Chemistry 261 W2015 Problem Sets

CHEM 261 – Introductory Organic Chemistry I

Problem Sets

Instructor: Christopher Cairo

University of Alberta
Department of Chemistry

CAIRO – University of Alberta page 1

Chemistry 261 W2015 Problem Sets

Problem Set 1
Instructions: Problem sets will be posted online at eClass as we complete each of the units
during the semester. These problems will be a mix of problems that I have written and assigned
problems in the textbook. Answers to non-textbook problems will be posted.

How NOT to do Organic problem sets: DO NOT read the problem while looking at
the answer key. You should use each problem set as a way to test yourself and how much you
understand about the course so far. Write out as many problems as possible – this is the best way
to learn and remember the material.

1.1 ) Write Lewis structures for the following:

a) HCl b) CH 2Cl2

c) CH2 CH 2 d) Cl2

e) NO2 f) HCN

g) CO2 h) CO

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Chemistry 261 W2015 Problem Sets

1.2 ) Assign formal charges to the indicated atoms in the following structures:
O H
a) b) H H
N
O
H

O
c) H H d)
O
N
H

H O
O
e) f)

C
g)

1.3 ) Write as many major resonance structures as possible for the following:

O
a) b)

c) d) N

e)

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Chemistry 261 W2015 Problem Sets

1.4 ) Write out the atomic orbitals and populate them with the indicated number of electrons:

a) Carbon with 6 e- b) N with 8 e-

1.5 ) Convert the following condensed structures to bond line structures:

a) CH3 (CH2 )3 COCH 3 b) (CH 3 )3 CCH2 CH3

c) CH 3OCH 3 d) CH2 CH(CH 2)3 OCH 3

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Chemistry 261 W2015 Problem Sets

1.6 ) Write condensed structures for the following:

OH
a) b)

c)

1.7 ) Count the number of carbon atoms in the following:

a) b)

c) d)

e)

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Chemistry 261 W2015 Problem Sets

1.8 ) Amino acids are important biomolecules as constituents of proteins. The acid shown below
is tyrosine.
tyrosine

OH
NH 2
HO

O
a) Identify each of the ionizable groups on the molecule.
b) Which of these has the lowest pKa?
c) Write an ionized form for each of these groups.
d) What would you predict to be the charge state for this compound in water at pH = 7?

1.9 ) As we saw in class (Notes pg. 19-20), the charge state of organic molecules can influence
their function. Consider the following conditions, and predict which of these is more likely to
penetrate a cell membrane (The membrane is a hydrophobic environment – much like an organic
solvent).
a) A basic compound is injected in an acidic solution.
b) An acidic compound is injected in an acidic solution.

1.10) Many of the reactions we will look at involve nucleophilic attack. Consider the following
reactions and write reaction mechanisms using curved arrows for each. Are there any similarities
between these?

a) OH O -Na+
+ NaH + H2

b)
OH O -Na +
+ Na + -OCH 3 + HOCH 3

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Chemistry 261 W2015 Problem Sets

1.11) Write reaction mechanisms for the following:

O O
a) OH - + H 2O +
OH O-

H H
+H O O
b) O + H2 O +
H OH OH

Cl
c) Cl- +

Cl O
d) +
Na- O Na+Cl- +

Also see textbook problems from Wade:

Chapter 1
1-1–1-19 (in chapter problems); 1-20–1-23, 1-26–1-28, 1-31, 1-33, 1-34–1-40, 1-45, 1-48, 1-53

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Chemistry 261 W2015 Problem Sets

Answer Key #1
1.1 ) Write Lewis structures for the following:

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Chemistry 261 W2015 Problem Sets

1.2 ) Assign formal charges to the indicated atoms in the following structures:
-1
O H
a) b) H H
N
O
H +1

O
c) H H d)
O
N
H +1 0

-1
H O
O
e) f)
+1

+1
C
g)

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Chemistry 261 W2015 Problem Sets

1.3 ) Write as many major resonance structures as possible for the following:

1.4 ) Write out the atomic orbitals and populate them with the indicated number of electrons:
a) Carbon with 6 e- b) N with 8 e-

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Chemistry 261 W2015 Problem Sets

1.5 ) Convert the following condensed structures to bond line structures:

a) CH 3(CH 2) 3COCH3 b) (CH3 )3CCH 2CH3

O

c) CH 3 OCH3 d) CH 2CH(CH 2) 3OCH 3

O O

1.6 ) Write condensed structures for the following:

OH
a) b)

CH 3CH2 CH(OH)CH 3 CH 3 CHCHCH2 CH 3

c)

CHC(CH 2) 2CH(CH 3 )2

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Chemistry 261 W2015 Problem Sets

1.7 ) Count the number of carbon atoms in the following:

a) b)

8 7

c) d)
6 5

e)

4
1.8) Amino acids are important biomolecules as constituents of proteins. The acid shown below
is tyrosine.
tyrosine

OH
NH 2
HO

a) Identify each of the ionizable groups on the molecule.

pKa of NH3+ pKa ~9

~10-11

OH
NH2
HO

pKa ~4.5

b) Which of these has the lowest pKa?

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Chemistry 261 W2015 Problem Sets

The acid group has the lowest pKa.

c) Write an ionized form for each of these groups.

O-
NH 3 +
-
O

d) What would you predict to be the charge state for this compound in water at pH = 7?

OH
NH 3 +
-O

O
At pH 7, only the acid and amine would be ionized, giving the molecule a net neutral charge.

1.9 ) As we saw in class (Notes pg. 18-19), the charge state of organic molecules can influence
their function. Consider the following conditions, and predict which of these is more likely to
penetrate a cell membrane.
a) A basic compound is injected in an acidic solution.

A basic compound (A) will be protonated (HA+) in an acidic solution. Therefore, it will not
cross a membrane well and will not enter the cell.

b) An acidic compound is injected in an acidic solution.

An acidic compound (HA) in acidic solution will be neutral, and should cross the membrane.
Once in a neutral environment it will become charged as A-.

1.10 ) Many of the reactions we will look at involve nucleophilic attack. Consider the following
reactions and write reaction mechanisms using curved arrows for each. Are there any similarities
between these?

a) OH O -Na+
+ NaH + H2

b)
OH O -Na +
+ Na + -OCH 3 + HOCH 3

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Chemistry 261 W2015 Problem Sets

1.11 ) Write reaction mechanisms for the following:

O O
a) OH - + H2O +
OH O-

H H O H
O+ O
b) + H2 O +
H OH OH

Cl
c) Cl- +

Cl O
d) +
Na- O Na+Cl- +

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Chemistry 261 W2015 Problem Sets

Problem Set #2

Instructions: Problem sets will be posted online at eClass as we complete each of the units
during the semester. These problems will be a mix of problems that I have written and assigned
problems in the textbook. Answers to non-textbook problems will be posted on eClass.

