The direct coupling of unactivated carboxylic acids with amines can be performed in toluene 110 °C in the absence of catalyst. The use of simple zirconium catalysts at 5 mol% loading gave amide formation in as little as 4 h.

Zirconocene dichloride (Cp(2)ZrCl(2)) has been shown to be an effective catalyst for the transamidation of primary amides with amines in cyclohexane at 80 °C in 5-24 hours. For favourable substrates, the reaction can be performed at temperatures as low as 30 °C.

This methodology is particularly useful for the direct synthesis of primary and N-methyl amides using urea as a stable and easy to manipulate nitrogen source.

No abstract

Transamidation of Primary Amides with Amines Catalyzed by Zirconocene Dichloride. -Zirconocene dichloride is found to efficiently catalyze acylation reaction with amides [cf. (III)], transamidation reaction [cf. (V), (VIII), (XI)] and the reaction with ethyl carbamate [cf. (XIII)]. -(ATKINSON, B. N.; CHHATWAL, A. R.; LOMAX, H. V.; WALTON, J. W.; WILLIAMS*, J. M. J.; Chem. Commun. (Cambridge) 48 (2012) 95, 11626-11628, http://dx.doi.org/10.1039/c2cc37427g ; Univ. Bath, Bath BA2 7AY, UK; Eng.) -G. Mueller