The electronic structure of barbituric acid has been investigated, keeping in mind the possibility of tautomerism. It has been found that the triketo form is the most stable, followed by the 4-hydroxy tautomer. The difference in their stabilities decreases on substitution at C₅. Substituents that allow a greater degree of delocalization with the ring system (nitro, bromo, thiol) stabilize the 4-hydroxy tautomer to a greater extent since it is planar. The AM1 method is found to be the best suited for studying the electronic structure of barbituric acid, as it gives the best agreement with the experimental geometries. Of the other two methods investigated, MNDO gives erroneous results for relative energies, while PM3 gives unsatisfactory geometries. The stabilities of the charged species resulting from deprotonation, and the radicals resulting from the removal of a hydrogen atom by heat treatment or irradiation with gamma rays, have also been investigated. Their electronic structures are also discussed.

Semiempirical SCF-MO studies of tautomerism in alloxan preclude the possibility of direct proton transfer in the gas phase due to the strain in the four-centred transition state, in which the proton being transferred is forced to come close to the positively charged carbon atom at the opposite corner 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 to ionic resonance. The N-H bond is almost broken, while the O-H bond is only partially formed in the transition state. The other stabilizing effect in aqueous solution is due to bulk solvent dielectric effects, which stabilize the transition state to a greater extent due to its higher dipole moment. Although the transition states for proton transfer to the neighbouring oxygen atoms on either side have comparable energies, as the mechanisms of proton transfer leading to the formation of the 2-hydroxy and 4-hydroxy tautomers are similar, bulk solvent effects are larger in the latter due to the higher dipole moment of the transition state. The reason is the almost complete separation of the two entities, i.e. the alloxan anion and the hydronium ion in the latter case, indicating that in this case a dissociative mechanism of the kind encountered in acid-base equilibria is operating.