A Guidebook to Mechanism in Organic Chemistry

Addition to Carbon-Oxygen Double Bonds

The reactivity sequence is well illustrated by the fact that acid
chlorides react readily with alcohols and amines to yield esters and
amides, respectively, while esters react with amines to give amides,
but the simple reversal of any of these reactions on an amide though
possible is usually very difficult.

(i) Base induced reactions

The example that has been the subject of most investigation is almost

certainly the alkaline hydrolysis of esters. This has been shown to be a

second-order reaction and, by the use of^180 labelli«gp*ha6 seen to

involve acyl-oxygen cleavage (cf. p. 35) in most cases

O O

II! 18 ©OH II „ 18

R C-I-OR' > RC—Oe + H—OR'

the labelled oxygen appearing in the alcohol but not in the acid anion

from the hydrolysis. The reaction is believed to proceed:

C

o fo o o

R_C—OEt =LR—C-LOEt R—C+ OEt -* R—C+HOEt

c *OH OH OH Oe

The rate-determining step is almost certainly the initial attack of ®OH

on the ester and the overall reaction is irreversible due to the insuscept­

ibility of R • COz® to attack by EtOH or EtO®. The alkaline hydrolysis

of amides, R-CO-NHR', follows a very similar course in which it is

e

RNH that undergoes expulsion. The action of ®OR in place of ®OH

on an ester results in transesterification to yield R-CO-OR' and the

action of amines on esters to form amides also follows an essentially

similar course:

^•NH.R

eO r®0 O

I CH? >H nt n 0

R—C—OEt R—C—OEt =E=i R—CJ-OEt ^= R—C+ OEt

®NH 2 R NHR * NHR

s @

It has been ishown that the conjugate base of the amine, RNH