Preparation And Characterization Of A Highly Stable Hybrid Organosilica Cellulose Derivative-based Chiral Stationary Phase

Optically pure compounds (or single enantiomer) play an important role in the areas such as biological medicine, agricultural chemicals, food additives and functional materials, showing a large market demand. With almost the same properties, separating enantiomers are a difficult task. To obtain a single enantiomer is mainly by means of chiral synthesis, asymmetric catalytic synthesis and racemic resolution method so far. Comparatively speaking, resolution is the most widely used, which can get two enantiomers at the same time. Chromatography is the most rapidly developed and most widely used among the existed resolution methods. The key to chiral resolution method based on chromatography is the preparation of chiral stationary phase (CSP). Among numerous reported CSPs, cellulose derivatives-based CSP has the advantages of larger capacity and broader chiral recognition, and is widely used in chiral chromatography. However, the current commercially available columns (Chiralcel OD and Chiralpak IB), which are generally prepared by coating or bonding on silica gel, have low cellulose loading (about 20 wt%), thus limiting their application in the field of preparative chromatography. Okamoto’s group reported for the first time the cellulose-3,5-dimethyl phenyl carbamate derivatives containing a small amount of 3-(triethoxy silicon) propyl carbamate(CDMPC) was used as a precursor to prepare organic-inorganic hybrid silica sphere (CSP-T) by the sol-gel reaction. The prepared CSP-T was determined to contain CDMPC up to 70%. CSP-T shows a higher loading than commercial columns. However, due to its high CDMPC content, CSP-T was easy to swell and partially dissolved in chloroform and other solvents, which limits its applicable scope of the mobile phases. Herein, I choose the more flexible silane coupling agent of 1,2-2 (triethoxy silicon) ethane (BTSE) instead of ethyl orthosilicate (TEOS), and then optimize the preparation process, and get a better organic inorganic hybrid silicon sphere (CSP-B).Firstly, the cellulose 3,5-dimethylphenylcarbamate (CDMPC) containing a small number of 3-(triethoxysilyl)propyl groups was obtained and the chemical structure was then confirmed via FT-IR and 1H NMR. by particle size distribution analysis and TGA for the information about proportion of organic and inorganic ingredient. The parameters including the concentration of surfactant, stirring speed, the concentration of the sol and gel aging time were examined in detail in order to obtain the silica spheres with uniform particle size. CDMPC and BTSE were first dissolved in a THF/H2O/heptanol/trimethylsilyl chloride (24:1:6:0.5=v/v/v/v=31.5 mL). This solution was then heated for 10 h at 80℃ and added dropwise into water (500 mL) containing sodium lauryl sulfate (0.2%) at 80℃ with mechanical stirring at 5 k rpm using a multidisperser.Finally, different CSPs-B with varied mole ratios of organic and inorganic ingredient were prepared, and were packed into a chromatographic column after end-capping. The CSP-B with organic content of 80% showed excellent chiral recognition. All enantiomers including six neutral substrates, three alkaline and one acidic were well resolved. In particular, enantiomers of 2,2,2-trifluoro-l-(9-anthryl)ethanol, metoprolol and 2-benzyl propionate were separated with enantioselectivity up to 3.00,2.48 and 2.55, respectively. CSP-B with 60% organic content was observed to be chemically and mechanically stable in acid, alkaline or even mobile phase containing chloroform, meanwhile keeping good chiral recognition performance. Comparatively, CSP-B with 50% organic content showed more excellent mechanical properties, despite the chiral separation performance was relatively lower. In addition, the loading of CSP-B was also investigated, and high loading was proved.In conclusion, CSP-B prepared in this work not only shows good chiral separation performance and high loading, but also excellent chemical and mechanical stability. This is superior to CSP-T when used as chromatographic packing material. The CSP-B remains the considerably good chiral recognition performance and mechanical properties in mobile phase containing chloroform, outperforming the traditional coating-type cellulose-based CSP. The hybrid CSPs prepared in this work is a promising packing material for preparative chiral chromatography.