cm-1

C-N stretching in Nitriles at 2250 cm–1

N=O stretching at 1550 and 1650 cm–1
S-H stretching at 2550 cm–1
S=O stretching at 1350 and 1150 cm–1

Analytical method based on different properties

Measured Analytical Methods
Measured Analytical Methods Property
Property
Mass to charge Mass Spectroscopy
Mass Gravimetric ratio

Rotation of Polarimetry, Optical rotatory dis-

Volume Volumetric
radiation persion (ORD) and Circular Dichro-
Electrical Potentiometry, Chronopotentiom- ism (CD)
potential etry
Thermal Thermal conductivity and enthalpy
Electrical Conductometry, Properties methods
Conductance
Titrimetic Analysis
Electrical Polarography, Amperometry
current, Titration A measured amount of a solution of unknown
concentration is added to a known volume of a second solu-
Quantity of Coulometer tion until the reaction between them is just complete; the
electricity concentration of the unknown solution (the titer) can then
be calculated.
Absorption of Spectrophotometry (UV, Visible, IR,
radiation X-ray), Calorimetry, Atomic absorp- Analyte (Titrant) An analyte is a weak base or acid. Its
tion spectroscopy, NMR and ESR structure is made from any compound that can be converted
to a strong acid or base.
Emission of Emission spectroscopy (UV, Visible,
Titrant The titrant is a strong acid or base that is slowly
radiation X-ray), Flame photometry, Fluores-
added to the analyte until it reaches any visible change in
cence, Radiochemical methods
the colour of the solution under observation.
Refraction of Refrectometry, Interferometry Indicator It is a pH marker added to the analyte that trig-
radiation gers a change in colour when equilibrium is reached. It should
have a weaker acid/base concentration than the analyte.
Scattering of Turbidimetry, Nephelometry, Ra-
radiation man Spectroscopy Acidimetry Volumetric analysis using standard solutions
of acids to measure the amount of a base present.
Diffraction of X-ray electron diffraction methods
Alkalimetry Volumetric analysis using standard solu-
radiation
tions of alkali to measure the amount of acid present.
 Analytical Chemistry  3.117

Standards endpoint of the normal titration. They are also useful if the
Certain chemicals which are used in defined concentrations reaction between the analyte and the titrant is very slow.
as reference materials.
Types of titrations
yy Primary standards
yy Secondary standards 1. Acid-base titration
Indicators for Acid-Base titration
Primary standards
Available in pure form, stable and easily dried to a constant Indicator Colour Range of Colour on
known composition. on Acidic Colour Basic Side
yy Stable in air. Side Change
yy High molecular weight.
Methyl Violet Yellow 0.0–1.6 Violet
yy Readily soluble.
yy Undergoes stoichiometric and rapid reactions. Bromophenol Blue Yellow 3.0–4.6 Blue

Methyl Orange Red 3.1–4.4 Yellow

Titration Method Primary Standards
Methyl Red Red 4.4–6.2 Yellow
Acid-base reactions Na2CO3, Na2B4O7, KH (C8H4O4), HCl

Complex forma- AgNO3, NaCl Litmus Red 5.0–8.0 Blue

tion reactions
Bromothymol Blue Yellow 6.0–7.6 Blue
Precipitation reac- AgNO3, KCl
tions Phenolphthalein Colorless 8.3–10.0 Pink

Redox reactions K2Cr2O7, Na2C2O4, I2 Alizarin Yellow Yellow 10.1–12.0 Red

Secondary standards pH meter and Conductivity metre can be used for end
A substance that can be used for standardisations, and point detection.
whose concentration of active substance has been deter-
2. Redox titration
mined by comparison to a primary standard.
Most commonly, a potentiometer or a redox indicator is
Standard solution used to determine the end point of the titration. For exam-
It is a solution of accurately known concentration prepared ple, when one of constituents of the titration is the oxidiz-
from a primary standard (a compound which is stable, of ing agent potassium dichromate, the colour change of the
high purity, highly soluble in water and of a high molar solution from orange to green is not definite and thus an indi-
mass to allow for accurate weighing) that is weighed accu- cator such as sodium diphenylamine is used. The analysis of
rately and made up to a fixed volume. wines for their sulfur dioxide content requires the use of iodine
as an oxidizing agent. In this case, starch is used as an indica-
Types of volumetric titrations tor; a blue starch-iodine complex is formed once an excess of
There are three types of volumetric titration, which are iodine is present, thus signalling the endpoint of the titration.
classified based on the rate of their reaction. Direct titra- Some redox titrations do not require an indicator, due
tion method (DTM) is a one-step titration process. Indirect to the intense colour of some of the constituents. For instance,
method (ITM) involves a two-step titration process. Back in a titration where the oxidizing agent potassium perman-
titration method (BTM) uses a three-step titration process. ganate (permanganometry) is present, a slightly faint
persisting pink colour signals the endpoint of the titration,
Back titration and no particular indicator is therefore required.
The term back titration is used when a titration is done Standardization of Potassium Permanganate or Cerium
“backwards”; instead of titrating the original analyte, one IV sulphate done by Sodium Oxalate or Arsenic III oxide.
adds a known excess of a standard reagent to the solution, Standardization of Potassium Dichromate is done by metallic
then titrates the excess. A back titration is useful if the end- iron. Standardization of Iodine is done by Sodium Thiosul-
point of the reverse titration is easier to identify than the phate or Arsenic III oxide.
3.118  Chapter 3

Application–Determination of Copper, Dissolved salt to ammonia. The amount of ammonia present (hence
oxygen, Chlorine, Arsenic IV, Sulphides. the amount of nitrogen present in the sample) is determined
by back titration. The end of the condenser is dipped into
3. Complexometric titration
a solution of boric acid. The ammonia reacts with the acid
These titrations are based on the formation of a complex and the remainder of the acid is then titrated with a sodium
between the analyte and the titrant. The chelating agent carbonate solution with a methyl orange pH indicator.
EDTA is very commonly used to titrate metal ions in solution.
Degradation Protein + H2SO4 → (NH4)2 SO4 (aq) + CO2 (g)
These titrations generally require specialized indicators that
+ SO2 (g) + H2O (g)
form weaker complexes with the analyte. A common exam-
ple is Eriochrome Black T for the titration of calcium and Liberation of ammonia (NH4)2 SO4 (aq) + 2NaOH →
magnesium ions. Indicators-Murexide, Solochrome Black, Na2SO4 (aq) + 2H2O (l) + 2NH3 (g)
Xylenol orange, Eriochrome Black etc. Capture of ammonia B (OH)3 + H2O + NH3 → NH4+
Application Determination of cations and hardness of + B (OH)4–
water. Back-titration B (OH)3 + H2O + Na2CO3 → NaHCO3
4. Zeta potential titration (aq) + NaB (OH)4 (aq) + CO2 (g) + H2O.
These titrations characterize heterogeneous systems, such
as colloids. Zeta potential plays role of indicator. One of the Precipitation Titration
purposes is determination of iso-electric point when surface Titrations with precipitating agents are useful for deter-
charge becomes 0. mining certain analytes. E.g., Cl– can be determined when
titrated with AgNO3.
5. Iodometry
Usual reagents are sodium thiosulfate as titrant, starch as an Detection of end point
indicator (it forms blue complex with iodine molecules—
though polyvinyl alcohol has started to be used recently as yy Chemical
well), and an iodine compound (iodide or iodate, depending ‡‡ Precipitation Type–Mohr’s method
on the desired reaction with the sample). ‡‡ Adsorption–Fajan’s method
The principal reaction is the reduction of iodine to ‡‡ For silver analysis–Volhard method
iodide by thiosulfate: yy Sensors–Potentiometric or amperometric
I2 + 2S2O32− → S4O62− + 2I−
6. Precipitation reactions The chemical types are also classified into:
1. Mohr method-Using Ag+ as a titrant in chlorides (or 1. Indicators reacting with titrant forming specific colour.
bromides) determination. 2. Adsorption indicators.
End point detection-small amount of sodium or potas-
sium chromate Indicators reacting with the titrant
2. Volhard method-Titration with thiocyanates, can be Two methods will be discussed where this type of indicators
used for Ag+ determination, or for indirect determina- are applied; namely: Mohr and Volhard.
tion (thorough back titration) of chlorides.
End point detection-Iron (III) thiocyanate complex I) Mohr method for determining chloride
3. Kjeldahl method or Kjeldahl digestion Chloride is titrated with AgNO3 solution. A soluble chro-
Quantitative determination of nitrogen in chemical mate salt is added as the indicator. This produces a yellow
substances. colour solution. When the precipitation of the chloride is
The method consists of heating a substance with sulphuric complete, the first excess of Ag+ reacts with the indicator to
acid, which decomposes the organic substance by oxidation precipitate red silver chromate:
to liberate the reduced nitrogen as ammonium sulphate. In
this step, potassium sulphate is added in order to increase 2 Ag+(aq) + CrO42–(aq) → Ag2CrO4(s)
the boiling point of the medium. Chemical decomposition
Yellow red ppt
of the sample is complete when the medium has become
clear and colourless (initially very dark). The Mohr method must be performed at a pH about
The solution is then distilled with sodium hydroxide 8. This method is useful for determining Cl– in neutral or
(added in small quantities) which converts the ammonium unbuffered solutions such as drinking water.
 Analytical Chemistry  3.119

II) Volhard titration rofluorescein (DCF) on the surface of the positively charged
This is an indirect titration procedure for the determination silver chloride particles formed in the precipitation titration
of anions that precipitate with silver like Cl–, Br–, I–, SCN-, when Ag+ ion is in excess.
and it is preferred in acid (HNO3) solution. A measured Application of PPtion Titration Determination of an-
excess of AgNO3 is added to precipitate the anion, and the ions such as halides, divalent anions, mercaptans.
excess of Ag+ is determined by back titration with standard
potassium thiocyanate solution: Non-aqueous titration
Ag+(aq) + Cl–(aq) → AgCl(s) + excess Ag+ Non-aqueous titration is the titration of substances
dissolved in non-aqueous solvents. It is the most com-
excess Ag+(aq) + SCN–(aq) → AgSCN(s) mon titrimetric procedure used in pharmacopoeial assays
The end point is detected by adding iron III (Fe3+) as and serves a double purpose: it is suitable for the titration
ferric ammonium sulfate which forms a soluble red com- of very weak acids and very weak bases, and it provides a
plex with the first excess of titrant. solvent in which organic compounds are soluble.
The most commonly used procedure is the titration of
Fe3+ (aq) + SCN–(aq) → [FeSCN]2+(aq) organic bases with perchloric acid in anhydrous acetic acid.
These indicators must not form a compound with
Non-aqueous solvents
the titrant that is more stable than the precipitate or the
colour reaction would occur on addition of the first drop of Aprotic solvents
titrant. These are neutral, chemically inert substances such as benzene
and chloroform. They have a low dielectric constant, do not
Adsorption indicators react with either acids or bases and therefore do not favour
The indicator reaction takes place on the surface of the ionization. Since dissociation is not an essential preliminary
precipitate. The indicator, which is a dye, exists in solution to neutralization, aprotic solvents are often added to ‘ionizing’
as the ionized form, usually an anion. solvents to depress solvolysis (which is comparable to hydroly-
sis) of the neutralization product and so sharpen the endpoint.
Principle of adsorption Protophilic solvents
Consider the titration of Cl– with Ag+. Before the equivalent These are basic in character and react with acids to form
point, Cl– is in excess and the primary layer is Cl– (go back solvated protons.
to precipitation process in gravimetry). This repulses the
indicator anions; and the more loosely held the secondary HB + Sol. ⇌ Sol.H+ + B–
(counter) layer of adsorbed ions is cations, such as Acid + Basic solvent ⇌ Solvated proton + Conjugate
Na +
: AgCl : Cl : : Na
– + base of acid
A weakly basic solvent has less tendency than a strong-
Beyond the equivalent point (end point as well), Ag+ ly basic one to accept a proton. Similarly, a weak acid has
is in excess and the surface of the precipitate becomes less tendency to donate protons than a strong acid. As a
positively charged, with the 1° layer being Ag+. This will result a strong acid such as perchloric acid exhibits more
now attract the indicator anion and adsorb it in the 2° strongly acidic properties than a weak acid such as acetic
(counter) layer: acid when dissolved in a weakly basic solvent.
AgCl : Ag+ : : indicator – On the other hand, all acids tend to become indistin-
guishable in strength when dissolved in strongly basic
The colour of the adsorbed indicator is different from solvents owing to the greater affinity of strong bases for
that of the unadsorbed indicator, and this difference signals protons. This is called the leveling effect. Strong bases are
the completion of the titration. The degree of adsorption of leveling solvents for acids, weak bases are differentiating
the indicator can be decreased by increasing the acidity. solvents for acids.
The titration of chloride using this kind of indicator is
called Fajan’s Method. Protogenic solvents
Fajan’s method is the most recent and most accurate These are acidic substances, e.g., sulphuric acid. They exert
silverhalide method. It is based on the adsorption of dichlo- a levelling effect on bases.
3.120  Chapter 3

Amphiprotic solvents The quantitative determination of a substance by the

They have both protophilic and protogenic properties. precipitation method of gravimetric analysis involves
Examples are water, acetic acid and the alcohols. They are isolation of an ion in solution by a precipitation reaction,
dissociated to a slight extent. The dissociation of acetic acid, filtering, washing the precipitate free of contaminants,
which is frequently used as a solvent for titration of basic conversion of the precipitate to a product of known composi-
substances, is shown in the equation below: tion, and finally weighing the precipitate and determining
its mass by difference. From the mass and known composi-
CH3COOH ⇌ H+ + CH3COO– tion of the precipitate, the amount of the original ion can
Here, the acetic acid is functioning as an acid. If a very be determined.
strong acid such as perchloric acid is dissolved in acetic
acid, the latter can function as a base and combine with Steps involved in gravemetric analysis
protons donated by the perchloric acid to form protonated 1. Coprecipitation
acetic acid, an onium ion:
This is anything unwanted which precipitates with the
HClO4 ⇌ H+ + ClO4– thing you do want. Coprecipitation occurs to some degree
CH3COOH + H+ ⇌ CH3COOH2+ (onium ion) in every gravimetric analysis (especially barium sulfate
and those involving hydrous oxides). You cannot avoid
Since the CH3COOH2+ ion readily donates its proton it—all you can do is minimize it by careful precipitation and
to a base, a solution of perchloric acid in glacial acetic acid thorough washing.
functions as a strongly acidic solution.
When a weak base, such as pyridine, is dissolved in 2. Surface adsorption
acetic acid, the acetic acid exerts its levelling effect and en- Here unwanted material is adsorbed onto the surface of the
hances the basic properties of the pyridine. It is possible, precipitate. Digestion of a precipitate reduces the amount
therefore, to titrate a solution of a weak base in acetic acid of surface area and hence the area available for surface
with perchloric acid in acetic acid, and obtain a sharp end- adsorption. Washing can also remove surface material.
point when attempts to carry out the titration in aqueous
solution are unsuccessful. 3. Occlusion
Visual indicators for non-aqueous titration This is a type of coprecipitation in which impurities are
trapped within the growing crystal.
Indicator Colour Colour Colour
change change change 4. Postprecipitation
basic neutral acidic Sometimes a precipitate standing in contact with the mother
Crystal violet violet blue- yellow- liquor becomes contaminated by the precipitation of an im-
(0.5 per cent in green ish-green purity on top of the desired precipitate.
glacial acetic acid)
5. Washing and filtering
α-Naphtholbenzein blue or orange dark- Problems with coprecipitation and surface adsorption may
(0.2 per cent in blue- green
be reduced by careful washing of the precipitate. With many
glacial acetic acid) green
precipitates, peptization occurs during washing. Here part
Oracet Blue B blue purple pink of the precipitate reverts to the colloidal form e.g.,
(0.5 per cent in
glacial acetic acid) AgCl (colloidal) AgCl (s)

Quinaldine Red magenta almost This results in the loss of part of the precipitate because
(0.1 per cent in colo the colloidal form may pass through on filtration. By washing
methanol) with ice cold water, this can be minimized.

6. Drying of solid
Gravemetric Analysis Generally, the solids are dried at about 120oC but condi-
Gravimetric analysis, which by definition is based upon the tions for drying can vary considerably. To determine the
measurement of mass, can be generalized into two types: correct drying regime, a thermogravimetric balance may
precipitation and volatilization. be used.
 Analytical Chemistry  3.121

Commercial Acids and Bases

Solution Formula Weight Molarity Normality Weight (%) Specific Gravity

Acetic acid 60.05 17.4 17.4 99.8 1.05

[CH3COOH]

Ammonia 35.05 14.8 14.8 57 0.90

[NH4OH]

Hydrochloric acid 36.46 12.1 12.1 37 1.19

[HCl]

Nitric acid 63.01 15.8 15.8 70 1.42

[HNO3]

Sulfuric acid 98.08 18.0 36.0 96 1.84

[H2SO4]

Phosphoric acid 97.1 14.8 44.6 85 1.70

[H3PO4]

Pharmaceutical Impurities x. The amount of drug substance administered per day.

Impurities in pharmaceuticals are the unwanted chemicals that y. Higher reporting thresholds should be scientifically
even in small amounts may influence the efficacy and safety of justified.
the pharmaceutical products. Impurity profiling is the identity z. Lower thresholds can be appropriate if the impurity is
as well as the quantity of impurity in the pharmaceuticals. unusually toxic.

Sources of Impurities
Thresholds for degradation products in Drug Products
Associated Related to Upon Aging Maximum daily dose (a) Reporting threshold (b,c)
with API Formulation ≤1 g 0.1%
1. Organic 1. Process /Method 1. Ingredient >1 g 0.05%
Impurities Related interaction Maximum daily dose (a) Reporting threshold (b,c)
2. Inorganic 2. Dosgae form 2. Functional <1 mg 1.0% or 5 μg TDI,
Impurities related group whichever is lower
3. Residual 3. Environment degradation
1 mg–10 mg 0.5% or 20 μg TDI,
Solvents related whichever is lower

ICH Guideline on Impurities >10 mg–2 g 0.2% or 2 mg TDI,

whichever is lower
Q3A Impurities in New Drug Substances
Q3B(R2) Impurities in New Drug Products x>2 g 0.10%
Q3C Guidelines for Residual solvents Maximum daily dose (a) Reporting threshold (b,c)
Q3D Guidelines for Elemental impurities <10 mg 1.0% or 50 μg TDI,
whichever is lower
Drug Substances Impurities thresholds
10 mg–100 mg 0.5% or 200 μg TDI,
Maximum Reporting Identification Qualification whichever is lower
daily threshold Threshold (z) threshold
Dose (x) (y, z) >100 mg–2 g 0.2% or 3 mg TDI,
whichever is lower
< 2g/day 0.05% 0.1% or 1 mg 0.15% or 1 mg
>2 g 0.15%
per day intake per day intake
(whichever is (whichever is a The amount of drug substance administered per day.
lower) lower) b Thresholds for degradation products are expressed ei-
> 2g/day 0.03% 0.05% 0.05% ther as a percentage of the drug substance or as total
3.122  Chapter 3

daily intake (TDI) of the degradation product. Lower N-methyl pyrrol- 48.4 4840
thresholds can be appropriate if the degradation product idone
is unusually toxic.
c Higher thresholds should be scientifically justified Pyridine 2 200
Toluene 8.9 890
Residual Solvents Xylenes 21.7 2170
Class I solvents: Solvents to be Avoided Known human
Methyl cyclo hex- 11.8 1180
carcinogens strongly suspected human carcinogens Envi-
ane
ronmental hazards.
Methyl butyl 0.5 50
Residual solvent Concentration limit (ppm) ketone
Benzene 2 ( Carcinogenic) Nitromethane 0.5 50
Carbon tetrachloride 4 (Toxic) Sulfolane 1.6 160
1,1 Dichloro ethene 8 (Toxic) Tetralin 1 100
1,2 Dichloro ethene 5 (Toxic)
1,1,2-Trichloro 0.8 80
1,1,1 trichloro ethane 1500 (Environmental hazard) ethane

Class II solvents: Solvents to be Limited Nongenotoxic ani- Class III Solvents: These are less toxic and possess lower
mal carcinogens or possible causative agents of other irre- risk to human health than class I or class II solvents. Long-
versible toxicity, such as neurotoxicity or teratogenicity. Sol- term toxicity or carcinogenicity not reported, which is
vents suspected of other significant but reversible toxicities. evident from the available data for the solvents under this
category. The use of class III solvents in pharmaceuticals
Solvent Permissible Concentration
daily exposure limit (ppm)
does not have any serious health hazard.
(mg/day) Solvents with Low Toxic Potential Solvents with low toxic
Acetonitrile 4.1 410 potential to humans; no health-based exposure limit is need-
ed. [NOTE—Class 3 residual solvents may have PDEs of up
Chlorobenzene 3.6 360 to 50 mg or more per day.]
Chloroform 0.6 60
Acetic acid Dimethyl Isobutyl acetate
Cyclohexane 38.8 3880 sulfoxide
1,2-Dichloroethene 18.7 1870 Acetone Ethanol Isopropyl acetate
Dichloromethane 6 600 Anisole Ethyl acetate Methyl acetate
1,1-Dimethoxy- 1 100 1-butanol Ethyl ether Propyl acetate
ethane
2-butanol Ethyl formate Pentane
N,N-Dimehtyl 10.9 1090
acetamide Butyl acetate Formic acid Methyl ethyl ketone

N,N-Dimethyl for- 8.8 880 Cumene Heptane Methyl isobutyl ketone

mamide 1- pentanol 1-propanol 2-propanol
1,2-Dioxane 3.8 380
Class IV Solvents: Class IV solvents, adequate toxicologi-
2-Ethoxyethanol 1.6 160
cal data is not available. The manufacturers should justify
Ethylene glycol 6.2 620 the residual levels for these solvents in pharmaceutical prod-
Formamide 2.2 220 ucts. The solvents under class IV are1, 1-diethoxy propane,
1-1-dimethoxy propane, 2-2-dimethoxy propane, methyl
Hexane 2.9 290
isopropyl ketone, isooctane, isopropyl ether, methyl tetrahy-
Methanol 30 3000 drofuran, petroleum ether, trichloro acetic acid.
 Analytical Chemistry  3.123

Guideline for Elemental Impurities ICH Q3D the risk assessment. For parenteral and inhalation products,
Three Class based on their Toxicity (PDE) and Occurrence the potential for inclusion of these elemental impurities
Type of Class Elemental Impurities should be evaluated during the risk assessment, unless the
route specific PDE is above 500 μg/day. The elements in this
Class 1 As, Cd, Hg & Pb
class include: Ba, Cr, Cu, Li, Mo, Sb, and Sn.
Class 2A Co, Ni & V
Other elements: Some elemental impurities for which
Class 2B Ag, Au, Ir, Os, Pd, Pt, Rh, Ru, Se & Tl PDEs have not been established due to their low inherent
Class 3 Ba, Cr, Cu, Li, Mo, Sb & Sn toxicity and/or differences in regional regulations are not
addressed in this guideline. If these elemental impurities are
* PDE-Permitted daily exposure present or included in the drug product they are addressed
Class 1: The elements, As, Cd, Hg, and Pb, are human by other guidelines and/or regional regulations and practices
toxicants that have limited or no use in the manufacture that may be applicable for particular elements (e.g., Al for
of pharmaceuticals. Their presence in drug products compromised renal function; Mn and Zn for patients with
typically comes from commonly used materials (e.g., compromised hepatic function), or quality considerations
mined excipients). Because of their unique nature, these (e.g., presence of W impurities in therapeutic proteins) for
four elements require evaluation during the risk assessment, the final drug product. Some of the elements considered
across all potential sources of elemental impurities and include: Al, B, Ca, Fe, K, Mg, Mn, Na, W and Zn.
routes of administration. The outcome of the risk assessment Permitted Daily Exposures(PDEs) for Elemental Impurities
will determine those components that may require additional
controls which may in some cases include testing for Class 1 Oral PDE Parenteral Inhalation
Element Class
elements. It is not expected that all components will require μg/day PDE, μg/day PDE, μg/day
testing for Class 1 elemental impurities; testing should Cd 1 5 2 2
only be applied when the risk assessment identifies it as the Pb 1 5 5 5
appropriate control to ensure that the PDE (permitted daily
As 1 15 15 2
exposure) will be met.
Hg 1 30 3 1
Class 2: Elements in this class are generally considered
Co 2A 50 5 3
as route-dependent human toxicants. Class 2 elements are
further divided in sub-classes 2A and 2B based on their V 2A 100 10 1
relative likelihood of occurrence in the drug product. Ni 2A 200 20 5
• Class 2A elements have relatively high probability of Tl 2B 8 8 8
occurrence in the drug product and thus require risk Au 2B 100 100 1
assessment across all potential sources of elemental Pd 2B 100 10 1
impurities and routes of administration (as indicated).
Ir 2B 100 10 1
The class 2A elements are: Co, Ni and V.
Os 2B 100 10 1
• Class 2B elements have a reduced probability of
Rh 2B 100 10 1
occurrence in the drug product related to their low
abundance and low potential to be co-isolated with Ru 2B 100 10 1
other materials. As a result, they may be excluded Se 2B 150 80 130
from the risk assessment unless they are intentionally Ag 2B 150 10 7
added during the manufacture of drug substances, Pt 2B 100 10 1
excipients or other components of the drug product.
Li 3 550 250 25
The elemental impurities in class 2B include: Ag, Au,
Ir, Os, Pd, Pt, Rh, Ru, Se and Tl. Sb 3 1200 90 20
Ba 3 1400 700 300
Class 3: The elements in this class have relatively low
toxicities by the oral route of administration (high PDEs, Mo 3 3000 1500 10
generally > 500 μg/day) but may require consideration in Cu 3 3000 300 30
the risk assessment for inhalation and parenteral routes. Sn 3 6000 600 60
For oral routes of administration, unless these elements are
Cr 3 11000 1100 3
intentionally added, they do not need to be considered during
3.124  Chapter 3

Multiple Choice Questions

1. Bending vibrations include all following except (P) NaCl
(a) Rocking (b) Stretching (Q) eSO4
(c) Twisting (d) Wagging (R) KBr
(S) AlCl3
2. For calibration of wave number scale in IR _______ is
used. (a) P, Q (b) P, S
(c) R, S (d) P, R
(a) Holmium filter (b) Polystyrene film
(c) Polyvinyl film (d) None 11. The region mostly used for IR spectroscopy is
3. For obtaining IR radiation Nernst filament should be (a) Near IR (b) Mid-IR
heated to _______°C. (c) Far IR (d) Very far IR
(a) 500–1000 (b) 1000–1500 12. Hexachlorobutadiene is preferred over Nujol as a
(c) 2000–2500 (d) 1000–1800 mulling agent because
4. CO2 not identified by IR spectroscopy it’s due to (a) It is non toxic
(a) CO2 has no dipole moment although C=O is polar (b) It does not give C–H vibration bands
(b) CO2 has no dipole moment since C=O is non-polar (c) It is transparent over IR range
(c) Optical activity of the system (d) It has very high boiling point.
(d) Both a and b 13. The band width in IR _____ due to H bonding.
5. Which of the following requires the most energy in IR? (a) Increases
(a) Wagging (b) Asymmetric bend (b) Decreases
(c) Twisting (d) Asymmetric stretch (c) Remains unchanged
(d) Cannot be predicted
6. Lasers are nowadays used as radiation source in visible
and IR regions because 14. Homo molecular molecules are IR inactive because
(a) It emits highly monochromatic light. (a) They cannot give vibrational spectra
(b) It emits coherent light (b) They have only stretching vibrations
(c) Little or no spreading of radiation as it propagates (c) They have no bending vibrations
(d) All the above are correct (d) The dipole moment does not change during
vibration
7. In far infrared region the radiation sources use is
15. Which of the following transitions will require more
(a) Incandescent lamp (b) Nernst glower
wavelengths?
(c) Globar sources (d) Mercury Arc
(a) Vibrational
8. In XY2 molecule vibration of atom is take place in same (b) Rotational
plan and only bond angle is change then it is called (c) Electronic
(a) Stretching vibration (d) Vibrational – Rotational
(b) Bending vibration
16. Which of the following prisms will you use for IR
(c) Scissoring vibration spectroscopy?
(d) Rocking vibration
(a) Glass prism
9. SiC rod heated to a high temperature is used as (b) Fused silica prism
(a) Source of light in IR (c) Prism coated with NaCl
(b) Detector in IR (d) All can be used
(c) Source of light in UV 17. Which of the following is not a thermal detector that
(d) Source of light in florimetry used in IR spectroscopy?
10. The IR spectrum of an organic liquid can be taken by (a) Thermocouple
placing it between a pair of polished plates made of (b) Photoconductive detector
 Analytical Chemistry  3.125

(c) Bolometer (a) Carbonyl compounds

(d) Golay pneumatic detector (b) Azo compounds
18. IR spectroscopy generally used to determine (c) Halogenated compounds
(d) Nitro compounds
(a) Molecular structure
(b) Functional group 27. Sample window suitable for IR of aqueous solution of
(c) Number of protons a compound is
(d) All of the above (a) KBr (b) CsBr
19. Pressed disk techniques for the sample preparation in (c) CaF2 (d) NaCl
IR involve the use of 28. In IR spectra, C–H stretching of aldehyde is at
(a) Salt plate (b) Nujol (a) 2850–2750 cm–1 (b) 1750–1725 cm–1
(c) KBr (d) All of the above (c) 2250–2150 cm –1
(d) 2100 cm–1
20. Why is the oxygen–hydrogen absorption of CH3OH is 29. In Raman spectroscopy optical system is made up of
such a broad band in the infrared? (a) Glass or quartz (b) NaBr or CaF2
(a) Rotational energy levels broaden the absorption (c) KBr or NaBr (d) All of the above
(b) Hyperconjugation resonance broadens the 30. Conjugation of C=C with C=O causes what effect on
absorption frequency of C=O bond in IR spectrum?
(c) Resonance broadens the absorption
(a) Lower the frequency
(d) Hydrogen bonding broadens the absorption
(b) Increase the frequency
21. Which of the following bonds would show the stron- (c) No change in frequency
gest absorption in the IR? (d) None of the above
(a) Carbon–hydrogen
31. Mercury lamp is used as radiation source in which
(b) Oxygen–hydrogen technique?
(c) Nitrogen–hydrogen
(a) Colorimetry
(d) Sulfur–hydrogen
(b) Flourimetry
22. Normally graph plotted in IR spectroscopy? (c) UV visible spectroscopy
(a) % T vs frequency (d) Infrared
(b) % T vs wave number
32. Which following source is used in Raman spectrometry?
(c) Absorbance vs wave number
(a) Hydrogen (b) Deuterium lamp
(d) Absorbance vs wavelength
(c) Xenon arc lamp (d) Helium/neon laser
23. The solvent not used in IR spectroscopy is
33. C=O bond in IR spectrum of acetic anhydride gives
(a) Chloroform (b) Carbon tetra chloride
peak at which frequency (in cm–1)?
(c) Carbon disulfite (d) Water
(a) 1760 (b) 1725
24. FT IR instrument does not contain (c) 1810 (d) (a) and (c)
(a) Monochromator
34. Which of following gas is present in Golay detector?
(b) Grattings are covering entire IR range
(a) Xenon (b) rgon
(c) Quartz made prism acts as monochromator
(c) Helium (d) Hydrogen
(d) None of the above
35. Rod of sintered silicon is present in which of following?
25. Which of the following sequence is the correct order
of C=O stretching in descending order? (a) Incandescent lamp (b) Nernst glower
(a) Ester, ketone, acid, amide (c) Globar source (d) Carbon dioxide laser
(b) Acid, amide, ketone, ester 36. Which is the right frequency (cm–l) order for O–H
(c) Ester, ketone, amide, acid bond IR spectrum?
(d) Amide, acid, ketone, ester (a) Phenols < 1º alcohol < 2º alcohol < 3ºalcohol
26. Fermi resonance is often observed in (b) 1º alcohol> 2º alcohol> 3ºalcohol> phenols
3.126  Chapter 3

(c) Phenols> 1º alcohol > 2ºalcohol> 3ºalcohol 47. In IR photo conducting detector can be constructed
(d) 1ºalcohol < 2º alcohol < 3º alcohol < phenols from
37. In IR spectra, alkyne has characteristic peak at (a) Lead sulfide
(b) Lead telluride
(a) 1680 cm–1 (b) 2150 cm–1
(c) Mercury cadmium telluride
(c) 2750 cm –1
(d) 1810 cm–1
(d) All of the above
38. What is Nujol?
48. Which of following compound is used Mull technique
(a) Hexachlorobutadiene
instead of Nujol?
(b) Hexachloropentadiene
(a) Hexachlorobutadiene
(c) Mineral oil
(b) KBr
(d) Heptachlorobutadiene
(c) Hexabromobutadiene
39. Wavelength 780 nm = ______________wave number (d) NaCl
(a) 7800 cm–1 (b) 12800 cm–1 49. In IR spectra, alkene have C=C stretching at
(c) 25000 cm–1 (d) 4000 cm–1
(a) 1280–1220 cml–1 (b) 1360–1300 cm–1
40. Wavelength 2.5 µm =_______________ wave number (c) 1680–1620 cm–1 (d) 2180–2150 cm–1
(a) 400 cm–1 (b) 4000 cm–1 50. What is the frequency range (in cm–1) for the carbonyl
(c) 250 cm–1 (d) 2500 cm–1 group of lactum ring in IR spectra?
41. In IR, pyroelectric detector is constructed from (a) 1620–1660 (b) 1720–1780
(a) Mercury cadmium telluride (c) 1660–1720 (d) 1780–1840
(b) Triglycine sulphate 51. Following are the frequency range (in cm–1) in IR
(c) Lead and telluride spectra for different groups containing (–C=O) Which
(d) Both (a) and (c) of following pair is not true?
42. Which is the right frequency (cm–l) order for C–O (a) Aldehyde: 1740–1720
bond IR spectrum? (b) Ketone: 1700–1650
(a) Phenols < 1° alcohol < 2” alcohol < 3° alcohol (c) Amide: 1680–1630
(b) 1° alcohol > 2° alcohol > 3° alcohol > phenols (d) Acid chloride: 1800
(c) Phenols > 1° alcohol > 2° alcohol > 3° alcohol 52. Which of following technique is used to detect the
(d) 1° alcohol < 2 alcohol < 3° alcohol < phenols hydrogen bonding in compound?
(a) UV visible spectroscopy
43. In a photo emissive tube, the following coating material
is used: (b) Infrared
(c) Flourimetry
(a) Silver
(d) Colorimetry
(b) Gold
(c) Oxides of K, Ag or Cs 53. In IR spectra, alkyne has characteristic peak at
(d) KBr (a) 1680 cm–1 (b) 2150 cm–1
(c) 2750 cm –1
(d) 1810 cm–1
44. One of the following wavelength regions is used for
near IR: 54. Fourier transform is
(a) 400 nm–800 nm (b) 800 nm–2.5 µm (a) A mathematical function
(c) 2.5 µm–25 µm (d) 25 um–0.04 cm (b) Used to convert from the time domain to the fre-
quency domain
45. What is the wavelength of mid-IR?
(c) Used in many modern analytical techniques
(a) 800–2500 nm (b) 2500–4000 nm (d) All of the above
(c) 4000–25000 nm (d) 25000–50000 nm
55. Hexachlorobutadiene is preferred over Nujol as a
46. Hook’s law is associated with mulling agent because
(a) IR (b) NMR (a) It is non toxic
(c) Mass (d) UV (b) It does not give C–H vibration bands
 Analytical Chemistry  3.127

(c) It is transparent over IR range 65. Basic principle underlying FT-IR is?
(d) It has very high boiling point (a) Polarization (b) Diffraction
56. Gratings are generally preferred over prisms for (c) Refraction (d) Interference
dispersive IR because: 66. Which solvent is normally used in IR spectroscopy?
(a) Better resolution is possible (a) DMSO–D6 (b) CS2 or CCl4
(b) Linear dispersion is achieved (c) H2O (d) Methanol
(c) Gratings are resistant to attack by water
67. What is the normal range of fingerprint region in IR?
(d) All are correct
(a) 8000–4000 cm–1 (b) 4000–1500 cm–1
57. The grating in IR spectrophotometer is made up of (c) 1500–500 cm –1
(d) 4000–500 cm
(a) Glass (b) Quartz
68. What is selection rule for a molecule to become IR active
(c) Alkyl halides (d) Polystyrene
in I.R. spectroscopy?
58. The most commonly used mulling reagent in IR is (a) Must show change in dipole moment
(a) CHCl3 (b) Must show dipole moment
(b) Nujol (c) Must show change in magnetic moment
(c) Hexachlorobutadienc (d) Must show magnetic moment
(d) Chlorofluoro carbon oil
69. Compound A with formula C2H7N shows the following
59. In alcohol, the –OH stretches approximately important bands in the IR spectra: (i) 3423 cm–1 (ii)
(a) 1725 cm–1 (b) 1660 cm–1 3236 cm–1
(c) 3345 cm –1
(d) 2300 cm–1 (a) –CH3 (b) –NH2
60. The region of an infra-red spectrum where many (c) –CN (d) =C=N
absorptions take place is known as the ____________ 70. In IR Spectroscopy the changes in electronic energy is
(a) Thumbprint region always associated with charges in
(b) Handprint region (a) Rotational energy
(c) Footprint region (b) Vibrational and rotational
(d) Fingerprint region (c) Vibrational, rotational and translational
61. Bolometer is made up of (d) All
(a) Two dissimilar metals 71. In Raman spectroscopy physical properties measured is
(b) Non-centro-symmetric crystal (a) Absorption of radiation
(c) Fused mixture of metal oxide (b) Scattering of radiation
(d) Pt strip in evacuated vessel (c) Emission of radiation
62. Which is used in calibration of IR instrument? (d) Rotation of radiation
(a) TMS (b) Glass 72. Globar sources is made of
(c) Metal halide (d) Polystyrene (a) Earth oxide Zirconia
63. Which material is used in pressed pellet technique? (b) Mercury
(a) Cholorofluoro carbon oil (c) Silicon dioxide
(b) NaCl (d) Silicon carbide
(c) Hexacholoro butadiene 73. In aldehydes, the C=O stretch approximately
(d) KBr (a) 1725 cm–1 (b) 1660 cm–1
64. What is multiplex advantage? (c) 2750 cm –1
(d) 3300 cm–1
(a) Decreased energy throughput 74. Which of the following statements are correct?
(b) Increased energy throughput (a) An IR detector which responds to heat changes is
(c) Increased N/S ratio more efficient than a photocell.
(d) Increased S/N ratio (b) A photocell detector is more useful in UV and visible
regions.
3.128  Chapter 3

(c) All the optical components of the instrument used (a) Gauss (b) esla
in optical regions of EM spectrum must be trans- (c) Weber (d) All of the above
parent towards the region being studied.
86. Position of signal in NMR spectrum indicates
(d) All are correct
(a) Number of different kind of the proton present in
75. Gratings are generally preferred over prisms for different environment
dispersive IR because (b) Electronic environment of each kind of proton
(a) Better resolution is possible (c) Relative number of protons of each kind
(b) Linear dispersion is achieved (d) Number of neighbouring proton present
(c) Gratings are resistant to attack by water
(d) All are correct 87. Which compound is used as an internal reference stan-
dard for aqueous solution in NMR?
76. NMR signal is obtained in 1,4-dioxane
(a) DMSO-d6
(a) 3 peaks (b) 2 peaks (b) CDCl3
(c) 1 peak (d) 4 peaks (c) 2,2-dimethy-l,2-silapentane-5-sulphonate
77. Reference compound used in NMR spectroscopy is (d) Hexachloro acetone
(a) Silane (b) Trimethylsilane 88. Intensities in NMR spectrum indicate
(c) Dimethylsilane (d) Tetramethylsilane (a) Number of different kinds of the protons present in
78. What is the delta value for TMS in NMR? different environment
(b) Electronic environment of each kind of protons
(a) 0 (b) 10
(c) Relative number of protons of each kind
(c) 5 (d) 7
(d) Number of neighbouring proton present
79. Radiofrequency radiation is associated with 89. Wave length used in the NMR (nuclear magnetic res-
(a) NMR (b) IR onance) is
(c) Mass spectroscopy (d) UV (a) 1010 nm to 1012 nm
80. Number of NMR signal generated by acetone is (b) 108 nm to 1010 nm
(c) 1010 µm to 1011 µm
(a) 2 (b) 6
(d) 108 µm to 1010 µm
(c) 3 (d) 1
90. Magic angle NMR is carried out at which angle?
81. The unit of magnetic field strength in NMR is
(a) 52.7 (b) 54.7
(a) Cycles/second (b) Gauss
(c) 56.7 (d) 58.7
(c) Pulse/second (d) Debye
91. The number of signals in NMR spectrum indicates _____
82. Solvent commonly used in NMR is
(a) Number of different kinds of protons present in
(a) Chloroform different environment
(b) Methanol (b) Electronic environment of each kind of proton
(c) Carbon tetrachloride (c) Relative number of protons of each kind
(d) Acetone (d) Number of neighbouring protons present
83. Rotation of electrons about the protons generates a 92. Which of following has the highest chemical shift
secondary magnetic field which opposes the applied (PPM)value?
magnetic field. The proton is said to be
(a) CH3I (b) CH3Br
(a) Shielded (b) H-bonded (c) CH3F (d) CH3Cl
(c) Deshielded (d) Shifted
93. How many PMR peaks are given by 1, 2- dichloro
84. What is δ value of aldehyde proton in PMR spectrum? propane?
(a) 1–2 (b) 4–5 (a) 2 (b) 3
(c) 7–8 (d) 9–10 (c) 4 (d) 5
85. Which is the unit of magnetic field? 94. Splitting of signal in NMR spectrum indicates
 Analytical Chemistry  3.129

(a) Number of different kinds of protons present in (a) 1 (b) 2

different environment (c) 3 (d) 4
(b) Electronic environment of each kind of proton
104. Presence of electronegative atom on NMR spectra cause
(c) Relative number of protons of each.
(a) Deshielding and upfield
(d) Number of neighbouring protons present
(b) Deshielding and downfield
95. Allyl alcohol has how many NMR peaks? (c) Shielding and upfield
(a) 2 (b) 3 (d) hielding and downfield
(c) 4 (d) 5
105. Coupling causes the peaks in 1H NMR spectra to be
96. Unit of coupling constant is
split __________
(a) Cycle per second (b) Hertz
(a) Into two peaks
(c) Both (d) None of the above
(b) Into multiple peaks equal to the number of hydro-
97. PMR of 2-methyl 1-pentene gives how many peaks? gen on surrounding atoms
(a) 3 (b) 4 (c) Into multiple peaks equal to the number of sur-
(c) 5 (d) 6 rounding carbon atoms
98. Presence of Si in TMS causes (d) Into multiple peaks equal to the number of hydro-
(a) Deshielding and upfield gen on surrounding atoms, plus one
(b) Deshielding and downfieJd 106. Environmental effects that occur in NMR is
(c) Shielding and upfield (a) Chemical shift (b) hemical exchange
(d) Shielding and downfield (c) Spin spin splitting (d) Both (a) and (b)
99. What is the multiplicity expected in the hydrogen 107. The pressure inside a mass spectrometer is
NMR spectrum for the hydrogen atoms marked by a (a) Lower than atmospheric pressure
“star” in the following compound? (b) Almost nil
O (c) Higher than atmospheric pressure
(d) Equal to atmospheric pressure
H 3C CH3
* 108. Telsa is a unit to express
(a) Frequency (b) Pressure
(a) Singlet (b) Triplet
(c) Voltage (d) Magnetic field strength
(c) Quartet (d) Heptet
109. One of the following compounds gives 3 signals in
100. Which of following is universal solvent in NMR?
NMR spectroscopy.
(a) CCI4 (b) DMSO-d6
(a) CH3–COOH (b) CH3–CH2–NH2
(c) CDCI3 (d) Hexachloroacetone
(c) CH3–O–CH3 (d) CH3–CH2–Cl
101. Unit of chemical shift δ is 110. Benzene gives ___________ NMR signal.
(a) Hz (b) ppm
(a) 1 (b) 2
(c) Cps (d) Unit less (c) 3 (d) 6
102. The C13 NMR spectrum of an unknown compound 111. The number of peaks shown by diethyl ether in an
shows 4 absorptions and the H1 NMR spectrum shows NMR spectrum are is
4 absorptions. Which of the following compounds is
(a) Four (b) Two
the unknown compound?
(c) One (d) Five
CH3 CH3 CH3
CH3 112. Nuclear magnetic moment is not shown by
(a) CH3 (b) (c) (d) H3C Cl
(a) 13C (b) 16O
CH3 (c) H
1
(d) 15N
103. m-dibromo benzene has how many PMR peaks? 113. In NMR spectroscopy radiation source used is
3.130  Chapter 3

(a) Radiofrequency source transmitter 123. Isotopic composition of 13 C in carbon is

(b) Tungsten lamp (a) 1.1% (b) 1.6%
(c) Xenon arc lamp (c) 10% (d) 0.99%
(d) Mercury vapour lamp
124. In NMR greater the deshielding of proton,
114. The method of expressing magnetic field strength is (a) Larger the value of δ or smaller value of τ
(a) Cycles/second (b) Pulses/second (b) Smaller the value of δ or larger value of τ
(c) Debye units (d) Gauss (c) Larger the value of δ and larger value of τ
115. A solvent used in NMR studies is (d) Smaller the value of δ and smaller value of τ
(a) Chloroform 125. 2-bromo propene gives NMR signal is
(b) Acetone (a) 2 (b) 3
(c) Carbon tetrachloride (c) 4 (d) 6
(d) Ethanol
126. The most intense peak in the mass spectrum is called
116. Rotation of electrons about the proton generates a (a) Mass peak (b) Metastable peak
secondary magnetic field which may oppose the applied (c) Base peak (d) M + 1 peak
magnetic field. The proton is then said to be
127. What is nuclear-Zeeman effect in NMR?
(a) Shielded (b) Shifted
(a) Transition from lower energy spin state to higher
(c) Hydrogen bonded (d) Deshielded
energy spin state
117. Coupling constant (J) value (b) Splitting of spin states in applied external magnetic
(a) Depends upon magnetic field field
(b) Is independent of field strength (c) Splitting of spin states in absence of field
(c) Depends upon reference standard used (d) Precessional motion of nuclei in applied magnetic
(d) Depends on solvents used field
128. Which is not a correct statement about chemical shift?
118. Anisotropic effect means
(a) Depends on applied external magnetic field
(a) Shielding of protons through space by counter
(b) Does not depend on applied external magnetic
magnetic field
field
(b) Shielding or deshielding of protons through space
(c) Dimensionless
by counter magnetic field
(d) Expressed in ppm
(c) Shielding or deshielding of protons through space
by applied magnetic field 129. Correct formula for gyro-magnetic ratio (γ) is
(d) Shielding of protons through space by applied (a) γ = magnetic moment/spin quantum number
magnetic field (b) γ = magnetic moment/spin angular moment
119. Spin quantum number I of 13C is (c) γ = spin angular moment/magnetic moment
(d) γ = spin quantum number/magnetic moment
(a) 0 (b) 1
(c) 1/2 (d) 3/2 130. How many PMR signals will come in NMR spectra of
iso-butylene.
120. 1 Telsa is equal to ______ gauss.
(a) 5 (b) 2
(a) 104 (b) 105 (c) 3 (d) 4
(c) 10 6
(d) 103
131. What is range of chemical shift (δ) in PMR spectra?
121. Cyclo butane have NMR signal is (a) 0 to 100 (b) 0 to 200
(a) 1 (b) 2 (c) 0 to 20 (d) 0 to 10
(c) 4 (d) 3 132. How many PMR signals will come in NMR spectra of
122. Coupling constant (J) value is expressed in unit is vinylchloride?
(a) Hertz (b) Cycle per cm (a) 2 (b) 3
(c) Cycle into second (d) cm (c) 4 (d) 5
 Analytical Chemistry  3.131

133. Proton NMR is useful for investigating the structure of 142. The inert gas used in the ionization stage of mass spec-
organic compounds because ____________ trometry is
(a) Organic compounds contain carbon atoms (a) Helium (b) rgon
(b) Organic compounds are mostly covalent (c) Xenon (d) Methane
(c) Hydrogen atoms are found in nearly all organic 143. The correct order for the basic features of a mass spec-
compounds trometer is _____________
(d) Organic compounds have low boiling points
(a) Acceleration, deflection, detection, ionization
134. Which of the following statements about tetramethyl- (b) Ionisation, acceleration, deflection, detection
silane is incorrect? (c) Acceleration, ionisation, deflection, detection
(a) It produces a single peak at δ = 10 (d) Acceleration, deflection, ionisation, detection
(b) It is inert 144. Principal involved in mass spectrometer is
(c) It is used to provide a reference against which
(a) Excitation of electron
other peaks are measured
(b) Electron impact bombardment
(d) It is volatile and can be easily distilled off and used
(c) Molecular vibration
again
(d) Splitting of electrons magnetic energy
135. In a triplet, the relative peak areas are in the ratio
145. A mixture of the following gases can be used in flame
_______
photometry to get a temperature of 3125°C:
(a) 1:1:1 (b) 1:2:1
(a) Hydrogen and nitrous oxide
(c) 1:3:1 (d) 1:4:1
(b) Acetylene and oxygen
136. All solvents are used to record NMR spectra except: (c) Hydrogen and air
(a) CDCI3 (b) DMSO-d6 (d) Hydrogen and oxygen
(c) C2H5 OH (d) Deutariated benzene 146. In mass spectroscopy positively charged ions can be
137. In mass spectrometry Br shows:
81 produced by
(a) M+1 peak (b) M+2 peak (P) Heating the sample
(c) M+3 peak (d) M+4 peak (Q) Bombarding the sample with high energy electrons
(R) Bombarding the sample with high energy protons
138. Klystron is used as radiation source in (S) Chemical oonization
(a) X-ray diffraction (a) Q, S (b) Q, R
(b) Electron spin resonance (c) P, R (d) P, S
(c) Mass spectrometry
147. In mass spectrum M-18 peak indicates loss of
(d) None of above
(a) Hydroxyl group (b) Hydrogen
139. In mass spectra, the most intense peak is the (c) Methyl group (d) Water molecule
(a) Base peak
148. In mass spectrum of yoluene, widely the meta stable
(b) Metastable ion peak peak appear at
(c) Fragment ion peak
(a) 91 m/e (b) 77 m/e
(d) Rearrangement ion peak
(c) 46.6 m/e (d) 64.5 m/e
140. Which of following ionization technique is used in
149. Metastable peaks have following all characteristics ex-
molecular weight determination of large biomolecule
cept
by using mass?
(a) These peaks are much broader that is they spread
(a) Electron impact (b) Chemical ionization
over mass units
(c) MALDI (d) None of the above
(b) These peaks are of high intensity
141. A mass spectrometer bombards molecules with a high (c) These peaks appear in the mass spectrum usually
energy electron beam in at non-integral m/e value
(a) Colloidal Phase (b) Liquid Phase (d) The meta stable ions can be detected by a double
(c) Solid State (d) Vapour Phase focusing mass spectrometer
3.132  Chapter 3

150. Removal of a single electron from a molecule results (a) NMR (b) Polarimetry
in the formation of (c) Mass spectrometry (d) pH determination
(a) Fragment ion (b) Metastable ion 161. Dropping mercury electrode is an important compo-
(c) Molecular ion (d) Rearrangement ion nent of
151. The reference electrode in potentiometry is ________ (a) HPLC (b) Spectrophotometer
(a) Dropping mercury electrode (c) Polarograph (d) Potentiometer
(b) Saturated calomel electrode 162. Conductivity cells are made up of
(c) Platinum electrode (a) Copper rods
(d) Glass electrode (b) Two parallel sheets of platinum
152. Nitrogen estimation is done by (c) Glass membranes with Ag/AgCl
(a) Kjeldahl method (b) Gasometry (d) Sb-SbP3
(b) Karl Fischer (d) None of the above 163. Quantitative analysis by polarography is based on
153. TGA curve is a plot (a) Electrode potential (b) Half-wave potential
(a) Weight vs temperature (c) Migration current (d) Limiting current.
(b) eight vs volume of titrant 164. Nernst equation is used to measure
(b) eight vs current E = EΘ + (RT/nF ) ln aMn +

(d) Weight loss vs temperature
(a) Conductance (b) Potential difference
154. Diazotisation titration is used for the assay of (c) Current (d) Resistance
(a) NSAIDs (b) Sulpha drugs
165. Glass transition temperature is detected through
(b) teroids (d) All of the above
(a) X-Ray diffractometery
155. Rotating platinum electrode used in amperometry (b) Solution calonmetery
rotates at ________ rpm. (c) Differential scanning calorimeter
(a) 6 (b) 600 (d) Thermogravimetric analysis
(c) 60 (d) 6000
166. Iodine number of fat is determining to know:
156. The end point of complexometric titrations is shown by (a) Free fatty acid
(a) Acid–base indicators (b) Average molecular size
(b) pM indicators (c) Relative unsaturation
(c) Colorimeter (d) All of the above
(d) pH meter
167. 100 ppm solution =
157. For conjugated acid-base pairs, following equation is (a) 100 µg/ml (b) 10% w/w
correct. (c) 10 µg/ml (d) 10 mg/ml.
(a) pKa = pKw – pKb (b) pKw = pKa – pKb
168. In MOHR’S method of precipitation titration which
(c) pKw = pKa + pKb (d) pKa = pKb indicator is used?
158. Analytical Method Validation is mention in _________ (a) Fluorescein (b) Potassium chromate
guidelines. (c) Ferric ion (d) NaCl solution
(a) EMEA (b) ICH
169. SnCl4 acts as Lewis acid because
(b) WHO (d) GMP
(a) It has six electrons and so need two electrons to
159. Robustness in used to determine complete octet
(a) Minor deliberate changes (b) It has eight electrons but can accept two more
(b) Inter- intraday studies electrons
(c) Interference from excipients (c) It has positive charge
(d) Major changes (d) None of the above
160. Conformation of drugs is commonly determined by: 170. Specific conductance (conductivity ‘k’) unit is
 Analytical Chemistry  3.133

