Synthesis of N-Substituted Ureas from Primary Amides

A Straightforward Synthesis of N-Substituted Ureas from Primary Amides: N. S. Rosa, T. Glachet, Q. Ibert, J.-F. Lohier, X. Franck, V. Reboul
Synthesis 2020, 52, DOI: 10.1055/s-0040-1707103

 

Substituted ureas are important compounds with a number of applications spanning materials science and drug discovery. Recently, Dr. Vincent Reboul, in collaboration with Dr. Xavier Franck from Normandy University (respectively in Caen and Rouen, France) and co-workers reported a direct and convenient synthesis of N-substituted ureas from primary amides via Hofmann rearrangement. The use of phenyliodine diacetate (PIDA) in the presence of an ammonia source (NH3 or ammonium carbamate) in MeOH led to very high yields of ureas. The synthesis of electron-poor carboxamides can also be performed with 2,2,2-trifluoroethanol (TFE) as the solvent, which increases the electrophilicity of the hypervalent iodine species.

Dr. Reboul said: “We amplified the synthetic utility of PIDA/NH3 couple. After the synthesis of sulfoximines from sulfides and diazirines from amino acids, we report the straightforward and rapid synthesis of primary ureas from amides.”

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