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Master Organic Chemistry Reaction Guide

Acidic Hydrolysis of Amides

Description: Treatment of amides with aqueous acid (and heat) gives carboxylic acids.

Notes: The vague, “H3O+” is shown here. In practice this procedure may involve aqueous HCl or H2SO4. Here is a link to a procedure.

Examples:

Notes: Example 1 shows the hydrolysis of a secondary amide with acid to give a carboxylic acid. Example two shows the hydrolysis of a tertiary amide to give a carboxylic acid and an amine. The third example shows the hydrolysis of a cyclic amide (a “lactam”) to give a linear product.

Mechanism:

This is a reaction mechanism that follows the classic “PADPED” pattern. Protonation of the oxygen (Step 1, arrows A and B) results in a charged species that undergoes addition by nucleophilic water (Step 2, arrows C and D). This is followed by proton transfer (Steps 3 and 4, arrows E and F) to NH2, giving a better leaving group NH3+ which then undergoes elimination (Step 5, arrows G and H) to give a protonated carboxylic acid which is then deprotonated by base (Step 6, arrows I and J).

mechanism for acidic hydrolysis of amides