Study On Continuous Flow Double Diazotization Technology And Application In The Systhesis Of M-difluorobenzene

m-Difluorobenzene is an important pharmaceutical chemical intermediate,it can be used in the synthesis of Fluconazol,Diflunisal and Fluoroquinolone drugs,etc.A process for m-phenylenediamine double diazotization via a continuous-flow reator followed by Balz-Schiemann reaction to synthesize m-difluorobenzene was described.The author developed the continuous-flow process of m-phenylenediamine double diazotization reaction,and diazonium salt pyrolysis process was studied,improved the preparation process of m-difluorobenzene.The chapter one briefly introduced the research progress of diazotization reaction and continuous-flow,summarized the synthetic methods of m-difluorobenzene which were reported in literatures,and made the corresponding evaluation.The chapter two exploited the technology of using the continuous flow substep reaction technique for double diazotization reaction of m-phenylenediamine after the traditional kettle type diazotization process.After the optimized reaction contidition such as the amount of fluoroboric acid,hydrochloric acid,sodium nitrite,reaction temperature,residence time,the optimized yield of m-phenylenediazonium difluoborate could be reached to 87.0%.Due to the instability of diazonium chloride,the exothermal effect of the double diazotization proceduce was very large.The side reactions,such as decomposition and azo-coupling could occur.Aiming at the existing problem of the process,the process was redesigned as fluoboric acid directly added to the amine salt with better thermal stability diazonium tetrafluoroborate in-situ after the diazotization of m-phenylenediazonium.Through the optimization of reaction parameters,the optimized yield of m-phenylenediazonium difluoborate could be reached to 95.1%.Next,the reclamation of acidic wastewater which generated in the continuous-flow of m-phenylenediamine double diazotization reaction was conducted.The chapter three optimized the fluorodediazoniation process technology of the diazonium tetrafluoroborate.Firstly,the way of batch charging,reaction temperature,reaction time,agitation condition,and other factors were studied.The purity of the product was 99.7%with75.3%yield,Moreover,the author use the method of anhydrous inert solvent,solid dispersant,metal catalyst to optimize the pyrolysis process of m-phenylenediazonium ditetrafluoroborate.At last,the process of Fe₂O₃ as metal catalyst,sulfolane as cosolvent,the purity of the product was 99.8%with 88.6%yield.The author synthesized m-difluorobenzene through Balz-Schiemann reaction using m-phenylenediamine as the raw material.Continuous-flow technology was applied to double diazotization of m-phenylenediamine and the pyrolysis process of the fluoroborate diazonium salt was optimized.The overall yield of two steps was 84.3%which was higher than that in literature.