Study On Synthetic Technology Of 1, 2-Dichloro-4-nitrobenzene And 2-Chloro-1-Fluoro-4-Nitrobenzene

One kind of medicine bearing a fluorinated ring system 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 former material of 2-chloro-1-fluoro-4-nailine that is intermediate of the medicine bearing a fluorinated ring, the optimization or improvement of technology for preparing 2-chloro-l-fluoro-4-nitrobenzene (FCNB) is the key to improve the yield and quality of product and reduce the cost of production. There are some problems in present industrialized production technology, such as using large amount of solvent, which is not be able to recover it 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, another new synthesis route: l,2-dichloro-4-nitrobenzene (DCNB) reacted with highly active form of KF, in presence of a phase transfer catalyst (PTC), was discussed.First, the preparation of l,2-dichloro-4-nitrobenzene, which l-chloro-4-nitrobenzene (PNCB) reacted with chlorine in a self-designed chlorinator, in presence of Lewis acid catalyst, .was investigated. By means of the Orthogonal Experiments design and single factor experiments, the influence of several reaction variables on the yield were examined and the optimum reaction conditions under the intervallic operation were obtained, the yield of l,2-diehloro-4-nitrobenzene was 83.26%. 3.26% higher than that reported by references. Moreover, the kinetics of chlorination under the defined sets of conditions was also studied.The average apparent activation energy of this chlorination process in temperature range of 95℃-105℃ was 69.68kJ.mol-1 and the kinetics equation was:where [P] is concentration of l-chloro-4-nitrobenzene, mol.dm"3.Second, using a simple and inexpensive recrystallizing process, .a highly active form KF was obtained. It was observed to be considerably more efficient in preparing FCNB than the KF form sold in market. The yield of FCNB increased over the latter was about 25%.The conversion of DCNB to FCNB, a nucleophilic aromatic substitution type reaction, at 140-160℃, with the recrystallized KF and Cetrimonium bromide(CTMAB) as catalyst was examined. The influence of several reaction variables on the yield was studied throughOrthogonal Experiments and the optimum reaction conditions of phase transfer catalysis fluorination wetfe obtained .Under these conditions, the yield of FCNB was 92.23%, 6% higher than that acquired by present technology in presence of certain solvent.The kinetics of this phase transfer catalyzing fluorination process under a limited number of defined sets of reaction conditions was also studied. The average apparent activation energy of this process in the temperature range of 145℃-165℃ was 72.87kJ.mol-1 and the kinetics equation was:where [D] is concentration of 1,2-dichloro-4-nitrobenzene, mol.dm-3. The results were obtained above can provide some design parameters and theoretical background for engineering design and industrialization of products.