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

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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).

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References

  1. 1.

    Otto, W. G.Angew. Chem. 1956,86, 181–182.

  2. 2.

    The Merck Index, 11th Edition; Budavari, S., Ed.; Merck: Rahway, NJ, 1989, p. 1146.

  3. 3.

    Dvornik, D.; Schilling, G.J. Med. Chem. 1965,8, 466–469.

  4. 4.

    Foltz, C. M.; Witkop, B.J. Am. Chem. Soc. 1957,79, 201–205.

  5. 5.

    Drefahl, G.; Hartmann, M.; Skurk, A.Chem. Ber. 1963,96, 1011–1015.

  6. 6.

    Ref. 2,, p. 1018.

  7. 7.

    Glaser, R.Magn. Reson. Chem. 1989,27, 1142–1147.

  8. 8.

    Lambert, J. B.Acc. Chem. Res. 1971,4, 87–94 and references therein.

  9. 9.

    Trommel, J.; Bijvoet, J. M.Acta Crystallogr. 1954,7, 703–709.

  10. 10.

    Clarke, F.J. Org. Chem. 1962,27, 3251–3253.

  11. 11.

    Portoghese, P. S.J. Med. Chem. 1967,10, 1057–1063.

  12. 12.

    Carlström, D.; Hacksell, I.Acta Crystallogr. Sec. B 1974,30, 2477–2480.

  13. 13.

    Phillips, D. C.Acta Crystallogr. 1954,7, 159–165.

  14. 14.

    Mathew, M.; Palenik, G. J.Acta Crystallogr. Sec. B 1977,33, 1016–1022.

  15. 15.

    Grunewald, G. L.; Creese, M. W.; Extine, M. W.Acta Crystallogr. Sec. B 1981,37, 1790–1793.

  16. 16.

    Fogassy, E.; Acs, M.; Faigl, F.; Simon, K.; Rohonczy, J.; Ecsery, Z.J. Chem. Soc., Perkin Trans. 2 1986, 1881–1886.

  17. 17.

    Hebert, H.Acta Crystallogr. Sec. B 1978,34, 610–615.

  18. 18.

    Bergin, R.; Carlström, D.Acta Crystallogr. Sec. B 1971,27, 2146–2152.

  19. 19.

    Gabe, E. J., Le Page, Y.; Charland, J.-P.; Lee, F. L.; White, P. S.J. Appl. Cryst. 1989,22, 384–387.

  20. 20.

    Larson, A. C.Acta Crystallogr. 1967,23, 664–665.

  21. 21.

    Zachariasen, W. H.Acta Crystallogr. 1963,16, 1139–1144.

  22. 22.

    Cromer, D. T.; Waber, J. T. InInternational Tables for X-ray Crystallography; Vol. IV; Ibers, J. A.; Hamilton, W. C., Eds.; Kynoch Press: Birmingham, UK; 1974, pp 99–101, Table 2.2B. (Present distributor Kluwer Academic Publishers, Dordrecht.)

  23. 23.

    Gilbert, K. E.; Gajewski, J. J.; Kreek, T. W.PCMODEL/MMX 4.51 for Macintosh II Computers; Serena Software: Bloomington, IN, 1993.

  24. 24.

    Allinger, N. L.J. Am. Chem. Soc. 1977,99, 8127–8134.

  25. 25.

    Allinger, N. L.; Sprague, J. T.J. Am. Chem. Soc. 1973,95, 3893–3907.

  26. 26.

    Müller, N.; Falk, A.BALL & STICK 3.05 Molecular Graphics Program for Apple Macintosh Computers; Cherwell Scientific Publishing: Oxford, UK, 1991.

  27. 27. (a)

    Rubenstein, S.CHEM3D-PLUS 3.1; Cambridge Scientific Computing: Cambridge, MA, 1990.

  28. 27. (b)

    Rubenstein, S.CHEM-DRAW PLUS 3.0.1; Cambridge Scientific Computing: Cambridge, MA 1989.

  29. 28.

    Sundin, A.MACMIMIC 2.1; Instar Software: Lund, Sweden, 1992.

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Correspondence to Robert Glaser.

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Glaser, R., Adin, I., Drouin, M. et al. Solid-state structure of (+)-phendimetrazine bitartarate, an anorexic drug. Struct Chem 5, 197–203 (1994). https://doi.org/10.1007/BF02262842

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Key words

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