Research On The Preparation Of Tens Of Micrometer Sized Chloromethylated Polystyrene Spheres

With the development of medical science, chiral pharmaceutical separation has become an urgent problem. High performance liquid chromatography (HPLC) chiral stationary phase method is regard as the fastest and most effective way for chiral separation and has been used widely. Chiral stationary phases are the central part of the chromatographic column. Although some commercial chiral stationary phases are available, however, the most traditional commercial chiral stationary phases are prepared with silica gel as substrate which has bad chemical stability, this restrict the application of these chiral stationary phases. So the synthesis of novel and high chemical resistance substrate of chiral stationary phases is current trend in chiral pharmaceutical research area.The optimum size of microspheres for chiral stationary phases is range from30μm to50μm. This can be explained by that, when the size of particles is small, the chiral stationary phases will be loaded too tightness which would need higher column pressure. When the size of particles is large, the gap between microspheres will be large which would lead the time samples stay in the column to be short, this is bad for the pharmaceutical separation. In this paper, three research parts were mainly done in order to get chloromethylated crosslinked polystyrene microspheres which can be used as the substrate of new chiral stationary phases.(1) The tens micron sized crosslinked polystyrene microspheres were produced by suspension polymerization in H2O medium with poly(N-vinyl pyrrolidone)(PVP) and polycing akohol (PVA) as composite dispersant,2,2’-azobisisobutyronitrile (AIBN) as a radical initiator and divinyl benzene (DVB) as a crosslinker. The effect of composite dispersant concentration and PVP/PVA ratio on particle size and size distribution of crosslinked PS microspheres were studied extensively. It was found that there are microspheres ranged from30μm to50μm prepared when use the PVP and PVA as composite dispersant. However, most of the particles are irregular particles. (2) Based on the synthetic process of the first part, the tens micron sized crosslinked polystyrene microspheres were produced by a new method which is between suspension polymerization and dispersion polymerization in ethanol/H2O medium poly (N-vinyl pyrrolidone)(PVP) and hydroxypropyl methul cellulose (HPMC) as composite dispersant,2,2’-azobisisobutyronitrile (AIBN) as a radical initiator, n-hexanol as the co-dispersant and divinyl benzene (DVB) as a crosslinker. The effect of ethanol/H2O ratio and n-hexanol on particle size and size distribution of crosslinked PS microspheres were studied extensively. It was found that when the concentration of PVP and HPMC is3wt%, volume ratio of H2O/ethanol/n-hexanol is30:19.5:0.5and after screening process, the mass percentage of microspheres ranged from30μm to50μm reached to76.83%.(3) Based on the synthetic process of the first part, the tens micron sized chloromethylated crosslinked polystyrene microspheres were produced by a new method which is between suspension polymerization and dispersion polymerization in ethanol/H2O medium poly (N-vinyl pyrrolidone)(PVP) and hydroxypropyl methul cellulose (HPMC) as composite dispersant, styrene and chloromethylated styrene as monomers,2,2’-azobisisobutyronitrile (AIBN) as a radical initiator, n-hexanol as the co-dispersant and divinyl benzene (DVB) as a crosslinker. The effect of n-hexanol concentration on particle size and size distribution of chloromethylated crosslinked PS microspheres were studied extensively. It was found that when the concentration of chloromethylated styrene was30wt%(based on the total mass of monomers), the concentration of PVP and HPMC is3wt%, volume ratio of H2O/ethanol/n-hexanol is30:19.5:0.5and after screening process, the mass percentage of chloromethylated crosslinked polystyrene microspheres ranged from30μm to50μm reached to83.22%.