Triazole-fused indolo[2,3-a]carbazoles: synthesis,structures, and properties

The synthesis, structure, and photophysical and electrochemical properties of triazole fused indolo[2,3-a]carbazole derivatives 2 - 5 are reported. The key step involved in the synthesis of triazole fused indolo[2,3-a]carbazole derivatives is the Cadogan ring closing reaction. 2-Hexyl-5,6-dinitro-2H-benzo[d][1,2,3]triazoles having 4,7-diaryl capping were subjected to the Cadogan cyclization reaction to obtain compounds 2-5 . In contrast to thiadiazole-fused indolo[2,3-a]carbazole 1 , bromination of triazole-fused indolo[2,3-a]carbazole 4 afforded only meta-dibrominated product with respect to the nitrogen of fused pyrrole rings on treatment with both N-bromosuccinimide (NBS) and elemental bromine. These compounds showed positive solvatochromism in their emission spectra. Incorporation of electron-donating substituent in the indole moiety resulted in the elevation of the highest occupied molecular orbital (HOMO) level. Density functional theory (DFT) calculations were performed to support the experimental findings.     

A new approach to the synthesis of pyrido[4,3-<Emphasis Type="Italic">b</Emphasis>]indole derivatives (γ-carbolines) <Emphasis Type="Italic">via</Emphasis> cyclization of enamino dinitriles

Reactions of 2-dicyanomethylidene-3-ethoxymethylidene-2,3-dihydroindole with various amines afforded enamino dinitriles and the corresponding pyrido[4,3-b]indoles (γ-carbolines). 3-Amino-4-cyano-5H-pyrido[4,3-b]indole reacted with cyclohexanone to give pentacyclic 13-amino-2,3,4,12-tetrahydro-1H-benzo[b]indolo[2,3-f]-1,8-naphthyridine. Alkylation of pyrido[4,3-b]indoles with various alkylating agents was studied.     

Novel indole syntheses by ring transformation of β-lactam-condensed 1,3-benzothiazines into indolo[2,3-b][1,4]benzothiazepines and indolo[3,2-c]isoquinolines

ortho-Nitrophenyl-substituted condensed 1,3-benzothiazines proved to be a useful core unit in indole syntheses under non-reductive conditions. Thus, the treatment of ortho-nitro-2-aryl-2a-chloro-4H-azeto[2,1-b][1,3]benzothiazin-1-ones with sodium methoxide in methanol provided indolo-1,4-benzothiazepines via a novel rearrangement. Through the sulfur extrusion reaction of indolo[2,3-b][1,4]benzothiazepines, further alkaloid-type indole derivatives, indolo[3,2-c]isoquinolines, were obtained. The structures of the new ring systems were determined by means of NMR spectroscopy.     

Study of Friedel-Crafts acetylation of indolobenzo[b]furans,indolobenzo[b]thiophenes,pyrrolocarbazole, and pyrrolophenothazine dioxide by1H NMR spectroscopy

The reactivity towards Friedel-Crafts acetylation of the new heterocyclic systems indolo[5,6-d]- and indolo[5,4-d]benzo-[d]furans, 3H pyrrolo[2,3-c]carbazole, indolo[7,6-d]-, indolo[4,5-d]- and indolo[5,4-d]benzo-[b]thiophenes and 3H-pyrrolo[2,3-c]phenothiazine-11,11-dioxide have been studied. Under acid conditions these heterocycles behave like indole to give dimerization products, but anomalies were observed in a number of cases. These principles have been established by detailed analysis of the ¹ H NMR spectra of the reaction products. Georgian Technical University, Tbilisi 380075. D. I. Mendeleev Russian Chemical Technological University, Moscow 125047. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1078–1091, August, 1995. Original article submitted June 12, 1995.     

