Overview

Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.

In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride ion. In the last step, the amide nitrogen is deprotonated by another equivalent of the amine to give the final substitution product.

If the amine is expensive, the reaction is performed with one equivalent of the amine and a second equivalent of an inexpensive base like triethylamine, pyridine, or sodium hydroxide.

Procedure

Besides hydrolysis and alcoholysis, aminolysis is another nucleophilic acyl substitution reaction involving ammonia or amines as nucleophiles.

Acid halides react with ammonia, producing primary amides. Primary amines give secondary amides, and secondary amines yield tertiary amides.

The aminolysis mechanism begins with a nucleophilic attack by the amine at the carbonyl carbon, forming a tetrahedral intermediate.

Next, the carbonyl is reconstructed, and the halide ion departs as a leaving group.

The last step involves deprotonation of the amide nitrogen by another equivalent of the amine, giving the substitution product along with the ammonium salt.

The reaction is typically carried out in excess amine, one equivalent for the nucleophilic attack and the second as a base in the final proton transfer step. 

However, if the amine is expensive, relatively inexpensive bases like pyridine or sodium hydroxide are used for deprotonation.