Solid‐state structure of orphenadrine hydrochloride and conformational comparisons with diphenhydramine hydrochloride and nefopam hydrochloride

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) ų, Z = 4, R(F) = 0.109, and R_W(F) = 0.131. Data were collected from poor crystalline material because of the low volume of the needle‐shaped crystals (0.025 × 0.025 × 0.15 mm³). 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.