14.26 : Nitriles to Carboxylic Acids: Hydrolysis

Nitriles undergo acid-catalyzed hydrolysis or base-catalyzed hydrolysis to form a carboxylic acid. These reactions proceed via an amide intermediate.

The acid-catalyzed mechanism involves the protonation of the nitrogen atom to make the carbon atom more susceptible to nucleophilic attack. The second step involves the nucleophilic attack by water on the nitrile carbon atom. Subsequently, deprotonation of the oxygen atom gives a tautomeric form of an amide, and protonation of the nitrogen forms a resonance stabilized intermediate. Next, the deprotonation yields an amide, which is followed by the protonation of the carbonyl oxygen. The second nucleophilic addition of water to the carbonyl carbon gives a tetrahedral intermediate, followed by deprotonation. Further, protonation of the nitrogen converts the amino group into a better leaving group. This is followed by the reconstruction of the carbonyl group by eliminating ammonia. Final deprotonation yields a carboxylic acid.

Base-catalyzed hydrolysis is another nucleophilic acyl substitution reaction. In this reaction, nitriles are treated in the presence of basic aqueous solutions to yield carboxylic acid. During base-catalyzed hydrolysis, the nucleophilic hydroxide ion attack the nitrile carbon atom. In the second step, the nitrogen atom gets protonated by water to remove the negative charge on the nitrogen to give the unstable enol tautomer of an amide. Next, hydroxide acting as a base deprotonates the oxygen atom to yield resonance stabilized intermediate, which upon protonation gives an amide. This is followed by the second nucleophilic attack by the hydroxide ion at the amide carbonyl carbon to give a tetrahedral intermediate. Subsequently, the carbonyl group is reconstructed with the departure of an amide ion as a leaving group. Lastly, deprotonation affords a carboxylate ion and ammonia, followed by acidification of the carboxylate ion to yield free acid.