Crystal Phase Analysis of Chiral Compounds Capable of Preferential Crystallization and Its Application to Optical Resolution

为了寻找具有择优结晶能力的手性化合物，分析它们的晶相，建立它们的光学拆分过程，本研究取得了以下成果。用差示扫描量热仪测定了两对优先结晶盐(顺-2-苯甲酰胺环己烷羧酸(1)和-乙基苄胺(2)，以及-甲基苄胺(3)和肉桂酸)的麦芽点，得到了具有外消旋混合物特征的二元相图。(&lt；plus-minus&gt；)-trans-2-benzamidocyclohexanecarboxylic酸和(&lt；正负)-3的盐被发现通过相互优先结晶过程可分解成一对对映体盐。以光学活性2为拆分剂，建立了一种实用的光学拆分酮洛芬(4)的方法。用差示扫描量热仪绘制了外消旋化合物的二元图，证实了4为外消旋化合物。合成了一种新的联苯型氧化二膦盐(5)，作为一种有望对对映体具有良好手性识别能力的手性配体，其结晶形态为聚集态。在没有任何外消旋的情况下，对拆分的5进行了立体专一性还原为光学纯的双膦。结果表明，(+)和(-)-苄基甲基苯基硅基乙酸(6)的熔点比外消旋的高，并且6在苯/正己烷混合溶剂中优先结晶。这被认为是优先结晶的有机硅化合物的第一个例子。

In order to search chiral compounds capable of preferential crystallization, to analyze their crystal phase, and to establish their optical resolution process, this research was undertaken and the following results were obtained.1. Malting points of two pair of preferentially crystallizable salts (cis-2- benzamidocyclohexanecarboxylic acid(1) and -ethylbenzyla*mine(2), and - methylbenzylamine(3) and cinnamic acid) have been measured with a differential scanning calorimeter, and binary phase diagrams which are characteristic of racemic mixture have been obtained.2. The salt of (<plus-minus>)-trans-2-benzamidocyclohexanecarboxylic acid and (<plus-minus>)-3 has been found to be resolvable into a pair of enantiomeric salts by mutual preferential crystallization proced3. A practical procedure for the optical resolution of Ketoprofen(4), an anti- inflammatory drug, has been established using optically active 2 as a resolving agent. Confirming that 4 crystallize as a racemic compound, a binary diagram of 4, which is characteristic of racemic compound, has been drawn with the differential scanning calorimeter.4. As a chiral ligand which is expected to have an excellent chiral-recognition ability for enantioface differentiating reaction, a new biphenyl-type diphosphine oxide (5) has been synthesized and has been found to crystallize as a conglomerate. Stereospecific reduction of the resolved 5 into optically pure diphosphine has been performed without any racemization.5. It has been found that the melting point of (+) and (-)-benzylmethyl- phenylsilylacetic acids (6) are higher than that of racemic one, and 6 is preferentially crystallizable from benzene/hexane mixed solvent. This deems to be the first example of the preferentially crystallizable organo- silicon compound.