Benzomorphan related compounds. XIV. Synthesis of 2-(2-pyrrolylmethyl)- and 2-(2-indolylmethyl)tetrahydropyridines and cyclization to pyrrolo[3,2-f]morphans

The synthesis of 2-{2-pyrrolylmethyl)- and 2-(2-indolylmethyl)tetrahydropyridines by condensation of 2-cyanopyridines with appropriate pyrrole or indole derivatives followed by ketone reduction, quaternization and sodium borohydride reduction are described. The acid-induced cyclization of 2-(2-pyrrolylmethyl)tetrahydropyridines affords 4,5,6,7,8,9-hexahydro-4,8-methanopyrrolo[2,3-d]azocine systems (pyrrolo[3,2-f]-morphans), although the method fails with N-benzyl substituted pyrroles. The acid treatment of 2-(2-indolylmethyl)tetrahydropyridines and of 2-indolyl tetrahydro-2-pyridyl ketones is not a suitable procedure for the preparation of indolo[3,2-f]morphans, because of the protonation of indole nucleus or carbonyl group, respectively.     

Alkylation of 6-(3-Indolyl)indolo[2,3-b]carbazole

The methylation and allylation of 6-(3-indolyl)indolo[2,3-b]carbazole were studied, and its trimethyl and mono-, di-, and triallyl derivatives were obtained.     

On the Synthesis and Reactions of Indole-2-carboxylic Acid Hydrazide

Summary.  Indole-2-carboxylic acid hydrazide was prepared and allowed to react with aromatic aldehydes in acidic medium to give the corresponding hydrazone derivatives in good yields. The hydrazones were cyclized to indolo[2,3-d]pyridazine derivatives by refluxing with acetyl chloride. The indole carbohydrazide was converted to 2-triazolylindoles which acted as starting materials for several indole derivatives. A number of new indole derivatives were also prepared and structurally confirmed. Received October 17, 2000. Accepted (revised) December 12, 2000     

Regio- and diastereoselective synthesis of new functionalized indolo[2,3-b]indole-pyrimidine based on C–N bond formation via a four-component reaction

A facile and diastereoselective synthetic procedure has been designed for the preparation of new substituted indolo[2,3-b]indole (IDID) moiety at position-5 of the pyrimidine ring by a one-pot four-component reaction of dimedone, aniline and substituted derivatives, barbituric acid/thiobarbituric acid and isatin under mild conditions. This method proceeds rely on a CsbndN bond formation under catalyst-free conditions affording a range of skeletally diversity 5-indolo[3,2-b]indole-pyrimidine-based heterocycles. 5-Indolo[2,3-b]indol-pyrimidine-2,4,6-trione and 5-indolo[2,3-b]indol-2-thioxo-pyrimidine-4,6-dione were obtained in EtOH solvent in high yield, short reaction time and diastereoselectivity. The structural diversities of the synthesized compounds have been confirmed spectroscopically, by IR ¹H- and ¹³C NMR, EI-MS spectra and elemental analyses which agree with the proposed structures.     

Heterocycles [h]-fused onto 4-oxoquinoline-3-carboxylic acid, Part VI [1]. Synthesis and X-ray structure of model indolo[3,2-b]- and [2,3-b]pyrido[2,3-f]quinoxaline-3-carboxylic esters

Cyclocondensation reaction of ethyl 7,8-diamino-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate with 1-methylisatin produced a separable mixture of the corresponding indolo[3,2-b]- and [2,3-b]pyrido[2,3-f]quinoxaline-3-carboxylates, of which the latter isomer predominates. On the other hand, interaction with 1H-isatin or 5-chloroisatin gave the respective indolo[2,3-b]pyrido[2,3-f]quinoxaline-3-carboxylates as the sole regiospecific products. The structures of these new pentacyclic derivatives are based on microanalytical, spectral (IR, MS, and NMR) and X-ray crystal structure data.     

N-Bromosuccinimide as an efficient catalyst for the synthesis of indolo[2,3-b]quinolines

The use of N-bromosuccinimide as a catalyst promoted the synthesis of polycyclic indolo[2,3-b]quinoline derivatives in good to high yields in the reactions of various aryl amines with indole-3-carbaldehyde at room temperature under mild conditions.     

Synthesis of derivatives of a new heterocyclic system,indolo[2,3-f][1,7]naphthyridine

3-(N"-Aryl-N"-chloroacetyl)amino-2-formylindoles were converted into 3-amino-1-aryl-2-oxo-1,2-dihydropyrido[3,2-b]indoles, which were used to synthesize derivatives of a new heterocyclic system, namely, indolo[2,3-f][1,7]naphthyridine. The structures of the resulting compounds were proved by IR and ¹H NMR spectroscopy and mass spectrometry.     

