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.

为了搜索能够优先结晶的手性化合物，分析其晶体相并确定其光学分辨率过程，进行了这项研究并获得以下结果。1。两对优先结晶的盐（CIS -2-苯甲酰二烷基二羧酸（1）和-Ethylbenzyla*矿山（2）和 - 甲基苯甲酰胺（3）和肉桂酸）的麦芽麦芽点已通过差异扫描钙钙和甲基苯甲酸（2）和 - 甲基苯甲酰胺（3）和肉桂酸进行了测量。 （<plus-minus>）的盐 - 已发现通过相互优先结晶过程3。使用光学活性2作为分辨剂建立了酮（4）光学分辨率（4）的实用程序。证实4结晶为一种外星化合物，用差分扫描量热仪绘制了4个二进制图4。作为一种手性配体，预计具有出色的手性识别能力来映射反应，已经合成了一种新的双苯基型二磷蛋白（5），并已被发现可以结晶为砾岩。已在没有任何种族化的情况下进行了分辨率5的立体特异性还原5。已经发现，（+）和（ - ） - 苯基甲基 - 苯基甲硅烷基乙酸（6）的熔点高于外围的熔点，而6则优先从苯/己烷混合溶剂中结晶。这认为是优先结晶的有机硅化合物的第一个例子。

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。