Study On Continuous Flow Synthesis Of Polyfluorophenols

Continuous flow chemistry is an emerging process technology in the field of synthetic chemistry,which has extensive and very important applications in many fields such as petrochemical,fine chemical,new drug process research and development,pharmaceutical and API process.Continuous flow chemistry technology demonstrates many advantages including safety,efficiency,accurate and controllable reaction parameters as well as thefeasibility of automation.These advantages are very unique especially for those reactions that involve the use of flammable or explosive reagents or have to be conducted under harsh conditions such such as high pressure or hightemperature.For this reason,in recent years,continuous flow chemistry technology involving organometallic reagents has received widespread attention from synthetic chemists and has made significant progress.However,there is still much room for improvement in this field.For example,the study of continuous flow chemistry in solidliquid mixed systems has always been a challenge in the development of such technologies.Polyfluorophenols are important in organic synthesis as key intermediates for drugs as well as liquid crystal materials.At present,the synthesis process of polyfluorophenol reported in literature mainly includes: synthesis of polyfluorophenol from polyfluoroaniline through diazotization hydrolysis;Polyfluorobromobenzene undergoes metallization reaction with Grignard reagent to generate polyfluorophenylboronic acid,which is then oxidized to synthesize phenol;Lithium esterification of trifluorobromobenzene;batch processes such as catalytic synthesis of precious metal reagents.These production processes have certain scale-up limitations,as well as many problems such as high costs,potential safety hazards,low efficiency,and serious pollution and waste.Therefore,it is necessary to develop a new,safe,efficient,green and economical production process route for the synthesis of polyfluorophenol.The research work of this paper is to develop a process method for synthesizing polyfluorophenol based on continuous flow technology with the participation of Grignard reagent.Taking the synthesis of 3,4,5-trifluorophenol as an example,the feasibility of the reaction route was first studied through a kettle reaction.Upon thorough condition optimizations,the product was successfully synthesized in high efficiency.The development of the optimized reaction conditions for the kettle reaction paves the way for the subsequent design and development of the continuous flow synthesis of 3,4,5-trifluorophenol.By setting up the flow system as well as adjusting the reaction parameters in detail,an efficient,safe,and continuous synthesis method of 3,4,5-trifluorophenol was successfully achieved using continuous flow chemistry technology.This work provides a solution for the further exploration of the synthesis of other fluorinated phenolic compounds or other important compounds based on continuous flow technology.