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

摘要

The structural investigations of a series of new bioactive imidazo[1,2-a]pyrimidines 1-6 were undertaken using IR, H-1 and C-13 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 H-1, C-13 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 O-H center dot center dot center dot O and O-H center dot center dot center dot 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, H-1 and C-13 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. (C) 2015 Elsevier B.V. All rights reserved.