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Discrimination in resolving systems II: Ephedrine‐substituted mandelic acids
Author(s) -
Valente Edward J.,
Miller Christopher W.,
Zubkowski Jeffrey,
Eggleston Drake S.,
Shui Xiuiqi
Publication year - 1995
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530070816
Subject(s) - chemistry , diastereomer , mandelic acid , solubility , crystallography , solvent , intermolecular force , ethanol , hydrogen bond , atom (system on chip) , stereochemistry , medicinal chemistry , molecule , organic chemistry , computer science , embedded system
Binary diastereomeric (‐) (1R,2S)‐ephedrine salts of various mandelic acids obtained from 95% ethanol show considerable differences in solubility. 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, and 3‐ and 4‐methylmandelic acids have been determined. Salts were found to be binary, without solvent of crystallization, and composed of double‐layered arrays of alternating anions and cations linked by H‐bonds normal to the layers. H‐bonding links charged donors and acceptors usually along a crystallographic 2‐fold screw axis. A striking discrimination 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 shorter H‐bonding chain of the (2R)‐mandelates which always occurs with ephedrinium ions in the fully extended conformation. Slightly greater packing efficiency and H‐bonding energies of the (2R)‐mandelate salts correlates with increased fusion points, lower solubilities (95% ethanol), and higher heats of fusion relative to the phase adopted by their diastereoisomers. In contrast, (2S)‐mandelate salts exhibit considerably more structural variability involving all three major ephedrinium conformations, and at least four distinct packing motifs. Mandelates with larger 3′‐substituents (Cl, Br, methyl) show similar property discriminations, but these occur with an opposing trend, that is, between phases in which the less‐soluble salts contain (2S)‐mandelates. Salts with 2‐bromomandelate do not show property disparities and their structures are dissimilar to the other phases. © 1995 Wiley‐Liss, Inc.