2.1 ) Rank the following molecules with increasing permanent dipole moment. Hint: First figure
out the molecular geometry!

a) HF b) CH4

c) NH3 d) CO2

e)
Cl Cl

2.2 ) Many biomolecules have polar functional groups. Sketch the approximate dipole of each of
the following structures.

O
a) b) O
H H H
N
H

c) d) HO H
OH N
O H

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Chemistry 261 W2015 Problem Sets

2.3 ) You may not realize that you are already familiar with the properties of organic molecules
that you encounter in everyday life. What can you say about the relative boiling points or
melting points of the following materials? Answer the questions below and rank these
materials in increasing melting/boiling points. Does your experience with some of these
materials fit with the trends we’ve discussed?

a) lighter fluid (butane). Is this a liquid at atmospheric conditions?

b) Gasoline (major component C5-C12 alkanes, such as heptane).
c) Natural gas (methane).
d) Cooking oil (linoleic acid, C18:2).
e) Butter (~30% oleic acid, C18:1).
f) Beeswax (major component palmitate, C16).
g) Kerosene (C12-C15 alkanes, such as dodecane).
h) Petroleum jelly (C25).

2.4 ) Line drawn structures are useful, but are only a static model of dynamic molecular
structures. Rationalize the following data and describe the inadequacies of the line model
drawn.

C-N Bond Length Typical C-N Bond Length

O
1.33 Å 1.47 Å

H 3C NH2

2.5 ) Hybrid atomic orbitals can be used to approximate molecular orbitals. Describe the hybrid
atomic orbitals of the following structures:
H H
a) b) H H
H H

2.6 ) Identify the hybridization of all the heavy atoms (non-hydrogen) in the following
strucuture:

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Chemistry 261 W2015 Problem Sets

Also see textbook problems from Wade:

Chapter 2
2-1–2-22 (in chapter problems); 2-23–2-38, 2-40, 2-42, 2-44

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Chemistry 261 W2015 Problem Sets

Answer Key #2
2.1 ) Rank the following molecules with increasing permanent dipole moment. Hint: First figure
out the molecular geometry! [Note: You cannot determine these dipole moments
quantitatively yet, the experimental values are included to validate our approximations.]

a) HF b) CH4
1.91 D 0D

c) NH3 d) CO2

1.47 D 0D

e)
Cl Cl
CH 4 ~ CO2 < NH3 < Cl Cl ~ HF

1.90 D

2.2 ) Many biomolecules have polar functional groups. Sketch the approximate dipole of each of
the following structures (These aren’t exact!)

O
a) b) O
H H H
N
H

c) d) HO H
OH N
O H

Note: The central bond here H H

would freely rotate, so the N
vector will be down the C- HO
C(O) bond.
O

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Chemistry 261 W2015 Problem Sets

2.3 ) You may not realize that you are already familiar with the properties of organic molecules
used in everyday life. What can you say about the relative boiling points or melting points of
the following materials? Answer the questions below and rank these materials in increasing
melting/boiling points.

Therefore the order from lowest to highest mp is:

c < a < b < g <d< e < h<f

Butane fluid is only a fluid when under pressure – that’s why it escapes your lighter as a gas.
Note that gasoline is made from shorter chain alkanes and makes a better fuel in cold climates
(like Edmonton!) when compared to kerosene, which would freeze at -10 °C. Additional degrees
of unsaturation make a big difference to the properties of cooking oil and butter.

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Chemistry 261 W2015 Problem Sets

2.4 ) Line drawn structures are useful, but are only a static model of dynamic molecular
structures. Rationalize the following data and describe the inadequacies of the line model
drawn.

C-N Bond Length Typical C-N Bond Length

O
1.33 Å 1.47 Å

H 3C NH2

O O

H 3C NH 2 H 3C NH 2

The C-N bond has more double

bond character due to
resonance, and is therefore
shorter than a single bond

2.5 ) Hybrid atomic orbitals can be used to approximate molecular orbitals. Describe the hybrid
atomic orbitals of the following structures:
H H
a) b) H H
H H

H H
H H
H H

1 X C-C sp2-sp2 (sigma) 1 X C-C sp-sp (sigma)

1 X C-C p-p (pi) 2 X C-C p-p (pi)
4 X C-H sp2-s (sigma) 2 X C-H sp-s (sigma)

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Chemistry 261 W2015 Problem Sets

2.6 ) Identify the hybridization of all the heavy atoms (non-hydrogen) in the following
strucuture:
O

sp2
O sp

sp3 sp2 sp
sp3

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Chemistry 261 W2015 Problem Sets

Problem Set #3

Instructions: Problem sets will be posted online at eClass as we complete each of the units
during the semester. These problems will be a mix of problems that I have written and assigned
problems in the textbook. Answers to non-textbook problems will be posted on eClass.

3.1) Generate the empirical formula, degree of unsaturation, and predict the major IR
absorbances for the following structures:

3.2) You are given a pure sample of an organic compound with a formula of C4H8O2. You obtain
an IR spectrum shown below and note the following major IR absorbances above 1500 cm-1:
3100 (br), 2971, 2940, 2880 and 1712 (s) cm-1. Which of the following structures would be
consistent with your data?

a) b) c) d)
HO O
O
OH OH
HO
O

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Chemistry 261 W2015 Problem Sets

3.3) For the following structures, predict important IR bands you would expect to observe:

a) b) c) d)

N
Br

Also see textbook problems from Wade:

Chapter 3
3-1–3-6 (in chapter problems); 3-12–3-19

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Chemistry 261 W2015 Problem Sets

Answer Key #3
3.1) Generate the empirical formula, degree of unsaturation, and predict the major IR
absorbances for the following structures:

a) C4H10O, saturated, IR: 3400 (br), 3000 cm-1

b) C7H8O, 4 DoU, IR: 3400 (br), 3000, 2900, 1600 cm-1
c) C9H12, 4 DoU, IR: 3100, 3000, 2900, 1600 cm-1 (also some small sharp bands ~ 1700, 1800,
1900, 2000 from the conjugated DBs)

3.2) You are given a pure sample of an organic compound with a formula of C4H8O2. You obtain
an IR spectrum shown below and note the following major IR absorbances above 1500 cm-1:
3100 (br), 2971, 2940, 2880 and 1712 (s) cm-1. Which of the following structures would be
consistent with your data?