Microwave‐assisted Synthesis of 6‐{(5‐Aryl‐1,3,4‐oxadiazol‐2‐yl)methyl}‐6H‐indolo[2,3‐b]quinoxalines

An efficient and convenient synthesis of a new series of 2‐{(6H‐indolo[2,3‐b]quinoxalin‐6‐yl)methyl}‐5‐aryl‐1,3,4‐oxadiazoles from readily available 1,2‐diaminobenzene and isatins under microwave irradiation conditions was disclosed. The 6‐{(5‐aryl‐1,3,4‐oxadiazol‐2‐yl)methyl}‐6H‐indolo[2,3‐b]quinoxalines were also prepared by the thermal cyclo‐condensation reaction of 2‐(6H‐indolo[2,3‐b]quinoxalin‐6‐yl)acetohydrazides with carboxylic acids in refluxing POCl₃. The microwave‐assisted synthesis was rapid and resulted in higher yield of the products at lower operating temperature with reduced waste generation in comparison with the thermal reaction protocol.     

Synthesis of 2,10,11-Trisubstituted Indolo[3,2-b]quinolines

A new method has been developed for the synthesis of derivatives of indolo[3,2-b]quinolines-11 based on N-oxidization of 2-nitro-10-substituted indolo[3,2-b]quinolines with subsequent conversion of the mixtures obtained into 2-nitro-11-substituted indolo[3,2-b]quinolinones-11. A series of 2-nitro-11-substituted indolo[3,2-b]quinolines was prepared.     

Azaindoles. V. Pyrido(4,3-b]indoles (γ-carbolines) fonctionnalisés sur leur sommet 4: Synthèse en une seule étape

In boiling diphenylether phenylhydrazine reacts with 1,2-dihydro-2-oxo-4-hydroxypyridines to give 3,4-dihydro-4-oxo(9H)-pyrido[4,3-b]indoles (γ-carbolines) in one step. Nucleophilic displacement of their 4-chloro derivatives by secondary amines affords both 3,4-disubstituted γ-carbolines and chlorination of 2,3-dimethyl-4-oxo(9H)pyrido[4,3-b]indoles, as well as methylation of 2-methyl-4-chloro-(9H)pyrido[4,3-b]indole leads to derivatives in the (3H)4-substituted pyrido[4,3-b] indole series.     

Indole and quinoline derivatives of 2,3-dihydro-l-benzothiepin-4(5H) one

By application of the Friedlander synthesis on 2,3-dihydro-l-benzothiepin-4(5H) one (4), the corresponding [4,5-b]quinoline derivatives 5a and 5b were obtained. Starting from the ketone (4) and by application of the Fischer indole synthesis, 1-benzolhiepino[4,5-b ]indole (6) and 1-benzothiepino[4,5-b]benzo[g]indole (7) were obtained. When β-naphthylhydrazine was used in the indolisation reaction, a mixture of 1-benzothiepino[4,5-b]benzo[e]indole ( 8 ) and 1-benzothiepino[4,3-b]benzo[e] indole (9) was obtained.     

Synthesis of pyridazino[4,5-b]indole derivatives from 2-(3-carboxy-1-methylindole)acetic acid anhydride

2-(3-Carboxy-1-methylindole)acetic acid anhydride ( 1 ) reacts with aryldiazonium salts to give 85–95% of the corresponding α-hydrazono anhydrides 2 . Treating 2 with boiling hydrazine hydrate in xylene, the respective 2-aryl-4-carbohydrazido-5-methyl-1-oxo-1,2-dihydro-5H/-pyridazino[4,5-b]indoles 3 were obtained (47–67%), and these compounds characterized as the respective benzylidene derivatives 4 . Compounds 2 react with amines (aniline, morpholine, piperidine) to give the respective 2-(3-carboxy-1-methylindole)aceta-mide 5 or the respective 2-aryl-4-carboxamido-5-methyl-5H-pyridazino[4,5-b]indole 6 , the product obtained depending on the structure of the aryl substituent. Boiling 2b (aryl = 4-chlorophenyl) with 5% sodium hydroxide gave (80%) 2-(3-carboxy-1-methylindole)acetic acid ( 7 ). Hydrolysis of 2b gave a mixture of 7 and 2-(3-carboxy-1-methylindolyl)-2-(4-chlorophenylhydrazono)acetic acid ( 8 ).     

