Selective synthesis of N-monomethyl amines with primary amines and nitro compounds

Abstract

N-Monomethyl amines are important building blocks in the synthesis of a range of valuable compounds, including dyes, surfactants, pharmaceuticals, agrochemicals, and materials. Furthermore, the N-methyl group plays an important role in various biological processes where some methylated drug candidates show enhanced activity compared to the non-methylated precursors as a result of the change in solubility, conformation, and metabolic activity. However, facile access to such compounds remains a fundamental challenge in organic synthesis owing to selectivity issues caused by overmethylation. Therefore, controllable synthesis of N-monomethyl amines by selective N-monomethylation of primary amines and nitro compounds is an important and challenging field in synthetic organic chemistry and catalysis. There is a need for a comprehensive review on catalytic N-monomethylation of primary amines and nitro compounds to motivate the advancements of this field. Herein, the development of N-monomethylation of primary amine and nitro compounds with homogeneous and heterogeneous catalysts is summarized. This article describes the development of the selective N-monomethylation of primary amines and nitro compounds by using various methylating agents, such as MeX, carbon dioxide, methanol, formaldehyde, formic acid and dimethyl carbonate. The basic principles and strategies to control selectivity of N-monomethylation of primary amines and nitro compounds with different methylating agents are also summarized. Finally, we will give some advice for future progress in this field. This review will promote the development of N-monomethylation of primary amines and other selective methylation.