Laboratory Manual of Pharmaceutical Chemistry-IA

(Organic Chemistry-I)
First Prof. Pharm. D, Second Semester (Pharm. 323)

Compiled and Edited By

Dr. Saeed Ahmed Lakho
Pharm. D, R.Ph,, M. Phil (Analytical Chemistry)
Ph. D (Pharmaceutical Chemistry)

Department of Pharmaceutical Chemistry, Faculty of Pharmacy,

University of Sindh Jamshoro, Sindh

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 CERTIFICATE

It is to certify that Miss/Mr………………………………………S/D/of…….………………………

Having Roll Number ……..……………………………………. of First Prof. Pharm. D
(Morning/Evening) has carried out the necessary practical work as approved by the
University of Sindh for Second Semester 2024.

Date

Subject Teacher

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 Table of Contents
S.No. Object tittle Page No.
Theory 4
1. Synthesis of Benzylideneaniline and calculate its percentage 8
yield
2. Synthesis of Phenyl-azo-2-naphthol and calculate its percentage 9
yield
3. Synthesis of α-glucose pentabenzoate and calculate its 10
percentage yield
4. Synthesis of phenyl benzoate by Schotten-Baumann Reaction 11
and calculate its percentage yield
5. Synthesis of p-nitroacetanilide and calculate its percentage yield 12
6. Synthesis of diazoaminobenzene and calculate its percentage 14
yield
7. Synthesis of Dibenzalacetone and calculate its percentage yield 15
8. Synthesis of Mucic Acid and calculate its percentage yield 16
9. Synthesis of p-nitroaniline and calculate its percentage yield 17
10. Sythesis of Benzoyl Alcohol and Benzoic acid by Cannizzaro 18
Reaction.

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THEORY OF PRACTICALS
Theory:
Organic Chemistry:
Organic chemistry is the study of the structure, properties, composition, reactions,
and preparation of carbon-containing compounds. Most organic compounds contain
carbon and hydrogen, but they may also include any number of other elements (e.g.,
nitrogen, oxygen, halogens, phosphorus, silicon, sulfur). The exception may be in
case of oxides and cyanides etc.
Functional groups:
Specific group of atoms combined to give a function in a molecule. or
In organic chemistry, a functional group is a substituent or moiety in a molecule that
causes the molecule's characteristic chemical reactions.
There are many functional groups in organic chemistry:
 Alkane, alkene, alkyne, aldehyde, ketone, ether, ester, carboxylic acid, amine,
imine, amide etc.
These all functional groups have different structures: and for each of these different
suffixes are used to denote them.
1. Alkanes: Alkanes have the general chemical formula CnH2n+2. In organic
chemistry, an alkane is saturated hydrocarbon. An alkane consists of hydrogen
and carbon atoms arranged in a tree structure in which all the carbon–carbon
bonds are single.
Methane CH4
2. Alkenes: Alkenes are class of hydrocarbons (e.g. containing only carbon and
hydrogen) unsaturated compounds with at least one carbon-to-carbon double
bond. General formula is CnH2n. Another term used to describe alkenes is
olefins. Alkenes are more reactive than alkanes due to the presence of the
double bond.
Ethene CH2=CH2
3. Alkyne: Alkynes are class of hydrocarbons (e.g. containing only carbon and
hydrogen) unsaturated compounds with at least one carbon-to-carbon triple
bond. General formula is CnH2n.

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4. Carbonyl Carbon: The carbon having double bond with oxygen. There is a
slight positive charge on carbon and slight negative on oxygen due to
electronegative oxygen.

