Solid-state structure and conformation of (Z)-2-(phenylbenzylidene)-3-quinuclidinone, an intermediate in the synthesis of quinuclidine derivatives

Abstract

(Z)-2-(2-phenylbenzylidene)-3-quinuclidinone, C2oHI9NO, Mr = 300.47D crystallizes in the monoclinic P21/c space group with a = 6.9809(2) /k, b = 19.0523(2) ik, c = 11.7733(1) ~k, = 100.92(2) ~ V = 1537.5(3) ~3, Z = 4, Dc = 1.298 g/cm 3, D~ = 1.29 g/cm 3 (flotation). Diffractometfic data, using CuKa radiation, X = 1.54178 A, were collected on plate-like crystals. The structure, solved by direct methods was refined to a final R value of 0.037 for the 2645 observed reflections with Fo > 3.0a(Fo). The molecule shows a trans conformation around the double bond. The quinuclidine and the diphenyl moieties present deformations in their geometric and conformational parameters due to the need of releasing intramolecular strains and/or nonbonded interactions.

Molecular structures of quinuclidinic neurokinin antagonists: 2-(2-Phenylbenzylidene)-3-(2-X-benzylamino) derivatives

“…The geometries of the double bond, of the 1-azabicyclo-[2,2,2]-octane moiety as well as that of the biphenyl group, are close to those observed for the (Z) form of the 2-(2-phenylbenzylidene)-3-quinuclidinone [13] and for similar compounds, distortions being caused by the substitution at positions 2 and 3 of the bicyclic system [15][16][17][18][19]. The angle C2--C9--C10 shows values not less than 130 ~ (considerably larger than the ideal value of 120~ while the angles N1--C2--C9 and C3--C2--C9 have values quite close to the ideal case.…”

“…The conformation of the biphenyl moieties in the compounds investigated is quite similar to that observed in the precursor (Z)-2-(2-phenylbenzylidene)-3-quinuclidinone [13] the low energetic barrier for rotation around the central bond. The environmental conditions as well as the intraand the intermolecular interactions are responsible in each crystal for fixing the value of this dihedral angle [23][24][25][26][27].…”

“…The small tilt contributes to the release of the intramolecular interactions of the C21 --H group and the N1 atom. The bond angle deformations observed in the three compounds follow the same trend found in the precursor molecule (Z)-2-(2-phenylbenzylidene)-3-quinuclidinone [13]. We tested the interaction of compounds A, B, and C with the three tachykinin receptors (NK-1, NK-2, and NK-3) by using binding techniques.…”