13.8: Preparation of Carboxylic Acids: Hydrolysis of Nitriles

Carboxylic acids can be prepared from nitriles via hydrolysis under aqueous acidic conditions. In base-catalyzed conditions, carboxylate anions are generated.

In acid-catalyzed hydrolysis, first, the nitrile nitrogen atom is protonated, rendering the cyano carbon atom more electrophilic.

This leads to an attack by the weak nucleophile—water. Next, deprotonation of the oxygen atom generates an imidic acid.

Then, the imidic acid tautomerizes to a more stable form, an amide, via two steps. The imidic nitrogen is first protonated to form a resonance stabilized protonated amide, which upon subsequent deprotonation, forms the amide.

Finally, the amide undergoes multi-step hydrolysis to generate the carboxylic acid.

Hydrolysis of nitriles is part of the two-step conversion of haloalkanes to carboxylic acids with introduction of an additional carbon to the starting haloalkane.

For example, ibuprofen—an anti-inflammatory drug—is synthesized via nitrile formation and its subsequent base hydrolysis.