Facile and convenient syntheses of 6,11-dihydro-5H-indeno[1,2-c]isoquinolin- 5-ones and 6,11-dihydro-5H-indolo[3,2-c]isoquinolin-5-one

[reaction: see text] The synthesis of 6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-ones from the base-promoted condensation reaction of homophthalic anhydride and 2-(bromomethyl)-benzonitrile and a convenient method for the synthesis of indolo[3,2-c]isoquinolinones are described.     

Palladium-Catalyzed Annulation of Allenes with Indole-2-carboxylic Acid Derivatives: Synthesis of Indolo[2,3-c]pyrane-1-ones via Ar-I Reactivity or C-H Functionalization

Two methodologies, one involving Ar-I reactivity and the other through C-H functionalization, for the formation of indolo[2,3-c]pyrane-1-ones via the corresponding allenes, are presented. A highly efficient approach to indolo[2,3-c]pyrane-1-one derivatives through the Pd-catalyzed regioselective annulation of allenes with 3-iodo-1-alkylindole-2-carboxylic acids is described. This method is fairly general for a wide range of allenes affording the respective indolo[2,3-c]pyrane-1-ones in good to excellent yields. In addition, a Pd(II)-catalyzed oxidative coupling of indole-2-caboxylic acid derivatives with allenes via direct C-H functionalization to afford the corresponding indolo[2,3-c]pyrane-1-ones in moderate to good yields has been developed.     

Reduction of 12-acetylaminoindolo[1,2-c]quinazolines. Preparation of derivatives of the new heterocyclic system indolo[3,2-d][1,3]benzodiazepine

Reduction of derivatives of 12-acetylaminoindolo[1,2-c]quinazoline yielded the corresponding 12-acetylamino-5,6-dihydroindolo[1,2-c]quinazolines, recyclization of which under the influence of dilute hydrochloric acid led to the formation of derivatives of the hitherto unknown system indolo[3,2-d][1,3]benzodiazepine.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 668–673, May, 1988.     

Nucleophilic displacement of aromatic fluorine,Part III,indoloquinolines and benzofuranoquinolines

Variously substituted indolo[2,3-c]quinolines, benzofurano[2,3-c]quinolines and their positional isomers indolo[3,2-c]quinolines and benzofurano[3,2-c]quinolines respectively, were prepared from both indole and quinoline derivatives by intramolecular nucleophilic displacement of aromatic fluorine. The formation of an indolo[2,3-d]benzazepine was also observed.     

Silver- and gold-mediated domino transformation: a strategy for synthesizing benzo[e]indolo[1,2-a]pyrrolo/pyrido[2,1-c][1,4]diazepine-3,9-diones

We reported a strategy for the synthesis of fused heterocyclic compounds benzo[e]indolo[1,2-a]pyrrolo/pyrido[2,1-c][1,4]diazepine-3,9-diones via an AgSbF(6)/gold-complex catalyzed one-pot cascade transformation. The strategy is tolerant of a broad range of substrates and affords a series of intriguing fused diazepinedione heterocycles.     

Synthesis of chiral pyrrolo[1,2-c]thiazoles via intramolecular dipolar cycloaddition of münchnones: an interesting rearrangement to pyrrolo[1,2-c]thiazines

Intramolecular dipolar cycloaddition of bicyclic münchnones, 5H,7H-thiazolo[3,4-c]oxazol-4-ium-1-olates, derived from cyclodehydration of 2-substituted-N-acylthiazolidine-4-carboxylic acids are reported. A range of new pyrrolo[1,2-c]thiazole derivatives (7, 14, 15, 20, 23, and 26) were obtained as single enantiomers from 2-phenylthiazolidines, 2-benzoylthiazolidines, and 2-methylthiazolidine-4-carboxylates. Pyrrolo[1,2-c][1,4]thiazine derivative 27 was also obtained from pyrrolo[1,2-c]thiazole derivative 26. The structures of methyl (2R,4R)-2-(p-methoxybenzoyl)thiazolidine-4-carboxylate (17a), methyl (2R,4R)-2-(p-methoxybenzoyl)-N-(prop-2-ynyloxyacetyl)thiazolidine- 4-carboxylate (18), and 3-oxo-4-phenyl-3,4,6,8-tetrahydro-1H-furo[3',4':2,3]pyrrolo[1,2-c][1,4]thiazine (27) were determined by X-ray crystallography. Chirooptical studies of the pyrrolo[1,2-c]thiazoles were done by confirming the absolute configuration at the chiral center C-3.     

