Study On Multistage Enantioselective Liquid–liquid Extraction Of Pharmaceutical Intermediates With ?-cyclodextrin Derivatives In Centrifugal Contactor Separators

In this paper,the centrifugal extraction technology was used for multistage extraction separation of 2-phenylbutyric acid(2-PBA),tropic acid(TA)and 2,3-diphenylpropionic acid(2,3-2-PPA)enantiomers with hydrophilic-?-cyclodextrin derivatives as extractants.Appropriate multistage equilibrium models were established for these enantiomers on the basis of single stage extraction model,mass conservation law and phase equilibrium equation.Matlab software was used to write simulation program and then the model was used to simulate and optimize the extraction process.A series of centrifugal extraction separation processes and process parameters were obtained,which provided scientific basis for design and scale-up for centrifugal contactor separators about 2-PBA,TA and 2,3-2-PPA.The main research work and corresponding results were as follows:In the liquid-liquid extraction process,the effects of experimental conditions on the distribution ratio(D)and enantioselectivity(?)including organic solvents,?-cyclodextrin derivatives,cyclodextrin concentration,pH and temperature were investigated.The best conditions could be concluded as follows: under the condition that 1,2-dichlorethane acted as organic solvent,and HE-?-CD acted as chiral extrant,and pH value was 3.00 and temperature was 278 K,the optimal separation factor for 2-PBA was 2.096;under the condition that butyl acetate acted as organic solvent and HE-?-CD acted as chiral extrant,and pH value was 3.00 and temperature was278 K,the optimal separation factor for TA was 1.606;under the condition that 1,2-dichlorethane acted as organic solvent,and SBE-?-CD acted as chiral extrant,and pH value was 3.00 and temperature was278 K,the optimal separation factor for 2,3-2-PPA was 1.422.Appropriate multistage equilibrium modelswere established for enantiomers based on the combination of single stage extraction model,mass conservation law and phase equilibrium equation.The matlab software was used to write simulation program and then the modelswere developed to simulate and optimize the extraction processes.Impacts of operating parameters on the extraction efficiency including the rotatingspeed,the volume flow ratios(W/O or O/W and W/F),extractant concentration,pH value of the aqueous phase as well as the number of stages were investigated.Important conclusion for these multistage processeswere drawn as follows: under the optimal conditions,the eeeq could reach up to 97% and 99% for 2-PBA with the number of stages of 60 and 82,respectively;the eeeqcould reach up to 97% and 99% for TA with the number of stages of 56 and 78,respectively;the eeeq could reach up to 97% and 99% for 2,3-2-PPA with the number of stages of 78 and 102,respectively.