手性环氧氯丙烷的合成及应用

论文编号:HG242  论文字数:12149,页数:25

摘要：手性环氧氯丙烷是一种极有价值的合成中间体，通过手性环氧氯丙烷为反应起始物，可以得到很多有用的高光学纯度药物中间体。本文通过比较文献报道的几种方法，选取了水解动力学拆分法。首先合成了(Salen)Co(Ⅲ)(OAc)催化剂，建立了快速可靠的气相色谱法来跟踪检测产物S-环氧氯丙烷的e.e.值（对映体过量值）。其次通过对拆分过程中e.e.值变化的跟踪分析，对反应条件进行单因素优化，发现反应在温度20℃，水用量为0.55当量，催化剂浓度为0.5mol%时，能够在10小时内得到e.e.值>99.5%的S-环氧氯丙烷。催化剂在回收并且重新络合醋酸再生三次后，仍然能够得到e.e.值>99.5%的S-环氧氯丙烷，也验证了反应过程中配体遭到破坏这一假设。接着用手性环氧氯丙烷来合成药物中间体（S）-6-氯-5-羟基-3-氧代-己酸异丁酯和（S）-4-氯-3-羟基丁酸乙酯。
 关键词：手性环氧氯丙烷；水解动力学拆分； Salen催化剂；（S）-6-氯-5-羟基-3-氧代-己酸异丁酯；
 （S）-4-氯-3-羟基丁酸乙酯

Abstract：Chiral epichlorohydrin is a very important intermediate in organic synthesis. It is very common and easy to start with chiral epichlorohydirn for the generation and manufacturing of optically active compounds. Compared with some other methods, the hydrolytic kinetic resolution (HKR) was chosen for the production of (S)-epichlorohydrin. The application of the salen catalysts led to higher chiral epichlorohydrin yield and higher optical purity of the product. First, the (salen)Co(Ⅲ)(OAc) catalyst was synthesized by a practical method, and the e.e. (enantiomeric excess) of the (S)-epichlorohydrin was determined by GC analysis. Then, the optimization of the reaction catalyzed by (salen)Co(Ⅲ)(OAc) was investigated through the mono-factor’s experiment. Under the condition that the temperature was 20℃, the water was 0.55 equivalent, and the concentration of the catalyst was 0.5mol%, the e.e. of the (S)-epichlorohydrin would reach 99.5% in 10 hours catalyzed by the new or the reused (salen)Co(Ⅲ)(OAc). Finally, use chiral epichlorohydrin to synthesize medicine intermediate (S)-6-chloro-5-hydroxy-3-oxo-hexanoic acid t-butylester and (S)-4-chloro-3-hydroxybutyronitrile.
Keywords: Chiral epichlorohydrin；Hydrolytic kinetic resolution(HKR)；Salen catalyst；(S)-6-chloro-5-hydroxy-3-oxo-hexanoic acid t-butylester； (S)-4-chloro-3-hydroxybutyronitrile