(a) Ohm cm–1 (b) Mho cm–1 (a) BaSO4

(c) Ohm cm (d) hm–1 cm–1 (b) NaCl
171. Ammonium purpurate (murexide) is used for determi- (c) Paracetamol
nation of (d) Ascorbic acid
(a) Sodium (b) Calcium 182. In thermogravimetric titration which of following
(c) Silver (d) Iron property is measured with ml of titrant?
172. Which of following primary standards used to stan- (a) Heat absorbed
dardize perchloric acid? (b) Heat evolved
(a) Potassium hydrogen phthalate (c) Change in temperature
(b) Sodium carbonate (d) All of the above
(c) KBr 183. Angle between source and detector in calorimeter is
(d) Oxalic acid (a) 90° (b) 45°
173. What is the reagent used for diazotization? (c) 180° (d) 60°
(a) NaNO2 + dilute HCl 184. IS0 9000 Series has five main type (ISO 9000, ISO
(b) KNO3 + dilute H2SO4 9001, ISO 9002, ISO 9003, ISO 9004). Which of them
(c) Zn + dilute H2SO4 are descriptive documents?
(d) Tin + H2SO4 (a) ISO 9000 & ISO 9002
174. How many grams of NaOH is required to prepare 100 (b) ISO 9001 & ISO 9002
ml 1M solution of NaOH? (c) ISO 9003 & ISO 9004
(a) 400 mg (b) 4 g (d) ISO 9000 & ISO 9004
(c) 200 mg (d) 2 g 185. 10 gauss = ________
175. How many significant figures in 0.002500? (a) 100 Tesla (b) 1000 Tesla
(a) 7 (b) 5 (c) 10000 Tesla (d) 100000 Tesla
(c) 4 (d) 2
186. Polarogram of a solution containing an electro-reduc-
176. In polymerase chain reaction renaturation is carried ible substance is obtained by plotting
out at what condition (temperature and time)? (a) Current vs Volume
(a) At 95ºC for 1 min (c) At 55ºC for 2 min (b) Current vs Potential
(b) At 95ºC for 2 min (d) At 55ºC for 1 min (c) Resistance vs Time
177. In polarography, half-wave potential indicates (d) Potential vs Volume
(a) Quality of compound 187. Paracetamol is assayed by
(b) Quantity of compound (a) Ceric ammonium sulphate
(c) Both of the above (b) I2
(d) None of the above (c) HPLC
178. Sulphafurazole is assayed by (d) KIO3
(a) 0.1 M NaOH (b) 0.1 M TBAH 188. Which of following is aprotic solvent?’
(c) 0.1M NaNO2 (d) 0.1M HClO4 (a) Benzene (b) Glacial acetic acid
179. Which of following is protogenic solvent? (c) Pyridine (d) Ethylenediamine
(a) Sulphuric acid (b) Formic acid 189. Which of following used as precipitating agent for
(c) Both (d) None of the above Ca2+ ion in gravimetric analysis?
180. 10 Faraday = _________ Coulomb. (a) BaCl2 (b) HNO3
(a) 96500 (b) 965000 (c) NH4SCN (d) H2C2O4
(c) 94600 (d) 946000 190. HCl reacts with Ba(OH)2 to give water and BaCl2. If
181. Which of following drug is analysed by gravimetry? 25.00 mL of an HCI solution reacts with 25.00 mL of
3.134  Chapter 3

a 0.2000 M Ba(OH)2 what is the molarity of the HCl (b) Right circularly polarized ray absorbed same as
solution?(hint: write out the reaction!) left circularly polarized ray
(a) 0.2000 M (b) 0.4000 M (c) Only right circularly polarized ray is absorbed
(c) 0.1000 M (d) None of these (d) Only left circularly polarized ray is absorbed
191. In polarography, to eliminate migration current which 202. Propranolol is assayed by
the of following is used? (a) 0.1 M NaOH (b) 0.1 M TBAH
(a) NaCI (b) KCI (c) 0.1 M NaNO2 (d) 0.1M HClO4
(c) NaOH (d) KOH 203. Protogenic solvent causes
192. Diclofenac sodium is assayed by (a) Enhance acidity of weak acid
(a) 0.1M NaOH (b) 0.1 M TBAH (b) Enhance basicity of weak base
(c) 0.1 M NaNO2 (d) 0.1 M HCIO4 (c) Enhance basicity of weak acid
193. Which of the following is used as indicator in non- (d) Enhance acidity of weak base
aqueous titration? 204. Fluorescein dye is used as adsorption indicator in Fa-
(a) Crystal violet (b) Quinaldine red jan’s method, what is its nature?
(c) Orcet blue (d) All of the above (a) Acidic (b) Basic
194. Which of following is not a primary standard? (c) Amphoteric (d) Neutral
(a) Sodium carbonate (b) KBr 205. What is pH range of methyl orange?
(c) Oxalic acid (d) NaOH (a) 3.1–4.4 (b) 1.2–2.8
195. For determination of the growth of bacteria in culture (c) 4.5–6.3 (d) 6.3–8.5
media which technique is used? 206. Assay of furosemide is carried out by
(a) X ray diffraction (b) Infrared
(a) Back titration with NaOH
(c) Turbidometry (d) All of the above
(b) Direct titration with NaOH
196. In redox titration, indicator electrode is (c) Back titration with HCI
(a) Pt wire (b) Ag wire (d) Direct titration with HCl
(c) Glass electrode (d) Hg electrode
207. The analyte is used in the form of a solution in flame
197. Assay of aspirin is carried out by photometry because it should undergo
(a) Back titration with NaOH (a) Evaporation (b) Condensation
(b) Direct titration with NaOH (c) Nebulisation (d) Precipitation
(c) Back titration with HCI
(d) Direct titration with HCl 208. Specifically used technique for identification of
RNA is
198. Specifically used technique for identification of DNA is
(a) Northern Blotting (b) Southern Blotting
(a) Northern Blotting (b) Southern Blotting (c) Dot Blotting (d) Western Blotting
(c) Dot Blotting (d) Western Blotting
209. In polarography apparatus ________________ is
199. Saccharimetry is the practical application of generated.
(a) Alkalimetry (b) Potentiometry (a) Polarogram (b) Polarograph
(c) Polarimetry (d) Aquametry (c) Polarometer (d) Polaroscope
200. Which source is used for DNA polymerase in PC? 210. Ascorbic acid injection assayed by
(a) E.coli (a) CAS (b) 2,6- Dichloro indophenol
(b) Staphylococcus species (c) I2 (d) KIO3
(c) Thermos aquaticus
211. Protophilic solvent is of _________ nature
(d) Plasmodium species
(a) Acidic (b) Basic
201. Circular dichromism is due to
(c) Neutral (d) Both (a) and (b)
(a) Right circularly polarized ray absorbed from left
circularly polarized ray 212. Calorimeter is used to:
 Analytical Chemistry  3.135

(a) Determine the heat of a reaction (a) Standard deviation (b) Mean
(b) Determine the heat given off/absorbed during (c) Mode (d) Median
some process
223. Nernst equation is used to measure
(b) Store the heat from a chemical reaction
(a) Current (b) Conductance
(d) None of the above
(c) Potential (d) Resistance
213. In Limit of Quantitation (LOQ), signal to noise ratio is
224. Which indicator is not used for weak base and strong
(a) 2:1 (b) 3:1 acid titration?
(c) 8:1 (d) 10:1 (a) Methyl orange (b) Methyl red
214. In refractometry, D line from sodium vapour lamp is (c) Bromocresol green (d) Thymol blue
used. What is the wavelength of it? 225. ________ method involves use of indicator like acidic
(a) 435.3 nm (b) 469.3 nm or basic dyes.
(c) 589.3 nm (d) 653.6 nm (a) Volhard’s method (b) Mohr’s method
215. What is included in the Karl Fischer reagent? (c) Fajan’s method (d) Gay-Lussac method
(a) odine, Pyrimidine, SO2 226. 1000 becquerel = ___________________
(c) odine, Pyridine, SO2 (a) 2.7 × 10–11 curie (b) 2.7 × 10–11 dps
(b) Iodine, Pyridine, SO2, Methanol (c) 103dps (d) 2.7 × 1011 curie
(d) Iodine, Pyridine, SO2, Ethanol 227. Which technique involves the identification of proteins?
216. What is the pH range of phenolphthalein? (a) Northern Blotting (b) Southern Blotting
(a) 3.1–4.4 (b) 8.3–11.0 (c) Dot Blotting (d) Western Blotting
(c) 4.5–6.3 (d) 6.3–8.3 228. Assay of the chloride ion in intraperitoneal dialysis
217. A litre of ethanol solution which contains 1.5 microli- fluid is carried out by
tres of ethanol has concentration of ________ ethanol. (a) Complexometric titration
(a) 1.5 ppb (b) 1.5 ppm (b) Gravimetric method
(c) 1.5 ppt (d) None of these (c) Mohr’s method
218. 10 curie = _______ (d) Karl Fischer titration
(a) 3.7 × 1011 dps (b) 3.7 × 109 becquerel 229. Which of following titrant is self indicator?
(c) 3.7 × 1011 RAD (d) 3.7 × 1010 REM (a) KMnO4
219. In thermogravimetric titration which of following (b) Potassium dichromate
property is measured with ml of titrant? (c) Cerric ammonium sulphate
(a) Heat absorbed (d) Both (a) and (c)
(b) Heat evolved
230. Saccharimetry is used for determination of sugars.
(c) Change in temperature Which of following technique is used in it?
(d) All of the above
(a) Polarography (b) Refractometry
220. In gel electrophoresis, DNA travels (c) Polarimetry (d) Iodometry
(a) Cathode to Anode
231. In diazotization titration, reference electrode is
(b) Anode to Cathode
(a) Glass electrode
(c) Positive to Negative
(b) Saturated calomel electrode
(d) Can not say
(c) Ag–AgCl electrode
221. IP assay of ferrous gluconate tablet is carried out by (d) Hydrogen electrode
(a) Ceriometry (b) Iodometry 232. Refrective index can be determined by using?
(c) Iodimetry (d) argentometry
(a) Abbe’s refrectometer (b) Refrecto calimeter
222. Precision is calculated by (c) Colorimeter (d) None of the above
3.136  Chapter 3

233. Compared to the rate of inorganic reactions, the rate of (a) In alkaline condition – pH > 9.0.
organic reactions generally is? (b) In acidic condition
(a) Slower because organic particles are ions (c) For titration of iodide and thiocyanate
(b) Slower because organic particles contains covalent (d) In all above conditions
bonds 242. Gay-Lussac method is also called
(c) Faster because organic particles are ions (a) Clear point method
(d) Faster because organic particles contains covalent (b) Argentiometric method
bonds
(c) Adsorption indicator method
234. In polymerase chain reaction denaturation is carried (d) Volhard’s method
out at what condition (temperature and time)?
243. The colour change for methyl red is ________________
(a) At 95°C for 1 min (b) At 95°C for 2 min when pH changes from acidic to alkaline.
(c) At 55°C for 2 min (d) At 55°C for 1 min
(a) Colourless to pink (b) Yellow to red
235. Faraday is unit of (c) Red to blue (d) Red to yellow
(a) Charge (b) Current 244. ____________________ is self-indicator and acidic
(c) Potential (d) Capacitance primary standard compound.
236. Which of following is right sequence in polymerase (a) Potassium permanganate
chain reaction? (b) Potassium hydrogen phthalate
(a) 1. Denaturation 2. DNA synthesis 3. Renaturation (c) Sulfamic acid
(b) 1. Denaturation 2. Renaturation 3. DNA synthesis (d) 2,4,6-trinitrobenzoic acid
(c) 1. Renaturation 2 DNA synthesis 3. Denaturation 245. _____________ is assayed by acid–base back titration.
(d) 1. DNA synthesis 2 Denaturation 3. Renaturation (a) Zinc oxide (b) Aspirin
237. Assay of sulpha drugs by nitrite titration using poten- (c) Lactic acid (d) All
tiometric end point detection is also known as 246. ______________ indicator shows blue colour at the
(a) Sigmoidal end point method end point.
(b) External end point method (a) Potassium permanganate
(c) Dead-stop end point method (b) Starch paste
(d) odometric end point method (c) Iodine
238. Solubility of AgCl is 0.0019 g/litre. Molecular weight (d) Diphenyl amine
of AgCl is 143.3. The calculated solubility product 247. ______________ acid is not used to perform redox ti-
constant (Ksp) of AgCl is _______________. tration using KMnO4 in acidic medium.
(a) 1.33 × 10–5 (b) 1.80 × 10–5 (a) HCl (b) HNO3
(c) 1.33 × 10 –10
(d) 1.80 × 10–10 (c) Both (d) None
239. The solution of slightly soluble electrolyte will be pre-
248. Purity of water is determined by
cipitated if
(a) Conductometer (b) HPLC
(a) Ion concentration product is less than its Ksp.
(c) Potentiometer (d) UV
(b) Ion concentration product is greater than its Ksp.
(c) Ion concentration product is equal to its Ksp. 249. Indicator used for complexometric titration
(d) It follows any of the above conditions. (a) Solochrome black (b) EDTA
240. Mohr’s method involves (c) Phenolphthalein (d) Methylene red
(a) Formation of coloured precipitates at the end point 250. Which equation is used for quantification of a sub-
(b) Formation of soluble coloured compound at the stance by Polarography?
end point (a) Ilkovic equation
(c) Formation of turbidity at the end point (b) Vandeemter
(d) Use of adsorption indicator (c) Langmuir equation
241. Mohr’s method is not applicable (d) Hilderband Scott equation
 Analytical Chemistry  3.137

251. The most commonly used detector in liquid chroma- 259. Tailing of peak in GLC is reduced by using
tography is (a) Dimethyl silane
(a) UV (b) etramethyl silane
(b) Electrical conductivity detector (c) Hexamethyl disilazane
(c) Refractive index (d) Trimethyl silane
(d) Polarography detector
260. Derivatisation techniques in HPLC are intended to
252. What useful information can be found from a Van enhance
Deemeter plot?
(a) Molecular weight (b) Detectability
(a) Optimum column temperature (c) Reversibility (d) Reproducibility
(b) Optimum mobile flow rate
(c) Selectivity factor 261. Which of following has strongest absorbent?
(d) All of above (a) Cellulose (b) Calcium carbonate
(c) Fuller’s Earth (d) Silica gel
253. Condition maintained in programmed temperature GC
(a) Temperature of entire column is raised 262. The stationzry phase used in gel permeation chroma-
(b) Temperature of detector is raised tography
(c) Temperature of sample injector is raised (a) Alumina
(d) Temperature of recorder is raised (b) Charcoal
254. In anion exchange chromatography what is the charge (c) Squalene
of counter ion? (d) Styrene divinyl benzene copolymer
(a) Negative (b) Positive 263. Band broadening is:
(c) Both of above (d) Cannot say (a) Directly proportional to column efficiency
255. In gel filtration chromatography which compound is (b) Inversely proportional to solvent efficiency
elute first? (c) Directly proportional to solvent efficiency
(a) Larger molecule (d) Inversely proportional to column efficiency
(b) Smaller molecule 264. Which of the following detector of gas chromatography
(c) Molecule with intermediate size is destructive type?
(d) Cannot say (a) Kathetormeter
256. Indicate the HPLC detector that is most sensitive to (b) Argon ionization detector
change in temperature: (c) Flame ionization detector
(a) PDA detector (d) Electon capture detector
(b) Refractive Index detector 265. Which of following HPLC detectors is not a solute
(c) Fluorescence detector property detector?
(d) Electrochemical detector (a) UV–Visible detector
257. What is the correct order of the retention in mixture of (b) Photo diode array detector
four compounds in normal phase chromatography? (c) Fluorescence detector
(a) Acetic acid > Ethanol > Acetone > Petroleum ether (d) Refractive index detector
(b) Acetic acid < Ethanol < Acetone < Petroleum ether 266. Band (peak) separation is
(c) Ethanol > Acetic acid > Acetone > Petroleum ether (a) Directly proportional to solvent efficiency
(d) Ethanol < Acetic acid < Petroleum ether < Acetone (b) Inversely proportional to solvent efficiency
258. Which carrier gas is use in GC containing electron (c) Directly proportional to column efficiency
capture detector? (d) Inversely proportional to column efficiency
(a) Hydrogen (b) elium 267. Choose the correct semirigid get used for exclusion
(c) Oxygen (d) Argon chromatography
3.138  Chapter 3

(a) Sephadex (b) Gelatin 277. Silica gel H has:

(c) Cellulose (d) Alumina (a) Starch as binder (b) Gelatin as binder
268. In limit of detection (LOD), signal to noise ratio is (c) Gypsum as binder (d) No binder
(a) 2:1 (b) 3:1 278. Tailing occurs due to
(c) 8:1 (d) 10:1 (a) Sample overloading
269. The length of analytical column is________. (b) Impurity
(a) 5–25 cm (b) 10–100 cm (c) More than one ionic species of compound
(c) 1–10 m (d) 40–50 cm (d) All of the above
270. One of the following statements is NOT true: 279. The mobile phase used in ion exchange chromatog-
(a) Precision represents reproducibility of measurement raphy is
(b) Accuracy expresses the correctness of measurement (a) Polar solvent
(c) Specificity means ability of method to detect the (b) Non-polar solvent
lowest possible concentration (c) Buffer solutions
(d) Limit of quantization is ability of method to quantify (d) All of the above methods
the lowest possible concentration 280. Qualitative analysis in GLC is based on
271. The parameter in the elution curve that is proportional (a) Time required for peaks to appear
to the concentration of a compound in gas chromato- (b) Peak height
graphic effluent is the (c) Peak area
(a) Number of peaks (d) All of the above
(b) Width of the peaks 281. In reverse phase chromatography which compound is
(c) Area under the peak most retained?
(d) Shape of the peak (a) Intermediate polar compound
272. The number of theoretical plates depends on (b) Least polar compound
(a) Length of the column (c) More polar compound
(b) HETP (d) Cannot say
(c) Both (a) and (b) 282. Which of following is not a masking agent?
(d) None of the above (a) Triethanolamine
273. Derivatizing agent for TLC of steroidal compound? (b) Potassium citrate
(a) Diphenylcarbazone (c) Ormaldehyde-acetic acid solution
(b) Bromothymol blue (d) Ammonium fluoride
(c) Antimony trichloride 283. Tailing of peak in GLC is reduced by using
(d) Ninhydrin
(a) Dimethyl silane
274. Silica gel G contains which of following binder? (b) Tetramethyl silane
(a) Starch (b) Gelatin (c) Hexamethyl disilazane
(c) Cellulose (d) Gypsum (d) Trimethyl silane
275. For base line separation value of R (resolution) 284. Which of following HPLC detector is a bulk property
(a) R > 0.5 (b) R > 1.5 detector?
(c) R ≥ 0.5 (d) R ≤ 1.5 (a) Refractive index detector
276. Derivatizing agent for TLC of lipid compound is (b) UV detector
(a) Antimony trichloride (c) Photo diode array detector
(b) Bromothymol blue (d) Flouresence detector
(c) Ninhydrin 285. ∆Rm number is a chromatographic parameter used to find
(d) Diphenyl carbazone out whether the compound belonging to homologous
series or not.
 Analytical Chemistry  3.139

(a) Rf value (b) Homologous series 295. In size exclusion chromatography the stationary phase
(c) Both (a) and (b) (d) None of the above used are
286. Quantitative analysis in GLC is based on (a) Alumina (b) Dextrose
(c) Agarose (d) Styrene
(a) Time required for peaks to appear
(b) Peak height 296. For amino acid analysis by HPLC derivatisation reagent
(c) Peak area used by UV absorption detector is
(d) Both (b) and (c) (a) 4-Nitrobenzyl-N-propylamine hydrochloride
(b) 4-Nitrobenzyloxyamine hydrochloride
287. In normal phase chromatography which compound is
(c) 3,5-Dinitro benzoyl chloride
eluted first
(d) 4-Nitrobenzyl-N-N’-disopropylisourea
(a) More polar compound
(b) Least polar compounds 297. The mobile phase in column chromatography acts as a
(c) Intermediate polar compound (a) Solvent for sample (b) Developer and as eluent
(d) Cannot say (c) As eluent only (d) Both (a) and (b)
288. Silica gel 60 F254 contains 298. In a normal phase mode, the following component is
(a) Gypsum as binder eluted first
(b) Fluorescent indicator (a) Hydrocarbons (b) Primary alcohol
(c) 254 µm particle size (c) Salicylic acid (d) Primary amine
(d) Both (a) and (b) 299. Chlorine or bromine substitution in aromatic compound
289. Which of following is used as a mobile phase in super- (a) Enhances fluorescence
critical fluid? (b) Does not change the fluorescence
(a) Carbon dioxide (b) Water (c) Quenches the fluorescence
(c) Acetic acid (d) Both (a) and (b) (d) Removes the fluorescence
290. What can be used to reduce tailing in gas chromatog- 300. The separation of components because of distribution
raphy? of components between two immiscible liquid phases
(a) Hexa methyl silane (b) Tetra methyl silane occurs in
(c) Glacial acetic acid (d) Trimethylamine (a) Paper chromatography
(b) Ion exchange chromatography
291. The principle of separation in GSC is
(c) High pressure thin layer chromatography
(a) Gel permeation (b) Adsorption
(d) HPLC
(c) Partition (d) Ion exchange
301. In chromatography if column length is constant and
292. In gas chromatography sample must be in the height of theoretical plate is decreases, then
(a) Solid state (b) Gas state (a) Peak width increases
(c) Liquid state (d) Crystal (b) Column separation efficiency decreases
293. In gas chromatography, derivatisation is desirable to (c) Number of theoretical plate decreases
(P) Improve the thermal stability of compounds (d) Olumn separation efficiency increases
(Q) Enable interaction with carrier gas 302. In chromatography compound X has retention time
(R) Introduce a detector oriented tag into the molecule 10.5 min and peak width is 0.7 min and compound Y
(S) Removes contaminants has retention time 15.5 min and peak width is 0.4 min
(a) P, Q (b) Q, R then resolution is
(c) P, R (d) P, S (a) 9.09 (b) 0.909
294. In HPLC the analytical performance improves when (c) 4.54 (d) 5.5
(a) Particle diameter is increased 303. In TLC Kiesleguhr material ________ is used as
(b) Particle diameter is decreased coating material
(c) Coarser particles are paired with shorter columns (a) Acidic nature (b) Alkaline nature
(d) Low temperature is used (c) Neutral nature (d) Amphoteric nature
3.140  Chapter 3

304. Principle of paper chromatography is 312. What is the λmax for the following compound? Use
(a) Adsorption (b) Partition the provided parameters for your calculation?
(c) Ion exchange (d) Affinity (a) 234 nm (b) 244 nm
305. Calculate the length of column if height of theoreti- (c) 273 nm (d) 283 nm
cal plate 0.234 cm and number of theoretical plate 313. Material used in sample handling of X-ray diffraction is
is 3550 (a) Glass (b) Quartz
(a) 15170.94 (b) 13291.2 (c) KBr (d) KHP
(c) 830.7 (d) 1120 314. Which of following conditions leads to decrease in
306. Steroid separation is by paper chromatography then fluorescence intensity?
paper used is (a) Increase in temperature or increase in viscosity
(a) Carboxyl paper (b) Acetylated paper (b) Increase in temperature or decrease in viscosity
(c) Kieselguhr paper (d) Silica paper (c) Decrease in temperature or decrease in viscosity
307. In chromatography capacity factor related to (d) Decrease in temperature or increase in viscosity
(a) Polarity of solvent 315. Water shows which transition?
(b) Number of theoretical plate (a) n – > π* (b) π – > π*
(c) The migration rate of solute (c) σ – > σ* (d) n – > σ*
(d) Resolution 316. Increase in conjugation causes
308. In radial paper chromatography sample is placed (a) Hypsochromic shift
(a) Near to outer surface of paper (b) Hyperchromic shift
(b) At the centre of the paper (c) Bathochromic shift
(c) At the bottom of the paper (d) Hypochromic shift
(d) On the top of the paper 317. In UV 1,3-butadiene shows which transition?
309. In TLC silica-G is used as coating material ‘G’ means (a) n – > π* (b) π – > π*
(a) Gelatin and used to improve solubility of silica (c) σ – > σ* (d) n – > σ*
(b) Gelatin and used as a binder 318. Which isomer of olefine has high λmax?
(c) Gypsum and used to improve solubility of silica (a) rans
(d) Gypsum and used as a binder (b) Cis
310. RP-HPLC method contains (c) Both have same λmax
(a) Stationary phase is polar and mobile phase is non- (d) Can not say
Polar 319. Turbidity is carried out at wavelength
(b) Stationary phase is non-polar and mobile phase is (a) 450 nm (b) 680 nm
polar (c) 530 nm (d) 600 nm
(c) Stationary phase is non-polar and mobile Phase is
non-polar 320. Which of the following techniques has the highest sensi-
tivity?
(d) Stationary phase is polar and mobile phase is
polar (a) UV spectroscopy (b) Colorimetry
(c) Infrared (d) Flourimetry
311. Which of following compounds shows peak in vacu-
um UV region? 321. X-ray is generated by cathode tube. Which filament is
used as cathode in it?
(a) Benzene (b) Butadiene
(a) Copper (b) Tungsten
(c) Methane (d) Naphthalene
(c) Mercury (d) None of the above
322. Most widely used radiation source in visible spectros-
copy is:
(a) Tungsten–halogen lamp
(b) Hydrogen-discharge lamp
 Analytical Chemistry  3.141

(c) Deuterium lamp (a) 0.1 to 1 nm (b) 0.01 to 10 nm

(d) Nernst glower (c) 10 to 100 nm (d) 0.1 to 10 nm
323. Which of the following techniques is based on Tyndall 335. R-band associated with which transition?
effect? (a) n – π* (b) π – π*
(a) Turbidimetry (c) σ – σ* (d) n – σ*
(b) Nephelometry
(c) Raman spectroscopy 336. Kirchhoff ’s law associated with
(d) All of the above (a) IR (b) NMR
324. Which transition requires the highest energy? (c) AAS (d) Raman spectroscopy
(a) n → n* (b) π → µ* 337. B, E and K bands are associated with which transition?
(c) σ → σ* (d) n → σ* (a) n – π* (b) π – π*
325. Flame photometry cannot be used for: (c) σ – σ* (d) n – > σ*
(a) Barium (b) Calcium 338. Fluorescence is due to which transition?
(c) Selenium (d) Sodium (a) n – π* (b) π – π*
326. In Raman spectroscopy optical system is made up of: (c) σ – σ* (d) n – σ*
(a) Glass or Quartz (b) NaBr or CaF2
339. For study of the free radicals which of following tech-
(c) KBr or NaBr (d) All of above niques is used?
327. Transmittance is defined as (a) Infrared spectroscopy
(a) log Io/It (b) og It/Io (b) Electron spin resonance spectroscoy
(c) It/Io (d) Io/It (c) Flourimetry spectroscopy
328. Which of following detectors has the most sensitivity? (d) UV spectroscopy
(a) Flame ionization detector 340. X-ray effect is based on
(b) Argon ionization detector (a) Outer shell electron transition
(c) Electron capture detector (b) Inner shell electron transition
(d) Kathetormeter (c) Rotation of molecule
329. Angle between source and detector in flourimeter is (d) None of the above
(a) 90° (b) 45° 341. Toluene shows transition of________ .
(c) 180° (d) 60° (a) n-π* (b) π-π*
330. Sample window used in UV is made up of (c) σ-σ* (d) n-σ*
(a) Quartz (b) Glass 342. A compound (mol wt.-200g/mol) has specific absor-
(c) Metal halide (d) Both (a) and (b) bance 100 at its A = 257. Find the molar absorptivity
331. Which of following source is used fluorescence of compound.
spectrometry? (a) 200 (b) 2000
(a) Tungsten (b) Deuterium arc lamp (c) 1000 (d) 100
(c) Xenon arc lamp (d) Helium/neon laser 343. Value of λmax for a particular compound
332. Conjugated diene shows which band? (a) Increases with increase in concentration
(a) K (b) B (b) Decreases with decrease in concentration
(c) E (d) R (c) Does not change
333. In ESR which waves are used? (d) Both of (a) and (b)
(a) Radiowaves (b) Near UV 344. In fluorimetry which of following is true:
(c) Far IR (d) Microwaves (a) Excitation wavelength > florescence wavelength
334. Wavelength used in X-ray diffraction spectroscopy (b) Excitation wavelength < florescence wavelength
3.142  Chapter 3

(c) Excitation wavelength = florescence wavelength 355. Angle between source and detector in nephalometer is
(d) None of the above (a) 90° (b) 45°
345. Which wave is used in densitometer? (c) 180° (d) 60°
(a) UV–Visible (c) Microwave 356. Xenon arc lamp is source of light in
(b) Infrared (d) None of the above (a) Spectrofluorimeter
346. Riboflavin can be easily analysed by which method? (b) IRspectroflurometer
(a) Nephelometry (c) Flame photometer
(b) Fluorimetry (d) Calorimeter
(c) Flame photometry 357. Match the following:
(d) Phosphorimetry (P) UV (1) Precessional motion
347. Pyridine shows which transition in UV region? (Q) IR (2) Electronic transitions
(R) NMR (3) Fragmentation
(a) n – π* (b) π – π*
(S) MASS (4) Vibrational motion
(c) Both (a) and (b) (d) n – σ*
(a) P2, Q4, R1, S3 (b) P2, Q4, R3, S1
348. Which of following compound has the highest λmax?
(c) P2, Q1, R3, S4 (d) P4, Q2, R1, S3
(a) CH3F < CH3CI < CH3I
(b) CH3I < CH3F < CH3CI 358. X-ray spectral line Kα doublet arises from transition
of electrons from
(c) CH3CI < CH3I < CH3Br
(a) M shell to K shell (b) L shell to M shell
(d) CH3I < CH3Br < CH3CI
(c) L shell to K shell (d) M shell to L shell
349. In naphthalene, which type of absorption band is
359. A mixture of the following gases can be used in flame
observed?
photometry to get a temperature of 2045°C
(a) R (b) B
(a) Hydrogen and nitrous oxide
(c) E (d) K
(b) Acetylene and oxygen
350. Angle between source and detector in turbidimeter is (c) Hydrogen and air
(a) 90° (b) 45° (d) Hydrogen and oxygen
(c) 180° (d) 60° 360. The process undergo by the analyte in flame photom-
351. Absolute configuration of a compound is determined etry is
by which technique? (a) Evaporation (b) Nebulization
(a) UV–Visible spectroscopy (c) Condensation (d) Precipitation
(b) Infrared 361. Base value of benzaldehyde is 250 nm. What would be
(c) Mass λmax of p-hydroxybenzalaldehyde
(d) X ray diffraction (a) 253 nm (b) 261 nm
352. In case of carbonyl compound which of following is a (c) 275 nm (d) 270 nm
forbidden transition? 362. For calibration of resolution in UV __________ is
(a) n–σ* (b) π–π* used
(c) σ–σ* (d) n–π* (a) Holmiun filter
353. ESR spectra only given by molecule have (b) Polystyrene
(c) Potassium dichromate
(a) Paired electron (b) Unpaired electron
(d) Toluene and hexane
(c) Positive proton (d) None of the above
363. Flame photometry is an example of
354. For determination of the growth of bacteria in culture
media which technique is used? (a) Atomic absortion spectrometry
(b) Atomic emission spectrometry
(a) X ray diffraction (b) Infrared
(c) Both (a) and (b)
(c) Turbidometry (d) All of the above
(d) None
 Analytical Chemistry  3.143

364. The phenomena of scattering of light occurs in (a) 5 × 10–5 (b) 4 × 10–5
(a) Aquamtery (b) Colorimetry (c) 4 × 10–4 (d) 5 × 10–2
(c) Spectrophotometry (d) Nephlometry 373. Bathchromic shift involves
365. Resolution of a spectrophotometer is (a) Increase in intensity of absorption
(a) Its wavelength range (b) Decrease in intensity of absorption
(c) Increase in wavelength of maxima absorption
(b) Its ability to distinguish adjacent absorption bands
(d) Decrease in wavelength of maxima absorption
(c) Its capacity for its continuous use
(d) All of the above 374. Benzene shows the following transition in UV spectra:
(a) σ → σ* (b) π → π*
366. The formula is (c) n → σ* (d) n → π*
(a) Molar Absorptivity(ε) = A1%1cm × mol.wt/1000
375. Which one of the following can be used as target mate-
(b) olar Absorptivity(ε) = A1%1cm × mol.wt/10 rial for X-ray production?
(c) Molar Absorptivity(ε) = A1%1cm × eq.wt/1000 (a) Sodium (b) Aluminium
(d) Molar Absorptivity(ε) = A1%1cm × eq.wt/100 (c) Copper (d) Xenon
367. A compound has a molecular weight of 297; an equiva- 376. ESR is applied to only those substances showing
lent of 148.5 and an A1%1cm of 742 at 309nm. Its molar paramagnetism which is due to the magnetic moment
absorptivity is (a) Neutrons (b) Protons
(a) 220.37 (b) 1101.857 (c) Paired electrons (d) Unpaired electrons
(c) 110.18 (d) 22037.4 377. n à π* is also known as
368. Increase in the extent of conjugation of a double-bonded (a) K-bands (b) R-bands
system results in (c) P-bands (d) B-bands
(a) Hyperchromic shift 378. In UV spectroscopy propane shows the following tran-
(b) Hypochromic shift sition:
(c) Hypsochromic shift (a) σ → σ* (b) n → σ*
(d) Bathochromic shift (c) π → π* (d) n → π*
369. In Bragg’s equation nλ = 2d sin θ, θ is the angle between 379. Emission of radiation is measured by ______ method.
(a) The direction of the incident beam and the reflected (a) Raman spectroscopy
beam (b) Flame photometry
(b) The surface of the crystal and the incident fluorescent (c) Interferometer
beam (d) Calorimetry
(c) The direction of the incident beam and the diffract- 380. Scattering of radiation is not measured by _____method.
ed beam (a) Raman Spectroscopy
(d) Two incident beams (b) Spectrophotometer
370. The electronic transition possible in Br2 is (c) Turbidometry
(a) σ → σ* (d) Nephalometry
(b) σ → σ* and n → σ* 381. The conjugation increases the lmax by
(c) σ → π* and π → π* (a) 5 nm (b) 10 nm
(d) σ → π* and n → π* (c) 20 nm (d) 30 nm
371. In UV spectroscopy the lowest energy is required for 382. The transition from excited state to ground state is called
transition of (a) Excitation (b) Absorption
(a) σ → σ* (b) n → σ* (c) Relaxation (d) Scattering
(c) π → π* (d) n → π* 383. The relationship between absorbance (A) and trasmit-
372. An organic compound ‘X’ has an absorption maxima at tance (T) can be given by
217 nm. Its Emax is 16,000. The absorbance is 0.64 when (a) A = 2 – log% T (b) T = 2 – log A
the cell length is 1 cm. Then molar concentration is (c) A = 2 + log T (d) T = 2 + log A
3.144  Chapter 3

384. The following is the example of absorption spectra: 393. Bathochromic shift depends on:
(a) Flourimetry (b) Flame photometry (a) Isolated double bonds
(c) X-ray diffraction (d) UV spectra (b) Conjugated double bond
385. The following is the example of emission spectra: (c) Thermal conductivity
(a) IR spectra (b) UV spectra (d) Absorption of light
(c) NMR spectra (d) Flourimetry 394. The value of extinction coefficient more than 100 is
known as:
386. The following light is measured in nephalometry
(a) Scattered (b) Reflected (a) Absorbed transition
(c) Dispered (d) Transmitted (b) Allowed transition
(c) Curved transition
387. The following light is measured in turbidimetry:
(d) Bonded transition
(a) Scattered (b) Reflected
(c) Dispered (d) Transmitted 395. When a molecule is excited by the absorption of radia-
tion it soon returns to its ground state by losing its ex-
388. The following gas has got a higher thermal conductiv- cess of energy emitted as radiation. This phenomenon
ity value: is known as:
(a) Nitrogen (b) Helium (a) Phosphorescence (b) Bathochromic shift
(c) Argon (d) Carbon (c) Electron emission (d) Fluorescence
389. The following is an example for atomic spectra: 396. When excitation of electrons by chemicals, the phe-
(a) UV spectra (b) Colorimetry nomena is called
(c) Flourimetry (d) Flame photometry (a) Chemiluminescence
390. Types of sources materials in UV–Visible spectros- (b) Photoluminescence
copy is (c) Electro chemiluminescence
(a) Hydrogen–deuterium lamp (d) Phosphorescence
(b) Tungsten lamp 397. ‘n’ electrons are present in
(c) Xenon arc lamp
(a) Methane (b) Ethylene
(d) All
(c) Acetylene (d) Propanol
391. What will be the absorption maxima (λmax) as per
398. Which transition is more susceptible towards hydrogen
Woodward–Fieser rule?
bonding?
Me
(a) n → π*
Me (b) π → π*
(c) n → σ*
(d) σ → σ*
(a) 234 nm (b) 229 nm 399. Correct energy value order for electronic transition in
(c) 244 nm (d) 239 nm UV is
392. What will be the absorption maxima (λmax) as per (a) n → π* < n → σ* < π → π * < σ → σ*
Woodward–Fieser rule? (b) n → π* < π → π* < σ → σ* < n → σ*
O (c) π → π < n → π* < n → σ* < σ → σ*
CH3 (d) n → π* < π → π* < n → σ* < σ → σ*
400. Most widely used detector in UV spectroscopy is
OCOCH3 (a) Bolometer
(b) Photomultiplier tube
(c) Photoemissive cell
(a) 257 nm (b) 263 nm (d) Pyroelectric detector
(c) 233 nm (d) 302 nm
 Analytical Chemistry  3.145

Answer Keys
1. (b) 2. (b) 3. (d) 4. (a) 5. (d) 6. (d) 7. (d) 8. (a) 9. (a) 10. (d)
11. (b) 12. (c) 13. (a) 14. (d) 15. (b) 16. (c) 17. (b) 18. (b) 19. (c) 20. (d)
21. (b) 22. (b) 23. (d) 24. (d) 25. (a) 26. (a) 27. (a) 28. (a) 29. (a) 30. (a)
31. (d) 32. (d) 33. (d) 34. (a) 35. (c) 36. (b) 37. (b) 38. (c) 39. (b) 40. (b)
41. (b) 42. (d) 43. (c) 44. (b) 45. (c) 46. (a) 47. (d) 48. (a) 49. (c) 50. (c)
51. (b) 52. (b) 53. (b) 54. (d) 55. (b) 56. (d) 57. (c) 58. (b) 59. (c) 60. (d)
61. (d) 62. (d) 63. (d) 64. (d) 65. (d) 66. (b) 67. (c) 68. (a) 69. (b) 70. (c)
71. (b) 72. (d) 73. (a) 74. (d) 75. (a) 76. (c) 77. (b) 78. (a) 79. (a) 80. (d)
81. (b) 82. (c) 83. (a) 84. (d) 85. (d) 86. (b) 87. (c) 88. (c) 89. (a) 90. (b)
91. (a) 92. (c) 93. (c) 94. (d) 95. (d) 96. (c) 97. (d) 98. (c) 99. (c) 100. (b)
101. (b) 102. (d) 103. (c) 104. (b) 105. (d) 106. (d) 107. (b) 108. (d) 109. (b) 110. (a)
111. (b) 112. (b) 113. (a) 114. (d) 115. (c) 116. (a) 117. (b) 118. (c) 119. (c) 120. (b)
121. (a) 122. (a) 123. (a) 124. (a) 125. (b) 126. (c) 127. (b) 128. (a) 129. (b) 130. (b)
131. (d) 132. (b) 133. (c) 134. (a) 135. (b) 136. (c) 137. (b) 138. (c) 139. (a) 140. (c)
141. (d) 142. (d) 143. (b) 144. (b) 145. (b) 146. (a) 147. (d) 148. (c) 149. (b) 150. (c)
151. (b) 152. (a) 153. (d) 154. (b) 155. (b) 156. (b) 157. (c) 158. (b) 159. (a) 160. (b)
161. (c) 162. (b) 163. (b) 164. (b) 165. (c) 166. (c) 167. (a) 168. (b) 169. (b) 170. (b)
171. (b) 172. (a) 173. (a) 174. (b) 175. (c) 176. (d) 177. (a) 178. (b) 179. (c) 180. (b)
181. (a) 182. (c) 183. (c) 184. (d) 185. (d) 186. (b) 187. (a) 188. (a) 189. (d) 190. (b)
191. (b) 192. (d) 193. (d) 194. (d) 195. (c) 196. (a) 197. (c) 198. (b) 199. (c) 200. (c)
201. (a) 202. (a) 203. (b) 204. (a) 205. (a) 206. (a) 207. (c) 208. (a) 209. (b) 210. (b)
211. (b) 212. (b) 213. (d) 214. (c) 215. (b) 216. (b) 217. (a) 218. (a) 219. (c) 220. (a)
221. (a) 222. (a) 223. (c) 224. (d) 225. (c) 226. (c) 227. (d) 228. (c) 229. (d) 230. (c)
231. (b) 232. (a) 233. (b) 234. (a) 235. (a) 236. (b) 237. (c) 238. (d) 239. (a) 240. (a)
241. (d) 242. (a) 243. (d) 244. (d) 245. (d) 246. (b) 247. (c) 248. (a) 249. (a) 250. (a)
251. (a) 252. (b) 253. (a) 254. (b) 255. (a) 256. (b) 257. (a) 258. (d) 259. (c) 260. (b)
261. (c) 262. (d) 263. (d) 264. (c) 265. (d) 266. (a) 267. (a) 268. (b) 269. (a) 270. (c)
271. (c) 272. (c) 273. (c) 274. (d) 275. (c) 276. (b) 277. (d) 278. (d) 279. (c) 280. (a)
281. (b) 282. (c) 283. (c) 284. (a) 285. (c) 286. (d) 287. (b) 288. (d) 289. (d) 290. (a)
291. (b) 292. (b) 293. (c) 294. (b) 295. (d) 296. (c) 297. (d) 298. (a) 299. (c) 300. (a)
301. (d) 302. (a) 303. (b) 304. (b) 305. (c) 306. (b) 307. (c) 308. (b) 309. (d) 310. (b)
311. (c) 312. (c) 313. (d) 314. (b) 315. (d) 316. (c) 317. (b) 318. (a) 319. (c) 320. (d)
321. (b) 322. (a) 323. (d) 324. (c) 325. (c) 326. (a) 327. (c) 328. (c) 329. (a) 330. (b)
331. (c) 332. (a) 333. (d) 334. (b) 335. (a) 336. (c) 337. (b) 338. (b) 339. (b) 340. (b)
341. (b) 342. (b) 343. (c) 344. (b) 345. (a) 346. (b) 347. (c) 348. (a) 349. (b) 350. (c)
351. (d) 352. (d) 353. (b) 354. (c) 355. (a) 356. (a) 357. (a) 358. (c) 359. (c) 360. (b)
361. (c) 362. (d) 363. (c) 364. (d) 365. (b) 366. (b) 367. (d) 368. (d) 369. (c) 370. (b)
371. (d) 372. (c) 373. (c) 374. (b) 375. (c) 376. (d) 377. (b) 378. (a) 379. (b) 380. (b)
381. (d) 382. (c) 383. (a) 384. (d) 385. (d) 386. (a) 387. (d) 388. (b) 389. (d) 390. (d)
391. (c) 392. (d) 393. (b) 394. (b) 395. (d) 396. (a) 397. (d) 398. (c) 399. (d) 400. (b)
 chapter 4
Biochemistry

Carbohydrates 1. Monosaccharides The monosaccharides is also called

Carbohydrates may be defined as polyhydroxyaldehyde simple sugar, compound which possessing free aldehyde
or ketones or compounds which produce them on (–CHO) or ketone (–C=O) group and 2 or more (–OH) group.
hydrolysis. The general formula of Monosaccharides is Cn (H2O)n
or CnH2nOn.
Classification of Carbohydrates

Monosaccharide General formula Aldose Sugar Ketose sugar

(–CHO) (–C=O)

Trioses C3H6O3 Glyceraldehyde Dihydroxyacetone

Tetroses C4H8O4 Erythrose Erythrulose

Pentose C5H10O5 D-Ribose D-Ribulose

D-Xylose D-Xylulose

Hexoses C6H12O6 D-Glucose Fructose

D-Galactose
D-Mannose

Heptoses C7H14O7 Glucoheptose Sedoheptulose

D-Sedoheptulose

Structural aspects of monosaccharides 2. Oligosaccharides It is a compound sugar which

Stereoisomers Are compounds that have the same yields two to ten molecules of same or different monosac-
structural formula but differ in their spatial arrangement of charides on hydrolysis.
atoms. It is an important character of monosaccharides. Accordingly, an oligosaccharide yeilding two molecules
Asymmetric carbon A carbon attached to four different of monosaccharides on hydrolysis is designed as a disaccha-
groups is called asymmetric carbon. And number of asym- ride, and the one yielding three molecules of monosaccharides
metric carbon determines the possible number of isomers of as a trissaccharides.
given compound which is equal to 2n. The general formula of disaccharides is Cn(H2O)n–1 and
trisaccarides is Cn(H2O)n–2.
E.g., Glucose has four chiral (asymmetric) centres so it
has a total of 16 isomers. yy Disaccharides: Sucrose, Lactose, Maltose, Cellobiose,
Glyceraldehyde has been chosen as the reference Trehalose, Gentiobiose, Melibiose.
carbohydrate to represent the structure of all other carbo- yy Trisaccharides: Rhamninose, Gentianose, Raffinose
hydrates. (=Malitose)
 Biochemistry  3.147

yy Tetrasaccharides: Stachyose, Scorodose Amino Acids and Proteins

yy Pentasaccharides: Verbascose
Chemical nature of the amino acids
Reducing sugar Non-reducing sugar
The α-amino acids in peptides and proteins (excluding pro-
 
Carbohydrate with a free al-  
Aldehyde or line) consist of a carboxylic acid (–COOH) and an amino
dehyde (at-1) or free ketone ketone group is (–NH2) functional group attached to the same tetrahedral
(at-2) group. ( Aldehyde or not free. carbon atom. This carbon is the α-carbon. Distinct R-groups,
ketone group is free) that distinguish one amino acid from another, also are
 
They are in hemiacetal or  
They are in acetal attached to the alpha-carbon (except in the case of glycine
hemiketal form. or ketal form. where the R-group is hydrogen). The fourth substitution on
the tetrahedral α-carbon of amino acids is hydrogen.
 
Do exhibit mutarotation.  
Do not exhibit
The carboxyl group and amino group are attached to
mutarotation.
the same carbon atom, hence amino acids are termed as
 
Do form osazones with  
Do not form α-amino acids.
phenyl hydrazine. osazones.
R O
 
Do form oximes with  
Do not form H
hydroxylamine. oximes. N Cα C
H OH
E.g., Glucose, Fructose, Lac- E.g., Sucrose (Invert H
tose, Maltose, Cellobiose sugar), Glycogen,
Inulin Classification of Amino acids

yy Sucrose is also known as cane sugar, mostly produced Amino Acid Symbol
by sugarcane and sugar beats and made up of α-D-
Glucose and β-D-fructose. Amino Acids with Aliphatic R-Groups
yy Sucrose is also known as Invert sugar because of
Glycine Gly–G
sucrose, as such is in dextrorotatory (+66.5°) but when
hydrolysed, sucrose becomes levorotatory (–28.2°). Alanine Ala–A
This process of change in optical rotation is known as
Valine Val–V
inversion, that is why sucrose is known as invert sugar.
yy Lactose (milk sugar) is made up of β-D-Glucose and Leucine Leu–L
β-D-Galactose.
yy Maltose is made up of two molecule of α-D-Glucose. Isoleucine Ile–I

3. Polysaccharides Polysaccharides (or simply glycan) Non-Aromatic Amino Acids with Hydroxyl R-Groups
consist of repeat units of monosaccharides or their deriva-
Serine Ser–S
tive held together by glycosidic bonds.
The main function of polysaccharide is structural and Threonine Thr–T
storage of energy.
Amino Acids with Sulphur-containing R-Groups
Polysaccharides are linear or branched polymers.
The general formula of polysaccharide is (C6H10O5)x. Cysteine Cys–C
Types of polysaccharides Methionine Met–M
Homopolysaccharides On hydrolysis, it gives only a
Acidic Amino Acids and their Amides
single type of monosaccharide.
E.g., Starch, Glycogen, Inulin, Cellulose, Pectin, Chitin, Aspartic Acid Asp–D
Dextrin
Heteropolysaccharides When polysaccharides are Asparagine Asn–N
made up of different types of sugar or their derivatives, they Glutamic Acid Glu–E
are referred as heteropolysaccharides.
E.g., Hyaluronic acid, Chondrotin, Heparin, Keratan Glutamine Gln–Q
Sulfate
3.148  Chapter 4

When the net charge of an amino acid or protein is

Basic Amino Acids
zero, the pH will be equivalent to the isoelectric point pI.
Arginine Arg–R
Optical properties of the amino acids
Lysine Lys–K
A tetrahedral carbon atom with four distinct constituents
Histidine His–H is said to be chiral. The one amino acid not exhibiting
chirality is glycine since its “R-group” is a hydrogen atom.
Amino Acids with Aromatic Rings Chirality describes the handedness of a molecule that is
observable by the ability of a molecule to rotate the plane of
Phenylalanine Phe–F polarized light either to the right (dextrorotatory) or to the
left (levorotatory).
Tyrosine Tyr–Y

Tryptophan Trp–W In acidic solutions,

zwitterions accept protons.
Imino Acids O O
+ – + +
H 3N CH C O +H H3N CH C O H
Proline Pro–P
R R
O O
There are two types of amino acids as per the nutri- +
H3N CH C
–
O + OH
–
H 2N CH C O H + H+
tional requirement.
R R
In basic solutions,
yy Essential amino acids are those that are not synthesized zwitterions lose protons.
by the body and are needed in the diet. Methionine,
threonine, tryptophan, valine, isoleucine, leucine
All of the amino acids in proteins exhibit the same
arginine histidine and phenylalanine are the essential
absolute steric configuration as L-glyceraldehyde. There-
amino acids.
fore, they are all L-α-amino acids. D-amino acids are never
yy Non-essential amino acids are those that are synthe-
found in proteins, although they exist in nature. D-amino
sized in the body and are not necessary in the diet.
acids are often found in polypetide antibiotics.
Glycine, alanine, serine, cysteine, tyrosine, proline,
Aromatic R-groups in amino acids absorb ultraviolet
aspartic acid and glutamic acid are the non-essential
light with an absorbance maximum in the range of 280nm.
amino acids.
The ability of proteins to absorb ultraviolet light is predomi-
nantly due to the presence of the tryptophan which strongly
Acid-base properties of the amino acids absorbs ultraviolet light.
Amino acids can undergo an intramolecular acid–base reac-
tion. Transfer of the H from the –COOH group to the –NH2 Peptide bond
group forms a neutral dipolar ion, an ion that has one (+) Peptide bond formation is a condensation reaction lead-
charge and one (–) charge. Neutral dipolar ions are known ing to the polymerization of amino acids into peptides and
as zwitterions. proteins. Peptides are small chains consisting of few amino
acids. A number of hormones and neurotransmitters are
R-COOH <——> R-COO– + H+
peptides. Additionally, several antibiotics and antitumor
R-NH3+ <——> R-NH2 + H+ agents are peptides. Proteins are polypeptides of greatly
divergent length. The simplest peptide, a dipeptide, con-
The equilibrium reactions, as written, demonstrate tains a single peptide bond formed by the condensation
that amino acids contain at least two weakly acidic groups. of the carboxyl group of one amino acid with the amino
However, the carboxyl group is a far stronger acid than group of the second with the concomitant elimination of
the amino group. At physiological pH, (around 7.4) the water. The presence of the carbonyl group in a peptide
carboxyl group will be unprotonated and the amino group bond allows electron resonance stabilization to occur such
will be protonated. An amino acid with no ionizable R- that the peptide bond exhibits rigidity not unlike the typical
group would be electrically neutral at this pH. This species –C=C– double bond. The peptide bond is, therefore, said
is termed a zwitterion. to have partial double-bond character.
 Biochemistry  3.149

H RΤ OH

H R OH H RΤ OH H R N C C

+ HOH
N C C + N C C N C C H O

H H O H H O H H O
dehydration synthesis peptide bond

Proteins Lipids
They are complex molecules made up of carbon, hydrogen, Saponification Value
oxygen and nitrogen (sometimes sulphur and phosphorus).
Proteins are used to synthesize enzymes (E.g., pepsin, yy Saponification is the base-catalysed hydrolysis of an
trypsin), hormones (E.g., insulin, adrenaline), carrier proteins ester.
(E.g., haemoglobin), contractile proteins (E.g., myosin, actin), yy Products of the reaction are–an alcohol and an ionized
structural proteins (E.g., collagen) and protective proteins salt which is a soap.
(antibodies). They also form skin pigments like melanin
and nucleic acids of the genetic material, DNA and RNA- Acid value
purines and pyrimidines. yy Number of mgs of KOH required to neutralize the free
Structure of proteins fatty acids in 1g of fat, that number indicates degree of
yy Their Primary structure is the amino acid sequence of rancidity.
the polypeptide chain.
yy Secondary structure is the local spatial arrangement of Iodine Value
a polypeptide’s backbone atoms. Common secondary yy Number of iodine (g) absorbed by 100 g of oil.
structures are alpha-helices and beta-strands. In both, yy Molecular weight and iodine number can calculate the
hydrogen bonding between backbone atoms holds the number of double bonds.
polypeptide chain in place. Alpha confirmation (Helical
coil) and Beta confirmation (Pleated sheet). Rancidity
yy Tertiary structure The overall three-dimensional shape yy Due to long exposure to air, a foul odour or smell comes
that results from the folding of a protein chain is the known as rancidity.
protein’s tertiary structure.
yy Triglyceride
yy In contrast to secondary structure, which depends
mainly on attraction between backbone atoms, tertiary
Oxidation (Air, Moisture, Light)
structure depends mainly on interactions of amino acid
Fatty acids
side chains that are far apart along the same backbone.
Lipase
The fourth and final level of protein structure, and the
most complex, is quaternary protein structure— Especially, C4 butyric acid and other short chain fatty
the way in which two or more polypeptide subunits as- acids in butter are the real problem.
sociate to form a single three-dimensional protein unit.
yy The individual polypeptides are held together by the
Fatty Acids No. of Carbons (Double bonds)
same non-covalent forces responsible for tertiary struc-
ture. In some cases, there are also covalent bonds and Palmitic acid 16 (0)
the protein may incorporate a non-amino acid portion.
Stearic Acid 18 (0)
Denaturation The loss of secondary, tertiary, or quarter-
nary protein structure due to disruption of non-covalent Oleic acid 18 (1)
interactions and/or disulfide bonds that leaves peptide bonds Myristic acid 14 (0)
and primary structure intact.
Linoleic acid 18 (2)
3.150  Chapter 4

Fatty Acids No. of Carbons (Double bonds) Nucleoside and Nucleotide Structure and
Nomenclature
Linolenic acid 18 (3)
H
N
Arachidonic acid 20 (4) N N

Lauric Acid 12 (0)

N N N
Capric Acid 10 (0) Pyrimidine
Purine

ml of KOH × N × 56 The derivatives of purine are called adenine and guanine,

AV = mg of KOH and the derivatives of pyrimidine are called thymine, cyto-
Weight of Sample
sine and uracil. The common abbreviations used for these
five bases are, A, G, T, C and U.

