Ethyl 2-Cyano-2-(4-nitrophenylsulfonyloxyimino)acetate-Mediated Lossen Rearrangement: Single-Pot Racemization-Free Synthesis of Hydroxamic Acids and Ureas from Carboxylic Acids

Abstract

Ethyl 2-cyano-2-(4-nitrophenylsulfonyloxyimino)acetate (4-NBsOXY) mediated Lossen rearrangement and its application for the synthesis of ureas is demonstrated. Required hydroxamic acids for the Lossen rearrangements were synthesized from carboxylic acids using the same reagent. Finally, reaction of an amine with the produced isocyanate resulted in urea. Good yields without racemization were achieved under milder and simpler reaction conditions. Reactions are compatible with common N-protecting groups, such as Boc, Fmoc, Cbz, and benzyl, as well as various OH protecting groups, such as (t)Bu and Bzl. Conversion from carboxylic acid to urea is achieved in one pot. Most importantly, byproducts Oxyma [ethyl 2-cyano-2-(hydroxyimino)acetate] and 4-nitrobenzenesulfonic acid can be recovered easily and can be recycled to prepare the reagent. Thus, the method is environmentally friendly and cost-effective.