Pyridyl-substituted [1,3]Dithiolo-[4,5-<Emphasis Type="Italic">b</Emphasis>][1,4]dithiine-2-thiones

We have obtained 5-(2-pyridyl)[1,3]dithiolo[4,5-b][1,4]dithiine-2-thione for the first time by cycloaddition of 2-ethynylpyridine to 4,5-dihydro-1,3-dithioltrithione (isotrithionedithiol). We have studied this thione, 5-(2-pyridyl)- and 5-(4-pyridyl)-5,6-dihydro[1,3]dithiolo[4,5-b][1,4]dithiine-2-thiones by mass spectroscopy and also IR, UV, ¹H and ¹³C NMR spectra. We have determined the crystal and molecular structure of 5-(2-pyridyl)-5,6-dihydro[1,3]dithiolo[4,5-b][1,4]dithiine-2-thione.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 429–434, March, 2005.     

1,3-Dipolar Cycloaddition of Ethyl Propiolate to 4,4-Dimethyl-4,5-dihydro-1,2-dithiolo-[5,4-c]quinoline-1-thiones

The interaction of ethyl propiolate with 4,4-dimethyl-4,5-dihydro-2,3-dithiolo[3,4-c]quinoline-1-thiones leads to 1,3-dithiol-2-ylidenes, 1,6,6a(l4)-trithiapentalene, or thiino[2,3-c]quinolines depending on the conditions.     

[3,4]-annulated pyrroles 1. Polynuclear heterocyclic systems based on pyrrolo[3,4-d]pyrimidine-2,4-dione

The intramolecular electrophilic substitution in 6-functionalized 1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-diones was used for the synthesis of pyrimido[4′,5′:3,4]-pyrrolo[1,2-a]quinoxaline-8,10(7H,9H)-dione, pyrimido[4′,5′:3,4]pyrrolo[2,1-c][1,2,4]benzo-triazine-8,10(7H,9H)-dione, and 2H-pyrimido[4′,5′:3,4]pyrrolo[1,2-a]indole-2,4,11(1H, 3H)-trione derivatives. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2180–2185, December, 2006.     

Identification of [1,3]dithiolo[4,5-d]dithiazolyl radicals by in situ EPR spectroscopy and cyclic voltammetry

The synthesis of [1,3]dithiolo[4,5-d]dithiazolium salts from readily available zinc chelate has been developed. Chlorination of 2-oxo and 2-(dicyanomethylene) (2-oxo-1,3-dithiole-4,5-diyl) diethanethioates with SO₂Cl₂ followed by condensation with Me₃SiN₃ produced 1,2,3-dithiazolium chlorides. The structure of 5-(dicyanomethylene)[1,3]dithiolo[4,5-d][1,3,2]dithiazol-1-ium tetrafluoroborate was confirmed by powder X-ray diffraction, and its chemical bonding pattern as well as charge transfer were studied within the QTAIM framework applied to the results of plane wave DFT periodic calculations. Reduction with triphenylantimony and electrochemical reduction of [1,3]dithiolo[4,5-d]dithiazolium salts by cyclic voltammetry, chronoamperometry, and microelectrolysis at a controlled potential on a platinum electrode in acetonitrile revealed the formation of [1,3]dithiolo[4,5-d]dithiazolyl radicals, which were characterized by EPR spectroscopy.     

Synthesis of derivatives of a new heterocyclic system pyrazolo[3,4-b]pyrido[1′,2′: 1,2]imidazo[4,5-d]pyridine

1-[4-Aminoarylpyrazolo[3,4-b]pyridin-5-yl]pyridinium chlorides undergo cyclization under reflux in tert-butanol in the presence of an excess of potassium tert-butoxide to form tetracyclic derivatives of pyrazolo[3,4-b]pyrido[1′,2′:1,2]imidazo[4,5-d]pyridine. The reaction scheme of the processes is proposed. The structures of the reaction products were confirmed by physicochemical methods. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 710–714, April, 2006.     

Studies on antibacterial agents. II. Synthesis and antibacterial activities of substituted 1,2-dihydro-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acids

A series of substituted 1,2-dihydro-6-oxo-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acids for the treatment of systemic infections was synthesized via 7-bromo-3-ethylthio-4,5-difluoro-2-methylindole (3), which was prepared by Gassman's indole synthesis in excellent yield. The synthesized pyrroloquinolines were tested for their antibacterial activities. 8-Fluoro-1,2-dihydro-2-methyl-9-(4-methyl-1-piperazinyl)-6-oxo-6H- pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid showed a potent antibacterial activity against gram-positive and gram-negative bacteria.     

Synthesis of pyrrolo[3,4-b]pyrroles and perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles

The 1,3-dipolar cycloaddition reactions of various N-tethered alkenyl aldehydes with some cyclic and acyclic amino acids have been studied. Some key sulfonamides having strategically positioned aldehyde and olefinic tether have been synthesized and effectively subjected to intramolecular azomethine ylide cycloaddition reaction resulting in a series of pyrrolo[3,4-b]pyrrole and its N-1-C-2 derivatives, and a series of novel heterotricyclic compounds, perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles, in good yields. The intramolecular cycloaddition reaction was found to be highly stereoselective to form only cis-fused cycloadducts in all cases.     

