title: 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.
authors.affiliation: Department of Chemistry, Ben-Gurion University of the Negev, Beersheva, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Glaser
authors.forename: S
authors.initials: S
authors.lastname: Geresh
authors.forename: J
authors.initials: J
authors.lastname: Blumenfeld
authors.forename: D
authors.initials: D
authors.lastname: Donnell
authors.forename: N
authors.initials: N
authors.lastname: Sugisaka
authors.forename: M
authors.initials: M
authors.lastname: Drouin
authors.forename: A
authors.initials: A
authors.lastname: Michel
mesh_terms: D000700:Analgesics / Q000737:chemistry*; D015394:Molecular Structure; D009340:Nefopam / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D012996:Solutions / Q000737:chemistry; D013237:Stereoisomerism; D014961:X-Ray Diffraction
chemical_list: D000700:Analgesics; D012996:Solutions; C080262:N-desmethylnefopam; D009340:Nefopam