Only D is consistent with the formula and IR. A would not show the stretch at 1745, B would be
missing the broad peak for the acid (3100), and C is the wrong formula (but would also lack the
carbonyl stretch). D is the correct answer.

3.3) For the following structures, predict important IR bands you would expect to observe:

a) b) c) d)

N
Br

a) This is an alkyl halide, there are no strong absorbances expected other than the C-H stretches
around 2800-3000 cm-1.
b) Here, we should see the C-H alkane stretches around 2800-3000 cm-1 , aromatic C-H stretches
around 3000-3100 cm-1 , and some alkene stretches around 1600 cm-1.
c) Alkane C-H at 2800-3000 cm-1, an alkene C-H at 3100 cm-1 (s), and a C=C stretch at 1620 cm-
1
.
d) The alkyl chain will only give absorbances at 2800-3000 cm-1, but the nitrile group should
give a sharp absorbance at ~2200 cm-1.

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Chemistry 261 W2015 Problem Sets

Problem Set #4

Instructions: Problem sets will be posted online at eClass as we complete each of the units
during the semester. These problems will be a mix of problems that I have written and assigned
problems in the textbook. Answers to non-textbook problems will be posted on eClass.

4.1. ) For the three hexane isomers shown below, predict their relative boiling points.

A B C

4.2. ) List the following compounds in order of increasing heat of combustion.

A B C

4.3. ) Name the following alkanes and cycloalkanes.

A B C D

4.4. ) Draw the potential energy diagrams of following compounds when there is a rotation of
360o about the C2-C3 bond. Place potential energy on the Y axis and rotation angle on the X
axis. Indicate all the maxima and minima with the appropriate conformations (you don’t
have to worry about precise values of the energy changes, just relative differences.).
(a) 2,2,3,3-tetramethylbutane
(b) 2,3-dimethylbutane

4.5. ) Draw the structure of trans-1,3-dibromocyclobutane. This compound has a non-zero dipole
moment. Use conformational analysis to rationalize this observation. Is cyclobutane planar?

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Chemistry 261 W2015 Problem Sets

4.6. ) The flat structure shown below illustrates the connectivity of glucose. Glucose actually
exists in the chair conformation with all substituents in the most stable orientation possible.

OH
O OH

HO OH
OH

(a) Draw a chair conformation of glucose with all substitutents in the correct
orientation around the ring
(b) Based on your drawing in (a), draw a Haworth projection which clearly shows the
cis-trans relationship of all of the substitutents.

4.7. ) For each of the following cyclohexane derivatives, indicate

(a) whether the molecule is a cis or trans isomer and
(b) whether it is in its most stable conformation.
If your answer to (b) is no, "flip" the ring and draw its most stable conformation.

Cl
F
OCH 3 OCH 3 Br OH
NH 2 H 3C
H 2N
CH3

A B C D E F

4.8. ) Think about cis- and trans- isomers of 1,3-di-tert-butylcyclohexane. One of these isomers
exists as a twist-boat conformation rather than a usual chair conformation. What special
feature does account for this observation?

Also see textbook problems from Wade:

Chapter 4
4-1–4-31 (in chapter problems); 4-32–4-46

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Chemistry 261 W2015 Problem Sets

Answer key #4
4.1. ) For the three hexane isomers shown below, predict their relative boiling points.

A B C
These are all isomers of C6H14. The only difference between them is the number of branch
points. Branching should decrease surface area and VDW interactions, so the predicted
ranking would be: A<C<B

4.2. ) List the following compounds in order of increasing heat of combustion.

A B C
These are all isomers of C5H10. The only difference in their heat of combustion should be due
to differences in ring strain. We would expect smaller rings to be higher in energy (and thus
less stable). So the order of increasing heat would be: A, C, B

4.3. ) Name the following alkanes and cycloalkanes.

A B C D

5 1 11
3 1
1
3 3
6 10 9
1 4
6
a. 5,6-dibutyl-decane.
b. trans-1-ethyl-3-propyl-cycloheptane
c. 1-cyclohexyl-3,3,9,9-tetracyclopropyl-undecane (a gecko?)
d. 3-cycopentyl-3,4-diethyl-hexane (or stick-man for short)

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Chemistry 261 W2015 Problem Sets

4.4. ) Draw the potential energy diagrams of following compounds when there is a rotation of
360o about the C2-C3 bond. Place potential energy on the Y axis and rotation angle on the X
axis. Indicate all the maxima and minima with the appropriate conformations (you don’t
have to worry about actual values of the energy changes).
(a) 2,2,3,3-tetramethylbutane

CH 3
CH 3CH 3
H 3C CH 3

H 3C
CH 3 CH
CH 3 CH 3 CH3 3
CH3
A B

Conformational Energy

B
B B
25.0

22.0

19.0

A A A
16.0
-180 -135 -90 -45 0 45 90 135 180
C(1)-C(2)-C(3)-C(4)(degrees)

(b) 2,3-dimethylbutane
H CH 3 CH 3CH 3
CH 3CH 3
H 3C CH 3 H3C CH 3

H3C H3C
CH 3 H CH 3
H H H
CH 3 CH 3 CH 3 H
H H
A B C D

Conformational Energy

C
13.0

11.0
D
D
B B
8.0

A A
6.0
-180 -135 -90 -45 0 45 90 135 180
C(1)-C(2)-C(3)-C(10)(degrees)

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Chemistry 261 W2015 Problem Sets

4.5. ) Draw the structure of trans-1,3-dibromocyclobutane. This compound has a non-zero dipole
moment. Use conformational analysis to rationalize this observation. Is cyclobutane planar?

Br Br
vs.
Br
Br
The dipoles in a flat cyclobutane would cancel out, but any bent conformation would result in
a small net dipole moment.

4.6. ) The flat structure shown below illustrates the connectivity of glucose. Glucose actually
exists in the chair conformation with all substituents in the most stable orientation possible.
OH
O OH

HO OH
OH
(a) Draw a chair conformation of glucose with all substitutents in the correct
orientation around the ring

HO
HO O OH
OH
HO
If we leave out the H atoms, this is the chair form.