Synthesis and Properties of 6-Amino-7-hetaryl-5-R-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles

We have established that when 5-chloro-6-[cyano(2,3-dihydro-1-R-benzo[d]azol-2-yl)methyl]-2,3-pyrazinedicarbonitriles are reacted with nucleophilic reagents (aliphatic and aromatic amines, hydrogen sulfide), annelation of the five-membered ring occurs on the [b] face of the pyrazine with formation of 6-amino-7-hetaryl-5-R-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles and 6-amino-7-(1H-benzo[d]imidazol-2-yl)thieno[2,3-b]pyrazine-2,3-dicarbonitrile respectively. Further heating with excess of acylating reagent leads to formation of a novel heterocyclic system 1H-benzo[4,5]imidazo[1,2-c]pyrazino[2',3':4,5]pyrrolo[3,2-e]pyrimidine. Reaction of vicinal dinitriles with hydrazine hydrate leads to the novel system 1H-pyrrolo[2',3':5,6]pyrazino[2,3-d]pyridazine.     

Acylation of pyrrolo[1,2-a]pyrazines

The acylation of pyrrolo[1,2-a]pyrazines with acetic anhydride and the acid chlorides of various carboxylic acids has been studied. It has been shown that pyrrole[1,2-a]pyrazines are selectively acylated at the α-position of the pyrrole ring when it is free. Products of the condensation of 1-methylsubstituted pyrrolo[1,2-a]pyrazines have been obtained for the first time in the process of acetylation. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, 263–272, February, 2008.     

Synthesis of 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones from 4-aryl-3-carbethoxy-6-(trifluoromethyl)-2-pyrones and their reaction with sodium azide leading to new carbostyril derivatives

Treatment of ethyl 4-aryl-6-(trifluoromethyl)-2-oxo-2H-pyran-3-carboxylates, prepared from 4,4,4-trifluorobutane-1,3-diones, PCl₅ and sodium diethyl malonate, with sulfuric acid afforded the intramolecular Friedel–Crafts acylation products, 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones, from which 2-(trifluoromethyl)-6H-pyrano[3,4-c]quinoline-4,5-diones were obtained via the Schmidt reaction in moderate yields. The latter reacted with sodium azide to give 2-oxo-4-(5-trifluoromethyl-1,2,3-triazol-4-yl)-1,2-dihydroquinoline-3-carboxylic acids in good yields.     

Pyrrolopyrimidines. 5. Reaction of 6-Amino-1,3-dimethylpyrrolo[3,4-d]pyrimidine-2,4(1H,3H)-diones with 1,3-Diketones

The reaction of 6-amino-1,3-dimethylpyrrolo[3,4-d]pyrimidine-2,4-dione with 1,3-diketones leads to formation of predominantly pyrimido[4',5':3,4]pyrrolo[1,2-b]pyridazine-2,4(1H,3H)-diones and, to a lesser extent, pyrimido[5',4':3,4]pyrrolo[1,2-b]pyridazine-1,3(2H,4H)-diones. The ease and direction of the cyclization reaction suggests a very -electron rich pyrrole ring in the initial state, especially in the position 7.     

Synthesis of 8-tert-Butyl-9-oxo-1,2,4-triazolo[4,5-b]-1,2,4-triazolo[3,4-c]-1,2,4-triazine

8-tert-Butyl-9-oxo-1,2,4-triazolo[4,5-b]-1,2,4-triazolo[3,4-c]-1,2,4-triazine has been synthesized by the interaction of 6-tert-butyl-3-hydrazino-1,2,4-triazolo[3,4-c]-1,2,4-triazin-5-one with formic acid. The conditions of carrying out the reaction are discussed. Spectral characteristics are given.     

Reactions of 5-[3-(trifluoromethyl)-phenyl]furan-2-carbaldehyde

The Knoevenagel condensations of 5-[3-(trifluoromethyl)phenyl]furan-2-carbaldehyde with seven compounds containing an active methyl or methylene group have been studied. The compounds used were: methyl 2-cyanoacetate, malononitrile, 2-furylacetonitrile, acetophenone, 2-thioxo-1,3-thiazolidin-4-one (rhodanine), 5,5-dimethylcyclohexane-1,3-dione (dimedone), and methyl 2-azidoacetate. The effect of microwave irradiation on the condensation reactions was studied and compared with “’classical”’ conditions. Thermolysis of methyl 2-azido-3-{5-[3-(trifluoromethyl)phenyl]-2-furyl}propenoate afforded methyl 2-[3-(trifluoromethyl)phenyl)]-4H-furo[3,2-b]pyrrole-5-carboxylate. (2E)-3-{ 5-[3-(Trifluoromethyl)phenyl]-2-furyl}propenoic acid was converted to the corresponding azide, which was cyclized on heating into 2-[3-(trifluoromethyl)phenyl)]-4,5-dihydrofuro[3,2-c]pyridin-4-one. The latter after successive action of POCl₃ and NH₂NH₂-Pd/C gave 2-[3-(trifluoromethyl)-phenyl]furo[3,2-c]pyridine. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 825–831, June, 2006.     

