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May 6, 2026Asian Journal of Organic Chemistry0 citations

Facile Construction of N ‐Methylated Tertiary Amines via Catalyst‐Free Consecutive Reductive Amination/ N ‐Methylation of Carbonyl Compounds With Amines Using DMSO and HCO 2 H/NEt 3

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JYJianbo YangJYJi YangHJHongzhe Jia

Key Points

  • This research aims to develop a one-pot synthesis method for N-methylated tertiary amines from carbonyl compounds and primary amines.
  • Catalyst-free, tandem reductive amination/N-methylation process.
  • Utilizes HCO2H/NEt3 mixture as reductant and DMSO as solvent.
  • Variety of carbonyl compounds and functional groups tested.
  • Produces N-methylated tertiary amines in 76%-96% yields.
  • Reacts with a diverse range of functional groups.
  • Scalable method applicable for synthesizing biologically important compounds.

Abstract

ABSTRACT A catalyst‐free, one‐pot tandem reductive amination/ N ‐methylation of carbonyl compounds with primary amines for the synthesis of N ‐methylated tertiary amines has been developed. Employing a HCO 2 H/NEt 3 (5/2) mixture as the reductant and DMSO as both solvent and methylating agent, this method rapidly produces N ‐methylated tertiary amines from a diverse range of substrates in 76%–96% yields within just 2 h and accommodates a wide variety of functional groups. Furthermore, this protocol is both scalable and directly applicable to the synthesis of pharmaceutically and biologically important compounds. A plausible mechanism for this transformation is outlined based on insights from control experiments and mechanistic investigations.

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Cite This Study

Yang et al. (2026) studied this question.

synapsesocial.com/papers/69fa8e8904f884e66b530e31https://doi.org/10.1002/ajoc.70416
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