Conformation of the nootropic agents 1-(4-methoxybenzoyl)-5-oxo-2-pyrrolidinepropanoic acid (CI-933) and 4-hydroxymethyl-1-benzyl-pyrrolidin-2-one (WEB-1868): X-ray crystal structures, theoretical MO calculations (AM-1) and 600 MHZ 1H NMR spectra

The crystal and molecular structures of the cognition activators 1-(4-methoxybenzoyl)-5-oxo-2-pyrrolidinepropanoic acid (CI-933) (1) and 4-hydroxymethyl-1-benzyl-pyrrolidin-2-one (WEB-1868) (2) have been determined by X-ray analysis. The conformations of the isolated molecules 1 and 2 have been deduced from AM1-type theoretical calculations. Whilst in 1 there are no hydrogen bonds, in 2 stabilization of the crystal occurs through effective inter- and intramolecular H----O(13) bonds. The five-membered ring in both 1 and 2 adopts an envelope conformation in the solid with C(3) at the flap displaced from the C(1), C(2), C(4), N(5) mean plane. Bond distances and angles are normal and comparable with previously known similar structures. In the crystal, the torsion angles C(1)-N(5)-C(6)-C(7) and N(5)-C(6)-C(7)-C(8) in 1 are 43.1° and 44.8°, respectively; the same torsion angles in 2 are −101° and 42°, respectively. Results of theoretical calculations correlate well with the conformation of 1 in the solid, whilst in the case of 2 these indicate that the conformation in the crystal should not be retained by the isolated molecule. The complete analysis of the very high field (600 MHz) 1H NMR spectra of both compounds in CDCl3, gives results well in line with the above established conformational features.