Inclusion Reaction Of Chiral Extraction Separation Of Aromatic Acid Enantiomers And Its Kinetics

Preparative techniques for the separation of drug enantiomers have a great interesting potential. Chiral extraction is a very important method for preparative separation of enantiomers. It has some regularity and a larger application range in contrasting to chemical resolution, fermentation and enzymatic transformation and chromatography. Reactive extraction is a very effective separation technique with great promise. In the thesis, distribution behaviors ofα-cyclohexyl-mandelic acid (α-CHMA) enantiomers and phenylsuccinic acid (PSA) enantiomers were examined in the aqueous-organic solvent of a two-phase systerm containing a chiral selector. And then, the extraction kinetics was studied using constant- interface area cell under the optimized system to provide theoretical bases and technique parameters for enantioseparation process. The main contents and results can be summarized as follows:1. Study on chiral extraction ofα-CHMA enantiomers and PSA enantiomers:The influence of the types of organic solvents and P-cyclodextrin derivatives (β-CDs), the concentrations of the extractants and enantiomers, pH and temperature on distribution ratio (k) and enantioselectivity (α) forα-CHMA and PSA enantiomers, was separately investigated using hydrophilicβ-CDs as chiral selectors. The extraction performance and chiral recognition mechanism were studied.The experimental results indicate that reactive extraction has strong chiral separation ability. hydroxypropyl-β-cyclodextrin(HP-β-CD), hydroxyethyl-β-cyclodextrin(HE-β-CD) and methyl-β-cyclodextrin (Me-β-CD) have higher recognition ability for S-α-CHMA enantiomer than that for R-α-CHMA enantiomer, among which HP-β-CD has the strongest separation ability. But theseβ-CDs have reversed recognition ability for phenylsuccinic acid enantiomers. In the optimized extraction process forα-CHMA enantiomers, the extraction performance ofα-CHMA is optimum by one stage extraction, and the distribution ratio for S-α-CHMAt(kS) and for R-α-CHMA(kR) and separation factor(α) are 4.77,2.36 and 2.02, respectively. In the extraction process for PSA enantiomers, the extraction performance of PSA is optimum by one stage extraction, and the distribution ratio for R-PSA (kR) and for S-PSA(kS) and separation factor(α) are 2.38,1.00 and 2.38, respectively. Meanwhile, organic solvents, concentration of extractants, pH and temperature have great effects on chiral separation ability.2. Study on the reactive extraction kinetics ofα-CHMA enantiomers, PSA enantiomers using HP-β-CD as extractant:The reactive extraction kinetics was determined in a stirred cell with a constant interfacial area. The extraction process was measured at various stirring speeds, interfacial areas, initial enantiomers concentration in organic phase as well as HP-β-CD concentration in aqueous phase. The experimental results demonstrate that, the exraction reaction kinetics is 'fast' for HP-β-CD extractionα-CHMA enantiomers, and the reactions between HP-β-CD and PSA enantiomers are also fast. The reactions have been found to be first order with respect to enantiomers and second order with respect to HP-β-CD with forward rate constants of 70584.8 L2/mol2·s and 18079.4 L2/mol2·s for S-α-CHMA and R-α-CHMA, respectively. The rate constants of HP-β-CD extraction PSA enantiomers are 32011.8 L2/mol2·s and 7408.7 L2/mol2·s for R-PSA and S-PSA, respectively. These data will be useful in the design of extraction processes.