Synthesis And Characterization Of Novel Heterocyclic Compounds Containing Indole Skeleton

Indole and its derivatives are a very important class of importantnitrogen-containing heterocyclic compounds, widely present in natural products.Indoles have tremendous applications in dyes industry, spices, organicintermediates synthesis, pharmaceuticals, and synthetic pesticides. Therefore, itis a significant work to the research on the synthesis reaction of the containingindole ring heterocyclic compounds. This thesis is mainly divided into five partsto present the synthesis and characterization of novel heterocyclic compoundscontaining indole skeleton.In the first part, the recent advance on the nature, synthesis, applications ofindole and its derivatives were reviewed on the basis of the survey of the relevant literature over the past decade.In the second part, two powerful methods for the synthesis of indole-basedchalcone derivatives is described, involving the ultrasound-assisted orsolvent-free Claisen-Schmidt condensation reaction of3-acetyl-2-chloro-1-(4-chlorobenzyl)indole (1) and various aromatic aldehydes(2a-n) in the presence of KOH as base. The ultrasound-assistedClaisen–Schmidt condensation reaction was carried out using1,4-dioxane assolvent to give14structurally novel indole-based chalcones (3a-n) in71.7-92.4%. Alternatively, under solvent-free conditions, the products3a-n wereobtained in compaprable yields of75.2-88.2%.In the third part, eleven novel cinnamoyl substitutedindole[3,2-b]quinoxaline derivatives (6a-6k) were synthesized in70.9%-85.0%yields through the reaction of N-substituted isatins (4a-4e) orN-substituted-5-tert-butyl-isatins (4f-4k) with o-phenylenediamine (5) inrefluxing glacial acetic acid. In addition, we also attempt to use H2O as a solventinstead of glacial acetic and tetra-butylammonium bromide as catalyst in the reacton. Under the modified reaction conditons, indole[3,2-b]quinoxalinederivatives (6a-6e) were synthesized in comparable yields of77.5%-81.8%.Particularly, the advantageous aspect of the method using water as solvent isenvironmentally acceptable, avoiding the use of hazardous and toxic solvents.As for the newly synthesized products6a-6k, we further carried out theiranalysis of the fluorescence emission spectrum.In the fourth part,1-(4-chlorobenzyl)indolin-2-dione (8) was firstsynthesized in95.0%yield through the reaction isatin (7) with4-chlorobenzylchloride. Then, the resulting8was underwent the reduction reaction withhydrazine hydrate to give the corresponding1-(4-chlorobenzyl)indolin-2-one (9)in83.0%yield, which was further reacted with acetic anhydride using DMAP ascatalyst to afford the desired intermediate3-acetyl-1-(4-chlorobenzyl)indolin-2-yl-acetate (10) in65.4%yield. Theintermediate was further hydrolyzed to afford the corresponding1-(1-(4-chlorobenzyl)-2-hydroxyindolin-3-yl)ethanone (11) in78.0%yield,which upon reacting with diazomethane as the methylating agent give the corresponding1-(1-(4-chlorobenzyl)-2-methoxyindolin-3-yl) ethanone(12) in62.1%yield. The alkylation reaction of1-(4-chlorobenzyl)indolin-2-one (9) withthe alkylation reagents in refluxing acetone in the presence of anhydrous KOHas base produced the corresponding1-(4-chlorobenzyl)-3,3-disubstituted-indolin-2-one (13a-13e) in77.3-85.2%. Interestingly, when indolin-2-one wasunderwent the alkylation reaction by the treatment with4-chlorobenzyl chlorideas alkylation reagent in refluxing DMF in the presence of anhydrous KOH andKI as catalyst, the productsof3,3-dialkylation product (14) was also obtained in24.7%yield besides1,3,3-tri-alkylation compounds (15)(48.7%yield). Thestructure of the compound15was confirmed by the X-ray crystal structure.Subsequently, the resulting ether14was further reacted with acetic anhydride orchloroacetyl chloride using DMAP as catalyst to give the correspondingN-acetylated product16and N-chloro-acetylated product17in90.2%and72.7%yields, respectively.In the five part, the1-(2-chloro-1-benzyl-1H-indol-3-yl)ethanone (18) wasselected as starting material to synthesize1-(1-benzyl-2-ethoxy-1H- indol-3-yl)ethanone (19) in72.5%yield in the presence of KOH as catalyst andethanol as solvent. Then the resulting compound19was further reacted withsubstituted isatins (20a-20i) to give the novel indole and quinoline-basedalkaloid analogues6-benzyl-6H-indolo[2,3-b]quinoline-11-carboxylic acid(21a-21i) in47.2-56.8%yields.All the synthesized compounds3a-n,6b-k,9-17,19,21a-i are novel andtheir structures were characterized by IR,1H NMR,13C NMR, and MS.