Ball-milling and cheap reagents breathe green life into the one hundred-year-old Hofmann reaction

Abstract

The Hofmann carbylamine reaction is a very attractive route for preparing isocyanides directly from primary amines. However, its environmentally friendly potential is reduced by the use of hazardous chloroform in large excess. Herein, we report an innovative and very efficient mechanically activated synthesis of isocyanides based on the reaction of amines with chloroform in the presence of solid NaOH and without extra-solvent addition.