SOLID-STATE STRUCTURE OF (-PHENDIMETRAZINE BITARTARATE, AN ANOREXIC DRUG())

The anorexic drug (+)-(2S, 3S, 4S)-phendimetrazine-2'R, 3'R)-bitartara te crystallized in the orthorhombic space group P2(1)2(1)2(1) and at 2 93 K: a = 7.7710(4), b = 13.1379(7), c = 15.9913(9) angstrom, V = 1632 .6(2) angstrom3, Z = 4, R(F) = 0.062, and R(w)(F) = 0.026. A chair con formation 2,3-trans-1,4-oxazine ring with equatorially oriented 2-phen yl,3-methyl, and N-methyl substituents was found as predicted by an ea rlier reported solid-state CP-MAS C-13-NMR investigation of crystallin e (+/-)-phendimetrazine bitartarate. The O-CH2-CH2-N torsion angle of -58.4(6)-degrees in the solid-state agrees nicely with the 56.0(7)-deg rees dihedral angle value estimated by H-1 NMR spectroscopy for the ma jor (equatorial N-methyl) phendimetrazine mesylate species in CD2Cl2 s olution. A common solid-state conformational arrangement was found for (+)-phendimetrazine and a series of six other anorexic drugs structur ally analogous to (+)-(2S, 3S)-pseudoephedrine. In this arrangement, N CH(Me)CPh has (S)-configuration, there is a (-)-gauche Me-CH-C-Ph tors ion angle, an antiperiplanar N-CH-C-Ph torsion angle, and the phenyl r ing approximately eclipses the C-H bond of the attached carbon (e.g., H-C-C(ipso)-C(ortho) ca. 4-degrees for 2,3-trans-phendimetrazine). Non bonded interactions involving the 3-methyl and the 2-phenyl groups ope n up the H-C-C(ipso)-C(ortho) angle in a series of solid-state structu res containing the epimeric (-)-(2R, 3S)-ephedrine moiety (e.g., ca. 4 5-degrees for molecular mechanics calculated 2,3-cis-phendimetrazine m odel).