The Synthesis Of Cellulose Tribenzoate As Chiral Stationary Phase And The Preliminary Study On Chiral Separation

Microcrystalline cellulose is a natural optical-active linear polymers, which could be derived to a series of new derivatives. Among them being commonly used as Chiral Stationary Phase, it mainly includes cellulose acetates, cellulose tribenzoates and cellulose trisphenylcarbamates. As the poor resistance to pressure, these derivatives can not be used as Stationary Phase for High Performnce Liquid Chromatography directly and must be commonly fixed on silica gel carrier firstly. Among these methods, the coating method and the bonding method were the most popular approach. The coating chiral stationary phase has relatively strong abilities on chiral separation because of maintaining the natural ordered structure of microcrystalline cellulose and a relatively narrow choice range of mobile phase because of dissolving easily in dichloromethane and chloroform so on. The bonding chiral stationary phase has a broad choice range of mobile phase on account of the force between derivatives and silica gel carriers being chemical bonds and weaker abilities on chiral separation on account of being destroyed the natural ordered structure of microcrystalline cellulose.Cellulose tribenzoates fixed on silica gel carrier has relatively strong abilities on chiral separation, on which all kinds of racemic compounds can be separated. It is one of chiral stationary phases of cellulose exhibiting widespread prospects of application. These fixing methods all have merits and demerits, and can mutual supply to some extent each other. On this thesis cellulose tribenzoates was synthesized in accordance with the method reported, which was prepared for chiral thin layer plates. The chiral separation abilities of cellulose tribenzoates prepared was investigated by resoluting the common chiral drugs and intermediates with chiral thin layer plates.Tribenzoyl-cellulose was synthesized by reaction of microcrystalline cellulose with benzoyl chloride. As the substitutional degree of celluse hydroxy being relative low, and the color of products being relative darker, tribenzoyl-cellulose by the reported techniques does not meet the requirements of chiral thin layer plates. And the synthetic technique is needed to be improved. On this thesis the best synthetical condition was decided by introducing the ultraphonic method, investigating the effects of various reaction conditions such as the reaction solvent, material ratio, temperature and time. The optimum conditions were as follows: the reaction solvent at 200ml pyridine and 15ml triethylamine per 5g MC, the ratio of benzoyl chloride and microcrystalline cellulose at 19.6ml:5g, reaction temperature at 70℃, the ultrasound time at 2h and the stirring time at 10h. Tribenzoyl-cellulose can be synthesized on this condition with being good in colour and being high (over 95.1%) in the substitutional degree. By characterized by IR spectrometry and element analysis it is the CTB we needed. Furthermore, according to the synthetic method of Tribenzoyl-cellulose, Nicotinoyl chloride was synthesized firstly, and reacted with cellulose secondly, cellulose triacidnicotinates was synthesized finally with the substitutional degree being over 94.7%.The mixture of CTB and microcrystalline cellulose in certain propotion was used as chiral stationary phase(CSP) of thin-layer chromatography. Optimized of mobile phases and visualization, five chrial drugs were separated on the CSP, such as ofloxacin, propranolol, phenylalanine,N-methyl-β-hydroxyl -phenylethylamine and atropine. Enantiomers obtained were characterized by specific rotation, melting point, IR and 1H-NMR spectrometry and these datas are consistent with the reported. Ofloxacin was separated by using acetonitrile - n- butyl alcohol - triethylamine ( 7:13:1 ) as developer and 365nm ultraviolet as color developing agent, and the Rf values of the two enatiomers are 0.94 and 0.83 respectively. Propranolol was separated by using n-hexane - isopropanol ( 11:9 ) as developer and Vanillin-Sulfuric acid as color developing agent, and the Rf values of the two enatiomers are 0.69 and 0.58 respectively. Phenylalanine was separated by using n- butyl alcohol -acetonitrile - water - acetic acid ( 16:2:2:1 ) as developer and ninhydrin as color developing agent, and the Rf values of the two enatiomers are 0.49 and 0.42 respectively. N-methyl-β-hydroxyl -phenylethylamine was separated by using acetonitrile - methanol (1:2) as developer and iodine vapor as color developing agent, and the Rf values of the two enatiomers are 0.77 and 0.72 respectively. Atropine was separated by using ethyl acetate- methanol-ammonia water stronger(16:4:1) as developer and bismuth potassium iodide as color developing agent, and the Rf values of the two enatiomers are 0.84 and 0.79 respectively.