Solvent-assisted catalysis mechanism on Keto-enol tautomerism of cyameluric acid

The keto-enol tautomerism of cyameluric acid, both in gas phase and in water and methanol solution, has been studied at the B3LYP/6-31++g(d,P) level of theory in this paper. The harmonic frequencies of all the structures are calculated. The results show that the transition states of the tautomerism are 4-membered ring conformations in gas phase, whereas 6-membered ring conformations in solution. In the first proton transfer, activation energy ΔE# is 56.4 and 50.9 kJ/mol for water and methanol solution, respectively, which is much lower than that in gas phase (163.2 kJ/mol). Solvent molecules (water and methanol) produce an important catalytic effect in the tautomerism, especially for methanol-solvated system. NBO analysis shows that there is a strong interaction between cyameluric acid and solvent molecules in transition states. AIM charge analysis indicates that the keto-enol tautomerism shows a certain degree of proton transfer character. From the reaction enthalpy and reaction rate point of view, keto-enol tautomerism in water-solvated and methanol-solvated system is easier than that in gas phase. The keto-enol tautomerisms are endothermic both in gas phase and in solution, so the enol forms are less stable than the keto ones.