Research On The Reaction Of Tri(Di)Fluoromethyl Diazomethane With Carboxylic Acids

Fluorine-containing compounds often possess desirable physical and biological properties and hence have wide applications in the area of pharmaceutical,material,agrochemical.Trifluoromethyl diazomethane and difluoromethyl diazomethane are important reagents for the easy introduction of CF₃ and CF₂ subunits.In this dissertation,we have investigated the important but overlooked reactivity of tri?di?fluoromethyl diazomethane with carboxylic acids and developed efficient methods for the synthesis of tri?di?fluoroethyl esters and N-tri?di?fluoroethyl imides.The major contents are as the following:Part one:We have found difluoromethyl diazomethane reacts readily with carboxylic acids;the conditions are operationally simple,mild,and tolerant of a broad range of functional groups.This allows the preparation of potentially useful difluoroethyl ester analogues of marketed drugs.For trifluoromethyl diazomethane,however,an unexpected interrupted esterification?a Mumm reaction?occurred to afford N-trifluoroethyl imides.DFT calculation was used to reveal this striking fluorine effect.Part two:Based on the aforementioned work,we have developed a general method for the access of N-difluoroethyl imides.The reaction of the carboxylic acids with difluoromethyl diazomethane was catalyzed by copper salt catalysts at 80^oC in acetonitrile,avoiding the competitive esterification.The features of this reaction are as the following:a)broad substrate scope and functional group compatibility.2)operational simplicity;3)no handling or transfer of difluoromethyl diazomethane.Part three:We have developed a general method for the synthesis of trifluoroethyl esters from the corresponding carboxylic acids,including sugars and marketed drugs.Hexafluoroisopropanol?HFIP?plays a key role in this transformation,by facilitating both the diazotization of trifluoroehtylamine and the ensuring esterification of carboxylic acids.We have also investigated the relationship between the concentration of HFIP and the reaction yield.The research conducted in this dissertation provides valuable information for the understanding the chemistry of tri?di?fluoromethyl diazomethane,and methods developed in this dissertation should find its application for the synthesis of important fluorine-containing compounds.