Difluorocarbene-promoted In Situ Isonitrile Involved Construction Of Organic Nitrogen-containing Compounds

Organic fluorine chemistry has many years of history.Molecular structural units containing fluorine have special biological properties and play a very important role in the chemical and pharmaceutical fields.Therefore,scientists often selectively insert fluorine atoms or fluorine-containing groups into organic molecules in drug design and functional material development.Trifluoromethyl and difluoromethyl are the most extensive groups of fluorine-containing groups,of which difluoromethyl is the most special.Difluoromethyl is strongly lipophilic and electron-absorbing,and can also interact with hydrogen bonds to enhance the biological activity of the molecule.The incorporation of difluoromethyl into the structure of molecules can modify their biological activity,and has received increasing attention from chemical researchers in the design and development of novel drugs and pesticides.Many chemical reactions involving difluorocarbenes reagents have been reported in recent years,such as the difluoromethylation of phenols,thiophenols,carbonyls,olefins,etc.In the context of such research,this thesis selects suitable difluorocarbene reagents,constructs a series of products using difluorocarbene reagents and develops a series of reactions,working as follows.（1）The direct construction of quinolines from o-alkenylaniline has been achieved using inexpensive and readily available,non-toxic and environmentally friendly sodium chlorodifluoroacetate,in combination with a metal additive,and a base.A range of substrates was expanded under optimal reaction conditions.The isoselenocyanate intermediate generated from o-alkenylaniline produces 2-Se H quinolines by participating in nucleophilic addition to the o-alkenyl group when a combination of difluorocarbene precursor and selenium is present.Further nucleophilic substitution of the intermediate can be accomplished in the presence of an external nucleophilic reagent such as an amine or a thio group.This allows the one-step multi-component preparation of various 2-functionalised quinoline products from o-alkenylaniline and nucleophilic reagents.（2）Based on the synthesis of isonitrile by the reaction of difluorocarbons and primary amines,a sulphur additive is added to the reaction system.One-step multi-component synthesis of thiourea products from amines,difluorocarbenes and sulphur additives in the presence of sodium bicarbonate and phenanthroline as catalysts.The reaction involves the insertion of a secondary amine and a sulphur additive into the N-C bond to synthesize thiourea,exploring the conditions of the reaction,expanding the substrate under optimal reaction conditions and exploring the suitability of the reaction.（3）We used[DPPE]⁺[Cu（CF₃）₄]^-as a difluorocarbene reagent to release difluorocarbene,with amine and acid as study substrates and triethylamine as base,and reacted for 18 h in nitrogen with NMP as solvent at 100 ^oC to obtain amides.The conditions of this reaction were explored,the substrates were expanded under optimal reaction conditions,the applicability of the reaction was explored and its application in drug molecules was attempted.