Reductive Mono-Alkylation of Aromatic Amines Using Nitriles

Abstract

Despite numerous literature precedents, selective mono-alkylation of primary amines for the synthesis of secondary amines remains a challenging in organic synthesis. Reported synthetic methods of secondary amines mainly include direct N-alkylation of primary amines using alkyl halides, amide reduction and reductive alkylation protocols although those methods possess serious limitations such as the concomitant overalkylation. The reductive alkylation of amines using aldehydes is one of the most important methods while the aldehyde is one of the environmentally-unfriendly reagents. We have found an environmentally-benign mono-alkylation method of aromatic amines under Pd/C-catalyzed hydrogenation conditions using nitriles as alkylating agents. The present method could be applied to the direct synthesis of secondary amines from aromatic nitro compounds.