isonitrile

Isonitrile, or isocyanide, is a functional group characterized by the formula R–N≡C, where R is an alkyl or aryl substituent. The group consists of a nitrogen atom bonded to a carbon that bears a triple bond to nitrogen. Isonitriles are a distinct class from nitriles (R–C≡N) and are known for a highly polarized N–C bond. They are versatile building blocks in organic synthesis and occur in various natural and synthetic compounds.

Structure and reactivity: The isonitrile group is strongly polarized. The terminal carbon is a reactive site for nucleophilic attack and for insertion into metal centers; nitrogen can coordinate to metals as well. This reactivity underpins many of its synthetic applications.

Preparation: The Hofmann isocyanide synthesis converts primary amines into formamides and then dehydrates them to give isocyanides. A second common route is the dehydration of formamides (R–NH–CHO) using reagents such as POCl3 in the presence of base.

Reactions and applications: Isocyanides are key components in multicomponent reactions, including the Passerini and Ugi reactions, enabling rapid assembly of complex molecules and peptidomimetics. They also participate in cycloadditions and various organometallic transformations, and are used as ligands in catalysis.

Safety and handling: Isocyanides often have pungent odors and can be toxic or irritating. They are typically handled in well-ventilated fume hoods with appropriate personal protective equipment. Proper storage and waste disposal are required due to potential health hazards.