Quantcast

Molecular structure of carphedon as studied by gas electron diffraction and quantum chemical calculations

Research paper by Denis N. Ksenafontov, Natalia F. Moiseeva, Anatoliy N. Rykov, Igor F. Shishkov, Heinz Oberhammer

Indexed on: 27 May '12Published on: 27 May '12Published in: Structural Chemistry



Abstract

The gas-phase structure and conformational properties of carphedon (C12H14N2O2, phenylpiracetam, 2-oxo-4-phenyl-1-pyrrolidineacetamide) have been determined by gas electron diffraction (GED) and quantum chemical calculations (B3LYP and MP2 with 6-31G and cc-pVDZ basis sets). Since quantum chemical calculations demonstrate that the orientation of the acetamide group is fixed by a strong intramolecular N–H(amide)···O(pyrrolidone) hydrogen bond, the number of possible conformers is reduced considerably. Depending on the conformation of the pyrrolidine ring, envelope with out-of-plane C4 atom and acetamide group on the same side of the plane (“+”) or envelope with C4 and acetamide group on opposite sides (“−”), and on the orientation of the phenyl ring, axial (Ax), or equatorial (Eq), four relevant conformations, Ax−, Ax+, Eq−, and Eq+, exist. According to both quantum chemical methods (B3LYP and MP2 with cc-pVDZ basis sets) these four conformers differ by less than 2 kcal/mol in free energies. However, the two methods predict different relative free energies. The GED data were analyzed with different models. With a single-conformer model the best fit of the experimental GED intensities (agreement factor Rf = 4 %) is obtained with the Ax+ conformer. Using a two-conformer model the fit improves considerable for a 50(11):50(11) mixture of Ax− and Eq+ conformers (Rf = 2.7 %). No further improvement is obtained with a three-conformer model and large uncertainties for relative contributions occur. The geometric parameters of gaseous carphedon are compared with those in the crystal phase, where two molecules are connected by two intermolecular N–H···O hydrogen bonds, and with gas-phase values of piracetam.