Base Formula Base (X=H) Nucleoside X=ribose or deoxyribose Nucleotide X=ribose phosphate

NH2 Cytosine, C Cytidine, C Cytidine monophosphate, CMP

N O
X

O Uracil, U Uridine, U Uridine monophosphate, UMP

NH

N O
X

O Thymine, T Thymidine, T (only deoxyribose) Thymidine monophosphate, TMP

H 3C
NH

N O
X
NH2 Adenine, A Adenosine, A Adenosine monophosphate, AMP

N N
N
N
X
O Guanine, G Guanosine, G Guanosine monophosphate, GMP

N NH
N
N NH2
X
 Biochemistry  3.151

yy The purine and pyrimidine bases in cells are linked to common site of phosphorylation of nucleosides found in
pentose sugar and in this form are termed, nucleosides. cells is the hydroxyl group attached to the 5′-carbon of the
yy The nucleosides are coupled to D-ribose or 2′-deoxy- ribose The carbon atoms of the ribose present in nucleotides
D-ribose through a β-N-glycosidic bond between the are designated with a prime (′) mark to distinguish them
anomeric carbon of the ribose and the N9 of a purine or from the backbone numbering in the bases. Nucleotides can
N1 of a pyrimidine. exist in the mono-, di-, or tri-phosphorylated forms.
yy The base can exist in two distinct orientations about the
N-glycosidic bond. These conformations are identified Chargaff’s rules
as, syn and anti. It is the anti-conformation that pre-
It was known that DNA is composed of nucleotides, each
dominates in naturally occurring nucleotides.
of which contains a nitrogen-containing base, a five car-
bon sugar (deoxyribose), and a phosphate group. In these
DNA RNA nucleotides, there is one of the four possible bases: adenine
1. Found in nucleus 1. Found in nucleus and (A), guanine (G), cytosine (C), or thymine (T) . Adenine
2. sugar is deoxyribose cytoplasm and guanine are purine bases, and cytosine and thymine are
3. Bases are A, T, C, G 2. Sugar is ribose. pyrimidine bases.
3. Bases are A, U, C, G Erwin Chargaff (1905-2002), an Austrian-American
biochemist from Columbia University, analyzed the base
DNA is a long polymer RNA is a polymer with a ri- composition of the DNA of various species. This led him to
with a deoxyribose and bose and phosphate back-
propose two main rules that have been appropriately named
phosphate backbone and bone and four different
four different bases: bases: adenine, guanine,
Chargaff’s rules.
adenine, guanine, cyto- cytosine, and uracil Nitrogen Bases in DNA
sine and thymine Chargaff's rule is not
obeyed due to single
stranded nature

Typically a double-strand- Single-stranded molecule

ed molecule with a long in most of its biological
chain of nucleotides roles and has a shorter
chain of nucleotides
Adenine       Guanine         Cytosine      Thymine
Pairing of Bases: A-T A-U (Adenine-Uracil),
(Adenine-Thymine), G-C (Guanine-Cytosine)
G-C (Guanine-Cytosine) Rule 1: Chargaff determined that in DNA, the amount
of one base, a purine, always approximately equals the
Deoxyribose sugar in DNA Ribose sugar is more amount of a particular second base, a pyrimidine. Spe-
is less reactive because of reactive because of C-OH cifically, that in any double-stranded DNA the number
C-H bonds. Stable in alka- (hydroxyl) bonds. Not
of guanine units equals approximately the the number of
line conditions. DNA has stable in alkaline condi-
cytosine units and the number of adenine units equals ap-
smaller grooves where tions. RNA on the other
the damaging enzyme hand has larger grooves proximately the number of thymine units. Human DNA
can attach which makes it which make it easier to is 30.9% A and 29.4% T, 19.9% G and 19.8% C. The rule
harder for the enzyme to be attacked by enzymes. constitutes the basis of base pairs in the DNA double he-
attack DNA. lix: A always pairs with T, and G always pairs with C. He
also demonstrated that the number of purines (A+G) al-
The helix geometry of The helix geometry of ways approximates the number of pyrimidines (T+C), an
DNA is of β-Form. RNA is of α-Form.
obvious consequence of the base-pairing nature of the
Storage and transmission Transfer the genetic code DNA double helix.
of genetic information. needed for the creation
Rule 2: In 1947 Chargaff showed that the composition of
of proteins from the
nucleus to the ribosome.
DNA, in terms of the relative amounts of the A, C, G and
T bases, varied from one species to another. This molecu-
lar diversity added evidence that DNA could be the genetic
yy Nucleosides are found in the cell primarily in their phos- material.
phorylated form. These are termed nucleosides. The most
3.152  Chapter 4

Bonding acid linked to tRNA, sequentially bind to the appropriate

codon in mRNA by forming complementary base pairs with
There are three different kinds of chemical bonds:
the tRNA anticodon. The ribosome moves from codon to
1. Ionic bonds (also called electrovalent bonds) are
codon along the mRNA. Amino acids are added one by one,
formed between atoms when one or more electrons are
translated into polypeptidic sequences dictated by DNA and
completely transferred from one atom to the other.
represented by mRNA. At the end, a release factor binds
2. Covalent bonds are formed between atoms when two
to the stop codon, terminating translation and releasing the
atoms share one or more pairs of electrons.
complete polypeptide from the ribosome.
3. Hydrogen bonds are formed between the positively-
charged hydrogen atom in one covalently-bonded
molecule and the negatively-charged area of another Genetic Code
covalently-bonded molecule. The genetic code consists of 64 triplets of nucleotides.
These triplets are called codons. With three exceptions,
DNA bases are held together by hydrogen bonds.
each codon encodes for one of the 20 amino acids used in
There are two hydrogen bonds between A and T and three
the synthesis of proteins. That produces some redundancy
hydrogen bonds between C and G.
in the code: most of the amino acids being encoded by more
than one codon.
Protein Synthesis One codon, AUG serves two related functions:
1. Transcription yy it signals the start of translation
yy it codes for the incorporation of the amino acid methio-
It is the process of creating a complementary RNA copy
from sequence of DNA. Both RNA and DNA are nucleic ac- nine (Met) into the growing polypeptide chain
ids, which use base pairs of nucleotides as a complementary The genetic code can be expressed as either RNA
language that can be converted back and forth from DNA to codons or DNA codons. RNA codons occur in messenger
RNA by the action of the correct enzymes. During transcrip- RNA (mRNA) and are the codons that are actually “read”
tion, a DNA sequence is read by RNA polymerase, which during the synthesis of polypeptides (the process called
produces a complementary, antiparallel RNA strand. As translation).
opposed to DNA replication, transcription results in an RNA
complement that includes uracil (U) in all instances where Properties of genetic codes
thymine (T) would have occurred in a DNA complement.
yy Genetic code is degenerate The occurrence of more than
Transcription can be explained easily in four or five
one codon per amino acid is called degeneracy. All amino
simple steps, each moving like a wave along the DNA.
acids except methionine and tryptophan have more than
1. DNA unwinds/“unzips” as the hydrogen bonds break. one codon, so that all the possible triplets have a meaning,
2. The free nucleotides of the RNA, pair with comple- despite there being 64 triplets and only 20 amino acids.
mentary DNA bases. Leucine, Serine and Arginine have six different codons.
3. RNA sugar-phosphate forms backbone. (Aided by yy Code contains punctuation codons Three codons do
RNA Polymerase.) not code for specific amino acids. These codons are
4. Hydrogen bonds of the untwisted RNA+DNA “ladder” called as nonsense codons. These nonsense codons
break, freeing the new RNA. cause termination of protein synthesis. AUG codon codes
5. If the cell has a nucleus, the RNA is further processed for starting of the gene and position where translation
and then moves through the small nuclear pores to the should begin. AUG codes for the initiation codon and
cytoplasm. because it codes for methionine, almost all newly synthe-
sized polypeptides have this amino acid at the start.
2. Translation yy Codon is commaless. There are no commas or some
specific nucleotide sequences to separate the codons,
“Biosynthesis of a protein or polypeptide in a living cell is
i.e., CCCAAAUUUGGG has four code words and
known as Translation”
upon translation, we have a tetrapeptide chain of
The ribosome binds to the mRNA at the start codon
pro-lys-phen-gly. So all the letters are used to code for
(AUG) that is recognized only by the initiator tRNA. The
one or other amino acid.
ribosome proceeds to the elongation phase of protein syn-
yy Codon is Triplet in nature.
thesis. During this stage, complexes, composed of an amino
 Biochemistry  3.153

Myoglobin Pyridoxal, Pyridoxamine Vitamin K

yy Myoglobin and hemoglobin are hemeproteins whose Pyridoxine
physiological importance is principally related to their Biotin (B7)
ability to bind molecular oxygen.
Cobalamin (B12)
yy Myoglobin is a monomeric heme protein found mainly
in muscle tissue where it serves as an intracellular stor- Folic Acid, Pantothenic acid
age site for oxygen. The tertiary structure of myoglo- Ascorbic Acid
bin is that of a typical water soluble globular protein.
Its secondary structure is unusual in that it contains
Thiamine
a very high proportion (75%) of α-helical secondary
structure. A myoglobin polypeptide is comprised of 8 H3C N NH2 S CH2CH2OH
separate right handed α-helices, designated A through
N N
H, that are connected by short non helical regions. CH2 + CH3
yy Each myoglobin molecule contains one heme prosthetic
group inserted into a hydrophobic cleft in the protein. yy Thiamin is derived from a substituted pyrimidine and
Each heme residue contains one central coordinately a thiazole which are coupled by a methylene bridge.
bound iron atom that is normally in the Fe2+, or ferrous, Thiamin is rapidly converted to its active form, thiamin
oxidation state. pyrophosphate, TPP, by thiamin diphosphotransferase.
yy TPP is necessary as a cofactor for the pyruvate dehy-
yy The oxygen carried by hemeproteins is bound directly to
drogenase and α-ketoglutarate dehydrogenase catalysed
the ferrous iron atom of the heme prosthetic group. Oxi-
reactions as well as the transketolase catalysed reactions
dation of the iron to the Fe3+, ferric, oxidation state renders
of the pentose phosphate pathway.
the molecule incapable of normal oxygen binding.
yy Thiamin deficiency causes Beriberi, Wernicke-Korsakoff
yy Hydrophobic interactions between the tetrapyrrole ring
syndrome.
and hydrophobic amino acid R groups on the interior of
the cleft in the protein strongly stabilize the heme protein Riboflavin
conjugate. In addition, a nitrogen atom from a histidine
R group located above the plane of the heme ring is coor-
dinated with the iron atom further stabilizing the interac-
tion between the heme and the protein.
yy Carbon monoxide also binds coordinately to heme iron
atoms in a manner similar to that of oxygen, but the
binding of carbon monoxide to heme is much stronger
than that of oxygen. The preferential binding of carbon
monoxide to heme iron is largely responsible for the as-
phyxiation that results from carbon monoxide poisoning. Riboflavin is the precursor for the coenzymes, flavin mono-
nucleotide (FMN) and flavin adenine dinucleotide (FAD).
Hemoglobin
The enzymes that require FMN or FAD as cofactors are
Adult hemoglobin is a [α(2):β(2)] tetrameric hemeprotein termed flavoproteins. Both classes of enzymes are involved
found in erythrocytes where it is responsible for binding in a wide range of redox reactions e.g., succinate dehydro-
oxygen in the lung and transporting the bound oxygen through- genase and xanthine oxidase.
out the body where it is used in aerobic metabolic pathways.
Niacin
6. Vitamins O O
Water Soluble vitamin Water insoluble vitamin
Thiamin (B1), Vitamin A NH2 OH
Riboflavin (B2) Vitamin D
N N
Niacin (B3) Vitamin E
Nicotinamide Nicotinic acid
3.154  Chapter 4

yy Niacin is required for the synthesis of the active forms kinase. Pyridoxal kinase requires zinc for full activity
of vitamin B3, nicotinamide adenine dinucleotide thus making it a metaloenzyme.
(NAD+) and nicotinamide adenine dinucleotide phos- yy Pyridoxal phosphate functions as a cofactor in enzymes
phate (NADP+). Both NAD+ and NADP+ function as involved in transamination reactions required for the
cofactors for numerous dehydrogenases e.g., lactate synthesis and catabolism of the amino acids as well as
dehydrogenase and malate dehydrogenase. in glycogenolysis as a cofactor for glycogen phosphor-
yy Niacin is not a true vitamin. ylase and as a co-factor for the synthesis of the inhibi-
yy Niacin deficiency causes pellagra. tory neurotransmitter γ-aminobutyric acid (GABA).
yy Isoniazid (see niacin deficiencies above) and penicilla-
Pantothenic acid mine (used to treat rheumatoid arthritis and cystinurias)
are two drugs that complex with pyridoxal and PLP
CH3OH O O
resulting in a deficiency of this vitamin.
HOCH2 C CH C NH CH2CH2 C OH
CH3 Biotin
O
C
HN NH
HC CH O
H 2C CH (CH2)4 C OH
S
yy Pantothenic acid is formed from β-alanine and pantoic
acid.
yy Pantothenate is required for synthesis of coenzyme A. Biotin is the cofactor required of enzymes that are involved
in carboxylation reactions e.g., acetyl-CoA carboxylase and
Vitamin B6 pyruvate carboxylase.

O
O Cobalamin
CH2OH H
C H yy Cobalamin is more commonly known as vitamin B12.
CH2OH C
HO CH2OH HO CH OH Vitamin B12 is composed of a complex tetrapyrrol ring
HO CH2OH HO CH22OH structure (corrin ring) and a cobalt ion in the center.
H 3C + H 3C + yy The reaction requiring vitamin B12 catalyses the conver-
H 3C N+ H 3C +
N
N N sion of homocysteine to methionine and is catalysed by
H H methionine synthase. This reaction results in the transfer
H H
Pyridoxine Pyridoxal of the methyl group from N5-methyltetrahydrofolate to
Pyridoxine Pyridoxal
hydroxycobalamin generating tetrahydrofolate (THF) and
CH2 NH2 methylcobalamin during the process of the conversion.
CH2 NH2
yy B12 deficiency-Pernicious anemia is a megaloblastic
HO CH2OH
HO CH2OH anemia resulting from vitamin B12 deficiency.
H 3C +
H 3C +
N
N Folic acid
H
H
Pyridoxamine
Pyridoxamine

yy Pyridoxal, pyridoxamine and pyridoxine are collectively

known as vitamin B6. All three compounds are efficient-
ly converted to the biologically active form of vitamin
B6, pyridoxal phosphate (PLP). This conversion is
catalysed by the ATP requiring enzyme, pyridoxal
 Biochemistry  3.155

Positions 7 and 8 carry hydrogens in dihydrofolate (DHF) yy Ascorbic acid also serves as a reducing agent and
Positions 5–8 carry hydrogens in tetrahydrofolate (THF) an antioxidant. When functioning as an antioxidant,
ascorbic acid itself becomes oxidized to semidehy-
yy Folic acid is a conjugated molecule consisting of a
droascorbate and then dehydroascorbate.
pteridine ring structure linked to para-aminobenzoic
yy Deficiency of vitamin C leads to the disease called scurvy.
acid (PABA) that forms pteroic acid. Folic acid itself
is then generated through the conjugation of glutamic
Vitamin A
acid residues to pteroic acid.
yy The function of THF derivatives is to carry and transfer Vitamin A consists of three biologically active molecules,
various forms of one carbon units during biosynthetic retinol, retinal (retinaldehyde) and retinoic acid.
reactions. The one carbon units are either methyl, meth- CH3 CH3 O
H3C CH3 11
ylene, methenyl, formyl or formimino groups. CH
yy Folate deficiency–The most pronounced effect of folate
deficiency on cellular processes is upon DNA synthesis.
This is due to an impairment in dTMP synthesis which CH3
leads to cell cycle arrest in S-phase of rapidly proliferat- All-trans-retinal
ing cells, in particular hematopoietic cells. The result is CH3
H 3C CH3 11
megaloblastic anemia as for vitamin B12 deficiency.
yy The inability to synthesize DNA during erythrocyte
maturation leads to abnormally large erythrocytes
termed macrocytic anemia. CH3 CH3
O=CH
Ascorbic acid 11-cis-retinal

CH2OH H 3C CH3 CH3 CH3

HO C H OH
O
O
CH3
Retinol
HO OH
yy Ascorbic acid is more commonly known as vitamin C. CH3 CH3
H 3C CH3
Ascorbic acid is derived from glucose via the uronic C–OH
acid pathway. The enzyme L-gulonolactone oxidase
O
is responsible for the conversion of gulonolactone to CH3
ascorbic acid.
yy The active form of vitamin C is ascorbic acid itself. The Retinoic Acid
main function of ascorbate is as a reducing agent in a
number of different reactions. yy Each of these compounds are derived from the plant precur-
yy Ascorbate is the cofactor for Cu+–dependent monooxy- sor molecule, β-carotene. Beta-carotene, which consists of
genases and Fe2+–dependent dioxygenases. two molecules of retinal linked at their aldehyde ends, is
yy Ascorbate has the potential to reduce cytochromes a and also referred to as the provitamin form of vitamin A.
c of the respiratory chain as well as molecular oxygen. yy Vision and the role of Vitamin A
yy The most important reaction requiring ascorbate as The photosensitive compound of most mammalian

a cofactor is the hydroxylation of proline residues eyes is a protein called opsin to which is covalently
in collagen. Vitamin C is, therefore, required for the coupled an aldehyde of vitamin A. The opsin of rod
maintenance of normal connective tissue as well as for cells is called scotopsin. The photoreceptor of rod cells
wound healing since synthesis of connective tissue is is specifically called rhodopsin or visual purple. This
the first event in wound tissue remodeling. compound is a complex between scotopsin and the
yy Vitamin C also is necessary for bone remodeling due to 11-cis-retinal (also called 11-cis-retinene) form of
the presence of collagen in the organic matrix of bones. vitamin A. Rhodopsin is a serpentine receptor imbedded
3.156  Chapter 4

in the membrane of the rod cell. Coupling of 11-cis- H3C CH3

retinal occurs at three of the transmembrane domains H3C
of rhodopsin. Intracellularly, rhodopsin is coupled to a H2C CH3
specific G-protein called transducin.
 When the rhodopsin is exposed to light it is
bleached releasing the 11-cis-retinal and opsin. Absorp- HO
tion of photons by 11-cis-retinal triggers a series of
conformational changes on the way to conversion Vitamin D3
all-trans-retinal. Active calcitriol is derived from ergosterol (produced
yy Vitamin A deficiency: It causes night blindness, hyper- in plants) and from 7-dehydrocholesterol (produced in the
keratinosis, keratinization of the cornea, a condition skin). Ergocalciferol (vitamin D2) is formed by uv irradiation
known as xerophthalmia. of ergosterol. In the skin 7-dehydrocholesterol is converted to
cholecalciferol (vitamin D3) following uv irradiation.
Vitamin D Cholecalciferol (or ergocalciferol) are absorbed from the
intestine and transported to the liver bound to a specific vitamin
Vitamin D is a steroid hormone that functions to regulate
D-binding protein. In the liver, cholecalciferol is hydroxylated
specific gene expression following interaction with its in-
at the 25 position by a specific D3-25-hydroxylase generating
tracellular receptor. The biologically active form of the hor-
25-hydroxy-D3 [25-(OH)D3] which is the major circulating
mone is 1, 25-dihydroxy vitamin D3 (1, 25-(OH)2D3, also
form of vitamin D. Conversion of 25-(OH)D3 to its biologically
termed calcitriol). Calcitriol functions primarily to regulate
active form, calcitriol, occurs through the activity of a specific
calcium and phosphorous homeostasis.
D3-1-hydroxylase present in the proximal convoluted tubules
CH3 of the kidneys, and in bone and placenta.
H3C Calcitriol functions in concert with parathyroid hor-
CH3
H3C mone (PTH) and calcitonin to regulate serum calcium and
H3C CH3 phosphorous levels.
Vitamin D deficiency: The main symptom of vitamin D
deficiency in children is rickets and in adults is osteomalacia.
HO
Ergosterol
Vitamin E
CH3
H 3C CH3 CH3 CH3 CH3
CH3 O
H3C H 3C (CH2)3 CH (CH2)3 CH (CH2)3 CHCH3
H3C CH3
HO

CH3
HO
yy Vitamin E is a mixture of several related compounds
7-Dehydrocholesterol known as tocopherols. The α-tocopherol molecule is
the most potent of the tocopherols.
CH3 yy The major site of vitamin E storage is in adipose tissue.
H3C CH3 yy The major function of vitamin E is to act as a natural
H3C antioxidant by scavenging free radicals and molecular
H2C CH3 oxygen.
yy In particular, vitamin E is important for preventing
peroxidation of polyunsaturated membrane fatty acids.
HO yy The vitamins E and C are interrelated in their antioxidant
capabilities.
Vitamin D2
yy Vitamin E deficiency-The major symptom of vitamin
E deficiency in humans is an increase in red blood cell
fragility.
 Biochemistry  3.157

Vitamin K Sr. No. Vitamins Precursor (Biosynthetic)

O
CH3 6 Pantothenic Beta-alanine + alpha J,
CH3
acid ~toisovaleric acid

O CH3 CH3 CH3 CH3

7 PABA Shikimic acid
Phylloquinone (vitamin K1) 8 Biotin Pimelic acid
O
CH3
9 Choline Serine
CH3
10 Folic acid Purine or Purine equivalent
O
CH3 CH3 CH3 CH3
Menaquinone-4 (vitamin K2) Mutarotation
O
CH3 Mutarotation – change in the optical rotation that occurs
by epimerization (that is the change in the equilibrium
H between two epimers, when the corresponding stereocenters
O interconvert). Cyclic sugars show mutarotation as α and β
Menadione (vitamin K3) anomeric forms interconvert. The optical rotation of the
Human use 6, 7 or 9 isoprene chains. solution depends on the optical rotation of each anomer and
The K vitamins exist naturally as K1 (phylloquinone) their ratio in the solution.
in green vegetables and K2 (menaquinone) produced by The two stereoisomeric forms of glucose, i.e., α-D-
intestinal bacteria and K3 is synthetic menadione. When glucose and β-D-glucose exist in separate crystalline
administered, vitamin K3 is alkylated to one of the vitamin K2 forms and thus have different melting points and specific
forms of menaquinone. roations. For example α-D-glucose has a m.p. of 419 K
The major function of the K vitamins is in the mainte- with a specific rotation of +112° while β-D-glucose has a
nance of normal levels of the blood clotting proteins, factors m.p. of 424 K and has a specific rotation of +19°. However,
II, VII, IX, X and protein C and protein S, which are synthe- when either of these two forms is dissolved in water and
sized in the liver as inactive precursor proteins. allowed to stand, it gets converted into an equilibrium mix-
Conversion from inactive to active clotting factor requires ture of α-and β-forms through a small amount of the open
a post-translational modification of specific glutamate (E) chain form.
residues. This modification is a carboxylation and the enzyme
Open chain
responsible requires vitamin K as a cofactor. The resultant
form (0.02%)
modified e residues are γ-carboxyglutamate (gla).
During the carboxylation reaction, reduced hydroquinone As a result of this equilibrium, the specific rotation
form of vitamin K is converted to a 2, 3-epoxide form. of a freshly prepared solution of α-D-glucose gradually
Vitamin K deficiency-Malabsorptive diseases can decreases from of +112° to +52.7° and that of β-D-glucose
result in vitamin K deficiency. gradually increases from +19° to +52.7°.
Important table

Sr. No. Vitamins Precursor (Biosynthetic)

1 Vitamin A Carotenoid

2 Vitamin D Acetyl-Mevalonic acid

3 Vitamin Pyrimidine phosphatase +
This change in specific rotation of an optically active
Bl/Thiamine Thiazole moieties compound in solution with time, to an equilibrium value, is
called mutarotation. During mutarotation, the ring opens and
4 Riboflavin/ Purine then recloses either in the inverted position or in the original
Vitamin B2
position giving a mixture of α-and-β-forms. All reducing car-
5 Nicotinic acid Reaction between Aspartic bohydrates, i.e. monosaccharides and disacchardies (maltose,
acid + glutaraldehyde- lactose etc.) undergo mutarotation in aqueous solution.
3-phosphate
3.158  Chapter 4

Isoelectric Point the lysine twice, and therefore use the R-group and amine
The isoelectric point (pI) - is the pH at which a particular pKa values (found at List of standard amino acids).
molecule or surface carries no net electrical charge. 9.06 + 10.54
Amphoteric molecules called zwitterions contain both pI = = 9.80
2
positive and negative charges depending on the functional
groups present in the molecule. The net charge on the The pH of an electrophoretic gel is determined by the
molecule is affected by pH of their surrounding environ- buffer used for that gel. If the pH of the buffer is above the pI
ment and can become more positively or negatively charged of the protein being run, the protein will migrate to the posi-
due to the loss or gain of protons (H+). The pI is the pH tive pole (negative charge is attracted to a positive pole). If
value at which the molecule carries no net electrical charge the pH of the buffer is below the pI of the protein being run,
or the negative and positive charges are equal. the protein will migrate to the negative pole of the gel (posi-
Surfaces naturally charge to form a double layer. In the tive charge is attracted to the negative pole). If the protein is
common case when the surface charge-determining ions are run with a buffer pH that is equal to the pI, it will not migrate
H+/OH-, the net surface charge is affected by the pH of at all. This is also true for individual amino acids
the liquid in which the solid is submerged. Again, the pI
is the pH value of the solution at which the surfaces carries Osazone
no net charge. Osazones are carbohydrate derivatives formed when sugars
The pI value can affect the solubility of a molecule at a are reacted with phenyl hydrazine.
given pH. Such molecules have minimum solubility in wa- The reaction involves formation of a pair of phenylhy-
ter or salt solutions at the pH that corresponds to their pI drazone functionalities, concomitant with the oxidation of
and often precipitate out of solution. Biological amphoteric the hydroxymethylene group adjacent to the formyl center.
molecules such as proteins contain both acidic and basic The reaction can be used to identify monosaccharides. It
functional groups. Amino acids that make up proteins may involves two reactions.
be positive, negative, neutral, or polar in nature, and togeth- Firstly glucose with phenyl hydrazine gives us glucose
er give a protein its overall charge. At a pH below their pI, phenylhydrazone by elimination of a water molecule from
proteins carry a net positive charge; above their pI they the functional group. The next step involves reaction of one
carry a net negative charge. Proteins can, thus, be separated mole of glucose phenylhydrazone with two moles of phenyl
according to their isoelectric point (overall charge) on a hydrazine (excess).
polyacrylamide gel using a technique called isoelectric fo- First phenyl hydrazine is involved in oxidizing the alpha
cusing, which uses a pH gradient to separate proteins. Iso- carbon to a carbonyl group, and the second phenyl hydrazine
electric focusing is also the first step in 2-D polyacrylamide involves in removal of one water molecule with the formyl
gel electrophoresis. group of that oxidized carbon and forming the similar carbon
nitrogen bond. The alpha carbon is attacked here because its
more reactive than the others. They are highly colored and
Calculation of pI crystalline compounds and can be easily detected. Glucose
For an amino acid with only one amine and one carboxyl gives broomstick shaped crystals with this whereas maltose
group, the pI can be calculated from the mean of the pKas gives sunflower shaped crystals.
of this molecule .

pK1 + pK 2 Carr Price Reaction

pI = A reaction of antimony trichloride and vitamin A in chlo-
2
roform solution that gives a blue color and is used for the
For amino acids with more than two ionizable groups, identification and assay of vitamin A.
such as lysine, the same formula is used, but this time the
two pKa’s used are those of the two groups that lose and Classification of Enzyme
gain a charge from the neutral form of the amino acid. Lysine 1. Oxidoreductases: catalyze the transfer of hydrogen or
has a single carboxylic pKa and two amine pKa values (one oxygen atoms or electrons from one substrate to another,
of which is on the R-group), so fully protonated lysine has a also called oxidases, dehydrogenases, or reductases. Note
+2 net charge. To get a neutral charge, we must deprotonate that since these are ‘redox’ reactions, an electron donor/ac-
ceptor is also required to complete the reaction.
 Biochemistry  3.159

Oxidases Use oxygen as an electron accep- 6. Ligases: catalyzes the synthesis of various (mostly CµX)
tor but do not incorporate in the bonds, coupled with the breakdown of energyµcontaining
substrate substrates, usually ATP.
Dehydrogenase Use molecule other than oxygen(e.g. Carboxylases Use CO2 as a substrate
NAD+) as an electron acceptor
Synthetases Link two molecule via an ATP depen-
Oxygenases Directly incorporate oxygen into the dent reaction
substrate
Peroxidase Use H2O2 as an electron acceptor Classification of amino acids
2. Transferases: catalyze group transfer reactions, I. Chemical classification: According to number of COOH
excluding oxidoreductases (which transfer hydrogen or and NH2 groups i.e. according to net charge on amino acid.
oxygen and are EC 1). These are of the general form ( A. Monobasic & monocarboxylic amino acids i.e. neu-
AµX + B ↔ BX + A ) tral or uncharged:
Methyltransferase Transfer of one carbon units be-
tween substrates
Aminotransferases Transfer of NH2 from amino acid
to keto acids
Kinases Transfer of PO3 from ATP to a 1. Glycine R= H
substrate 2. Alanine R= CH3
Phosphorylases Transfer of PO3 from inorganic 3. Branched chain amino acids: R is branched such as in:
phosphate(P) to a substrate a. Valine R= isopropyl group
3. Hydrolases: catalyze hydrolytic reactions. Includes li- b. Leucine R= isobutyl group
pases, esterases, nitrilases, peptidases/proteases. These are c. Isoleucine R = is isobutyl group
of the general form ( AµX + H2O ↔ XµOH + HA ) 4. Neutral Sulfur containing amino acids: e.g. Cysteine
and Methionine. Cysteine, not involved in proteins.
Phosphatase Removal of PO3 from substrate
It is dimer of cysteine linked by S-S bond (oxidized
Phosphodiesterases Cleavage of Phosphodiester form)
bond such as those in Nucleic 5. Neutral, hydroxyl amino acids: e.g. Serine and Threo-
acid nine
Protease Cleavage of amide bond such as 6. Neutral aromatic amino acids:
those in proteins a. Phenyl alanine
4. Lyases: It catalyze non-hydrolytic (covered in EC 3) re- b. Tyrosine: - it is p- hydroxy phenyl alanine
moval of functional groups from substrates, often creating a c. Tryptophan:
double bond in the product; or the reverse reaction, ie, ad- 7. Neutral heterocyclic amino acids:
dition of function groups across a double bond. It includes a. Tryptophan: contains indole ring
decarboxylases and aldolases in the removal direction, and b. Proline: In proline, amino group enters in the ring
synthases in the addition direction. formation being α-imino group so proline is an
α-imino acid rather than α-amino acid
Decarboxylases Produce CO2 via elimination reactions B. Basic amino acids: Contain two or more NH groups or
Aldolases Produce Aldehyde via elimination nitrogen atoms that act as base i.e. can bind proton. At phys-
reactions iological pH, basic amino acids will be positively charged.
Synthases Link two molecule without involve- e.g. Lysine, Arginine: contains guanido group, Histi-
ment of ATP dine
C. Acidic Amino acids: at physiological pH will carry
5. Isomerases: It catalyzes isomerization reactions, includ- negative charge.
ing racemizations and cis tran isomerizations. e.g. Aspartic acid (aspartate) and Glutamic acid (gluta-
Racemases Interconvert L and D stereoisomers mate). Aspargine and Glutamine: They are amide forms of
aspartate and glutamate in which side chain COOH groups
Transfer of group between atoms
Mutases are amidated. They are classified as neutral amino acids.
within a molecule
3.160  Chapter 4

II. Classification according to polarity of side chain (R): 3. amide group: as in glutamine and aspargine
A. Polar amino acids: in which R contains polar hydro- 4. NH2 group or nitrogen act as a base (basic amino
philic group so can forms hydrogen bond with H acids) : as lysine, arginine and histidine
O. In those amino acids, R may contain: 5. COOH group (acidic amino acids): as aspartic and
1. OH group : as in serine, threonine and tyrosine glutamic acid
2. SH group : as in cysteine

B. Non polar amino acids: T= tryptophan Th= threonine P= phenyl alanine (*= ar-
R is alkyl hydrophobic group which can’t enter in hydro- ginine and histidine are semiessential)]
gen bond formation. 9 amino acids are non-polar (glycine, 3. Non essential amino acids: These are the rest of
alanine, valine,leucine, isoleucine, phenyl alanine, trypto- amino acids that are formed in the body in amount enough
phan, proline and methionine) for adults and children. They are the remaining 10 amino
acids.
III. Nutritional classification: IV. Metabolic classification: according to metabolic or
1. Essential amino acids: These amino acids can’t be degradation products of amino acids they may be:
formed in the body and so, it is essential to be taken in diet. 1. Ketogenic amino acids: which give ketone bodies .
Their deficiency affects growth, health and protein synthesis. Lysine and Leucine are the only pure ketogenic amino acids.
2. Semiessential amino acids: These are formed in the 2. Mixed ketogenic and glucogenic amino acids:
body but not in sufficient amount for body requirements es- which give both ketonbodies and glucose.These are: iso-
pecially in children. leucine, phenyl alanine, tyrosine and tryptophan.
Summary of essential and semi-essential amino acids: 3. Glucogenic amino acids: Which give glucose. They in-
[V= valine i= isoleucine l= lysine l= leucine A = argi- clude the rest of amino acids. These amino acids by catabolism
nine* H= histidine* M= methionine yields products that enter in glycogen and glucose formation.
 Biochemistry  3.161

Classification of Lipids II. Sphingophospholipids: Sphingosine is the alcohol

1. Simple Lipids: Esters of fatty acids with alcohols. in this group of phospholipids
These are mainly of two types e.g., sphingomyelin
a. Fats & Oils (Triacyglycerols): These are esters of (b) Glycolipids: These lipids contain a fatty acid, car-
fatty acids with glycerol. The difference between at and oil bohydrate and nitrogenous base. The alcohol is sphingosine,
is only physical. Thus, oil is a liquid while fat is a solid at hence they are also called as glycosphingolipids. Glycerol
room temperature and phosphate are absent e.g., cerebrosides, ganglioside
b. Waxes: Esters of fatty acids (usually long chain) (c) Lipoproteins: Macromolecular complexes of lipids
with alcohols other than glycerol. These alcohols may be with proteins.
liphatic or alicyclic. Cetyl alcohol is most commonly found (d) Other complex lipids: Sulfolipids, aminolipids and
in waxes. lipopolysaccharides are among the other complex lipids.
2. Complex (or compound) lipids: These are esters of 3. Derived lipids: These include glycerol and other
fatty acids with alcohols containing additional groups such alcohols, fatty acids, mono and diacylglycerols, lipid (fat)
as phosphate, nitrogenous base, carbohydrate, protein etc soluble vitamins, steroid hormones, hydrocarbons and ke-
They are further divided as follows; tone bodies.
(a) Phospholipids: They contain phosphoric acid and 4. Miscellaneous lipids: These include a large number
frequently a nitrogenous base This is in addition to alcohol of compounds possessing the characteristics of lipids e.g.,
and Fatty acids. carotenoids, squalene, hydrocarbons such as pentacosane
I. Glycerophospholipids: These phospholipids con- (in bees wax), terpenes etc
tain glycerol as the alcohol e.g. lecithin, cephalin
3.162  Chapter 4

Important Biochemistry Pathway (Cycle)

1. Citric acid cycle (Krebs cycle, TCA cycle)

 Biochemistry  3.163

Summary of TCA cycle: one FADH2, and one nucleoside triphosphate (either
• The citric acid cycle (Krebs cycle, TCA cycle) is a near- ATP or GTP).
ly universal central catabolic pathway in which com- • Besides acetyl-CoA, any compound that gives rise to a
pounds derived from the breakdown of carbohydrates, four- or five-carbon intermediate of the citric acid cycle
fats, and proteins are oxidized to CO2, with most of - for example, the breakdown products of many amino
the energy of oxidation temporarily held in the electron acids—can be oxidized
carriers FADH2 and NADH. During aerobic metabolism, by the cycle.
these electrons are transferred to O2 and the energy of The citric acid cycle is amphibolic, serving in both
electron flow is trapped as ATP. catabolism and anabolism; cycle intermediates
• Acetyl-CoA enters the citric acid cycle (in the mito- can be drawn off and used as the starting material for
chondria of eukaryotes, the cytosol of prokaryotes) as a variety of biosynthetic products.
citrate synthase catalyzes its condensation with oxaloac- When intermediates are shunted from the citric acid
etate to form citrate. cycle to other pathways, they are replenished by several
• In seven sequential reactions, including two decarboxyl- anaplerotic reactions, which produce four-carbon interme-
ations, the citric acid cycle converts citrate to oxaloac- diates by carboxylation of three-carbon compounds; these
etate and releases two CO2.The pathway is cyclic in that reactions are catalyzed by pyruvate carboxylase, PEP car-
the intermediates of the cycle are not used up; for each boxykinase, PEP carboxylase, and malic enzyme. Enzymes
oxaloacetate consumed in the path, one is produced. that catalyze carboxylations commonly employ biotin to ac-
• For each acetyl-CoA oxidized by the citric acid cycle, tivate CO2 and to carry it to acceptors such as pyruvate or
the energy gain consists of three molecules of NADH, phosphoenol pyruvate.
TCA cycle regulatory enzymes
Enzyme Stimulators Inhibitors Comments
Pyruvate Acetyl-CoA ADP Several hormones alter the amount of this
carboxylase enzyme: Insulin ↓, Cortisol ,Glucagon
Pyruvate CoA, NAD, Ca2+ ,Mg2+ , Acetyl-CoA, NADH, Effect of Mg2+: ATP binds Mg2+ with higher
dehydrogenase pyruvate, insulin phosphorylation and affinity than ADP; high free Mg2+ means low
ATP ATP Concentration. Mg and Ca activate the
phosphatase.
Citrate synthase NAD, CoA, ADP Citrate, Long chain --
High [oxaloacetate] acyl-CoA, ATP, NADH,
and [acetyl-CoA], succinyl-CoA
Isocitrate Ca2+, ADP ATP, NADH Isocitrate dehydrogenase is probably the
dehydrogenase most important regulatory enzyme in the
TCA
cycle.
α-Ketoglutarate Ca2+ NADH, succinyl-CoA --
dehydrogenase

2. HMP SHUNT synthesis of pentose (5-carbon) sugars. There are two dis-
tinct phases in the pathway. The first is the oxidative phase,
Also known as: in which NADPH is generated, and the second is the non-
• Pentose shunt oxidative synthesis of 5-carbon sugars. This pathway is an
• Hexose monophosphate shunt alternative to glycolysis. While it does involve oxidation of
• Phosphogluconate pathway glucose, its primary role is anabolic rather than catabolic.
• It occurs in the cytosol. For most organisms it takes place in the cytosol; in plants
The pentose phosphate pathway (also called Phosphoglu- most steps take place in plastids.
conate Pathway, or Hexose Monophosphate Shunt [HMP
shunt]) is a process that serves to generate NADPH and the
3.164  Chapter 4

Functions in the cell is to prevent oxidative stress. It reduces the co-

The primary functions of the pathway are: enzyme glutathione, which converts reactive H2O2 into
1. To generate reducing equivalents, in the form of H2O. If absent, the H2O2 would be converted to hydroxyl
NADPH, for reductive biosynthesis reactions within cells. free radicals, which can attack the cell. Significantly, eryth-
2. To provide the cell with ribose-5-phosphate (R5P) rocytes utilize the reactions of the PPP to generate large
for the synthesis of the nucleotides and nucleic acids. amounts of NADPH used in the reduction of glutathione It
3. Although not a significant function of the PPP, it can is also used to generate hydrogen peroxide for phagocytes
operate to metabolize dietary pentose sugars derived from
the digestion of nucleic acids as well as to rearrange the
carbon skeletons of dietary carbohydrates into glycolytic/
Phases of HMP shunt
gluconeogenic intermediates. Oxidative phase
Located exclusively in the cytoplasm, the pathway In this phase, two molecules of NADP+ are reduced to
is one of the three main ways the body creates molecules NADPH, utilizing the energy from the conversion of glu-
with reducing power, accounting for approximately 60% of cose-6-phosphate into ribulose 5-phosphate.
NADPH production in humans. One of the uses of NADPH
 Biochemistry  3.165

CH2OPO32- CH2OPO32
- COO-
H 2O NADP O CH2OH O H
NADP H+ NADP+H C
O NADP+H O H C OH C
H H H
H H H OH
HO C H H C OH + CO2 C
O
CH H H phosphopentose
CH lactonase 6 phosphogluconate H C OH
Glucose-6-phosphate H C OH H C OH isomerase
CH dehydrogenase dehydrogenase
OH OH OH H C OH
H C CH2OPO32-
H OH H OH CH2OPO32-
CH2OPO32-

Regulation 100:1 in liver cytosol. This makes the cytosol a highly-re-

Glucose-6-phosphate dehydrogenase is the rate-controlling ducing environment. Formation of NADP+ by a NADPH-
enzyme of this pathway. It is allosterically stimulated by utilizing pathway, thus, stimulates production of more
NADP+. The ratio of NADPH:NADP+ is normally about NADPH.

3. Glycolysis Pathway (Embden-Meyerhof Pathway)

HO
O Starch degradation,
OH ----
Sucrose degradation
OH OH
OH
Glucose ATP
Hexokinase
O ADP+Pi
O P O
O
O OPP, Starch degradation,
OH ----
Phase -1 Preparatory Phase

Sucrose degradation
OH OH
OH
Glucose-6-phosphate
Glucose phosphate isomerase
O
O P O OH
O
O HO ---- OPP,Sucrose degradation
OH
OH
Fructose-6-phosphate
PPi or ATP
Pyrophosphate or ATP dependent
phosphofructokinase
Pi or ADP+Pi
O O
O P O O P O
O
O O
HO
OH
OH
Fructose-1,6-bisphosphate

Fructose bisphosphate aldolase

O OH TPI O
O
OPP ---- O P O O HO O P O
O O
Glyeraldehyde-3-phosphate Dihydroxyacetone phosphate
NAD++Pi
Glyceraldehyde phasphate
dehydrogenase
O OH NADH
O P O O NADP+
O
Phase -1 Pay Off Phase

O Glyceraldehyde 3- phosphate dehydrogenase

O P O NADPH
O
1,3-Bisphoglycerate
NAD++Pi
NADH NAD+
Bisphosphoglycerate
O O O
ATP HO HO
O OH OH OH
O P O O O MDH O OH
O OH Oxaloacetate Malate
3-Phosphoglycerate
HCO3
- - --

Phosphoglyerate mutase PEPC

H2O H2O
TCA cycle
O O ADP+Pi ATP
O P O O P O --
O O O --
HO O O O
Enalase PK
OH OH OH
2-Phosphoglycerate Phosphoenolpyruvate Pyruvate
3.166  Chapter 4

Glycolysis • Stage 3 is the harvesting stage. 4 mols of ATP and 2

• T
 he Glycolytic pathway describes the oxidation of glu- mols of NADH are gained from each initial mol of glu-
cose to pyruvate with the generation of ATP and NADH. cose. This ATP is a result of substrate-level phosphory-
• It is also called as the Embden-Meyerhof Pathway lation
• Glycolysis is a universal pathway; present in all organ- • Glyceraldehyde-3-phosphate is oxidized to pyruvate.
isms: from yeast to mammals. Keeping in mind that each molecule of glucose yields 2
• In eukaryotes, glycolysis takes place in the cytosol molecules of glyceraldehyde 3-phosphate, the total inputs
• Glycolysis is anaerobic; it does not require oxygen and the outputs of all the 10 glycolytic reactions may be
• In the presence of O2 pyruvate is further oxidized to CO2 written as follows
• In the absence of O2, pyruvate can be fermented to lac- Net Reaction: Glucose + 2NAD+ + 2 Pi + 2 ADP = 2 pyru-
tate or ethanol. vate + 2ATP + 2NADH + 2H2O
Thus, three things happen simultaneously in glycolysis:
(a) Glucose is oxidized to pyruvate.
The 3 stages of Glycolysis
(b) NAD+ is reduced to NADH.
•  tage 1 is the investment stage. 2 mols of ATP are con-
S (c) ADP is phosphorylated to form ATP.
sumed for each mol of glucose. There can be no EMP pathway without all 3 events which
• Glucose is converted to fructose-1,6-bisphosphate. means that NAD, ADP and Pi, as well as glucose, must be
• Glucose is trapped inside the cell and at the same time present. Further, 2 moles of ATP are generated in glycoly-
converted to an unstable form that can be readily cleaved sis. A summary of the steps in which ATP is consumed or
into 3-carbon units. formed is given in Table.
• In stage 2 fructose-1,6-bisphosphate is cleaved into
2,3carbon units of glycerladehyde-3-phosphate.

