Synthesis of Hydroxamic Acids by Activation of Carboxylic Acids with N,N′-Carbonyldiimidazole: Exploring the Efficiency of the Method

Abstract

Activation of carboxylic acids with N,N′-carbonyldiimidazole followed by the reaction with anhydrous or aqueous hydroxylamine hydrochloride was demonstrated to be an operationally simple method for the synthesis of hydroxamic acids in good yield and high purity after aqueous workup. The potential by-product, N,O-diacylhydroxylamine, is cleanly transformed to hydroxamic acid in these reaction conditions.

Keywords:

• Activation
• N,N-carbonyldiimidazole
• carboxylic acid
• hydroxamic acid
• hydroxylamine

ACKNOWLEDGMENT

Partial financial support from the European Regional Development Fund (VPD1/ERAF/CFLA/05/APK/2.5.1/000029/014) is gratefully acknowledged.

Notes

^a Method A: addition of solid NH₂OH·HCl; method B: addition of aqueous 2 M NH₂OH·HCl (2 eq) after activation of carboxylic acid.

^b Crystallized from water.