New Radical Reaction Of N-sulfonyl-1,2,3-triazole

N-sulfonyl-1,2,3-triazole is an important class of organic synthon,which is widely used in the construction of nitrogen-containing heterocyclic compounds.N-sulfonyl-1,2,3-triazole can form nitrogen anions,carbene intermediates which are formed by heating,Lewis acids,metals,etc.,and the formed carbene intermediates then occur 1,3-Intercalation,cyclopropanation,ring expansion,formation of Yelide,rearrangement and other reactions,but there are few reports of new reactions in free radical chemistry.This may be due to the fact that there is no effective method to control the generation of such triazole radicals.In this paper,through unexpected scientific discoveries,a new type of radical C-H functionalization reaction based on N-sulfonyl-1,2,3-triazole was developed,and a new strategy based on S_N2-like reaction mechanism was developed.Controlled formation of ring N substituted triazole free radicals.We have developed not only enables efficient,green and environmentally friendly synthesis of triazole derivatives with important biological activities,but also achieves high regioselectivity.The thesis includes five chapters:The first chapter introduces the research background and related research progress of N-sulfonyl-1,2,3-triazole chemical structure characteristics,chemical conversion,medicinal chemistry application.It mainly introduces the conversion of triazole as a carbene precursor and the chemical conversion to form nitrogen anions,as well as the challenges and necessity of developing free radical reactions.Chapter 2 introduces the highly regioselective free radical reaction of N-sulfonyl-1,2,3-triazole in air.This reaction only needs oxygen as an oxidant,and a high N~2 selective triazole derivative can be achieved without a metal catalyst,with a yield of up to 93%,and no N~1 selective product is observed in the reaction,showing high regioselectivity.At the same time,we conducted an in-depth exploration of the reaction mechanism using controlled experiments and DFT theoretical calculations,and found that the initiation of carbon radicals can attack the N-sulfonyl-1,2,3-triazole ortho-N atom to initiate the homolysis of the N-substituted sulfonyl group.Leaving in the form of free radicals,undergoing a S_N2-like reaction mechanism,generating triazole free radicals and further converting into N~2 selective products,the steric hindrance effect in the reaction process leads to high regioselectivity.In the third chapter,because the N~2-1,2,3-triazole skeleton plays an important role in the discovery of new anti-cancer drugs,we used the synthetic method developed in Chapter 2 to synthesize more N~2-1,2,3-triazole derivatives,and introduces the synthesis of raw materials of some compounds in detail.In Chapter 4,we conducted a preliminary phenotypic biological activity screening of the obtained compounds and found that these compounds have a good inhibitory effect on colorectal cancer cells HCT116 and osteosarcoma cells SJSA-1,providing a new anti-cancer drug may.Chapter 5 is the experimental part..In this paper,based on the chemical properties of N-sulfonyl-1,2,3-triazole,N-sulfonyl-1,2,3-triazole and tetrahydrofuran were studied by means of tetrahydrofuran/tetrahydrothiophene free radical initiation.The free radical reaction of tetrahydrothiophene has developed a new strategy of controlled initiation of ring N substituted triazole radicals,expanded the new chemical field of ring N substituted triazole radicals,and developed more The new reaction of free radicals replacing triazole laid the foundation.