5-Fluorouracil tautomers

X,Y=0,S,Se,Te], has been undertaken.628 The stabilities of different tautomeric forms of 4-hydroxycoumarins have been evaluated629 by MNDO calculations, and the four lowest-energy oxo-hydroxy tautomers of 5-fluorouracil have been studied630 using density functional methods. Semiempirical calculations have been carried out on the keto-enol tautomerism of triazolopyrimidines.631 A base-catalysed keto-enol tautomer-ism has been proposed632 to be responsible for the observed deuterium exchange of the hydrogens at the 3-position of diazepam when the molecule is treated with alkaline deuteriated methanol. 

The CNDO/2 calculations correctly predict tautomers 32 of uracil and thymine to be more stable than tautomers 28. It is interesting to observe that 5-fluorouracil is predicted to be more easily converted into lactim form 28 than uracil and thymine, considering that 5-fluorouracil is mutagenic. As to the relative stability of uracil tautomers, the different approaches give different results. For instance, the tt-SCF MO calculations including a-polarization effectpredict the relative stability of uracil tautomers to be 32 > 31 > 29 > 28 > 27, while the CNDO/2 approach gives the order 32 > 27 > 31 > 29 > 30 > 28. 

Scanlan, M. J., and Hillier, I. H. (1984). J. Am. Chem. Soc. 106, 3737—ab initio (3-21G) calculations for different tautomers of uracil, thymine, 5-fluorouracil, and cytosine solvent effects (continuous model) on stabilities of the tautomers. 

Tautomeric equilibria of uracil, thymine, and 5-fluorouracil in solution are sensitive to the solvent polarity and, in contrast to the gas-phase equilibria, to the nature of the 5-substituent. In all the cases, however, the dioxo tautomer 158a is still the most stable. In low polarity solvents, such as dioxane, the order of stability is similar to that in the gas phase and unaffected by the 5-substituent (01MI103). In more polar acetonitrile and water, the tautomer 158c (for uracil and thymine) or 158e (for fluorouracil) is better stabilized by solvation than other tautomers, as confirmed by the reaction field... 

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