Synthesis And Characterization Of Heterocyclic Compounds Containing Iodo-Substituted Indole Skeleton

Indole-containing heterocyclic compounds as a class of the most important organic molecules are widely presence in natural products.Due to their wide range of biological and pharmacological activities indole-based heterocycles have been more and more applied in the fields of medicine and organic chemistry.In recent years,the construction of new small molecules containing the indole moiety have played an important role in the development of new drugs.Therefore,it is interesting and meaningful work for the design and synthesis of structurally new indole-based heterocyclic compounds.This thesis is mainly divided into five parts:In the first part,the recent advance on synthesis and applications of heterocyclic compounds containing halogenated indole skeleton were reviewed on the basis of the survey of the relevant literature over the past decade.In the second part,5-iodoindolin-2-one 2,obtained by the reduction of 5-iodoisatin 1 with hydrazine hydrate,was subjected to formylation and acetylation reaction by using N,N-dimethylformamide or N,N-dimethylacetamide with POCl3 to form Vilsmeier reagent to afford the corresponding 2-chloro-5-iodo-1H-indole-3-carbaldehyde 3a and 3-acetyl-2-chlorine-5-iodoindole 3b,respectively.Subsequently,the resulting 3a and 3b were respectively alkylated at the nitrogen atom to give the corresponding N-alkyl-2-chloro-5-iodo-3-indole-carbaldehydes 4a-4e and N-alkyl-3-acetyl-2-chloro-5-iodoindoles 4f-4j.The newly synthesized 4a-4j were further underwent the condensation reaction with guanidine nitrate to give the unreported 9H-pyrimido[4,5-b]indol-2-amine 5a-5j in acceptable yields of 40-66%.In the third part,5-(methyl/ethyl/tert-butyl)isatin and 7-(methyl/ethyl)isatin were firstly iodinated to obtain the corresponding 7-iodo-substituted isatins 6-10,among which 6-10 as well as 1 were further underwent the alkylation reaction at the nitrogen position to give the corresponding N-alkyl-5-iodoisatin 1a~1e,N-alkyl-5-(methyl/ ethyl/tert-butyl)-7-iodoisatins 6a~6e,7a~7e,8a~8e and N-alkyl-7-(methyl/ethyl/ tert-butyl)-5-iodoisatins 9a~9e,10a~10e,respectively.Compounds 1a~1e,6a~6e,7a~7e,8a~8e,9a~9e,and 10a~10e were then further subjected to the condensation reaction with 1,2-diaminobenzene in refluxing acetic acid to afford a series of novel 6H-indolo[2,3-b]quinoxaline derivatives 11aa~11bd in good yields of 78-88%.In the fourth part,1-alkyl-5-iodoisatin 1a~1e,1-alkyl-5-(methyl/ethyl/tert-butyl)-7-iodoisatins 6a~6e,7a~7e,8a~8e were used as the substrates to conduct the condensation reaction with thiosemicarbazide in refluxing 1,4-dioxane as the solvent with the presence of potassium carbonate as the base to furnish new 5H-[1,2,4] triazine[5,6-b] indole-3-thiol derivatives 12a~12t.In the fifth part,the compound 3-acetyl-2-chloride-1-methyl-5-iodoindole 4f as the starting substrate reacted with isatin derivatives in 10% aqueous ethanol media with the presence of KOH as the base to give a series of 9-iodine-6-methyl-6H-indole[2,3-b]quinoline-11-carboxylic acid derivatives 13a~13i.All the newly-synthesized compounds(5a~5j,11aa~11bd,12a~12t,13a~13i)are novel and their structures have already been characterized by IR,1H NMR,13 C NMR and HRMS.