Synthesis of Indolo and benzimidazoquinazolines and benzodiazepines

Indolo[1,2-c] quinazolines, indolo[1,2-d] [1,4]benzodiazepines, indolo [1,2-d] [1,4]benzodi-azepin-6-ones and benzimidazo[1,2-d] [1,4] benzodiazepin-6-ones were synthesized. In an acid medium, the indoloquinazolines were produced from 2-(o-aminophenyl)indole and acyl halides. However, in the presence of sodium acetate, the acylated amine was obtained and was cyclized to the indolobenzodiazepinones using sodium hydride. The syntheses are described in detail and characterization data are given.     

Synthesis of pyrimido [4,5-c] pyridazine (4-deazafervenulin), pyrazolo[3,4-d] pyrimidine and 6-(pyrazino-1-yl)pyrimidine derivatives

The synthesis of several pyrimido[4,5-c]pyridazine (4-deazafervenulin) ( 1 ), pyrazolo[3,4-d]-pyrimidine ( 2 ) and 6-(pyrazino-1-yl)pyrimidine ( 9 ) analogs has been accomplished from 6-hydrazinouracil ( 3 ). This compound could not be used as starting material for the preparation of indolo[3,2-c]pyridazino[3,4-d]pyrimidine derivatives ( 8 ) because it yielded the corresponding hydrazones ( 7 ).     

Synthesis of 8-desbromohinckdentine A1

Hinckdentine A is an alkaloid isolated from the bryozoan Hincksinoflustra denticulate. This natural product contains a novel and unique 11b,12,13,14,15,16-hexahydroazepino[4',5':2,3]indolo[1,2-c]quinazoline ring system that has not previously been synthesized. We have synthesized 8-desbromohinckdentine A from a 2-aryl indole by first preparing the quaternary center of the natural product and then building the seven-membered lactam and dihydropyrimidine rings onto this intermediate to form the framework of hinckdentine A.     

Ind-N-alkylation of rutaecarpine and synthesis of two novel related heterocyclic ring systems: Indolo[1′,2′:3,4]pyrazo[1,2-α]quinazoline and indolo[1′,2′:3,4] [1,4] diazepino[ 1,2-α]quinazoline

The failure to obtain the N-(13)alkylrutaecarpines ( 1d,e,f ) by heating rutaecarpine ( 1a ) with neat alkyl halides at 120° is discussed in comparison with the facile reaction with methyl iodide. In contrast, with alkyl halide-potassium carbonate in acetone, the corresponding N-(13)alkyl-rutaeearpines ( 1d-l ) are obtained in good yield. By use of 1,3-diiodopropane and 1,2-dibromo-ethane, this reaction provides a facile route to 12a and 13 which are derivatives of the heretofore unknown indolo[1,2′:3,4]pyrazo[1,2-α]quinazoline and indolo[1,2 :3,4][1,4]diazepino[1,2-α]quinazoline ring systems.     

Some reactions of 3-halogenocinnolines catalysed by palladium compounds

3-Bromo- or 3-iodo-cinnoline (and 4-substituted analogues) are condensed with terminal alkynes in the presence of Pd and Cu compounds as catalysts to give the 3-alkynyl-derivatives. When 4-chloro- or 4-phenoxy-compounds are used, the products react with amines, in the presence of copper(I) iodide, to form pyrrolo[3,2-c]cinnolines and with hydrazines to give either the same ring system or a pyrazolo[4,3-c]cinnoline. Hydrolysis of 3-alkynyl-4-phenoxycinnoline to 3-alkynyl-4(1H)-cinnoline, followed by cyclisation, yields the furo[3,2-c]cinnoline. Attempts to condense 3-halogenocinnolines with alkenes gave variable results: 3-phenyl ethenyl- and 3(2-pyridylethenyl)-4-(1H)-cinnolinones were obtained but 3-bromocinnoline gave the 3,3′-bicinnolinyl. Action of palladium acetate in the presence of ethyl acrylate converted 3-bromo-4-phenoxycinnoline into benzofuro[3,2-c]cinnoline and 3-bromo-4-phenylaminocinnoline into indolo[3,2-c]cinnoline.     

