Synthesis And Characterization Of 7-Bromo(Hydrogen)-5-(Methyl, Ethyl, Tert-Butyl) Hetero-Cyclic Compounds Containing Indole Skeleton

Indole ring system as one of the most ubiquitous heterocycles in nature, has been becoming an important structural component in many pharmaceutical agents, such as antidepressant, anticonvulsant, antifungal, antiviral and antiinflammatory, particularly in discovery of new antitumor agents. In recent years, increasing numbers of researchers from both industry and academia have embarked on the development of new indole-based small molecules as potent antitumor agents. Therefore, it is a significant work to the research on the synthesis reaction of the containing indole ring heterocyclic compounds. This thesis is mainly divided into five parts to present the synthesis and characterization of novel heterocyclic compounds containing indole skeleton.In the first part, the recent advance on the nature, synthesis, applications of indole and its derivatives were reviewed on the basis of the survey of the relevant literature over the past decade.In the second part, 4-alkyl-anilines as the starting materials were first underwent the Sandmeyer reaction to give the corresponding 5-alkyl-isatins(1a-1c), which were subjected to the conditions PEG-400 as green solvents, NBS as the brominating agent to give 7-bromo-5-alkyl-isatin(2a-2c).(1c),(2a-2c) were futher alkylated at the nitrogen atom to give(3a-3t);(3a-3e),(3p-3t) followed by in situ reduction using hydrazine hydrate to obtain the oxindole products(4a-4j).(4a-4j) were subjected to the acetylation reaction by the treatment with acetic anhydride in the presence of a catalytic amount of N,N-dimethylaminopyridine to afford the intermediates of 2-acetoxy-3-acetyindoles, which were used in next step without further purification. Subsequently, the hydrolysis reaction of the arising ester functions of the intermediates was carried out in tetrahydrofuran(THF) with the presence of 5%NaOHaq. at room temperature to give the targeted compounds 3-acetyl-1-hydrocarbon-2-hydroxy-5-alkyl-indole(5a-5j).In the third part, eighteen novel bromine-substituted indolo[3,2-b]quinoxaline derivatives(7a-7r) were synthesized in 78.8%-93.9 % yields through the reaction of 7-Br-5-alkyl-N- hydrocarbon(H)-isatins(2a-2c, 3f-3t) with o-phenylenediamine(6) in refluxing glacial acetic acid. As for the newly synthesized products(7a-7r), we further carried out their analysis of the fluorescence emission spectrum. We found that such compounds have good fluorescence properties, is expected to become a very promising light-emitting materials.In the fourth part, twenty-four novel bromine-substituted-5H-[1,2,4]triazino[5,6-b]ind- ole-3-thiol derivatives(9a-9x) were synthesized in 72.9%-93.9 % yields through the reaction of 5-(tert-butyl)indoline-2,3-dione(1c), 7-Br-N-H-5-alkyl-indoline-2,3-dione(2a-2c), 7-Br(H)-N-hydrocarbon-5-alkyl-indoline-2,3-dione(3a-3t) with thiosemicarbazide(8) in refluxing H2 O and 1, 4-dioxane mixed solvent, under anhydrous potassium carbonate alkali conditions.In the fifth part, 5-(tert-butyl)indoline-2,3-dione(1c) as a substrate was reducted in aqueous hydrazine hydrate to the preparation of 5-(tert-butyl)indolin-2-one(10) in 82.8% yield. Then 5-(tert-butyl)indolin-2-one(10) was underwent the Vilsmeier-Hacck reaction to give 1-(5-(tert-butyl)-2-chloro-1H-indol-3-yl)ethan-1-one(11), which was further alkyled to give 1-(5-(tert-butyl)-2-chloro-1-methyl-1H-indol-3-yl)ethan-1-one derivatives(12a-12e). Then the resulting compound 1-(5-(tert-butyl)-2-chloro-1-methyl-1H-indol-3-yl)ethan-1-one(12a) was further reacted with substituted isatins(13a-13n) to give the novel indole and quinoline-based alkaloid analogues 9-(tert-butyl)-6-methyl-6H-indolo[2,3-b]quinoline-11- carboxylic acid(14a-14n) in 34.6%-50.2 % yields.All the synthesized compounds(2a, 2c, 3g, 3h, 3j-3t, 4b-4j, 5a-5j, 7a-7r, 9a-9x, 10, 11, 12a-12 e, 14a-14n) are novel and their structures were characterized by IR, 1H NMR, 13 C NMR, and MS or HRMS.