Amides to Carboxylic Acids: Hydrolysis

Amides undergo hydrolysis in aqueous acid or aqueous base to give carboxylic acids. These reactions are slow and require heating.

Acid-catalyzed amide hydrolysis begins with the carbonyl oxygen protonation, followed by the nucleophilic addition of water to the carbonyl carbon, forming a tetrahedral intermediate.

Further, deprotonation of the tetrahedral intermediate and protonation of the nitrogen converts the amino group into a better leaving group.

Next, the carbonyl group is re-formed by eliminating ammonia. Final deprotonation yields a carboxylic acid.

Notably, ammonium ion, a weak acid, is formed as a by-product, driving the equilibrium towards products.

Basic hydrolysis of amides is another nucleophilic acyl substitution involving hydroxide as a nucleophile.

The mechanism begins with the nucleophilic attack of the hydroxide ion at the carbonyl carbon, forming a tetrahedral intermediate.

Subsequently, the carbonyl group is reconstructed with the departure of an amide ion.

Final deprotonation yields a carboxylate ion and ammonia. This step drives the reaction to completion, pushing the equilibrium towards the product.

Acidification of the carboxylate ion gives free acid.