2-Dicyanomethylidene-3-ethoxymethylidene-2,3-dihydroindole in the synthesis of fused tri- and tetracyclic systems

The reactions of 2-dicyanomethylidene-3-ethoxymethylidene-2,3-dihydroindole with hydrazine hydrate and phenylhydrazine afforded 2,3-diamino-4-cyanopyrido[4,3-b]indole and 3-amino-2-anilino-4-cyanopyrido[4,3-b]indole, respectively, and the reactions of the latter compounds with dimethylformamide diethyl acetal were studied. The reactions of 2,3-diamino-4-cyanopyrido[4,3-b]indole with benzaldehyde, ethyl acetoacetate, and acetylacetone were investigated. First representatives of new heterocyclic systems, viz., [1,2,4]triazolo[1’,5’:1,6]-pyrido[4,3-b]indole and pyrazolo[1’,5’:1,2]pyrido[4,3-b]indole, were synthesized. The structure of ethyl 6-cyano-5-[(E)-(dimethylamino)methylideneamino]-2-methyl-7H-pyrazolo-[1’,5’:1,2]pyrido[4,3-b]indole-1-carboxylate was established by X-ray diffraction.     

Synthesis of substituted indolizino[8,7-<Emphasis Type="Italic">b</Emphasis>]indoles from harmine and their biological activity

The reaction of harmine with phenacyl bromides or ethyl bromoacetate gives quaternized harmine derivatives. The cyclization of the phenacylharminium salts yields the corresponding 2-aryl-11H-indolizino[8,7-b]indoles. Vilsmaier-Haack formylation of 11H-indolizino[8,7-b]indoles leads to the corresponding 3,10-bisformyl derivatives. The acylation proceeds selectively at C(3) to give 3-acetyl-2-aryl-11H-indolizino[8,7-b]indole.     

Regioselectivity of cyclization of 3-allyl(propargyl)sulfanyl-5<Emphasis Type="Italic">H</Emphasis>-[1,2,4]triazino[5,6-<Emphasis Type="Italic">b</Emphasis>]indoles

The interaction of 3-allylsulfanyl-5H-[1,2,4]triazino[5,6-b]indole with iodine led to 1-iodomethyl-1,2-dihydro[1,3]thiazolo[2',3':3,4][1,2,4]triazino[5,6-b]indol-11-ium pentaiodide with an angular structure, on the basis of which 1-iodomethyl-1,2-dihydro[1,3]thiazolo-, 1-methylidene-1,2-di-hydro[1,3]thiazolo, and 1-methyl[1,3]thiazolo derivatives were obtained. The intramolecular cyclization of 3-propargyl(allyl)sulfanyl-5H-[1,2,4]triazino[5,6-b]indoles under the influence of concentrated sulfuric acid led to linear annelated products:3-methyl[1,3]thiazolo[3',2':2,3][1,2,4]tri-azino[5,6-b]indole or its 2,3-dihydro derivative.     

A Selective C−H Deprotonation Strategy to Access Functionalized Arynes by Using Hypervalent Iodine

Described here is an efficient method to access highly functionalized arynes from unsymmetrical aryl(mesityl)iodonium tosylate salts. The iodonium salts are prepared in a single pot from either commercially available aryl iodides or arylboronic acids. The aryne intermediates are generated by ortho‐C?H deprotonation of aryl(mesityl)iodonium salt with a commercially available amide base and trapped in a cycloaddition reaction with furan in moderate to good yields. Coupling partners for the aryne intermediates beyond furan are also described, including benzyl azide and alicyclic amine nucleophiles. The regio‐ and chemoselectivity of this reaction is discussed and evidence for the spectator aryl ligand of the iodonium salt as a critical control element in selectivity is presented.