Step Reaction Consumption Gain of ATP

of ATP
1 Glucose Glucose 6-phosphate 1
3 Fructose 6-phosphate Fructose 1, 6-diphosphate 1
7 1, 3-diphosphoglycerate 3-phosphoglycerate 1 2 2
10 Phosphoenolpyruvate Pyruvate 1 2 2
2 4
Net gain of ATP 4 2 2

4. Cholesterol Biosynthesis Pathway 5. KETOGENESIS

Cholesterol is biosynthesized from 2-carbon metabolic in-
Ketogenesis is the biochemical process by which organ-
termediate, acetyl-CoA hooked end to end involving a num-
isms produce a group of substances collectively known
ber of enzymatic reactions and finally get converted into the
as ketone bodies by the breakdown of fatty acids and
27-carbon molecule of cholesterol.
ketogenic amino acids.
The process of cholesterol synthesis has five major steps:
Ketone bodies are three chemicals that are produced when
1. Acetyl-CoAs are converted to 3-hydroxy-3-methyl-
fatty acids are broken down in excess. Production of these
glutaryl-CoA (HMG-CoA) Cholesterol.
compounds is called “ketogenesis”, and this is necessary
2. HMG-CoA is converted to mevalonate.
in small amounts. Ketone bodies are produced from ace-
3. Mevalonate is converted to the isoprene based mol-
tyl-CoA, mainly in the mitochondrial matrix of liver cells
ecule, isopentenyl pyrophosphate (IPP), with the
when carbohydrates are so scarce that energy must be ob-
concomitant loss of CO2
tained from breaking down of fatty acids.
4. IPP is converted to squalene.
The three ketone bodies, each synthesized from acetyl-
5. Squalene is converted to cholesterol.
CoA molecules, are:
 Biochemistry  3.167

Acetoacetyl-CoA
thiolase
Acetyl-CoA Acetoacetyl-CoA
Cytosol

HMG-CoA
synthase OH O
O
HMG-CoA
HMG-CoA OH SCoA
ER

reductase
O OH
Mevalonate
Mevalonate OH OH
kinase
Peroxisome

Mevalonate-5-P

Mevalonate-5-PP

Isopentenyl
adenosine
Dimethylallyl-PP Isopentenyl-PP tRNAs

Farnesyl diphosphate OPPi

synthase
Prenylated proteins
Farnesyl-PP (15 C) Heme A
Dolichol
Squalene Ubiquinone
synthase
Squalene
(30 C)
Squalene
epoxidase
Squalene epoxide
Oxidosqualene
cyclase
ER

Lanosterol HO
(30 C)
Peroxisome

7-Dehydrocholestrol Desmosterol

7-DHC Desmosterol
reductase reductase
Cholesterol (27 C)

HO
3.168  Chapter 4

O O
CoA CoA 2 Acetyl-CoA
H3C S H 3C S

Thiolase
CoA-SH

O O
CoA Acetoacetyl-CoA
H 3C S

Acetyl-CoA
HMG-CoA synthase
CoA-SH

OH CH3 O -hydroxy- β-methylglutaryl-CoA

CoA (HMG-CoA)
O OH S

HMG-CoA lyase
Acetyl-CoA

Ο Ο
Acetoacetate
H3C Ο
NADH + H+
D- β-hydroxybutyrate
Non-enzymatic NAD+ dehydrogenase
decarboxylation

CO2
Ο ΟΗ Ο
H 3C CH3 Ο
Acetone D- β-hydroxybutyrate

• Acetoacetate, which can be converted by the liver Regulation:

into β-hydroxybutyrate, or spontaneously turn into Ketogenesis may or may not occur, depending on levels of
acetone available carbohydrates in the cell or body. This is closely
• Acetone, which is generated through the decar- related to the paths of acetyl-CoA
boxylation of acetoacetate, either spontaneously or • When the body has ample carbohydrates available
through the enzyme acetoacetate decarboxylase. It as energy source, glucose is completely oxidized to
can then be further metabolized either by CYP2E1 CO2; acetyl-CoA is formed as an intermediate in
into hydroxyacetone (acetol) and then via propylene this process, first entering the citric acid cycle fol-
glycol to pyruvate, lactate and acetate (usable for lowed by complete conversion of its chemical en-
energy) and propionaldehyde, or via methylglyoxal ergy to ATP in oxidative phosphorylation.
to pyruvate and lactate. • When the body has excess carbohydrates available,
• β-hydroxybutyrate (not technically a ketone accord- some glucose is fully metabolized, and some of it
ing to IUPAC nomenclature) is generated through is stored in the form of glycogen or, upon citrate
the action of the enzyme D-β-hydroxybutyrate de- excess, as fatty acids. (CoA is also recycled here.)
hydrogenase on acetoacetate. • When the body has no free carbohydrates avail-
 Biochemistry  3.169

able, fat must be broken down into acetyl-CoA in that produces urea ((NH2)2CO) from ammonia (NH3).
order to get energy. Acetyl-CoA is not being recy- This cycle was the first metabolic cycle discovered (Hans
cled through the citric acid cycle because the citric Krebs and Kurt Henseleit, 1932), five years before the
acid cycle intermediates (mainly oxaloacetate) have discovery of the TCA cycle. The urea cycle consists of
been depleted to feed the gluconeogenesis pathway, five reactions: two mitochondrial and three cytosolic. The
and the resulting accumulation of acetyl-CoA acti- cycle converts two amino groups, one from NH4+ and
vates ketogenesis. one from ASP, and a carbon atom from HCO3−, to the
relatively nontoxic excretion product urea at the cost of
four "high-energy" phosphate bonds (3 ATP hydrolyzed
6. Urea Cycle to 2 ADP and one AMP). Ornithine is the carrier of these
The urea cycle (also known as the ornithine cycle) is a carbon and nitrogen atoms.
cycle of biochemical reactions occurring in many animals

Reactions of the urea cycle

Step Reactants Products Catalyzed by Location

1 NH3 + HCO3− + 2ATP carbamoyl phosphate CPS1 mitochondria

+ 2ADP + Pi
2 carbamoyl phosphate + ornithine citrulline + Pi OTC mitochondria

3 citrulline + aspartate + ATP argininosuccinate + ASS cytosol

AMP + PPi
4 argininosuccinate Arg + fumarate ASL cytosol

5 Arg + H2O ornithine + urea ARG1 cytosol

In the first reaction, NH4+ + HCO3− is equivalent to NH3 The two NADH produced can provide energy for the
+ CO2 + H2O. formation of 4 ATP (cytosolic NADH provides only 1.5
Thus, the overall equation of the urea cycle is: ATP due to the glycerol-3-phosphate shuttle who transfers
NH3 + CO2 + aspartate + 3 ATP + 2 H2O → urea + fu- the electrons from cytosolic NADH to FADH2 and that
marate + 2 ADP + 2 Pi + AMP + PPi gives 1.5 ATP), a net production of one high-energy phos-
Since fumarate is obtained by removing NH3 from as- phate bond for the urea cycle. However, if gluconeogenesis
partate (by means of reactions 3 and 4), and PPi + H2O → is underway in the cytosol, the latter reducing equivalent
2 Pi, the equation can be simplified as follows: is used to drive the reversal of the GAPDH step instead of
2 NH3 + CO2 + 3 ATP + H2O → urea + 2 ADP + 4 Pi generating ATP.
+ AMP The fate of oxaloacetate is either to produce aspartate
Note that reactions related to the urea cycle also cause via transamination or to be converted to phosphoenolpyru-
the production of 2 NADH, so the urea cycle releases slight- vate, which is a substrate for gluconeogenesis.
ly more energy than it consumes. These NADH are pro-
duced in two ways: Regulation:
One NADH molecule is reduced by the enzyme gluta- N-Acetylglutamic acid (NAG): The synthesis of carbamoyl
mate dehydrogenase in the conversion of glutamate to am- phosphate and the urea cycle are dependent on the presence
monium and α-ketoglutarate. Glutamate is the non-toxic of NAcGlu, which allosterically activates CPS1. NAcGlu
carrier of amine groups. This provides the ammonium ion is an obligate activator of Carbamoyl phosphate synthase.
used in the initial synthesis of carbamoyl phosphate. Synthesis of NAcGlu by NAGS is stimulated by both Arg,
The fumarate released in the cytosol is converted to ma- allosteric stimulator of NAGS, and Glu, a product in the
late by cytosolic fumarase. This malate is then converted to transamination reactions and one of NAGS's substrates,
oxaloacetate by cytosolic malate dehydrogenase, generating a both of which elevated when free amino acids are elevated.
reduced NADH in the cytosol. Oxaloacetate is one of the keto So Glu not only is a substrate for NAGS but also serves as
acids preferred by transaminases, and so will be recycled to an activator for the urea cycle.
aspartate, maintaining the flow of nitrogen into the urea cycle.
3.170  Chapter 4

Substrate concentrations: The anomalous substrate buildup is not without cost,

The remaining enzymes of the cycle are controlled by the however. The substrate concentrations become elevated all
concentrations of their substrates. Thus, inherited deficien- the way back up the cycle to NH4+, resulting in hyperam-
cies in cycle enzymes other than ARG1 do not result in sig- monemia (elevated [NH4+]P).
nificant decreases in urea production (if any cycle enzyme Although the root cause of NH4+ toxicity is not com-
is entirely missing, death occurs shortly after birth). Rather, pletely understood, a high [NH4+] puts an enormous strain
the deficient enzyme's substrate builds up, increasing the on the NH4+-clearing system, especially in the brain (symp-
rate of the deficient reaction to normal. toms of urea cycle enzyme deficiencies include intellectual
 Biochemistry  3.171

disability and lethargy). This clearing system involves HO NH3+

GLUD1 and GLUL, which decrease the 2-oxoglutarate
(2OG) and Glu pools. The brain is most sensitive to the CH O
CH2 C
depletion of these pools. Depletion of 2OG decreases the
rate of TCAC, whereas Glu is both a neurotransmitter and a O
precursor to GABA, another neurotransmitter. L-Tyosine

H4 biopterin
TYROSINE
7. Biosynthesis of Catecholamines HYDROXYLASE
Catecholamines are derived from the amino acid tyrosine. H2 biopterin
catecholamines are epinephrine (adrenaline), norepineph- OH
rine (noradrenaline), and dopamine, all of which are pro- HO NH3+
duced from phenylalanine and tyrosine. Release of the
hormones epinephrine and norepinephrine from the adrenal CH O
CH2 C
medulla of the adrenal glands is part of the fight-or-flight
response. O
Dopa
Tyrosine is created from phenylalanine by hydroxyl-
ation by the enzyme phenylalanine hydroxylase. Tyrosine is
PLP
also ingested directly from dietary protein. Catecholamine- DOPA
secreting cells use several reactions to convert tyrosine DECARBOXYLASE
serially to L-DOPA and then to dopamine. Depending on CO2
the cell type, dopamine may be further converted to norepi- OH
nephrine or even further converted to epinephrine. HO
Catecholamines are produced mainly by the chromaffin
cells of the adrenal medulla and the postganglionic fibers of CH2
the sympathetic nervous system. Dopamine, which acts as CH2 NH3+
a neurotransmitter in the central nervous system, is largely Dopamine
produced in neuronal cell bodies in two areas of the brain-
O2
stem: the substantia nigra and the ventral tegmental area. DOPAMINE
The similarly melanin-pigmented cell bodies of the locus β-OXIDASE Cu2+
ceruleus produce norepinephrine. Vitamin C
Steps for Biosynthesis of different catecholamine: OH
1) Tyrosine is hydroxylated to Dihdroxy Phenyl HO
Alanine(DOPA) by Tyrosine Hydroxylase en-
zyme, that require BH4(Tetra hydrobiopterine) and CH2
CH2 NH3+
NADPH. The reaction is similer to hydroxylation to
Phenylalanine to form Tyrosine. Tyrosine hydroxy- OH
lase (Tyrosinase) meant for catecholamine synthesis Norepinephrine
is different for the one require for melanin synthesis.
2) DOPA Decarboxylase, a pyridoxal phosphate (BP-6-) PHENYLETHANOL- S-Adenosylmethionine
dependent enzyme, forms Dopamine from decar- AMINE N-METHYL-
boxylation of DOPA. TRANSFERASE
3) Subsequent hydroxylation of Dopamine by Dopa- S-Adenosylhomocysteine
mine- β-oxidase then forms norepinephrine. The OH
enzyme requires molecular oxygen, vitamin C and HO
copper ion for its activity.
4) In Adrenal medulla, Phenyl ethanolamine-N- meth- CH2 CH3
CH2 N
yltransferase utilizes S-adinosyl methionine(SAM)
H2+
to methylate the primary amine of Norepinephrine, OH
forming Epinephrine. Epinephrine
3.172  Chapter 4

Multiple Choice Questions

1. α-D-glucose and β-D-glucose both are (a) Proline (b) Tyrosine
(a) Keto-aldo pairs (b) Anomers (c) Tryptophan (d) Phenylalanine
(c) Epimers (d) Stereoisomers 12. The cyclic hemiacetal formation in D-Glucose involves
2. Compounds that have the same structural formula bond formation between
but different spatial configuration are called (a) C-1 and C-4 (b) C-1 and C-5
(a) Epimers (b) Anomers (c) C-2 and C-5 (d) C-1 and C-2
(c) Stereoisomers (d) Optical isomers 13. Cori cycle is
3. One of the following is a reducing sugar: (a) Reuse of glucose (b) Synthesis of glucose
(a) Isomaltose (b) Sucrose (c) Uptake of glucose (d) Both (a) and (b)
(c) Trehalose (d) None of the above 14. Invert sugar is
4. An L-isomer of monosaccharide formed in human (a) Galactose
body during uronic acid pathway is (b) Mannose
(a) L-Xylulose (b) L-Erythrose (c) Fructose
(c) L-Ribulose (d) L-Fructose (d) Hydrolytic product of sucrose
5. Which of the following is an epimeric pair? 15. Generally all proteins contain
(a) Glucose and fructose (a) More than 50 amino acids
(b) Lactose and maltose (b) Different amino acids less than 50
(c) Galactose and mannose (c) Only a few amino acids
(d) Glucose and mannose (d) 300 amino acids occurring in nature
6. One of the following is an enzyme required for glycolysis
16. An example of sulphur-containing amino acid is
pathway:
(a) 3-Amino butanoic acid
(a) Pyruvate carboxylase
(b) 2-Amino-3-methylbutanoic acid
(b) Pyruvate kinase
(c) 2-Amino-3-thiobutanoic acid
(c) Fructose-6-phosphatase
(d) 2-Amino-3-mercaptopropanoic acid
(d) Phosphokinase
7. Glucose tolerance is decreased in one of the following 17. At isoelectric pH, a mixture of amino acids in solution
disease: would be predominantly:
(a) Diabetes insipidus (b) Addison’s disease (a) Zwitter ions (b) Nonpolar molecules
(c) Hypo pituitarisme (d) Diabetes mellitus (c) Hydrophilic (d) Positive and monovalent
8. In carbohydrate metabolism all of the following 18. Dispensible amino acids
hormones is involved except: (a) Can not be synthesized by the body
(a) Glucagon (b) ACTH (b) May be synthesized in the body to meet biological
(c) Vasopressin (d) Insulin needs.
9. For converting glucose to glycogen in liver an essential (c) Have no role in the metabolism
component is (d) May be synthesized in the body in diseased states
(a) UTP (b) GTP 19. The technique for purification of proteins that can be
(c) GLU-1 (d) Lactic acid made specific for a given protein is
10. Phenylalanine is the precursor of (a) Gel filtration chromatography
(a) Histamine (b) Dopamine (b) Thin layer chromatography
(c) Tyrosine (d) Thyroxin (c) Affinity chromatography
(d) Electrophoresis
11. One of the following amino acids contains special
group pyrrolidine: 20. Amino acid tryptophan could be considered as pre-
cursor of
 Biochemistry  3.173

(a) Meltonin (b) Thyroid hormones (c) Thyroid gland

(c) Methionine (d) Phenylephrine (d) Adrenal medulla
21. The enzyme dopamine β-hydroxylase which catalyses 32. The basic amino acid is
conversion of dopamine to norepinephrine requires (a) Lysine (b) Proline
(a) Vitamin C (b) Vitamin A (c) Leucine (d) Tyrosine
(c) Vitamin K (d) Vitamin B1 33. For adrenaline synthesis the precursor amino acid is
22. Pulses are deficient in _______________ amino acid. (a) Alanine (b) Proline
(a) Lysine (b) Tyrosine (c) Phenylalanine (d) Cystine
(c) Methionine (d) Crystine 34. Amino acids are soluble in
23. _________, a water-soluble vitamin is absent in eggs. (a) Ammonia (b) Water
(a) Biotin (b) Niacin (c) Chloroform (d) Benzene
(c) Ribofalvin (d) Ascrobic acid
35. Optically active compounds are capable of
24. Primary structure of a protein is formed by (a) Rotating plane of polarized light
(a) Disulphide bonds (b) Hydrogen bonds (b) Emitted the light radiation
(c) Peptide bonds (d) Amine bonds (c) Showing same chemical properties
25. Semi-essential amino acid is (d) Different chemical reaction
(a) Valine (b) Histidine 36. SGOT level in an adult is
(c) Asparagine (d) Serine (a) 15–45 units/dl (b) 10–50 units/dl
26. Alanine can be synthesized from (c) 5–15 units/dl (d) 5–40 units/dl
(a) Pyruvate and glutamate 37. Zymogen is
(b) Glycine and α-ketoglutarate (a) An inactivated enzyme
(c) Pyruvate and α ketoglutarate (b) An activated enzyme
(d) Asparate and pyruvate (c) An intracellular enzyme
27. Glycine can be synthesized from (d) An extracellular enzyme
(a) Serine (b) Threonine 38. Xanthoproteic test is positive for
(c) Betaine (d) All of these (a) Sulphur amino acids
(b) Indole ring containing amino acids
28. Non-protein amino acids are
(c) Aromatic amino acids
(a) Ornithine
(d) α-amino acids
(b) β-alanine
(c) γ-amino butyric acid 39. Michaelis–Menton equation is used to explain the effect
of substrate concentration on
(d) All of these
(a) Carbohydrate (b) Protein
29. Allergic reactions are mediated by (c) Lipid (d) Enzyme
(a) IgE (b) IgG
40. Low plasma level of tryptophan and other neutral amino
(c) IgA (d) IgD
acid leads to the disorder is known as
30. A Zwitter ion is a (a) Maple syrup disease
(a) Molecule containing negative ion (b) Wilson’s disease
(b) Molecule containing positive ion (c) Hartnup’s disease
(c) Molecule containing positive and negative ionic (d) Wolman’s disease
group 41. A dietary deficiency in the quantity of protein results in
(d) None of these
(a) Alkaptonuria
31. Synthesis of calcitonin takes place in (b) Marasmus
(a) Parathyroid glands (c) Richner–Hanhart syndrome
(b) Anterior pituitary glands (d) Kwashiorkar
3.174  Chapter 4

42. The normal range of total serum bilirubin is 51. Due to the riboflavin deficiency _________ is caused.
(a) 0.2–1.2 mg/100 ml (a) Pellagra (b) Mental deterioration
(b) 1.5–1.8 mg/100 ml (c) Cheilosis (d) Dermatitis
(c) 2.0–4.0 mg/100 ml 52. Vitamin B6 deficiency may occur during tuberculosis
(d) Above 7.0 mg/100 ml therapy with
43. A test to evaluate the detoxifying function of liver is (a) Isoniazid (b) Rifampicin
(a) Serum albumin: globulin ratio (c) Sulpha drugs (d) Thamibutole
(b) Galactose tolerance test 53. Xanthurenic Acid Index’ is a reliable criterion for the
(c) Hippuric acid test deficiency of vitamin
(d) Prothrombin time (a) Pantothenic acid (b) Thiamin
44. Fat-soluble vitamins have properties like (c) Pyridoxal (d) Riboflavin
(a) Stored in liver 54. For determination of amino acid sequence of a protein
(b) One or more propene units ____________ is used.
(c) Soluble in alcohol (a) Ninhydrin reagent (b) Biuret reagent
(d) All these (c) Milons reagen (d) Sanger reagent
45. Precursor of vitamin A, β-carotene is oxidatively 55. The deficiency of folate causes
cleaved by (a) Pernicious anaemia
(a) Hydroxylase (b) Megaloblastic anaemia
(b) Oxygenase (c) Macrocytic anaemia
(c) β-Carotene dioxygenase (d) Hemolytic anaemia
(d) Reductase 56. Folic acid contains
46. Carr–Price reaction is used to detect (a) Pteridine (b) p-Amino benzoic acid
(a) Vitamin E (b) Vitamin B12 (c) Glutamic acid (d) All of these
(c) Aspartic acid (d) Vitamin A 57. Vitamin A is synthesized from
47. Deficiency of vitamin D causes (a) γ-Carotene (b) β-Carotene
(a) Tuberculosis of bone (c) α-Carotene (d) All of these
(b) Ricket and osteomalacia 58. The molecule of vitamin A1 contains
(c) Pellagra (a) β-Carotene ring (b) β-Lonone ring
(d) Beri-beri (c) Naphthalene ring (d) α-Lactone ring
48. Vitamin D absorption is increased in 59. A chemical name of vitamin K3 is
(a) Contents of diet (a) Phylloquinone (b) Menadione
(b) Alkaline pH of intestine (c) Menaquinone (d) Napthoquinone
(c) Neutral pH of stomach
60. The rhodopsin contain non-protein part is
(d) Acid pH of intestine
(a) Retinal (b) Retinol
49. One international unit (IU) of vitamin D is defined as (c) Carotene (d) Retinoic acid
the biological activity of
61. Vitamin K regulates the synthesis of blood clotting factors:
(a) 0.025 µg of ergosterol
(a) VII (b) IX
(b) 0.025 µg of 7-dehydrocholecalciferol
(c) X (d) All of these
(c) 0.025 µg of cholecalciferol
(d) 0.025 µg of ergocalciferol 62. Vitamin which has anti-oxidant properties is
(a) Vitamin A (b) Vitamin C
50. One of the following vitamins is synthesized by bacteria
in the intestine (c) Vitamin D (d) Vitamin E
(a) Vitamin A (b) Vitamin K 63. Severe deficiency of ________ causes xerophthalmia.
(c) Vitamin D (d) Vitamin E (a) Vitamin D (b) Vitamin B2
 Biochemistry  3.175

(c) Vitamin B6 (d) Vitamin A (a) Vmax value is increased

64. Antisterility vitamin is (b) Km value is increased
(a) Biotin (b) Riboflavin (c) Km value is decreased
(c) Vitamin E (d) Vitamin K (d) Concentration of active enzyme is decreased
65. Thymine is characterized as a 75. The specificity of the enzyme is mostly dependent on
(a) Water-soluble vitamin (a) Glucose
(b) Fat-soluble vitamin (b) Pyruvate
(c) Purine base (c) Xanthurenic acid
(d) Pyrimidine base (d) Thiamine pyro phosphate
66. All of following is antagonist for folic acid except 76. The specificity of the enzyme is mostly dependant on
(a) Aminopterin (b) Trimethoprim (a) Co-enzyme (b) Apoenzymes
(c) Sulfonamides (d) Isoniazid (c) Proenzymes (d) Isozymes
67. Calcitriol is 77. How many number of net ATP generated during oxida-
(a) 1,25-dihydroxy cholecalciferol tion of one molecule of palmitate?
(b) 1-hydroxy cholecalciferol (a) 14 (b) 21
(c) 25,26-dihydroxy cholecalciferol (c) 129 (d) 96
(d) 25-hydroxy cholecalciferol 78. Factors affecting enzyme activity is
68. Which of the following vitamin act as a respiratory (a) Temperature (b) pH
catalyst? (c) Concentration (d) All of these
(a) Riboflavin (b) Pyridoxine
79. Glucose absorption is promoted by
(c) Niacin (d) Vitamin E
(a) Vitamin A (b) Vitamin E
69. Vitamin B12 contains ___________ metal. (c) Ascorbic acid (d) Thiamin
(a) Copper (b) Iron
80. Zellweger syndrome occurs due to the:
(c) Cobalt (d) Lead
(a) Absence of peroxisomes
70. Nonsteroidal antiinflammatory drugs, such as aspirin (b) Deficiency of vitamin B12
act by inhibiting the activity of the enzyme:
(c) Deficiency of acyl CoA dehydrogenase
(a) Lipoxygenase (b) Cyclooxygenase (d) Overproduction of ketone
(c) Phospholipase A2 (d) Lipoprotein lipase
81. Ketosis is generally associated with the disease:
71. Holoenzyme is
(a) Nephritis (b) Diabetes Insipidus
(a) Functional unit of enzyme (c) Edema (d) Diabetes mellitus
(b) Made of apoenzyme
(c) Coenzyme 82. Conversion of HMG-CoA to the mevalonate by the
(d) All of these reduction is catalysed by
(a) HMG-CoA reductase
72. Enzymes, which are produced in inactive form in the
(b) HMG-CoA synthetase
living cells, are called
(c) Thiolase
(a) Co-enzyme (b) Apoenzymes
(d) Mevalonate kinase
(c) Proenzymes (d) Isozymes
83. One of the following amino acids is used as an
73. Vitamin B2 is the precursor for
antibiotic
(a) Co enzyme pyridoxal phosphate
(a) Thyroxine (b) Ornithine
(b) Co enzyme thiamine pyrophosphate
(c) Homoserine (d) Azaserine
(c) Co enzyme FMN
(d) Co enzyme NADP 84. Sulfur-containing B-complex vitamin is
74. In reversible non-competitive enzyme activity (a) Biotin (b) Niacin
inhibition (c) Pyridoxine (d) Riboflavin
3.176  Chapter 4

85. One of the following vitamins is known as pellagra (a) Copper acetate and glacial acetic acid
preventive factor of Goldberg: (b) Resorcinol in hydrochloric acid
(a) Biotin (b) Niacin (c) Copper sulphate in sulphuric acid
(c) Riboflavin (d) Pyridoxine (d) Phenylhydrazine in hydrochloric acid
86. Adenylate cyclase is activated by 95. Poisoning of morphine causes
(a) Insulin (a) Metabolic acidosis (b) Respiratory alkalosis
(b) Vitamin K (c) Metabolic alkalosis (d) Respiratory acidosis
(c) Prostaglandin E1 96. Which enzyme hydrolyses starch?
(d) Glucagon (a) Invertase (b) Amylase
87. Coenzyme A is derived from the vitamin: (c) Sucrase (d) Maltase
(a) Niacin (b) Pantothenic acid 97. One of the following amino acid is nonessential
(c) Pyridoxine (d) Biotin (a) Arginine (b) Valine
88. The Michaelis–Menten constant, Km is defined as (c) Glutamate (d) Lysine
(a) Substrate concentration to produce half maximal 98. The oxidation of glucose to pyruvate and lactate is
velocity in an enzyme catalysed reaction known as
(b) Dependent on the enzyme concentration (a) Glycolysis (b) Gluconeogenesis
(c) Substrate concentration to produce half minimal (c) Glycogenesis (d) Glycogenolysis
velocity in an enzyme catalysed reaction
(d) Numerically equal to ½Vmax 99. Citric acid cycle is also known as
(a) Uronic acid cycle
89. ‘Lock and key’ theory was proposed by
(b) Reductive pathway of carbohydrate
(a) Koshland (b) Emil Fischer (c) Krebs cycle
(c) Mehler (d) Sanger (d) Synthesis of glucose from non-carbohydrate
90. Allosteric inhibitor of hexokinase enzyme is precursor
(a) Glucose-6-phosphate 100. Embden–Meyerhof pathway is also known as
(b) Palmitate (a) Hexose monophosphate shunt
(c) AMP (b) Oxidative pathway of carbohydrate
(d) ATP (c) Krebs cycle
91. The non-protein, organic and low molecular weight (d) Glycolysis
substance, bound to an enzyme and essential for the 101. One of the following is oxidative pathway of glucose
activity of enzyme is known as
(a) Gluconeogenesis
(a) Holoenzyme (b) Coenzyme
(b) Hexose mono phosphate shunt
(c) Isoenzyme (d) Apoenzyme
(c) Glycogenolysis
92. When in enzyme inhibition Km value is unchanged and (d) Lipogenesis
Vmax is value is decreased then it known as
102. Generation of ATP during citric acid cycle is
(a) Allostreric inhibition
(a) 8 (b) 22
(b) Reversible non-competitive inhibition
(c) 24 (d) 30
(c) Reversible competitive inhibition
(d) Irreversible inhibition 103. Glycolysis reaction is regulate by catalyze the irrevers-
ible reaction by all of the following enzyme except
93. If two monosaccharides differ from each other in their
configuration around single specific carbon atom other (a) Hexokinase (b) Phosphofructokinase
than anomeric carbon they are known as (c) Pyruvate kinase (d) Phosphoglycerate kinase
(a) Epimers (b) Enediols 104. The inhibition of glycolysis by oxygen is known as
(c) Stereoisomers (d) Optical isomers (a) Crabtree effect
94. Chemically Barfoed’s reagent is (b) Pasteur effect
 Biochemistry  3.177

(c) Rapaport–Leubering effect (a) Anomers (b) Epimers

(d) Krebs effect (c) Mutarotaiton (d) Tautomerization
105. In citric acid cycle citrate is convertinged in to isocitrate by 115. Krebs Cycle is known as amphibolic because
(a) Aconitase (b) Isocitrate dehydrogenase (a) Catabolic in nature
(c) Citrate synthase (d) Succinate dehydrogenase (b) Anabolic in nature
106. In tricarboxylic acid cycle citrate synthase enzyme is (c) Both anabolic and catabolic in nature
inhibited by (d) Either anabolic or catabolic in nature
(a) ADP (b) AMP 116. Lyase means
(c) NAD +
(d) Succinyl Co-A (a) Enzymes specialized in the addition or removal of
water, ammonia, etc.
107. The enzymes of tricarboxylic acid cycle are located in
(b) Enzymes that brings about hydrolysis of various
(a) Cytosol
compound
(b) Mitochondrial matrix
(c) Enzymes that catalyse the transfer of functional
(c) Cytosomal fraction of the cell groups
(d) Liver (d) Enzymes involved in all the isomerization reaction
108. All of the following are precursors for gluconeogenesis 117. Multienzyme complexes means
except
(a) It is made up of a single polypeptide
(a) Lactate (b) Pyruvate (b) Some of the enzymes which possess more than one
(c) Acetyl Co-A (d) Glycerol polypeptide chain
109. Gluconeogenesis is regulated by (c) Possessing specific site to catalyse different reaction
(a) ACTH (b) Glucagon in a sequence
(c) Progesterone (d) Insulin (d) Enzymes made up of apoenzyme and coenzyme
110. Glycogen synthesis is increased in one of the following 118. Hexokinase is classified as a
conditions: (a) Oxidoreductases enzyme
(a) If insulin level is increased (b) Transferases enzyme
(b) If glucagon level is increased (c) Hydrolases enzyme
(c) If norepinephrine level is increased (d) Lyases enzyme
(d) If glucose level is increased 119. Most of the enzymes of the higher organism show
111. Van Gierke’s disease occurs because of optimum activity around
(a) Glucose level is decreased (a) pH 1–2 (b) pH 10–11
(b) Glucagon level is decreased (c) pH 6–8 (d) pH 4–6
(c) Glycogen accumulates in hepatocytes and renal cells 120. Thiamin pyrophosphate is derived from
(d) Lactic acid level is increased
(a) Thyroxine (b) Thiamine
112. In hexose mono phosphate shunt glucose 6-phosphate (c) Tryptophan (d) Niacin
is converted in to 6-phosphogluconolactone by
121. As per IUB enzyme activity is expressed in
(a) Glucose 6-Phosphate dehydrogenase
(a) Micromol (b) Katal
(b) Transketolase
(c) Miligram (d) Mcrogram
(c) Gluconolactone hydrolase
(d) Phosphogluconate dehydrogenase 122. Serum glutamate pyruvate transminase is used for
diagnose of
113. Uronic acid pathway is concerned with synthesis of
(a) Hepatitis
(a) Vitamin A (b) Vitamin D
(b) Acute pancreatics
(c) Vitamin C (d) Glucose
(c) Myocardial infarction
114. The process of shifting of hydrogen atom from one car- (d) Rickets
bon atom to another to produce enediols is known as
3.178  Chapter 4

123. For cancer of prostate gland one of the following (a) DNA contains Cytosine and RNA contains Ad-
enzymes is used enine
(a) Amylase (b) Alkaline phosphate (b) RNA contains Adenine and RNA contains Cytosine
(c) Acid phosphate (d) Aldolase (c) DNA contains Thymine and RNA contains Uracil
(d) RNA contains Guanine and RNA contains Ad-
124. Indole ring is present in _________amino acid
enine
(a) Tyrosine (b) Proline
(c) Tryptophan (d) Lysine 135. In DNA structure width of double helix is
(a) 5 nm (b) 8 nm
125. Gaucher’s disease occurs due to the deficiency of
(c) 1 nm (d) 2 nm
(a) Ceramidase (b) Hexosaminidase
(c) Sphingomyelinase (d) β Glucosidase 136. Structure of polydeoxyribonucleotide segment is held by
(a) Peptide bonds
126. One of the following hormones decreases the cholesterol
synthesis (b) Phospho bonds
(c) Phosphodiester bonds
(a) Insulin (b) Thyroxine
(d) Amide bond
(c) Glucagon (d) Growth hormone
137. In DNA structure aAdenine makes the hydrogen bond
127. The protein component of lipoprotein is known as
only with
(a) Chylomicron (b) Apoprotein
(a) Thiamine (b) Guanine
(c) Phophoprotein (d) None of the above
(c) Cytosine (d) Uracil
128. According to the Frederickson’s classification of hy-
138. In Z-DNA confirmation of DNA helix the number of
perliporoteinemias in Type IV
base pairs present in each turn is
(a) Increased IDL level
(a) 10 (b) 11
(b) Increased LDL level
(c) 12 (d) 13
(c) Increased VLDL level
(d) Increased HDL level 139. The sugar present in RNA is
(a) Ribose (b) Deoxyribose
129. In HDL ___________ of triacylglycerol is present.
(c) Fructose (d) Pentose
(a) 88% (b) 55%
(c) 12% 140. In RNAs cellular composition of ribosomal RNA is
(d) 98%
(a) 5–10% (b) 10–20%
130. The two products in the β-oxidation of odd chain fatty
(c) 50–80% (d) 20–50%
acids are
(a) Acetyl CoA and malonyl CoA 141. rRNA function is to
(b) Propionyl CoA and acyl CoA (a) Transfer genetic information from genes to
(c) Succinyl CoA and malonyl CoA ribosomes
(d) Propionyl CoA and acetyl CoA (b) Provide structural framework for ribosomes
(c) Trnasfer aminoacid to mRNA
131. Hypocholesterolemia is observed in the disorder (d) Involve in the selection of protein for export
(a) Diabetes mellitus (b) Thyrotoxicosis
142. Which of the following enzymes is NADPH dependent?
(c) Hyperthyrodism (d) Nephrotic syndrome
(a) Malic enzyme
132. One of the following amino acids contains hydroxyl (b) HMG CoA reductase
group: (c) Lactate dehyrogenase
(a) Threonine (b) Leucine (d) Tyramine dehyrogenase
(c) Valine (d) Glutamine
143. By the non-oxidative deamination process enzyme
133. Acidic amino acid is histidase act on histidine to convert in
(a) Lysine (b) Arginine (a) Threonine (b) Pyruvate
(c) Histidine (d) Glutamic acid (c) Urocanate (d) Homoserine
134. DNA and RNA differ in their structure: 144. Oxidative amination mostly takes place in
 Biochemistry  3.179

(a) Liver and kidney 156. Citrullinemia is due to defect in which of the following
(b) Liver and intestine enzyme?
(c) Kidney and urinary tract (a) Carbamoyl phosphatase synthase
(d) Brain (b) Arginase
145. In transamination process all transaminase require (c) Ornithin transcarbomylase
__________ co-enzyme. (d) Arginosuccinate synthase
(a) Lipoic acid (b) TPP 157. Which amino acid is the precursor of melanine?
(c) FMN (d) PLP (a) Alanine (b) Tyrosine
146. Urea cycle is known as (c) Aspartic acid (d) Lysin
(a) Embden–Meyerhof pathway 158. Hyperlipoproteinemia type III is due to elevated plasma
(b) Krebs–Henseleit cycle level of which of the lipoproteins?
(c) Krebs cycle (a) LDL (b) VLDL
(d) Kurt Henseleit cycle (c) IDL (d) Chylomicrone
147. Tocopherols prevents the oxidation of 159. Jamaican vomiting sickness disease is due to
(a) Vitamin D (b) Vitamin A (a) Hypoglycin C (b) Haemoglobin
(c) Vitamin C (d) Vitamin B12 (c) Hypoglycin A (d) Both (a) and (b)
148. For the synthesis of creatine all of the following amino 160. Krabbe’s disease occurs due to defect in
acids are required except (a) β-glucosidase
(a) Glycine (b) Arginine (b) β-galactocidase
(c) Cysteine (d) Methionine (c) Sphingomylein metabolism
149. Hypervitaminosis of vitamin A causes (d) Hexosaminidases A
(a) Xeropthalmia (b) Pernicious anemia 161. HMP shunt occurs in
(c) Keratomalacia (d) Dermatitis, loss of hair (a) Mitochondria (b) Cytosol
150. Storehouse of ammonia in biological system is (c) Both (a) and (b) (d) None of the above
(a) Glutamine (b) Glutamate 162. The reaction catalysed by hexokinase in glycolysis is
(c) Creatine (d) Urea dependent on
151. Lesch–Nyhan syndrome occurs due to deficiency of (a) ATP (b) Mg+
which enzyme? (c) Both (a) and (b) (d) ADP
(a) PRPP synthetase (b) Xanthine oxidase 163. In Krebs cycle oxalosuccinate is converted to
(c) HGPRT (d) Glucose-6-phosphatase α-ketoglutarate by which enzyme?
152. Orotic aciduria can be treated by a diet rich in (a) α-ketoglutarate dehydrogenase
(a) Adenine (b) Guanine (b) Isocitrate dehydrogenase
(c) Uridine (d) All of the above (c) Succinate dehydrogenase
(d) Aconitase
153. Menke’s disease is due deficiency of which of the fol-
lowing? 164. Fluroacetate is the inhibitor of which enzyme in Krebs
cycle?
(a) Iron (b) Copper
(a) α-ketoglutarate dehydrogenase
(c) Molybdenum (d) Sodium
(b) Isocitrate dehydrogenase
154. Which is the storage form of iron? (c) Succinate dehydrogenase
(a) Ferritin (b) Hemosiderin (d) Aconitase
(c) Both (a) and (b) (d) None of the above
165. Cori’s disease is due to defect in which of the following
155. Krebs–Henseleit cycle occurs in enzyme?
(a) Mitochondria (b) Cytosol (a) Glucose-6-phosphatase
(c) Both (a) and (b) (d) Kidney (b) Amylo-α-1,6-glucosidase
3.180  Chapter 4

(c) Phospho fructokinase 173. This carbohydrate acts as lubricant of synovial fluid and
(d) Liver glycogen phosphorylase contributes to tensile strength and elasticity of cartilages
166. What is the starting material of retinol? and tendons. It is also an important component of skin.
(a) Butyraldehyde and formic acid (a) Cellulose (b) Glycogen
(b) Beta-ionone and methylvinyllactone (c) Starch (d) Hyaluronic acid
(c) Ribulose 174. It is the most important polysaccharide in human diet:
(d) Beta -ionone and methyl lactone (a) Heparine (b) Starch
167. What is the starting material of pantothenic acid? (c) Glycogen (d) Cellulose
(a) Ribose 175. In which form glucose is stored in muscle and liver?
(b) Beta ionone and methyl lactone (a) Cellulose (b) Glycogen
(c) Benzaldehyde and l-o-Butraldehyde (c) Starch (d) Condroitin sulfate
(d) Formaldehyde and isobutyraldehyde 176. The compound 5,7,8-trimethyltocol is commonly
168. According to the chemical and biological classifications known as ..
of fatty acids, we can classify palmitic acid as: (a) α-tocopherol (b) ß-tocopherol
(a) Monounsaturated and essential (c) γ-tocopherol (d) Menaquinone
(b) Polyunsaturated and essential 177. L-amino acid dehydrogenase is an enzyme that can
(c) Saturated and essential catalyse the oxidation of different L-amino acids. It
(d) Saturated and non- essential cannot catalyse the oxidation of D-amino acids or
169. A premature baby, shortly after birth, presents with other L-compounds. Based on these characteristics we
rapid breathing, intercostal retractions, and grunting can say that this enzyme shows:
sound while breathing. A blood gas analysis reveals low (a) Absolute specificity over substrate
oxygen and acidosis. A diagnosis of respiratory dis- (b) Allosteric regulation
tress syndrome is quickly made. This syndrome is seen (c) Relative specificity over substrate
in newborns with immature lungs whose pneumocytes (d) Specificity of action
do not synthesize enough:
178. Inactive precursors of some enzymes that are activated
(a) Phosphatidyl choline
through hydrolysis reactions are called:
(b) Phosphatidyl inositol
(a) Apoenzyme (b) Holoenzymes
(c) Sphingosin
(c) Prosthetic groups (d) Zymogens
(d) Sphingomyelin
179. These enzymes have different structure but the same
170. The following compounds are phospholipids:
catalytic function. Frequently they are oligomers made
(a) Lecithin and sphingomyelin from different polypeptide chains. These enzymes are
(b) Plasmalogens and cerebrosides called:
(c) Diacylglycerols and cephalins
(a) Allosteric enzymes (b) Isozymes
(d) Glycerol and gangliosides (c) Lyases (d) Proenzymes
171. Name the enzymes involved in conversion of oxaloac- 180. The necessary coenzyme for transamination reactions is
etate to α-ketoglutarate
(a) Aminotransferases (b) FAD
(a) Isocitrate dehydrogenase
(c) Transcatalase (d) FMN
(b) Fumarase
(c) Aconitase 181. In glucose metabolism, name the enzymes catalysing
(d) Thiolase the following step: Conversion of glucose to glucose-6-
phosphate?
172. Which kind of enzymes catalyses the activation or
(a) Hexokinase
inactivation of other proteins and enzymes by phos-
(b) Glucokinase
phorylation of specific amino acid residues in the
protein that acts as substrate: (c) Glucose-6-phosphate dehydrogenase
(d) Phosphofructokinase
(a) Cyclases (b) Kinases
(c) Proteases (d) Phosphatase 182. The amino acid lysine is symbolized as
 Biochemistry  3.181

(a) K (b) R 193. Which of the following conjugations is not done by

(c) L (d) H microsomal enzyme?
183. Which of the following residue in DNA exists pre- (a) Sulfate conjugation
dominantly as the keto tautomer? (b) Gultathione conjugation
(c) Acetylation
(a) Cytosine (b) Guanine
(d) Glucuronidation
(c) Alanine (d) Thymidine
194. Which vitamin deficiency causes cheilosis?
184. D-galactose upon reduction gives
(a) Thiamine (b) Riboflavin
(a) D-sorbitol (b) D-Ribitol
(c) Pyridoxine (d) Biotin
(c) D-Dulcitol (d) D-Mnnitol
185. Glycoprotein laminin functions as 195. Which of the following tests is specific for ketohexoses?
(a) Transporter (a) Molisch test (b) Benedict’s test
(b) Blood clotting (c) Barfoed’s test (d) Seliwanoff’s test
(c) Antigens 196. Hopkins-Cole reaction is for which type of amino acid?
(d) Cell recognition and adhesion (a) Aromatic amino acid
186. What is the common name of cis-9-octadecanoic acid? (b) Imidazole ring
(a) Oleic acid (b) Linoleic acid (c) Indole ring
(c) Lauric acid (d) Palmitoleic acid (d) None of the above

187. For vitamin D1 197. The following protein/polypeptide has a quaternary

(a) 1 IU is contained in 7 6mg of standard preparation structure.
(b) 1 lU is present in 0.344 µg of standard preparation (a) Chymotrypsin (b) Haemoglobin
(c) 1 IU is contained in 0.025 µg of standard preparation (c) Insulin (d) Myoglobin
(d) 1 lU is present in 7 µg of standard preparation 198. Maltose is composed by
188. Tyrosine gives the entire test positive except _______ (a) Glucose + Galactose
(a) Xanthoprotic reaction (b) Fructose + Galactose
(b) Folin-Coicalteau’s test (c) Glucose + Fructose
(c) Millons reaction (d) Glucose + Glucose
(d) Hopkins-Cole reaction 199. Protein X is formed by two chains with 80 amino acids in
189. Which of the following test is specific for the ketone one chain and 58 in the other. These two chains are linked
bodies? by disulfide bonds and all the essential amino acids are
(a) Rothera’s test (b) Gammelin’s test present in the structure, but not all the non-essential amino
acids. With this information, we can say that this protein is:
(c) Hay’s test (d) Fouchet’s test
(a) A globular protein
190. Which of the following tests are positive for bile salts? (b) A fibrous protein
(a) Hay’s test (b) Patternkofer’s test (c) A conjugated protein
(c) Both (a) and (b) (d) None of the above (d) A complete protein
191. Which method is used for blood glucose estimation? 200. An amino acid that yields acetoacetyl CoA during the
(a) Alkaline picrate method catabolism of its carbon skeleton would be considered:
(b) Diacyl monoxime method (a) Glycogenic
(c) Folin Wu method (b) Ketogenic
(d) Bromocresol green dye method (c) Glycogenic and ketogenic
192. Which of the following does not cause haemolysis in (d) Neither glycogenic nor ketogenic
GP6D? 201. The NH3 produced in muscle degradation of nitroge-
(a) Primaquine (b) Sulfonamide nated compounds is transported through blood to the
(c) Asprin (d) Penicillin liver using ___________ as carriers.
3.182  Chapter 4

(a) Alanine and glutamine (a) B1 (b) Riboflavin

(b) Urea and alanine (c) B7 (d) Niacin
(c) NH4 and glutamate 212. Which vitamin decreases circulatory free fatty acid in
(d) Glutamate and glutamine adipose tissue?
202. Nitric oxide and urea have in common __________ as (a) Riboflavin (b) Ascorbic acid
an immediate precursoramino acid. (c) Biotin (d) Niacin
(a) Aspartate (b) Arginine
213. Which vitamin is only synthesized by microorganism
(c) Glutamate (d) Phenylalanine
and not by plant or animal?
203. The correct conformation of complex proteins is (a) Riboflavin (b) Ascorbic acid
achieved with the help of (c) Biotin (d) Cobalamin
(a) Chaperones (b) Hing domain
214. The reaction given by two or more peptide linkages is?
(c) Zinc figures (d) None of the above
(a) Biuret test (b) Ninhydrin test
204. Which of the following immunoglobulins has B-cell (c) Xanthoproteic test (d) Pauley’s test
receptor as major function?
215. How many base pairs are present in each turn of
(a) IgA (b) IgE
β-form of DNA helix?
(c) IgD (d) IgG
(a) 9 (b) 10
205. What is the starting material of biotin? (c) 11 (d) 12
(a) Bisbenzyl succinic acid
(b) Ribulose 216. Which of the following is the inhibitor of isocitrate
dehydrogenase in Krebs cycle?
(c) Beta-ionone and methylvinyl lactone
(d) Beta -ionone and methyl lactone (a) ATP (b) AMP
(c) ADP (d) NAD
206. What is the starting material of ascorbic acid?
(a) Beta -ionone and methyl lactone 217. In muscular dystrophy serum level of which enzyme is
(b) Benzaldehyde and isobutraldehyde elevated?
(c) Ribose (a) Acid phosphatase
(d) Ribulose (b) Creatinine phosphokinase
(c) Amylase
207. Which of the following occurs due to defect in (d) Aldolase
uroporphyrinogen decarboxylase?
218. In Wilson’s disease serum level of which enzyme de-
(a) Protoporphyria
creases?
(b) Hereditary coporphyria
(c) Porphyria cutaneatarda (a) Amylase
(b) Ceruloplasmin
(d) Acute intermittant porphyria
(c) Glucose-6-phosphate dehydrogenase
208. The P:O ratio for oxidation of FADH2 is? (d) Creatine phosphokinase
(a) 1 (b) 2 219. In visual cycle, iodopsin gives which pigment?
(c) 3 (d) 4
(a) Red
209. Which of the following is the sulfur-containing (b) Green
compound involved in decarboxylation reaction? (c) Yellow
(a) Choline (b) Lipoic acid (d) Blue
(c) Inositol (d) Niacin 220. Caprylic acid chemically is
210. Which one is described as “vitamin in search of disease”? (a) CH3[CH2]4COOH
(a) Vitamin A (b) Vitamin C (b) CH3[CH2]6COOH
(c) Vitamin E (d) Vitamin H (c) CH3[CH2]8COOH
(d) CH3[CH2]10COOH
211. Wernicke–Korsakoff syndrome is due to deficiency of
vitamin?
 Biochemistry  3.183

Answer Keys
1. (b) 2. (c) 3. (a) 4. (a) 5. (d) 6. (b) 7. (d) 8. (c) 9. (a) 10. (c)
11. (a) 12. (b) 13. (d) 14. (d) 15. (a) 16. (d) 17. (a) 18. (b) 19. (c) 20. (a)
21. (a) 22. (c) 23. (d) 24. (c) 25. (b) 26. (a) 27. (d) 28. (a) 29. (a) 30. (c)
31. (c) 32. (a) 33. (c) 34. (b) 35. (a) 36. (d) 37. (a) 38. (c) 39. (d) 40. (c)
41. (d) 42. (a) 43. (c) 44. (d) 45. (c) 46. (d) 47. (b) 48. (d) 49. (c) 50. (b)
51. (c) 52. (a) 53. (c) 54. (d) 55. (b) 56. (d) 57. (d) 58. (a) 59. (b) 60. (a)
61. (d) 62. (d) 63. (d) 64. (c) 65. (d) 66. (d) 67. (a) 68. (a) 69. (c) 70. (b)
71. (d) 72. (c) 73. (c) 74. (d) 75. (b) 76. (b) 77. (c) 78. (d) 79. (d) 80. (a)
81. (d) 82. (a) 83. (d) 84. (a) 85. (b) 86. (d) 87. (b) 88. (a) 89. (b) 90. (a)
91. (b) 92. (b) 93. (a) 94. (a) 95. (d) 96. (b) 97. (c) 98. (a) 99. (c) 100. (d)
101. (b) 102. (c) 103. (d) 104. (b) 105. (a) 106. (d) 107. (b) 108. (c) 109. (b) 110. (a)
111. (c) 112. (a) 113. (c) 114. (d) 115. (c) 116. (a) 117. (c) 118. (b) 119. (c) 120. (b)
121. (b) 122. (a) 123. (c) 124. (c) 125. (d) 126. (c) 127. (b) 128. (c) 129. (a) 130. (d)
131. (a) 132. (a) 133. (d) 134. (c) 135. (d) 136. (c) 137. (a) 138. (c) 139. (a) 140. (c)
141. (b) 142. (b) 143. (c) 144. (a) 145. (d) 146. (b) 147. (b) 148. (c) 149. (d) 150. (a)
151. (c) 152. (c) 153. (b) 154. (c) 155. (c) 156. (d) 157. (b) 158. (c) 159. (c) 160. (b)
161. (b) 162. (c) 163. (b) 164. (d) 165. (b) 166. (b) 167. (d) 168. (b) 169. (a) 170. (a)
171. (a) 172. (b) 173. (d) 174. (b) 175. (b) 176. (a) 177. (c) 178. (d) 179. (b) 180. (a)
181. (a) 182. (a) 183. (d) 184. (c) 185. (d) 186. (a) 187. (c) 188. (d) 189. (a) 190. (c)
191. (c) 192. (d) 193. (d) 194. (b) 195. (d) 196. (a) 197. (b) 198. (d) 199. (d) 200. (b)
201. (a) 202. (b) 203. (a) 204. (c) 205. (a) 206. (c) 207. (c) 208. (b) 209. (b) 210. (c)
211. (a) 212. (d) 213. (d) 214. (a) 215. (b) 216. (a) 217. (d) 218. (c) 219. (b) 220. (b)
 chapter 5
Medicinal Chemistry

Drugs Acting On ANS Sr. no Name of drug R

Adrenergic System 1 Naphazoline
yy Adrenergic neurotransmitter: Chemically, it is cate- CH2
cholamine like Adrenaline, Noradrenaline, Dopamine.
yy Biosynthesis: L-tyrosine use as bioprecursor.
yy Type of receptor:
(1) α-adrenergic receptor: ­
α1 and α2
(2) ­β
­
-adrenegic receptor: β1
, β2, β3 2 Tetrahydrozo-
yy Metabolism: Catecholamine metabolism occurs by line
two enzymes:
(1) COMT – Catechol-O-methyltransferase
(2) MAO – Monoamine oxidases

Direct acting agent 3 Oxymetazoline H3 C

(1) Selective α1 agonist:
CH 2 C(CH 3 )3
Sr. Name of Characteristics Side ef-
no drug fects
H3 C OH
1 Phenyeph- Used as mydriatic Bradycar-
rine when cyclopegia dia 4 Xylometazoline H3 C
is not require
and nasal CH 2 C(CH 3 )3
decongestant

2 Methox- Used as nasal Bradycar- H3 C

amine decongestant dia

3 Midodrine N-glycyl prodrug –

of desglymido-
drine. Selective α2 agonist
General structure:
(2) Non-selective α agonist:
General structure Cl
H
R N N
R N
N N
H Cl H
 Medicinal Chemistry  3.185

(5) Clenbuterol
Sr. no Name of drug R Characteristic (6) Salmeterol, Formoterol, Levabuterol are long acting
agent.
1 Clonidine –H Used in migraine,
glaucoma, opioid yy Use: It is used in Asthma and as uterine relaxant to
withdrawal delay premature labour.
syndrome
Common side effect:
2 Apraclonidine –NH2 Used in glucoma yy Tachycardia, Arrythmia, Vasodialation

3 Brimonidine – Used in glucoma Indirect acting agent

4 Guanabenz – –
It acts by release of endogenous catecholamines.

General structure:
5 Guanafacine – –
CH CH NH2
Dual α and b agonist
yy Example is Dobutamine: It exists as a pair of R
R′
enantiomer.
yy (+) enantiomer: β 1 and β2 agonist and (–) enantiomer:
α1 agonist. Sr. no Name of drug R R′ Character-
yy It is a racemic mixture used in CHF as I.V. istic

b-Adrenergic agonist 1 Amphetamine CH3 H It is MAO

inhibitor
(1) Non selective: and CNS
Example is Isoproterenol: It is a powerful bronchodi- stimulant
alator used in asthma. and
(2) Selective β2 agonist: appetite
suppressant
General structure:
2 Hydroxyamphet- CH3 OH It gives
R CH CH2 NH C(CH3)3 amine with
OH atropine
to produce
R′ Mydriasis.
R″
3 p-tyramine H OH Not used
(Pirbuterol contain pyridine ring instead of phenyl ring) clinically.

Sr. no Name of drug R R′ R″ yy L-pseudoephedrine which is threo isomer of ephedrine

and nasal decongestant.
1 Salbutamol CH2OH OH H

2 Terbutaline OH H OH Sympathomimetic agent with mix

mechanism of action
3 Pirbuterol CH2OH OH H
(1) D-ephedrine It is erythro racemate of ephedrine and
4 Orciprenaline – – – used in asthma, nasal decongestant.
(Metoproter-
(2) Metaramenol It is given parenterally during spinal
enol)
anaesthesia to prevent acute hypotensive state.
3.186  Chapter 5

α-Adrenergic Antagonist
(1) Non-selective blocker:

Sr. no Name of drug Characteristics Side effects

1 Tolazoline It is imidazoline deriva- –

tives.
CH 2

N NH

2 Phentolamine It is imidazoline deriva- –

tives.
N CH 3
CH 2
HO
N NH

3 Phenoxybenamine It forms aziridinium ion Miosis, nasal congestion,

which irreversibely block postural hypotension.
OCH2 CH CH3 receptor.

N CH2 CH2 Cl
CH2

Use: Management of hypertension associate with b-Adrenergic antagonist-Chemical

pheochromocytoma. classification:
yy Arylethanolamine derivatives:
(2) Selective a1 blocker:
General structure:
yy Tamsulosin: It aryl sulfonamide uro selective drug.
yy Side effect: Failure of ejaculation. R CH CH2 NH C(CH3)3
yy Prazosin, Terazosin, Doxazosin, Trimzosin etc. OH

(3) Selective a2 blocker: Sr. no Name of drug R Characteristics

(1) Rauwolscine and Yohimbine obtain from Rauwolfia 1 Dichloro- (Cl)2–C6H4 Carcinogenic
alkaloids. isoproterenol
(2) Mirtazepine: It is an antidepressant which also block
5-HT receptor 2 Pronethanol C6H5 Cause thymic
tumour
The ergot alkaloid like ergocrystin, ergocryptine,
3 Sotalol NH–SO2– Used in arrhyth-
ergocornine are derivatives of lysergic acid which is also α
CH3 mia also.
blocker.
 Medicinal Chemistry  3.187

Aryloxy propanolamine derivatives: General structure:

O CH2 CH CH2 NH C (CH3)2
O CH2 CH CH2 NH C(CH3)2
OH R

OH

Sr. Name of Fused ring R Characteristics

no drug
R 1 Propano- H It metabolises to
lol 4-OH propanolol
Sr. Name of R Characteristics which b blocker
no drug with sympathmi-
metic activity.
1 Practolol –NHCOCH3 – It causes brn-
choconstriction,
2 Metopro- –CH2–CH2–OCH3 Used in angina,
hypoglycemia.
lol myocardial infar-
action 2 Pindolol H –
3 Esmolol –CH2–CH2– Ultra short acting
N
COOCH3 agent. (half life- H
10 min) and use 3 Nadolol CH3 It is used in
HO
in arrhythmia angina and very
4 Atenolol –CH2–CO–NH2 Used in angina long acting agent
HO
(half life is 20 hr)
5 Betaxolol –CH2–CH2–O– Used in glaucoma,
CH2–Cyclopropyl long acting agent.
yy The other is timolol which contain 1, 2, 5 thiadiazole
Fused ring contains aryloxy propanolamine deriva- ring and morpholine ring at 4 position.
tives: Use: It is used in migraine and myocardial infaraction.

Note
The drugs which used in glaucoma are (1) Carteolol (2) Timolol (3) Levobunolol

All β-blocker use as racemic mixture except Levobunolol, Timolol, Penbutolol.

Cholinergic System
Synthesis and destruction of ACh
It is synthesized from choline acetylase and destruct by cholinesterase.

