Solid-State Structure of Orphenadrine Hydrochloride and Conformational Comparisons with Diphenhydramine Hydrochloride and nefopam hydrochloride

Abstract

The solid-state structure of (±)-orphenadrine hydrochloride [(CH3)2NCH2CH2OCH(o-CH3C6H4)(Ph) · HCl], a skeletal muscle relaxant drug, was determined by single-crystal X-ray diffraction analysis. Orphenadrine hydrochloride gave crystals belonging to the monoclinic P21/n space group, and at low temperature (92 K), the following parameters were found: a = 6.923 (4), b = 7.508 (5), c = 33.22 (3) Å, V = 1720 (3) Å3, Z = 4, R(F) = 0.109, and RW(F) = 0.131. Data were collected from poor crystalline material because of the low volume of the needle-shaped crystals (0.025 × 0.025 × 0.15mm3). A molecular mechanics model was calculated by using an input structure based on atomic coordinates of the crystallographically determined molecular structure. The resulting molecular mechanics model and the structure determined by X-ray crystallography have the same molecular conformation. Whereas both solid-state (±)-orphenadrine hydrochloride and diphenhydramine hydrochloride [(CH3)2NCH2CH2OCH(Ph)2 · HCl] have synclinal N–C–C–O and antiperiplanar NC–C–O–CAr2 torsion angles, the former has a helical arrangement for Ar2CH, as expected, and the phenyl rings in the latter are disposed in a nonhelical, “open-book” arrangement.