Quinine Derivative Bonded The Hybrid Mesoporous Silicas Chiral Stationary Phase: Preparation And Application In Liquid Chromatography

Chirality is one of the material properties. Most of the chiral drugs wereracemate. While due to the sites of the single enantiomer was clear, it has become ahot spot. So the technologies of separation and analysis have been emerging. Amongthem, the chiral stationary phases were widely used.Spherical aminopropyl-functionalized ethane-bridged periodic mesoporousorganosilicas (APEPMOs) were bifunctionalized, meaning that it contained bothaminopropyl and ethane functional groups. Aminopropyl which is electron-richfunctional groups will facilitate subsequent modification. And they had sphericalmorphology, ordered mesostructure, large specific surface areas, high capacity andgood mechanical strength. In addition, APEPMOs had better permeability and hadcertain advantages in fast analysis. So, APEPMOs have been identified as apromising stationary phase for liquid chromatography. Thus far, there are still only afew reports on the preparation of spherical APEPMOs. And for quinine derivatives,most researchers have been committed to the preparation of quinine derivativesbonded chiral stationary phases and the resolution of chiral enantiomers in normalphase high performance liquid chromatography. While there were a few research onthe influence of mobile phase in reversed phase high performance liquidchromatography (RP-HPLC). Therefore, it is necessary for the research of preparationof quinine derivative bonded spherical APEPMOs chiral stationary phase and theapplication in RP-HPLC.In this thesis, the object focused on the development a novel kind of chiralstationary phase. We synthesized (APEPMOs), which were suitable for HPLCstationary phase, and then bonded with O-9-(tert-butyl carbamoyl) quinine (QN). Thechromatographic performance of the chiral column was demonstrated by several chiral drugs in RP-HPLC.A synthetic approach for synthesizing spherical aminopropyl-functionalizedethane-bridged periodic mesoporous organosilicas (APEPMOs) is reported. Themesoporous material was prepared by a one-step co-condensation of1,2-bis(triethoxysilyl)ethane (BTSE) and3-aminopropyltriethoxysilane (KH-550)using cetyltrimethylammoniumchlorine (C18TACl) as a template with the aid of aco-solvent (methanol) in basic medium. Then O-9-(tert-butyl carbamoyl) quininebonded APEPMOs chiral stationary phases was synthesized withazobisisobutyronitrile (AIBN) as initiator. The APEPMOs and chiral stationaryphases were characterized by scanning electron microscopy (SEM), nitrogen sorptionmeasurement, Fourier transform infrared spectroscopy (FT-IR) and elemental analysis.The slurry method was used to packing QN bonded APEPMOs chiral stationaryphases into the25cm stainless steel column with chloroform-dioxane (50/50, V/V) asslurry.The chromatographic performance of the chiral column was demonstrated byseveral chiral drugs in RP-HPLC. Three of them were baseline separation (Rs>1.5).In order to get optimal separation, column temperature, flow rate and the proportionof chiral additives, were also investigated. Three drugs were mandelic acid,2-chloromandelic acid and ketoprofen.Finally, the reproducibility and stability of the chiral column were alsoinvestigated. In order to investigate the reproducibility of the column,2-chloromandelic acid was separated on three batches of the chiral column. Itindicated that the reproducibility was well. In addition,2-chloromandelic acid wasseparated on one of the columns within a month. The result showed that the stabilityof the column was not very well. Probably due to the amount of the chiral reagentswhich bonded on the mesoporous silicas, some of the chiral drugs failed to achieve the baseline separation.