Organic Chemistry

Section 17.12 Hydroxide-Ion-Promoted Ester Hydrolysis 697

This reaction is called a hydroxide-ion-promoted reaction rather than a base-cat-
alyzed reaction because hydroxide ion increases the rate of the first step of the reaction
by being a better nucleophile than water—not by being a stronger base than water—and
because hydroxide ion is consumed in the overall reaction. To be a catalyst, a species
must not be changed by or consumed in the reaction (Section 17.11). So hydroxide ion
is actually a reagent rather than a catalyst. Therefore, it is more accurate to call the
reaction a hydroxide-ion-promotedreaction than a hydroxide-ion-catalyzedreaction.
Hydroxide ion promotes only hydrolysis reactions, not transesterification reactions or
aminolysis reactions. Hydroxide ion cannot promote reactions of carboxylic acid deriva-
tives with alcohols or with amines because one function of hydroxide ion is to provide a
strong nucleophile for the first step of the reaction. Thus, when the nucleophile is sup-
posed to be an alcohol or an amine, nucleophilic attack by hydroxide ion would form a
product different from the product that would be formed from nucleophilic attack by an
alcohol or amine. Hydroxide can be used to promote a hydrolysis reaction because the
same product is formed, regardless of whether the attacking nucleophile is or
Reactions in which the nucleophile is an alcohol can be promoted by the conjugate
base of the alcohol. The function of the alkoxide ion is to provide a strong nucleophile
for the reaction, so only reactions in which the nucleophile is an alcohol can be pro-
moted by its conjugate base.

PROBLEM 22

a. What species other than an acid can be used to increase the rate of a transesterification

reaction that converts methyl acetate to propyl acetate?

b. Explain why the rate of aminolysis of an ester cannot be increased by or

You have seen that nucleophilic acyl substitution reactions take place by a mecha-
nism in which a tetrahedral intermediate is formed and subsequently collapses. The
tetrahedral intermediate, however, is too unstable to be isolated. How, then, do we
know that it is formed? How do we know that the reaction doesn’t take place by a one-
step direct-displacement mechanism (similar to the mechanism of an reaction) in
which the incoming nucleophile attacks the carbonyl carbon and displaces the leaving
group—a mechanism that would not form a tetrahedral intermediate?

transition state for a hypothetical one-step

direct-displacement mechanism

O

C

R

HO OR

δ− δ−

SN 2

H+,HO-, RO-.

+

CH 3 CH 2 O−

excess

+ CH 3 OH

OCH 2 CH 3

CH 3 CH 2 OH

OCH 3

C

O

C

O

H 2 O HO-.

HCl

OCH 3

+ + H 2 OCH 3 OH

R

C

O

R OH

C

O

O−

reversible reaction

NaOH

OCH 3

+ + H 2 OCH 3 OH

R

C

O

R

C

O

irreversible reaction