A Straightforward Synthesis of N-Substituted Ureas from Primary Amides

Nathalie Saraiva Rosa (1) , Thomas Glachet (1) , Quentin Ibert (1) , Jean-François Lohier (1) , Xavier Franck (2) , Vincent Reboul (1)

1 LCMT - Laboratoire de chimie moléculaire et thioorganique
2 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse

A direct and convenient method for the preparation of N-substituted ureas is achieved by treating primary amides with phenyliodine diacetate (PIDA) in the presence of an ammonia source (NH3 or ammonium carbamate) in MeOH. The use of 2,2,2-trifluoroethanol (TFE) as the solvent increases the electrophilicity of the hypervalent iodine species and allows the synthesis of electron-poor carboxamides. This transformation involves a nucleophilic addition of ammonia on the isocyanate intermediate generated in situ by a Hofmann rearrangement of the starting amide.

Keywords: isocyanate; Hofmann rearrangement; Isocyanates; Hypervalent iodine; Amides; Ureas; Amide; Urea

Domains: Chemical Sciences

Nathalie Saraiva Rosa, Thomas Glachet, Quentin Ibert, Jean-François Lohier, Xavier Franck, et al.. A Straightforward Synthesis of N-Substituted Ureas from Primary Amides. Synthesis: Journal of Synthetic Organic Chemistry, 2020, 52 (14), pp.2099-2105. ⟨10.1055/s-0040-1707103⟩. ⟨hal-02569464⟩