Hofmann rearrangement

Schematic of the Hofmann rearrangement. Reagents: primary amide, chlorine or bromine gas, base, water, heat. Product: primary amine.

The Hofmann rearrangement is an organic reaction used to convert a primary amide to a primary amine using a halogen, base, water, and heat. The reaction begins with deprotonation of the amide by the base to form an anion which then attacks the halogen to form a N-haloamide. A second deprotonation by the base provides an anion that rearranges to an isocyanate intermediate and releases a halide anion. The isocyanate is then attacked by water which after a series of proton transfer step results in a zwitterionic intermediate, containing an ammonium cation and a carboxylate anion. Thermal conditions result in the explosion of carbon dioxide gas and quenching of the ammonium cation to the amine product.[1]


Mechanism of the Hofmann rearrangement. Isocyanate intermediate.


Hofmann, A. W. Ber. Dtsch. Chem. Ges. 1881, 14, 2725–2736.