Structural investigations of a series of 1,6-aryl-7-hydroxy-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-ones with potential antinociceptive activity

•Structural analysis of new bioactive imidazo[1,2-a]pyrimidines were undertaken.•All compounds were characterized by IR, 1H and 13C NMR, X-ray and DFT methods.•Keto–enol tautomeric equilibrium were investigated using DFT method.

The structural investigations of a series of new bioactive imidazo[1,2-a]pyrimidines 1–6 were undertaken using IR, 1H and 13C NMR spectroscopic analysis, X-ray crystal structure determinations and theoretical calculations. The compounds 1–6 were obtained by condensation of the respective 1-aryl-4,5-dihydro-1H-imidazol-2-amine hydrobromide and diethyl phenylmalonate in presence of sodium methoxide in methanol and for these compounds the equilibrium between possible O10-enol/O11-keto (a), O11-enol/O10-keto (b) and O10,O11-diketo (c) tautomeric forms were investigated in the gaseous phase, solution and crystalline state. Spectroscopic studies 1H, 13C NMR and IR allowed for the identification of the compounds 1–6 but they did not indicate explicitly their tautomeric forms present in solution and in the solid state. The X-ray analysis showed that the molecules of all investigated compounds exist as the O10-enol/O11-keto (a) tautomeric form in the crystalline state. The hydroxyl and carbonyl groups characteristic for existing tautomeric form are involved in a strong intra- and/or intermolecular OH⋯O and OH⋯N hydrogen bonds. The theoretical calculations at DFT/B3LYP/6-311++G(d,p) level showed that two tautomeric forms (a) and (c) can coexist both in gas phase and the solution with the population of them being in the relation (a) > (or ≫) (c). The comparison of the experimentally recorded IR, 1H and 13C spectra with the corresponding spectra theoretically calculated for all possible tautomeric forms of 1–6 shows that the correlation of experimental and theoretical spectra can be used to a limited extent for the identification of tautomeric forms.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide