A sustainable twist on the Ritter reaction: iron-based deep eutectic solvents as a green route to amide synthesis

Abstract

A sustainable and scalable Ritter reaction protocol has been developed for the efficient amidation of diverse secondary and tertiary alcohols with both aliphatic and aromatic nitriles, employing a reusable FeCl₃·6H₂O/glycerol Lewis acidic deep eutectic solvent. The method features mild, aerobic conditions and broad substrate scope, and delivers yields of up to 98% without chromatographic purification. CHEM21 green metrics underscore the significantly reduced environmental footprint of this approach, establishing it as a greener and more efficient alternative to conventional amide synthesis protocols. The practical utility of the method is further demonstrated by the gram-scale synthesis of drug Chlodantane, showcasing its potential for sustainable applications in pharmaceutical manufacturing.