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)

An 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'-tetrame-thylethylenediamine (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 H-1 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.