The stereochemistry of a nine-membered ring analogue of nefopam, a nonnarcotic analgesic drug

Robert Glaser, Dror Shiftan, Marc Drouin

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The solid-state structure of a (±)-homonefopam hydrogenfumarate salt having an-O(CH2)3N-fragment was determined by single-crystal X-ray diffraction analysis. Homonefopam hydrogenfumarate gave crystals belonging to the monoclinic P21/c space group, and at ambient temperature a=10.220(1), b=18.187(2), c=10.687(2)A, Β=94.43(1)‡, V=1980.5(5)å3 Z=4, R(F)=0.039, Rw=0.039, RW (F)=0.025. The1H NMR spectrum of homonefopam hydrochloride in CD2Cl2 solution showed two species (7:1 ratio) at the prototropic shift-nitrogen inversion slow exchange limit. The solution-state major species has the same conformation and trans-to-phenyl axial N-methyl disposition found in the crystal as evidenced by three antiperiplanar vicinal3J (HH) coupling constants in the oxytrimethyleneamino fragment and vicinal coupling constants involving the N-H proton. The R-ratio method was used to estimate 64(2)‡ O-C(3)-C(4)-C(5) and 75(3)‡ C(3)-C(4)-C(5)-N(6) dihedral angles for the major species in CD2Cl2 solution in accord with its proposed structure. The finding of C(3)-C(4) bond time-averaged magnitude3J (HH) values and severe broadening of signals from other minor species protons suggests conformational heterogeneity for the solution-state minor species.

Original languageEnglish
Pages (from-to)25-35
Number of pages11
JournalStructural Chemistry
Issue number1
StatePublished - 1 Feb 1995


  • C NMR spectroscopy
  • H NMR spectroscopy
  • Stereochemistry
  • X-ray crystallography
  • conformation


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