(b) Based on your drawing in (a), draw a Haworth projection which clearly shows the
cis-trans relationship of all of the substitutents.
OH
O OH

HO OH
OH
Again, we leave out the H atoms for clarity, and you see that all the hydroxyl groups are
trans to their neighboring groups.

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Chemistry 261 W2015 Problem Sets

4.7. ) For each of the following cyclohexane derivatives, indicate

(a) whether the molecule is a cis or trans isomer and
(b) whether it is in its most stable conformation.
If your answer to (b) is no, "flip" the ring and draw its most stable conformation.
Cl
F
OCH 3 OCH 3 Br OH
NH 2 H 3C
H 2N
CH3

A B C D E F

trans, no trans, yes trans, yes trans, yes cis, no trans, yes

Cl
F OH
CH 3

4.8. ) Think about cis- and trans- isomers of 1,3-di-tert-butylcyclohexane. One of these isomers
exists as a twist-boat conformation rather than a usual chair conformation. What special
feature does account for this observation?

cis trans

stable
H

H
stable
In the cis isomer, the conformation with both t-butyl groups equatorial is clearly the most stable.
In the trans isomer, neither chair form can alleviate the axial interactions between one of the t-
butyl groups and the other axial H’s. Therefore, the twist boat conformation allows relief from
some of the H-t-butyl axial interactions at the expense of H-H axial interactions.

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Chemistry 261 W2015 Problem Sets

Problem Set #5

Instructions: Problem sets will be posted online at eClass as we complete each of the units
during the semester. These problems will be a mix of problems that I have written and assigned
problems in the textbook. Answers to non-textbook problems will be posted on eClass.

5.1) Rank the relative stability of the carbocation structures shown below (from most stable to
least stable).

5.2) Draw a hypothetical reaction coordinate diagram for an exothermic reaction that has only
one transition state and no intermediates. Label the starting material, products, transition state,
and G‡.

5.3) Modify your drawing in 5.2 to illustrate what would happen if the transition state were
stabilized. Would this increase or decrease the rate of reaction?

5.4) Modify your drawing in 5.2 to illustrate what would happen if the starting materials were
de-stabilized. Would this increase or decrease the rate of reaction?

5.5) Draw the expected products for the reactions shown below. Indicate the major products
where possible if a mixture is expected to occur.

a)
Cl2

hv, 25° C

b)
Cl2

hv, 25° C

c)
Br2

hv, 25° C

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Chemistry 261 W2015 Problem Sets

5.6) Two reaction coordinate diagrams are shown below. Answer the following questions
regarding these diagrams.
a) Which of these reactions is endothermic?
b) Which of these reactions could happen ‘spontaneously’? And what does this mean?
c) Both A and B have a ‘valley’ in the middle. What does this portion of the diagram
represent?
d) Label the Transition state(s) in each coordinate as “TS”.
e) Label each diagram with the G‡ – are these different sizes for the two reactions?

Also see textbook problems from Wade:

Chapter 5
5-1–5-33 (in chapter problems); 5-34–5-44, 5-46–5-50

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Chemistry 261 W2015 Problem Sets

Answer key #5
5.1) Rank the relative stability of the carbocation structures shown below (from most stable to
least stable).

5.2) Draw a hypothetical reaction coordinate diagram for an exothermic reaction that has only
one transition state and no intermediates. Label the starting material, products, transition state,
and G‡.

TS

SM

PROD

5.3) Modify your drawing in 5.2 to illustrate what would happen if the transition state were
stabilized. Would this increase or decrease the rate of reaction?

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Chemistry 261 W2015 Problem Sets

5.4) Modify your drawing in 5.2 to illustrate what would happen if the starting materials were
de-stabilized. Would this increase or decrease the rate of reaction?

5.5) Draw the expected products for the reactions shown below. Indicate the major products
where possible if a mixture is expected to occur.

5.6) Two reaction coordinate diagrams are shown below. Answer the following questions
regarding these diagrams.
a) Which of these reactions is endothermic?

Reaction B is endothermic – the product is higher in energy than the starting material.
Reaction A is exothermic, it gives up energy as the products are formed.

b) Which of these reactions could happen ‘spontaneously’? And what does this mean?

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Chemistry 261 W2015 Problem Sets

Reaction A would happen spontaneously – as long as there is enough thermal energy to

overcome the activation energy to reach the product.

c) Both A and B have a ‘valley’ in the middle. What does this portion of the diagram
represent?

This is an intermediate. Intermediates are species that exist for a discreet time between
transition states.

d) Label the Transition state(s) in each coordinate as “TS”.

Both of the ‘peaks’ in the diagrams are transition states.

e) Label each diagram with the G‡ – are these different sizes for the two reactions?

They are different – G‡ is determined by the energy to get over the first transition state.
Since the starting point of both reactions is different, the G‡ is different.

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Chemistry 261 W2015 Problem Sets

Problem Set #6

Instructions: Problem sets will be posted online at eClass as we complete each of the units
during the semester. These problems will be a mix of problems that I have written and assigned
problems in the textbook. Answers to non-textbook problems will be posted on eClass.

6.1) Convert the following Fisher projections to 3D projections:

A
CHO CHO
H OH H OH
CH 2OH CH 2OH

B C
CHO B
CHO
H OH HO H
HO H H OH
H OH HO H
CH 2OH CH 2OH
C

D E
CH2 OH CH 2 OH
HO H H OH D,E
H OH HO H
HO H H OH
CH2 OH CH 2 OH

6.2) Give IUPAC names for the following compounds:

A

Br
B

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Chemistry 261 W2015 Problem Sets

6.3) Provide a conformational analysis of the following derivatives. Show both chair forms for
each structures as part of your analysis.

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Chemistry 261 W2015 Problem Sets

6.4) For each of the pairs shown below, indicate the relationship between the compounds. Are
they the same, constitutional isomers, stereoisomers – and if so what kind of stereoisomer?
Br Br
a)
Br Br

Br Br
b)
Br Br

Br Br
c)
Br Br

d)
Cl Cl

e)
Cl Cl

f)
Cl Cl

6.5) The structure below is a drug molecule. How many isomers of this compound might you
predict are present in a sample? Why?

HO

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Chemistry 261 W2015 Problem Sets

6.6) Many organic chemistry textbooks (but not ours this year!) contain a passage regarding the
stereochemistry of a drug known as thalidomide, which was used for a brief period in the 1960s
as a treatment for morning sickness in pregnant women. The textbooks may even suggest that
each enantiomer of thalidomide has distinct biological activity. Were this so, it is posited that the
tragedy of birth defects caused by one isomer could have been avoided if only one enantiomer
had been used. This myth has been perpetuated in the chemical literature to dramatize the
importance of stereochemistry.

