Quantum chemical prediction of structure and stability of the benzodihydropyrimidine tautomers

Abstract

B3LYP/maug-cc-pVTZ and MP2/maug-cc-pVTZ calculations show that 3,4-dihydro-quinazoline and its 2- and/or 4-methyl and -phenyl substituted derivatives in solution (chloroform, DMSO, methanol) are only by 0.3 kcal/mol–2.2 kcal/mol more stable than the respective tautomeric 1,4-dihydroquinazolines (the available literature experimental stability data are not coherent). In the gas phase, 2- and/or 4-substituted tautomers of 3,4-dihydroquinazoline are also energetically preferred (B3LYP/maug-cc-pVTZ, MP2/maug-cc-pVTZ and CCSD/cc-pVDZ calculations lead to the same conclusion). In vacuum, 1,4-dihydro tautomer is by 0.1 kcal/mol–0.2 kcal/mol more stable only for unsubstituted dihydro-quinazoline. The observed tautomeric preference was found almost independent on substitution and solvent used. The optimization procedure used shows that the pyrimidine ring in dihydropyrimidines studied is not planar. Noncoplanarity of the 2-phenyl ring and C = N bond in the respective compounds studied is responsible for the weakened conjugation of these two moieties.