The Study Of The Synthesis Of 2, 4-Dichlorofluorobenzene As The Organic Intermediate For Synthesizing Ciprofloxacin

The fluoroquinolone antibacterial agent has drawn wide attention and developed rapidly in clinical application because of its biologically active,good effect and low toxicity. The total demand is increasing. So, as the organic intermediate for synthesizing ciprofloxacin,a broadspectrum antibiotics,The demand of 2,4-dichlorofluorobenzene is increasing also.At present the domestic factories take 2,4-Dinitrochlorobenzene as raw material. But because this craft must adopt high-temperature fluorination, consequently concentration of 2,4-dichlorofluorobenzene would exceed its explosive limit (The explosive limit of 2, 4-dichlorofluorobenzene in air is 2-22%)[22]. The process is extremely unsafe,therefore it is a popular topic to research a new synthesis route with temperate condition easy to control and safe process and low cost.This research has carried on the generalized analysis to kinds of synthesis routes of 2,4-Dichlorofluorobenzene at home and abroad, and thought that the synthesis process taking o-Dichlorobenzene as raw material is a ideal one with its temperate condition easy to control and safe process.But At present its cost is higher than the process taking 2,4- dinitrochlorobenzene as raw material,So the synthesis process has not been applied to industrialized production.Research in three aspects is studied in this thesis: (1) Through many experiments,the effects of mixed acid nitratiny reagent and its constitute and the proportion of reactant,as well as the reaction temperature and time ,on the nitrating reaction were studied.(2) There are some problems in present industrialized production technology, such as using large amount of solvent, which is not be able to be recovered completely and polluting environment, higher reaction temperature and side reactions, and etc. In order to delete the solvent's pollution to surroundings and improve the yield of product, the method of Phase transfer catalysis fluorination without solvent was adopted,and the influence of several reaction variables on the yield was studied through Orthogonal Experiments of L9(34) .(3) The technology coupling chlorination with distillation is adopted in chlorination phase.it not only can promote reaction balance to raise the yield by distilling 2,4-dichlorofluorobenzene with reaction,but also raise the purity of production to purify produce. Through experimental result research, the affect factors such as the reaction temperature , the flux of chlorine,[NO2?]and solicitation reagent in the preparation of 2,4- dichlorofluorobenzene from 2-Chloro-1-fluoro-4-nitrobenzene via reactive distilled chlorate were investigated.The result of above three aspects indicates: (1) under these optimize conditions,the yield of nitrating reaction is 95.52%, the yield of phase transfer catalysis fluorination is 90.03%, the yield of chlorination is 87.5%,and the reaction total yield is 75.47%, which are higher than the yields reported, the purity of product is 98.5%.So it has enhanced the reaction total yield greatly and decreased its cost. (2) With CTMAB as catalyst, the influence of several reaction variables on the yield was studied through Orthogonal Experiments and the optimum reaction conditions of phase transfer catalysis fluorination were obtained .Under these conditions, the craft not only can alleviate environmental pollution and reduce the consumption of KF and solvent ,but also obtain 90.3% of the reaction yield,5.4% higher than that acquired by the optimum technology in presence of DMSO as solvent.So it has made the great progress.The method studied in this research from o-Dichlorobenzene is a ideal route to synthesize 2,4- dichlorofluorobenzene, which has temperate condition easy to control,safe process,low cost and good quality of products; The method of Phase transfer catalysis fluorination without solvent is better than present technology in presence of DMSO as solvent in many aspects; In a word,it is worth being promoted by the domestic correlative factories. The optimum technology can replace the process taking 2,4- Dinitrochlorobenzene as raw material.