Studies on Prototropic Tautomerism in Neutral and Monoanionic Forms of Pyrimidines by Nuclear Magnetic Resonance Spectroscopy

Abstract

Abstract NMR methods have been applied to evaluation of prototropic tautomerism, N(1)H ⇌ N (3) H, in several selected pyrimidines, viz. the neutral forms of Isocytosine and 2-alkylthiopyrimidone-4, and the monoanionic forms of uracil, 5-fluorouracil and 4-thiouracil. The predominant tautomeric species of the neutral forms could be estimated only qualitatively from 1H chemical shifts. For the monoanionic forms this procedure was not applicable, for reasons which are discussed in detail. For the monoanionic form of uracil, 13C chemical shifts of C(5) provided a suitable criterion for quantitative estimation of the populations of the two known tautomeric species. However, the potential scope of this procedure appears somewhat limited. By contrast, the values of the vicinal proton-proton coupling constants, J (5,6), provided both necessary and adequate criteria for quantitative evaluation of the tautomer populations for all the neutral and monoanionic forms. The results were in satisfactory agreement with those obtained by optical spectroscopic methods. In some instances the results obtained in this way may be more reliable than those derived from optical methods. The range of applicability, and utility, of NMR methods to studies on protropic tautomerism in pyrimidines are critically assessed.