Solution- and solid-state structures of N-desmethylnefopam hydrochloride, a metabolite of the analgesic drug.

Abstract

The solid-state structure of (+/-)-N-desmethylnefopam hydrochloride (1), a metabolite of the analgesic drug, was determined by single-crystal X-ray diffraction analysis. Compound 1 gave crystalline prisms belonging to the orthorhombic Pcab space group, and at ambient temperature (293 K), a = 9.939(2), b = 14.479(1), c = 20.148(3) A, V = 2899.5(8) A3, Z = 8, R(F) = 0.045, and Rw(F) = 0.025. The benzoxazocine ring of crystalline 1 is twisted into the boat-flattened (chair) [BfC] conformation, the phenyl ring resides in a relatively sterically unhindered exo-type ring position, whereas the O atom and NCH2Ar occupy sterically hindered positions between "boat" and "chair" regions. Dissolution of BfC crystalline 1 in CD2Cl2 solvent affords a dynamic conformational equilibrium (involving the putative twist-chair-flattened (chair) conformer) as shown by line broadening and weighted time-averaged vicinal coupling constants [-OCH2CH2N- segment] in the 1H NMR spectrum. The solution-state weighted time-averaged 50(1) degrees O-CH2-CH2-N dihedral angle, calculated by the R-ratio method, shows that the BfC conformation is the major contributor to time-averaged structure.

Cite this paper

@article{Glaser1993SolutionAS, title={Solution- and solid-state structures of N-desmethylnefopam hydrochloride, a metabolite of the analgesic drug.}, author={Robert E. Glaser and Shimona Geresh and Jared Blumenfeld and Deborah Donnell and Noriko Sugisaka and Marie Drouin and Andr{\'e} G. Michel}, journal={Journal of pharmaceutical sciences}, year={1993}, volume={82 3}, pages={276-81} }