ammonolysis

Ammonolysis is a chemical reaction in which ammonia (NH3) reacts with a substrate to form nitrogen-containing products, typically amines or amides. In practice, the term is used for nucleophilic substitutions in which ammonia replaces a leaving group, or for the conversion of carbonyl derivatives by reaction with ammonia to yield amides.

Common substrates include esters and acyl chlorides, which react with ammonia to produce amides. Esters such as ethyl acetate can undergo ammonolysis to give acetamide and alcohol under suitable conditions, while acyl chlorides react more readily to form primary amides and hydrogen chloride. Alkyl halides can also undergo ammonolysis with ammonia to furnish primary amines, though subsequent reactions can lead to secondary or tertiary amines with excess ammonia.

Reaction conditions vary by substrate but often require elevated temperature and excess ammonia. Ammonia can be used as a gas or dissolved in solvent, and reactions may be conducted with or without catalysts. Water and other nucleophiles present can compete with ammonolysis, so conditions are typically chosen to favor substitution by ammonia.

Mechanistically, ammonolysis proceeds by nucleophilic substitution: nucleophilic attack of NH3 on a carbonyl carbon in acyl derivatives with formation of a tetrahedral intermediate and subsequent expulsion of the leaving group, or by SN2 attack on alkyl halides. The process is widely used in organic synthesis to prepare amides and amines and has applications in polymer chemistry and pharmaceutical manufacturing. Safety considerations include the toxic and corrosive nature of ammonia and the potential generation of corrosive byproducts.