Role of lactam vs. lactim tautomers in 2(1H)-pyridone catalysis of aromatic nucleophilic substitution

Abstract

3-Ethylaminocarbonyl-2(1H)-pyridone 1 and 3-ethoxycarbonyl-2(1H)-pyridone 2 have been synthesised and tested as catalysts for the aromatic nucleophilic substitution of fluoride by piperidine in 2-fluoro-5-nitrobenzonitrile 3. A kinetic model which takes into account the dimerisation of the catalysts has been developed, which allows a quantitative analysis of measured data. 3-Ethylaminocarbonyl-2(1H)-pyridone 1 exists exclusively as a lactam tautomer, either monomeric or dimeric but 3-ethoxycarbonyl-2(1H)-pyridone 2 exists as a lactim monomer, whereas its dimer exists in the lactam form. Despite such differences, these two compounds exhibit similar catalytic efficiencies for the reaction studied, suggesting that lactim and lactam tautomers have comparable efficiencies in tautomeric catalysis.