Recent New Developments in Hofmann, Curtius, Schmidt, Lossen, and Related Reactions

Abstract

The Hofmann, Curtius, Schmidt, and Lossen rearrangements are decomposition reactions from carboxylic acids and their derivatives to amines and their derivatives with one less carbon atom. These reactions, which involve nucleophilic migrations from a carbon atom to an electron-deficient nitrogen center to give an isocyanate as a key intermediate and conversion to an amine derivative, have been widely used since their discovery owing to their practicality in replacing carboxy groups with amino groups. When the starting material is a carboxylic acid or its derivatives, these reactions proceed through an isocyanate intermediate, which can be isolated in a non-nucleophilic solvent in the case of the Curtius and Hofmann reactions. The key isocyanate intermediate reacts readily with various nucleophiles to give amines, ureas, urethanes, thioureas, and amides, rendering such rearrangement reactions via this versatile intermediate very attractive. In the Schmidt reaction with aldehydes or ketones as starting materials, denitrogenation is performed via azidoalkanols to give the corresponding nitriles or amides. The Lossen rearrangement reaction is the rearrangement of hydroxamic acids to isocyanates. This chapter reviews recent advances in Hoffmann, Curtius, Schmidt, Lossen, and related reactions over the last decade.