Synthesis Of 2H-indazole Direct Alkylation And 3-sulfonylthioflavone

This dissertation contains two chapters.Chapter one:As a bicyclic fused ring of pyrazole and benzene ring,2H-indazole is a dominant skeleton widely used in pharmaceutical chemistry and material science.The molecular shape and electrostatic distribution of 2H-indazole play an important role in the interaction with enzymes and receptors,so it exists in many commonly used drugs and bioactive molecules.The indozole compounds have shown good activity and therapeutic effect in the treatment of many diseases.Therefore,derivatization with indazole as the mother nucleus is a common structural transformation strategy for pharmaceutical chemists.The development of new methods for derivatization of indazole has also become one of the major challenges in the field of pharmaceutical chemistry.At present.The oxoalkylation,aromatization,acylation,trifluoromethylation,nitration,thiocyanidation,sulfonylation,phosphorylation and bromination of indazole were developed.However,there is little research on the direct alkylation of 2H-indazole.In this dissertation,a green synthesis method of direct alkylation of 2H-indazole C3 was developed by coupling decarboxy C（sp~3）-C（sp~2）between2-aryl-2H-indazole and alkyln-hydroxy-phthalimide ester with dimethyl carbonate as a unique green medium.We designed a direct alkylation reaction with transition-metal-free in visible light catalysis by using 2-phenyl-2H-indozole as the model substrate and cyclohexyl NHPI as the alkyl free radical donor.Then,the photocatalyst,solvent,alkali were screened and optimized respectively to determine the optimal reaction conditions.Then,the application range and sensitivity of substrate were studied.The alkylation of 2H indozole skeleton can be completed quickly and efficiently through the visible light catalysis method without metal participation.In addition,the method has been successfully applied to the late structural modification of carboxy drugs,which can introduce the indazole skeleton rapidly.We also constructed a new type of unnatural amino acid by using this method.Chapter two:Sulfone has unique biological and pharmaceutical activities,plays an important role in the fields of drugs and pesticides,and is also a multifunctional synthetic intermediate in organic synthesis.Thioflavonoid derivatives,as their bioelectronic and other platoons,also show good biological properties.They are often found in many molecules with drug activity,and they have received great attention due to their unique biological activity in antibacterial,antitumor and antimalarial drugs and other drugs.The traditional methods of thioflavone synthesis mostly need heavy metal catalysis and harsh reaction conditions.In this chapter,we developed sulfonation of ethynone and sulfonylhydrazine mediated by Na I/TBHP,and obtained 3-sulfoalflavones under mild reaction conditions.We designed a reaction for the synthesis of 3-sulfonylated thioflavonoids without the participation of transition metal by using methylthioalkynone and ptoluenesulfonyl hydrazide as model substrates.And then screened and optimized the model reaction by evaluating different iodide reagents,oxidants,oxidants equivalent and solvents,and finally determined the reaction conditions and the applicable range of the substrate.Compared with the traditional methods,the method has the characteristics of metal-free,simple operation,mild condition,short reaction time and wide functional group capacity.The conversion of the synthesized 3-sulfoyl thioflavone intoβ-carbonylsulfone also show that it can be used as a useful building block in organic synthesis,which lay a foundation for the later modification and biological activity research of the drug.