Note
(1) Drug that inhibits ACh synthesis:
e.g., Hemicholinium, Vesamicol.
(2) Drug that inhibits Ach release:
(a) Botulinium toxin: It causes botulism (food poisioning) and used in eyelid spasm treatment.
(b) β-bungarotoxin: It contains protein in venom of snake of Cobras family
3.188  Chapter 5

Acetylcholine receptor COOCH3

Nicotinic receptor
1. NM­muscle type N
2. NN­neurone type
(3) Oxotremorine: Used in Alzheimer’s disease.
Muscarinic receptor
M1—Neural type cause CNS excitation Anti-Cholinesteras
M2—Cardiac type cause inhibition Classification
M3—Glandular cause vasodialation and smooth muscle (1) Reversible Cholinesterase
contraction and increase salivery, gastric secretion. (a) Carbamate derivatives
M4—CNS Increase locomotor activity. Physostigmine: It is obtained from Physostigma
M5—Not clear. venenosum
It contains tertiary nitrogen which is non-polar hence
Cholinergic Agonist becomes lipid soluble.
Classification
(1) Choline ester derivatives:
General structure:
CH3 O
H H
H 3C N C C O C R’’

R R’ Metabolism
CH3
yy Hydolysis forms eseroline
yy Oxidation forms rubreserine and then serine blue and
Sr. Name of R R′ R″ Characteristics brown.
no drug
Neostigmine It contains quaternary nitrogen which is
1 Methacho- CH3 H CH3 S form is active made of compound hydrophilic.
line
CH3 H3C
2 Bethanechol H CH3 NH2 Use in bladder CH3
hypotenia. N O N+
H3C CH3
3 Carbachol H H NH2 It is used in
glaucoma O
when response
is not obtained Metabolism: Hydrolysis to 3-hydroxy phenyl methyl
by pilocrpine. derivative.

The others which do not contain quaternary ammonium Pyridostigmine

group are CH3

(1) Pilocarpine: It contains imidazole and tetrahydro- N O

furan ring, obtained from Pilocarpus jaborandi and H3C
Pilocarpus microphyllus species. O

C2H5 CH2
N
N+
O O N
CH3
(2) Arecoline: It is obtained from Areca catechu and con- Use: All are acting medium and used in treatment of
tains 1,2,5,6-Tetrahydro Pyridine ring. myasthenia gravis.
 Medicinal Chemistry  3.189

Edrophonium Irreversible type

Use: In diagnosis of Myasthenia gravis. Organophsphrous compound
It is potent anti-curare agent use to alleviate overdose (1) Malathion and Parathion: Both oxidized to Malaoxon
of d-tubocurarine. and Paraoxon which more potent.
(2) Ecothiophate: It is only hydrophilic organophosphrous
Ambenonium compound which use in glaucoma.
All alzheimer’s drug like Donepezil, Rivastigmine, (3) Dyflos (Diisopropyl fluoro phosphate):
Gallantamine, Tacrine (acridine derivative), etc., are anti- (4) Isofluorophate
cholinesterse. (a) Carbamate derivatives: Carbaryl, Propoxur

Note
Malathion, Parathion, Carbaryl, Propoxur, etc., all are used in insecticide and nerve gas for chemical warfare.

Cholinesterase reactivator (3) Synthetic derivatives

yy Pralidoxime: It is used in organophosphate poisoning (a) Amino alcohol ester derivatives:
and also antagonist Neostigmine and Pyridostigmine.
Sr. no Name of the drug Characteristics

1 Clindinium It contains quincli-

dine ring
N CH NOH Used in peptic
CH3 ulcer and ulcerative
colitis.

Anti-cholinergic agent 2 Cyclopentolate It is used as Mydriat-

ic and in cyclopegia.
(1) Naturally occurring
3 Dicyclomine Used in motion
Sr. No Name of drug Characteristics sickness, irritable
bowel syndrome.
1 Atropine It is a racemic
4 Glycopyrrolate It is potent M 1
mixture of
antagonist.
hyoscymine.
Used in peptic ulcer.
It is used as
mydriasis, 5 Methantheline –
antispasmodic,
anticholinesterase 6 Eucatropine –
poisoning.
7 Oxyphenylcyclimine –
2 Hyoscyamine Levo form is active.
Use in motion
sickness. (b) Amino alcohol ether derivatives: Used in Parkin-
son disease.
3 Hyoscine –
Sr. no Name of the drug Characteristics
(2) Semisynthetic derivatives 1 Benztropine It relieves Tremor and
yy Homatropine, Hyoscine butyl bromide. Rigidity.
yy Ipratropium and Tiotropium: It is quaternary ammo-
2 Orphenadrine It relieves only rigidity.
nium derivative of atropine and used in asthmatic attack.
3.190  Chapter 5

(c) Amino alcohol derivatives yy Isosorbide nitrate: It is a bicyclic form of sorbitol.

• It is given sublingually or as chewable tablet.
Sr. no Name of the drug Characteristics • Specific side-effect: Tachycardia
1 Biperiden It blocks nicotinic induced yy Erythrityl tetranitrate:
convulsions because of yy Pentaerythritol tetranitrate: It is a powerful explosive
potent nicotinolytic. and must be diluted with lactose or mannitol.
yy Mechanism of action: The nitrate release nitric oxide
2 Procyclidine It is used in parkinson’s which binds with –SH group of enzyme and carries out
disease. dephosphorylation of myosin light chain and relaxation.
3 Tridihexethyl It is used in Parkinson Calcium channel blocker
disease.
yy Mechanism of action: It inhibits phosphorylations
of myosin light chain phosphate and prevents binding
(d) Aminoamide derivatives with actin and prevents contraction.

Sr. no Name of the drug Characteristics 1. Phenyl alkyl amine derivative:

(a) First generation agent: Verapamil
1 Isopropamide Antispasmodic, antise-
cretory yy Metabolism: By N-demethylation to Norverapamil
which is active.
2 Tropicamide It is potent M-4 antagonist
and is used as mydriatic yy Specific side-effect: Bradycardia, constipation.

(e) Miselleneous OMe

MeO
Pirenzepine: It is M-1 receptor antagonist.
Drotraverine: Novel agent, used as anti-spasmodic by MeO CH3
inhibit PDE-4.
Darcifenacin, Tolterodine, and Oxybutynin: All are N
MeO
selective M-3 antagonist and used to inhibit micturition. CN

H3C CH3
Drug Acting on CVS Verapamil
Anti-anginal agent
yy Angina pectoris: When imbalance between oxygen 2. 1, 4 dihydropyridine derivatives
supply and oxygen demand in myocardium occurs this
Nifedipine is first generation drug, the remaining drugs in
is called as angina pectoris.
below table are second generation.
yy Types of angina:
1. Classical (stable) angina General structure:
2. Variant (prinzmental) angina H
yy Classification of anti anginal drugs: H3 C N R2
1. Nitrate derivative:
(a) short acting drugs: CH 3 COO R3
yy Amyl nitrate/isopentyl nitrate: Currently used in R 2′
cyanide poisoning treatment.
yy Glyceryl trinitrate (nitroglycerin): It is given sub-
lingually and duration of action is 30 min. R 3′
Specific side effect: Postural hypotension, Methhaemoglo- General Structure of
binemia, Monday morning sickness. 1, 4 Dihydropyridine
 Medicinal Chemistry  3.191

Sr no Name of drug R2 R3 R2′ R3′

1 Nifedipine CH3 –COOCH3 NO2 H

2 Amlodipine CH2–O–C2H4–NH2 –COOC2H5 Cl H

3 Felodipine CH3 –COOC2H5 Cl Cl

4 Nimodipine CH3 –COO–C2H4–OCH3 H NO2

5 Nicardipine CH3 –COO–C2H4–N–C6H5–CH2 H NO2

6 Nitrendipine CH3 –COO–C2H5 H NO2

Note: Nimodipine can cross BBB, so it is used in cerebral vasospasm

Newer third generation drugs (3) Dipyridamol: It increases adenosine (natural vasodi-
(1) Lacidipine: It contains additional α blocking lator) which is a coronary dialator.
activity.
(2) Monatepil: It contains additional anti-artherosclerotic Antihyperlipidemic Drugs
activity. These antihyperlipidemic drugs are specifically used in
Common side effect: Ankle odema. artherosclerosis.

Benzothiazepine derivative: Diltiazem yy Classification of antihyperlipidemic drugs:

HMG-CO-A reductase inhibitors

OCH3 yy Mechanism of action: They inhibit cholesterol biosyn-
thesis by inhibiting HMG-CO-A.
yy They also decrease LDL level by increasing LDL
S
precursor by recognizing apo-B 100.

O General structure:
N CH3 HO O
O O
O
H 3C N O
CH3 R C O

Potassium (K+) channel opener CH3

Nicorandil, Pinacidil and Cromakalim are potassium chan-
nel opener and bronchodialator which are used in angina as
well as in asthma. H 3C

Miscellaneous Sr. no Name of drug R

(1) Khellin: Natural drug obtained from fruits and seeds
1 Lovastatin –CH(CH3)–CH2–CH3
of Ammi visnaga.
2 Simvastatin –C(CH3)2–C5H11
(2) Papaverine: Powerful coronary dialator.
3.192  Chapter 5

Note
For obtaining inhibitory activity on HMG-CO-A, lactone ring must hydrolyse to open ring hydroxyl acid.

yy Pravastatin: It is same in structure as lovastatin, the yy Fluvastatin: It contains indole ring and heptanoic acid
only difference is that it contains open ring hydroxyl as side chain.
acid instead of lactone ring. yy Cerivastatin and Rosuvastatin
yy Atorvastatin:
Specific side-effects:
O OH OH O (1) Myalgia
(2) Rhabdomylosis (Myositis)
N N OH (3) Angio-odema
H
Fibric acid derivative: (General structure)
CH3
R O COOR′

F CH3

Sr. no Name of drug Characteristics Specific side ef- Metabolism

fects

1 Clofibrate – Myalgia Hydrolysis

(R′= -C2H5, R= -Cl) Rhabdomylosis (clofibric acid)

2 Fenofibrate More lipophilic – –

R=Cl−C6H5−C=O, R=CH−
(CH3)2

3 Ciprofibrate Acid derivative – –

R=CH−(Cl)2, R′=H

4 Beclofibrate – – –
R′=C2H5 , R=Cl-C6H5-CH2-

yy Gemifibrozil: (2) Colestipol: High mol.wt granular copolymer of tetra-

ethyl pentamine and epichlorohydrin.
CH3 (3) Cosevelam: Recent drug which does not cause consti-
CH3
pation.
O − CH2 − CH2 − CH2 − C − COOH • Mechanism of action: Bile acid is required for
cholesterol absorption so this resin binds with it
CH3 and decreases cholesterol level in body.
CH3
(4) Miscelleneous:
yy Side-effect: Anaemia, Leukopenia. • Niacin:
• Side effect: Vasodialation, palpitation.
Bile acid binding resin • Probucol: It is two tertiary butyl phenol linked to
(1) Cholestyramine: It is styrene copolymer of divinyl dithio propyl group.
benzene and quaternary ammonium compound. • Mechanism of action: It inhibits sterol biosynthesis.
• Side effect: Constipation • Side effect: Diarrhoea.
 Medicinal Chemistry  3.193

Anti-arrythmic agent yy Normal impulse initiated in SA node or pacemaker

cell.
Arrhythmia: When there is abnormality of rate, origin
or conduction of cardiac muscle, there is lack of rhythm. Types of arrhythmia
(1) Extrasystoles: Premature beat from ectopic focus.
Phases of cardiac action potential
(2) Paroxysmal tachycardia: Heart rate increases up to
yy Phase-0—Influx of sodium occurs at threshold poten- 150–200 beat/min
tial and depolarization occurs. (3) Atrial flutter: Rapid, regular pulse is 180–300 beat/
yy Phase-1—Initiation of influx calcium occurs. min
yy Phase-2—Calcium influx occurs and contraction takes (4) Atrial fibrillation: Rapid, continous, irregular beat.
place. (5) Ventricular fibrillation:
yy Phase-3—Potassuim efflux occurs and repolarization
occurs and resting potential takes place. Classification
yy Phase-4—Slowly, depolarization occurs and reaches Class-I: Drug which blocks sodium channel (membrane
threshold potential. stabilizing agent)

Class-IA drugs: Drug which slows down depolarization.

Sr. no Name and structure of drug Characteristics Specific side-effects Metabolism

1 CH = CH2 -Dextro isomer of Cinchonism Hydroxylation

quinine obtained Convulsion
OMe from cinchona.
N -Increases digoxin
toxicity.
H
C – OH

N
Quinidine sulfate

2 -Amide derivative Lupus syndrome N-acetylation

H2N CONHCH2CH2 – N(C2H5)2 of procaine. Agranulocytosis (NAPA)
-Ganlion blocker (active)
Procainamide

3 Disopyramide It acts by ATP and Anticholinergic N-dealkylated

Pinene receptor. side effect.

Class-Ib drugs: Mechanism of action: It decreases repolarization.

Sr. no Name of the drug Characteristics Specific side-effects Metabolism

1 CH3 Used for ventricular arrythmia. Paresthesias N-dealkylation

Convulsion (active)

NHCOCH2N(C 2H5)2

CH3

Lidocaine
3.194  Chapter 5

2 Phenytoin It is used for digitalis induced ar- Hypertrophy Hydroxylation

terial and ventricular arrhythmia. Anaemia
Osteomalacia

3 Mexiletine – Bradycardia Hydroxylation

4 Tocainide Only used in ventricular type Agranulosotosis –

Thrombocytopenia

5 Aprinidine – –

Class-Ic agent

Sr. no Name and structure of drug Characteristics Metabolism

1 H2 C C C O R and S isomer Hydroxylation

H2 sodiumchannel (active)
O – CH2 – CH – CH2 – NH – C3 – H7 Blocker and S is β-blocker.

OH
Propafenone

2 Encainide – –

3 Flecainide It contains piperidine ring O-dealkylated

4 Moricizine It contains morpholine –

ring.

yy Mechanism of action: It strongly slows down depolar- It is used as antiarrythmic agent.

ization in phase-0. yy Class-III agent:
yy Class-II agent: yy Mechanism of action: It prolongs repolarization.
yy Various β-blockers like Propanolol, Esmolol, Sotalol.

Sr. no Name and structure of drug Characteristics Specific side ef-

fect

1 O C4 H9 Due to iodine, it is Slate-grey or

I highly blue skin.
lipophilic and inhibits
conversion of T4 to T3
CO O – CH2 – CH2 – N – R

I
R= (C2H5)2
Amiodarone

2 Bretylium tosylate It is used parentrally. –

 Medicinal Chemistry  3.195

Methane sulfonamide derivatives Class-IV agent.

1. Vearapamil: It is given with digoxin to patients with
1 Sotalol. L-isomer of – poor by controlled artrial fibrillation.
sotalol having b
2. Diltiazem:
and K+ channel
blocking activity Anti-hypertensive agent
while
yy Drug acting on Renin angiotensin system:
D-isomer has only
K+ channel block- (1) Renin inhibitor
ing activity Example: Propanolol, Clonidine, Enalkiren, Ramikiren,
2 Dofetlide – – Terlakiren, Zankiren, Diltiazem.

3 Ibutilide – –
(2) ACE inhibitor
yy Mechanism of action:
4. Azimilide – – (1) It inhibits conversion of angiotensin–I to angio-
(Imidazolinedione tensin-II
derivative)
(2) It also increases bradykinin level and vasodialation.

Sr. no Structure and name of drug Characteristics Specific side- Metabo-

effects lism

1 Thiol group Hyperthermia –

increase bind to Dysguesia
zinc of ACE. Cough
HS CH2 CH(CH3)CO N
Renal stenosis.
COOH
Captopril

2 COOC2H5 Alanine contains Devoid of Ester

prodrug. Dysguesia. hydrolysis
CH NH CH CO N Enalprilate
R (diacid-
CH3 form
Enalpril (active)
Enalpril R=COOH

3 COOC2H5 Lysine contain- – –

ing
CH NH CH CO N drug
not
R
prodrug.
(CH2)4 NH2

Lisinopril R=COOH

4 Benzapril It contains – –
Benzazepine
ring.

5 Quinapril It contains –
Isoquinoline Ring.

6 Ramipril It contains – –
Pyrrolidine ring

7 Fosinopril Phosphorous
Contains ACE inhibitor.
3.196  Chapter 5

(3) Angiotensin-II antagonist with AT1 receptor blocker:

General structure:

N NH CH 2 R
N N

SAR: It contains tetrazole ring which bind to AT1 receptor.

Sr. no Structure and name of the drug Characteristics Specific side-effects Metabolism

CH2 OH It contains Imidazole ring. – 5–CH2OH

convert into
Cl COOH group
1 Losartan, R = N
which is15
N times more
C4H 9 potent than
parent.
COOH It is valine containing drug. – –
CH – CH – (CH3)2
Valsartan, R = N
2 C=O
C4 H 9

3 Candesartan It contain R= benzimidazole – Ester hydroly-

ring with ester group. sis to acid.
4 Telmisartan It contains R=COOH group … – –
which binds to AT1 receptor

yy Specific side effect: Fetal damage, Hyperkalemia.

(4) Only Angiotensin-II inhibitor: Saralasin which need parentral route.
yy Vasodialator
1. Arteriolar agent
Sr. no Structure and name of drug Characteristics Specific side-effects Metabolism
It acts by nitrate mecha- Lupus syndrome Benzylic oxida-
N
1 nism. Nasal stuffness. tion
N And acetylation.
(inactive)
NH – NH2
Hydralazine
It requires metabolic activa- Hirsutism (So use in –
2 tion by sulfotransferase for alopecia)
N antihypertensive use. Tachycardia.
Sodium and water
N retention.

H2 N N NH2
O
Minoxidil
 Medicinal Chemistry  3.197

Sr. no Structure and name of drug Characteristics Specific side-effects Metabolism

N CH3 It is like thiazide diuretic Hyperglycemia. –

but causes sodium and
NH water
3 Cl S retention.
O O
Diazoxide

2. Arteriolar and venous dialator:

Sr. no Structure and name of drug Characteristics Specific side-effects Metabolism

1 Sod.nitroprusside Acts by nitrate mecha- Thiocynate toxicity. Metabolized to

nism Perspiration. thiocynate.

2 Pinacidil It contains pyridine ring. – –

3 Cromakalim It contains cromane ring. – Active isomer is lemaka-

lim.

Drug acting on sympathetic system:

1. Central sympatholytic agent:

Sr. no Structure and name of drug Characteristics Specific side-effects Metabolism

1 α-methyl dopa It acts on α2 receptor. Postural hypoten- –

sion

2 Clionidine It is α2 agonist and imidazoline Bradycardia P-hydroxy

derivative. Constipation derivative.

3 Guanabenz It is α2 agonist. – –

4 Guanafacine It contain guanidine ring. – –

2. Catecholamine depletor and adrenergic neuron blocker:

Sr. no Structure and name of drug Characteristics Specific side-effects Metabolism

1 Reserpine It depletes Diarrhoea, Methyl reserpate and 3, 4,

catecholamine. Bradycardia 5 trimethoxy benzoic acid.

2 Guanethidine It contain azocine – N-oxide.

ring. Carboxy derivative.
N CH2-CH2-NH-C-NH2

NH

3 Debrisoquine – – –

4 Guanoxon – – –

5 Bretylium – – –

6 Bethanidine – – –
3.198  Chapter 5

3. Ganglion blocker
3 Doxazosin, Long acting
yy Quaternary ammonium compounds: Hexametho- CO O and water
nium, Pentolinium, Chlorocondamine. R= soluble
compound.
yy Secondary amine derivative: Mecamylamine O
yy Tertirey amine derivative: Pempidine, Trimetho- 4 Quinazosin –
phan. R = –CH2–CH= CH2
yy Drug acts by reflex mechanism: Protoveratrine
Specific side effect: (1) First dose hypertension
obtained from veratrum alkaloids.
(2) Postural hypotension (3) Impotence.
Use: Specifically in management of hypertension associated
4. Selective a1 blocker: (General structure)
with Pheochromocytoma.
Non selective α blocker
MeO N (1) Phenoxybenzamine
N N R (2) Phentolamine
(3) Tolazoline
N Use: In pheochromocytoma and clonidine withdrawal
MeO syndrome.
NH 2 5. Mixed α and β blocker
yy Labetalol: It is used to treat hypertension during pregnancy.
yy Carvadilol: It contains antioxidant property.
6. β blocker: Detailed study in ANS.
Sr. no Structure and name of drug Characteristics
7. Diuretics: Thiazide, loop and potassium sparing di-
1 Prazosin, – uretics also used. (Detail in diuretics)
R= CO The compound which promotes flow of urine by increasing
O excretion of sodium and water is called as diuretics.
2 Terazosin, Long acting Classification:
agent. 1. High Celling diuretics
R= CO a. Sulfamoyl derivative: (loop diuretic because it acts in
O ascending loop of henle)

Sr. no Structure and name of drug Characteristics Metabolism Side-effects

1 Furosemide It is anthrnilic acid By Glucuro- –

derivative. nide
Cl NH – CH2 It has 60% bioavailability. pathway
O

NH2 – SO2 COOH

2 Bumetanide It has 100% bioavailability. By CPY-450 –

NH – C4 H9 It is meta amino benzoic pathway.
acid derivatives.
C6H5 – O

NH2 – SO2 COOH

 Medicinal Chemistry  3.199

3 Piretanide It contains pyrrolidine ring – –

4 Torasemide It is inactivate-SH group – Hepato

of enzyme and decreases Toxicity
sodium reabsorption. and Diar-
rhoea.

b. Ethacrynic acid (phenoxy acetic acid derivatives) yy Note: Thiazide diuretics cause lithium and digoxin
toxicity.
Cl
yy Common side effect: (1) Gitelmann’s syndrome
(2) Bartter’s syndrome.
CH 2 =C – CO O – CH2 – COOH
(b) Quinazolinone derivative:
C 2 H5 General structure:
Cl

c. Organomercurial H
Cl N R
Example:
N
(1) Mersalyl NH2 – SO2 R′
(2) Merbaphen O
(3) Meralluride
(4) Mercaptomerin
(5) Chlormerodrin Sr. no Name of drug R R′
yy Mechanism of action: They first release mercury ion 1 Quinethazone –C2H5 H
which inactivates –SH group of enzyme. 2 Metolazone –CH3 –CH3–C6H5
yy Note: It is given as I.M or subcutaneously except
Chlormerodrin which is given orally.
(c) Pthalimidine derivative/1-oxo isoindole derivative:
yy Common side effect of High celling diuretics:
Example is Chlorthalidone
(1) Hypokalemia (2) Hypocalcemia.
(d) Indole derivative:
(1) Moderately potent diuretics: Example is Indapamide
(a) Thiazide diuretics/Benzothiadiazine derivative: (2) Weak diuretics:
General structure: (a) Osmotic diuretics:
R6 N R3 yy Non-electrolyte type: (1) Mannitol (2) Sorbitol (3) Urea
(4) Isosorbide (Bicyclic form of sorbitol)
NH yy Mechanism of action: It forms hypertonic solution
NH2 – SO2 S which causes water to pass from body to kidney tubule.
O O
yy Electrolyte type:
yy Example: NaCl, KCl, Sodium carbonate, Sodium
Sr. no Name of drug R3 R6 acetate, etc.
(b) Xanthine alkaloids/Purine derivative: General
1 Hydrochlorthiazide H Cl structure:
2 Hydroflumethiazide H CF3 R3
O
3 Triclomethiazide CH–(Cl)2 Cl N
N
4 Bendroflumethia- CH2–C6H5 CF3
N R1
zide O N
5 Polythiazide CH2-S–CH2–CF3 Cl R7
3.200  Chapter 5

Sr. no Name of drug R1 R3 R7

yy Theophyline: Most active diuretics.

1 Theophylline CH3 CH3 H (c) Potassium sparing diuretics:

2 Theobromine H CH3 CH3 yy Mechanism of action: It blocks sodium reabsorption
3 Caffeine CH3 CH3 CH3 and decrease potassium excretion.

Sr. no Structure and name of drug Characteristics Metabolism Side-effects

1 Triamterene It contains pteridine In liver, convert, into It is very

H2N N N NH2 ring. active metabolite. photosensi-
It is given with thia- tive.
zide is counteract
N hyperkalemic effect.
N
NH2

2 Amiloride It contains pyrazine It is not metabolized. –

Cl N CO – NH – C – NH2 ring
and amidine moiety.
NH It is 10 times more
potent than triam-
H2 N N NH2 terene.

3 Spironolactone It is potent aldoste- It is metabolized to Gyneco-

O rone antagonist as it canrenone (which does mastia
prevents it binding. not contain thioacetyl Atrophy
O It causes digoxin group at 7 position) which
toxicity. is antagonist to aldoste-
rone.

O S – C – CH 3
O

4 Eplerenone Aldosterone antago- It contains carbomethoxy –

nist. group at seven positions.

(d) Carbonic anhydrase inhibitor Example:

yy Mechanism of action: Carbonic anhydrase is found General structure:
in many sites such as renal cortex, eye, CNS, gastric NH2 – SO2 S NH – CO – CH3
mucosa, and pancreas. This enzyme catalyses the
reversible hydration of CO2 to carbonic acid. N N
R
CO2 + H2O–carbonic anhydrase-----H+ + HCO3-
Sr. no Name of drug R Characteristics
yy The diuretics inhibit the carbonic anhydrase enzyme
at the proximal convoluted tubules cause reduction 1 Acetazolmide H It is also use in
in H+ ions for Na +–H+ exchange CO 2 reabsorption glaucoma, seizure.
from glamerular filtrate is suppressed and HCO 3–
excretion is increased and facilitates K+ secretion. 2 Methazolamide CH3 –
 Medicinal Chemistry  3.201

6. Anti-diabetic agent (3) Long acting

Type of diabetes: Sr. no Insulin preparation

(1) Type-1 dibetes (IDDM)/juvenile onset: 1 Protamine zinc insulin

Insulin deficiency occurs due to destruction of β
2 Ultralente
cell.
(2) Type-2 diabetes (NDDM)/Maturity onset. 3 Glargine insulin
Insulin resistance occurs.
For type-2 diabetes
Insulin: It contains 51 amino acids arranged in chain-A 21
(A) Sulfonylurea derivative
and chain-B contains 30 amino acid and both connected
by two sulphur bridge, and synthesized from proinsulin General structure:
(84 amino acid).
Classification R SO2 – NH – CO – NH – R
A. For Type-1 diabetes: Various insulin preparations
are used. (1) First generation drugs:

(1) Short acting agent Sr. no Name of drug Characteristics Metabolism

1 Tolbutamide – P-hydroxy
Sr. no Insulin preparation
R=CH3, R′=C4H9 derivatives.
1 Regular insulin (active)

2 Amorphous insulin zinc suspension (Semi- 2 Chloroprop- Used in diabe- Hydroxy

lente) amide tes insipidus derivatives.
R=Cl, R′=C3H7 and gives
3 Insulin aspart disulfiram like
effect, causes
4 Insulin lispro jaundice.

3 Acetohexamide – Reduction
(2) Intermediate acting R=CH3–CO– (ketone to
R′=Cyclohexane alcohol)
Sr. no Insulin preparation ring (inactive)
Hydroxyl-
1 Globin zinc insulin ation (active)

2 Lente suspension 4 Tolazamide – –

R=CH3,
3 NPH (Neutral protamine hagedorn) R′=Azepine ring

(2) Second generation drugs:

Sr no. Name of drug Characteristics Metabolism

1 Glibenclamide (glyburide) Inhibiting ATP-sensi- 4-hydroxy

tive derivatives.
O O O potassium channels
S
O N N
H H
C
N
H
OCH
3.202  Chapter 5

Sr no. Name of drug Characteristics Metabolism

2 Glipizide Pyrazine containing N-acetyl de-

drug rivatives.
Diuretic action.

HN

HN O

O=S=O

O NH

CH3

3 Glimepiride – –

4 Gliclazide It has antiplatlet ac- –

tion.

(3) Third generation drugs: (B) Non-sulfonyl urea derivative or Meglinide

• Glybonuride is more potent than tolbutamide and derivative: (contain D-phenylalanine)
forms six inactive metabolites. yy Repaglinide
• Mechanism of action: They act on sulfonylurea yy Nateglinide
receptor on pancreatic cell membrane and block
(C) Biguanide derivative
ATP sensitive potassium channel.
• Note: All Sulfonyl urea derivatives except gliben- General structure:
clamide cross placenta and cause hypoglycemia at
birth. R – NH – C – NH – C – NH2
• Common side effect: All stimulate appetite, Leuko-
penia, photosensitivity. NH NH
 Medicinal Chemistry  3.203

(1) Phenformin: R = –C6H5–CH2–CH2 Intermediate acting drug (duration of action 3 to 6 h)

(2) Metformin: R = (CH3)2–N– Sr. Name of R R′ R″
no drug
yy Mechanism of action: They increase glucose uptake
and decrease insulin resistance. 1 Amobar- C2H5 –CH2–CH2–CH (CH3)–CH3 H
bital
Common side effect: (1) Lactic acidosis (2) Vit B12
deficiency 2 Butabar- C2H5 –CH (CH3)–CH2–CH3– H
bital
(D) Alpha glucosidase inhibitors
• Acarbose: It is a naturally occurring oligosac- Short acting: (duration of action–< 3h)
charide.
Sr. no Name of R R′ R″
• Miglitol: It is desoxy nojirimycin derivative and drug
chemically piperidinetriol derivative.
1 Pentobar- –C2H5 –CH (CH3)– H
• Varcabose: bital CH2–CH2–CH3–
(E) Thiazolidinediones derivative 2 Secobarbital –CH2– –CH (CH3)– H
• Rosiglitazone CH=CH2 CH2–CH2–CH3

• Pioglitazone 3 Cyclobarbital –C2H5 Cyclohexene H

• Mechanism of action: They activate PPAR-γ and 4 Heptabar- –C2H5 Cycloheptene H
enhance transcription of insulin responsive gene bital
and increase insulin sensitivity.
• Side effect: Myalgia, Mild anaemia. Ultra short acting: ( duration of action <1 h)
• Interaction: They inhibit ketoconazole absorption. Sr. no Name of R R′ R2
drug
Drugs Acting on CNS 1 Thiopental C2H5 –CH–(CH3)– S
1. Sedative and hypnotics CH2–CH2–
Chemical Classification CH3

(1) Barbiturates: General structure—Chemically, it 2 Thiamylal –CH2– –CH (CH3)– S

is tri keto saturated pyrimidine derivative. CH=CH2 CH2–CH2–
CH3

R″ 3 Hexobar- C2H5 Cyclohex- R″=CH3

bital ene
O N O
Benzodiazepine: General Structure
R′ NH
R R1
O O
N
Long acting drug (duration of action–>6 hr)
Sr. no Name of drug R R′ R″ N
R7
1 Mephobar- C2H5 C6H5 CH3
X
bital

2 Phenobar- C2H5 C6H5 H

bital
yy Hydroxyl group contains benzodiazepine drug at
3 Barbital C2H5 C2H5 H
third position:
3.204  Chapter 5

General structure:
Sr. no Name of drug R1 R7 X
H3C N
1 Oxazepam H Cl H

2 Lorazepam H Cl Cl N
3 Temazepam CH3 Cl H
R7 N
yy Non-hydroxy benzodiazepine drug: Does not contain X
3-OH group.

Sr. Name of drug R1 R7 X

Midazolam
no

1 Diazepam CH3 Cl H Sr. no Name of drug R1 R7 X

2 Nitrazepam H NO2 H 1 Alprazolam Fused triazole ring Cl H

3 Clonazepam H NO2 Cl 2 Triazolam Fused triazole ring Cl Cl

4 Prazepam CH2–cyclopropyl Cl H 3 Midazolam Fused imidazole Cl F

5 Quazepam CH2–CF3 Cl F
Newer benzodiazepine Drug
Example is Zolpidem, Zaleplon.
Triazolobenzodiazepine Drug Mechanism of action: It facilitates GABA activated
It contains fused triazole ring. Except midazolam which chloride channel and increase GABA concentration.
contains imidazole ring. Pharmacokinetics profile:

Sr. no Drug Plasma half life Metabolism (Metabolite) Plasma half life of metabo-
(h) lite

1 Triazolam 2–4 Hydroxylation <6h

Midazolam 2–4 Hydroxylation <6h

2 Diazepam, 20–40 Nordazepam 60 h

Chlordiazepoxide

3 Flurazepam 1 Desmethyl flurazepam 60 h

(2) Ureides derivative: (7) Acetylene derivative: Methyl pentynol, Ethchloro-

Example: Apronalide, Bromasuvalum, Capuride, Cabromal. vynol, Ethinamate.
All are bromine containing compounds are very toxic
because of bromism. Local anesthetics
(3) Piperidinedione derivative: Chemistry
Example : Methgyprylon, Glutethimide. yy All local anaesthetics are weak base and Pka is 8 to 9
(4) Chloral derivative: Chlorobutanol, Dichlorophenazone. so not completely ionized at physiological pH so easily
(5) Carbamate derivative: Meprobamate which is cen- penetrate nerve and axonal membrane.
tral muscle relaxant and anti-anxiety. yy All local anaesthetics contains lipophilic group like
(6) Amide derivative: Triacetamide, Valuoctamide, aromatic ring which attach to hydrophilkc moiety by
Oxonamide Ester or Amide linkage.
 Medicinal Chemistry  3.205

Aromatic ring-------Ester or amide linkage-----Basic amino (2) Alkyl ester of p-amino benzoic acid.
side chain
Example: Benzocaine
yy All above contain moiety except benzocaine which
does not contain basic amino group.
yy Mechanism of action: H2N C-O-C 2H5
They block increase in sodium conductance by S6 trans- O
membrane helical domain of channel protein.
(3) Ester of benzoic acid:
Chemical Classification
Example:
(A) Ester derivative:
(1) Amino alkyl ester of para amino benzoic acid. (1) Cocaine: It is obtained naturally from Erythroxylum
coca.
General structure: (2) Piperocaine and Cyclomethycaine: Both contain
C-O-CH2-CH2-N R piperidine ring.
O (B) Amide derivative
R'
H2N
General structure:

Sr. no Name of drug Characteristic Metabolism CH3

1 Procaine Ester
R and R′=C2H5 hydrolysis
NH–CO –R
2 Tetracaine It contains butyl By
(Ametho- additional chain cholinester-
caine) at 4th position ase
R and R′= CH3 CH3

Sr. no Name of drug Characteristics Metabolism Side-effects R

1 Lidocaine It is also used in N-dealkylation CH2–N–(C2H5)2

ventricular arrhythmia. (glycine xylide)
(active)

2 Prilocaine N-dealkylation Methaemoglobinemia CH (CH3)2–NH–C3H7

3 Bupivacaine Levo form is use N-dealkylation Cardiotoxic (If racemic

mixture is used)
N
C 4 H9

4 Mepivacaine N-dealkylatiion

N
CH 3

5 Ropivacaine N-dealkylation

N
C 3 H7
3.206  Chapter 5

Application profile:
Sr. no Method Drugs
Sr. no Method Drugs 6 Epidural anaesthesia Lidocaine, Bupiva-
1 Surface anaesthesia Lidocaine, Ametho- caine
caine, Benzocaine

2 Infiltration anaesthesia All

NSAIDS
yy It is also called as non-opioid analgesic.
3 IV anaesthesia Lidocaine, Prilocaine yy Mechanism of action: It inhibits cyclooxygenase
4 Nerve block anaesthesia All enzyme (COX) so inhibit a production of prostaglandin.

5 Spinal anaesthesia Lidocaine, Ametho- Chemical Classification:

caine (1) Salicylate and salicylic acid derivative:

Sr. no Name and structure of drug Characteristics Metabolism Side-effects

1 COOH -Irreversibly block COX-1 Ester hydrolysis in 30 -Reye’s syndrome

and COX-2 min of administration -Gastric irritation
OCOCH3 -Also obtained from spi- to salicylate
rea plant (active)

Aspirine

2 COOH It contains hydropho-

bic aryl group provide
OH strongly potent as antiin-
flammtory
Than aspirin.

F F
DiflunisalDiflunisal

3 It is esterification of
COO NHCO–CH3 paracetamol and aspirin
which is long acting.
OCOCH3

4 Sulfasalazine Used in ulcerative colitis

yy Common side effect: Salicylism

Sr. Name of R R′ R″ Character-
(2) N-anthranilic acid derivative: no drug istics
General structure: 1 Mefenamic CH3 CH3 H It is
R R' acid metabolised
by
COOH
oxidation.
NH Diacid
form
R'' (inactive)
 Medicinal Chemistry  3.207

yy Common side effect: Haemolytic anaemia,

Sr. Name of R R′ R″ Character-
no drug istics
Diarrhoea
(3) Aryl propionic acid derivative:
2 Flufenamic H CF3 H Five times
acid more potent General structure:
than
mefenamic
acid. R' CH-COOH
3 Meclof- Cl CH3 Cl CH3
enamic acid R

Sr. no Name of drug Characteristic Metabolism Side effect

1 Ibuprofen R=H, R′= CH2CH(CH3)2 S (+) is active Hepatotoxicity,

Constipation

2 Phenoprofen R= O–C6H5, R′=H S (+) is active (35 times more potent) Hydroxylation Anti-platlet

3 Ketoprofen R= C=O–C6H5

4 Flurbiprofen R=F, R′=C6H5 Used topically to prevent miosis

during ocular surgery.

5 Indoprofen Contain 1-oxo iso indole ring.

6 Naproxen Dextrorotatory drug and if re- 6-desmethyl Used in acute

CH–COOH places COOH by OH/CHO, retains Naproxen gout also
activity. (inactive)
CH3
MeO

(4) Aryl and Hetero aryl acetic acid derivative:

Sr. no Drug Characteristic Metabolism Side effects

1 Diclofenac sodium It decreases – Acidity

CH 2 COONa arachidonic acid
level in leuko-
cyte.
NH It raises lithium
Cl Cl and digoxin level
in plasma.

2 Aciclofenac It is prodrug of – –
CH2-CO-CH2-COOH O diclofenac.

OH
Cl O
H
N O

Cl
3.208  Chapter 5

Sr. no Drug Characteristic Metabolism Side effects

3 Ketorolac It contains pyrol- Used in Glucuronida-

lidine ring. migraine tion

4 Tolmetin It is pyrole acetic Oxidation

acid derivative. (diacid) (in-
active)

(5) Enolic acid derivative/Benzothiazine derivative: (6) Aniline and p-Aminophenol derivative:
General structure: General structure:
R NHCOCH3
CO–NH–R'

N R''
S
O O
OR
yy Common side effect: Peptic ulcer, toxicity.
Sr. Name of R Characteristics Metabolism
Sr. Name of R R′ R″ Characteris- no drug
no drug tics
1 Phenacetin C2H5 Prodrug of O-dealkylation
1 Piroxicam OH CH3 Long acting paracetamol
Half life (45h)
Used in 2 Paracetamol H Cause It forms N-
N acute gout. hepatotoxicity, acetyl p-ben-
thrombocyto- zoquinone (at
2 Isoxicam OH CH3 CH3 penia, anaemia toxic dose)

(7) Pyrazole/Pyrazoline derivative: (potent analgesic

N O and antipyretic)
yy Antipyrine (phenazone): Use as analgesic in otic
3 Meloxi- H N H preparation.
cam yy Aminopyrine
S CH3 yy Analgine (Metamizol)
yy Common side effect: Agranulocytosis
(8) Indole acetic acid derivatives

Sr. no Structure and name of drug Characteristics Side effects

1 Indomethacin S (+) is active and given as IV in infants. Leukopenia

CH2 –COOH p-Anisidine Hallucinogen
MeO (p-methoxy aniline) is used as starting Psychosis
material for synthesis.
CH3 Contraindicatd in epilepsy, pregnancy.
N
C=O

Cl
 Medicinal Chemistry  3.209

Sr. no Structure and name of drug Characteristics Side effects

2 Sulindac It is prodrug (half life is 8 h) by reduction Diarrhoea

to form sulfide metabolite which is active.
CH 2 COOH (half life is 16.4 h).
F
It is contraindicated with aspirin because
CH 3 of decrease in sulfide blood level.

CH

CH 3 SO

(9) 3, 5 pyrazolidinedione derivative.

Sr. no Structure and name of drug
yy Example is Phenylbutazone
2 Rofecoxib
C 4 H9 O
SO2

N C 6 H5
O N C6 H5
C 6 H5
O O
yy Metabolism: By hydroxylation form, oxyphenyl-
butazone (active). (B) Second generation drug/Isoxazole derivative:
yy Side effect: (1) Agranulocytosis (2) Aplastic
anaemia (3) Bone marrow depression (4) Steven General structure:
Jhonson syndrome (5) With salicylate black stool
O
form. H3C N
(10) Nefopam: It is a recently introduced drug which does
not inhibit prostaglandin synthesis and as potent as
morphine. R-NH2-SO2-C6H5 C6H5
(11) Selective COX-II inhibitors: It is potent NSAIDs.
(A) First generation drugs: Sr. no Name of drug R Characteristic

1 Valdecoxib H
Sr. no Structure and name of drug
2 Paracoxib –COC2H5 It is given parentrally.
1 Celecoxib
CH3
(C) Third generation drug:
Example: (1) Etocoxib (2) Lumaricoxib.

Note: All selective COX-II inhibitor cause CVS toxicity.

N C6 H5 (12) Miscelleneous:
CF3 N
Example: (1) Nimesulide: It is aryl sulfonamide derivative.
3.210  Chapter 5

NH-SO2 -CH3 B. Fluorobutyrophenone derivative (General structure)

R
O F C-CH2-CH2-CH2 N
R'
O
O2N
Sr. Name of R R′
Anti-Psychotic drugs (neuroleptic, major no. the drug
tranquillizer)
1 Halopridol OH Cl
Classification
1. Typical antipsychotic drugs
A. Phenothiazine derivative CF3

General structure: 2 Trifluperi- OH

dol
S
3 Droperidol Contain fused benz-
imidazolinone.
N R'
(C) Thioxanthene derivative:
CH 2 -CH 2 -CH 2 -R
Example is Thiothixene having Z isomer which is clinically
Aliphatic side chain contain drug: active.

Sr. no Name of the drug R R′ S

1 Chlorpromazine N–(CH3)2 Cl SO 2 -N-(CH 3)2

2 Triflupromazine N–(CH3)2 CF3 CH-CH 2 -CH 2 N N CH 3

Piperidine side chain drug:

(D) Dibenzoxazepine derivative: (General structure)
Sr. no Name of drug R R′

1 Thioridazine SCH3 O
Cl

--CH 2 CH 2 N
N
N
Piperazine side chain contain drug:
Sr. no Name of drug R R′
N
1 Trifluperazine N N CF3 R
CH3

Sr. no Name of drug R

2 Prochlorpera- N N Cl
CH3 1 Loxapine CH3
zine
2 Amoxapine H
3 Perphenazine N N CH 2 -CH 2 -OH Cl
B. Atypical antipsychotic:
4 Fluphaenazine N N CH 2 -CH 2 -OH CF3 Dibenzdiazepine derivative: Clozapine which is selective
D2 and 5-HT2a blocker
 Medicinal Chemistry  3.211

Side effect:
N
Cl yy Gum hypertrophy
yy Megaloblastic anaemia
yy Osteomalacia
N
yy Hyperglycemia
N
Use: In all type of seizures except petit-mal type.

N B. Succinimide derivative:

CH 3 General structure:
R'
Dibenzthiazepine derivative: Metiapine, Clothiapine,
quetiapine. R''
O N O
S
R R

N Sr. no Name of the drug = R″ R′ =R

N 1 Phensuximide C6H5 H CH3

2 Methsuximide C6H5 CH3 CH3

N 3 Ethosuximide C2H5 CH3 H
CH3
yy Side effect: Bone marrow depression.
Clothiapine: R = Cl yy Use: Specifically in petit-mal seizure.
Metiapine : R = CH3 yy Mechanism of action: They block T-type calcium
• Indole derivative: Molindone, Sertindol, oxypertine. channel.
• Benzoquinoline derivative: Tetrabenazinre C. Oxazolidinedione derivative: General structure
• Fluorobutyrophenone derivative: Risperidone
• Benzodiazepine derivative: Olanzapine R'
O
R''
5. Anti convulsant O N O
A. Hydantoin derivative CH3
General structure:
Sr. no Name of drug R′ R″
R' H
N 1 Trimethadione CH3 CH3
R''
2 Paramethadione CH3 C2H5
O N O
R Metabolism: By N-demethylation trimethadione converts
into dimethadione which is T-type calcium channel blocker.
Sr. no Name of drug = R″ R′ =R
D. Iminostilbene derivative or urea derivative.
1 Phenytoin C6H5 C6H5 H Example is Carbamazepine
2 Mephenytoin C6H5 C2H5 CH3

3 Ethotoin C6H5 H C2H5

N
Mechanism of action: It blocks sodium channel.
Metablosim: Hydroxylation CO–NH2
3.212  Chapter 5

Metabolism: Oxidation (10, 11 epoxide form) (active) but Sr. no Name of drug R R′
cause aplstic anaemia also.
Recently, Oxacarbazepine is used which contains oxo 1 Imipramine N (CH3)2 –
group at 10 position and no aplastic anaemia. 2 Triimipramine N (CH3)2, On C-2 of –
Propyl chain there
E. Aliphatic carboxylic acid derivative: Valproic
is a substitution
acid or Sodium valproate
of –CH3 (Methyl)
It is dipropyl acetic acid derivative which is used in pe- group
tit mal seizure.
3 Desipramine NH–CH3
F. Phenyltriazine derivative 4 Amitriptyline – N (CH3)2
Example is Lamotrigine which contains triazine ring. 5 Nortriptyline – NH–CH3
G. Benzodiazepine derivative: Clonazepam, Diaz-
epam, Clobazepam. yy Common side effect: Anticholinergic type, postural
hypotension.
H. Barbiturates yy Metabolism-By N-demethylation of imipramine to
Desoxybarbiturates: Primidone desipramine. (ACTIVE)
B. Selective serotonin reuptake inhibitors (SSRI)
I. Miscellaneous
yy Examples are Fluoxetine, Fluvoxamine, Citalopram,
yy Gabapentin: It is cyclic GABA analogue and block T- Sertaline, and Paroxetine.
type calcium channel. yy General plasma half life is 15–24 h except fluoxetine
yy Vigabatrine: It inhibits GABA transaminase (96 h)
yy Tiagabine: It is nipecotic acid derivative and inhibit yy Common side effect: Anorexia, Insomnia, Anorgasmia.
GABA reuptake. yy Interaction: Serotonin reaction with MAO.
yy Zonsamide and Topiramate: It is aryl sulfonamide C. MAO Inhibitor
derivative. MAO-A inhibitor is Anti depressant, MAO-B inhibitor is
yy Carbonic anhydrase inhibitor: Acetazolamide Anti pakinsonism
Classification:
Anti-depressent
1. Hydrazine derivative:
Classification Phenelzine
A. Tricyclic antidepressant: (Nor-adrenaline reup-
take inhibitor)
CH2-CH2-NH-NH2
i. Tertiary amine derivative: Imipramine, Trimipramine,
Amitryptyline, Doxepine Iproniazid
ii. Secondary amine derivative: Desipramine, Nortryp-
tyline, protryptyline, amoxepine, maprotiline
N CO–NH–NH–CH–(CH3 )2
General structure:
Nialamide
Isocarboxazide: It contains Isoxazole ring.
2. Cyclopropylamine derivative:
N yy Pargyline
yy Clorgyline
CH2-CH2-CH2-R yy Tranylcypromine
yy Selegiline (selective MAO-B inhibitor)

CH-CH-NH2

C
CH-CH2-CH2-R' H2
 Medicinal Chemistry  3.213

Side effect: SAR for Morphine like drugs

yy Cheese reaction General Structure
yy Postural hypotension.
16
D. Non-selective uptake inhibitor 17
N R
yy Venlafaxine 10 9 Tertiary
yy Duloxetine nitrogen
1 11 8
yy Hyperforin: Obtained from natural St Jhon’s wart. 15 Alicyclic
14
12 unsalurated linkage
Miscellaneous 2 7
yy Trazodone and Bupropion 13
yy Raboxetine: Selective NA reuptake inhibitor, and 3 5 6 Alcoholic
4 OH
causes anti cholinergic side effect. HO O hydroxyl group
yy Mirtazepine Ether bridge
Phenolic hydroxyl
Narcotic-analgesic (Opioid analgesic) group

yy The narcotic analgesics are also called as opiate The structural activity relationship is studied due to the
analgesics. These are mainly obtained from unripe modifications of the following parts of morphine.
capsules of papaver somniferum (Opium poppy) (1) Modifications on aromatic ring system
plant. The important alkaloid is isolated from opium is (2) Modifications on alicyclic ring system
morphine. The other alkaloids isolated from opium are (3) Modifications of tertiary nitrogen
codeine, Papaverine and thebain. (4) Modifications of ether Bridge
Classification I. Modifications on aromatic ring system
1. Morphine Analogues: yy An aromatic phenyl ring is essential for activity.
Morphine Sulphate, Codeine Phosphate, Ethyl Morphine, yy Modifications of C3 Phenolic hydroxyl group decreases
Diacetyl morphine (Heroin), Hydro morphoneHCl, Oxy analgesic activity.
morphone.HCl, Apo morphine.HCl, Hydrocodone, Oxy yy Making the Phenolic–OH group by etherification to
codone, Dihydromorphine, Dihydro codeine methyl ether (Codeine) and ethyl ether (ethyl morphine)
results in about one tenth of analgesic activity of
2. Morphinan Analogues: morphine. Because Phenolic –OH group binds with
Levorphanol tartarate, Dextro methorphan, Butorphanol opiate receptor by hydrogen bonding easily. But ethers
are not easily hydrolysed.
3. Morphan Analogues:
yy Esterification of 3–OH group gives compounds more
Metazocine, Cyclazocine, Pentazocine. active than morphine.
4. 4-Phenyl Piperidine Analogues: yy Substances other than 3-position in the aromatic ring
results in a reduction of opioid actions. But 1-fluoro
Meperidine.HCl (Pethidine.HCl), Di phenoxylate.HCl,
codeine possesses some analgesic activity as that codeine.
Fentanyl citrate, Anileridine.HCl, Phenoperidine, Alphap-
rodine.HCl, Loperamide.HCl. II. Modifications on alicyclic ring system
5. Phenyl propylamine Analogues: yy The C-6-α-OH group is methylated, esterified, oxidized,
removed or replaced by halogen in order to get more
Methadone.HCl, Dextro propoxyphene.HCl, Metho Trime-
potent analgesics. But there is also a parallel increase in
prazine.
toxicity. Example: Codeine, heroin, chloro morphone.
6. Miscelleneous: yy The saturation of double bond at C-8 position gives
Tramadol, Tilidate, Nexeridine, Sulfentanil. more potent compounds. Example: Dihydromorphine,
Dihydrocodeine.
7. Narcotic Antagonists: yy Introduction of 14 –OH in dihydro from gives more
Nalorphine, Naloxone, Levellorphan, Naltrexene, Cyclazo- potent 14–hydroxy dihydro codeinone and 14–hydroxy
cine, Propiram, Profadol dihydro morphinone.
3.214  Chapter 5

yy Bridging of C6 and C14 through ethylene linkage gives (1) Morphine like ring contains derivatives:
etorphine which is 200 times more potent than morphine. General structure
yy Introduction of any new substituents at 5th position
N R''
does not enhance the activity except 5–methyl dihydro
morphine and azidomorphines.
III. Modifications of 30 Nitrogens
yy Replacement of N–CH3 by N–C2H5 results in slight
fall in analgesic response. More hydrophobic groups
such as propyl, pentyl, hexyl and phenylethyl gives an OR O OR'
increase in activity.
yy N-allyl and N-cycloalkyl methyl functions gives the Sr. no Name of drug R R′ R″
narcotic antagonistic properties. 1 Morphine H H CH3
yy N-Phenyl ethyl group enhances the analgesic activity in
2 Codeine –CH3 H CH3
desmorphine, codeine and heterocodeine.
3 Heroin –CH3C –CH3–C CH3
IV. Modifications of Ether Bridge =O =O
yy Breaking of Ether Bridge and opening of piperidine 4 Pholcodeine H H O–CH2CH2–
ring decreases the activity. Morpholine
Mechanism of action 5 Nalorphine H H CH2–CH=CH2
The pharmacological actions of opiods are mediated by sev- 6 Naltrexone H H CH2–Cyclopropyl
eral types of opiate receptors in the CNS. 7 Nalbuphine H H CH2–Cyclobutyl
1. There are three major types of opiod receptors:
(i) Mu (m)–op3 receptors–produce analgesia, (2) Methadone derivatives:
respiratory depression, Euphoria and addiction. General structure:
(ii) Kappa (K)–op2 receptors–produce dysphoria,
Euphoria and addiction. R'''
(iii) Delta (d)–op1 receptors–G–proteins–linked
receptors. R'' C R
2. Morphine binds to m receptor and induces change in
shape and opens the ion channel in cell membrane. R'
So K+ ion can flow out of the cell, hyperpolarizes
membrane potential. Therefore the frequency of action Sr. no Name of drug R R′ R″ R′″
potential firing is decreased; resulting in a decrease in 1 Methadone C6H­5 C6H5 C=O– –CH2–CH
ion neuron excitability. C2H5 (CH3)–N (CH3)2
3. The increase in permeability decreases the influx of
Ca into nerve retinal and reduces neuro transmitter 2 propoxyphene C6H5 CH2– O– CH (CH3)–CH2–
release. Both the effects shut down the nerve and block C6H5 C=O– N (CH3)2
pain message. C2H5
4. Kappa receptor is directly associated with Ca channel.
(3) Meperidine derivatives:
When an agonist binds to K receptor, the Ca channel
is closed. Since Ca is necessary for neurotransmitter it General structure:
cannot pass on pain message. R4
5. When agonist binds with d (delta) receptor, the receptor
changes its shape and triggers a messenger protein (G R4 R3
protein) to carry a message to a neighboring enzyme
with catalyses the formation of cyclic adenosine
monophosphate. The G protein inactivates the enzyme N
R3 R6
by preventing the synthesis of cyclic AMP. This acts as
a second messenger is the transmission of pain signed
R1
and stops the pain.
 Medicinal Chemistry  3.215

yy All penicillins has Penam ring as a basic moiety.

