The possible catalytic effects of 2-pyridone and its tautomeric form 2-hydroxypyridine on the aminolysis reaction of p-nitrophenyl acetate with n-butylamine have been theoretically studied at the B3LYP/6-31+G(d,p) level of theory. Solvent effect of chloroform is assessed using the MP2/CPCM/6-31++G(d,p)//B3LYP/6-31+G(d,p) method. In our work, three possible mechanisms are considered for the title reaction. The first mechanism is concerted via a four-membered ring transition state assisted by supramolecular effect of the catalyst. The second mechanism undergoes two sequential steps, where the intermolecular proton transfer bridged by the catalyst is the rate-determining process. And the third mechanism, forming a zwitterionic intermediate, is also stepwise via three steps, nucleophilic addition, double-proton transfer, and elimination of leaving group. Our calculations give a detailed picture of the whole stepwise pathway through zwitterionic intermediates for the first time, and indicate that this mechanism is the most favored pathway both in the gas phase and in chloroform. (C) 2011 Elsevier B.V. All rights reserved.