Base catalysed rearrangement of N-alkyl-O-acyl hydroxamic acids: synthesis of 2-acyloxyamides

Abstract

Activated N-alkyl-O-acyl hydroxamic acid derivatives 21a–t undergo thermal and base catalysed rearrangement to give 2-acyloxyamides 22a–t in good to excellent yields (50–100%). A range of inorganic and organic bases were screened for their efficiency in mediating the rearrangement 21 to 22, however, simple organic bases such as Et₃N were found to be the most efficient. Both aromatic and aliphatic derived O-acyl groups were tolerated in the reaction. The electronic nature of the O-acyl group was found to effect the rate of the rearrangement with electron withdrawing groups (21l and 21o) increasing the observed rate and electron donating groups (21m and 21n) decreasing the observed rate. Cross-over experiments with 21a and 21h indicated a mechanism involving the intermediacy of free acyloxy anions. The requirement of a readily enolisable proton adjacent to the carbonyl group of the amide was found to be neccessary for the rearrangement as 21r and 21t both failed to rearrange under the reaction conditions investigated.