N O
NH
O O

An excellent review on the stereochemistry of pharmaceuticals (Agranat et al., Nature

Reviews Drug Discovery, 2002, 1, 753-768) points out the two major fallacies with this
claim:
1. The set of experiments used to establish the difference in the activity of the
enantiomers was conducted in mice. For various reasons, the rabbit is a better
model of human gestation, and in that model system no such difference is found.
2. Under physiological conditions, a single enantiomer of thalidomide will racemize
– therefore negating the advantage of a pure stereoisomer.

(a) Identify the stereogenic centre in thalidomide.

(b) Propose a mechanism for racemization of the molecule.

Also see textbook problems from Wade:

Chapter 6
6-1–6-24 (in chapter problems); 6-25–6-34

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Chemistry 261 W2015 Problem Sets

Answer key #6
6.1) Convert the following Fisher projections to 3D projections:

6.2) Give IUPAC names for the following compounds:

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6.3) Provide a conformational analysis of the following derivatives. Show both chair forms for
each structures as part of your analysis.
recall:
CH3
H CH 3
A equivalent
H stability H
CH 3 H
CH 3

CH 3 H
B
H
H H3 C
H more
stable Axial Equatorial

6.4) For each of the pairs shown below, indicate the relationship between the compounds. Are
they the same, constitutional isomers, stereoisomers – and if so what kind of stereoisomer?

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Br Br
a) Same molecule (rotation by 180)
Br Br

Br Br
b) enantiomers
Br Br R,R vs. S,S

Br Br
meso compound
c) R,S and R,S
Br Br

no chirality, same molecule

d)
Cl Cl

mixed drawing - racemization at methyl position

e) this is really a mixture of diastereomers.
The stereogenic C is 1S(left) or 1R
Cl Cl

f) enantiomers
Cl Cl 1S,2R and 1R,2S

Cl Cl

Cl
6.5) The structure below is a drug molecule. How many isomers of this compound might you
predict are present in a sample? Why?

ambiguous drawing means that this is a racemic

O compound, but it contains stereogenic
centre. One form is more potent than the other
HO and is now marketed as a single enantiomer.

racemic ibuprofen

O
O
HO
HO

(R)-ibuprofen (S)-ibuprofen, 'dexibuprofen'

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Chemistry 261 W2015 Problem Sets

6.6 ) Thalidomide:

(a) Identify the stereogenic centre in thalidomide.

O
H
N O
NH
O O
(b) Propose a mechanism for racemization of the molecule.

O
H B
N O O
NH
O O N O
NH
O -
O O
H
N O H+
NH
O O

Acid catalyzed is also reasonable (first protonate the carbonyl).

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Chemistry 261 W2015 Problem Sets

Problem Set #7

Instructions: Problem sets will be posted online at eClass as we complete each of the units
during the semester. These problems will be a mix of problems that I have written and assigned
problems in the textbook. Answers to non-textbook problems will be posted on eClass.

7.1. ) Given the following reaction mechanisms, draw the expected products. Be sure to note
stereochemistry in the product(s) if necessary.

Br
NaOH
a) SN2
O

I NaCN
b) SN2

H2O
c) SN1
Br
50 C

OTs
d) CH3OH
SN1
50 C
Br

e) NaNH2
E2

f) NaOH
E2
Br

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7.2. ) Draw the carbocation intermediate and products of the following reaction:
I
H 2O

MeO 50 C

7.3. ) Starting from (R)-2-bromopentane, provide reaction conditions for synthesizing the
structures shown below.
HS
a)

O
b)

O
c)

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7.4. ) For the following substrates and reaction conditions, draw the structures of the reaction
product(s) expected. Identify the reaction mechanism responsible.

NaOEt
a)
Br
50 C, EtOH

Br NaOC(CH3
b)
50 C, t-buta

CH3OH
c) Br
50 C

NaOC(CH3
d) Br
50 C, t-buta

Cl NaI
e)
50 C, Aceto

Cl MeOH
f)
25 C

MeOH
g) (S)-3-iodo-3-methylhexane
25 C

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7.5. ) Two reaction conditions are shown below. Provide a rationale for why a reacts much
slower than b.

H2 O
a) H3 C Br H 3C OH
50 C

H2 O
b) H 3C Br + NaI H 3C OH
50 C

7.6. ) Rate equations can be used to determine the mechanism of a given reaction. An example is
given in the following excercize:
a. Write the rate equation for the SN2 reaction below.
NaOH
Br OH
50 C

b. Write the rate equation for the SN1 reaction below.

H2 O
Br OH
50 C

c. Based on the rate equations you’ve written, predict what you would observe for the following
conditions:
i. Reaction a, performed in low concentration of NaOH.
ii. Reaction a, performed in high concentration of NaOH.
iii. Reaction b, performed in low concentration of H2O.
iv. Reaction b, performed in high concentration of H2O.

Also see textbook problems from Wade:

Chapter 7
7-1–7-40 (in chapter problems); 7-41–7-57, 7-60, 7-63

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Answer key #7
7.1. ) Given the following reaction mechanisms, draw the expected products. Be sure to note
stereochemistry in the product(s) if necessary.

Br OH
NaOH
a) SN2
O O

I NaCN CN
b) SN2

H 2O
c) SN1
Br 50 C OH

OTs OTs O
d) CH 3OH O OMe
SN1 S
CH 3
50 C O

Br
NaNH2 Et Br CH Et
e) 3
E2 H
H CH 3 CH 3
H CH3

f) NaOH Br
E2 H H
Br
H CH 3

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7.2. ) Draw the carbocation intermediate and products of the following reaction:
I OH
H 2O
O
MeO 50 C
O

1:1 racemic mixture

OH

O
7.3. ) Starting from (R)-2-bromopentane, provide reaction conditions for synthesizing the
structures shown below.
SH Br
a) NaSH +

O Br
b) NaOEt +

O
Br
O
c) NaOAc +

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7.4. ) For the following substrates and reaction conditions, draw the structures of the reaction
product(s) expected. Identify the reaction mechanism responsible.

a) NaOEt SN2
Br O
50 C, EtOH

Br NaOC(CH3)3
b) E2
50 C, t-butanol

CH3OH
c) Br SN1 O
50 C

NaOC(CH3)3
d) Br E2
50 C, t-butanol

Cl I
NaI
e) SN2
50 C, Acetone

Cl OMe
MeOH
f) SN1
25 C

MeOH SN1 O
g) (S)-3-iodo-3-methylhexane
I 25 C

SN2 I
NaI
h) (R)-2-bromo-heptane
Br 50 C, MeOH

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7.5. ) Two reaction conditions are shown below. Provide a rationale for why a reacts much
slower than b.

