The structure and conformations of piracetam (2-oxo-1-pyrrolidineacetamide): Gas-phase electron diffraction and quantum chemical calculations

Abstract

The geometric structure of piracetam was studied by quantum chemical calculations (DFT and ab initio), gas electron diffraction (GED), and FTIR spectroscopy. Two stable mirror symmetric isomers of piracetam were found. The conformation of pyrrolidine ring is an envelope in which the C4 atom deviates from the ring plane, the angle between the planes (C3 C4 C5) and (C2 C3 C5) is 154.1°. The direction of the deviation is the same as that of the side acetamide group. The piracetam molecule is stabilized in the gas phase by an intramolecular hydrogen bond between the N9H 2 group and the oxygen O6, bonded to C2. The principal structural parameters ( r e, Å and ∠ e, degrees; uncertainties are 3 σ LS values) were found to be: r(С3 С4) = 1.533(1), r(C4 C5) = 1.540(1), r(N1 C5) = 1.456(1), r(C2 C3) = 1.520(1), r(N1 C7) = 1.452(1), r(C7 C8) = 1.537(1), r(N1 C2) = 1.365(2), r(C8 N9) = 1.360(2), r(C2 O6) = 1.229(1), r(C8 O10) = 1.221(1), ∠ C2 N1 C5 = 113.4(6), ∠ N1 C2 C3 = 106.9(6), ∠ N1 C7 C8 = 111.9(6), ∠ C7 C8 N9 = 112.5(6), ∠ N1 C2 O6 = 123.0(4), ∠ C3 N1 C7 = 120.4(4), ∠ C7 C8 O10 = 120.2(4), ∠ C5 N1 C2 O6 = 170(6), ∠ C3 C2 N1 C7 = 178(6), ∠ C2 N1 C7 C8 = 84.2, ∠ N1 C7 C8 O10 = 111.9. [Display omitted]