Kishore Natte, H. Neumann, R. V. Jagadeesh
Nov 7, 2017
Citations
0
Influential Citations
0
Citations
Journal
Nature Communications
Abstract
N-Methylated amines play an important role in regulating the biological and pharmaceutical properties of all kinds of life science molecules. In general, this class of compounds is synthesized via reductive amination reactions using high pressure of molecular hydrogen. Thus, on laboratory scale especially in drug discovery, activated (toxic) methyl compounds such as methyl iodide and dimethyl sulfate are still employed, which also generate significant amounts of waste. Therefore, the development of more convenient and operationally simple processes for the synthesis of advanced N-methylamines is highly desired. Herein, we report the synthesis of functionalized and structurally diverse N-methylamines directly from nitroarenes and paraformaldehyde, in which the latter acts as both methylation and reducing agent in the presence of reusable iron oxide catalyst. The general applicability of this protocol is demonstrated by the synthesis of >50 important N-methylamines including highly selective reductive N-methylations of life science molecules and actual drugs, namely hordenine, venlafaxine, imipramine and amitriptyline.N-methylated amines display high biological activity in living organisms. Here, the authors show the convenient synthesis of a wide range of biologically relevant N-methylamines via reduction of nitrobenzenes using a recyclable iron catalyst and paraformaldehyde without additional hydrogen pressure.