Change of tautomeric equilibria, intramolecular interactions and π-electron delocalization when going from phenol to uracil

Abstract

To study the N-aza effects on tautomeric equilibria, intramolecular interactions and π-electron delocalization in six-membered hydroxy derivatives, quantum-chemical calculations were performed for isolated phenol ( 1), its aza derivatives ( 2– 20), and uracil ( U). All possible tautomers–rotamers were considered for each derivative, and all possible tautomeric interconversions were analysed. An introduction of the N-aza group at 2-, 4- and/or 6-position in the phenol ring dramatically affects tautomeric equilibria. Although effects of the N-aza group(s) are not very high (<5 kcal mol −1), they are sufficient to change the tautomeric preferences and the relative stabilities of individual tautomers. These changes partially explain, why the di-NH form (instead of more aromatic di-OH form) predominates for molecular uracil, and why the rare NH–CH form of uracil has exceptional stability. Profitable and unprofitable intramolecular interactions seem to be similar for azaphenols and uracil. The HOMED (harmonic oscillator model of electron delocalization) index, based on the original idea of the HOMA (harmonic oscillator model of aromaticity) index, describes well π-electron delocalization for phenol, azaphenols and uracil. Generally, the HOMED index diminishes when the number of the N-aza groups increases in the ring. It also decreases when going from OH through NH to CH tautomers.