β-环糊精衍生物多级离心手性萃取分离药物中间体的研究

发布时间：2018-04-27 01:14

本文选题：手性分离 + 多级离心萃取　；参考：《湖南理工学院》2017年硕士论文

【摘要】：本论文以亲水性β-环糊精衍生物为手性萃取剂,对药物中间体(2-苯基丁酸、托品酸与2,3-二苯基丙酸对映体)的多级离心萃取分离过程进行了研究。联立液-液萃取理论模型与质量守恒定律,结合相平衡方程,分别建立了相应的离心萃取的数学模型,运用Matlab软件编写程序,建立的模型用于模拟和优化多级离心萃取分离过程,得到了一系列的离心萃取分离过程的规律以及工艺操作参数,为分离这3种药物中间体以及离心萃取器的设计和放大提供了科学依据。本论文的主要研究工作和结果如下:1.液-液萃取实验,分别考察了有机溶剂、环糊精种类、温度、水相pH等因素对分配比(D)和分离因子(α)的影响。得到了相应的最佳萃取条件。在278 K下,以1,2-二氯乙烷为有机溶剂,羟乙基-β-环糊精(HE-β-CD)为手性萃取剂,水相pH为3.0,萃取2-苯基丁酸的分离因子最佳为2.096。以乙酸丁酯为有机溶剂、羟乙基-β-环糊精(HE-β-CD)为手性萃取剂、水相pH为3.0,萃取托品酸的分离因子最佳为1.606。以1,2-二氯乙烷为有机溶剂、璜丁基-β-环糊精(SBE-β-CD)为手性萃取剂、水相pH为3.0,萃取2,3-二苯基丙酸的分离因子最佳为1.422。2.联立液-液萃取理论与质量守恒定律,结合相平衡方程,建立多级离心萃取过程模型,运用Matlab平台编写程序,模拟多级离心萃取过程各因素的影响。通过实验与模型模拟,考察了离心机转速、两相流量比(W/O、O/W和W/F)、环糊精浓度、水相pH值、以及萃取级数等因素对多级离心萃取性能的影响。结论如下:在最佳操作条件下,分离2-苯基丁酸对映体,eeeq达到97%与99%以上所需的萃取级数分别为60级与82级;分离托品酸对映体,eeeq达到97%与99%以上所需的萃取级数分别为56级与78级;分离2,3-二苯基丙酸,eeeq达到97%与99%以上所需的萃取级数分别为78级与102级。
[Abstract]:In this paper, using hydrophilic 尾 -cyclodextrin derivatives as chiral extractant, the separation process of 2-phenylbutyric acid, tropinic acid and enantiomers of 2-diphenyl propionic acid was studied. The theoretical model of simultaneous liquid-liquid extraction and the law of conservation of mass, combined with the equation of phase equilibrium, were used to establish the corresponding mathematical model of centrifugal extraction, and the program was written by using Matlab software. The model is used to simulate and optimize the separation process of multistage centrifugal extraction. It provides a scientific basis for the separation of these three drug intermediates and the design and amplification of centrifugal extractors. The main work and results of this thesis are as follows: 1. The effects of organic solvent, type of cyclodextrin, temperature and pH of aqueous phase on the partition ratio (D) and separation factor (伪) were investigated. The optimum extraction conditions were obtained. At 278K, the best separation factor of 2-phenylbutyric acid was 2.096, with 1h2- dichloroethane as organic solvent and hydroxyethyl 尾 -cyclodextrin HE- 尾 -CD) as chiral extractant. The pH of aqueous phase was 3.0, and the separation factor of 2-phenylbutyric acid was 2.096. When butyl acetate was used as organic solvent, hydroxyethyl 尾 -cyclodextrin (HE- 尾 -CD) was used as chiral extractant, pH was 3.0 in aqueous phase, the best separation factor was 1.606. The best separation factor for extraction of 2-diphenylpropionic acid was 1.422.2 with 1 ~ (2 +) -dichloroethane as organic solvent, Juan Ding Ji-尾 -cyclodextrin (SBE- 尾 -CDCD) as chiral extractant, pH = 3.0 in aqueous phase. The simultaneous liquid-liquid extraction theory and mass conservation law combined with phase equilibrium equation were used to establish a multistage centrifugal extraction process model. The program was compiled by using Matlab platform to simulate the influence of various factors in the multistage centrifugal extraction process. The effects of centrifuge speed, two-phase flow ratio (W / O / O / W and W / F), concentration of cyclodextrin, pH value of water phase and extraction order on the performance of multistage centrifugal extraction were investigated by experiments and model simulation. The results are as follows: under the optimum operating conditions, the extraction order required for the separation of 2-phenylbutyric acid enantiomers is 60 and 82, respectively, when the enantiomers are 97% and 99% respectively. The order of extraction required for separation of enantiomeric enantiomers of tropinic acid is 56 and 78, respectively, and the extraction order for separation of enantiomeric enantiomers of tropicanoic acid is 97% and 99%, respectively, and the order of extraction is 78 and 102 for separating the enantiomeric enantiomers of tropicaric acid, which are above 97% and 99%, respectively.
【学位授予单位】：湖南理工学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O658.2;TQ460.1

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