Cu(Ⅱ)-PIFA Mediated Cascade Reaction Of Indole And Imidazole Radicals And Synthesis Of Oxadiazoles

In organic synthesis,the application of radical chemistry into the synthesis and design of new reactions is one of the directions that many chemists are exploring at this stage.Despite the continued popularity of radical reactions in organic synthesis,the field is far from exhausted and much remains to be explored.For example,nitrogen-centered radicals have not received the attention they deserve,which have considerable synthetic potential,and remains largely underappreciated because the generation of nitrogen-centered radicals is relatively difficult compared to the generation of carbon-centered radicals.Among the methods to generate nitrogen-centered radicals,strategies to directly convert N–H bonds to the corresponding nitrogen-centered radicals are rarely reported because most of them require harsh reaction conditions.Considering that compounds containing imidazole and indole skeletons occupy an important position in organic chemistry,medicinal chemistry,pharmacology,toxicology and other disciplines,if we can start from simple and readily available imidazole and indole substrates,through the radical strategy to construct complex and diverse nitrogen heterocyclic structures in one step is not only in line with the concept of green chemistry and sustainable chemical development,but also can be applied to the synthesis of a series of complex molecules such as drug molecules,natural products and functional materials.In addition,among nitrogen-containing heterocyclic compounds,oxadiazoles are special structural compounds with broad pharmacological activities,and have shown great potential as therapeutic agents for various diseases.Based on the above,this dissertation will combine the properties of copper catalysts widely used in radical chemistry to elaborate the direct conversion of N-H bonds to the corresponding nitrogen-centered radicals and apply it to the construction of complex molecules,while at the same time A new class of 5H-[1,2,4]oxadiazolo[4,5-a]pyrimidine derivatives were prepared,characterized and tested.This dissertation including 4 chapters.The first chapter mainly introduces the development of nitrogen radical chemistry in recent decades,the method application of radical cascade reaction,the application of copper catalyst and hypervalent iodine reagent in radical synthesis chemistry and the synthesis of oxadiazoles.In the second chapter,a one-pot multi-component cascade reaction strategy between benzimidazole,indole,and NXS was developed through a combination of Cu（II）catalyst and PIFA mediated by initiating the formation of benzimidazole nitrogen-centered radicals.This strategy realizes the formation of nitrogen radicals centered on the aromatic nitrogen atoms in the ring for the first time,and on this basis,the radical-level combined synthesis of substituted 3-haloindole-benzimidazole compounds is realized for the first time.It provides a reference direction for the subsequent work on the direction of nitrogen radicals.In the third chapter,on the basis of the work in Chapter 2,the combination of Cu（II）catalyst and PIFA was used to successfully realize the formation of（benz）imidazole nitrogen center free radical,and then a one-pot multi-component cascade reaction strategy between（benz）imidazole,indole and Na N₃ was realized.This strategy broadens the methods available for the formation of nitrogen-centered radicals in compounds containing N–H bonds,and two classes of azide-biindole compounds as well as a class of biindole compounds were successfully synthesized for the first time.In the fourth chapter,a new class of 5H-[1,2,4]oxadiazolo[4,5-a]pyrimidine derivatives were prepared,characterized and tested,the synthesis method was optimized by screening the reaction conditions,and a reasonable mechanism was proposed.On this basis,their antibacterial and anticancer potentials were tested against 13 strains and 5 human cancer cell lines,respectively,and some new compounds containing 5-bromopyrimidine moieties showed weak to moderate antibacterial efficacy against Gram-positive strains.In addition,it also exhibited selective antiproliferative activity against the HCT116 cell line.