Study On The Synthesis Of Isoindolinone Compounds And Sulfonylation Of Quinoline N-Oxide

Five-membered heterocyclic skeleton of isoindolinone and heteroaromatic sulfone compounds are widely found in various natural products,because of its high pharmacological and biological activity,which is widely used in medicine,materials and organic pigments,and other industries.Therefore,it is of great theoretical significance and broad application prospect to explore the efficient and green synthesis method of these skeleton compounds.This thesis focus on the methodological studies of the C-H activation and ring-closing reaction which were initiated quinoline compounds as a targeting group and the C-H activation reaction after modification of quinoline compounds.The main contents include two parts,which are divided into four chapters to discuss.In the first chapter we discuss some of the application and synthetic research progress of isoindolinone compounds,which include non-metallic catalysis and metal catalysis and C-H activation of compounds with dentate groups.And the transition metal catalyzed C-H activation and ring-closing reaction of the compounds with the dentate group is a highly efficient and easy way to build five-ring skeleton,and has been a wide range application in the synthesis of a variety of existing heterocyclic skeleton.Through the comprehensive discussion on the progress of the research on N-heterocyclic compounds,we have been able to proceed with the next methodological work.In the second chapter,on the basis of the previous synthetic methods,we use aryl acyl chloride and aldehyde as the starting materials,each through a simple reaction to quickly obtain aryl aramid and gededium bromide substrate,and then systematically studied the C-H activation and ring-closing reactions of the two-part coupling substrate catalyzed by Ni???/ Ag???and optimized the reaction conditions.The synthesis of 18 target compounds was achieved with the highest yield of 81%.Moreover,through a series of explored experiments of mechanism,the possible reaction mechanism were put forward to explain the reaction process of the method.The third chapter is a review of the synthesis of sulfone compounds and the progress of the research on the C-H activation of quinoline N-oxide.This paper lists the representative literature in these years to describe the evolving integrated profile of quinoline skeleton sulfonation reaction.By combing the C-H activation,especially the sulfonylation reaction of the different sites of the quinolines,We summarize the advantages and disadvantages of the various reactions in different methods,which provides a reference for the next step works of C-H activation.In the fourth chapter,we developed a method for the preparation of heterocyclic aromatic sulfones by that KI/K₂S₂O₈ catalyzed quinoline C-2 sulfonylation on the basis of literature research.Quinoline was used as the starting material,and the quinoline N-oxide substrate was prepared by a simple reaction;Then,the C-H activation reaction was carried out and the reaction conditions and the adaptability of the substrate were investigated and discussed in detail,the 15 target compounds with the yield of 49% to 85% were obtained;And then a possible reaction mechanism was discussed through a series of explored experiments of mechanisms.This method is simple and efficient,and has great advantages in the related sulfonylation modification,which provides a methodological basis for the further study of sulfone skeleton compounds.In this thesis,33 compounds have been synthesized,these compounds are identified by ¹H,¹³ C NMR and mass spectrum.