Preparation And Enantioseparation Characteristics Of Chiral Stationary Phases Drived From Chitosan Urea Derivatives

Among the several chromatographic enantioseparation methods,the high-performance liquid chromatography(HPLC)with chiral stationary phases(CSPs)has become the most effective way for both the analytical and preparative separations of chiral compounds.Among the many kinds of CSPs so far developed for HPLC,the CSPs derived from cellulose and amylose are well known due to their high chiral recognition towards a wide range of compounds.Since cellulose and amylose derivatives such as cellulose tris(3,5-dimethylphenylcarbamate)(CDMPC)and amylose tris(3,5-dimethylphenylcarbamate)(ADMPC)can highly swell or dissolve in some organic solvents,the coating-type CSPs based on these polysaccharide derivatives can only work in a limited range of eluents.Meanwhile,immobilized CSPs with good solvent resistance often show a poorer chiral recognition ability compared to the corresponding coated-type CSPs.The goal of this work is developing CSPs with excellent enantioseparation capability and high tolerance against organic mobile phases.Therefore,a new way to prepare chitosan alkyl urea from chitosan has been established,and a series of new CSPs based on chitosan alkyl urea derivatives were prepared.The enantioseparation capability and the tolerability to organic solvents of these CSPs were evaluated.The works in this thesis can be summarized as follows:(1)Chitosan((?)v : 1.46×10~5)of ultrahigh degree of deacetylation(DD)was prepared by employing water-NaOH and n-pentanol-NaOH as the reaction systems in sequence.It was first reacted with methyl chloroformate yielding N-methoxyformylated chitosan,which was then converted to chitosan alkyl urea through amine-ester exchange reaction.The as-prepared chitosan alkyl urea derivatives were characterized by FT-IR and NMR spectra,and the degree of substitution(DS)of alkyl group on chitosan alkyl urea were determined according to integrals in the corresponding ~1H NMR spectra.The results reveal that the amino group in chitosan could be almost completely converted to ureido group.In addition,theoretical calculation was carried out to explain the relationship between the structure and reactivity of amines.It was found that the reactivity of amines depends mainly on the electron cloud density of nitrogen,and aliphatic primary amines of low stereohindrance are suitable for the amine-ester exchange reaction in this work.(2)A series of chiral selectors were prepared by derivatizing five diffefently chitosan alkyl urea with 3,5-dimethylphenyl isocyanate and were characterized by FT-IR,NMR and elemental analysis.The selectors were then coated on 3-aminopropyl silica gel to afford novel CSPs.The enantioseparation capability of CSPs was evaluated with twenty chiral compounds.In comparison with CSPs derived from CDMPC and ADMPC,the CSPs prepared in this work also possess excellent enantioseparation capability.The tolerability of the CSPs to organic solvents was also tested,the results show all the CSPs could work in pure ethyl acetate,pure acetone,and four of them could be analyzed with a mobile phase of pure tetrahydrofuran(THF)without loss of their enantioseparation capability.The tolerability against organic solvents had improved significantly compared to the existing coated-type CSPs.(3)Four chitosan n-octyl ureas with different viscosity-average molecular weights were prepared from chitosan,and then modified by six phenyl isocyanates of different substituents on their phenyl ring affording a new series of chiral selectors,which were coated on 3-aminopropyl silica gel to obtain another series of CSPs.This series of chiral selectors were insoluble in ethyl acetate and acetone,and swelled in THF at different extent.The chiral separation capability and the tolerability against organic solvents of these CSPs were investigated.The separation results indicated that the enantioseparation capability was related to the nature,position and number of the substituents located on phenyl ring.These CSPs demonstrated an equivalent or even better enantioseparation capability in comparison with that of the former series of CSPs and the CSPs of CDMPC and ADMPC under the same conditions.In addition,they also exhibited a stronger tolerability to organic solvents and could be analyzed with a mobile phase of pure ethyl acetate,acetone or THF.In summary,a method to prepare chitosan alkyl urea with high DS has been established.Two series of chitosan alkyl urea derivatives CSPs have been prepared.Compared to the existing coated-type CSPs,the all CSPs prepared in this thesis exhibited an excellent enantioseparation capability and possessed a better tolerability against organic solvents,thus demonstrating very good application perspectives.