5. Aldehyde: Any organic compound in which a carbon atom shares a double

bond with an oxygen atom, a single bond with a hydrogen atom, and a single
bond with another atom or group of atoms. OR carbonyl carbon bonded with
Carbon and hydrogen with single bond or two hydrogen atoms by single bond.
6. Amide: It is usually an organic compound that contains a functional group
consisting of an acyl group (R–C=O) linked to a nitrogen atom: The simplest
amides are derivatives of ammonia (NH3) in which one hydrogen atom has
been replaced by an acyl group.
7. Carboxylic Acid: In organic chemistry, a carboxylic acid is an organic acid
that contains a carboxyl group (-COOH) attached to an R-group. The general
formula of a carboxylic acid is R−COOH or R−CO₂H, with R referring to the
alkyl, alkenyl, aryl, or other group.
8. Ester: In chemistry, an ester is a compound derived from an acid in which the
hydrogen atom of at least one acidic hydroxyl group of that acid is replaced
by an organyl group.
9. Acid Halide: A compound derived from an acid in which the hydrogen atom
of at least one acidic hydroxyl group of that acid is replaced by halide group.
10.Ketone: This is functional group of organic compounds with the structure
R−C−R', where R and R' can be a variety of carbon-containing substituents.
Ketones contain a carbonyl group −C−. The simplest ketone is acetone, with
the formula (CH₃)₂CO.

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Schiff Base:
Schiff bases are a vast group of compounds characterized by the presence of a double
bond linking carbon and nitrogen atoms, the versatility of which is generated in the
many ways to combine a variety of alkyl or aryl substituents. In organic chemistry,
a Schiff base (named after Hugo Schiff) is a compound with the general structure R-
C=N-R (R=alkyl or aryl, but not hydrogen).
Origin: Compounds of this type are both found in nature and synthesized in the
laboratory.
Classification: They can be considered a sub-class of imines, being either secondary
ketimines or secondary aldimines depending on their structure. The term is often
synonymous with azomethine which refers specifically to secondary aldimines.

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Uses:
Schiff bases have been investigated in relation to a wide range of contexts, including
antimicrobial, antiviral and anticancer activity. They have also been considered for
the inhibition of amyloid-β aggregation.
p-nitroacetanilide Theory: The organic compound p-nitro acetanilide can be
prepared from the acetanilide through nitration. When acetanilide is treated with the
nitrating mixture, that is, a mixture of sulphuric acid and nitric acid, it forms p-nitro
acetanilide. Also, along with p-nitro acetanilide, as a minor product, o-nitro
acetanilide is also formed. Since o-nitro acetanilide is much soluble in alcohol, it is
so easy to isolate p-nitro acetanilide through crystallization.
It is a type of electrophilic substitution reaction. Here, the electrophile -NO2 will
attach the para position because the -NHCOCH3 is considered as an electron
releasing group. And nitro anilines will be prepared by this form of reaction, since
if it is not possible to nitrate aniline, the amino group would be oxidised with a nitrate
mixture. Also, in order to protect the amino group from oxidation, first, acetanilide
is nitrated to produce p-nitro acetanilide and then on hydrolysis to produce p-
nitroaniline, which is difficult to obtain by direct nitration.

Mucic Acid:

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 EXPERIMENT 1
Object: Synthesis of Benzylideneaniline and calculate its percentage yield.

Procedure:

1. Mix 4.2 g (4.0 mL) of purified benzaldehyde and 4.1 g (4.0 mL) of redistilled
aniline in a small evaporating dish.
2. Heat on a boiling water bath for 20 minutes.
3. Stir the mixture frequently with a glass rod; globules of water soon appear on
the surface of the oil.
4. Cool the basin in water and stir well; the oil recrystallize.

Result:

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 EXPERIMENT 2
Object: Synthesis of Phenyl-azo-2-naphthol and calculate its percentage yield.

Procedure:
1. Dissolve 2.5 g (2.45mL) of pure aniline in 8 mL of concentrated hydrochloric
acid and 8 mL of distilled water in a conical flask or small beaker. (Solution
A).
2. Dissolve 2.0 g of sodium nitrite in 10 mL of water (Solution B).
3. Diazotize solution A with help of solution B. (Solution C).
4. Prepare a solution of 3.9 g of pure 2-naphthol (β-naphthol) in 22.5 mL of 10%
sodium hydroxide solution in 250 mL beaker (Solution D). Cool the solution
to 5° by immersion in an ice bath, assisted by the direct addition of about 10-
15 g ice.
5. Stir the solution D vigorously and add the cold diazonium salt solution
(Solution C) very slowly; a red color develops and red crystals of phenyl-azo-
2-naphthol soon separate.
6. When all the diazonium salt solution has been added, allow the mixture to
stand in an ice bath for 10 minutes with occasional stiring.
7. Filter the solution through a Buchner funnel with gentle suction.
8. Recrystallize the product with glacial acetic acid (30-35mL).
9. The yield of phenyl-azo-2-naphthol is 6.0 g. It has m.p of 131°.

