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

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 tBu 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.