Sr. no Name of drug R1 R3 R4 R′3 R′4
S
1 Meperidine CH3 H COOC2H5 H H
Penam Ring
2 Bemindone CH3 H COOC2H5 OH H N

3 Trimeperidine CH3 CH3 OCOC2H5 H H 1-Aza-4-thia-Bicyclo [3.2.0] heptane

Chemotherapy Classification
1. Fermentation derived penicillin
Antibiotics
b-Lactam Antibiotics-Penicillin and Me
S Me
Cephalosporin Penicillin R NH
It is obtained from Penicilin Notatum and Penicillin Chrys- N OH
ogenam. O
O
O
Ring A
R
6-APA H
Me
S Me Ring B Benzyl Penicillin (Pen-G)
R NH
N OH Phenoxy methyl CH2O
O penicillin (Pen-V)
O
O

yy Ring A is a four membered β-Lactam ring (cyclic am- 2. Semi synthetic penicillanase resistance
ide) penicillin: Parenteral Penicillin
yy Ring B is a five membered Thiazolidine ring E.g., Methicillin, Nafcillin
yy Degradation product of penicillin:
• At acidic pH-Penillic Acid Me
S Me
• At basic pH-Penicilloic acid R NH
yy Certain strands of micro organism destroy
N OH
β-Lactam antibiotics enzymatically like Penicilla- O
O
nase or β-Lactamase (Open the β-Lactam ring).
O
Stereochemistry and IUPAC of β-Lactam ring CH3O R

H H Me Methicillin
S Me
R NH
CH3O
N OH
O O
O
yy It has total three chiral carbon like 3, 5 and 6. Nafcillin
yy All synthetic and semi synthetic penicillin having same
absolute configuration (like 3S and 5R, 6R).
yy Acyl amino and carboxylic acid Trans to each other. C2 H5O
yy The lead molecule in the discovery of semi synthetic
penicillin is 6 amino penicillinic acid (6-APA). Methicillin-2, 6-Dimethoxy phenyl penicillin
yy 6-APA structurally derived from L-Valine and L-cysteine Nafcillin-2-Ethoxy-1-Napthyl-Penicillin
3.216  Chapter 5

3. Semi synthetic penicillanase resistance penicillin: Oral Penicillin

yy It contains isoxazole as a basic moiety.
yy 5-Hydroxy methyl penicillin derivative is a metabolite.
yy It is applicable to penicillin sensitive patients.
Me
S Me
R NH
N OH
O
O
O
R
CH3

Oxacillin O
N
Cl CH3

Cloxacillin O
N
Cl CH3

Dicloxacillin O
N
Cl

yy Oxacillin-5-Methyl-3-Phenyl-4-isoxazolyl penicillin
yy Cloxacillin-5-Methyl-3-(2-chlorophenyl)-4-isoxazolyl penicillin
yy Dicloxacillin-5-Methyl-3-(2, 6-di chlorophenyl)-4-isoxazolyl penicillin

Note
Extra halogen is responsible for increasing fraction bound to protein in the plasma potentially reduce the concentration
of free antibiotics in plasma and tissue.

4. Semi synthetic penicillanase sensitive Ticarcillin is an isoster of carbencillin, and it having

broad spectrum parental penicillin thiophene ring azlocillin.
(Anti psedomonal penicillin-Ticarcillin, Carbencillin) Me
S Me
Me R NH
S Me
Me
R NH S Me N OH
R O O
NH
N OH O
O N OH
O O
O O R
R O
R
COOH Mezlocillin CH-
COOH NH
Carbencillin CO
Carbencillin COOH O N
COOH
Ticarcillin N
Ticarcillin S SO2CH3

S Azlocilin: SO2CH3 is replaced by H.

 Medicinal Chemistry  3.217

Azlocillin and mezlocillin have Oxoimidazolidino yy Penicillin is unstable under acidic and basic condition so
basic moiety. manipulation of polar amide groups leads to increased
Piperacillin: has dioxo piperizine potency as well as chemical and physical stability.
yy Introduction of chemical inducer/precursor in culture
Me
S Me medium leads to increasing quantity as well as quality
R NH of penicillin production.
N OH E.g., phenyl acetic acid is added as a chemical inducer
O O in production of 6-APA.
O yy Some bacteria like gram negative bacilli are resistant
to action of penicillin due to production of β-lactamase
R
enzyme. So many semi synthetic penicillin were devel-
Piperacillin CH- oped by manipulation of C-6 polar amide group.
yy Increasing steric hindrance at α carbon of acyl group
NH increases resistance to staphylococcal β-lactamase like
CO substitution of Aromatic (Phenyl, Napthyl) ring or any
O N heterocyclic ring (Isoxazoyl-Oxacillin, Cloxacilln) or
ring substitution at ortho position (2, 6 dimethoxy
substitution on phenyl ring of methicillin) and (2 ethoxy
O N substitution on napthayl ring of Nafcillin).
SO2CH 3 yy Incorporation of an ionized/polar/acidic substitution on
α carbon of side chain of benzyl carbon atom of benzyl
SAR of penicillin penicillin increasing activity against gram negative bacilli.
yy All β-lactam antibiotics contain 4 membered β-lactam E.g., Ampicillin, Amoxicillin, Carbencillin
rings fused with N atom and tetrahedral carbon to a yy All natural penicillins are dextrorotatory.
second heterocyclic ring. Depot preparation of penicillin-having limited water
solubility and release drug over a longer periods.
Penicillin Thiazolidine
E.g., Procaine Penicillin-Amine salt of penicil-
(Penam Ring) 1 lin G with procaine
S Benzathin Penicillin
5 2
Hydrabamine penicillin
4 NH Mechanism of b-lactam antibiotics
3

Thienamycin b-lactam Pyrrolidine yy Inhibition of bacterial cell wall synthesis by inhibiting

(Carbapenam) the synthesis/production of peptidoglycan.
yy Cell wall of bacteria is essential for normal growth and
N development.
N
O yy Peptidoglycan is an essential constitutent of bacterial
cell wall, and it is a heteropolymeric components of
Clavulanic acid Oxazolidine
cell wall responsible for the providing stability.
(Oxapenam) O yy Glycan chain is made up of two alternating amino
N sugar (NAM-N-Acetyl muramic acid) and (NAG-N-
Acetyl Glucosamine) by peptide linkage.

Cephalosporin Dihydrothiazine
b lactam rings Name of ring Examples
(Cepham Ring) S
Penam Penicillin
N
R
COOH
3.218  Chapter 5

Cepham ring IUPAC-5-Thia-1-Aza-Bicyclo[4.2.0] Oct-

b lactam rings Name of ring Examples
2-ene
Cepham Cephalosporins yy Ring A is a four membered β-Lactam ring (cyclic
amide)
yy Ring B is a six membered Dihydrothizine ring.
yy Cephalosporin having cepham as a basic moiety
yy Like 6-APA in penicillin, 7-Amino cephalosporic
Cephem ..................... acid is a lead molecule for synthesis semi synthetic
cephalosporin
Carbapenam Thienamycin, yy Cephalosporin C-True cephalosporin or 7-ACA
Imipenam, yy Cephalosporin P-Acidic antibiotics or Steroidal
Meropenam
antibiotic (Fusidin)
Biapenam
yy Fusidin-It is sodium salt of fusidic acid.
Carbapenem (β lactamase yy Cephalosporin N-Derivative of 6-APA, Also
inhibitors) known as Synnnematin N now a days, it is known as
Penicillin N.
yy Semi synthetic cephalosporin prepared by modifica-
Oxapenam Clavunic acid
tion in
(β lactamase yy Acylation of 7-Amino cephalosporic acid.
inhibitors) yy Reduction of 3-Acetyloxy group.

Cephalosporic Acid (Cephalosporin C)

Penam-1, Salbactum, NH2 H H
1-Dioxide Tazobactam S O
HO NH CH2

O O N O
O
COOH
Monobactam Saulfazecin, Alfa amino adipoyl side chain
Aztreonam,
Tigemonam (If α Amino adipoyl side chain is removed from
(β lactamase Cephalosporin C by breaking of amide bond to structure
resistance agent) of 7ACA)

Macrolide Antibiotics
Cephalosporin
Sources: Actinomycetes
Source: Cephalosporium Acremonium
Common Structural features of Macrolide antibiotics
yy A many membered (12, 14 and16 atoms) lactone ring-
Ring A hence named Macrolide
yy Various ketonic and –OH functional group.
Ring B yy Glycosidically linked to 6-deoxy sugar
R2 NH S
Picromycin first identified drug of Macrolide
antibiotics.
O N R1
O yy E.g., Spiramycin, Oleanlomycin, Erythromycin
COOH yy Semi-synthetic derivative of erythromycin
 Medicinal Chemistry  3.219

• Roxithromycin Pharmacokinetic
• Dirithromycin
• Clarithromycin yy All macrolides are destroyed by acidic pH so it is
• Azithromycin always formulated in enteric coated tablet form.

Mechanism of Action Spectrum of Activity

yy It binds selectively to a specific site on 50S ribosomal
unit to prevent the translocation step of bacterial pro- yy Active against gm+ve cocci, bacilli and gm-ve cocci
tein synthesis. yy Also active against H.Influenza, mycoplasma pneumonia,
yy It does not bind to mammalian ribosomes. N.Gonorrhoea and legionella

Erythromycin-Streptomyces Erythraeus
Erythromycin
O
H3C CH3 C–6
OH OH H3C
H3C CH3
OH N – CH3
Aglycon Moeity HO
H3C
(14 atoms) O O Glycon part
H3C O
O O
CH3
CH3
O O – CH3
CH3
H3C
OH

Glycon Part

yy Commercial product is Erythromycin A which is yy Specifically used to treat Lyme disease caused by
different from Erythromycin B in having –OH group at Borrelia Burdorferi.
12 position of aglycon.
Azithromycin, prepared by Beckmann rearrangement of
yy Erythronolide-Aglycon part of Erythromycin
9-Oxime followed by N-methylation and reduction of re-
yy Glycon part-1. Basic ring-Desosamine 2. Neutral
sulting ring expanded lactam.
ring-cladinose
Nitrogen containing 15 membered rings Macrolide is
While in case of Erythromycin C, it has Mycarose as a known as Azalides.
neutral glycon part instead of Cladinose
yy It does not act as enzyme inhibitors (Cyto-P-450
yy It acts as Enzyme inhibitors (Cyto-P-450 oxidase) for oxidase) for other drugs.
other drugs. yy Removal of 9-keto group-increasing stability of
yy Like Theophylline, Hydroxy coumarine, Benzodi- azithromycin to acid catalysed degradation. These
azepine (Alprazolam, Midazolam), carbamazepine. change also increase lipid solubility.
Cyclosporine, Anti histaminic drugs
Dirithromycin-Having 9N, 11 O-Oxazine ring
yy While activity of terfenadine and astimizole is potenti-
ate by Erythromycin.
yy Stability of Erythromycin is at or neutral pH (7) Chloramphenicol
Clarithromycin-6-methyl ether derivative of Eryth- Sources: Streptomyces Venezuelae
romycin. (6-OH group is methylated to 6-OCH3). yy Broad spectrum antibiotic
yy It acts as Enzyme inhibitors (Cyto-P-450 oxidase) for yy Now a days, it is prepared by synthetic route from
other drugs. p-Nitro acetophenone.
3.220  Chapter 5

Acylamido Metabolism
propanediol Major route: Formation of 3-O-Glucrodination
side chain Minor route: Reduction of p-Nitro group to amino
OH Cl Mechanism of action: Inhibition of protein synthesis
H by binding with 50s subunits of ribosomes.
N Cl
O2N Use
O yy Meningitis
HO yy Active against gm+ve and gm-ve bacteria that is resis-
Chloramphenicol tant to PenicillinG and ampicillin.
yy Active against H.Influenza, S.Typhi, S.Pneumonia,
yy It has two chiral carbons, so a total of four (4) isomers
B.fragilis and N.meningitis
are possible D-erythro, L-erythro, D-threo and L-threo.
yy In UTI
yy Among these four isomers, D-threo isomer is
yy Rickettsial infections as “Rocky mountain Spotted
most active. The prodrug of Chloramphenicol viz.,
Fever”
Chloramphenicol palmitate (USP) which is a tasteless
product is intended for pediatric usage. Adverse Effect: Grey baby syndrom

Note
Chloramphenicol has a bitter taste so it is always available in Palmitate and Succinate ester form and acts as prodrug.

Aminoglycoside Aminoglycosides Obtained from

Chemically, it is aminosugar obtained from actinomyces.
Tobramycin Streptomyces tenebrarius
Classification: Gentamycin Micromonospora purpurea

Streptomy- Kanamycin Gentamy- Neomycin Neomycin Streptomyces fradiae

cin family family cin family family
Framycetin Streptomyces decaris
Streptomycin Kanamycin Gentamycin Neomycin
Paramomycin Streptomyces Rimosus
Dehydro- Amikacin Sisomycin Framycetin
Amikacin Semisynthetic derivative of Kanamy-
Streptomycin
cin A
It has 2 Tobramy- Netilmycin Paramo-
Netilmycin Semisynthetic derivative of Sisomy-
amino sugar cin mycin-Anti
cin
amoebic
agent Sisomycin
It has 2 It has 2
amino amino sugar
sugar Chemistry
Not given
parentraly,
yy Amino sugar linked glycosidically
is topically yy All have at least one amino hexose and some have a
applied pentose lacking an amino group (Streptomycin, Neomycin,
Paramomycin).
yy 1, 3-Diamino cyclohexane central ring present in
Aminoglycosides Obtained from Kanamycin, Neomycin, Gentamycin and Tobramycin.
Streptomycin Streptomyces Griseus yy All aminoglycosides are available in sulphate form.
yy They do not enter in CNS, bone or connective tissue
Kanamycin Streptomyces kanamyceticus because they exist as polycation at physiological pH.
 Medicinal Chemistry  3.221

Streptomycin Mechanism of action

HN
The aminoglycoside acts directly on bacterial 30s ribosomal
NH NH2 unit to inhibit the protein synthesis.
OH HN
H2N OH Adverse effect
NH Streptidine
O OH yy Ototoxicity
O yy Nephrotoxicity
L-Streptose yy Neuromuscular paralysis due to decrease ach release
OHC
HO O yy Allergic reaction
H3C
HO
O N-Methyl- Tetracycline
HO
NHCH3 L-Glucosamine yy Carbon atom 4, 4a, 5, 5a, 6 and 12a are potentially
OH
chiral.
yy Oxytetracycline and doxycycline each with 5α-OH
Streptomycin substituents have six asymmetric centres while others
yy On acid hydrolysis, Streptomycin yields Streptidine have only five asymmetric centres.
and Streptobiosamine (L-Streptose and N-Methyl-L- yy The basic ring present in Tetracycline is polycyclic nap-
Glucosamine) thacene carboxamide.
yy Streptomycin A having D-ribose and Streptomycin B yy All Tetracycline are amphoteric in nature.
having mannose sugar part. yy At pH-7, it is converted into Zwitterion.
yy Ability to undergo epimerization at C-4 in solution of
Neomycin neutral pH range (7).
yy It does not having anti-.bacterial but anti fungal activity. Me
Me
yy Basic Structure: Neosamine C----Deoxystreptamine---
D-Ribose------Neosamine C R1 R3 N
R2 H H H
Paramomycin OH

yy Basic structure: D-glucosamine----Deoxystreptamine

-----D-Ribose------Neosamine B/C NH
yy It is structurally similer to neomycin.
yy Used in GIT infection by salmonella and anti amoe- OH O
bic agent. OH O OH O

Tetracyclin
Amikacin
Acylation of 1-amino group of deoxystreptamine ring of
Kanamycin A with L-Amino hydroxyl butyric acid. Me Me
R1 R3 N
Gentamycin R2 H H
H
OH
Basic structure: Purpurosamine---Deoxystreptamine-
--Gasosamine
Used in Tularemia a lymphoid disease. NH

Netilmycin OH
OH O
Chemically it is 1-N-ethyl sisomycin. O OH O
Epi tetracyclin
Anti Bacterial Spectrum
yy Broad spectrum antibiotics yy Tetracycline forms chelate complex with many metals
yy Effective on Aerobic gm-ve bacilli and Aerobic gm+ve like calcium, magnesium and iron. Chelates are usually
and gm–ve cocci insoluble in water which impaired absorption of tetracycline
yy Anerobic bacteria are resistant to aminoglycoside. in presence of milk, Ca, Mg and Al containing antacids.
3.222  Chapter 5

yy Affinity of tetracycline for calcium causes them to be Me Me

incorporated into newly forming bones and teeth as R1 R4 N
tetracycline-calcium orthophosphate complex. R2 R3
H H
yy Deposition of these antibiotics in teeth causes yellow OH
discoloration. H
yy In pregnancy, Tetracycline is distributed into milk of N R5
lactating mother and it crosses the placential barrier
into fetus causing harmful effect on bone and teeth of OH O
child. OH O OH O

Name R1 R2 R3 R4 R5 Source

7-Chlorotetracyclin Cl CH3 OH H H S.aureofaciens

Oxyetracyclin H CH3 OH OH H S.rimosus

Doxycyclin H CH3 H OH H Semisynthetically from Oxyetracyclin

Tetracyclin H CH3 OH H H Semisynthetically from 7-Chlorotetracy-

clin

Demeclocyclin Cl H OH H H Mutant strain of S.aureofaciens

Methacyclin H =CH2 OH H Semisynthetically from Oxyetracyclin

Minocyclin N (Me)2 H H H H Semisynthetically from Oxyetracyclin

Rolitetracyclin H CH3 OH H X Semisynthetically from tetracyclin

Lymecycline H CH3 OH H Y Mannich base of tetracyclin

3. Novobiocin
X= CH2 N yy Source: S.Niveus
yy The structure contains substituted benzoic acid, Cou-
Y= – CH2
marin and sugar part.
NH CH (CH2)4 NH2
yy Glycon part is Noviose
COOH yy Aglycon part is Novobiocic acid
4. Fosfomycin
Miscellaneous Class Antibiotics
yy Source: S.fradie
Lincomycin and clindamycin yy Synthetically, it is derivative of Phosphoric acid.
yy Source: S.lincolnensis yy Mechanism of action: Interferes in first step in bacte-
yy Sulphar containing antibiotics rial cell wall.
yy It acts on 50s ribosomal sub unit. yy It is having an epoxy ring in its structure.
yy It having pyrrolidine ring attached with sugar part.
2. Polypeptide Antibiotics Anti amoebic agent
yy Source: Bacilli Species Amoebiasis: It is an infection of the mucous membrane
of the large intestine where “Entamoeba Histolytica” is a
yy Anti TB antibiotics-Capreomycin, Viomycin
causative organism.
yy Anti tumor antibiotics: Bleomycin, Actinomycin
yy Glucopeptide: Vancomycin Classification:
yy Others: Polymixin, Bacitracin, Colistin (1) Luminal Amoebicides
yy All are in cyclic nature (except: Gramicidine) yy Effective for organism presents in bowel lumen.
 Medicinal Chemistry  3.223

yy It is very effective because of poor oral absorption, so Drugs R1 R2

drugs remains in intestine for a long time.
Metronidazole –CH3 –CH2CH2OH
e.g., Diloxamide Furoate, Teclozan, Etofamide
Tinidazole –CH3 –CH2CH2SO2C2H5
Timorazole H
O N–CO–CHCl 2 –CH2CH 2 N O
O Dichloro
O CH 3
acetamide
chain Morpholine Ring
Furan ring

yy It is a prodrug, dichloro acetamide derivative used to Mechanism of action: –NO2 group participates in en-
treat chronic amoebiasis. dogenous reduction as an electrone acceptor. Since its redox
potential is lower than protein (Ferredoxin) which is found
yy Adverse effect: Urticaria, Pruritis, Flatulence
in anaerobic organism, so nitro group is reduced and reduced
form of metronidazole interferes in carbohydrate metabo-
8-Hydroxy quinolines Derivative
lism and nucleic acid synthesis.
yy Example, Di-iodohydroxyquin (Iodoquinol), Iodochlo-
yy Antibiotics are not used alone, they are always used
rohydroxyquin (Clioquinol)
along with other amoebicidal agent.
yy All are halogenated 8-Hydroxy quinolines derivatives
yy Except Paramomycin, all antibiotics exert an indirect
I trophozoitocidal action.
Carbarsone:
Oxine
Quinophenol yy It is an organic arsenical compound used in treatment
Oxyquinoline of acute and chronic amoebiasis.
I N
Mechanism of action: Anti amoebic agents due to
OH the presence of arsenic metal in their structure, exert
Iodoquinol amoebicidal action by non-specifically inactivating the
enzyme containing –SH (Sulfhydral) group.
Adverse effect: Optic neuropathy
Glycobiarsol: A bismuth salt of phenyl arsenic acid.
Contraindication: Drug therapy increases plasma io-
yy It is least favoured due to toxicity.
dine level. This agent must be used with caution in patients
hypersensitive to iodine or with thyroid dysfunction. Systemic Amoebiasis
Mechanism of action: It kills trophozoites and cysts in E.g., Metronidazole, Tinidazole, Chloroquin, Emetine and
intestinal tract by chelating ferrous ion which is essential Dehydroemitine
for protozoal metabolism. Emetine -It is an alkaloid obtained from the roots of Ip-
Adverse effect ecac plant (Cephalis ipecacuanha).
Blurred vision, Optic neuropathy, Peripheral neuropathy Dehydroemitine -It is synthetic analog of emetine, hav-
2) Luminal Trophozotocidal Agents: ing better activity than emetine.
They attack on intestinal trophozoites and are effectively Mechanism of action: It affects the protein synthesis
used to treat invasive intestinal amoebiasis. by inhibiting translocation of the peptidyl-t-RNA on ribo-
E.g., Metronidazole, Tinidazole-Nitroimidazole dérivatives somes resulting in the inhibition of polypeptide side chain.
Antibiotics –Tetracycline, Erythromycin, Paramomycin Miscellaneous Agents
R1 E.g., Chlorbetamide, Chlorphenoxamine, Phanquone

R2 N Anti Malarial Agents

lmidazole Ring Malaria in humans is caused by the infection with protozoa
N parasites of the genus plasmodium. These parasites spend an
NO2 asexual phase in man and sexual phase in female anopheles
3.224  Chapter 5

mosquito. Out of several hundred known anopheles species, Adverse Effects

the four species, the which infect the man are: yy Cinchonism, Nocturanal leg cramps
yy Plasmodium Falciparum yy High dose of quinine may produce a quinidine like
yy Plasmodium Vivax depressant effect on heart cause vasodilation and may
yy Plasmodium Malariae produce hypotension.
yy Plasmodium Ovale SAR
yy 2° Alcohol in the structure of quinine alkaloids is
Classification responsible for the activity, R1 (–OCH3) and R2
1. Quinoline Derivative (–CH=CH2) group not responsible for activity.
Cinchona alkaloids yy Quinine antagonizes the action of physostigmine on
skeletal muscle by exerting Curare like effect.
E.g., Quinine, Quinidine, Cinchonine, Cinchodine
yy Due to low therapeutic index, it is not used alone and
2° alcohol is always used in combination (Primaquin, Pyrimeth-
H amine and Sulphonamide)
Quniclidine 4-Amino quinoline derivatives
HO C N ring E.g., Chloroquine, Hydroxychloroquine, Amodiaquine
R1 R2 NHCH(CH3)CH 2CH2CH2N(C2H5)2
4-Quinoline

N
4-Quinoline
Drugs R1 R2 Optical Absoluate Cl N
isomer configuration
(d/l) (R/S) Chloroquin
Quinine –OCH3 –CH=CH2 l (–) S Mechanism of action: It is concerted in parasitized red
cells where it binds to double strand DNA. This results in
Quinidine –OCH3 –CH=CH2 d (+) R
inhibition of DNA and RNA polymerases function.
Cinchonine H –CH=CH2 d (+) S yy It is used for treatment of all types of malaria except
Cinchodine H –CH=CH2 l (–) R “Chloroquin resistance plasmodium falciparum”.
SAR: 7-chloro, 30 Amine and amino alkyl side chain is
All four derivatives of 4-Quinoline methanol which required for activity
are linked with a substituted quinclidine moiety.
Quinine (l-isomer) having anti-malarial activity while Metabolite: Desethyl chloroquin, Bidesethyl chloroquin
it’s d-isomer Quinidine having anti arrythmatic agent. Adverse effect
Quinine-Most active ingredients (5%) of cinchona yy Bone marrow depression, Ratinopathy
bark yy Hemolysis in patients with glucose-6-phosphate dehy-
yy It has schizonticidal and gametocidal for Plasmodium drogenase deficiency
vivex species. yy Photo allergic dermatitis since it accumulates into the
yy SC and IM injection form is not used due to local tissue skin
damage.
Amodiaquin
yy Many a times, it is administered with pyrimethamine,
sulfadoxine, doxyclcline or mefloquin. Mechanism of action: Ferriprotoporphyrin IX, which
yy It is affected against erythrocytic Merozoites. is released by plasmodium containing erythrocytes acting
yy It is used in chloroquin resistance plasmodium falciparum as chloroquin receptor. The combination of Ferriprotopor-
infection. phyrin IX and chloroquin cause lysis of parasite’s and/or
yy High dose of quinine may cause quinidine, like depres- erythrocyte membrane.
sant effect on heart causes vasodilation and may causes yy The quinone imine system is similar to the acetamino-
hypotension. phen toxic metabolite.
 Medicinal Chemistry  3.225

Hydroxychloroquin:-OH group on ethyl group of MeO

diethyl amino group.
4-Quinoline
8-Amino quinoline
E.g., Primaquin, Pamaquin, Quinocide-having asymmetric N
center in their structure but Pentaquin does not have it.
Adverse effect R
yy Hemolytic anemia *
R = -NH-CH-CH2 -CH2 -CH2 -NH2 Primaquin
yy Leucopenia
yy Methemoglobinemia CH 3
Metabolite *
R = -NH-CH-CH 2 -CH 2-CH2 -N(C 2H5)2 Pamaquin
5-Hydroxy primaquin and 5-Hydroxy 6-desmethyl primaquin
Mechanism of action: Interferes in protein synthesis CH 3
with enzyme and with erythrocyte phospholipids metabo- *
R = -NH-CH 2-CH 2-CH 2-CH-NH 2 Quinocide
lism in parasite.
yy Primaquin inhibits gametocyte stage, leavo isomer is CH 3
less active than dextro isomer.
2. 9-Aminoacridines derivatives
Quinacrine, Acriquin, Aminoacrichin
R9
MeO R2

Acridine Ring

N Cl
*
R = -NH-CH-CH 2 -CH 2 -CH 2 -N(C 2 H5 )2 Quinacrine

CH 3
*
R = -NH-CH 2 -CH 2 -CH 2 -CH 2 -N(C 2 H5 )2 Acriquin

R = -NH-CH-CH 2 -CH 2 -CH 2 -NH2 Aminoacridine

CH 3
Quinacrine, Pamaquin and Chloroquin having similer side
chain

yy They all have acridine ring in their structure. 3. 2, 4-Diaminnopyrimidine Derivative

yy Yellow pigmentation of skin and yellow colour appears yy Pyrimethamine, Trimethoprim
in the urine along with acridine dye. yy Used in exoerythrocytic and erythrocytic phase of disease
Adverse effect: Mechanism of action
yy Aplastic anemia It causes selective inhibition of the protozoal enzyme
DHFR (Dihydro folate reductase) to disturb the protozoal
Mechanism of action: DNA synthesis and finally death of Protozoal cells.
yy It acts at many sites within the cells including intercala- SAR points
tion of DNA strands • Electron donating group at C-6 position
yy It is tumorigenic and mutagenic in nature and used as • Cl at Para position
sclerosing agent. • Two rings are not separated by carbon atom.
3.226  Chapter 5

Pyrimethamine: Used in chloroquin resistant falciparum Doxepine ring

malaria CH 3
NH2
N O
H3 C
H2 N Cl O
Endoperoxide O
N H H
linkage
CH 2 CH 3 O
Pyrimethamine CH 3
OMe
N O
Artimisinin
H2 N CH 2 OMe
yy Artemether and artemotil are oil soluble/non-polar
N
methyl/ethyl salt of artimisinin.
Trimethoprim OMe
yy Artesunate is water soluble/polar hemisuccinate salt of
4. Bigunides Artemisinin.
yy It is a prodrug and is not active until it is not metabo-
lized in-vivo to dihydrio triazine. Anti Fungal Agent
yy Prongunil (Chloroguanil) is metabolized to active Classification
triazine ring having anti malarial activity. 1. Inhibition of fungal cell wall synthesis:
5. Atovaquone: It is napthoquinone derivative used in E.g., Capsofungin
combination of prongunil administered in ratio (2.5:1)
2. Bind to fungal cell membrane ergosterol
Mechanism of action: It interferes with deoxythymi-
dylate synthesis by inhibiting dihydro folate reductase en- E.g., Amphotericin-B, Nystatin, Natamycin-Polyene
zyme. Antibiotics

6. Sulphone and sulphonamide yy As the name indicates; Polyene, so the structure con-
tains many double bonds.
yy Long acting sulphonamide used in combination with
Pyrimethamine/Trimethoprim. yy A series of –OH group on acid derived portion of the ring.
E.g., Dapson yy A glycosidically linked deoxyaminohexose called
Myosamine.
7. Miscellaneous yy 28 membered polyene antibiotics: Natamycin (Pentene-5
yy Mefloquin double bond)
yy Antibiotics: Doxycycline, Clindamycin, lincomycin, yy 36 membered polyene antibiotics: Nystatin (Hexene-
Chloramphenicol Six double bond, Amphotericin-B-Heptane-Seven
yy Halofantrine: It is phenanthrene derivative double bond)
yy Artimisinin: It is a natural product excreted from the
dry leaves of Artemisia anna. Amphotericin-B-“streptomyces nodosus”
yy Key structure to be “Trioxane” ring consisting endo- Side effect:
peroxide and doxepine oxygen. yy Nephrotoxicity
yy Artimisinin is reduced to dihydroartemisinin, having yy Hypokalemia
an asymmetric carbon forms. yy Pain at site of injection and thrombophlebitis
 Medicinal Chemistry  3.227

Cryptococcosis: Fungal inspection of CNS. Tolnaftate:

Drug Interaction yy It is thioester of β-Napthol. It inhibits Squalene
yy Flucytosin has synergistic action with Amphotericin B, Epoxidase enzyme.
because it facilitates the penetration of flucytosin
through fungal cell wall.
yy Aminoglycoside and other nephrotoxic drugs enhance N O
toxicity of Amphotericin B
yy Concomitant use of Diuretic should be avoided. S
Nystatin:-“streptomyces noursei”
Aglycon part of nystatin is known as Nystatinolide and 4. Inhibition of ergosterol synthesis
glycon part is myosamine. Example, Miconazole, Clotrimazole, Ketoconazole, Fluco-
Natamycin:-‘streptomyces natalensis’ nazole, Itraconazole, Voriconazole
Basic moiety is imidazole, except Itraconazole and
3. Inhibition of ergosterol + lanosterol synthesis Fluconazole having two triazole ring.
E.g., Terbinafine, Naftifine, Butenefine.
Mechanism of Action: Azole group of antifungal
Mechanism of Action agent binds to fungal cytochrome P-450-dependant
Squalene Squalene 14α-demethylase enzyme that is responsible for the
Epoxidase Epoxidase
Squalene Squalene lanosterol demethylation lanosterol to ergosterol.
cyclase
Epoxide
Ketoconazole
Inhibit Lanosterol 14-Alfa
Squalene Demethylase Cis-2S, 4R is 4.5 times more active than 2R, 4S
Epoxidase
Drug Interaction: H2 receptor antagonist and anti cho-
linergic agents that inhibit gastric secretion and interfere
Naftitin and Terbinafine with its oral absorption.
Ergosterol
Amphotericin B and Ketoconazole antagonize each
other.
Fluconazole: Inhibits cyt-P-450 oxidase causes increase
in plasma level of cyclosporine, Phenytoin, Oral hypogly-
CH 3 caemic agent (Tolbutamide, Glipizide, Glyburide)
H
N Allyl amine 5. Inhibition of nucleic acid synthesis
+ group
Flucytosine
NH2
F
N
Naftifine
Allyl amine derivative: Terbinafine, Naftifine O N
yy Tolnaftate is not allyl amine but inhibits the squalene
epoxidase, that is why it is considered under allyl amine H
group. 4-amino-5-fluoro-2(1H)-pyrimidone
yy Terbinafine is more potent than Naftifine, and also has
oral activity against onychomycosis (Ringworms of yy Orally active antifungal agent.
nails). yy Used for the infection of candida and cryptococcus.
3.228  Chapter 5

Mechanism of Action: Causative Organism: Mycobacterium Tuberculosis

Active transport Classification
with Pyrimidine First Line Agent Second Line Agent
Pyrazinamide p-Amino salicylic acid (PAS)
Rifampicin Capreomycin
5 Flucytosine 5 Flucytosine(In) Isoniazide Cycloserine
(Out) Streptomycin Ethionamide
Reaction catalysed Ethambutol Prothionamide
by Cytosine Macrolide antibiotics
deaminase Fluoroquinolones

Isoniazide: (INH)
Enter into pathway RNA & 5 Fluoro uracil
DNA synthesis. yy It is hydrazide of iso nicotinic acid.
yy Structure of INH is similer to Pyridoxine (Vit B6).
yy Bacteriostatic in action
Mechanism of action
causes faulty RNA synthesis cause cell death
INH inhibits Mycolase Synthase, an enzyme necessary for
Adverse Effect: Bone marrow depression leading to the biosynthesis of mycolic acid (essential constitute of
leucopenia and thrombocytopenia. mycobacterial cell wall).

6. Disruption of mitotic spindle and inhibition of O C–NH–NH2

fungal mitosis.
E.g., Griseofulvin Pyridine ring
yy It is obtained from Fungus Penicillium Griseofulvum.
yy It has Benzofuran derivative. N
Use: Ring worm infection of body, hair, feet and nails Isoniazide
caused by species of dermatophytic fungi including tricho- Metabolism: N-Acetylation, depends upon transfer of
phyton, Epidermophyton. acetyl group from coenzyme A by N-Acetyl transferase.
yy Fungistatic agent Rate of acetylation is genetically controlled.
yy Allergic reaction: Rash, urticaria, Git upset
7. Miscellaneous agents: Ciclopirox, Haloprongin, Patients
Undecylenic agent
8. Topical agents for dermatophytosis
Keratolytic agent: salicylic acid, α-Hydroxy compound
yy Adult have an acidic, fatty substance in or on the skin
known as Sebum which having anti fungal activity. So
that’s why, fatty acids like propionic acid, undecylenic Slow Acylator Rapid Acylator
agent, Triacetin is used as anti-fungal agent. yy Rate of INH metabolism is slow
yy Whitfield Ointment: 6% Benzoic acid + 3% Salicylic yy Prolong plasma level of INH
acid.
Acetyl hydrazine: Toxic metabolite of INH which is
responsible for hepatotoxicity.
Anti-Tuberculosis Agent
Tuberculosis: It is a disease of respiratory transmission. Adverse Effect
A person gets infected when he comes in contact with the yy Peripheral Neuritis-Co administration of Pyridoxine (Vit
environment contaminated with viable tuberculi bacilli. B6) with INH prevents the symptom of peripheral neuritis.
It spreads through coughing, sneezing and shouting of yy GIT disturbance (Constipation, Loss of appetite)
infected person. yy Hepatotoxicity
 Medicinal Chemistry  3.229

yy Dryness of mouth (xerostomia) than 9 months can cause Reterobulbar Neuritis-

impairement of visual activity and red green colour
Drug Interaction
discrimination.
yy Antacid (Aluminum Hydroxide)-Inhibits the absorption yy Ethambutol decreases renal excretion and it may
of INH. produce gouty arthritis.
yy PAS-Inhibits metabolism. yy Contraindicated in pregnancy and children below
yy INH also inhibits the metabolism of Phenytoin and 2 years.
carbamazepine. yy Monthly eye examination of patient is necessary when
Stereptomycin-Aminoglycoside antibiotic patient is treated with EMB.
yy Bacteriostatic in action Rifampicin
yy Used always in combination yy It is orally active bactericidal semi synthetic derivative
yy Nephrotoxicity and ototoxicity are major side of rifamycin B.
effects. yy It is obtained from Streptomyces mediterranei.
yy Sterptomycin resistance strain treated with kanamycin yy It is also known as Ansamycin antibiotics.
and viomycin.
Mechanism of action
Ethambutol/EMB/Myambutol
yy It strongly binds to the β subunit of bacterial ‘DNA
Ethambutol dependent RNA polymerase’ enzyme. Thereby inhibits
the RNA synthesis of bacteria. Mammalian RNA poly-
CH2OH CH2OH
merase does not bind to rifampicin.
Adverse effect
C2H5–CH–NH–CH2–CH2–NH–CH–C2H5
* * yy Hepatitis-risk may increase when used in combination
ETHYLENE-DIAMINO-DI-1-BUTANOL with INH.
yy Flu like syndrome characterized by fever, chills, myal-
gias and thrombocytopenia.
yy Activity of EMB is streospecific, dextro isomer having
maximum activity than leavo form. yy Rifampicin imparts a harmless red orange colour to
yy It has two chiral centres. urine.

Mechanism of action Drug Interaction

yy It inhibits “Arabinosyl transferase enzyme” to prevent po- yy Rifampicin has enzyme induction property hence ac-
lymerization of arabinoglycan in mycobacterial cell wall. celerates the metabolism of several drugs like oral
yy Ethambutol if used in dose of 25 mg/kg/day for more contraceptive, anti-coagulants and protease enzyme.

Metabolism routes of RMP

Rifampicin

Hydrolysis Deacetylation Oxidation Demethylation

(3-formyl RMP N-demethyl RMP
(25-deacetyl RMP)
rifamycin)

Active Principle
Metabolite Metabolite
3.230  Chapter 5

Pyrazinamide: (PZA) yy Because of sour taste and irritant nature, this drug is
mainly used in form of its Na+, K+ and Ca+ salts.
O Mechanism of action: Same as sulphonamide
N
NH Adverse effect
Pyrazine
yy Crystalluria
ring N yy Lupas like syndrome
Pyrazine carboxamide yy GIT irritation
yy It is pyrazine analog of nicotinamide. Thiacetazone
yy Principle metabolite is Pyrazinoic acid (Active metab- Thiacetazone
olite) and 5-Hydroxy pyrazinoic acid.
NH 2
H
Mechanism of Action C NHCOCH
yy PZA enters the cell wall of M.tuberculosis via passive S N N
diffusion and it is converted to pyrazinoic acid (Active H
metabolite) by pyrazinamidase enzyme. Then later it Chemically, it is thiosemicarbazone derivative.
inhibits myco bacterial fatty acid synthase-I enzyme
Cycloserine
and disturpts mycolic acid synthesis needed for myco-
bacterium cell wall synthesis. Cycloserine
H2N
Second line Agent
3-Isoxazolidone basic moeity
Ethionamide O
O N
S
H
C–NH 2 yy Analog of D alanin
yy Chemically, D-4-amino3-isoxazolidone.
yy Broad spectrum antibiotics.
yy Steriochemically similar to D-Serine.
N R
Adverse Effects
R = –C2H5 = Ethionamide-2 ethyl thiosonicotinamide yy Peripheral Neuritis
R = –C3H7 = Prothionamide-2-propyl thiosonicotinamide yy Tremors
yy Prothionamide/Ethionamide are congeners of thionico- yy Psycotic
tinamide. yy Behavioral changes
yy It is also known as Thioamide analog of Isoniazide. Capreomycin and Viomycin: Peptide Antibiotics
Mechanism of Action yy Both antibiotics are basic peptides in nature.
yy Capreomycin-Streptomyces capreolus
yy It may interfere in peptide synthesis by acting as antime-
yy Viomycin-Streptomyces pumilus
tabolite and inhibiting the incorporation of sulfur (-SH)
yy Capreomycin is more potent and less toxic than
containing amino acid. (Cysteine, methionine)
viomycin.
p-Amino Salicylic acid: (PAS) yy Nephrotoxicity, skin rashes and ototoxicity are major
side effects.
COOH
OH Anti Leprotic Agent
yy Leprosy is a chronic disease caused due to acid fast
bacilli which produce nodules in the skin and loss of
sensation in affected region.
NH2 yy It is also known as Hansen’s disease.
 Medicinal Chemistry  3.231

yy Lepra reaction-It is hypersensitivity reaction not occuring yy It is orally active phenazine dye with bactericidal action.
as a result of allergy to drug but they should considered yy The imino group directly attached with phenazine ring
as allergic reaction to metabolite product of infected is known as Riminophenazine.
microorganism. yy Mechanism of action: Interfering with replication of
bacteria.
Types of leprosy
yy Used in dasone resistant leprosy.
1. Tuberculoid Leprosy: Presence of infection in restricted
area. Dapson treatment is required. Adverse effects
2. Lepromatous Leprosy: Infection is spread in wide yy Red brown discoloration of skin.
area of body, so multi-drug treatment is required. yy Abdominal pain with loose stool due to deposition of
3. Indeterminate Leprosy: It is the early stage of disease, clofazimine crystal in intestinal mucosa.
m.o are not multiplied to the extent to induce lepra yy Conjunctiva pigmentation
reaction. yy Photo toxicity
4. Borderline leprosy: Tuberculoid leprosy and Lepro- Antibiotic used in Leprosy
matous leprosy are two extreme forms of the disease.
All forms that lie in between these two forms is known yy Fluoroquinolone: Ofloxacin, Sparfloxacin
as borderline leprosy. yy Macrolide: Claritheomycin
yy Tetracyclin: Minocycline
Treatment
Chaulmogric acid
Dapson, clofazimine, Rifampicin, Thicetazone, Prothion-
amice, Ethionamide, Chaulmogric acid yy The oil of chaulmoogra and hydnocarpus are used since
ancient times in treatment of leprosy.
Cytotoxic antibiotics: Actinomycin, Mitomycin
yy The oil is extracted from the ripe seed of Hydnocarpus
Dapsone anthelmintica and Hydnocarpus heterophylla.
yy It contains Glycerides of chaulmogric acid and hydno-
yy Mechanism of action: It inhibits folic acid synthesis.
carpic acid.
yy Bacteriostatic in action.
Dapsone Chaulmogric Acid Hydnocarpic Acid
O
H2N S NH 2 (CH2 12 -COOH (CH2 10 -COOH
O
4,4'-Diamino phenyl sulfone
Anti Cancer Agent
yy It may produce methanoglobunaemia in person having
Glucose-6-phosphate defiance. Cancer: It refers to a disease of cells that show uncon-
yy Sulfone Syndrome-If dapson is used for more than two trolled proliferation, dedifferentiation, invasiveness and the
months. ability to metastasis (Spread to distal part of body).
yy Acedapsone: N-acetyl derivative of Dapson.
Causes of cancer
Clofazimine:
yy Exposure to carcinogenic hydrocarbon or excessive
Clofazimine radiation.
Cl yy Hereditary factors involved in chromosomal abnor-
malities, enzyme, defence mechanism, hormonal
imbalance.
CH3 yy Cultural factors: like diet, smoking, drinking, sexual
CH3 habits
N N yy Occupational Factors: including ionization radiation,
H
Phenazine chemicals and other carcinogenic substance like coal
ring N N tar, Mustard gas, chromium, Nickel and asbestos
H Cl yy Virus: can cause cancer in animal but not in humans.
3.232  Chapter 5

Tumor Classification
1. Benign Tumor: Slow growing, resembles to normal 1. Alkylating Agent
cell, remain localized and not harmful.
2. Malignant Tumor: Proliferate rapidly, Manifest A. Nitrogen mustard derivative
dedifferentiation, invasiveness-attacking to other cells. E.g., Cyclophosphamide, Chlorambucil
Ability to metastasis and damages to surrounding cells. Mechanism of alkylating agent

Cl
+

R N R N + Cl–
Cl Cl
3° Amine Cl
+ Ethylene R–N_
R N Iminium O
O H
N N
N N H
SN2
Cl N N NH2
N N NH2 ODNA O
ODNA O

ODNA
ODNA

yy The chemotherapeutic agent having the common Ifosfamide

properties of becoming strong electrophile through
formation of carbonium ion, which in turn reacts with 2 chloro ethyl CH 2CH 2Cl
nucleophile moiety of target molecule (DNA). substituton on N O
yy That means N-7 of guanine is particularly susceptible to rings N atom in P
the formation of a covalent bond with Alkylating agents. the structure of O NHCH2-CH2Cl
Mechlorthamine Cyclophosphsmide
Cl Melphalan: Phenylalanine analogues alkylating agent.
Busulfan: Alkyl Sufonate derivative
H3C N
_
yy Use: Chronic myelogenous leukemia
Cl yy Sulphar Stripping: In which interaction with Thio
(-SH) compounds such as Glutathion or cystein residue
results in loss of two equivalent methan sulfonic acid.
yy Effective in Hodgkin’s disease.
Adverse effect: Bone marrow depression and hair loss Chlorambucil
Cyclophosphamide: (Latent Drug)
ClCH2CH2
H
N CH 2CH 2CH 2COOH
N O
Oxaazaphospharine ClCH2CH 2
P
(Basic moeity) O N(CH2-CH2Cl)2
yy Adverse Effect: Dose related and rapidly reversible
yy Metabolite: Phosphoramide Mustard (Having Antitu- neutropenia.
mor activity) and Acrolein (Toxic to urinary bladder)
yy Acreloin toxicity is decreased by IV/Oral administration of Nitrosourea derivative
sodium salt of 2-mercaptoethane sulphonic acid (MESNA) Carmustine, Lomstine, Semustine, Chlorozotocin, Strepto-
yy Adverse Effect: Alopecia, Leukopenia zotocin
 Medicinal Chemistry  3.233

Carmustine: It crosses BBB, so it is used to treat brain Antagonist of metabolite involved in nucleic acid synthesis:
tumour.
(a) Glutamate antagonist:
Adverse Effect: Delayed myosupression, Thrombocytope-
E.g., Azaserine, DON
nia
Mechanism of action
Chlorozotocin, Streptozotocin

CH 2OH 5-phosphoribosyl pyrophosphate (5-PRPP)

R = -CH3 (STREPTOZOTOCIN) Glutamate as cofactor
R = -CH2CH2Cl (CHLOROZOTOCIN) 5-phosphoribosylamine cytidine triphosphate (5-PRCTP)
OH OH
OH NHCON-R Glutamate as cofactor

Uridine Triphosphate (UTP)

N=O

yy It is broad spectrum antibiotics containing Nitrosourea. yy DON is more potent since it resembles the normal
cofactor L-glutamine than azaserine
Mechanism of action: yy Use: Sarcoma and Leukemias
yy At physiological conditions, it will produce chemically
(b) Folic acid antagonist or Antifolics:
reactive species like ISOCYNATE which may cause
carbamylation of amino acid and protein resulting yy E.g., Aminopterin, Methotrexate, Trimetrexate–All of
inhibition of DNA replication. these have Pteridine as basic nucleus.
yy Mechanism of action: Competative inhibition of
Aziridines Dihydrofolate reductase.
yy Ionosonic acid-required for RNA synthesis and Thymi-
Thitepa, Benzotepa, Altretamine dylic acid-required for DNA synthesis.
S yy Toxicity: Stomatitis, Hepatic dysfunction and throm-
S bocytopenia
+
N P N N P N
Purin base antagonists: E.g., 6-Thioguanine,
N H 6-Mercaptopurin-Purin as basic ring
N

Aziridinyl Cation act as Electrophile S S

Thiotepa
H N H N
Precaution: Thitepa is highly toxic to bone marrow so N N
high blood count is necessary during the therapy.
N N H2N N N
Antimetabolite agent
H H
Amino acid inhibitors: Tyrosine analogues
6-Mercaptopurin 6-Thioguanine
Vitamin and coenzyme antagonists
E.g., Riboflavin analogues Mechanism of action
2
Metabolic degradation of 6-MP
1 + Guanase
1
6-Thioxanthin
1 1 2
Oxidize by xanthin oxidase
6, 7-Dimethyl-10-D-ribityl=Isoriboflavin Thiouric acid
7, 8-Dimethyl-10-d-ribityl=Galactoflavin
yy Isoriboflavin and Galactoflavin causes deficiency of yy Allopurinol: Xanthine oxidase inhibitors potentiate
riboflavin and controls Lymphosarcoma. the activity of 6-MP and also increases the toxicity.
3.234  Chapter 5

yy Azathiopurin: Anti tumor agent but not active than Cytotoxic antibiotics
6-MP-So it is used as immunosuppressive agent in organ
transplant. Anthracycline Antibiotics
yy Fludrabin and vidrabine: Anti-viral agent

Vidrabine Anthracyclines derivative Miscellaneous class

Daunorubicin Actinomycin
Mechanism of action Doxorubicin Mithramycin
yy Adenine arabinside Hypoxanthine arabinoside Carminomycin Bleomycin
derivative Resistance to tumor Idarubicin Mitomycin C
yy It is also known as Adenine arabinoside-Streptomyces Epirubicin
Arabinoside
yy Sugar part-D-arabinose O OH O
R4
Fludrabin: 2-fluoro derivative of vidrabine is also known
OH
as fludrabine.

Pyrimidine Antagonist R1 O OH
E.g., 5-Fluorouracil (Antimetabolite of uracil), Cytrabin
H3C
Mechanism of action: R2 O

Thymidylate Synthase R3
2' Deoxy Thymidylate H2N
uridylate
Drugs R1 R2 R3 R4
5-Fluoro uracil inhibit
Daunorubicin –OCH3 H –OH H

yy Resulting in diminishing of the DNA biosynthesis. Doxorubicin –OCH3 H –OH –OH

yy Fluorouracil is anabolized to 2’ deoxy ribose mono Carminomycin –OH H –OH –OH

phosphate which is potent inhibitors of thymodylate
Idrabicine H H –OH H
synthase.
yy Tegafur: It is a prodrug, after metabolism, it is converted Epirubicin –OCH3 –OH H –OH
into 5-Fluoro uracil. (Epimer of Doxorubicin)
yy Capcitabine: Tumor selective and tumor activated pro- yy Anthracycline occurs as a glycosides of anthracyclinone.
drug of 5-Fluorouracil. yy The glycosidic linkage usually involves the 7-OH
yy Gamcitabine: It inhibits Ribonucleotide reductase and group of anthracyclinone and β anomer of a sugar with
compate 2-deoxy xytidine triphospahte for incorpora- L-configuration.
tion into DNA. These effect producing cell specific cy- yy Anthracyclinone-Aglycon containing anthraquinone
totoxicity. chromophore within linear hydrocarbon skeleton.
yy Use: Adenocarcinoma of pancreas.
Mechanism of action
yy Cytrabine: Cytosine arabinoside
yy Mechanism of action: Cytrabine anabolized to triphos- Drug intercalates into DNA inhibit Topoisomerase-II
phate derivative inhibits the conversion of cytidylic
acid to 2’ deoxy cytidylic acid.
Yields oxygen radicals
yy It also inhibits the DNA dependant DNA polymerase
enzyme and miscoding following incorporation into
DNA and RNA. Inhibits DNA synthesis
 Medicinal Chemistry  3.235

yy Daunorubicin and Doxorubicin is obtained form Plant Products

S.Pencetium.
Vinca alkaloids:
yy Daunorubicin-It is a glycoside formed between dauno-
mycinone and L-Daunosamine, and Doxorubicine is its yy It is dimeric indole alkaloid obtained from Catharan-
14-OH derivative. thus Roseus, family Apocynaceae.
yy Indole containing moiety known as Cathranthine
Metabolism yy Indoline containing moiety known as Vindoline
yy Daunorubicin 13-OH derivative (Daunorubicinol) yy E.g., Vincristine, Vinblastine, Vinrosidine and
Clave to aglycon Vinleuroside.
yy Doxorubicin 13-OH derivative (Adriamycinol) yy Mechanism of action: It causes mitotic arrest by
promoting the dissolution of microtubule in cell.
Miscellaneous yy Use: Acute leukaemia, Hodkin’s Disease, lymphocyte
Actinomycin: Having Phenoxazine nucleus. lymphoma, Breast carcinoma.
Source: S.antibioticus
Hetrocyclic Amine as an anti cancer agent
It is also known as dactinomycin.
yy Isolated from Chinese tree Camptotheca acuminate.
Mechanism of action: Drug inhibits DNA-depen- yy E.g., Camptothecin, Hydroxy Camptothecin
dant RNA polymerase that inhibits the DNA and RNA yy Use: Colorectal and Ovarian cancer.
synthesis.
Lactone (Alkaloids) as an anti cancer agent
Bleomycin yy Podophylotoxin and Deoxypodophylotoxin are
yy Source: S.verticillus obtained from Himalaya shrub Podophyllam Emodi
yy Bleomycin and their analogues occur naturally as blue and P.Peltatum.
copper chelates. yy Mechainism of action: It inhibits mitosis by destroying
the structural organization of mitotic apparatus.
Mechanism of action: Bleomycin forms a complex
with Fe(II) converts into the hydroxy and superoxide radi- Taxol derivative
cals that will clave Phosphodiestarase bond of DNA and ul- yy E.g., Paclitaxel and Docetaxel
timately cause degradation of DNA strand. yy It is obtained from western yew tree Taxus Bravifolia.
yy M/A: It binds with β-Tubulin subunit of microtubule
Mitomycin C and appears to antagonize the disassembly of the key
Source: S.Caespitosus cytoskeletal protein and arrest in mitosis follows.
This compound has three carcinostatic functions like Colchicine:
yy Quinone yy Main use: Terminating acute attack of Gout
yy Carbamate yy M/A: It inhibits mitosis at metaphase by disorienting
yy Aziridine the organization of spindle and esters.