Result:

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 EXPERIMENT 3
Object: Synthesis of α-glucose pentabenzoate and calculate its percentage yield.

Procedure:
1. Dissolve 0.5 g of glucose in 25 ml of water in a conical flask.
2. Add 2.0 ml of redistilled benzoyl chloride.
3. In to the mixture, add 15 ml of NaOH solution (10%).
4. Stopper the flask and shake vigorously at frequent intervals until odor of
benzoyl chloride disappears (about 15 minutes) and a crystalline product
separates.
5. Collect the crystals by suction filtration and wash well with water.
6. Recrystallize the crude product from ethanol or methylated spirit.
7. The yield of α-glucose pentabenzoate is 1.7g and m.p 184°.
Result:

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 EXPERIMENT 4
Object: Synthesis of phenyl benzoate by Schotten-Baumann Reaction and calculate
its percentage yield.

Procedure:

1. Dissolve 2.5 g of phenol in 38 ml of 10 % sodium hydroxide solution

contained in a 100 ml conical flask.
2. Add 5.5 g (4.5 ml) of redistilled benzoyl chloride, cork the flask securely and
shake the mixture vigorously for 10 minutes.
3. At the end of this period the reaction is usually practically complete and a
solid product is obtained.
4. Filter off the solid ester with suction, break up the lumps on the filter, wash
thoroughly with water and drain well.
5. Recrystallize the crude ester from methylated spirit.
6. The yield is 4.1 g, m. p. 69°.

Result:

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 EXPERIMENT 5
Object: Synthesis of p-nitroacetanilide and calculate its percentage yield.

Materials Required
A. Chemicals: Acetic acid, Acetanilide, Fuming Nitric acid, Concentrated
Sulphuric acid, Ethyl alcohol.
Glasswares: Conical flask, Filter paper, Dropping funnel, Pipette, Buchner funnel,
Glass rod.
Procedure
 Take 3 grams of finely powdered acetanilide in a clean beaker and then dissolve it
by adding glacial acetic acid by carefully stirring the content at room temperature.
 Now, warm the mixture gently to dissolve acetanilide completely.
 Then, cool the solution and slowly add the concentrated sulphuric acid with constant
stirring. By doing so, the solution becomes warm. Then, keep the mixture in an ice-
bath, and a clear solution is obtained.
 Now, add fuming nitric acid dropwise through a dropping funnel with constant
stirring to the cool solution.
 During this whole process, always maintain the temperature below 20℃.
 Once the addition of nitric acid is over, the beaker can be removed from the freezing
mixture bath and allowed to stand at room temperature for half an hour.
 In a beaker, pour the mixture into 100 grams of crushed ice and stir well.
 By doing so, large crystals of p-nitro acetanilide are obtained and then filter those
crystals via filter paper.
 The separated p-nitro acetanilide is washed with cold water to remove excess acid.
 It is then crystallized from ethyl alcohol. Now, dry the crystals in filter paper folds
and weigh them to know the yield.



Observations
Let us look at the sample observations, which are tabulated below:

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Result:

Precaution:
 Temperature has to not exceed extra than 20 degree C.

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 EXPERIMENT 6
Object: Synthesis of diazoaminobenzene and calculate its percentage yield.

Requirements:

Chemicals: aniline, hydrochloric acid, sodium nitrite, sodium acetate, light

petroleum.

Glasswares: Conical flask (100 ml), Buchner funnel, beaker.

Procedure:

1. In a 100 ml conical flask place 40 ml of water, 12 g (10 ml) of concentrated

hydrochloric acid and 7 g (6.9 ml) of pure aniline.
2. Shake vigorously and then add 25 g of crushed ice.
3. Run in a solution of 2.6 g of sodium nitrite in 6 ml of water, with constant
shaking during a period of 5 minutes.
4. Allow to stand with frequent shaking for 5 minutes and add a solution of 10.5g
of crystallized sodium acetate in 20 ml of water during 5 minutes.
5. A yellow precipitate of diazoaminobenzene begins to form immediately;
allow to stand with frequent shaking for 20 minutes and do not allow the
temperature to rise above 20°.
6. Filter the yellow diazoaminobenzene on a buchner funnel, wash it with 100
ml of cold water, drain as completely as possible and spread it on a sheet of
filter paper to dry. The yield of crude diazoaminobenzene, m.p. 91° is 7.8 g.
Recrystallize 1 g from light petroleum, b. p 60-80°, the pure compound, m.p
97° us obtained.

