TY - JOUR
T1 - Solution‐ and solid‐state structures of N‐desmethylnefopam hydrochloride, a metabolite of the analgesic drug
AU - Glaser, Robert
AU - Geresh, Shimona
AU - Blumenfeld, Jeanine
AU - Donnell, David
AU - Sugisaka, Nobuyuki
AU - Drouin, Marc
AU - Michela, Andre
PY - 1993/1/1
Y1 - 1993/1/1
N2 - 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 1 H NMR spectrum. The solution‐state weighted time‐averaged 50(1)° O‐CH2‐CH2‐N dihedral angle, calculated by the R‐ratio method, shows that the B/C conformation is the major contributor to time‐averaged structure.
AB - 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 1 H NMR spectrum. The solution‐state weighted time‐averaged 50(1)° O‐CH2‐CH2‐N dihedral angle, calculated by the R‐ratio method, shows that the B/C conformation is the major contributor to time‐averaged structure.
UR - http://www.scopus.com/inward/record.url?scp=0027289170&partnerID=8YFLogxK
U2 - 10.1002/jps.2600820312
DO - 10.1002/jps.2600820312
M3 - Article
C2 - 8450422
AN - SCOPUS:0027289170
SN - 0022-3549
VL - 82
SP - 276
EP - 281
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 3
ER -