Ring conformation and ester orientation in dihydropyrimidinecarboxylates: a combined theoretical (ab initio, density functional) and X-ray crystallographic study

Ab initio (RHF and MP2) and density functional (B3LYP) calculations with basis sets ranging from 3-21G(*) up to 6-31 + G** on dihydropyrimidine-5-carboxylates 4 are performed. At all levels of theory a slight preference (approximate to 1 kcal mol(-1)) for a cis ester orientation (4a) is found, as proposed for the receptor-bound geometry in biologically active dihydropyrimidine derivatives. For the ring conformation a strong dependence on the computational procedure is observed, Calculations with basis sets lacking polarization functions on first row heavy atoms (3-21G(*), 6-31G, 6-311G) lead to planar ring geometries. Inclusion of polarization functions yields puckered boat conformations, The puckering amplitudes increase in the order Q(RHF) < Q(B3LYP) < Q(MP2). With MP2 unrealistically strong deviations from planarity are predicted. By single-crystal X-ray analysis an almost planar ring conformation is found. Energy differences between planar and puckered geometries are negligible with RHF and B3LYP ( < 1 kcal mol(-1)), whereas with MP2 somewhat larger Delta E values (1.5-2.6 kcal mol(-1)) an calculated, especially when diffuse functions are included. (C) 1998 Elsevier Science B.V. All rights reserved.