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

优先结晶手性化合物的晶相分析及其在光学拆分中的应用

• 批准号: 63550615
• 负责人: NOHIRA Hiroyuki
• 金额: $ 1.15万
• 依托单位: Saitama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63550615/
• 关键词: Optical Resolution; Preferential Crystallization; Mutual Preferential Crystallization; Differential Scanning Calorimeter; Binary Melting point Diagram; Determination of Optical Purity; Optically Active Phosphine; Optically Active Organo-silicon Com

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.

为了寻找具有优先结晶能力的手性化合物，分析其晶相，建立其光学拆分方法，本研究进行了以下工作.用差示扫描量热法测定了顺式-2-苯甲酰氨基环己烷甲酸（1）和-乙基苄胺（2），-甲基苄胺（3）和肉桂酸两对优先结晶盐的麦芽点，得到了外消旋混合物的二元相图.反<plus-minus>式-2-苯甲酰胺基环己烷甲酸和反<plus-minus>式-3的盐可以通过相互优先结晶的方法拆分成一对对映体盐。以光学活性化合物2为拆分剂，建立了一种实用的抗炎药酮洛芬（4）的光学拆分方法。证明4是外消旋体，用差示扫描量热仪绘制了外消旋体的二元相图.合成了一种新的联苯型双膦氧化物（5），作为一种对映异构体区分反应具有良好手性识别能力的手性配体，并发现其结晶为聚集体。拆分的5立体定向还原成光学纯的二膦已进行，没有任何外消旋化。发现（+）和（-）-苄甲基苯硅基乙酸（6）的熔点比外消旋体高，且6在苯/己烷混合溶剂中优先结晶。这被认为是可优先结晶的有机硅化合物的第一个实例。

项目成果

Hiroyuki NOHIRA, Kazuhiko SAIGO, Misako NOHIRA, Daiyou TERUNUMA: Optically Active Compounds---Their Industrial Organic Chemistry. Asakura-shoten, 129 (1989)

Hiroyuki NOHIRA、Kazuhiko SAIGO、Misako NOHIRA、Daiyou TERUNUM：光学活性化合物——他们的工业有机化学。

Daiyou TERUNUMA: "The Synthesis of Optically Active N,N-dimethyl-2-methylphenyl-o-tolylsiloxy)ethylamine (Silaorphenadrine)" Nippon Kagaku Kaishi, (1990).

Daiyou TERUNUM：“光学活性 N,N-二甲基-2-甲基苯基-邻甲苯基硅氧基）乙胺（Silaorphenadrine）的合成”Nip​​pon Kagaku Kaishi，（1990）。

山中宏,野平博之,照沼大陽他: "日本化学会編季刊化学総説光学異性体の分離" 学会出版センタ-, 238 (1989)

Hiroshi Yamanaka、Hiroyuki Nohira、Taiyo Terunuma 等：“化学评论季刊，光学异构体的分离”，日本化学会编辑，学会出版中心，238（1989）

Hiroyuki Nohira: "Optical Resolution of α-Ethylbenzylamine and Its Application as a Resolving Agent" Bull.Chem.Soc.Jpn.61. 1395-1396 (1988)

Hiroyuki Nohira：“α-乙基苄胺的光学拆分及其作为拆分剂的应用”Bull.Chem.Soc.Jpn.61 (1988)。

Hiroyuki Nohira: "Synthesis and Mesomorphic Properties of Ferroelectric Liquid Crystals with a Fluorinated Asymmetric Frame" Molecular Crysals and Liquid Crystals. (1990)

Hiroyuki Nohira：“具有氟化不对称框架的铁电液晶的合成和介晶性质”分子晶体和液晶。