Synthesis 2018; 50(10): 2041-2057
DOI: 10.1055/s-0037-1609342
paper
© Georg Thieme Verlag Stuttgart · New York

Latent Brønsted Base Solvent-Assisted Amide Formation from Amines and Acid Chlorides

Rikuto Otsuka
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan   Email: ohwada@mol.f.u-tokyo.ac.jp
,
Kazuo Maruhashi
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan   Email: ohwada@mol.f.u-tokyo.ac.jp
,
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan   Email: ohwada@mol.f.u-tokyo.ac.jp
› Author Affiliations
This work was supported financially by the University of Tokyo. All authors acknowledge this support.
Further Information

Publication History

Received: 19 January 2018

Accepted after revision: 20 February 2018

Publication Date:
20 March 2018 (online)


Abstract

Weakly basic amines, including even neutral amines such as nitroaniline and aminocarboxylic acids, react with acid chlorides very efficiently in N,N-dimethylacetamide (DMAC), without addition of a base, to give the corresponding amides in high yields. The role of DMAC and related solvents as latent Brønsted bases was studied in these amidation reactions. Less basic amines, such as aromatic amines, reacted with benzoyl chloride faster than more basic aliphatic amines.

Supporting Information

 
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