DISCRIMINATION IN RESOLVING SYSTEMS .2. EPHEDRINE-SUBSTITUTED MANDELIC-ACIDS

Binary diastereomeric (-) (1R,2S)-ephedrine salts of various mandelic acids obtained hem 95% ethanol show considerable differences in solubi lity. Structures and some properties of the less-soluble (L) and more- soluble (M) solid phases of (-)-ephedrine with unsubstituted mandelic acid, 2-, 3-, and 4-monosubstituted halo (F, Cl, Br) mandelic acids, a nd 3- and 4-methylmandelic acids have been determined. Salts were foun d to be binary, without solvent of crystallization, and composed of do uble-layered arrays of alternating anions and cations linked by H-bond s normal to the layers. H-bonding links charged donors and accepters u sually along a crystallographic 2-fold screw axis. A striking discrimi nation is evident in that the (2R)-mandelate salts typically display a compact four-atom chain as the H-bonding repeating unit [N-+-H ... O( -C--O)... H-N',C-2(1)(4)] while the (2S)-mandelate salts adopt a more dimensionally variable six-atom chain repeating unit [N-+-H ... O-C--O ... H- N',C-2(2)(6)]. Two distinct packing schemes display the shorte r H-bonding chain of the (2R)-mandelates which always occurs with ephe drinium ions in the fully extended conformation. Slightly greater pack ing efficiency and II-bonding energies of the (2R)-mandelate salts cor relates with increased fusion points, lower solubilities (95% ethanol) , and higher heats of fusion relative to the phase adopted by their di astereoisomers. In contrast, (2S)-mandelate salts exhibit considerably more structural variability involving all three major ephedrinium con formations, and at least four distinct packing motifs. Mandelates with larger 3'-substituents (Cl, Br, methyl) show similar property discrim inations, but these occur with an opposing trend, that is, between pha ses in which the less-soluble salts contain (2S)-mandelates. Salts wit h 2-bromomandelate do not show property disparities and their structur es are dissimilar to the other phases. (C) 1995 Wiley-Liss, Inc.