Unexpected synthesis of indolo[1,2-c]quinazolines by a sequential Ugi 4CC-Staudinger-aza-Wittig-nucleophilic addition reaction

A new sequential Ugi-Staudinger-aza-Wittig-nucleophilic addition reaction was developed to construct indolo[1,2-c]quinazoline derivatives, starting from the easily accessible 2-azidobenzaldehyde, carboxylic acid, 2-acylaniline and isocyanide. It is noteworthy that this is the first report of the cyclization of the Ugi adduct to give a dihydroindole ring system with two quaternary carbon centers, via the nucleophilic addition reaction of the methine group to the carbonyl group.     

First nucleophilic aromatic substitution of annelated pyrazole.

3-Chloropyrazolo[3,4-c]quinoline 5, 3-chloropyrazolo[3,4-c]isoquinoline 6, 1,2-dihydro-1,2-dimethylpyrazolo[3,4-c]quinolin-3-one 8, and 1,2-dihydro-1,2-dimethylpyrazolo[3,4-c]isoquinolin-3-one 10 were obtained by acid-induced nucleophilic aromatic substitution (S(N)H) of H-3 in N-hydroxypyrazolo[3,4-c]quinoline 1b and in N-hydroxy pyrazolo[3,4-c]isoquinoline 3b. In the acid-induced chlorination, 3b was far more reactive than 1b, whereas the related N-hydroxypyrazolo[4,3-c]quinoline 2b and N-hydroxypyrazolo[4,3-c]isoquinoline 4b were completely unreactive toward S(N)H under identical conditions.     

Unusual reaction of 2-(trifluoromethyl)-1,2-dihydro-3lambda(6)-thieno- [2,3-c]chromen-3,3,4-triones with hydrazine as a new route to 3-hydrazinopyridazine derivatives

Oxidation of 2-(trifluoromethyl)-1,2-dihydro-4H-thieno[2,3-c]chromen-4-ones 2 with H(2)O(2) in AcOH gives 2-(trifluoromethyl)-1,2-dihydrothieno[2,3-c]chromen-3,3,4-triones 3, which are transformed into 3-hydrazinopyridazine derivatives 4 in high yields by treatment with hydrazine hydrate in ethanol.     

Novel heterocyclic systems based on 8-R-4,5-dihydro-4,4-dimethyl-[1,2]dithiolo[3,4-c]quinoline-1-thiones

Based on the reaction of 8-R-4,5-dihydro-4,4-dimethyl[1,2]dithiolo[3,4-c]quinoline-1-thiones with oxalyl chloride followed by the reactions of 1,3-dipolar cycloaddition and diene synthesis with participation of acetylenedicarboxylic acid dimethyl ester, we have developed approaches to synthesis of novel polycondensed heterocyclic systems: [1,2]dithiolo[3,4-c]pyrrolo[3,2,1-ij]quinoline-4,5-dione, 6-(1,3-dithiol-2-ylidene)-1,2-dioxo-5-thioxo-7H-pyrrolo[3,2,1-ij]quinoline and 4,5-dioxospiro(pyrrolo)-[3,2,1-ij]thiopyrano[2,3-c]quinoline-11,2′-[1,3]dithiole. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 610–615, April, 2006.     

