4-苯基噁唑烷-2-硫酮对映体的模拟移动床色谱分离
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摘要
为了实现4-苯基噁唑烷-2-硫酮对映体的拆分,采用三带模拟移动床(simulated moving bed,SMB)色谱体系。该体系以甲醇为流动相,单键合β-环糊精手性填料为固定相,色谱柱规格为长100mm,直径10mm,设置洗脱带Ⅰ:2根色谱柱;精制带Ⅱ:1根色谱柱;吸附带Ⅲ:1根色谱柱,Ⅰ带独立。用线性理想模型描述4-苯基噁唑烷-2-硫酮对映体在色谱单柱的色谱行为。将单柱理想模型与2-1-1模式的结点模型结合,建立SMB色谱模型,用SMB色谱模型描述连续进样时4-苯基噁唑烷-2-硫酮对映体在SMB体系的分离情况。模型计算与实验结果表明:连续进样下,通过调整切换时间不能同时得到高纯度的2个对映体。实验中选择间歇进样,可以同时获得实际纯度大于98.0%的2个对映体。
To realize the separation of 4-phenyloxazolidine-2-thione enantiomers,three-zone simulated moving bed(SMB)chromatography system was employed.In this SMB system,β-cyclodextrin-bonded chiral silica gels was used as the stationary phase,methanol as the mobile phase,the size of a column was 100 mm in length and 10 mm in diameter,and the three zones included the independent eluting zoneⅠ with two columns,the refining zoneⅡ with one column and the desorbing zoneⅢ with one column.The ideal model based on the linear adsorption isotherm was used to describe the chromatographic behaviors of 4-phenyloxazolidine-2-thione enantiomers.SMB chromatographic model established by the combination of the ideal model of the single column and the node model of 2-1-1mode was used to describe SMB separation process of 4-phenyloxazolidine-2-thione enantiomers.The results of model calculation and experiment showed that under the condition of continuous feeding,it was unable to obtain the two enantiomers with higher purities at same time by adjusting the switching time.When intermittent feeding was done,the obtained purities of the two products were more than 98.0% simultaneously.
To realize the separation of 4-phenyloxazolidine-2-thione enantiomers,three-zone simulated moving bed(SMB)chromatography system was employed.In this SMB system,β-cyclodextrin-bonded chiral silica gels was used as the stationary phase,methanol as the mobile phase,the size of a column was 100 mm in length and 10 mm in diameter,and the three zones included the independent eluting zoneⅠ with two columns,the refining zoneⅡ with one column and the desorbing zoneⅢ with one column.The ideal model based on the linear adsorption isotherm was used to describe the chromatographic behaviors of 4-phenyloxazolidine-2-thione enantiomers.SMB chromatographic model established by the combination of the ideal model of the single column and the node model of 2-1-1mode was used to describe SMB separation process of 4-phenyloxazolidine-2-thione enantiomers.The results of model calculation and experiment showed that under the condition of continuous feeding,it was unable to obtain the two enantiomers with higher purities at same time by adjusting the switching time.When intermittent feeding was done,the obtained purities of the two products were more than 98.0% simultaneously.
引文
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[2]YU Y Y,WOOD K,LIU Y A.Simulation and comparison of operational modes in simulated moving bed chromatography[J].Industrial and Engineering Chemistry Research,2015,54(46):11576-11591.
[3]SONG J Y,KIM K M,LEE C H.High-performance strategy of a simulated moving bed chromatography by simultaneous control of product and feed streams under maximum allowable pressure drop[J].Journal of Chromatography A,2016,1471:102-117.
[4]PARK C,NAM H G,HWANG H J,et al.Development of a three-zone simulated moving bed process based on partial-discard strategy for continuous separation of valine from isoleucine with high purity,high yield,and highproduct concentration[J].Process Biochemistry,2014,49:324-334.
[5]许青青,孔利云,李敏,等.模拟移动床色谱法分离纯化链甾醇[J].分析化学,2013,41(6):851-855.XU Qingqing,KONG Liyun,LI Min,et al.Separation and purification of desmosterol by simulated moving bed chromatography[J].Chinese Journal of Analytical Chemistry,2013,41(6):851-855.(in Chinese)
[6]GONG R,LIN X,LI P,et al.Experiment and modeling for the separation of guaifenesin enantiomers using simulated moving bed and Varicol units[J].Journal of Chromatography A,2014,1363:242-249.
[7]ANDRADE N A S,SECCHI A R,SOUZA J M B,et al.Nonlinear model predictive control applied to the separation of praziquantel in simulated moving bed chromatography[J].Journal of Chromatography A,2016,1470:42-49.
[8]RIBEIRO A E,GOMES P S,PAIS L S,et al.Chiral separation of flurbiprofen enantiomers by preparative and simulated moving bed chromatography[J].Chirality,2011,23:602-611.
[9]陈韬,陈贤铬,徐俊烨,等.模拟移动床色谱法拆分甲霜灵对映体[J].色谱,2016,43(1):68-73.CHEN Tao,CHEN Xian’ge,XU Junye,et al.Enantioseparation of metalaxyl racemate by simulated moving bed chromatography[J].Chinese Journal of Chromatography,2016,43(1):68-73.(in Chinese)
[10]LIN X,GONG R J,LI J X,et al.Enantioseparation of racemic aminoglutethimide using asynchronous simulated moving bed chromatography[J].Journal of Chromatography A,2016,1467:347-355.
[11]伍贻康,杨永青,胡祺.手性噁唑烷-2-硫酮类化合物的合成方法:中国CN1557809[P].2004-12-29.WU Yikang,YANG Yongqing,HU Qi.Synthetic method of chiral oxazolidine-2-thione compounds:China,CN1557809[P].2004-12-29.(in Chinese)
[12]VELAZQUEZ F,OLIVO H F.The application of chiral oxazolidinethiones and thiazolidinethiones in asymmetric synthesis[J].Current Organic Chemistry,2002,6(4):303-340.
[13]CRIMMINS M T,CHAUDHARY K.Titanium enolates of thiazolidinethione chiral auxiliaries:versatile tools for asymmetric aldol additions[J].Organic Letter,2000,2(6):775-783.
[14]VIGNESH S V,HARIPRASAD K,ATHAWALE P,et al.Optimal strategies for transitions in simulated moving bedchromatography[J].Computers and Chemical Engineering,2016,84:83-95.
[15]HORVATH K,FAIRCHILD J N,KACZMARSKI K,et al.Martin-synge algorithm for the solution of equilibrium-dispersive model of liquid chromatography[J].Journal of Chromatography A,2010,1217:8127-8135.