Valente E J, Miller C W, Zubkowski J, Eggleston D S, Shui X
Department of Chemistry, Mississippi College, Clinton, USA.
Chirality. 1995;7(8):652-76. doi: 10.1002/chir.530070816.
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', C2(1)(4)] while the (2S)-mandelate salts adopt a more dimensionally variable six-atom chain repeating unit [+N--H...O--C(-)--O...H--N', C2(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.
从95%乙醇中获得的各种扁桃酸的二元非对映体（-）（1R，2S）-麻黄碱盐在溶解度上表现出显著差异。已确定了（-）-麻黄碱与未取代扁桃酸、2-、3-和4-单取代卤代（F、Cl、Br）扁桃酸以及3-和4-甲基扁桃酸的低溶解度（L）和高溶解度（M）固相的结构和一些性质。发现这些盐是二元的，没有结晶溶剂，由通过垂直于层的氢键连接的交替阴离子和阳离子的双层阵列组成。氢键通常沿着晶体学的2重螺旋轴连接带电的供体和受体。一个显著的区别很明显，即（2R）-扁桃酸盐通常显示一个紧凑的四原子链作为氢键重复单元[+N--H...O（-C（-）--O）...H-N'，C2（1）（4）]，而（2S）-扁桃酸盐采用一个维度变化更大的六原子链重复单元[+N--H...O--C（-）--O...H--N'，C2（2）（6）]。两种不同的堆积方式展示了（2R）-扁桃酸盐较短的氢键链，其总是与完全伸展构象的麻黄碱离子一起出现。（2R）-扁桃酸盐稍高的堆积效率和氢键能与熔点升高、较低的溶解度（95%乙醇）以及相对于其非对映异构体所采用的相更高的熔化热相关。相比之下，（2S）-扁桃酸盐表现出更多的结构变异性，涉及所有三种主要的麻黄碱构象以及至少四种不同的堆积模式。具有较大C3'取代基（Cl、Br、甲基）的扁桃酸盐显示出类似的性质差异，但这些差异呈现相反的趋势，即低溶解度盐含有（2S）-扁桃酸盐的相之间的差异。2-溴扁桃酸盐的盐没有显示出性质差异，并且它们的结构与其他相不同。
