Selective mono-N-methylation of amines using methanol as a methylating reagent over heterogeneous Ni catalysts

Abstract

Mono-N-methyl functionalization is one kind of important organic transformation, as mono N-methylamines are present in a variety of pharmaceutical and agrochemical applications. The use of methanol for the synthesis of mono-N-methylated amines remains a great challenge owing to the inertness of methanol as well as the second methylation of mono-N-methylated amines. Herein, supported Ni nanoparticle catalysts (Ni/ZnAlO_x-600) were effective for this transformation and various substrates were mono-N-methylated with yields of 75.3–97.3% at 160–180 °C. We have developed a method showing a promising potential methodology for the sustainable synthesis of N-methylamines and pharmaceuticals directly from amines with methanol.