Theoretical study of the mechanism of proton transfer in tautomeric systems: Alloxan

Semiempirical SCF-MO studies of tautomerism in alloxan preclude the possibi lity of direct proton transfer in the gas phase due to the strain in the fo ur-centred transition state, in which the proton being transfer-red is forc ed to come close to the positively charged carbon atom at the opposite corn er of the four-membered ring. However, in aqueous solution, the activation barrier reduces appreciably, not only due to reduction in strain, but also due to charge separation in the transition state, which is stabilized due t o ionic resonance. The N-H bond is almost broken, while the O-H bond is onl y partially formed in the transition state. The other stabilizing effect in aqueous solution is due to bulk solvent dielectric effects, which stabiliz e the transition state to a greater extent due to its higher dipole moment. Although the transition states for proton transfer to the neighbouring oxy gen atoms on either side have comparable energies, as the mechanisms of pro ton transfer leading to the formation of the 2-hydroxy and 4-hydroxy tautom ers are similar, bulk solvent effects are larger in the latter due to the h igher dipole moment of the transition state. The reason is the almost compl ete separation of the two entities, i.e. the alloxan anion and the hydroniu m ion in the latter case, indicating that in this case a dissociative mecha nism of the kind encountered in acid-base equilibria is operating.