Studies On Introducing Trifluoromethylthio And Difluoromethylselenium Groups Into Aromatic Rings By New Sulfur/selenium Reagents

Fluorine atoms play an important role in medicine,pesticides,materials,and other industries for its special properties.Since the advent of 5-fluorouracil,the research on fluorine-containing drugs has gradually increasing.At present,fluorine-containing drugs account for 30%of the total drug market share.How to introduce fluorinated groups is a hot topic for organic chemists and pharmaceutical chemists.However,there are still many shortcomings in the methods of introducing fluorinated groups with sulfur/selenium elements.Therefore,the development of new fluorinated group introduction reagents with sulphur/selenium elements is one of the focuses of organic chemists at present.Based on the work of predecessors and our laboratory,two fluorinated group introducing reagents were developed and their applications were studied.The first work is the trifluoromethylsulfonyl hydrazine protected by tert-butoxycarbonyl group,which is catalyzed by copper to achieve trifluoromethylthiolation of electron-rich aromatics.This reaction substrate has good applicability,the product can reach a medium yield,and can carry out gram-scale reaction indicated that has the potential for large-scale use.In this paper,the reaction mechanism was studied in detail.It was proved that trifluoromethyl sulfonyl hydrazine protected by tert-butoxycarbonyl group could produce bis-trifluoromethyl dithioether as an important intermediate in the reaction system,and then reacted with electron-rich aromatic compounds to produce corresponding thioether products.The second work is to use Se-(difluoromethyl)-4-methylbenzenesulfonoselenoate as a difluoromethylselenol reagent and proceed from aryl amine substrates by one-pot diazotization under visible-light photocatalysis.The preparation of aromatic difluoromethylselenide without metal participation is realized through aromatic radical pathway.The substrates of this reaction have good applicability,and the target compounds can reach medium to good yields.In addition,we also used this reagent to modify the fluorinated group of drug molecule directly in the later stage,and the yield was medium to good.In this paper,the reaction mechanism was studied in detail.It was proved that Se-(difluoromethyl)-4-methylbenzenesulfonoselenoate could produce difluoromethyl bisselenide as an important intermediate under light,and then reacted with aryl radicals to produce corresponding difluoromethylselenol products.