cyanation

Cyanation is a chemical transformation that introduces a cyano group (-CN) into an organic molecule, yielding a nitrile. Nitriles are valuable intermediates in organic synthesis and appear in pharmaceuticals, agrochemicals, and materials. Cyanation can be accomplished by several complementary strategies, each with distinct substrate scope and conditions.

One major class is nucleophilic cyanation, which uses cyanide sources such as sodium or potassium cyanide to substitute leaving groups on substrates such as aryl or alkyl halides. In aryl chemistry, copper- or palladium-catalyzed cyanations of aryl halides or aryldiazonium salts (the Sandmeyer approach) are widely used to access arenitriles; alkyl cyanides are formed by SN2 substitutions of suitable alkyl electrophiles with cyanide under appropriate conditions. Other routes involve substitution of nitro groups or esters in specialized cases.

A second class is electrophilic cyanation, which employs reagents that transfer a CN+ unit to nucleophilic or electron-rich substrates, enabling cyanation of enolates, arenes, and alkenes under milder conditions and often with better functional-group tolerance.

A third class is radical cyanation, frequently enabled by photoredox or radical pathways, delivering nitriles by addition of a CN-containing radical to alkenes or alkynes in the presence of a cyanating agent.

A fourth class is hydrocyanation, in which hydrogen cyanide or a safe surrogate is added across carbon–carbon multiple bonds to form nitriles, a method useful for rapidly building nitrile-containing motifs.

Cyanation provides direct access to nitriles, which can be further transformed to amides, carboxylic acids, amines, or heterocycles. Practical considerations include substrate compatibility and the toxicity of cyanide reagents, requiring careful handling and disposal.