amidination

Amidination is a chemical transformation in which an amidino group, typically written as RC(=NH)NR'R'', is introduced into an organic substrate to give an amidine or amidinium product. The amidine functional group is characterized by a C=N–NH– linkage and is a common motif in medicinal chemistry and catalysis due to its basicity and hydrogen-bonding properties.

One common route to amidination involves converting a nitrile into an amidine. In these methods nitriles are activated and treated with ammonia or primary/secondary amines under dehydrating or activating conditions, leading to the formation of the amidine after nucleophilic addition to the nitrile carbon and subsequent capture of an imidoyl intermediate with loss of water or other small byproducts. The exact reagents and conditions vary, but dehydration and sometimes acid or Lewis acid catalysis are typical features.

A second approach uses amidinyl transfer reagents that deliver the amidino fragment directly to a nucleophile, such as an amine or an activated carbon center. Reagents like imidoyl chlorides and related activated species enable a more direct installation of the –C(=NH)NR2 group under milder conditions. Some variants proceed through surface- or solution-phase imidoyl intermediates that are subsequently trapped by nitrogen nucleophiles.

Amidination products are generally basic and can exist as amidines or protonated amidinium salts. They serve as versatile building blocks in the synthesis of pharmaceutical agents, agrochemicals, and ligands for metal complexes. The field continues to expand with aims to improve regio- and chemoselectivity, expand substrate scope, and develop milder, more sustainable methods.