Synthesis And Characterization Of Heterocyclic Compounds Based 7-ethylindolin-2-one

Indole ring system as one of the most ubiquitous heterocycles in nature showed potent biological and pharmacological activity activities.Many pharmaceutical agents containing the indole structural component display antidepressant,anticonvulsant,antifungal,antiviral and anti-inflammatory properties.Particularly,many newly-developed antitumor drug also contain the indole moiety.As a consequence,the synthesis of new families of indole-based heterocyclic compounds is a significant and meaningful work in organic synthesis field.Herein,we conducted the synthesis of 7-ethylindole based heterocycles.The thesis is mainly divided into five parts as follows:In the first part,the recent advance on the nature,synthesis and applications of indole derivatives were reviewed on the basis of the survey of the relevant literature over the past decade.In the second part,7-ethylindoline-2,3-dione(1)as the raw material was subjected to the reduction reaction with hydrazine hydrate to give 7-ethylindolin-2-one(2).The resulting 2 was then subjected to the ClaisenSchmidt condensation reaction with various aromatic aldehydes,heteroaromatic aldehydes as well as ferrocenecarboxaldehyde(3a-3t)in the presence of piperidine as base and ethanol as solvent to afford the corresponding(Z)-3-benzylidene-7-ethylindolin-2-one derivatives(4a-4t).In the third part,7-ethylindolin-2-one(2)was first underwent the recation with 2-chloroacetyl chloride to give the corresponding 5-(2-chloroacetyl)-7-ethylindolin-2-one(5).The resulted 5 was then underwent the Handseh reaction with thioamide as well as thiourea in the mixted solvents of tetrahydrofuran(THF)and ethanol at reflux tempetature to afford the desired 7-ethyl-5-(2-alkylthiazol-5-yl)indolin-2-one(6a-6v).In the fourth part,7-ethylindolin-2-one(2)was first subjected to the Vilsmeier-Haack reaction to give the corresponding 2-chloro-7-ethyl-1H-indole-3-carbaldehyde(7a)and 3-acetyl-2-chloro-5-ethyl-1H-indole(7b),which were then underwent the alkylation reaction in refluxing acetone to obtain the corresponding N-alkyl-2-chloro-7-ethyl-3-formyl/acetylindoles(8a-8j)with good yields.Finally,compounds 8a-8j were reacted with hydroxylamine hydrochloride to produce the corresponding oximes(9a-9j).In the fifth part,N-alkyl-7-ethylindoline-2,3-dione(10a-10e),which were obtained by the N-alkylation of 7-ethylisatin(1)was conducted the reduction reaction by the treatment using hydrazine hydrate to obtain the oxindole products(11a-11e),which were further subjected to the acetylation reaction with acetic anhydride in the presence of a catalytic amount of N,N-dimethylaminopyridine(DMAP)to afford the intermediates of 2-acetoxy-3-acetylindoles.The intermediates were directly treated by 5% aq.NaOH in tetrahydrofuran(THF)at room temperature without isolation and purification to give the targeted compounds 3-acetyl-1-hydrocarbon-2-hydroxy-7-ethyl-indole(12a-12e).All the synthesized compounds are novel and their structures were characterized by IR,1H NMR,13 C NMR,and MS or HRMS.