Prof. J.

Leighton Organic Chemistry UN2443_001 10/08/25

Relevant Reading for Substitution and Elimination Reactions: Chapter 11.

1. Predict the product - including stereochemistry, where relevant - of the following reactions. (Note
that many different nucleophiles are effective in SN2 reactions, and I am using some of them here
that you have not seen before. What they have in common is that they are good nucleophiles
(nucleophilicity is roughly correlated with basicity, that is, strong bases are usually also good
nucleophiles). What they also have in common is that they are sterically small, which is important
given the sensitivity of SN2 reactions to steric hinderance.)

a. D H b. Me Br
Na+ OMe Na+ SMe
Me Cl

Br
c. I H d.
Ph C C Na+ C N
Me Et

2. It has been observed that whereas compound A undergoes SN2 reactions, compound B does not.
Provide an explanation for this observation. Begin by drawing each compound in its most stable
chair conformation. Next, draw in the large lobe of the σ* C-Br orbital. Then evaluate the trajectory
of the nucleophile as it approaches the σ* C-Br orbital.
Br OCH3
A
+ OCH3
t-Bu t-Bu

Br OCH3
B Not formed:
+ OCH3
t-Bu t-Bu

3. Provide an explanation for the trend shown below regarding the rate of reaction in SN2 reactions..

R-Br + NH2 R-NH2 + Br

Br Br Br Br

fastest slowest
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4. Rank the following SN1 (or “solvolysis”) reactions from fastest to slowest.
H 3C H 3C F2HC F2HC
EtOH EtOH
Br OEt Br OEt
H 3C H 3C H 3C H 3C
A B
H 3C H 3C H 3C H 3C
SiMe3
FH2C FH2C H 2C FH2C
EtOH EtOH
Br OEt Br OEt
H 3C H 3C H 3C H 3C
C D
H 3C H 3C H 3C H 3C

5. Rank the following SN1 (or “solvolysis”) reactions from fastest to slowest.

H 3C H 3C H 3C H 3C
EtOH EtOH
F OEt Cl OEt
H 3C H 3C H 3C H 3C
A B
H 3C H 3C H 3C H 3C

H 3C H 3C H 3C H 3C
EtOH i-PrOH
Br OEt Cl OEt
H 3C H 3C H 3C H 3C
C D
H 3C H 3C H 3C H 3C

6. Predict the product of the following reaction, including stereochemistry.

H 3C Br
MeOH

Et Br
(enantiomerically pure)
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7. Predict the major product(s) of the following reactions.
a. Br
CH3
+ OCH3

t-Bu

b. CH3
Br
+ OCH3

t-Bu

8. Recall that we said in class that E2 reactions will tend to give the more thermodynamically stable
alkene product as the majpr product. For example, in the reaction shown below, product A
(elimination of Ha) is formed preferentially over product B (elimination of one of the Hb’s), because
A is a trisubstituted alkene while B is a less stable monosubstituted alkene:

CH3
elimination of Ha
H major
H 3C product
H 3C CH3
A CH3
Br OCH3
Ha
CH3
H CHb3
elimination of Hb H minor
H 3C product
B

However, this tendency of E2 reactions to produce the more highly substituted alkene product is
only observed when the base is sterically small, like H3CO-. If the same reaction is carried out using
the much sterically larger t-BuO- as the base, then B will be the major product. Provide an
explanation for this observation.

CH3
elimination of Ha minor
H
H 3C product
H 3C CH3
A CH3
Br Ot-Bu
Ha
CH3
H CHb3
elimination of Hb H major
H 3C product
B
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9. Predict the major product(s) of the following reactions.

a. Br

+ Ot-Bu

t-Bu Br

b.
Br
+ OCH3
CH3

c.
Br
+ Ot-Bu
CH3