Organic Chemistry

acetic anhydride

Section 17.9 Reactions of Acid Anhydrides 689

17.9 Reactions of Acid Anhydrides

Acid anhydrides do not react with sodium chloride or with sodium bromide because
the incoming halide ion is a weaker base than the departing carboxylate ion
(Table 17.1).

Because the incoming halide ion is the weaker base, it will be the substituent expelled
from the tetrahedral intermediate.

An acid anhydride reacts with an alcohol to form an ester and a carboxylic acid,
with water to form two equivalents of a carboxylic acid, and with an amine to form an
amide and a carboxylate ion. In each case, the incoming nucleophile—after it loses a
proton—is a stronger base than the departing carboxylate ion. In the reaction of an
amine with an anhydride, two equivalents of the amine or one equivalent of the amine
plus one equivalent of a tertiary amine such as pyridine must be used so that sufficient
amine is present to react with the proton produced in the reaction.

All the reactions follow the general mechanism described in Section 17.7. For
example, compare the following mechanism for conversion of an acid anhydride
into an ester with the mechanism for conversion of an acyl chloride into an ester
presented on p. 687.

OCH 3

O

CH 3

CH 3 C O CCH 3

Cl

O− O

C C + Cl−

O

OCH 3

+

CH 3

C Cl− no reaction

O

C

O

+ H 2 O

CH 3

+ CH 3 CH 2 OH

benzoic anhydride

2

benzoic acid

acetic anhydride ethyl acetate acetic acid

+

CH 3 CH 2 CH 2 CH 3

+ 2 CH 3 NH 2

O

propionic anhydride N-methylpropionamide

CH 3 CH 2 NHCH 3 CH 3 CH 2 O− H 3 NCH 3

+ +

OOH

O CH 3

C

O

C

O

C

O

C

O

C

O

C

O

C

O

C

O

C

O

CH 3 OCH 2 CH 3

C

O

CH 3 OH

C

O

CH 3 OCH 3

O O

H 3 CCOCH 3 OCH 3

+

OCH 3

BHB+

CH 3 O CH 3

OCH 3

H

+

O−

+ CH 3 OH

H 3 C C O

O−

mechanism for the conversion of an acid anhydride into an ester (and a carboxylic acid)

C C −

OO

C

CH 3

OO

C

OO

C

OO

C