Organic Chemistry

Section 17.10 Reactions of Esters 691

transesterification

serine hydroxyl

group

CH 3 CO ++HOCH 2

O

CH 3 C OCH 2

O

−OOC

HO

−OOC

acetylsalicylate

aspirin

enzyme

active

acetylated enzyme

inactive

salicylate

acetyl

group

ASPIRIN

A transesterification reaction that blocks prosta-

glandin synthesis is responsible for aspirin’s activi-

ty as an anti-inflammatory agent. Prostaglandins have several

different biological functions, one of which is to stimulate

inflammation. The enzyme prostaglandin synthase catalyzes the

conversion of arachidonic acid into a precursor of

prostaglandins and the related thromboxanes (Section 26.5).

PGH 2 ,

arachidonic acid PGH 2

prostaglandins

thromboxanes

prostaglandin synthase

group reacts with aspirin (acetylsalicylic acid) in a transesterifi-

cation reaction and becomes acetylated. This inactivates the en-

zyme. Prostaglandin therefore cannot be synthesized, and

inflammation is suppressed.

Prostaglandin synthase is composed of two enzymes. One of

the enzymes—cyclooxygenase—has a group (called a

serine hydroxyl group because it is part of the amino acid called

serine) that is necessary for enzyme activity. The CH 2 OH

CH 2 OH

Thromboxanes stimulate platelet aggregation. Because aspirin in-

hibits the formation of it inhibits thromboxane production

and, therefore, platelet aggregation. Presumably, this is why low

levels of aspirin have been reported to reduce the incidence of

PGH 2 ,

strokes and heart attacks that result from blood clot formation.

Aspirin’s activity as an anticoagulant is why doctors caution

patients not to take aspirin for several days before surgery.

The reaction of an ester with an amine is not as slow as the reaction of an ester with
water or an alcohol, because an amine is a better nucleophile. This is fortunate, be-
cause the rate of the reaction of an ester with an amine cannot be increased by acid or
by or (Problem 20). The aminolysis of an ester can be driven to completion
by using excess amine or by distilling off the alcohol as it is formed.

In Section 7.10, we saw that phenols are stronger acids than alcohols. Therefore,
phenoxide ions are weaker bases than alkoxide ions which means that
phenyl esters are more reactive than alkyl esters.

CH 3 CH 3

is more reactive than

phenyl acetate

pKa = 10.0

methyl acetate

O

OH

pKa = 15.5

CH 3 OH

OCH 3

C

O

C

O

(ArO-) (RO-),

CH 3

+

CH 3 excess

CH 3 (CH 2 ) 4 NH 2 + CH 3 OH

OCH 3 NH(CH 2 ) 4 CH 3

C

O

C

O

HO- RO-

3-D Molecule:

Phenyl acetate