H2 O
a) H3 C Br H 3C OH
50 C

H2 O
b) H 3C Br + NaI H 3C OH
50 C

Iodide is a better nucleophile than bromide, and bromide is a good leaving group. The
addition of sodium iodide leads to displacement of the bromide to form methyl iodide in an
SN2 reaction. This new substrate can react with water to provide the final product. Since
iodide is a better leaving group for SN2, the reaction goes faster than in water alone.

H 2O
H 3C OH 2+ H3 C OH
slow
H3 C Br
I- H 2O
H 3C I H3 C OH2 + H 3C OH
f ast fast

7.6. ) Rate equations can be used to determine the mechanism of a given reaction. An example is
given in the following exercise:
a. Write the rate equation for the SN2 reaction below.
NaOH
Br OH
50 C rate=k[RX][NaOH]

b. Write the rate equation for the SN1 reaction below.

H2 O
Br OH
50 C rate=k[RX]

c. Based on the rate equations you’ve written, predict what you would observe for
the following conditions:
i. Reaction a, performed in low concentration of NaOH.
The reaction should be slowed, it is first order in NaOH.
ii. Reaction a, performed in high concentration of NaOH.
The reaction should go faster.
iii. Reaction b, performed in low concentration of H2O.
The reaction rate is not dependant on water, so there will be no change.
iv. Reaction b, performed in high concentration of H2O.
The reaction rate is not dependant on water, so there will be no change.

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Chemistry 261 W2015 Problem Sets

Problem Set #8

Instructions: Problem sets will be posted online at eClass as we complete each of the units
during the semester. These problems will be a mix of problems that I have written and assigned
problems in the textbook. Answers to non-textbook problems will be posted on eClass.

8.1 ) Determine the degree of unsaturation (DoU) for the following formulas and structures:
(You can use the formula in the notes, or just count rings and double bonds).

i ii iii iv

C6H10 C6H12 C6H12O C5H11N

O O
viii
O N
v vi vii
O O O
H N

8.2 ) Which of the following alkene structures is the most stable?

i ii iii iv v

8.3 ) What are the expected products if the following alcohols are treated with concentrated acid
(such as conc. H3PO4 or 20% H2SO4)?

OH HO
HO
OH

i ii iii iv

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8.4 ) Rank the following carbocation structures in order of increasing stability:

H H

H H

i ii iii iv

8.5) The two substrates shown below are subjected to reaction conditions that should favor and
E2 reaction.
a. Draw the product(s) of each reaction.
b. What is the likely relative rate of these two reactions? Which will be fastest?
c. Explain your answer to b using conformational diagrams of the substrates.

NaNH 2

Br

NaNH 2

Br

Also see textbook problems from Wade:

Chapter 8
8-1–8-29 (in chapter problems); 8-30–8-47, 8-55

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Chemistry 261 W2015 Problem Sets

Answer key #8
8.1 ) Calculate the degree of unsaturation for the following formulas and structures: (You can use
the formula in the notes, or just count rings and double bonds).

i ii iii iv

C6H10 C6H12 C6H12O C5H11N

O O
viii
O N
v vi vii
O O O
H N

i. 2 DoU
ii. 1
iii. 1
iv. 1
v. 2
vi. 1
vii. 4
viii. 8 – this compound is an active ingredient of pesticides like RAID (tetramethrin)

8.2 ) Which of the following alkene structures has the greatest heat of hydrogenation?

i ii iii iv v

iv. Is the most stable, and has the smallest heat of hydrogenation. v. is the
least stable, and has the largest heat of hydrogenation.

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8.3 ) What are the expected products if the following alcohols are treated with concentrated acid
(such as conc. H3PO4 or 20% H2SO4)?

OH HO
HO
OH

i ii iii iv

8.4 ) Rank the following carbocation structures in order of increasing stability:

H H

H H

i ii iii iv

least stable iii < iv < i < ii most stable

8.5) The two substrates shown below are subjected to reaction conditions that should favor and
E2 reaction.
a. Draw the product(s) of each reaction.
b. What is the likely relative rate of these two reactions? Which will be fastest?
c. Explain your answer to b using conformational diagrams of the substrates.

unfavorable conformation

NaNH 2 CH3 slow

Br

Br H CH3

H f ast
NaNH 2 H
CH 3
CH 3
Br Br
major minor
f avored conformation

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Chemistry 261 W2015 Problem Sets

Problem Set #9

Instructions: Problem sets will be posted online at eClass as we complete each of the units
during the semester. These problems will be a mix of problems that I have written and assigned
problems in the textbook. Answers to non-textbook problems will be posted on eClass.

9.1 ) For the reaction shown below, write out a complete mechanism that includes all side-
products and shows the movement of electrons. Indicate important intermediates and the final
product.

HBr

ether

9.2 ) Explain the observed reaction products shown below:

HBr Br
Br
ether
Br

observed not-observed

9.3 ) Draw the products of the following reactions:

Cl2
i

Cl2
ii

Br2

iii

Br2
iv

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9.4 ) Draw the products of the following reactions:

HBr

HBr
ii

HBr
iii H2O

Br2
iv
H2O

Br2
v
H2O

1) BH3
vi
2)NaOH, H2O2

H2 (xs)
vii Pd/C

D2 (xs)

viii Pd/C

O H2 (xs)

Pd/C
ix

1) BH3
x
2)NaOH, H2O2

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9.5 ) Draw the products in the following single- and multi-step reactions:

1) OsO4

i 2) NaHSO3 , H 2O

KMnO 4
ii
KOH, H 2O, heat

1) O3
iii
2) Zn, HOAc

Br 1) NaNH 2
iv
2) Br 2

HBr
v

1) BH 3
vi
2) NaOH, H2 O2
3) HBr, heat

1) BH 3
vii 2) NaOH, H2 O2
3) NaNH 2
4) CH 3I
1) NaNH 2

viii 2)
Br

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9.6 ) Propose a multi-step sequence from the starting material shown that gives the indicated
final product. You may use any alkyl halides or other reagents discussed in class for your
answer.
?

