Water Solvent Method for Esterification and Amide Formation between Acid Chlorides and Alcohols Promoted by Combined Catalytic Amines: Synergy between N‐Methylimidazole and N,N,N′,N′‐Tetramethylethylenediamine (TMEDA)

Abstract

AbstractAn efficient method for esterification between acid chlorides and alcohols in water as solvent has been developed by combining the catalytic amines, N‐methylimidazole and N,N,N′,N′‐tetramethylethylenediamine (TMEDA). The present Schotten–Baumann‐type reaction was performed by maintaining the pH at around 11.5 using a pH controller to prevent the decomposition of acid chlorides and/or esters and to facilitate the condensation. The choice of catalysts (0.1 equiv.) was crucial: the combined use of N‐methylimidazole and TMEDA exhibited a dramatic synergistic effect. The catalytic amines have two different roles: (i) N‐methylimidazole forms highly reactive ammonium intermediates with acid chlorides and (ii) TMEDA acts as an effective HCl binder. The production of these intermediates was rationally supported by a careful 1H NMR monitoring study. Related amide formation was also achieved between acid chlorides and primary or secondary amines, including less nucleophilic or water‐soluble amines such as 2‐(or 4‐)chloroaniline, the Weinreb N‐methoxyamine, and 2,2‐dimethoxyethanamine.