Study On Radical Trifluoromethyl(thio)lation Of Aromatic Alkenes

Fluorinated organic compounds are widely used in the fields of medicine,pesticide and material science due to their unique properties.The introduction of trifluoromethyl（sulfur）groups into drug molecules can greatly improve the physicochemical properties and biological activity of the core structure,making it more stable in acidity,lipophilicity,dipole moment,biological stability and metabolic stability.and many other aspects to meet application needs.In the field of pharmaceutical sciences,fluorinated organic compounds are also one of the main directions in drug design.In recent decades,aromatic compounds have made impressive achievements in the direction of trifluoromethyl（thio）lation reactions.However,traditional trifluoromethyl（thio）lation reactions still have some shortcomings,such as poor instability of trifluoromethyl（thio）lation reagents,difficult synthesis,more expensive and harsh reaction conditions.This thesis is dedicated to explore the design and synthesis of new trifluoromethyl（thio）lation reagents and new reaction methods for traditional reagents,including the synthesis of new oxime ester-based trifluoromethyl（thio）lation reagents and the use of cheap and easily available sodium trifluoromethanesulphinate（Na SO₂CF₃）and stable and easy-to-prepare silver trifluoromethylthio reagent（Ag SCF₃）to investigate the trifluoromethyl（thio）lation reactions of aromatic ethylene compounds.New approaches of trifluoromethyl（thio）lation of aromatic ethylenes were investigated in the following three aspects:In the first part,two photosensitizers trifluoroacetic acid oximes were designed and one of them,benzophenone O-trifluoroacetoxime,was successfully synthesized,while its properties in the direction of aryl ethylene trifluoromethylation reactions were initially explored.On the one hand,4,4’-bis（N,N-dimethylamino）benzophenone oxime was synthesized by the addition condensation reaction of 4,4’-bis（N,N-dimethylamino）benzophenone and hydroxylamine hydrochloride,which further underwent nucleophilic substitution reaction with trifluoroacetic anhydride to obtain trifluoroacetic acid-4,4’-bis（N,N-dimethylamino）benzophenone oxime esters.On the other hand,the synthesis of coumarin-based trifluoroacetic acid oxime esters was attempted in a three-step reaction using 4-diethylaminosalicylaldehyde as the raw material.Finally,the reaction properties of the new oxime ester-based trifluoromethylation reagents with unactivated aryl ethylene were initially explored under radiation of visible light.In the second part,C-H trifluoromethylation of aryl ethylene was explored to obtain a series of trifluoromethyl aryl ethylene analogues and a new method of trifluoromethylation reaction was developed.Using arylethene as the reaction substrate,and cheap and easily available sodium trifluoromethane sulfinate（Na SO₂CF₃）as the trifluoromethyl source,under the action of sodium bromate,the rapid construction of C_sp2-CF₃ was realized.Moderately low yields enabled the preparation of a series of trifluoromethyl aryl vinyl compounds.The research system can react well under mild conditions,and the operation is simple and easy to realize,which provides a simple and convenient method for the synthesis of trifluoromethyl aryl vinyl compounds.In the third part,the free radical trifluoromethylthiochemical reactions of arylalkyl difluoroethylene were investigated.A series of hydroxylated trifluoromethanesulphide and trifluoromethanesulphide coupling products were obtained by using safe and inexpensive ammonium persulphate as the oxidant and silver trifluoromethanesulphide as the trifluoromethanesulphide base source and reacting in dimethyl sulfoxide at 60°C for 14 h.The reaction substrate expansion study revealed that the system has good compatibility for both electron absorption and electron supply and can be used as a synthetic strategy for new fluorine-containing compounds with important theoretical research significance and potential applications.