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Structural Chemistry

, Volume 5, Issue 3, pp 197–203 | Cite as

Solid-state structure of (+)-phendimetrazine bitartarate, an anorexic drug

  • Robert Glaser
  • Itay Adin
  • Marc Drouin
  • André Michel
Article

Abstract

The anorexic drug (+)-(2S, 3S, 4S)-phendimetrazine-2′R, 3′R)-bitartarate crystallized in the orthorhombic space groupP212121 and at 293 K∶a=7.7710(4),b=13.1379(7),c=15.9913(9) Å,V=1632.6(2) Å3,Z=4,R(F)=0.062, andR w (F)=0.026. A chair conformation 2,3-trans-1,4-oxazine ring with equatorially oriented 2-phenyl,3-methyl, andN-methyl substituents was found as predicted by an earlier reported solid-state CP-MAS13C-NMR investigation of crystalline (±)-phendimetrazine bitartarate. The O-CH2-CH2-N torsion angle of −58.4(6)° in the solid-state agrees nicely with the 56.0(7)° dihedral angle value estimated by1H NMR spectroscopy for the major (equatorialN-methyl) phendimetrazine mesylate species in CD2Cl2 solution. A common solid-state conformational arrangement was found for (+)-phendimetrazine and a series of six other anorexic drugs structurally analogous to (+)-(2S, 3S)-pseudoephedrine. In this arrangement, NCH(Me)CPh has (S)-configuration, there is a (−)-gaucheMe-CH-C-Ph torsion angle, an antiperiplanarN-CH-C-Ph torsion angle, and the phenyl ring approximately eclipses the C-H bond of the attached carbon (e.g., H-C-Cipso-Cortho ca. 4° for 2,3-transphendimetrazine). Nonbonded interactions involving the 3-methyl and the 2-phenyl groups open up the H-C-Cipso-Cortho angle in a series of solid-state structures containing the epimeric (−)-(2R, 3S)-ephedrine moiety (e.g., ca. 45° for molecular mechanics calculated 2,3-cis-phendimetrazine model).

Key words

Phendimetrazine X-ray crystallography conformation configuration stereochemistry CNS stimulant 

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Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Robert Glaser
    • 2
  • Itay Adin
    • 2
  • Marc Drouin
    • 1
  • André Michel
    • 1
  1. 1.Département de ChimeUniversité de SherbrookeSherbrookeCanada
  2. 2.Department of ChemistryBen-Gurion University of the NegevBeer-ShevaIsrael

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