Synthesis and antibacterial activities of novel 2,5-diphenylindolo[2,3-e] pyrazolo[1',5':3",4"]pyrimido[2",1"-c] [1,2,4]triazines

The formation of (E)-3-{2-(2,5-diphenylpyrazolo[1,5-c]pyrimidin-7-yl)hydrazono}indolin-2-ones 3 has been achieved by condensation of equimolar amounts of 7-hydrazino-2,5-diphenylpyrazolo[1,5-c]pyrimidine (1) and isatin (or isatin derivatives) 2 at room temperature. The (E)-products could be isomerized into corresponding the (Z)-3 isomers. Reactions of the latter fused heterocyclic hydrazones towards different electro-philic reagents yielded the corresponding 3-substituted derivatives 4-7. Dehydrative cyclisation of the hydrazones 3 using phosphorus oxychloride afforded the 2,5-diphenyl- indolo[2,3-e]pyrazolo[1',5':3",4"]pyrimido[2",1"-c][1,2,4] triazines 13. The polyfused heterocyclic ring system 13 underwent electrophilic substitution reactions at position 4 rather than at position 3. The 3-bromo isomer of 17 was prepared by a sequence of reactions starting from 2,5-diphenylpyrazolo[1,5-c]pyrimidine-7(6H)-thione (11). The orientation of the electrophilic attack was supported by spectroscopic and chemical evidence. Some of the synthesized compounds were found to possess slight to moderate activity against the microorganisms Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa.     

Regiospecific synthesis of 3-substituted imidazo[1,2-a]pyridines,imidazo[1,2-a]pyrimidines,and imidazo[1,2-c]pyrimidine

3-Substituted imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, and imidazo[1,2-c]pyrimidine were obtained regiospecifically in yields of 35-92% in one pot by reaction of 2-aminopyridines or 2-(or 4-)aminopyrimidines, respectively, with 1,2-bis(benzotriazolyl)-1,2-(dialkylamino)ethanes.     

Cascade intermolecular Michael addition-intramolecular azide/internal alkyne 1,3-dipolar cycloaddition reaction in one pot

A rapid one-pot protocol for the synthesis of indole-based polyheterocycles via a sequential Lewis acid catalyzed intermolecular Michael addition and an intramolecular azide/internal alkyne 1,3-dipolar cycloaddition reaction has been described. The generality of the method has been demonstrated by treating a series of aromatic/aliphatic 2-alkynyl indoles with substituted (E)-1-azido-2-(2-nitrovinyl)benzenes to furnish annulated tetracyclic indolo[2,3-c][1,2,3]triazolo[1,5-a][1]benzazepines in good yields.     

低价钛促进的苯并咪唑并[1,2-c]喹唑啉衍生物的合成

利用低价钛试剂促进的2-邻硝基苯基苯并咪唑与原甲酸酯或丙酮或固体光气的反应, 合成了一系列苯并咪唑并[1,2-c]喹唑啉衍生物, 化合物的结构经IR, 1H NMR, MS和元素分析确定, 化合物4c的结构经单晶X射线衍射分析进一步确证. 该方法具有原料易得、操作简便和产率高等优点.     

1,2,3-benzotriazines. II. Reactions of benzimidazo[1,2-c][1,2,3]benzotriazines and naphth[1′,2′(2′,1′):4,5]imidazo[1,2-c][1,2,3]benzotriazine

A number of methyl- and halogeno-substituted benzimidazo[1,2-c][1,2,3]benzotriazines were subjected to a series of hydrolytic cleavages in acid media. The reactions of these compounds with dilute sulfuric acid yielded 2-(o-hydroxyphenyl)benzimidazoles. Concentrated hydrochloric acid produced a mixture of 2-(o-chlorophenyl)- and 2-(o-hydroxyphenyl)benzimidazoles. Hydrogen chloride in ethanol caused the formation of 2- phenylbenzimidazoles contaminated with small amounts of 2 - (o-chlorophenyl)benzimidazoles. The benzimidazo[1,2-c][1,2,3]benzotriazines underwent the Sandmeyer reaction to form 2-(o-chlorophenyl)- and 2-(o-bromophenyl)benzimidazoles in excellent yields. These reactions illustrated the behavior of these 1,2,3-triazines as internal diazonium compounds. Naphth[1′,2′(2′,1′):4,5]imidazo[1,2-c][1,2,3]benzotriazine behaved similarly. Bromination of some benzimidazo[1, 2 - c][1,2,3]benzotriazines in aqueous medium yielded bromine-substituted [1,2-c][1,2,3]benzotriazines.