Optimization For The Preparation Of Chiral Stationary Phases Drived From Acylated And Carbamylated Chitosans Derivatives

High-performance liquid chromatography(HPLC)based on chiral stationary phase(CSP)has been one of the best technology to separate and detect enantiomers.Therefore,it is very important to develop the novel CSPs with powerful enantioseparation abilities and high tolerance to organic solvents for chiral separation and the related fields.In recent yeas,some research groups have reported a number of excellent CSPs based on chitosan derivatives,which have powerful separation capability and high tolerance to organic solvents.However,the relationship between the structure and properties of the chitosan derivatives chiral selectors(CSs)is still unclear.For example,it is not clear whether the properties of CSPs prepared from organism-different chitosans are accordingly different or not.At the same time,the chiral separation performance of CSP is closely related to its preparation method(the capping group of the carrier,the amount of CS coated on the carrier and the particle size of silica gel).In order to clarify these problems,the following works have been implemented in this thesis:(1).In order to study the relationship between structure and properties of N-cycloalkyformylated chitosan derivatives,chitosan with high deacetylation degree was prepared by using nature chitin as raw material.The chitosan was modified with cyclopentanecarboxylic anhydrides and 3,5-dimethylphenyl isocyanate in sequence to afford chitosan bis(3,5-dimethylphenylcarbamates)-(N-cyclopentylformamide).The chitosan derivative was coated on 3-aminopropyl silica gel to obtain a CSP.The organic solvent tolerance and enantiomeric separation performance of the CSP were compared with those of the CSPs containing N-cyclopropylcarbonyl,N-cyclobutylcarbonyl and N-cyclohexylcarbonyl at the 2-position of chitosan.It was found that solvent tolerability and enantioseparation performances of the chiral selectors obviously differed with the variation of the substituent at 2-position of glucosamine skeleton.All CSs exhibit good organic solvent tolerance in both acetone and ethyl acetate.At the same time,the chiral selector with three-membered ring possessed much more preferable tolerability against tetrahydrofuran than the others with four-,five-or six-membered ring at 2-position.Enantioseparation results revealed that most of the chiral selectors exhibited powerful chiral recognition and enantioseparation abilities,and the chiral selector with five-membered ring possessed the best enantioseparation performance.The corresponding coated-type chiral stationary phases prepared from these chitosan-based chiral selectors were able to be complementary with each other and applied as promising chiral separation materials for enantiomeric separations.(2).In order to disclose the influence of different sources of chitosan on the performance of the prepared CSPs,chitosans with high deacetylation degree were prepared from shrimp shell and crab shell,and were modified by octanoic anhydride and two kinds of phenyl isocyanate affording four CSs.The CSs were two chitosan bis(3,5-dimethylphenylcarbamate)-(octanamide)s derived from the shrimp shell and the crab shell,and two chitosan bis(3,5-dichlorophenylcarbamate)-(octanamide)s prepared from the shrimp shell and the crab shell.Then the CSs were coated on 3-aminopropyl silica gel to provide two Shrimp-CSPs and two Crab-CSPs.The two CSPs with the same substituent(methyl or chloro)and derived from source-different chitosans were close in enantioseparation capability.In addition,the swelling capacity of the CSs was tested in acetone,ethyl acetate and THF,respectively.The two CSs with the same substituents exhibited close swelling capacities,revealing the corresponding CSPs possess equivalent tolerability against organic solvents.The circular dichroism(CD)spectra of the two series of CSs were measured.The results showed that the peak shapes and positions of the shrimp-and crab-CSs with the same substituent group are quite consistent,indicating there was no significant difference in the suprastructure of the two CSs.Therefore,the chitins available from crab and shrimp shells are both applicable for the development of enantiomeric separation materials,depending on the accessibility of chitins.On the other hand,there were still slight differences in chromatographic separation results.The separation performance of crab-CSP seemed to be better;and there were two analytes were separated by the CSPs of chitosan bis(3,5-dichlorophenylcarbamate)-(octanamide)s with reversed elution orders.The observed results in this work differ from those reported in the literature.(3).Chitosan bis(4-methylphenylcarbamate)-(isobutylurea)was prepared in this thesis.Three CSPs with different capping groups were obtained by coating the chitsan bis(4-methylphenylcarbamate)-(isobutylurea)on 5?m methyl silica gel,3-aminopropyl silica gel and trimethyl silica gel,which were prepared from methyltriethoxysilane,3-aminopropyltriethoxysilane and trimethylchlorosilane.Comparing the enantioseparation results,it was found that CSP with 3-aminopropyl as the capping group showed the best chiral separation performance.By using 3-aminopropyl silica gel as the support,three CSPs were prepared with different fed amounts(17%,20% and 23%)of the CS.The enantioseparation performance of the CSPs was tested and compared.The result showed that the CSP prepared with the fed amount of 20% had the best enantioseparation performance.Under different chromatographic conditions,the enantioseparation performance of two CSPs prepared from 5-?m and 7-?m silica gel with 3-aminopropyl as the capping group and with the fed amount of 20% was tested and compared.The enantioseparation evaluation demonstrated that the former CSP derived from 5-?m silica gel was better than the latter one in enantioseparation performance.According to the preparation method which results in a CSP with the best chiral separation performance,a CSP was prepared again and the enantioseparation performance of the two CSPs prepared in two batches was tested and compared.It was found that the two CSPs exhibited very similar enantioseparation capabilities implying the preparation process of the CSP was repeatable.In summary,some CSPs with good separation performance and high tolerance to organic solvents were prepared.The structure-performance relationship of N-cycloalkycarbonyl chitosan derivatives was clarified;the performance of CSPs prepared from source-different chitosans was compared;the preparation process of the CSP was optimized in terms of capping group,fed amount for coating and particle size of silica gel.The trends observed in this thesis will be helpful in developing novel enantioseparation materials.