Work

A Dual‐Functional Approach: Temperature‐Dependent Selective N‐Methylation of Amines with Methanol via Skeletal Copper Catalysts

Year: 2025

Type: article

Abstract: Selective N‐methylation with green methylating agents is a highly attractive yet challenging topic in organic synthesis and pharmaceutical production. Herein, a skeletal Cu‐based catalyst was developed for the selective N‐methylation of amines using renewable methanol under relatively mild conditions. By simply modulating the reaction temperature, the CuZnAl‐1.5 catalyst enabled tunable synthesis of N‐monomethylated and N,N‐dimethylated amines. A wide range of amines were efficiently methylated in high yields. Kinetic and mechanistic studies revealed a borrowing hydrogen pathway, with N‐monomethylation exhibiting a lower activation energy. The active Cu surface was identified as the key site for methanol activation to form aldehyde intermediate, whose concentration critically influenced product selectivity. The role of Zn in catalyst preparation and catalysis was also elucidated. The catalyst demonstrated excellent applicability in various synthetic scenarios, underscoring the potential of skeletal Cu‐based systems for methylation reaction with methanol.

Source: ChemCatChem

DOI: 10.1002/cctc.202402126