14.17 : Reactions of Acid Anhydrides

The reactions of acid anhydrides are analogous to the reactions of acid chlorides and proceed via a nucleophilic acyl substitution. They only differ in the identity of the leaving group. During an acid chloride reaction, the leaving group is a chloride ion, and the by-product is hydrochloric acid. However, in an acid anhydride reaction, the leaving group is a carboxylate ion, and the by-product is a carboxylic acid.

The reaction of acid anhydrides involves the nucleophilic attack at one carbonyl group, while the second carbonyl group becomes part of the leaving group.

The acid anhydrides are hydrolyzed with water to give two equivalents of carboxylic acid. In alcoholysis, alcohol functions as a nucleophile and reacts with an acid anhydride to form an ester and a carboxylic acid.

Acid anhydrides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively. One carboxylic acid molecule is formed as a by-product in each case.

Acid anhydrides are reduced to primary alcohols in the presence of a strong reducing agent like lithium aluminum hydride. However, it is possible to stop the reaction at the aldehyde by using a milder reducing agent like diisobutylaluminum hydride or lithium tri(t-butoxy) aluminum hydride.

Organomagnesium halides, commonly known as Grignard reagents, convert acid anhydrides to tertiary alcohols, which proceed via a ketone intermediate. Lithium dialkyl cuprate, known as Gilman reagents, selectively reduces acid anhydrides to ketones.

All the acid anhydrides reactions involve the loss of half of the anhydrides as the leaving group. This makes the anhydrides inefficient as starting materials. However, one exception is the formation of half-esters and half-amides from cyclic anhydrides.