?
OH

HO
OH

?
Br O

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Chemistry 261 W2015 Problem Sets

9.7 ) Draw the products of the following reactions.

Br2

h

HBr

HBr
peroxides

HBr

O SOCl2
OH

O O
H2N
Cl O

9.8 ) Write out the mechanism of the radical addition shown below. Classify steps as initiation,
propagation, and termination.

Br2

h

HBr

peroxides

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9.9 ) Write out the stepwise mechanism for the formation of a dimer in the polymerizations
shown below. Draw the repeating unit structure of the product.

F R
F
F
Radical initiator
F

O
Cl + H2N
Cl NH2
O

Also see textbook problems from Wade:

Chapter 9
9-1–9-6, 9-10–9-45 (in chapter problems); 9-46, 9-48–9-51

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Chemistry 261 W2015 Problem Sets

Answer key #9
9.1 ) For the reaction shown below, write out a complete mechanism that includes all side-
products and shows the movement of electrons. Indicate important intermediates and the final
product.

HBr

ether

Br-
HBr Br
ether

9.2 ) Explain the observed reaction products shown below:

HBr Br
Br
ether
Br

observed not-observed

ring strain
Electrophilic addition results in a tertiary carbon next to a
highly strained cyclobutane. The strain can be relieved by an
alkyl shift, which gives a secondary carbocation. This cation
can react with the bromide ion to give one of the product, or
else re-arrange in another alkyl shift to a tertiary carbocation,
which gives the second observed product.

secondary tertiary
carbocation carbocation

9.3 ) Draw the products of the following reactions:

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Cl2 Cl Cl
i +
Cl Cl

Cl2 Cl Cl
ii +
Cl Cl

Br2 Br
Br
+
iii
Br
Br
CH3 CH3
Br Br H Br Br H
Br2
iv + H Br + Br H
H CH3 H CH3
Br Br
CH3 CH3

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Chemistry 261 W2015 Problem Sets

9.4 ) Draw the products of the following reactions:

HBr
Br
i

HBr
Br
ii

HBr OH
iii H2O
Br
OH
Br2
iv
H2O

OH OH
Br2 +
v
H2O Br Br

HO
1) BH3
vi
2)NaOH, H2O2

H2 (xs)
vii Pd/C

D2 (xs)

Pd/C D D
viii
D D
O
O H2 (xs)

Pd/C
ix
OH

1) BH3
OH
x
2)NaOH, H2O2

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9.5 ) Draw the products in the following one- or two-step reactions:

slightly favored
1) OsO4 OH OH
+
i 2) NaHSO3, H2O
OH OH
O
KMnO4 HO
ii OH
KOH, H2O O
heat

1) O3 O
O
iii
2) Zn, HOAc
Br Br
Br Br Br
1) NaNH2
iv +
2) Br2

Br
HBr
v

SN1 E1
1) BH3
vi +
2) NaOH, H2O2 OH Br
3) HBr, heat

1) BH3
vii 2) NaOH, H2O2 OH O
3) NaNH2
4) CH3I
1) NaNH2

viii 2)
Br

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Chemistry 261 W2015 Problem Sets

9.6 ) Propose a two- or three-step sequence from the starting material shown that gives the
indicated final product. You may use any alkyl halides or other reagents discussed in class.

1) BH3 1) NaNH2

2)NaOH, H2O2 OH 2) O
Br

?
OH

HO
OH

OH O O
1) NaNH2 1) OsO4

2) 2) NaHSO3, H2O HO
Br OH

?
Br O

Br 1) O3 Br O NaNH2 O

2) Zn, HOAc

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Chemistry 261 W2015 Problem Sets

9.7 ) Draw the products of the following reactions.

Br2

h Br

HBr

Br

Br
HBr
peroxides

HBr
Br

O SOCl2 O

OH Cl

O O O
H2N O
Cl O N
H
O

9.8 ) Write out the mechanism of the radical addition shown below. Classify steps as initiation,
propagation, and termination.
Br Br
2 Br
Br2 H initiation
H
h

propagation

Br
Br

termination

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Chemistry 261 W2015 Problem Sets

HBr OR initiation 2 OR
RO
peroxides
H
Br propagation
Br
propagation
propagation

(still a Br radical H
Br Br
generated)
Br

9.9 ) Write out the stepwise mechanism for the formation of a dimer in the polymerizations
shown below. Draw the repeating unit structure of the product.

F
F R F F
R F F
F R
F F
F F F F F
Radical initiator
F F F F

F F

F F n

teflon
O O
O-
Cl + H2N
Cl NH2 Cl Cl
O NH2+

H2N

O O
O O Cl-
Cl Cl
NH NH2+

H2N H2N

O
H
N
N
H n
O

Nylon-4,2

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Chemistry 261 W2015 Problem Sets

Problem Set #10: Retrosynthesis

An Introduction to Retrosynthetic Analysis:

At this point you have been exposed to a number of organic reactions, and as this repertoire of
reactions expands we can address more complex problems. The tools of organic chemistry can
be used to construct complex molecules. Although this course only includes a tiny fraction of
known reactions – they can be used to prepare relatively complex structures. At its heart,
synthesis is series of logic problems. You need to analyze a structure, determine its component
functional groups, and decide on a strategy for assembling the molecule from simple starting
materials.

The most commonly used analysis for these types of problems is known as a “retrosynthetic
analysis”. As the name implies, this is based on working backwards from the complex structure
to simple starting materials. The process begins with analyzing the molecular structure.

Major issues to consider:

1) Carbon skeleton
2) Functional groups
3) Regiochemistry
4) Stereochemistry

Let’s examine a simple synthetic target:

Example 1:

OH
A quick analysis:
1) Carbon skeleton: 2-methyl-pentane
2) Functional groups: secondary alcohol
3) Regiochemistry: alcohol is vicinal to a tertiary carbon
4) Stereochemistry: none given

The next step is to propose a reverse reaction – a reaction whose product is the structure
we are analyzing. This is also called a “retrosynthetic step” and is represented with a
double arrow:

OH

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The target alcohol could have been formed by the non-Markovnikov addition across the
2-methyl-2-pentene structure. We can propose additional steps to simplify the structure
more:
Br

Br

The alkene could have been generated from an E2 reaction of an alkyl halide. Two
substrates are possible for this reaction. One of these alkyl halides can be made easily by
radical halogenation of 2-methyl-pentane. The alkane is a simple enough starting material
that we can consider this a complete analysis.

