Study On Visible-Light-Induced Tri/Difluoroalkylation Of Benzo[d]isoxazoles

As the most abundant halogen element in the earth's crust,the fluorine atom contains only 12 species in natural organic matter.At the same time,the fluorine atom is an element having a radius similar to that of a hydrogen atom and having the strongest electronegativity.After introducing a group containing one or more fluorine atoms into an organic molecule,the fluorine atom has physical,chemical,and biological properties to its parent molecule.With great changes,the research on organic fluorine chemistry has gradually become a focus in the fields of medicine,pesticides,materials,and life sciences.As an important biomedical molecular skeleton,benzo[d]isoxazoles has extremely high biological activity and drug properties.It is found in a large number of drugs such as tranquilizers and anticancer antibiotics.However,its related research has been relatively scarce and lacking in recent years.And related research is based on the destruction of its original structure.Visible light catalysis has been widely used in organic synthesis in recent years due to its advantages of safety,high efficiency,low energy consumption,atomic economy,and good chemical selectivity.It has become a reliable and effective method in organic synthesis.Therefore,this dissertation combines the advantages of photocatalytic methods to study the functional modification of fluoroalkylation of benzisoxazole.The main research content is as follows:(1)Visible-light-induced trifluoroalkylation of benzo[d]isoxazolesIntroduction of the trifluoromethyl group(CF3-)into the drug molecule can increase its chemical and metabolic stability,enhance its lipophilicity,bioavailability,and ability to bind to proteins,so the trifluoromethyl group(CF3-)is often introduced as a medicine or pesticide molecule.Therefore,in the first part of this thesis,combining the light-induced organic reaction method,the optimal reaction conditions were obtained by optimizing the conditions of photocatalyst,base,and solvent,and the high yield of benzoxazole was successfully achieved.Trifluoroalkylation.At the same time,the structure of the product was characterized and analyzed by means of nuclear magnetic resonance(NMR),mass spectrometry(MS),elemental analysis(EA),infrared(IR)and single crystal X-ray diffraction(CCD).Subsequently,the universality of the reaction conditions was verified by substrate extension,and the reaction mechanism was discussed based on experimental phenomena and literature reports.(2)Visible-light-induced difluoroalkylation of benzo[d]isoxazolesDifluoromethylene is often used in the design of medicines,pesticides,materials,and bioactive molecules.On the one hand,due to its strong metabolic stability,difluoromethylene(-CF2-)can often be seen as similar to oxygen(O),carbonyl(-CO-)and methylene(-CH2-)organisms.The electron isosteresis;on the other hand,because in the functionalized difluoromethyl substituent(RCF2,R ? H),the electron-withdrawing effect of the difluoromethylene group affects the electronic properties of the adjacent functional group R,chemical properties and reactivity.However,the study of similar difluoromethyleneation is relatively rare compared to the rapidly developing trifluoromethylation.At the same time,taking into account the lack of defects in the application of fluoroalkylated products in the first part of the paper,the second part of the study based on the first part of the research situation,optimized to explore the influence of photocatalyst,base,solvent and other conditions on the reaction,to obtain the best reaction conditions,the difluoroalkylation of benzisoxazole was successfully achieved,and the substrate was selectively expanded.According to experimental phenomena and literature reports,the reaction mechanism was discussed.In addition,reference literature methods further modify the difluoroalkylation products to achieve the goal of product synthesis and conversion applications.