Practice problems 3: Substitution or elimination?

CHM 235
Answer key Minger
Predict the major organic product of each of the following reactions. Write the name of the
mechanism by which the product is formed and make notes about how you arrived at your
conclusion. The first three are done for you to suggest a general method of how to analyze
these problems.

CH3 CH3ONa E2. Sterically hindered

1. substrate; strong base,
Cl CH3OH good leaving group.
CH3

CH2CH3 CH2CH3
CH2CH3
2. +
OCH3 CH3
Cl CH3OH CH3 OCH3
CH3

SN1/E1. Sterically hindered

substrate can form a stable
+
carbocation. Weak base/
poor nucleophile. Notice the
mixture of inversion and
retention of configuration in
the substitution products.
Some E1 product may also
form.

CH3 CH3
Br CN
NaCN
3.
DMSO

SN2. Excellent nucleophile, excellent leaving group.

Polar aprotic solvent is a clue to SN2 pathway. (Cyanide
can also effect E2 reaction.)

OCH3 H2SO4 E1. Dehydration conditions work

4.
the same on OR as they do on OH.
The O in the OCH3 group is protonated
and the reaction proceeds in an
identical manner as what we have seen
with alcohols. Note that the double/single/
double bond pattern formed, called
conjugation, is particularly stable.

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 CH3 KBr CH3
SN2. Secondary substrate, good nucleophile,
5.
I DMSO H polar aprotic solvent. Inversion of configuration.
H Br

E2. Substrate is quite hindered.

LDA is a strong, sterically hindered base
CH3 LDA CH3 (and a poor nucleophile because of its
6. steric hindrance) that is used for
I CH3 DMF CH3
elimination reactions. Conjugation of the
new double bond with the benzene
ring (see #4) is also favorable.

H3C Br
H3C HBr
7. +
Br H3C
EtO 0 oC
CH3 CH3
CH3
SN1. The EtO group gets protonated by HBr and leaves as ethanol,
(Et = CH2CH3) forming a carbocation which is then captured by bromide, a good
nucleophile. Low temp discourages elimination pathway. Planar
carbocation is attacked from above or below by bromide, resulting in
product mixture.

KN3 CH3 SN2. Secondary substrate; azide is a

8. CH3
good nucleophile; polar aprotic solvent.
I H DMF H N3
Inversion of configuration.

E2. Steric hindrance prevents

methoxide from nucleophilic attack.
H3C Br CH3ONa Bromide is an excellent leaving group
9.
and conjugation of the new double bond
DMSO
with the ring (see #4) is an additional
driving force. Steric hindrance is a more
important factor than the polar aprotic
solvent. If the nucleophile can't approach,
no solvent can help that!

H3C H3C AcO

10.
Cl OAc + CH3
O

OH O
OAc =
O

SN1. Polar protic solvent (acetic acid) that's a weak nucleophile and tertiary substrate encourage
unimolecular substitution. Notice mixture of retention and inversion of configuration in product.
E1 elimination is possible as well.

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 CH3 H3PO4 E1. Dehydrating conditions give the alkene
11.
after carbocation rearrangement.
OH

Br KOH(aq)
12.
OH (dilute)

SN2. The first step is a deprotonation. In the presence of hydroxide ion, the alcohol will be
deprotonated (compare pKa values of water and alcohols to estimate the extent of this
deprotonation):

Br Br
KOH
OH O O

There could also be some direct displacement of bromide ion by hydroxide, although the
proton transfer shown above is faster:

HO
Br OH

OH OH

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