Selenization And 1,6-Addition Reaction Of 2-(Bromodifluoromethyl) Benzothiazoles

Due to the unique properties of difluoroalkyl（-CF2-）,its introduction into organic molecules will significantly improve the physical and chemical properties of the parent molecules,thus strengthening the role of bioactive molecules in the human body.Therefore,in recent years,people have gradually developed a series of synthetic methods of difluoroalkyl compounds,which have been widely used in medicine,agrochemical and functional materials.2-（bromodifluoromethyl）benzothiazole compounds are a new type of benzothiazole ring compounds containing CF₂Br.Considering the huge potential biological activity of benzothiazole derivatives,it is necessary to further study the reaction of 2-（bromodifluoromethyl）benzothiazole.At present,2-（bromodifluoromethyl）benzothiazole compounds can introduce difluoroalkyl into organic molecules through cross-coupling reaction,aldol reaction,olefin series cyclization reaction and S_RN1 reaction of thiophenol,and introduce benzothiazole structural units at the same time.Therefore,starting with the substrate design,this paper studied the following three methods to construct difluoroalkyl-linked benzothiazole derivatives:1.Study on the efficient synthesis of 2-（bromodifluoromethyl）benzothiazoleAn efficient method for debromination and selenization of 2-（bromodifluoromethyl）benzothiazole and diaryl diselenides catalyzed by copper was developed.The optimum conditions of the reaction are as follows:at 100°C,using 2-aminobenzenethiol as substrate,5equivalents of difluorobromoacetic acid as catalyst and raw material,chlorobenzene as solvent,a yield of up to 88%can be obtained after 18-48 hours of reaction.The method has the advantages of mild reaction conditions,simple operation,one-step reaction and a wide range of substrates.2.Copper-catalyzed debromination and selenization of 2-（bromodifluoromethyl）benzothiazole with diaryl diselenidesAn efficient method for copper-catalyzed debromination of 2-（bromodifluoromethyl）benzothiazole and diaryl diselenides was developed.The optimum conditions of the reaction are as follows:Cu（OAc）₂（20 mol%）,KOH（1.5 eq）,1,10-phenanthroline（40 mol%）,and the yield of 48%-85%can be obtained by reacting in 100°C for 13 hours in DMF solvent.The reaction can synthesize the selenyl derivative of difluoromethylene benzene in good to excellent yield.By adding TEMPO as free radical trapping agent,we basically excluded the reaction mechanism of free radicals,and proposed a possible mechanism according to the reports in the literature.3.1,6-addition reaction of 2-（bromodifluoromethyl）benzothiazole and p-benzoquinone methideA new method for the synthesis of difluoromethylene compounds from 2-（bromodifluoromethyl）benzothiazole and p-methylene benzoquinone（p-QMs）by 1,6-conjugated addition was developed.The optimum conditions of the reaction are as follows:Cu（50 mol%）,Cu（OAc）₂（20 mol%）,NMP（1.0 m L）,DIPEA（4.0 eq）,reaction at 100°C for4 hours,a yield of 60%and 80%can be obtained.The reaction has a wide range of functional group compatibility,various substrates can maintain more than medium yield,and the halogen in the molecule can be further modified,which increases the possibility of heterocyclic structure diversity.it shows the potential for further application in the research of medicine and agrochemistry.