Simple, Mild, and Practical Esterification, Thioesterification, and Amide Formation Utilizing p‐Toluenesulfonyl Chloride and N‐Methylimidazole

• DOI: 10.1002/adsc.200303093
• Publication Date: 2003-11-20T18:12:43Z
• Authors: Kazunori Wakasugi; Akira Iida; Tomonori Misaki; Yoshinori Nishii; Yoo Tanabe
• Keywords: Racemization; Amide; Acyl chloride; Primary (astronomy); Nucleophilic acyl substitution

Abstract We have developed an efficient method for the esterification or thioesterification of equimolar amounts carboxylic acids and alcohols thiols using a novel reagent, p ‐toluenesulfonyl chloride (TsCl) together with N ‐methylimidazole. The present is simple, mild, reactive, uses readily available economical reagents. choice amine critical method. amine, ‐methylimidazole, has two roles: (i) as HCl scavenger initial smooth generation mixed anhydrides between TsCl (ii) successive formation highly reactive ammonium intermediates from anhydrides. This could be applied to various types acids, alcohols, thiols: a) several functionalities were tolerated; b) ‐Cbz amino smoothly esterified without racemization; c) labile 1β‐methylcarbapenem key intermediate pyrethroid insecticide, prallethrin, successfully prepared. related amide primary secondary amines was also performed. proposed reaction mechanism involves producing acylammonium intermediates. production these rationally supported by careful 1 H NMR monitoring study.