Synthesis And Characterization Of Novel Heterocyclic Compounds Containing Halo-substituted Indole Skeleton

In a nature’s collection of biologically active heterocycles, halo-substituted indolesand its derivatives are an important class of nitrogen-containing heterocyclic compounds.Indoles have tremendous applications in dyes industry, spices, organic intermediates synthesis,pharmaceuticals, and synthetic pesticides. Therefore, it is a significant work to synthesis ofthe indole containing heterocyclic compounds. This thesis is mainly divided into five parts.In the first part, the recent advance on synthesis and applications of the indolederivatives were reviewed on the basis of the survey of the relevant literature over the pastdecade.In the second part,4-haloanilines as the starting materials were first underwent theSandmeyer reaction to give the corresponding halo-functionalized isatins1a-1c, which werefurther alkylated at the nitrogen atom to give2a-2o followed by in situ reduction usinghydrazine hydrate to obtain the oxindole products3a-3o.3a-3o were subjected to theacetylation reaction by the treatment with acetic anhydride in the presence of a catalyticamount of N,N-dimethylaminopyridine to afford the intermediates of2-acetoxy-3-acetylindoles, which were used in next step without further purifucation. Subsequently, thehydrolysis reaction of the arising ester functions of the intermediates was carried out intetrahydrofuran (THF) with the presence of5%NaOHaq. at room temperature to give thetargeted compounds3-acetyl-1-hydrocarbon-2-hydroxy-5-halo-indole4a-4o.In the third part, fifteen novel halo-substituted indole[3,2-b]quinoxaline derivatives5a-5o were synthesized in72.5%-88.7%yields through the reaction of N-substituted halo-isatins2a-2o with o-phenylenediamine in refluxing glacial acetic acid. As for the newlysynthesized products5a-5o, we further carried out their analysis of the fluorescence emissionspectrum.In the fourth part, eighteen novel5-hydrocarbyl-8-halo-5H-[1,2,4]triazino[5,6-b]indole-3-thiol derivatives7a-7j,9a-9h were synthesized in40.3%-75.5%yields through thereaction of N-substituted halo-isatins2a-2o or halo-isatins with thiosemicarbazide usinganhydrous potassium carbonate as a base in refluxing. In the fifth part,5-fluoro-isatin1a as a substrate was reducted in80%aqueous hydrazinehydrate to the preparation of5-fluoro-indol-one10in75%yield. Then5-fluoro-indol-one10was underwent the Vilsmeier-Hacck reaction to give1-(2-chloro-5-fluoro-1H-indol-3-yl)ethanone11, which was further alkyled to give1-(2-chloro-5-fluoro-1-alkyl-1H-indol-3-yl)ethanone12a-12e；In addition10could also reacted with aryl or hetaryl aldhydes to giveindole-containing chalcone dervatives13a-13h via Claisen-Schmidt condensation reaction in75.2-88.2%yields.All the synthesized compounds are novel and their structures were characterized by IR、1H NMR、13C NMR and MS.