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

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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.