Ester-Amide Exchange Reactions Using 2-Pyridone derivatives as Tautomeric Catalysts

The application of 2-pyridone as a tautomeric catalyst for ester-amide exchange reactions was investigated. This compound was found to be most effective at accelerating these reactions when 4-nitrophenyl acetate was used as an acylating agent in toluene. Primary amines without branching at the α-position were determined to be the most suitable substrates. Various 2-pyridone derivatives having an electron-donating group at the 5-position (including methoxy and pirrolidino groups) exhibited superior performance. Acylation reactions of mixtures of primary and secondary amines preferentially acylated the latter compounds in the absence of a catalyst or with N,N-dimethylaminopyridine (DMAP) as the catalyst, whereas primary amines were acylated in the case that a 2-pyridone derivative with a pirrolidino group was employed. The reaction mechanism associated with this preferential acylation process was evaluated and is discussed herein.