Zirconocene-Catalyzed Transamidation of Primary Amides with Amines

Williams et al. have reported a zirconocene-catalyzed transamidation of primary amides with amines to give corresponding amides. In previous methods for the direct amidation of primary amides, high temperature conditions and large amounts of catalysts were needed to complete the reaction. However, this reaction is catalyzed by 5 mol% of zirconocene dichloride (Cp₂ZrCl₂) and in cyclohexane at 30–100 ºC for 5–24 hours，which are milder conditions than previously reported. Meanwhile, this catalytic reaction applies to the reaction of ethyl carbamates with primary amines to give the corresponding mono-substituted ureas. They demonstrate the transamidation reaction mechanism involving a zirconium amide by isotope labeling studies.