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

Robert Glaser, Itay Adin, Marc Drouin, André Michel

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The anorexic drug (+)-(2 S, 3 S, 4 S)-phendimetrazine-2 ′R, 3 ′R)-bitartarate crystallized in the orthorhombic space group P212121 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, and Rw(F)=0.026. A chair conformation 2,3-trans-1,4-oxazine ring with equatorially oriented 2-phenyl,3-methyl, and N-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 (equatorial N-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 (+)-(2 S, 3 S)-pseudoephedrine. In this arrangement, N CH(Me)CPh has (S)-configuration, there is a (-)-gauche Me-CH-C-Ph torsion angle, an antiperiplanar N-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 (-)-(2 R, 3 S)-ephedrine moiety (e.g., ca. 45° for molecular mechanics calculated 2,3-cis-phendimetrazine model).

Original languageEnglish
Pages (from-to)197-203
Number of pages7
JournalStructural Chemistry
Volume5
Issue number3
DOIs
StatePublished - 1 Jun 1994

Keywords

  • CNS stimulant
  • Phendimetrazine
  • X-ray crystallography
  • configuration
  • conformation
  • stereochemistry

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