Synthesis Of Difluoromethoxy-containing Aromatic Boronic Acids

Difluoromethoxy compounds are an important class of fluorine-containing intermediates,which can improve the biological activity of compounds while retaining the biochemical properties of fluorine atoms.Boric acid compounds containing difluoromethoxy aromatic ring are an important synthetic building block.The introduction of difluoromethoxy functional groups into drug molecules can effectively improve the lipophilicity and biological activity of the molecules,thereby enhancing the efficacy of the drug.In this subject,the synthesis of difluoromethoxy aromatic boronic acid compounds was studied based on the structural characteristics of different substrates.The route of introducing difluoromethoxy groups into organic molecules by different difluorocarbene reagents was investigated,and sodium difluorochloroacetate was finally determined as the fluorine source.Regarding the introduction of borate groups,the method of catalyst catalysis is mainly used,and three metal complex catalysts containing palladium(II),iridium(I)and nickel(II)are investigated,and the introduction of palladium catalyst into borate is determined Group method,this method has good universality for aromatic ring substrates.When introducing the boric acid group,the method of obtaining the target compound by the one-step reaction of n-butyllithium and the palladium catalyst was first introduced into the borate group and then redoxed to boric acid to obtain the target compound.This subject also investigated the influence of different functional groups in the substrate on the reaction.It was found that the introduction of electron-withdrawing groups would reduce the reaction yield,and the substrate with electron-donating groups had a higher yield.On this basis,the feed ratio of the raw materials and various reaction conditions in the synthesis step were investigated in detail,and a better synthetic route for the synthesis of the target compound was obtained.12 Target compounds were synthesized in this project,including 4 pyridine rings and 8 benzene rings.The target products were all characterized and confirmed by ~1H NMR,MS and IR.This method has a series of advantages,such as simple and easy raw materials,short route,simple operation,high yield,and easy to realize industrialized production.This research provides a technological reference for the synthesis of difluoromethoxy aromatic boronic acids,and lays a foundation for the synthesis of new fluorine-containing compounds.