What question did this study set out to answer?

The study aims to establish an efficient transamidation system for aromatic amines using potassium tert-butoxide.

July 4, 2026Letters in Organic Chemistry0 citations

t-BuOK-Mediated Transamidation System for Aromatic Amines and Multiple Acyl Donors

JYJiang YangXinjiang Agricultural University QLQin Xiao LiXinjiang Uygur Autonomous Region Product Quality Supervision and Inspection Institute ZLZhang Zhen LinXinjiang Agricultural University

Key Points

The study aims to establish an efficient transamidation system for aromatic amines using potassium tert-butoxide.
Developed a transamidation system using t-BuOK for 49 amide compounds synthesis.
Conducted mechanistic investigations, including radical scavenger and 18-crown-6 studies.
Synthesis performed at mild reaction conditions, achieving trifluoroacetylation at room temperature.
Successfully synthesized 49 amide compounds with yields between 30% to 96%.
Reaction proceeds through a K+ dual-coordination-driven pathway, effectively activating amines and acyl donors.
Achieved room-temperature synthesis, demonstrating a green route for fluorine-containing pharmaceutical intermediates.

Abstract

Abstract: A potassium tert-butoxide (t-BuOK)-mediated transamidation system for aromatic amines has been established in this study, enabling efficient transition-metal-free transamidation between aromatic amines/heterocyclic amines and multiple acyl donors. A total of 49 amide compounds were synthesized with yields ranging from 30% to 96%. Notably, the protocol features mild reaction conditions (≤50 °C, no microwave assistance) and achieves room-temperature trifluoroacetylation of heterocyclic amines, providing a green route for the synthesis of fluorine-containing pharmaceutical intermediates and complex heterocyclic amide skeletons. Mechanistic investigations, including radical scavenger experiments and 18-crown-6 chelation studies, reveal that the reaction proceeds via a K+ dual-coordination-driven nucleophilic addition-elimination pathway. Specifically, K+ acts as a hard Lewis acid to form an "aniline-K+-acyl donor" ternary complex, synergistically activating both the nucleophilic amine and electrophilic acyl donor, thereby facilitating amide C-N bond cleavage and target product formation.

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