A Straightforward Synthesis of N-Substituted Ureas from Primary Amides

Abstract

A direct and convenient method for the preparation of N-substituted ureas is achieved by treating primary amides with phenyliodine diacetate (PIDA) in the presence of an ammonia source (NH3 or ammonium carbamate) in MeOH. The use of 2,2,2-trifluoroethanol (TFE) as the solvent increases the electrophilicity of the hypervalent iodine species and allows the synthesis of electron-poor carboxamides. This transformation involves a nucleophilic addition of ammonia on the isocyanate intermediate generated in situ by a Hofmann rearrangement of the starting amide.