Enantioselective Extraction Of Racemic Drugs In A Cascade Of Centrifugal Contactor Separators

In the thesis, four systems have been studied. One system is fractional extraction of pantoprazole was investigated with HP-β-CD in aqueous phase and isobutyl D-tartrate in organic phase as enantioselective extractants in annular centrifugal contactors. Based on homogeneous reaction mechanism multistage enantioselective liquid-liquid extraction equilibrium models were developed combining with the law of mass conservation and liquid-liquid equilibrium equations. Simulated program has been written by Matlab package. Multistage enantioselective liquid-liquid extraction for chiral separation of OBN and EQU and AMB enantiomers was studied through experiments and simulations. The model has been used to optimize the process of multistage enantioselective liquid-liquid extraction, optimal technological parameters were obtained, which provided scientific basis for the industrial applications of chiral separation of racemates and the design and amplification of centrifugal contactor separators. The main works and results are as follows:1. Multistage enantioselective liquid-liquid extraction for biphasic recognition chiral separation of PAN enantiomers: Continuous separation of pantoprazole enantiomers by biphasic recognition chiral extraction(BRCE) in a cascade of centrifugal contactor separators was studied. The BRCE system consists of isobutyl D-tartrate(D-IBTA) in organic phase and hydrophilic-β-cyclodextrin(HP-β-CD) in aqueous phase. the effect of W/O ratio, extractant D-IBTA concentration, and number of stages on the purity and yield of the product was investigated. A higher D-IBTA concentration and a smaller W/O ratio can result in higher purity in raffinate phase and lower in extract phase. More stages are required to obtain higher purities in both product streams. The desired enantiomer can be obtained by asymmetric separation,i.e. by varying the phase ratio, Without the need of increasing the number of stages.The optimal conditions for symmeyric separation involves W/O ratio of 5 and0.1mol/L D-IBTA, Which can make the eeeq up to 0.48 and Yeq to 68%. The technology is potentially applicable to scale production.2. Multistage enantioselective liquid-liquid extraction for chiral separation of OBN enantiomers: A model for multistage enantioselective liquid-liquid extraction(ELLE) of oxybutynin(OBN) enantiomers was built on the basis of single-stage model for chiral extraction of OBN enantiomers and the law of mass conservation in a counter-current cascade of centrifugal contactor separators(CCSs). A series of experiments concerning influence of the extract phase/washing phase ratio(W/O),extractant concentration, pH value, temperature and the number of stages Were conducted to verify the multistage equilibrium model. By simulation and optimization,optimal process parameters for the symmeyrical separation of OBN enantiomers,namely, pH of 5, HP-β-CD concentration of 0.1 mol/L and W/F of 5 at temperature of278 K are obtained. with the optimal process parameters, the eeeq can be up to 97%with the number of stages of 100.3. Multistage enantioselective liquid-liquid extraction for chiral separation of EQU enantiomers: A model was built on the base of single-stage model for chiral extraction of EQU enantiomers and the law of mass conservation. A series of experiments of the extract phase/washing phase ratio(W/O), extractant concentration and pH value have been conducted to verify the multi-stage equilibrium model. The model was applied to predict the symmetrical separation of EQU enantiomers. By simulation, optimal process parameters for the symmetrical separation of EQU enantiomers can be obtained,namely, pH of 7, HP-β-CD concentration of 0.1 mol/L and W/F of 8 at temperature of 278 K are obtained. With the optimal process parameters, the eeeq can be up to 95% with the number of stages of 100.4 、 Multistage enantioselective liquid-liquid extraction for chiral separation of AMB enantiomers: A model was built on the base of single-stage model for chiral extraction of AMB enantiomers and the law of mass conservation. A series of experiments of the extract phase/washing phase ratio(W/O), extractant concentration and pH value have been conducted to verify the multi-stage equilibrium model. The model was applied to predict the symmeyric separation of AMB enantiomers. By simulation, the multistage enantioselective liquid-liquid extraction of AMB enantiomers can be optimized.