| Visible light catalysis utilizes light to excite photocatalysts to initiate chemical reactions,enabling chemical bond cleavage and recombination.Compared with traditional heating reactions,visible light catalysis has the advantages of mild conditions,green cleaning and simple reaction device.Thanks to the development and utilization of photocatalysts,visible light catalysis has been widely applied in the field of organic synthetic chemistry.Chemists have reported a series of visible light catalytic reaction systems,and developed a variety of complex structure organic molecules synthesis methods,demonstrating the synthetic value and application potential of visible light catalysis.As important structural units,3,4-dihydroisoquinolin-1（2H）-ones and indolines are widely present in many biologically active molecules and have important physiological activities.In the field of military specialty drug research,many synthetic methods have been developed and successfully adopted in the synthesis of these two compounds.By introducing specific functional groups to 3,4-dihydroisoquinolin-1（2H）-one and indoline compounds,it is possible to further increase metabolic stability,improve cytomembrane permeability and change pharmacokinetic properties to enhance medication effect.It is of great significance for these two types of compounds to be applied in the development of military specialty drugs.The introduction of the substituent at the 3-position can significantly improve the biostability of the 3,4-dihydroisoquinoline-1（2H）-one compounds,and the adoption of fluoroalkyl groups can obviously ameliorate the hydrophobic property and metabolic stability of the indolines.Accordingly,this thesis aims to develop a highly efficient synthetic method for the development of 3-substituted-3,4-dihydroisoquinolin-1（2H）-one compounds and fluoroalkylindolines.The visible light catalyzed free radical synthesis reaction system was designed,and the following two aspects of research work were carried out:（1）A synthetic method for the formation of 3-methyl-3,4-dihydroisoquinoline-1（2H）-one compounds with no metal participation by visible light catalysis under mild conditions was developed.The optimum conditions for the selection of photocatalysts,solvents and additives were determined by using organic dye EosinY Na as photocatalyst,MeCN/H2O as solvent and DBU as additive.The reaction system is simple and convenient to operate at room temperature,the functional group of the substrate is compatible,and the reaction can be exte nded to the gram scale.Spectroscopic analysis experiments show the optical properties of the reaction system.Finally,through a series of mechanism validation experiments,the process of nitrogen free radical generation,free radical addition and free radical quenching was firstly elucidated.Furthermore,a reasonable reaction mechanism was proposed and the reaction mechanism was further verified by means of theoretical calculation.（2）A method for synthesizing fluoroalkylindolines with visible light catalysis and no metal participation is proposed.By screening a series of photocatalysts,solvents and additives,the optimal reaction conditions of organic dye EosinY Na as photocatalyst,MeCN/H2O as solvent and TMEDA as additive were determined.The reaction conditions are mild and the operation is simple,and several iodine fluorination reagents react well under the optimized system.The free radical process of the reaction is verified by free radical trapping experiments.Combined with the literature reports,the possible mechanism of the reaction was reasonably inferred.In this thesis,a simple synthesis method of 3-methyl-3,4-dihydroisoquinoline-1（2H）-one and fluoroalkylindoline compounds was established by means of visible light catalysis.The method has mild reaction conditions,good functional group compatibility and uses an organic dye EosinY Na as a photocatalyst.A reasonable reaction mechanism was inferred by spectral analysis and a series of mechanism validation experiments,which improved a novel synthetic route for these two compounds. |
