Experimental and theoretical investigations on the tautomerism of 1-phenyl-2-thiobarbituric acid and its methylation reaction

In the present study, 1-phenyl-2-thiobarbituric acid (1) was synthesized and the tautomerism of this compound was investigated by FT-IR spectroscopy, X-ray analysis and 1H NMR study as well as quantum chemical calculations. It is found that compound 1 exists in triketo form in the solid state and in CDCl3 solution while tautomerization was observed in DMSO-d6, DMF-d7 and CD3OD solution. The geometry optimization of eight possible tautomers of 1-phenyl-2-thiobarbituric acid was performed in gas phase and in different solvents using COSMO method. The calculated results are in good accordance with experimental data. Additionally, the methylation reaction of 1-phenyl-2-thiobarbituric acid was investigated for the first time by combination of experimental and theoretical methods. The methylation product might be varied with three possible isomers because of the structural features of 1-phenyl-2-thiobarbituric acid. We identified the obtained methylation product by X-ray diffraction and FT-IR spectroscopy, and transition state search and energy calculation were conducted to elucidate experimental data, the results revealed that the theoretical calculations are consistent with experimental data.

► Synthesis and structural identification of thiobarbituric derivatives are presented.
► Tautomerism form was investigated by experimental methods and quantum calculations.
► The methylation site was identified experimentally and theoretically.