Result:

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 EXPERIMENT 7
Object: Synthesis of Dibenzalacetone and calculate its percentage yield.
Procedure:
1. In 150 ml conical flask place a cold solution of 5 g of sodium hydroxide pellets
in 50 ml of water and 40 ml of alcohol (Ethanol).
2. Whilst swirl, the contents of the flask, add a mixture of 5.3 g (5.1 ml) of pure
redistilled benzaldehyde and 1.5 g (1.9 ml) of acetone.
3. Shake frequently and maintain the temperature at 20-25 °C for 15 minutes by
immersion of the flask in a bath of cold water.
4. Filter off the precipitated dibenzalacetone at the pump and wash it with cold
water to eliminate the alkali as completely as possible.
5. Dry the solid at room temperature upon filter paper to constant weight. The
theoretical yield is 5.3 g and m.p. 105-107 °C.

Result:

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 EXPERIMENT 8
Object: Synthesis of Mucic Acid and calculate its percentage yield.
Procedure:
1. Place 5 g of lactose in an evaporating dish and add 50 ml of dilute nitric acid
(1:1).
2. Warm gently in a fume cupboard (hood): a vigorous reaction ensues.
3. Continue the evaporation until the volume is reduced to about 10 ml.
4. The mixture becomes thick and pasty owing to the separation of mucic acid.
5. When cold, dilute with 15 ml of water filter at the pump and wash crude acid
with a little cold water.
6. Purify the mucic acid by dissolving it in the minimum volume of dilute (2N)
sodium hydroxide solution and precipitating with dilute hydrochloric acid:
do not allow the temperature to rise 25 degree.
7. Melting point of mucic acid is 212-213°.

Result:

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 EXPERIMENT 9
Object: Synthesis of p-bromoaniline and calculate its percentage yield.
Procedure:
1. Dissolve 7.5 g of p-bromoacetanilide in 15 ml of boiling ethanol (or
methylated spirit) contained in a 100 ml round bottom flask equipped with a
4” double surface condenser.
2. Add a solution of 4 g of potassium hydroxide pellets in 5 ml of water.
3. Reflux for 30 minutes and dilute with 60 ml of water; fit the flask with a wide
delivery tube leading to a condenser set for downward distillation.
4. Distill the mixture (wire gauze or air bath) until 35 ml of distillate (alcohol
and water) are collected.
5. Pour the residue into 75 ml of cold water.
6. The p-bromaniline separates as an oil which soon solidifies.
7. Melting point of p-bromoaniline is 66°.

Result:

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 Experiment 10
Object: Sythesis of Benzoyl Alcohol and Benzoic acid by Cannizzaro Reaction.
Procedure:
1. Dissolve 12.5 g of potassium hydroxide pellets in 60 ml of water contained in
200 ml round bottom flask and add to the solution 21.1 g (20 ml) of freshly
distilled, purified benzaldehyde.
2. Fit the 5” Liebig condenser to the flask and reflux the mixture for 1 hour,
preferably in an air bath.
3. Cool the reaction mixture; if necessary add just sufficient water to dissolve
any precipitated potassium benzoate.
4. Pour the liquid into a separatory funnel.
5. Shake the solution in order to ensure thorough extraction of the benzyl alcohol
by the ether, separate the lower aqueous solution and carry out one further
extraction with 20 ml of ether.
6. Pour the aqueous solution (remaining from the ether extraction) with stirring
into a mixture of 30 ml of concentrated hydrochloric acid, 30 ml of water and
about 50 g of crushed ice.
7. Filter off the precipitated benzoic acid at the pump, wash it with a little cold
water and drain and recrystallize from boiling water (150-200 ml).
8. Melting point of benzoyl alcohol is 205.5° and benzoic acid is 8.8°.

Result:

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