The final step of the analysis is to propose the forward synthesis. This is simply the
forward version of each of our retrosynthetic steps. Now we need to provide conditions
and analysis of any side products or issues likely to be encountered.

Br 2 NaNH 2 1) BH3
Br
h 2) H 2O2 , H 2O
OH

selective halogenation trisubstituted non-Markov.

at highest subs. carbon alkene f avored add'n to less subs
side of alkene

One of the advantages of retrosynthetic analysis is the ability to identify multiple pathways to
solve the same problem. This provides a set of choices for a chemist to use. For example, one
route could be based on a very cheap starting material, while another could have a very difficult
or non-selective step. Sometimes these issues are not revealed until the actual experiment is
done. For virtually all retrosynthetic analysis there are many correct answers!

Another example which has multiple solutions:

Example 2:

+ CH 3Br

Br
+

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Here the first retrosynthetic step can break one of two C-C bonds, each on the opposite
side of the alkyne. To decide on which branch is better, we need to consider each of the
component steps and the availability of starting materials.
The forward synthesis for these two possible routes could take the form of:

Na CH 3Br
Na

Br

Na
Na

Both of these routes are acceptable solutions to the problem. If one of the alkyne
derivatives is cheaper or easier to work with (the longer chain may be less volatile, for
example) we might favor that strategy.

These problems get progressively more complex as issues of regiochemistry and stereochemistry
are introduced. However, the essence of solving the problem is always to logically disassemble
the target structure using reactivity that you already know.

The following retrosynthetic problems will require a command of organic reactions that have
been presented and a grasp of the logic of retrosynthesis.

Retrosynthetic Problems:

10.1 ) Propose a retro- and forward synthesis of the following compounds:

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Stereochemistry of alkene additions:

Several of the reactions we’ve discussed have expected stereochemical outcomes. The most
versatile of these are additions to alkenes. Alkene additions often have both regiochemical and
stereochemical aspects.

First, consider a simple bromonium addition. The first step forms a strained bromonium
intermediate. However the second step results in attack by a nucleophile and ring opening
(forming a halo-hydrin, for example). The second step should have some expected
regiochemistry.

Nu Nu
Nu Br
Br
Br

Nu Br
+ enantiomer Br
Nu Nu

f avored pathway

In a differentially substituted alkene, we would expect to observe nucleophilic attack

preferentially at the higher substituted C. The rationale for this is that this position can better
stabilize the partial positive charge that develops in the SN2-like transition state.

H 3C H H
Nu H 3C Br
Br Br
Nu
H 3C H H 3C H Nu
+ enantiomer

H CH 3 Nu H CH 3
Br
Br Nu Br
H 3C H H 3C H
Nu
+ enantiomer

Another way to take advantage of the bromonium ion structure is to use cis- and trans- alkenes.
Each of these will react to give different relative stereochemistry (still a mixture of enantiomers)
that can be useful in retrosynthetic analysis.

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10.2 ) Propose a retro- and forward synthesis of the following compounds. Include an analysis of
the stereochemistry. Note: you will not be able to synthesize single enantiomers, however you
should be able to solve the problem to generate the products shown along with its enantiomer.

starting from:

O OH
HO
i. OH
HO
HO O

Br

ii.
Br

OH

iii.
OH

OH

iv.
OH

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Answer key #10

10.1 ) Possible solutions (remember there are others!):

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Chemistry 261 W2015 Problem Sets

starting from:

i.

1) NaNH2
2) CH3CH2Br

Li, NH3

dissolving metal
reduction

O PBr3
HO Br
ii. OH
HO
O
HBr would add to alkene!
KMnO4
KOH, heat

O X
OH O Br
HO OH
O HO
cyclize O
NaNH2

O
X OH
HO
O

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Chemistry 261 W2015 Problem Sets

iii. 1) Br2

2) NaNH2

HBr
and peroxides

Br NaNH 2

Br

H 2 (xs)
Pd/C

Br

Br

10.2 ) Possible solutions:

starting f rom:

O OH O
Br
i. OH OH
HO HO
HO O see 9.1.ii O

1) OsO4

O 2) NaHSO 3, H2 O
OH
HO
O O OH
OH
HO
see 9.1.ii HO O

Br + enantiomer

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Chemistry 261 W2015 Problem Sets

Br
ii.
Br 1) HBr, peroxides

2)

Li, NH3

Br
Br2

Br

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Chemistry 261 W2015 Problem Sets

Br
Br 2 1) NaNH2 Br
h 2) HBr
peroxides
Li, NH3 H 2 (1 eq)
dissolving metal Lindlar's

1) OsO4

2) NaHSO 3, H2O

OH OH

OH OH

+ enantiomer + enantiomer

CAIRO – University of Alberta page 78

Chemistry 261 W2015 Problem Sets

Problem Set #11

Instructions: Problem sets will be posted online at eClass as we complete each of the units
during the semester. These problems will be a mix of problems that I have written and assigned
problems in the textbook. Answers to non-textbook problems will be posted on eClass.

11.1 ) Write the products of the following single and multi-step reactions.

CAIRO – University of Alberta page 79

Chemistry 261 W2015 Problem Sets

1) CH3MgBr
O
2) H3O+

O O 1) NaBH4

O 2) H3O+

1) CH3MgBr
O
2) H3O+
O

OH
1) Na

2)
Br

OH
H2N
O SOCl2

1)O3
2)Zn, HOAc

1) Na 1) NaBH4

2) 2) H3O+
OMe
Br

CAIRO – University of Alberta page 80

Chemistry 261 W2015 Problem Sets

Also see textbook problems from Wade:

Chapter 10
10-1–10-25 (in chapter problems); 10-26–10-39

Chapter 11
11-1–11-29 (in chapter problems); 11-30–11-46, 11-48

CAIRO – University of Alberta page 81

Chemistry 261 W2015 Problem Sets

Answer key #11

11.1 ) Write the products of the following single and multi-step reactions.
1) CH3MgBr
O OH
2) H3O+

O O 1) NaBH4 O OH
O 2) H3O+ O

1) CH3MgBr
O
2) H3O+
O OH

OH O
1) Na

2)
Br

OH Cl HN
H2N
O SOCl2
O O

1)O3
2)Zn, HOAc

O OH O
1) Na HN 1) NaBH4 HN
O
HN
2) O O
2) H3O+
O OMe
Br

CAIRO – University of Alberta page 82