Mechanism of action: The quinine, carbamate ang Etoposide and Teniposide:

aziridine arranged in its natural state so by chemical and en- yy It is a semisynthetic derivative of Podophyllotoxins.
zymatically reduced to hydroquinone derivative followed by yy It has cytotoxic effect on G2 phase.
loss of methanol resulting formation of Indohydroquinone yy It causes protein linked DNA strand breaks by inhibit-
becoming bifunctional Alkylating agent capable of cross ing Topoisomerase-II.
linking double helical DNA.
Hormones and Their Antagonists
Mithramycin Tamoxifen
yy Aurolic acid derivative obtained from S.Plicatus. yy Selective estrogen receptor modulator
yy Anti estrogen drugs
Mechanism of action: It inhibits “DNA dependant RNA yy Use: Advanced breast cancer in post menopausal
polymerase enzyme”. women.
3.236  Chapter 5

Flutamide Enzyme as an Anticancer

yy It is non-steroidal anti-androgen drugs. yy L-Asparginase and Pegaspagenase
yy Use: Prostate cancer yy Potent immunosuprresive agent.

Aminoglutethimide
yy It inhibits Desmolase enzyme which prevent the con- STEROIDS
version of cholesterol to pregnalone. Steroids: Saturated derivatives of Phenanthrene and Ring
yy Use: Adrenocortical carcinoma, Cushing’s Syndrome D is Cyclopentane ring.
Mitotane Basic Moiety in Steroids
yy Highly selective effect on adrenal gland. 12 17
13
11
Aromatase Inhibitors
C D 16
1 9
Generation Steroidal Non steroidal
10 Moiety in
Basic 8 Steroids
14
2 15
First Testolac- Aminoglutethimide A
tone 5
B
3 7
Second Formestane Fedrozole 4 6

Third Exemastane Anstrazole, Letrozole, Vora- Cyclopentano Perhydro Phenanthrene

zole 1,2 Cyclopentano Phenanthrene
H
Leuprolide: Synthetic non-peptide analogue of naturally H
occurring gonadotrophin-relesing hoemones, (LnRH)

Signal Tranduction Inhibitors Gonane (C = 17)

yy Microbial product Staurosporin CH3 CH3

CH3
Immunotherapy
yy Levamisole is used in colon cancer

H H
Interferon α-2a/2b
5 .-Estrane (C = 18) 5 . -Androstane (C = 19)
yy Highly purified protein containing 165 amino acids.
yy Interferon α-n3: It is glycoprotein. CH3
BCG: Bacillus calmette Guerin CH3
CH3
yy Connaught BCG: It is freeze dried suspension of attenu- CH3
ated strains of Mycobacterium Bovis. CH3

Hydroxy Urea
H
Cisplatin 5 . -Pregnane (C = 21) Cholastane (C=27)
yy It is potent inhibitor of DNA polymerase.
yy Cisplatin is Cis-dichlorodiamineplatinum II yy Meaning of α-Behind the plane
yy E.g., Oxaliplatin and Ormaplatin yy Meaning of β-Above the plane
 Medicinal Chemistry  3.237

Nomenclature and Numbering of Some Stereochemistry

Steroids yy In 5α steroids-A/B rings are in Trans form
OH OH yy In 5 β steroids-A/B rings are in Cis form
CH3 H CH3 H yy Cholastane, Androstane and Pregnane exist in two
conformation
H CH3
1. Chair form
H 2. Boat Form
HO O Chair form are more stable than boat form due to less
17 -Estradiol Testasterone
angle strain hence all steroids are exist in chair form.
(Estra-1, 3, 5 (10)-triene-3, (17 β-Hydroxy
17 β diol) androst-4-ene-3one) Classification of Steroid
OH
(1) Anti-inflammatory agent: Cortisone
O CH2 (2) Sex hormone: Estrogen, Progesterone, Testosterone
CH3 (3) Oral Contraceptive: Norethisterone
O OH (4) Cardiac Steroids: Digitoxigenin
Cortisone
CH3 (17,21-Dihydroxy (5) Diuretics:Spironolactone, K-Prorenoate
pregn-4-ene-3,11,20 trione) (6) Antibiotic: Fusidic acid
(7) Neuromuscular blocker: Pancuronium
O (8) Vitamin-D precursor: Ergosterol

Nomenclature of Steroids Biosynthesis of Steroidal Hormones

yy Steroids are secreted from endocrine gland like
CH3 CH3 ovaries, testes and adrenal gland
yy Female sex hormone-Estrogen and Progesterone
CH3 CH3 9 yy Male sex hormone-Androgen
14
8 8 yy Adrenocorticoids-Glucocorticoids and Minerocor-
ticoids
H yy Starting material for all steroid synthesis is Cholesterol
H yy And overall mechanism of steroid hormone action in
5 . -Androst-8(14)-ene 5 . -Androst-8-ene regulation of gene expression.
( Double bond is not (When double bond is in
In sequence) sequence, we only mention the
number at d.b starts)
Sex Hormone: Oestrogen
yy Hormone activity is controlled by GnRH hormones
OH like FSH, LH/ICSH and Luteoprin/Prolactin
Missing of Methyl Group CH3 C2H5
yy LHRh agonist-Nafarelin
H Function of sex hormone:
yy Regulate ovulation in women
yy Spermatogenesis in men
(a) Naturally occurring estrogens: Estradiol, Estriol
17 . -ethyl-19-norandrost-4-en-17 -ol and Estrone

When methyl group is missing from basic moiety, then yy Starting Material
we have to write nor at which number of carbon is the meth- Testosterone------------------------------------Estradiol
yl group removed. Androstenedione------------------------------Estrone
3.238  Chapter 5

O
CH3
Meerwein Pondro Reaction
H Alluminium-i-propoxide
LiAlH 4
H Reduction

HO
Estrone
(3-Hydroxy estra-1,3,5(10)triene-17-one)
OH
CH3 R

H
HO
R=H 17B-Estadiol
R=C CH Ethinyl Estradiol

Synthesis of Estriol

O O OAC
CH3 CH3
H3C CH3
O
H 3C H
Iso propyl acetate

HO ACO
Estrone
(3-Hydroxy estra-1,3,5(10)triene-17-one)
Epoxidation

O
HO O

OAC
OH CH3 O
CH3 H
OH
H LiAlH4
H
Reduction
H
HO ACO
Estriol
(Estra-1,3,5(10)triene,3,16,17B triol)
 Medicinal Chemistry  3.239

(b) Stallion Estrogen: equilenin and equilin Metabolism

(c) Synthetic and Non-steroidal Oestrogen: 17 Estradiol
[O]
C2H5
[O] [O]
HO OH 2-hydroxy metabolite Oestrone Estriol

C2H5 Uses
Diethyl Stilbesterol yy Oral contraceptive
(E)- . -Diethyl Stilbene-4,4 diol yy In case of Menopause
yy In abdominal watering bleeding
yy Influences ovarian development
Trans diethyl stibesterol is potent estrogenic activity
than Cis-diethyl stibesterol Anti Estrogen/Ovulation Stimulant:/Fertility
It is synthesized from Anisaldyhyde and Anethol drugs or Anti Tumor agent
E.g., Clomiphene, Tamoxiphen, Ethamoxytriphetol
Uses
yy Inhibition of lactation (C2H5 )2NCH2CH2O
yy Breast and prostate cancer
yy Secondary amenorrhoea due to ovarian insufficiency Cl
Diethyl amino C C
Dienosterol
ethyl side chain

CH3 Clomiphene
CH
(CH3 )2NCH2CH2O
HO OH
CH C2H5
C C
CH3 Dimethyl amino
ethyl side chain
Dienestrol
((E,E)-4,4' di(ethylidene)ethylene diphenol) Tamoxiphene

yy The starting material for synthesis of dienosterol is yy Ethamoxytriphetol-Strong anti oestrogenic activity
p-Hydroxy propiophenone. yy Danazol-Weak androgenic activity
yy Tamoxiphene and clomiphene are aminoether deriva-
CH3 tive of stilbene
yy Cis isomer of tamoxiphene is estrogenic rather than ant
H3C estrogenic
yy Tamoxiphene and clomiphene are used in estrogen de-
OH
pendent mammary (breast) carcinoma
HO CH3
Side effects
Benzestrol
yy Enlargement of ovaries and visual disturbance
H3C
OH Progestin (Gestagens)
E.g., Progesterone, 19-nor testosterone
This class of hormones is secreted from corpus luteum
HO CH3
and it is responsible to maintain the vascularity of uterine
Hexestrol endometrium, and also inhibit oxytocin release.
3.240  Chapter 5

Mechanism of action Androgen and Anabolic Agent

It increases the level of FSH and LH production by yy It is a male sex hormone synthesized from cholesterol.
hypothalamus by blocking of feedback inhibition of ovary yy E.g., Testosterone
produced estrogen.
Androgenic/Male Sex Characteristic
Progesterone yy Normal development
O yy Functioning and maintenance of male sex organ and
Me
Me male sex characteristic.

Me Anabolic/Muscle Building Activity

yy It causes nitrogen retention by increasing the rate of
protein synthesis and decreasing the rate of protein
O catabolism and ultimately promote the new tissue
formation.
4-Pregnene-3,20-dione
OH
Synthesis of progesterone Me
Disogenin--------Pregnenolone------Progesterone
Chelesterol--------Pregnenolone------Progesterone Me
Metabolism
Metabolism: Progesterone is metabolized to
5β-pregnanediol glucronide O
(a) C-6 Substituted 17α-acetoxy Progesterone Testosterone
Medroxy progesterone acetate and Megastrol acetate
(b) Dehydrogesterone OH
Me
Chlormadione acetate
(c) Derivative of testosterone: Ethisterone, Norethis- Me
terone

Ethisterone First synthetic progestin and orally active

O
androgen
Dehydrotestosteron
Ethisterone CH
OH Active form of testosterone
Me C
IUPAC of Testosterone: 17β-Hydroxy-4-androstene-3-
Me one
Dehydrotestosterone: Reduction of C-4-C-5 bond
from testosterone.
Steroidal skeleton having minimum requirement to
O
have androgenic activity.
17 . -Ethynyl testosterone
SAR
(d) Derivative of 19-Nor testosterone:
yy 5α-Androstane has androgenic activity, ring expansion
E.g., : 19-nor testosterone, nor ethynodrel, Norgestrel, and contraction leads to loss of activity.
Lynesterol yy Introduction of SP2 hybridized carbon atom in Ring A
Norgestrel Leavo isomer is actively known as levonorg- renders rings more planner resulting greater anabolic
estrel used as an oral contraceptive. activity. Eg. Methandrosterone.
 Medicinal Chemistry  3.241

Metabolism Vaginal Contraceptive

yy Oxidation of 17β –OH group → Androstenedione → 1. Surface active agent/-SH binding agent:
Reduction to give Androsterone ■ Nonoxynol-9, otoxynol
yy Testosterone → 5α dihydrotestosterone which acts as 2. Bactericides:
invivo androgens ■ Phenyl mercuric acetate, Benzethonium chloride
Side Effects 3. Acids: Boric acid, Tartric acid, Phenol
yy Musculinization in women-growth of facial hair
yy Edema Interceptive/Abortifacients
yy On chronic treatment, anabolic steroids can suppress yy PGE2 and PGF2α
the production of testosterone.
MifepristoneProgesterone antagonists
Testolactone Danazol A gonadotropin inhibitor in females.
yy First generation steroidal aromatase inhibitors Gossypol Phenolic compound isolated from cotton
yy Used in Breast cancer seed oil having directly spermatogenic activity. Only leavo
yy Purely anabolic but minimum androgenic activity isomer of gossypol is active as a male fertility regulating
agent.
Testolactone
Me Miscellaneous Contraceptive Methods
O O
Me Male-Vasoctomy, Female-Tubectomy
Adrenal Cortex hormones
O
Adrenal Gland
Anti Androgen
E.g., Cyproterone, BOMT, Nonsteroidal Flutamide Adrenal Medulla Adrenal Cortex
Mechanism of action: They do not prevent dihydrotes-
tosterone formation but inhibit the nuclear retention of di- Secrete Catecholamine Secrete Adrenocorticoids
hydrotestosterone in prostate. Adrenaline
Cyproterone: It competes with receptor at receptor site.
yy Adrenal Cortex is regulated by Hypothalamus-pitutary
gland.
Oral Contraceptive
Noretynodrel, Mestranol, EthinylEstradiol, Trans diethyl-
stilbesterol, Ethisterone, Lybesterol Classification

F3C NHCOCH(CH3)2

O2 N Glucocorticoids Minerocorticoids
Flutamide CH3
O E.g: Hydrocortisone
Me OCOCH3 and Cortisone
Regulate Carbohydrate, Influence salt and water
Me balance
Protein and
Lipid metabolism Hence control blood volume
and blood pressure
O
Cl E.g: Aldosterone
Cyproterone Acetate 11-Desoxy Corticosterone
3.242  Chapter 5

Hydrocortisone Prednisolone yy Dexamethasone-In the structure of Triamacinalone,

O CH2OH O CH2OH 16α-OH group is substituent with 16α-methyl group.
Me OH Me OH It is 5 times more potent anti inflammatory agent.
HO HO
Me Me Trimcinolone
CH 2OH
O
O O
Me OH
Cortisone Prednisone HO OH
O CH2OH
CH2OH Me
Me OH O
O Me OH
Me O
F
Me
O
O
O
yy Fluprednisolone, Fludrenolone, Fluoromethalone and
Flucinolone are potent anti-inflammatory agent.
Cortisone IUPAC: 4-Pregnene-17α, 21-diol-3, 11,
20-trione Minerocorticoids
Hydrocortisone/Cortisol: 4-Pregnene-17α, 11, yy Reabsorption of Na+ from distal tubule of kidney.
21-triol-3, 20-dione yy Increase urinary excretion of both K+/H+ ions.
Prednisone and prednisolone is 1-Dehydro derivative Glucocrticoids
of cortisone and hydrocortisone.
yy Glucocrticoids inhibits the action of Vitamin D and in-
hibits the formation of new tissue.
SAR yy In CVS, overdose of corticosteroids leads to hyperten-
yy Substituent’s (16 α-OH, 16 α-Methyl, 16 β-Methyl, 16 sion due to high Na+ concentration.
α, 17 α-Ketals) like on cortisone decrease minerocor- yy Skelatal Muscle: Overdose of corticosteroids causes
ticoid activity. hypokalemia which leads to muscle weakness.
yy Substituent’s (9 α-F, 21-OH, 2 α-Methyl, 9 α –Chloro)
like on cortisone increase minerocorticoid and gluco- Contraindication
corticoid activity. yy Peptic ulcer
yy 9 α-F substitutions increase the anti-inflammatory yy Glucoma
activity. yy Diabetes
yy Triamacinalone have 9α-F, 16α-OH substitution in the yy Psychoses
structure of Prednisolone. yy Heart disease
Important Medicinal Agent with its structure, basic ring, IUPAC name, Starting material for synthesis and special properties

Name of Drug Structure Basic Ring Pres- IUPAC Name Starting Material Remarks
ent in structure For Synthesis
Propanolol Basic Moiety: (R,S)-1- α-Napthol + Side Effect:
Napthalene isopropylamino-3- (1- naph- Epichlorhydrine 1. Bronchitis,
thyloxy) 2. Hypoglycemia
Aryloxy propanol- propan-2-ol Contraindicating in
amine derivatives Bronchial Asthma

Other Uses:
Migraine, Anxiety
Timolol Basic Moiety: (S)-1-((1,1- Cynoamide + Supur- Use in Migraine,
1,2,5-Thiadiazole Dimethylethyl)amino)-3-((4- monochloride Glaucoma and
and Morpholin (4-morpholinyl)-1,2,5-thi- Myocardial Infarc-
adazol-3-yl)oxy)-2-propanol tion

Atenolol Basic Moiety: (R, S)-4-(2-hydroxy-3- iso- 4-Hydroxyphenyl Use in angina

Aryloxy propylaminopropoxy) - acetamide
propanolamine phenylacetamide. + Epichlorhydrine

Nifedipine Basic Moiety: Dimethyl 1,4-dihydro-2,6- Methylacetoace- Angio edema

Dihydropyridine dimethyl-4- (2- nitrophenyl) tate+2- nitro Benzal- 1st generation
pyridine-3,5-dicarboxylate dehyde + Ammonia calcium channel
blocker

Atorvastatin Basic Moiety: (3R,5R)-7-[2-(4- --- Side Effect:

Pyrrole Fluorophenyl)-3-phenyl- 1. Myalgia
4-(phenylcarbamoyl)- 2. Rhabdomylosis
5-propan-2-ylpyrrol- 3. Angio-odema
1-yl]-3,5-dihydroxyhepta-
noic acid
Important Medicinal Agent with its structure, basic ring, IUPAC name, Starting material for synthesis and special properties

Clofibrate Basic Moiety: 2-(4-Chlorophénoxy)- 4-Chlorophenol+ Ac- Side Effect: Litho-

Phenoxy ester 2-méthylpropanoate etone+ Chloroform genicity of Bile
Gall stone forma-
tion

Metabolite: Clofi-
bric acid
Clonidine Basic Moiety: 2-[(2,6-dichlorophenyl) 2,6-dichloroaniline Side Effect:
Imidazoline imino]- imidazolidine hy- +NH4SCN + N-(2,6- 1. Dizziness,
drochloride dichlorophenyl) 2. Drowsiness
thiourea 3. Impotence

Salbutamol Basic Moiety: (RS)-1-(4-hydroxy-3- hy- 4-Hydroxy-3- Hy- Side Effect:

Phenol droxymethylphenyl)- droxyl Methyl 1. Flushing,
2-(tert-butylamino) ethanol Benzaldehyde 2. Muscle cramps

β -Adrenergic
agonist
Prazosin Basic Moiety: 2-[4-(2-furoyl)piperazin- 2,4-Dichloro-6,7- Di- Side Effect:
Quinazoline + Pi- 1-yl]- 6,7- dimethoxyquin- methoxyquinazoline 1. First dose Hypo-
perazine + Furan azolin-4-ylamine hydrochlo- tension,
ride 2. Failure of ejacula-
tion( Impotency)
Selective α1
blocker

Pilocarpine Basic Moiety: 3S,4R)-3-ethyldihydro-4-[(1- 2-Ethyl-3-Carboxy- Made from leaves

Imidazole and methyl- 1H-imidazol- 5-yl) 2-Butyrolactone + of the tropic plant
Tetrahydrofuran methyl]furan-2(3H)-one Thionyl Chloride + Pilocarpus jaborandi
nitrate Diazomethane and Pilocarpus mi-
crophyllus species

Use in Glaucoma
and Dryness of
mouth (Xerosto-
mia)
Important Medicinal Agent with its structure, basic ring, IUPAC name, Starting material for synthesis and special properties

Physostigmine Basic Moiety: Pyr- (3aS,8aR)-1,3a,8-Tri- Pethoxymethyl Alkaloid isolated

rolidine+ Carba- methyl-1,2,3,3a,8,8a- aniline + α-Bromo from Physostigma
mate hexahydropyrrolo[2,3-b] propionyl bromide venenosum
indol-5-yl methylcarba- Metabolism:
mate Hydolysis form es-
eroline , Oxidation
forms rubreserine
and then serine
blue and
brown.

Indomethacin Basic Moiety: 1-(4-chlorobenzoyl)- p-Anisidine S (+) is active

Indole derivatives 5-methoxy-2- methylindol- +NaNO2/HCl
3-ylacetic acid Contraindicated in
epilepsy, preg-
nancy.

Ibuprofen Basic Moiety: (R,S)-2-(4-isobutylphenyl) Isobutyl Benzene S(+) is active,

Phenyl 1-methyl propionic acid
acetic acid

Mefenamic Basic Moiety: N- N-2,3-Xylyl anthranilic acid 2,3- Xylidine + Contraindicate with
Acid phenyl Anthranilic 2-Chlorobenzoic acid Aspirin
acid

Sulindac Basic Moiety: (Z)-5-Fluoro-2-methyl-1-[p- Glyoxalic acid It is prodrug (half

Indane Derivative (methylsulfinyl)benzyli- life is 8 hr) by
dene]indene-3-acetic acid reduction to form
sulfide metabolite
which is active.(half
life is 16.4 hr).
Side Effect:
Diarrhoea
Important Medicinal Agent with its structure, basic ring, IUPAC name, Starting material for synthesis and special properties

Diclofenac Basic Moiety: 2-[(2, 6-dichlorophenyl)- 2-Chlorobenzoic acid It raise lithium and
Biphenyl ring amino] phenyl acetate and 2,6-Dichloroani- digoxin level in
line plasma

It decreases arachi-
donic acid level in
leukocyte.

Tolbutamide Basic Moiety: 1-butyl-3-p-toluenesulfonyl p- Toluene Metabolite: Form

Sulphonylurea urea Sulfonylamide + hydroxyl active
Derivative Butyl isocyanate derivative

Chlorprop- Basic Moiety: 1-(p-Chlorophenyl p- Chloro Use in Diabetes

amide Sulphonylurea sulfonyl)-3-propylurea Benzene Sulfonyl- insipidus and give
Derivative amide+ Disulfiram like ef-
Propylisocyanate fect, Cause jaundice

Glibenclamide Basic Moiety: 1-[4-{2-(5-chloro-2- me- 2-Methoxy-5-Chloro- Inhibiting ATP-

Sulphonyl urea thoxybenzamido)- ethyl} benzoic sensitive
derivatives benzenesulphonyl]-3-cyclo- acid chloride + potassium channels
hexylurea Phenylethylamine
2nd generation Sul-
fonylurea derivative

Chlorthiazide Basic Moiety: Ben- 6-chloro-1,1-dioxo-2H- 3-Chloroaniline + Side Effect:

zothiadiazine 1,2,4-benzothiadiazine- Chlorosulphonic acid 1. Gitelmann’s syn-
7-sulfonamide drome
2. Bartter’s syn-
drome
Acetazolamide Basic Moiety: N-(5-sulphamoyl-1,3,4-thia- Hydrazine Hydrate Carbonic Anhy-
1,3,4-Thiadiazole diazol-2-yl)- acetamide Or 5-Amino, 2 Mer- drase Inhibitor,
capto- 1,3,4-thiadia- Used in Glaucoma
zole
Important Medicinal Agent with its structure, basic ring, IUPAC name, Starting material for synthesis and special properties

Furosemide Basic Moiety: 4-Chloro-N-Furfuryl-5-Sul- 2,4- Dichloroacetic Loop Diuretics

Anthranilic acid phamoyl acid+ClSO2OH By
derivative Anthranilic acid amidation reaction

Hydralazine Basic Moiety: 1-hydrazinona Phthalide/ Hy- Side Effect:

Hydrochloride Pthalazine phthalazine droxyphthalide 1. Lupus syndrome
2. Nasal stiffness
It acts by nitrate 3. Drug of choice
mechanism. in hypertensive
emergency
Phenytoin Basic Moiety: 5,5-Diphenyl α-Bromo Side Effect:
Sodium Imidazolidine-2,4- imidazolidine-2,4-dione diphenyl acetyl urea Gum Hypertrophy
dione sodium + Alcoholic ammonia Megaloblastic
anemia
It blocks sodium Osteomalacia
channel Hyperglycemia

In all type of sei-

zures except petit-
mal type.
Phenobarbi- Basic Moiety: 5-Ethyl-5-phenyl- Diethyl malonate + Side Effect:
tone 2,4,6 Tri Oxo Py- 2,4,6(1H,3H,5H)-pyrimidi- Urea 1. Hangover effect
rimidine or 2,4,6 – netrione 2. Drowsiness
Pyrimidone 3. Dizziness

Long acting drug

Diazepam Basic Moiety: 7- Chloro-1,3-Dihydro- 2-Amino 5-Chloro- Metabolite: Form
Benzodiazepine 1-Methyl-5-Phenyl- 1,4- benzophenone active Nordazepam
Benzodiazepin-2-one by N-demethyl-
ation

Skeletal muscle
relaxants
Important Medicinal Agent with its structure, basic ring, IUPAC name, Starting material for synthesis and special properties

Chlorproma- Basic Moiety: [3-(2-chloropheno- thia- m-Chloro aniline + Side Effect:

zine Phenothiazine zin-10- yl)propyl]dimethyl O-Chloro benzoic 1. Insomina,
amine hydrochloride acid 2. Anxiety,
3. Impotence
4. Extrapyramidal

Typical antipsy-
chotic drugs
Haloperidol Basic Moiety: 4-[4-(4-chlorophenyl)-4-hy- 4-chlorobutyryl Side Effect:
Fluorobutyrophe- droxy-piperidino]- 4`-fluo- Chloride + p- Chloro 1. Insomnia,
none robutyrophenone methyl styrene 2. Anxious

Lignocaine Basic Moiety: 2- Diethylamino-2,6-Di- 2,6-Dimethylaniline Lignocaine ad-

Xylene methylacetanilide + Chloroacetic acid ministered with
adrenaline

Captopril Basic Moiety: 1-[(2S)-3-mercapto-2- tert- Butylprolinate Side Effect:

Carboxy Proline methylpropionyl]-L- proline + 3-thio-2-methyl 1. Hyperthermia
propionic acid 2. Dysguesia
(Metallic taste)
3. Brassy Cough
4. Renal stenosis.

It also increases
bradykinin level
and vasodilation
Losartan Basic Moiety: Bi- 2-butyl-4-chloro-1-{[2'-(1H- -- Metabolism:
pheyl + Tetrazole tetrazol-5-yl)biphenyl-4-yl] 5-CH2OH Convert
+ Imidazole methyl}-1H-imidazol-5-yl) into COOH Group,
methanol Which is 15 time
more potent than
parent.
Important Medicinal Agent with its structure, basic ring, IUPAC name, Starting material for synthesis and special properties

Naproxen Basic Moiety: (2S)-2-(6-methoxynaphtha- α Chloromethyl- COX-I and II

Naphthalene len-2-yl)propanoic acid 6-methoxynaphtha- inhibitors,
( Propionic lene Dextrorotatory
Acid derivative) drug
Used in acute
gout
Aceclofenac Basic Moiety: 2-[2-[2-(2,6-dichloroanilino) 2-[(2, 6-dichlorophe- It is prodrug of
Diphenyl amine or phenyl]acetyl]oxyacetic nyl)- amino] phenyl Diclofenac.
Phenyl acetic acid acid acetate (Diclofenac)
derivative and Benzyl bromo-
acetate

Piroxicam Basic Moiety: 1,1 4-hydroxy-2-methyl-1,1- ---- Oxicam derivative

Dioxo Benzothi- dioxo-N-pyridin-2-yl-{6},2-
azine and Pyridine benzothiazine-3-carbox- Common side ef-
amide fect:
1. Peptic ulcer
2. Long acting
Half-life (45h)

Used in
acute gout

Rofecoxib Basic Moiety: 3-(4-methyl Phenyl acetic acid + Selective cyclooxy-

Furan-5-one sulfonylphenyl)-4-phenyl- Ethylbromoacetate genase-2 (COX-2)
2H-furan-5-one inhibitor
All selective COX-II
inhibitor (Celecox-
ib, Valdecoxib and
Etoricoxib) cause
CVS toxicity

Procaine Basic Moiety: 2-(diethyl amino) ethyl 4- Amino benzoic Benzoic acid
Benzoic acid 4-aminobenzoate acid ethyl ester+ derivative with
derivative 2-Diethyl amino local anesthetic
Amino alkyl ester ethanol+ Sodium and antiarrhythmic
of para amino ethoxide properties, it is me-
benzoic acid tabolized to PABA
Important Medicinal Agent with its structure, basic ring, IUPAC name, Starting material for synthesis and special properties

Benzocaine Basic Moiety: Ben- Ethyl 4-aminobenzoate PABA + Ethanol Benzocaines is an

zoic acid derivative ester of paraamino-
Alkyl ester of benzoic acid, lack-
p-amino benzoic ing the terminal
acid diethylamino group
of procaine
Diltiazem Basic Moiety: [(2S,3S)-5-[2- 4- Methoxy Benz- Calcium-channel
Benzothiazepine (dimethylamino)ethyl]-2-(4- aldehyde + Methyl blocker.
methoxyphenyl)-4-oxo-2,3- chloro acetate It inhibits phos-
dihydro-1,5-benzothiaze- phorylation
pin-3-yl] acetate of myosin light
chain phosphate
and prevents bind-
ing
with actin and pre-
vents contraction
Valsartan Basic Moiety: (2S)-3-methyl-2-[pentanoyl- L- Valine methyl ester Valsartan is a spe-
Biphenyl and Tet- [[4-[2-(2H-tetrazol-5-yl)phe- HCl via Suzuki cou- cific and selective
razole nyl]phenyl]methyl]amino] pling reaction type-1 angiotensin
butanoic acid II receptor (AT1)
antagonist
It is valine contain-
ing drug.
Telmisartan Basic Moiety: 2-[4-[[4-methyl-6-(1- 4-( Hydroxymethyl) Non-peptide
Benzimidazoles methylbenzimidazol-2-yl)- phenyl boronic acid angiotensin II
and Biphenyl 2-propylbenzimidazol-1-yl] + 2- receptor antagonist
system methyl]phenyl]benzoic acid ( 2- bromophenyl)- 4, It contains tetrazole
+ 4-dimethyl 2 Oxa- ring which bind to
zoline AT1 receptor
Important Medicinal Agent with its structure, basic ring, IUPAC name, Starting material for synthesis and special properties

Hydrochloro- Basic Moiety: 6-chloro-1,1-dioxo-3,4-di- 3-Chloroaniline + Short acting thia-

thiazide Benzothiadiazine- hydro-2H-1{6},2,4-benzothi- Chlorosulphonic acid zide diuretic
7-sulfonamide adiazine-7-sulfonamide It inhibit Na+/Cl-
reabsorption from
the distal convo-
luted tubules in the
kidneys
Side effect: Hypo-
glycemia
Amiloride Basic Moiety: 3,5-diamino-6-chloro-N- 5,6-diaminouracil Antikaliuretic-
Pyrazine (diaminomethylidene) + Glyoxal diuretic agent
Ring and amidine pyrazine-2-carboxamide Potassium-sparing
moiety. diuretic
It is 10 times more
Potent than triam-
terene.

Spironolac- Basic Moiety: S-[(7R,8R,9S,10R, Androstenolone - 3R Competitive aldo-

tone 17 - Spironolac- 13S, 14S,17R)-10,13- - hydroxy-5-andro- sterone antagonist
tone corticosteroid dimethyl-3,5'-dioxospi sten-17-one+ So- Metabolite: Can-
ro[2,6,7,8,9,11,12,14,15,16- dium amide in liquid renone - It causes
decahydro-1H- ammonia digoxin toxicity.
cyclopenta[a]phenan-
threne-17,2'-oxolane]-7-yl] Side Effect:
ethanethioate 1. Gynecomastia
2. Atrophy

Metformin Basic Moiety: 3-(diaminomethyl Dimethyl amine + Metformin is an

Guanidine / Bigu- idene)-1,1-dimethylguani- dicyanodiamide oral antihypergly-
anide dine cemic agent that
improves glucose
tolerance in pa-
tients with NIDDM,

Side effect: Weight

gain
Important Medicinal Agent with its structure, basic ring, IUPAC name, Starting material for synthesis and special properties

Pentobarbi- Basic Moiety: 5-ethyl-5-pentan-2-yl-1,3- 1-methyl butyl-ethyl Short acting

tone 2,4,6 Tri Oxo Py- diazinane-2,4,6-trione malonic ester + urea Barbiturates
rimidine or 2,4,6 –
Pyrimidone

Thiopental Basic Moiety: 5-ethyl-5-pentan-2-yl- Diethyl malonate+ Ultra short acting

2-sulfanyli- 2-sulfanylidene-1,3-diazi- sodium metal Barbiturates
dene-1,3-diazi- nane-4,6-dione General Anesthet-
nane-4,6-dione ics agent

Oxazepam Basic Moiety: 7-chloro-3-hydroxy-5-phe- 6-chloro- Hydroxyl group

Benzodiazepin- nyl-1,3-dihydro-1,4-benzo- 2-chloromethyl- contains benzodi-
2-one diazepin-2-one 4-phenylquina- azepine drug at
phenylquinazolin- third position
3-oxide + Sodium
hydroxide

Clonazepam Basic Moiety: 5-(2-chlorophenyl)-7-ni- 2-chloro- Non-hydroxy

Benzodiazepin- tro-1,3-dihydro-1,4-benzo- 2'nitrobenzophenon benzodiazepine
2-one diazepin-2-one + 2-bromoacetyl
bromide + Ammonia

Triazolam Basic Moiety: 8-chloro-6-(2- 2- Glycylamino-2,5- Use in insomnia

Benzodiazepine chlorophenyl)-1-methyl- dichlorobenzeno-
fused with Traizole 4H-[1,2,4]triazolo[4,3-a][1,4] phenone + Pyridine
benzodiazepine

Alprazolam Basic Moiety: 8-chloro-1-methyl-6-phe- 2,6-dichloro- Use in insomnia

Benzodiazepine nyl-4H-[1,2,4]triazolo[4,3-a] 4-phenylquinoline +
fused with Traizole [1,4]benzodiazepine hydrazine
Important Medicinal Agent with its structure, basic ring, IUPAC name, Starting material for synthesis and special properties

Chlordiazepox- Basic Moiety: 7-chloro-4-hydroxy-N- 2-amino-5-chloro- Metabolite:

ide 1,4-benzodiazepin- methyl-5-phenyl-3H-1,4- benzophenone + Nordazepam
2-imine benzodiazepin-2-imine hydroxylamine

Carbamaze- Basic Moiety: benzo[b][1]benzazepine- 5H – dibenzo[b, f ] Iminostilbene de-

pine Benzazepine 11-carboxamide azepine + fremy’s salt rivative
Tricyclic Antide- Recently, Oxacar-
pressant. bazepine is used
which contains oxo
group at 10 posi-
tion and no aplastic
anaemia.

Used in Trigemi-
nal Neuralgia and
Mania
Imipramine Basic Moiety: Di- 3-(5,6-dihydrobenzo[b] 10,11-dihydro-5H- Tertiary amine
hydro Benzazepine [1]benzazepin-11-yl)-N,N- dibenz[b,f ]azepine derivative
Tricyclic Antide- dimethylpropan-1-amine + 3-dimethylami-
pressant. nopropylchloride + Side effect:
sodium azide 1. Anticholinergic
type,
2. Postural hypo-
tension.
Chlorampheni- D-threo isomer is 2,2-dichloro-N-[(1R,2R)-1,3- p-Nitro acetophe- Binds to the bacte-
col most active. dihydroxy-1-(4-nitrophenyl) none. rial 50S ribosomal
propan-2-yl]acetamide subunit and inhibit
protein synthesis
Side effect: Grey
baby syndrome
Use in Rocky moun-
tain Spotted Fever
Important Medicinal Agent with its structure, basic ring, IUPAC name, Starting material for synthesis and special properties

Metronidazole Basic Moiety: 2-(2-methyl-5-nitroimid- Ethane-1,2 diamine Luminal Tropho-

Nitro-imidazole azol-1-yl)ethanol + cyanomethane + zotocidal Agents
Zinc and also used in
H. pyroli. treatment

Side effect:
Metallic taste
Primaquine Basic Moiety: 4-N-(6-methoxyquinolin- 4-methoxy-2-ni- Primaquin inhibits
8-Amino Quinoline 8-yl)pentane-1,4-diamine troaniline and gametocyte stage,
glycerol leavo isomer is
less active than
dextro isomer.

Contraindicated in
G6PD deficiency
Fluconazole Basic Moiety: 2-(2,4-difluorophenyl)- 2,4 diflourobenzene It inhibits the fun-
Triazole 1,3-bis(1,2,4-triazol-1-yl) + chloroacetyl chlo- gal lanosterol 14
propan-2-ol ride + aluminium alpha-demethylase
hydroxide which thereby pre-
vents the formation
of ergosterol which
is an essential
component in the
fungal cell mem-
brane.
Ketoconazole Basic Moiety: 1-[4-[4-[[(2S,4R)-2-(2,4- 2,4-dichlorophenacyl Inhibits 14-alpha
Piperazin and dichlorophenyl)-2- bromide + glycerol Demethylase
Dioxolan (imidazol-1-ylmethyl)-1,3-
dioxolan-4-yl]methoxy] Side effect:
phenyl]piperazin-1-yl] Reduced cortico-
ethanone steroids synthesis
and thereby used
in Cushing’s Syn-
drome
Important Medicinal Agent with its structure, basic ring, IUPAC name, Starting material for synthesis and special properties

Clotrimazole Basic Moiety: 1-[(2-chlorophenyl)-diphe- 2-chlorotriphenyl Inhibits biosyn-

Imidazole nylmethyl]imidazole methylchloride + thesis of the sterol
imidazole + triethyl- ergostol
amine

Miconazole Basic Moiety: 1-[2-(2,4-dichlorophenyl)- 2,4 dicholoro Azole group of

Imidazole 2-[(2,4-dichlorophenyl) phenacyl bromide + antifungal agent
methoxy]ethyl]imidazole imidazole binds to fungal
cytochrome P-
450-dependant
14α-demethylase
enzyme that is
responsible for
the demethylation
anosterol to ergos-
terol.
Isoniazid Basic Moiety: Pyridine-4-carbohydrazide 4-cyanopyridine + Synthetic derivative
Hydrazide of Nico- water + NaOH of nicotinic acid
tinic acid, Adverse Effect:
Basic Moiety: 1. Peripheral
Pyridine Neuritis
2. Always advisable
with vitamin B6
(Pyridoxine),
3. Hepatotoxicity
Ethambutol Basic Moiety: (2S)-2-[2-[[(2S)-1-hydroxy- Nitropropane + It inhibits “Arabi-
Diethyl amine butan-2-yl]amino]ethyl- formaldehyde nosyl transferase
derivative amino]butan-1-ol enzyme” to prevent
(dextro isomer polymerization of
having arabinoglycan in
maximum activity mycobacterial cell
than leavo form) wall.
Important Medicinal Agent with its structure, basic ring, IUPAC name, Starting material for synthesis and special properties

Cyclophospha- Basic Moiety: N,N-bis(2-chloroethyl)- Bis(2-chloroethyl) Alkylating

mide 1,3,2-oxaza- 2-oxo-1,3,2{5}-oxaza- amine + phospho- agents (Nitrogen
phosphinan phosphinan-2-amine rous oxychloride mustard deriva-
tive)
Metabolite: Phos-
phoramide Mustard
(Having Antitumor
activity) and
Acrolein (Toxic to
urinary bladder)
Methotraxate Basic Moiety: (2S)-2-[[4-[(2,4-diaminop- N-(4-methylamino- Dihydro folate
2,4-diamino teridin-6-yl)methyl-me- benmethylamino- reduactase(DHFR)
pteridin thylamino]benzoyl]amino] benzoyl) inhibitors
pentanedioic acid glutaminic acid +
2-amino-4-hydroxyl-
6-bromomethylpter-
idine
Tamoxifen Basic Moiety: 2-[4-[(Z)-1,2-diphenylbut- Ethyl dezoxy benzoin Selective estrogen
Tamoxifen has the 1-enyl]phenoxy]-N,N-di- + 4-methoxyphenyl receptor modula-
same nucleus as methylethanamine magnesium bromide tors (SERMs),
diethylstilbestrol Estrogenic and an-
but possesses tiestrogenic effects,
an additional Used in Osteopo-
side chain (trans rosis.
isomer) which
accounts for its
antiestrogenic
activity
Flutamide Basic Moiety: To- 2-methyl-N-[4-nitro- 4-nitro-3-trifluo- Active metabolite
luidine derivative, 3-(trifluoromethyl)phenyl] romethylaniline + 2-hydroxyflutamide
Non-steroidal anti- propanamide isobutyric competitively block
androgen acid chloride dihydrotestoster-
one
 Medicinal Chemistry  3.257

Multiple Choice Questions

1. Which of the following is β-halo alkyl amine derivative? 11. Which of long acting beta blocker is used for glaucoma?
(a) Phenotamine (b) Tolazoline (a) Timolol (b) Levabunolol
(c) Phenoxybenzamine (d) None (c) Carteolol (d) Betaxolol
2. Which of the following is aryl sulfonamide derivative? 12. Timolol contains which of following basic rings:
(a) Tamsulosin (b) Prazosin (a) 1,2,5-Thiadiazole and morpholine
(c) Metaraminol (d) None (b) 1,2,4-Thiadiazole and morpholine
3. Which of the following drug is used as mydriatic when (c) 1,4-Thiazole and morpholine
cyclopegia is not required? (d) None
(a) Phenylephrine 13. The muscarinic receptor contains which of the follow-
(b) Phenoxybenzamine ing amino acids as residue for parasympathetic activity?
(c) Hydroxyamphetamine (a) Aspargine (b) Aspartic acid
(d) None (c) Glutamic acid (d) Glutamine
4. Phenoxybenzmine acts 14. Which of the following is use in the diagnosis of
(a) Directly on alpha receptor myasthenia gravis?
(b) By irreversibly block alpha receptor (a) Physostigmine (b) Neostigmine
(c) By form ethylene iminium ion. (c) Both (d) None
(d) All of the above
15. Which of following is hydrophilic organophosphate
5. Which of following imdazoline derivative is selective compound?
α2 agonist?
(a) Parathion (b) Malathion
(a) Naphazoline (b) Tolazoline (c) Ecothiophate (d) None
(c) Clonidine (d) None
16. Which of following is selective novel M-3 antagonist?
6. Clonidine is used as:
(a) Drotaverine (b) Pirenzepine
(a) Glucoma
(c) Darcifenacin (d) All
(b) Migraine
(c) Opioid withdrawal syndrome 17. The basic ring present in pilocarpine is:
(d) All (a) Tetrahydrofuran and Indole
7. Dipivefrin is prodrug of (b) Tetrahydofuran and Imidazole
(a) Adrenaline (b) Noradrenaline (c) Tetrahydrofuran and Pyrole
(c) Both (d) None (d) None
8. Which of following drug inhibits dopa hydroxylase in 18. Which of following synthetic anticholinergic deriva-
noadrenaline synthesis? tive is used in Parkinson disease?
(a) Levodopa (b) Carbidopa (a) Amino alcohol ester
(c) Disulfiram (d) Alpha methyl dopa (b) Amino alcohol ether
9. Which of following selective β2 -agonists contains (c) Amino amide
pyridine ring? (d) None
(a) Albuterol (b) Pirbuterol 19. Phenoxybenzmine acts:
(c) Terbutaline (d) None
(a) By forming aziridinium ion which blocks α receptor
10. Which of following selective β2–agonists is not metabo- (b) By irreversibly blocking α-receptor
lized by COMT? (c) By forming ethylene iminium ion which blocks
(a) Albuterol (b) Terbutaline α-receptor
(c) Pibuterol (d) All (d) All of above
3.258  Chapter 5

20. Which of following is used in Alzheimer disease? (a) Diethyl stilbesterol

(a) Ambenonium (b) Dexamethasone
(b) Demecarium (c) Trans stilbene
(c) Oxotremorine (d) Chlortrienisene
(d) Arecoline 32. Which of the following have estrogenic activity?
21. What is the starting material for synthesis of salbutamol? (a) Gossypol (b) Genistein
(a) Phenyl acetonitrile (c) Coumesterol (d) Both (b) and (c)
(b) Methyl salicylate 33. Which of the following have anti estrogenic activity?
(c) 4-Hydroxy propiophenone (a) BOMT (b) Flutamide
(d) Mesitylene derivatives (c) Cyproterone (d) All of the above
22. Oxime is not used as antidote for 34. Which of the following is a progesterone antagonist?
(a) Neostagmine (b) Echothiophate (a) Mifepristone (b) Gossypol
(c) Dyflos (d) Tabun (c) Danazol (d) Both (a) and (b)
23. Which of the following has bicyclic structure? 35. For a molecule to exhibit antihistaminic activity the
(a) Clidinium bromide distance between the aryl and aliphatic N should be?
(b) Pyridostigmine (a) 5–6 A° (b) 4–5 A°
(c) Ecothiophate iodide (c) 2–3 A° (d) 1–2 A°
(d) Tropicamide
36. 17 β-Hydroxyandrost-4-en-3-one is
24. Clonidine, metronidazole and tinidazole have which of (a) Estriol (b) Prosgesterone
the group in common? (c) Testosterone (d) Floxymestrenone
(a) Quinidine (b) Benzimidazole
37. Hypoglycemic agent with 1-(hexa hydro-1H-azepin-
(c) Imidazoline (d) None of the above
1-yl)-3-(p-tolyl sulphonyl) urea is
25. Pseudoepedrine is a (a) GliCiazide (b) Tolazamide
(a) Erythro isomer (b) Threo isomer (c) Tolbutamide (d) Gliburide
(c) Meso isomer (d) Racemic mixture 140.
38. 3-Hydroxy-estra-1,3,5 (10)-trien-17-ones is
26. Which isomer of propranolol is more active? (a) Estradiol (b) Estrone
(a) Meso (b) Levo (c) 3-Hydroxyestrone (d) Dienesterol
(c) Dextro (d) Racemic 39. Which is TXA2 synthesis inhibitor (imidazole analogue)?
27. Which one of the following drugs does not act through (a) Dazoxiben (b) Ridogrel
G protein coupled receptors?
(c) Moxonidine (d) Aspirin
(a) Epinephrine (b) Dopamine
(c) TSH (d) Acetylcholine 40. Compounds that have both TXA2 synthetase inhibition
as well as TXA2 receptor blocking activity is
28. A steroid nucleus having 19 carbon is _________
(a) Androstane (b) Estrane (a) Dazoxiben (b) Ridogrel
(c) Gonane (d) Cholestane (c) Moxonidine (d) Aspirin

29. Which of the steroids have neuromuscular blocking 41. Which reagent is used for the conversion of hydrocor-
activity? tisone acetate to cortisone acetate?
(a) Estrogen (b) Pancuronium (a) CrO3 (b) Se03
(c) Fusidin (d) Digitoxigenin (c) HOBr (d) m-CPBA
30. 17-β-hydroxyl androst-4-ene-3-one is IUPAC of 42. Cimetidine is developed from which of the following
(a) Testosterone (b) Estradiol compounds?
(c) Estriol (d) Cortisone (a) Metiamide (b) Ranitidine
31. Anesaldehyde is a starting material for synthesis of (c) Procainamide (d) None of above
 Medicinal Chemistry  3.259

43. Pregnenolone on addition of 3C unit gives _________ (a) Clioquinol (b) Cicloprox
(a) Cardenoloids (b) Bufedenoloids (c) Haloprogin (d) 5-Flucytosin
(c) Steroidal moiety (d) All 55. The basic ring present in cicloprox is
44. 11-β, 21-dihydroxypregn 4-ene-3,18,20-trione is (a) 2-Pyridone (b) 2-Piperidone
(a) Aldosterone (b) Progesterone (c) 2-Pyridine (d) 2-Pyrrolidine
(c) Cholesterole (d) Cortisol 56. Coloroquin act by inhibiting following enzyme
(a) DNA and RNA polymerase
45. Which of the following substituent does not increase (b) DNA gyrase
glucocorticoid activity?
(c) Dihydro folate reductase
(a) 9-α-fluoro (b) 1-hydroxy (d) DNA synthase
(c) 6-α-methyl (d) 21- hydroxyl
57. The anti arrythmatic drug quinidine is a
46. Cholesterol contains which of the following? (a) (+) Stereoisomer of quinine
(a) 1 double bond and 1 OH group (b) (–) Stereoisomer of quinine
(b) 2 double bond and 1 OH group (c) (+) Racemic mixture of quinine
(c) 2 double bond and 2 OH groups (d) None of the above
(d) 1 double bond and 2 OH groups
58. The anti- malarial drug quinine contains
47. Which of the following corticosteroids does not have (a) Quinoline ring
17-α,21-diol system? (b) Quinclidine ring
(a) Triamcinolone (c) Isoquinoline ring
(b) Methyl prednisolone (d) Both (a) and (b)
(c) Medrysone
59. Amodiaquine Iminoquinone is ___________ product
(d) Pregnenolone of amodiaquin.
48. The starting material used for the synthesis of hista- (a) Oxidized (b) Reduced
mine is (c) Alkylating (d) None of the above
(a) S-Histidine (b) L-Histidine 60. Following drugs have a asymmetric centre except
(c) D-Histamine (d) None
(a) Primaquin (b) Pamaquin
59. Which of following drug causes terfenadine cardiotox- (c) Quinocide (d) Pentaquin
icity?
61. 4-diethyl amino 1-methyl butyl amino is side chain of
(a) Erythromycin (b) Azithromycin following agents
(c) Both (d) None
(a) Chloroquin (b) Primaquin
50. Which of following is metabolite of hydroxyzine? (c) None of the above (d) Both (a) and (b)
(a) Astemizole (b) Cetrizine 62. Which sulphonamide is not used in diuretics?
(c) Loratadine (d) Terfenadine (a) Tolbutamide (b) Bumetanide
51. The basic ring present in nizatidine is (c) Chlorthalidone (d) Furesemide
(a) Imidazole (b) Furan 63. Which is following is not a prodrug?
(c) Thiazole (d) None (a) Progunil (b) Sulfasalazine
52. Which of following is propylamine derivative? (c) Prontosil red (d) Trimethoprim
(a) Antazoline (b) Triprolidine 64. Sulfonamides are metabolized by humans principally by
(c) Azotidine (d) None (a) Acetylation (b) Deamination
53. Which of following inhibits ketoconazole absorption? (c) Oxidation (d) Conjugation
(a) Ranitidine (b) Nizatidine 65. Which is the major side effect of sulfonamide?
(c) Cimetidine (d) Famotidine (a) Crystalurea (b) Peripheral neuritis
54. Which agent is used in Athlet’s foot? (c) Kernictus (d) All of the above
3.260  Chapter 5

66. Mafenide acetateis generally effective against (c) Methyl ester of is nicotinic acid+ Phenyl hydrazine
(a) Clostridum welchi (d) Methyl ester of is isonicotinic acid+ Methyl
(b) M. tuberculosis hydrazine
(c) Haemophyllas ducreyi 78. Which of the following adverse effects is not associ-
(d) None of the above ated with INH?
67. Which is basic ring present in sulfomethoxazole? (a) Hepatotoxicity (b) Xerostomia
(a) Oxazole (b) Isoxazole (c) Peripheral neuritis (d) Ototoxicity
(c) Thiazole (d) None of the above 79. Match the following
68. Which is the basic ring present in sulfadiazine? MOA Drugs
(a) Pyridine (b) Pyrimidine 1. Inhibit arabinosyl transfarase a. Rifampin
(c) Pyridazine (d) Piperidine 2. Inhibits DNA dependent RNA
69. Which sulfonamide after metabolism is converted into polymerase b. Thiacetazone
sulfapyridine and 5-amino salicylic acid? 3. Inhibits folic acid synthesis c. Myambutol
(a) Sulfacetamide (b) Sulfamethoxazole 4. Inhibits fatty acid synthase I d. Pyrizinamida
e. Ethionamide
(c) Sulfadiazine (d) Sulfasalazine
(a) 1-c, 2-a, 3-b, 4-d (b) 1-c, 2-a, 3-b, 4-e
70. Which sulfonamides produces “Orange yellow color
to urine” under alkaline condition? (c) 1-c, 2-a, 3-e, 4-d (d) 1-c, 2-a, 3-d, 4-b
(a) Sulfacetamide (b) Sulfamethoxazole 80. Which of the following adverse effects is not associ-
(c) Sulfadiazine (d) Sulfasalazine ated with rifampin?
71. Which isomer of emetine is clinically useful? (a) Flu-like syndrome (b) Xerostomia
(a) Levo (b) Dextro (c) Hepatitis (d) Red orange color to urine
(c) D (d) L 81. Which isomer of ethambutol is clinically active?
72. Which alkaloid is used to treat amoebiasis? (a) Dextro (b) Levo
(a) Ipecac (b) Theophylline (c) Threo (d) Erythro
(c) Brucine (d) Aconite 82. Monthly eye examination is required with following
73. Glycobiarsol is used in drug treatment
(a) Antimalarial (b) Anti amoebic (a) Ethambutol (b) Pyrazinamide
(c) Anticancer (d) Antiashtamatic (c) Ethionamide (d) Streptomycin
74. Which nitroimidazole derivative has morpholino moiety? 83. Lupas like reaction is side effect of
(a) Tinidazole (b) Ornidazole (a) Ethambutol (b) PAS
(c) Timorazole (d) Metronidazole (c) Ethionamide (d) Streptomycin
75. Which antibiotic has direct action on trophozoito- 84. Cycloserine is analogue of
cidal? (a) D-alanine (b) D-serine
(a) Paramomycin (b) Neomycin (c) L-serine (d) L-alanine
(c) Natamycin (d) Erythromycin 85. Which antibiotic is also known as ansamycin antibiotics?
76. Which is not a true for isoniazid? (a) Polyene (b) Macrolide
(a) It is hydrazide of isonicotinic acid (c) Rifampin (d) Tetracycline
(b) Structurally similar to pyridoxine 86. Orally active phenazine dye is present in
(c) It inhibit Mycolase Synthase (a) Pyrizinamide (b) Thiacetazone
(d) It is hydrazide of nicotinic acid (c) Clofazimine (d) Prothionamide
77. Isoniazid is synthesized from 87. Which is the principle metabolite of rifampin?
(a) Methyl ester of isonicotinic acid+ hydrazine (a) 25-desacetylated RMP
(b) Methyl ester of nicotinic acid+ hydrazine (b) 3-formyl RMP
 Medicinal Chemistry  3.261

