From 2‑Hydroxypyridine to 4(3H)‑Pyrimidinone: Computational Study on the Control of the Tautomeric Equilibrium

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Molecules, spectroscopy, kinetics, environment, & general theory, 2013-11, Vol.117 (47), p.12668-12674
• Main Authors: Galvão, Tiago L. P, Rocha, Inês M, Ribeiro da Silva, Maria D. M. C, Ribeiro da Silva, Manuel A. V
• Format: Article
• Language: English
• Subjects: Ab initio calculations; Atomic and molecular physics; Calculations and mathematical techniques in atomic and molecular physics (excluding electron correlation calculations); Chemical bonds; Computation; Derivatives; Electronic structure of atoms, molecules and their ions: theory; Electronics; Entrances; Exact sciences and technology; Hydrogen Bonding; Hydrogen bonds; Molecular Structure; Nuclei; Physics; Pyridones - chemistry; Pyrimidines; Pyrimidinones - chemistry; Quantum Theory; Thermodynamics
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/jp410004x

In this work is investigated why the entrance of a nitrogen atom in the ring of cis-2-hydroxypyridine and 2-pyridinone, resulting in cis-4-hydroxypyrimidine and 4(3H)-pyrimidinone, respectively, shifts the tautomeric equilibrium from the hydroxyl form, in the pyridine derivative, to the ketonic form, in the pyrimidine derivative. The conclusions obtained for these model systems allow us to understand how to control the gaseous-phase keto–enol tautomeric equilibrium in nitrogen heterocyclic rings and justify the tautomeric preference in pyrimidine nucleobases. The experimental and computational energetics of tautomeric equilibrium were interpreted in terms of the aromaticity, intramolecular hydrogen bonds, and electronic delocalization, evaluated using nucleus independent chemical shifts, quantum theory of atoms in molecules, natural bond orbital analysis, and the thermodynamic changes of appropriate reactions.