Synthesis Of Thiazole-fused Heterocycles Based On Multi-component Reactions

Nitrogen-containing and sulfur-containing heterocyclic compounds are widely found in nature,among which thiazole-containing heterocyclic compounds are an important branch.Among nitrogen-containing and sulfur-containing heterocyclic compounds,benzothiazole,imidazo[2,1-b]thiazole and other heterocyclic compounds are very important.They are not only the basic structural units of some drug molecules and functional materials,but also play an important role in medicine,pesticides,materials and other aspects.Benzothiazole derivatives are used as fluorescent indicators,ligands for catalytic reactions,anti-tumor drugs,anti tuberculosis drugs and other aspects.Some drug molecules,such as anticancer antibiotics,antidiabetics and inhibitors,contain imidazo[2,1-b]thiazole skeleton.Although a large number of literatures have been reported on the synthesis of the two kinds of compounds,it is still the goal of many researchers to seek green,simple and efficient research methods to synthesize functional nitrogen-containing sulfur-containing heterocyclic compounds.In this thesis,researches were mainly carried out on the synthesis of polysubstituted benzothiazole and imidazo[2,1-b]thiazole derivatives,the contents are as follows:(1)Synthesis of polysubstituted benzothiazole.Two kinds of structurally significant 2-(2-aminophenyl)benzothiazoles were selectively generated by the copper-catalyzed aerobic C-C bond cleavage of isatins.Morpholine served not only as a reactant but a promoter in the three-component assembly of 2-(2-aminophenyl)benzothiazoles.Also it proved to be an efficient additive for the formation of free amino 2-(2-aminophenyl)benzothiazoles.The reaction conditions are simple and highly chemical selective.One pot method is used to construct multiple C heteroatom bonds.Oxygen is used as a green oxidant,Our protocol provides a new way for the synthesis of polysubstituted 2-(2-aminophenyl)benzothiazole.(2)Benzo[4,5]imidazo[2,1-b]thiazole derivatives were synthesized by acid promoted cyclization.A series of benzo[4,5]imidazo[2,1-b]thiazole derivatives with important pharmacological properties were prepared by the cascade cyclization of benzimidazole with trans nitrostyrene and elemental sulfur.The method has the advantages including multi-component,simple operation,easily accessible raw materials,inorganic sulfur as the sulfur source,and no transition metal catalyst.