(c) RMP-quinone 98. Match the following

(d) N-demethylated RMP A. Penicillin-F 1. Phenoxy methyl penicillin
88. Which is long-acting sulphonamide? B. Penicillin-G 2. Pent-2-enlypenicillin
(a) Sulphadoxine (b) Sulphacetamide C. Penicillin X 3. p-Hydroxy benzylpenicillin
(c) Sulphasalazine (d) Sulphadiazine D. Penicillin V 4. Benzly penicillin
E. Penicillin K 5. n-Heptyl penicillin
89. Which is not true point in case of sulphonamide SAR?
(a) N-4 site can be modified to produce prodrug (a) A-2, B-4, C-3, D-1, E-5
(b) Benzene ring is necessary for activity (b) A-5, B-4, C-3, D-1, E-2
(c) N-1 of sulphonamide must be substituted (c) A-4, B-2, C-3, D-1, E-5
(d) Heterocyclic ring on N-1 yielded potent compound (d) A-3, B-4, C-2, D-1, E-5
90. The starting material for the synthesis of sulphadiazine is 99. Which of the following is a β-lactam antibiotic?
(a) Guanidine + formyl acetic acid (a) Penicillin + cephalosporin
(b) Propionitrile + ethyl acetate (b) Streptomycin + gentamycin
(c) Guanithidine + formyl acetic acid (c) Minocyclin + doxycycline
(d) Propionitrile + formyl acetic acid (d) Chloramphenicol
91. Which floro quinolone does not contain cycloprpane 100. Which isomer of ampicillin is clinically more active
ring at N-1 position than others?
(a) Gatifloxacin (b) Ciprofloxacin (a) D-(–) (b) D-(+)
(c) Sparfloxacin (d) Ofloxacin (c) L-(–) (d) L-(+)
92. Peptidoglacan is made up of ______________ amino 101. β-lactamase inhibitor clavunic acid is
sugar part. (a) 1,1-dioxo penicillanic acid
(a) N-acetyl glucosamine+N-acetyl muramic acid (b) Carbapenam
(b) N-acetyl biosamine+N-acetyl muramic acid (c) Cepham
(c) N-acetyl glucosamine+ N-acetyl glucosamine (d) 1-oxapenam structure, which has no acyl amino
(d) N-acetyl muramic acid+ N-acetyl muramic acid side chain

93. Which is not true in case of penicillin? 102. Which is an example of penam 1,1-dioxide?
(a) Good oral absorption but relatively acid labile (a) Sulbectam (b) Tazobactam
(b) Ineffective against Gram-negative bacilli (c) Clavunic acid (d) Both (a) and (b)
(c) Useful against Gram-positive cocci 103. Which is an example of monobectam?
(d) Highly stable to acid /base (a) Sulfazecin (b) Aztreonam
94. 2,6-Dimethoxy phenyl penicillin is IUPAC of (c) Tigemonam (d) All
(a) Methicillin (b) Ampicillin 104. Which drug inhibits mycobacterial RNA polymerase
(c) Amoxicillin (d) Carbencillin and is very useful in treating Mycobecterium avium
95. Which of the following is broad-spectrum penicillin? complex?
(a) Oxacillin (b) Methicillin (a) INH (b) Ethionamide
(c) Ampicilline (d) Azlocillin (c) Capreomycin (d) Rifambutin

96. Which of the following is a broad-spectrum ureido 105. Clavunic acid has a beta lactam ring fused with
penicillin? (a) Thienyl system (b) Thiadiazole
(a) Carbenicillin (b) Methicillin (c) Thiazolidone (d) Oxazolidone
(c) Ticarcillin (d) Azlocillin 106. 4-chloro benzophenone is a starting material of
97. Which of the following is a anti pseudomonal (a) Mebendazole (b) Albendazole
penicillin? (c) Thibendazole (d) None of above
(a) Carbenicillin (b) Methicillin 107. Which of the following agent has trioxane ring?
(c) Ampicillin (d) Azlocillin
3.262  Chapter 5

(a) Artemether (b) Metronidazole (a) Phenothiazine (b) Phenoxazone

(c) Halofantrine (d) Prongunil (c) Naphtoquinone (d) None
108. Which of the following is not an alkylating agent? 119. Indoline-containing moiety present in vinca alkaloid is
(a) Cyclophosphamide known as
(b) 6-Mercaptopurin (a) Catranthine (b) Vindoline
(c) Chlorambucil (c) Vinleuroside (d) Vinrosidin
(d) Thiotepa 120. Which of the following is a semisynthetic derivative of
109. Which of the following agents has aziridine moiety? podophyllotoxin?
(a) Dacarbazine (b) Busulfan (a) Etoposide (b) Mithramycin
(c) Altretamine (d) Thiotepa (c) Paclitaxel (d) Colchicine
121. Which of the following drugs is used as anti androgen
110. Acreloin toxicity is associated with:
in prostate cancer?
(a) Cyclophosphamide
(a) Flutamide (b) Aminoglutethimide
(b) 6-Mercaptopurin
(c) Mitotane (d) All
(c) Melphalan
(d) Dacarbazine 122. Which of the following drug is used as SERM in
advance breast cancer?
111. Which of the following drug is a phenyl alanine
(a) Flutamide (b) Aminoglutethimide
derivative?
(c) Mitotane (d) Tamoxifen
(a) Chlorambucil (b) Carmustine
(c) Melphalan (d) Dacarbazine 123. Which of the following agents is used to cure tumour?
(a) L-aspargin (b) L-asparginase
112. Which of the following drugs is not a derivative of (c) Pegaspargase (d) Both (b) and (c)
nitrosourea?
124. Tolcapone is a
(a) Streptozocin (b) Carmustine
(c) Lomustine (d) All of the above (a) Catechol-O-methyltransferase (COMT) inhibitors
(b) Antimuscarinic agents
113. Which of the following drugs is a purine base antagonist? (c) Inhibitors of MAO-B
(a) Fludrabin (b) 6-Mercaptopurin (d) Dopa decarboxylase inhibitor
(c) Cladrabin (d) All of the above
125. Which of the following is an anti fungal antibiotic?
114. Which of the following drugs is pyrimidine base (a) Erthromycin (b) Bleomycin
antagonist? (c) Cycloserine (d) Cycloheximide
(a) Cytrabin (b) Tegafur
126. Topically used sulphonamide is
(c) Capcitabin (d) All of above
(a) Sulphadoxine
115. All cytotoxic antibiotic have anthracyclin ring, except (b) Sulphamethoxazole
(a) Doxorubicin (b) Epirubicin (c) Silversulphadiazine
(c) Iadrubin (d) Dactinomycin (d) Dapsone
116. Anthracyclinone antibiotics differ from each other by 127. Rituxumab belongs to which type of monoclonal
(a) Location of phenolic –OH group antibody?
(b) Location of –OCH3 group (a) Murine
(c) Both (a) and (b) (b) Chimeric
(d) None (c) Humanized
117. Adriamycinol is 13-OH metabolite of: (d) Human monoclonal antibody
(a) Doxorubicin (b) Daunorubicin 128. Sulfasalazine is a prodrug that is activated in the intes-
(c) Iadrubin (d) Dactinomycin tine by bacterial enzymes. The enzyme responsible is:
(a) Azoreductase
118. Actinomycin having basic ring is
(b) Choline esterase
 Medicinal Chemistry  3.263

(c) Glucuronyltransferase (c) Pyrantel pamoate-spastic paralysis

(d) Amylase (d) Levamisole-flaccid paralysis
129. In cephalosporins, a higher resistance to hydrolysis by 139. Which of the following is not from an active metabolite?
β-Iactamase is shown when _________? (a) Cyclophosphamide (b) Thio-tepa
(a) The amino group is acylated (c) Nitrosoureas (d) Melphalan
(b) Replacement of sulphur with oxygen
140. Whch is the principle alkylator that is formed from
(c) Oxidation of ring sulphur to sulfoxide or sulfone
cyclophosphamide?
(d) Introduction of C-7 α-methoxy group
(a) Aldophosphmide
130. Which of the following is not present in macrolide? (b) 4-ketocyclophosphamide
(a) A large lactone ring (c) 4-hydroxycyclophosphamide
(b) A glycosidically linked amino sugar (d) Phosphoramide mustard
(c) A spiroketal group
141. Which of the antineoplastic agent is metabolized by
(d) A ketone group
xanthine oxidase?
131. Which of the following contains diethylamino sub- (a) 6-Mercaptopurine (b) Cholrambucil
stituents? (c) Aminopterine (d) None of the above
(a) Doxycycline (b) Minocycline
142. Diloxanide furoate is a furonyl ester of a phenol and it
(c) Methacycline (d) Demeclocycline
is synthesized starting from
132. Polyene antibiotics such as amphotericin-B most likely (a) 0-chlorophenol (b) p-chlorophenol
(a) Inhibits bacterial DNA synthesis (c) m-chlorophenol (d) p-aminophenol
(b) Binds to prokaryotic ribosomes
143. Which of following is second-generation quinolone
(c) Acts as anti metabolitis
antibiotic?
(d) Reacts with sterols in the membrane
(a) Ciprofloxacin (b) Ofloxacin
133. β-lactamase inhibitor calvulanic acid is (c) Sparfloxacin (d) Nalidixic acid
(a) Carbapenam (b) L-oxopenam
144. Which of the following is not correct?
(c) Cepham (d) None of the above
(a) Alopecia and cystitis due to acrolein the cyclo-
134. Which of the following compounds contains isoxazole phosphamide metabolite
group? (b) Cirtrovorum factor given in methotraxate toxicity
(a) Cloxacillin (b) Thiabendazole (c) Cytrabine inhibits DNA polymerase
(c) Benzimidazole (d) Albendazole (d) Mitomycin acts as alkylating agent at position 7
135. What is the chemical name of penicillin V? 145. Which of the statements is correct?
(a) Phenoxy methyl penicillin (a) Amino glycoside inhibition is concentration
(b) Benzyl penicillin dependent
(c) D-α-amino-p-hydroxy ethyl penicillin (b) β-lactam inhibition is time dependent
(d) 2,6-dimethoxyphenyl penicillin (c) Macrolide inhibition is concentration dependent
136. Which of the following does not cause hepatitis? (d) Only (a) and (b) are correct
(a) Ethambutol (b) Isoniazid 146. Which of the following acts directly on the cell mem-
(c) Rifampin (d) Pyrazinamide brane of microorganism affecting permeability?
137. Which of the following belongs to class NNRTI? (a) Penicillin (b) Nystatin
(a) Ritonavir (b) Abacavir (c) Tetracycline (d) Erythromycin
(c) Nevirapine (d) Lamivudine 147. At which place does penicillin have a carboxylic acid
138. The following pairs are correct except? group?
(a) Ivermictin-tonic paralysis (a) C-3 (b) C-2
(b) Piperazine-flaccid paralysis (c) C-6 (d) C-7
3.264  Chapter 5

148. Which of the following is not a synthetic drug? 157. Which of the following statement is incorrect?
(a) Isoniazide (b) Rifampin (a) Resistance to quinolones due to chromosomal
(c) Pyrazinamide (d) Ethionamide mutation producing enzyme DNA gyr
149. What is the mechanism of PAS? (b) Diuretic + trimethoprime-thrombocytopaenia
(c) Quinolone is more active at acidic pH
(a) Inhibits mycolic acid synthesis (d) Levofloxacin oral bioavailablity-is 100%
(b) Inhibits folic acid synthesis
158. Which of the following drugs belongs to ansamycin
(c) Inhibits DNA dependent RNA polymerase
group?
(d) Makes the tuberculosis organism susceptible to
reactive oxygen (a) Neomycin (b) Rifampicin
(c) Mithramycin (d) Bleomycin
150. Which pair is not matching?
159. Which of the following is without heterocyclic ring?
(a) Penicillin Inhibits transpeptidase
(b) Fluoroquinotone Inhibits enzyme topoisomerase (a) Nelfinavir (b) Loviride
(c) Dapsone Inhibits DHF reductase enzyme (c ) Troviridine (d) Zidovudine
(d) Ethambutol Inhibits arabinosyltranferases 160. Which of the following has imidazole nucleus?
151. Which of the statements is true? (a) Ciclopirox (b) Butaconazole
(a) Pyrazinamide is more active in alkaline media (c) Griseofulvine (d) Co-trimoxazole
(b) Ethambutol partially crosses BBB 161. Which is the potent inhibitor of tymidylate synthase?
(c) Streptomycin is also used in leprosy (a) Naftifine (b) 5-fluocytosine
(d) Both (a) and (c) (c) Ciclopirox (d) Ketoconazole
152. Which of the following paired incorrectly? 162. Which is an inhibitor of sterol-14-α-demethylase?
(a) Zidovudine Thymadine analogue (a) Naftifine (b) 5-fluocytosine
(b) Lmivudine Deoxycytidine analogue (c) Ciclopirox (d) Ketoconazole
(c) Abacavir Guanosine analogue
163. Which of the following is the antifungal antibiotic?
(d) Stavudine Adenosine analogue
(a) Naftifine (b) 5-fluocytosine
153. Which combination is effective against hepatitis C? (c) Nystatine (d) Nafimidone
(a) Interferon α + Ribavarin 164. What is the starting material for synthesis of ritonavir?
(b) Zidovudine + Lamivudine
(a) Pichlorohydrine
(c) Acylovir + Famciclovir
(b) Dioxolane
(d) Both (a) and (d)
(c) Hydrocinnamyl chloride
154. Which of the following mono clonal antibody is used (d) Phenylalanine
as anticancer agent?
165. Which of the following is synthesized from
(a) Rituximab (b) Muromonab 5-chloroantranilic?
(c) Trastutuzumab (d) (a) and (c) (a) Efavirenz (b) Emivjrdine
155. Primaquine is synthesized from? (c) Loviridine (d) Nevirapine
(a) Toluene (b) Anisole 166. Which of the following is thiazole analogue?
(c) Phenol (d) p-nitro phenol (a) Nelfinavir (b) Ritonavir
156. The active metabolite of anticancer cyclophospha- (c) Saquinavir (d) Loviride
mide is 167. Amodiaquine is a derivative of
(a) N-hydroxy cyclophosphamide (a) 3-Amino quinoline
(b) N-methyl cyclophosphamide (b) 4-amino quinoline
(c) N-acetyl cyclophosphamide (c) 2-amino quinoline
(d) N-propyl cyclopqosphide (d) 5-amino quinoline
 Medicinal Chemistry  3.265

168. What is the mechanism of action of levamisole? (a) Linezolid (b) Polymyxin
(a) Nicotine-like action, stimulating and subsequently (c) Ciprofloxacin (d) Penicillins
blocking neuromuscular junction 178. Which of the statement is correct?
(b) Reversal inhibition of S-adenosyl-L′-methionine-
(a) Sulfonamides resistance due to change in binding
n-decarboxylase
site at acetyl transferase
(c) Stimulates acetylcholine trasferase
(b) Tetracycline resistance due to efflux protein in cell
(d) Stereospecific inhibitor of alcohol reductase membrane
169. C-12 position is a part of the keto-enol tautomer in (c) Chloramphenicol resistance due to change in porin
which of the following systems? channel
(a) Macrolides antibiotics (d) Both (a) and (c)
(b) Penicillins 179. Which of following is anthranilic acid derivative?
(c) Tetracyclines
(a) Furosemide (b) Bumetanide
(d) Aminoglycoside antibiotics
(c) Ethacrynic acid (d) None
170. The cephalosporin antibiotic with a cyanomethyl side
180. In AT-II angtagonist, the functional group responsible
chain is _________
for AT-1 receptor blocking activity is
(a) Cephalexin (b) Cefadroxil
(a) Imidazole (b) Tetrazole
(c) Cefamandole (d) Cephacetrile
(c) Triazole (d) None
171. The antibiotic with imine functionality is?
181. Which of following is ultra short acting cardioselective
(a) Ampicillin (b) Roxithromycin beta blocker?
(c) Doxycyclin (d) Chloramphenicol
(a) Atenolol (b) Nebivolol
172. The naturally occurring tetracyclines contain which of (c) Esmolol (d) None
the following?
182. The adverse effect of MG COA-reductase inhibitor is:
(a) α-C4 dimethyl amino substituent
(a) Myalgia
(b) α-C3 dimethyl amino substituent
(b) Myositis and rhabdomylosis
(c) α-C3-C4 keto enol group
(c) Angio-oedema
(d) α-C3 dihydroxy substituent
(d) All of the above
173. β-lactum inhibitor clavulanic acid is
183. Cholestyramine is copolymer of:
(a) Carbapenam (b) 1-Oxopenam
(a) Divinyl benzene with epichlorohydrin
(c) Cepham (d) None of the above
(b) Tetraethylpentamine with quaternary ammonium salt
174. An imidazole aromatase inhibitor which is used to reduce (c) Divinyl benzene with quaternary ammonium salt
estrogen level is? (d) Tetraethylpentamine with epichlorohydrin
(a) Mitotane (b) Paramethasone 184. Lovastatin is obtained from which of following
(c) Emestine (d) Anastrazole microorganism?
175. Finasteride acts as 5-α-reductase inhibitor because of (a) Aspergiilus niger and Monoscus ruber
which property? (b) Aspergiilus terreus and Monoscus rubber
(a) It has C-1-2 double bond (c) Penicillium citrinium and Monoscus rubber
(b) It has C-1-5 double bond (d) Penicillium citrinium and Aspergiilus terreus
(c) It is nonsteroidal
185. Increased risk of arthrosclerosis is associated with
(d) It has 3-keto group decreased serum level of
176. Which sulphonamide does not contain free aromatic
amino group? (a) LDL (b) HDL
(a) Dapsone (c) Triglyceride (d) VLDL
(b) Mefenide
(c) Trimethoprim (d) None of the above 186. Clofibrate increases toxicity of
177. Which of the following causes inhibition of protein (a) Phenytoin (b) Tolbutamide
synthesis? (c) Coumarin (d) All of the above
3.266  Chapter 5

187. Which of following drug causes Monday morning 198. Drug used for the treatment of acute attack of gout
sickness? is _________
(a) Isosorbide dinitrate (a) Colchicine (b) Probenicide
(b) Glyceryl trinitrate (c) Sufipyrazone (d) Allopurinol
(c) Isosorbide mononitrate 199. Bumetanide contains _________
(d) None
(a) Phenoxy group at 4th position
188. For antianginal activity, the nitrate derivative must be (b) Phenoxy group at 5th position
metabolized into: (c) Phenoxy group at 3rd position
(a) Nitric oxide (b) Nitrous oxide (d) Does not contain any phenoxy group.
(c) Both (d) None 200. Increased risk of artheroscerosis is associated with
189. Which of following diuretics inactivate sulfahydryl decreased serum level of
(–SH) group of enzyme? (a) LDL (b) HDL
(a) Furosemide (b) Bumetanide (c) Triglyceride (d) VLDL
(c) Ethacrynic acid (d) None 201. Intermediate in biosynthesis of cholesterol is
190. Diuretics mean _________ (a) Mevalonic acid and Isopentenyl pyrophosphate
(a) Drugs which increases blood pressure (b) Mevanolic acid and Aldosterone
(b) Drugs which increases blood flow (c) Isoprenaline and Aldosterone
(c) Drugs which increases urine flow (d) Isoprenaline and Isopentenyl phosphate
(d) Drugs which decreases urine flow 202. Which of the following causes Bartter’s syndrome____
191. High ceiling diuretics is _________ (a) Loop diuretics (b) Osmotic diuretics
(a) Ethacrinic acid (b) Bumetanide (c) Thiazide diuretics (d) K+ sparing diuretics
(c) Furosemide (d) All of the above 203. Digoxin absorption is decreased by which of the fol-
192. Osmotic diuretics are used lowing drug:
(a) To cure higher blood pressure (a) Metoclopramide and sucralfate
(b) For treatment of glaucoma. (b) Metoclopramide and cholestyramine
(c) To cure gout (c) Both (a) and (b)
(d) Both (a) and (b) (d) None of above

193. Metabolite of a spironolactone is _________ 204. To avoid lithium toxicity patient using lithium carbonate
for mood disorder should not be prescribed
(a) Amrinone (b) Milrinone
(a) Acetazolamide (b) Furosemide
(c) Canrinone (d) Samzonone
(c) Mannitol (d) Hydrochlorthiazide
194. Hearing loss is side effect of one of _________
205. Patients taking digoxin for CHF are found to have
(a) Acetazolamide (b) Aldosterone elevated cholesterol level for whom which agent
(c) Amiloride (d) Hydroclorethiazide should not be prescribed with it?
195. Furosemide contains _________ ring (a) Lovastatin (b) Cholestyramine
(a) Furan (b) Thiazole (c) Clofibrate (d) Niacin
(c) Oxazole (d) Imidazole. 206. One of following diuretics is similar to that of diazoxide:
196. Sulphonamide group is present at thiazide diuretic at (a) Acetazolamide (b) Furosemide
position (c) Mannitol (d) Chlorthiazide
(a) 3 (b) 6 207. Which of following drugs have 1,3,4 thiadiazole ring?
(c) 7 (d) 9
(a) Amiloride (b) Dichloropenamide
197. Most serious side effect of spironolactone is (c) Acetazolamide (d) None
(a) Hyperkalemia (b) Hypokalemia 208. Digoxin has the following characteristics _________
(c) Hypernatremia (d) Hyponatremia
 Medicinal Chemistry  3.267

(a) Its action is terminated by metabolism 219. Increase plasma concentration of digoxin occurs by
(b) Plasma half-life is 20 hours following drug:
(c) Used in atrial fibrillation by increased force of (a) Omeprazole (b) Phenylbutazone
contraction (c) Quinidine (d) (b) and (c)
(d) Both (b) and (c)
220. The synthesis of following drug is;
209. IUPAC name of amrinone is
Cl Cl
(a) 5- amino (3,4’dipyridin)-6-one
(b) 4-amino 3-4’dipyridin)-6-one AlCl3
(c) 5-amino (3-4’dipyridin)-4-one O-CH2COOH + propionyl chloride X
HCHO
(d) 4-amino (3-4’dipyridin)-3-one
210. PDE-III inhibitor (a) X = ethacrynic acid
(a) Inhibits Na+-K+ ATPase pump (b) X = meclofenamic acid
(b) Inhibits hydrolysis of C-AMP (c) Both
(c) Both (a) and (b) (d) None
(d) None of the above 221. 3,5-diamino-N-(amino imino methyl)-6-chloropyrazine
211. Increased plasma concentration of digoxin occurs due to carboxamide is
(a) Omeprazole (b) Phenylbutazone (a) Torsemide (b) Amiloride
(c) Quinidine (d) Both (b) and (c) (c) Furosemide (d) Metiamide

212. The plasma half life of digoxin is: 222. In thiazide diuretics electron withdrawing group must
(a) 5–7 days (b) 20 hours be at:
(c) 40 hours (d) 48 hours (a) Fifth position (b) Sixth position
(c) Seventh position (d) Eight position
213. The sugar present in strophanthin-G is:
(a) Rhamnose (b) Digitoxose 223. The utllity of sulfone group in thiazide diuretics is for:
(c) Cymarose (d) None of the above (a) Increase potency of drug
214. Which of following is not benzimidazole derivative: (b) I.M administration
(a) Vesverinone (b) Sulmazole (c) I.V administration
(c) Milrinone (d) Pimabendan (d) None
215. In digitalis glycoside 17th position of steroidal ring is 224. Which of following drugs cause digoxin toxicity?
substituted by (a) Triamterene (b) Eplerenone
(a) ά,β unsaturated five-member lactone ring (c) Amiloride (d) Spironolactone
(b) ά,β unsaturated six-member lactone ring
225. Which of following drug conjugate with glucuronic acid?
(c) ά,β unsaturated five-member pyrone ring
(d) ά,β unsaturated five-member lactum ring (a) Bumetanide (b) Ethacrynic acid
(c) Furosemide (d) Calomel
216. The basic ring present in atorvastatin is:
(a) Indole (b) Pyrrole 226. Which of following is more potent diuretics?
(c) Napthalene (d) None of the above (a) Amidarone (b) Hydrochlorthiazide
217. Predict product obtained by treating 6-chloro-3,5- (c) Indapamide (d) None
diamino pyrazine 2-methyl carbonate with guanidine. 227. Gitelmann’s syndrome is found in which of following
(a) Amiloride (b) Hydrochlor thiazide diuretics?
(c) Triamterene (d) Furosemide (a) Loop diuretics (b) Osmotic
218. To avoid lithium toxicity patient using lithium carbonate (c) Thiazide (d) Xanthine
for mood disorder should not be prescribed 228. The site of action of thiazide diuretics is on:
(a) Acetazolamide (b) Furosemide (a) Proximal part (b) Distal part
(c) Mannitol (d) Hydrochlorthiazide (c) Loop of Henle (d) All
3.268  Chapter 5

229. Which of following drugs go 100% into systemic (a) Nitredipine (b) Nimodipine
circulation? (c) Nicardipine (d) Nifedipine
(a) Piretanide (b) Furosemide 241. The substrate for ACE is
(c) Bumetanide (d) Ethacrynic acid (a) Dipeptidyl carboxypeptidase
230. Which of following is potassium sparing diuretic? (b) Dipeptidyl oxytripeptidase
(a) Xipamide (c) Both
(b) Muzolimin (d) None
(c) Dichlorophenamide 242. Plasma half life of angiotensin-II is:
(d) Eplerenone
(a) 15min (b) 1 min
231. In thiazide diuretics position 7 is very important and is (c) 1hour (d) None
occupied by:
243. The group responsible for AT-1 receptor blocking
(a) Methyl group (b) Chloro group
activity is
(c) Sulphamoyl group (d) None
(a) Imidazole (b) Tetrazole
232. Thiazide diuretics cause following toxicity? (c) Triazole (d) None
(a) Potassium toxicity
244. Rofecoxib should not be given if patient is already
(b) Lithium toxicity taking
(c) Calcium toxicity
(a) Anxiolytic (b) Antidiabetic
(d) Digoxin toxicity
(c) ACE inhibitor (d) All
233. Which of the following ACE inhibitor is not bound to 245. One of following diuretics is similar to that of
plasma or bound 0.1 %? diazoxide?
(a) Captopril (b) Enalpril (a) Acetazolamide (b) Furosemide
(c) Lisinopril (d) Quinapril (c) Mannitol (d) Chlorthiazide
234. Which of following causes constipation?
246. Which of following drug is used in digitalis-induced
(a) Nifedipine (b) Diltiazem arrhythmia?
(c) Nitroglycerine (d) Verapamil
(a) Lidocaine (b) Amiodarone
235. Which of following is used in cerebral vasospasm?
(c) Tocainide (d) Phenytoin
(a) Nitredipine (b) Nicardipine
(c) Nimodipine (d) Isradipine 247. The basic ring present in amiodarone is
(a) Benzothiazole (b) Benzopyrole
236. Nifedipine blocks ___________ calcium channel?
(c) Benzofuran (d) Phenothiazine
(a) T-type (b) N-type
(c) P-type (d) L-type 248. The antiarrythmic activity of propefenone is given by
237. Plasma half life of renin is (a) R-enantiomer
(a) 30 min (b) 15 min (b) S-enantiomer
(c) 1min (d) 60 min (c) R and S enantiomer
(d) None of the above
238. Bradykinin is
(a) Nonapeptide (b) Heptapeptide 249. Which of following drug is used specially in ventricu-
(c) Octapepetide (d) Decapeptide lar arrhythmia?
(a) Lidocaine (b) Tocainide
239. Which of following drug metabolites is more potent
than parent? (c) Propafenone (d) All of the above
(a) Valsartan (b) Losartan 250. Which of following drugs contraindicates in ventricu-
(c) Telmisartan (d) Verapamil lar arrhythmia?
(a) Verapamil (b) Quinidine
240. Which of following contains tertiary amino group in
side chain? (c) Amiodarone (d) Sotalol
 Medicinal Chemistry  3.269

251. Which of following is not methane sulfonamide R. Cause slate-gray discoloration of skin.
derivative? S. Is potassium channel blocker
(a) Sotalol (b) Ibutalide (a) P, Q are right but R,S are wrong
(c) Dofetilide (d) Azimilde (b) P, Q, R are right but S is wrong
252. Chemical name of hydralazine is (c) All are correct
(a) 1-Hydrazinophthalazine (d) P,R,S are right but Q is wrong.
(b) 4-Hydrazinophthalazine 262. Following drugs act as an arterials vasodilators
(c) N, N-Diaminothalazine except one
(d) Phthalic hydrazine (a) Hydralazine (b) Minoxidil
253. Which of following contraindicates with sulfa drug? (c) Diazoxide (d) Sodium nitroprusside
(a) Procainamide (b) Disopyramide 263. Minoxidil is synthesized by:
(c) Lidocaine (d) Moricizine (a) Shaw synthesis (b) Chichibabin synthesis
254. Which of following is used in digitalis-induced (c) Pinner synthesis (d) Hantzch pyridine synthesis
arrhythmia? 264. Verapamil is synthesized by
(a) Propafenone (b) Amiodarone (a) Shaw synthesis
(c) Phenytoin (d) All (b) Chichibabin synthesis
255. Which of following is insulin secretogogue? (c) Pinner synthesis
(d) Hantzch pyridine synthesis
(a) Liraglutide (b) Pramlintide
(c) Exenatide (d) Both (a) and (c) 265. The starting material used for synthesis of pro­
256. Which of following is not short acting insulin panolol is:
preparation? (a) α-napthol and epichorohydrin
(a) Insulin lispro (b) Insulin aspart (b) α- napthol and chloropropanol
(c) Glargine insulin (d) None (c) β-napthol and epicholrohydrin
(d) All
257. Which of following phenylalanine derivative is used in
type-2 diabetes? 266. In which of following ACE inhibitor ester hydrolysis is
not present?
(a) Miglitol (b) Phenformin
(c) Repaglinide (d) Rosiglitazone (a) Enalpril (b) Quinapril
258. Which of following sulfonylurea derivatives contains (c) Ramipril (d) Lisinopril
pyrazine ring? 267. The amino acid present in lisinpril is:
(a) Glibenclamide (b) Glimrpride (a) Proline (b) Lysine
(c) Glibonuride (d) Glipzide
(c) Both (d) None
259. Which of following derivatives causes lactic acidosis
and cynocobalamine deficiency? 268. IUPAC name of nifedipine is:
(a) Sulfonyl urea (b) Meglinide (a) 1,4-dihydro-2,6-dimethyl-4-(3-nitro phenyl)-3,5
(c) Biguanide (d) Thiazolidinedione pyridine carboxylic acid dimethyl ester
260. Metformin have the following property except (b) 1,4-dihydro-2,6-dimethyl-4-(2-nitro phenyl)-3,5 pyr-
idine carboxylic acid dimethyl ester
(a) It activates GLUT-1 transport and increase glucose
uptake (c) 1,4-dihydro-2,6-dimethyl-4-(2-nitro phenyl)-3,5
(b) It absorbs vitamin B-12 pyridine carboxylic acid methyl ethyl ester
(c) It causes lactic acidosis (d) 2,4-dihydro-1,6-dimethyl-4-(3-nitro phenyl)-3,5
(d) It activates GLUT-4 transport and contraindicates pyridine carboxylic acid dimethyl ester
in pregnancy 269. Which of following α-glucosidase inhibitors is
261. Amiodarone de­oxynojirimycin dvt?
P. Contain benzfuran ring and benzoyl ring. (a) Miglitol (b) Acarbose
Q. Is use in supraventricular tachycardia. (c) Varcabose (d) Nateglinide
3.270  Chapter 5

270. Which of following is newer insulinomimetic agent? 280. The starting material for clonidine synthesis is _________
(a) Lisophyllin (b) Aminoguanidine (a) 2,6-Dichloroaniline + Ammonium thiocynate
(c) Vanadium salt (d) All (b) 2,5-Dichloroaniline + Ammonium thiocynate
271. IUPAC name of prazosin is: (c) 2,4-Dichloroaniline + Ammonium thiocynate
(a) 1-(4-amino 6,7 dimethoxy-2-quinzolinyl)-4- (d) 3,4-Dichloroaniline + Ammonium thiocynate
(2-furoyl) piperazine 281. Prazosin contains __________ as the basic moiety.
(b) 1-(3-amino 6,7 dimethoxy-2-quinzolinyl)-4- (a) Quinoline (b) Isoquinoline
tetrahydro-(2-furoyl) piperazine (c) Quinazoline (d) None
(c) 1-(5-amino 6,7 dimethoxy-2-quinzolinyl)-4- 282. What is the starting material of captopril?
(2-furoyl) pyrazine
(b) Acetoacetic acid (b) Methacrylic acid
(d) 1-(4-amino 6,7 dimethoxy-2-isoquinzolinyl)-4-
(c) Alanine (d) Formic acid
(2-furoyl) piperazine
283. What is the IUPAC name of ethacrynic acid?
272. The basic ring present in guanthedine is
(a) [2,3-dichloro-4-(2-methylenebutyryl)phenoxy]
(a) Azepine (b) Azocine
acetic acid
(c) Benzepine (d) Aziridine
(b) [2,3-dichloro-4-(2-methylenebutyryl)phenoxy]
273. Chemically diltiazem is propionic acid
(a) 1,4 dihydropyridine derivative (c) [2-chloro-4-(2-methylenebutyryl)phenoxy] acetic
(b) phenyl alkyl amine derivative acid
(c) benzothiazepine derivative (d) [2,3-dichloro-4-(2-ethylenebutyryl)phenoxy]
(d) None acetic acid
274. Which of following enantiomers of verapamil is cal- 284. Acetazolamide is synthesized via which of the follow-
cium channel blocker? ing intermediate?
(a) Levo (b) Dextro (a) 1-amino-2-mercapto-1,3-thiazole
(c) Racemic (d) None (b) 5-amino-2-mercapto-1,3,4-thiadiazole
(c) 1-amino-2-mercapto-1,3-thiazole
275. Chemically nifedipine is
(d) 5-amino-2-mercapto-1,3,4-tetrazole
(a) 1,4 dihydropyrimidine derivative
(b) 2,4 dihydropyrimidine derivative 285. Simvastatin has which of the following rings?
(c) 1,4 dihydropyridine derivative (a) Indole (b) Pyrrole
(d) 2,4 dihydropyridine derivative (c) Naphthyl (d) Pyridine
276. The utility of thiol group in ACE inhibitor is 286. Fluvastatin has which of the following rings?
(a) To increase binding to caboxylate group of ACE (a) Indole (b) Imidazole
(b) To increase binding to zinc (co-factor) ion of ACE (c) Naphthyl (d) Pyrrole
(c) To form hydrophobic interaction with peptide linkage 287. Naproxen is a derivative of _________
(d) None of this. (a) Arylpropionic acid
277. The antihypertensive drug with a tetrazole nucleus is (b) Arylethanoic acid
(a) Diazoxide (b) Valsartan (c) Arylpropionic ester
(c) Taludipine (d) Fosinopril (d) Arylpropionic ether .
278. Antianginal drug useful for the emergency treatment of 288. Ibuprofen contains _________
cyanide poisoning is (a) α-methyl group on acetic acid moiety
(a) Aspirin (b) Glyceryl trinitrate (b) β-methyl group on acetic acid moiety
(c) Amyl nitrate (d) Dipyridamole (c) α-methyl group on propionic acid moiety
279. Amiodarone has _________ basic nucleus. (d) β-methyl group on propionic acid moiety.
(a) Benzothiazole (b) Benzophenone 289. One of the following is a pro-drug _________
(c) Benzofuran (d) Benzopyrrole
 Medicinal Chemistry  3.271

(a) Ketoprofen (b) Naproxan 300. Which of the following gives oil of wintergreen during
(c) Pyroxicam (d) Sulinadac urine excretion?
290. Sulfide metabolites of one of the following is active (a) Aspirin (b) Salicylamide
(a) Ketoprofen (b) Naproxen (c) Methylsalicylate (d) None
(c) Pyroxicam (d) Sulinadac 301. Rofecoxib should not be given if the patient is already
291. One of the following is a selective COX-2 inhibiter taking
_________ (a) Anxiolytic (b) Antidiabetic
(a) Paracetamol (b) Nimesulide (c) ACE inhibitor (d) All
(c) Valdecoxib (d) None 302. Toxic metabolite of paracetamol which causes hepato-
292. One of the following is an inflammation-inducing toxicity is
substance used in experimental pharmacology. (a) N-acetyl p-benzoquinone imine
(a) Cellulose (b) HPMC (b) N-acetyl p-benzoquinone amine
(c) Carrageen (d) Guar gum. (c) O-dealkyl acetaminophen
(d) None
293. Phenylbutazone is a _________
303. Metabolism of paracetamol occurs by
(a) Pyrazolone derivative
(b) Pyrazolidinedione derivative. (a) Glucuronide and glycine
(c) N-arylanthranilic acid derivative. (b) Glucuronide and sulphate
(d) None of the above. (c) Glutathione and sulphate
(d) Glutathione and sulphate
294. One opioid analgesic which does not inhibit PG
synthesis is _________ 304. Which of following is a natural vasodialator?
(a) Celecoxib (b) Nafopam (a) Bradykinin (b) Adenosine
(c) Ketorolac (d) Antipyrine (c) Both (d) None
295. The isoxazole ring is present in which of following 305. Which isomer of ibuprofen is more active?
drug? (a) S (–) isomer (b) R (–) isomer
(a) Valdecoxib and paracoxib (c) S (+) isomer (d) R (+) isomer
(b) Celecoxib and rofecoxib 306. Benorylate is polymeric condensation of
(c) Celecoxib and valdecoxib
(a) Acetyl salicylate ester of B-napthol
(d) Paracoxib and celecoxib
(b) Acetyl salicylate ester of paracetamol
296. Which of the following drug is given parentrally? (c) Acetyl salicylate ester of piroxicam
(a) Celecoxib (b) Rofecoxib (d) None
(c) Valdecoxib (d) Paracoxib 307. Starting material for ibuprofen is
297. Which of the following drug is a prodrug? (a) Isobutyl benzene
(a) Nimesulide (b) Indomethacine (b) Isopropyl benzene
(c) Diclofenac (d) Nabumetone (c) Isobutyl acetophenone
298. Pyrazole derivative causes following side effects (d) None
____________ 308. Plasma half-life of piroxicam is
(a) Bonemarrow depression (a) 30 hours (b) 2 hours
(b) Leucopaenia (c) 45 minutes (d) 45 hours
(c) Agranulocytosis
309. Which of following drug causes anaphylaxis?
(d) All
(a) Tolmetin (b) Nimesulide
299. Basic ring present in valdecoxib is _________
(c) Indomethacin (d) Zomepirac
(a) Pyrazole (b) Furan
(c) Isoxazole (d) None 310. Phenylbutazone is a _________
3.272  Chapter 5

(a) Pyrazolone derivative blocker

(b) Pyrazolidinedione derivative. (c) Dibenzazepine derivative and D-4 and 5HT-2a
(c) N-arylanthranilic acid derivative blocker
(d) None of the above (d) Dibenzazepine derivative and D-2 and 5HT-2a
blocker
311. One opoid analgesic which does not inhibit PG
synthesis is _________ 320. The nipecotic acid derivative act by
(a) Celecoxib (b) Nafopam (a) GABA-α-agonist
(c) Ketorolac (d) Antipyrine (b) Blocking calcium channel
(c) Inhibiting GABA transaminase
312. Which of following bound 99% to protein?
(d) Inhibit GABA reuptake
(a) Ibuprofen (b) Flubiprofen
(c) Naproxen (d) All 321. Which of the following butyrophenones contains
benzimidazolinone side chain?
313. Metabolism of paracetamol occurs by
(a) Haloperidol (b) Droperidol
(a) Glucuronide and glycine
(c) Penfluridol (d) Trifluperidol
(b) Glucuronide and sulphate
(c) Glutathione and sulphate 322. Metabolism of phenacetin occurs by
(d) Glutathione and sulphate (a) N-dealkylation (b) O-dealkylation
(c) Hydroxylation (d) None of above
314. Which of following is a natural vasodialator?
(a) Bradykinin (b) Adenosine 323. Which of following drugs gives oil of wintergreen dur-
(c) Both (d) None ing urinary excretion?
(a) Aspirin (b) Salicylamide
315. Which isomer of ibuprofen is more active?
(c) Methyl salicylate (d) All of above
(a) S (–) isomer (b) R (–) isomer
(c) S (+) isomer (d) R (+) isomer 324. Which of following drugs causes lithium and digox-
in toxicity?
316. Basic ring system in triamterene is
(a) Nimesulide (b) Diclofenac
A. N B. N
N (c) Indomethacin (d) Rofecoxib
325. 5,5-Diphenyl hydantoin is prepared by condensing
A. N B. N N
(a) Benzil and urea
C. N N D. N N (b) Benzyl cynamide and ethyl carbamate
(c) Phenyl ethyl malonic ester and urea
N
C. N D. N N (d) Ethyl butyl malonic ester and urea
317. Identify the name of drug of following structure: 326. Amodiaquine is
CH2 − CH2 − CO − CH3 (a) 7-Chloro-4-(4-diethylamino methyl 4-hydroxy
-phenyl) quinoline
(b) 7-Chloro-4-(3-diethylamino methyl 4-hydroxy
MeO
-anilino) quinoline
(a) Naproxen (b) Nimesulide (c) 6 Ethoxy-8-(4-diethylamino methyl 4-hydroxy
(c) Nabumetone (d) None -phenyl) Isoquinoline
318. Patient suffering from status epileptics and already (d) 5-Chloro-4-(4-diethylamino propyl phenyl)
takeing folic acid tablet should not be given quinoline
(a) Valproic acid (b) Phenytoin 327. Barbiturates are
(c) Lamotrigine (d) All (a) Derived from malonic acid
319. Clozapine is (b) Cyclic ureides
(a) Dibenzoxazepine derivative and D-2 blocker (c) Urea derivatives
(b) Dibenzoxazepine derivative and D-4 and 5HT-2a (d) All of the above
 Medicinal Chemistry  3.273

328. Phenobarbital is classified as a (a) Alkyl substituents at 3-position decreases the

(a) Short-acting barbiturate activity
(b) Long acting-barbiturate (b) N-substituent at 1-position should be small
(c) Intermediate acting barbiturate (c) A phenyl or pyridyl at 5-position decreases the activity
(d) Ultra-short-acting barbiturate (d) The presence of electron-attracting substituent at
position 7 is required for activity
329. Promethazine contains
(a) 2-Dimethyl amoni propyl side chain 338. Diphenhydramine is synthesized from
(b) 2-Diethyl amoni propyl side chain (a) Toluene and benzoic acid
(c) Chloro diphenyl methane side chain (b) Benzene and benzyl chloride
(d) None of the above (c) Diphenyl ether and benzyl chloride
(d) Benzene and benzyl chloride
330. Sedative action of barbiturate is due to substituent at
C-5. It is due to 339. Chemical nomenclature of procaine is?
(a) High lipophilicity of group at C-5 position (a) 2-D iethylaminoethyI 4-aminobezoate
(b) N, N-DiethyI4-aminobenzoate
(b) Electronic withdrawing effect
(c) 4-Aminobenzamidoethyl amine
(c) Sterric effect
(d) 4-Amino-2-diethylaminoethyl benzoate
(d) Low lipophilicity of group at C-5position
340. Dimethyl [3-phenyl-3(2-pyridyl)-propyl]amine is the
331. Selective serotonin reuptake inhibitors is IUPAC name of _________
(a) Mianserin (b) Doxepin (a) Pheniramine (b) Benzocaine
(c) Fluoxetine (d) Amoxapin (c) Phenolphthalein (d) Phenformine
332. Theophylline chemically is a 341. The IUPAC name of glutethimide is
(a) 1,3,7-Trimethyl xanthine (a) 3-ethyl, 3’phenyl-2, 6-piperidine dione
(b) 1,3,7-Triethyl xanthine (b) p-sulfonamido-chloroimido benzoic acid
(c) 1,3-Dimethyl xanthine (c) 3-(5-nitrofurfurylideneamino) oxazolidin-2-one
(d) 3,7-Dimethyl xanthine (d) 2-(2-fluorobiphenyl-4-yl) propionic acid
333. Morphine undergoes microsomal oxidation by 342. Morphine and heroine differ from each other by
(a) N-dealkylation (a) Methyl group on nitrogen
(b) Aromatic hydroxylation (b) Acyl group at C3 and C6
(c) Oxidative deamination (c) Absence of d ring
(d) Acyl group at C4 and C6
(d) O-dealkylation
334. IUPAC name of diclofenoac is 343. IUPAC name of below structure is
CH3
(a) Sodium 2-[(2,6-dichlorophenyl} amino] phenyl
acetate NH
+
(b) Sodium 2-[(2-chlorophenyl) amino] phenyl acetate CH3
(c) Sodium 3-[(2,6-Dichlorophenyl) amino] phenyl N Cl
acetate
(d) Sodium 2-[(6-chlorophenyl} amino] phenyl acetate S
335. Paracetamol undergoes metabolism by A.

(a) N-hydroxylation (b) Deamination (a) 3-(3-chlorophenothiazin-10-yl)propyl-N ,

(c) O-dealkylation (d) Oxidative deamination N-dimethyl NH4Cl
(b) 2-(3-chlorophenothiazin-10-yl) propyl-N,N-di-
336. Risperidone belongs to class of methyl NH4CI
(a) Benzisoxazole (b) Butyrophenone (c) 3-(3-chlorophenoth iazin-10-yl)isopropyl-N,
(c) Benzimidazole (d) DihydroindoJone N-dimethyl NH4CI
337. One of the following is false about benzodiazepines. (d) 2-(3-chlorophenothiazin-10-yl)propyl-N,N-di-
Identify. methyl NH4Cl
3.274  Chapter 5

Answer Keys
1. (c) 2. (a) 3. (a) 4. (d) 5. (c) 6. (d) 7. (a) 8. (c) 9. (b) 10. (c)
11. (d) 12. (a) 13. (b) 14. (d) 15. (c) 16. (c) 17. (b) 18. (b) 19. (d) 20. (c)
21. (c) 22. (a) 23. (c) 24. (c) 25. (b) 26. (b) 27. (c) 28. (a) 29. (b) 30. (a)
31. (a) 32. (d) 33. (d) 34. (d) 35. (b) 36. (c) 37. (b) 38. (b) 39. (a) 40. (b)
41. (d) 42. (a) 43. (b) 44. (d) 45. (c) 46. (a) 47. (c) 48. (a) 49. (a) 50. (b)
51. (c) 52. (b) 53. (c) 54. (a) 55. (a) 56. (a) 57. (a) 58. (d) 59. (a) 60. (d)
61. (d) 62. (a) 63. (d) 64. (a) 65. (d) 66. (a) 67. (b) 68. (b) 69. (d) 70. (d)
71. (a) 72. (a) 73. (b) 74. (c) 75. (a) 76. (d) 77. (a) 78. (d) 79. (a) 80. (b)
81. (a) 82. (a) 83. (b) 84. (a) 85. (c) 86. (c) 87. (d) 88. (a) 89. (c) 90. (a)
91. (d) 92. (a) 93. (d) 94. (a) 95. (c) 96. (d) 97. (a) 98. (a) 99. (a) 100. (a)
101. (d) 102. (d) 103. (d) 104. (d) 105. (d) 106. (a) 107. (a) 108. (b) 109. (d) 110. (a)
111. (c) 112. (d) 113. (d) 114. (d) 115. (d) 116. (a) 117. (a) 118. (b) 119. (b) 120. (a)
121. (a) 122. (d) 123. (d) 124. (a) 125. (c) 126. (c) 127. (b) 128. (a) 129. (b) 130. (b)
131. (d) 132. (d) 133. (c) 134. (a) 135. (a) 136. (a) 137. (c) 138. (d) 139. (b) 140. (c)
141. (a) 142. (c) 143. (a) 144. (d) 145. (d) 146. (b) 147. (a) 148. (c) 149. (b) 150. (c)
151. (b) 152. (d) 153. (a) 154. (d) 155. (a) 156. (a) 157. (c) 158. (b) 159. (a) 160. (b)
161. (b) 162. (d) 163. (b) 164. (b) 165. (c) 166. (d) 167. (c) 168. (a) 169. (b) 170. (a)
171. (b) 172. (c) 173. (b) 174. (d) 175. (a) 176. (d) 177. (a) 178. (b) 179. (a) 180. (b)
181. (c) 182. (d) 183. (c) 184. (b) 185. (b) 186. (d) 187. (b) 188. (a) 189. (c) 190. (c)
191. (d) 192. (d) 193. (c) 194. (d) 195. (a) 196. (c) 197. (a) 198. (a) 199. (a) 200. (b)
201. (a) 202. (c) 203. (c) 204. (d) 205. (a) 206. (d) 207. (c) 208. (c) 109. (a) 210. (b)
211. (d) 212. (c) 213. (a) 214. (c) 215. (a) 216. (b) 217. (a) 218. (d) 219. (d) 220. (a)
221. (c) 222. (b) 223. (b) 224. (d) 225. (c) 226. (b) 227. (c) 228. (b) 229. (c) 230. (d)
231. (c) 232. (b) 233. (c) 234. (d) 235. (c) 236. (d) 237. (b) 238. (a) 239. (b) 240. (c)
241. (a) 242. (b) 243. (b) 244. (c) 245. (d) 246. (d) 247. (c) 248. (c) 249. (d) 250. (a)
251. (d) 252. (a) 253. (a) 254. (c) 255. (d) 256. (c) 257. (c) 258. (d) 259. (c) 260. (d)
261. (c) 262. (d) 263. (b) 264. (d) 265. (a) 266. (d) 267. (c) 268. (b) 269. (b) 270. (c)
271. (a) 272. (b) 273. (c) 274. (b) 275. (c) 276. (b) 277. (b) 278. (c) 279. (c) 280. (a)
281. (c) 282. (b) 283. (a) 284. (b) 285. (c) 286. (a) 287. (a) 288. (a) 289. (d) 290. (d)
291. (c) 292. (c) 293. (b) 294. (b) 295. (a) 296. (d) 297. (d) 298. (c) 299. (c) 300. (c)
301. (c) 302. (a) 303. (b) 304. (b) 305. (c) 306. (b) 307. (a) 308. (d) 309. (d) 310. (b)
311. (b) 312. (d) 313. (b) 314. (b) 315. (c) 316. (c) 317. (c) 318. (b) 319. (c) 320. (d)
321. (b) 322. (b) 323. (c) 324. (c) 325. (b) 326. (b) 327. (d) 328. (b) 329. (d) 330. (a)
331. (c) 332. (c) 333. (a) 334. (a) 335. (b) 336. (a) 337. (c) 338. (b) 339. (a) 340. (d)
341. (b) 342. (b) 343. (a)
 chapter 6
Inorganic Chemistry

1. TOPICAL PREPARATION emollient influence on an inflamed area of the body.

Astringent Emolient
It is the substance that tends to shrink or constrict body Any preparation or substance that has a softening or
tissues, usually locally after topical medicinal application soothing effect, especially when applied to the skin.
and it also precipitates the protein.
Adsorbent
Demulcent Having capacity or tendency to adsorb or cause to
It is a medicine or other preparation that has a soothing or accumulate on a surface.

Compounds Chemical Formula Category/Use Analysed by Charactaristics

Zinc Oxide ZnO Astringent and Acidimetric ZnO Ointment –15%

protective back titra- Concentration
tion

Calamine Chemically, it is Astringent and – Used as lotion and

ZnO with small protective ointment
amount of Ferric
Oxide

Zinc Stearate {CH3 (CH3)16COO}Zn Astringent and Complexo- Used as a Dusting Powder
Antimicrobial metric titra-
agents tion

Alum (Hydrated KAl(SO4)2.12H2O. Astringent Gravimetry Used in concentration

potassium aluminium Pharmaceutical or precipi- 0.5–5%
sulfate-potassium alum) aid tation by
in stypic pencil ammonia
which stop the
bleeding from
small cuts

Titanium Dioxide TiO2 Protective and Complexo- –

Pharmaceutical metric titra-
aid tion

Hydrogen Peroxide H2O2 Germicides Oxidation

Deodorants reduction
titration

Potassium Permenganate KMnO4 Anti infective Oxidation 0.006–2%

and Antiseptic reduction
titration