4-Oxo-3,4-dihydroquinazolinyl- and Benzimidazolylacetonitriles in Annelation Reactions of a Haloquinoline Ring

The interaction of 4-oxo-3,4-dihydroquinazolinyl- and benzimidazolylacetonitriles with 2,6-dihalobenzaldehydes leads to 3-(2,6-dihalophenyl)-2-(4-oxo-3,4-dihydro-2-quinazolinyl)acrylonitriles and 2-(1H-benzo[d]imidazol-2-yl)-3-(2,6-dihalophenyl)acrylonitriles respectively. As a result of intramolecular cyclization of these nitriles 4-halo-12-oxo-12H-quino[2,1-b]quinazoline-6-carbonitriles and 4-halobenzo[4,5]imidazo[1,2-a]quinoline-6-carbonitriles respectively are formed.     

Nitration of Pyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrazines

We have synthesized nitro derivatives of pyrrolo[1,2-a]pyrazines using a nitrating mixture and acetyl nitrate. We have obtained the products of oxidation of the side chain of 1,6-substituted pyrrolo[1,2-a]-pyrazines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1579–1586, October, 2005.     

Formylation of pyrrolo-[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrazines

The formylation of pyrrolo[1,2-a]pyrazines containing alkyl, aryl, or hetaryl substituents in positions 1 and 6 of the heterocycle has been studied. It has been shown that formylation of 1-phenyl-and 1-(2 thienyl)pyrrolo[1,2-a]pyrazine occurs selectively at the α-position of the pyrrole ring. In all of the remaining examples the reaction course depends on substituent, reagent ratio, and reaction time. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 88–93, January, 2008.     

Synthesis of Some New Fused and Polyfused [1,2,4]Triazolo-[3,4-<Emphasis Type="Italic">b</Emphasis>][1,3,4]thiadiazepines

7-[1,3-Dithiolan-2-ylidene]-3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine-6,8-dione and 7-[5-oxo-1,3-dithiolan-2-ylidene]-3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]-thiadiazepine-6,8-diones were obtained by treating 3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazepine-6,8-diones with CS₂ and chloroacetyl chloride, respectively. Treatment of the above compounds with mercaptoacetic acid gave 1,2-dibromoethane or the corresponding spiro polyfused heterocycles. Some other triazolothiadiazepine derivatives including spiro polyfused compounds were also synthesized. __________ Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 8, 1256–1264, August, 2005.     

Trifluoroacetylation of pyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrazines

A study was carried out on the reaction of pyrrolo[1,2-a]pyrazines containing an alkyl, aryl, or aralkyl substituent at C-1 with trifluoroacetic anhydride. Trifluoroacetylation products may be formed either by reaction in the pyrrole ring or at the aryl or aralkyl groups at C-1. Products of electrophilic substitution at C-6 are formed in the trifluoroacetylation of pyrrolo[1,2-a]pyrazines containing at C-1 a substituent bulkier than a methyl group but lacking substituents at C-6 (the α-position of the pyrrole ring). __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1226–1233, August, 2007.     

Investigations on 2,3′-biquinolines 22. Novel and convenient method for the synthesis of benzo[5,6]indolizino-[2,1-<Emphasis Type="Italic">b</Emphasis>]quinolinium-13-thiolates and benzo-[5,6]indolizino[1,2-<Emphasis Type="Italic">c</Emphasis>]quinoline-6(5H)-thiones

We have developed a method of synthesis of benzo[5,6]indolizino[2,1-b]quinolinium-13-thiolates and 5,6-dihydrobenzo[5,6]indolizino[1,2-c]quinoline-6-thiones based on the reaction of the corresponding 1′, 2′-dialkyl-1′,2′-dihydro-2,3′-biquinolines and 1′,4′-dialkyl-1′,4′-dihydro-2,3′-biquinolines with sulfur in DMF. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 849–851, June, 2007.     

Aromatization with dearylation on Hantzsch cyclocondensation of 4-(dimethylamino)benzaldehyde,cyclohexane-1,3-diones,and some 1,3-[N,C]dinucleophiles

The Hantzsch three-component cyclization of 4-(dimethylamino)benzaldehyde, cyclohexane-1,3-diones, and some 1,3-[N,C]-dinucleophiles (5-amino-3-methyl-1-phenylpyrazole, 3,5-dimethoxyaniline, and 4-amino-1,3-dimethylpyrimidine-2,6-dione) proceeds in boiling acetic acid with the splitting off N,N-dimethylaniline and the formation of polycondensed heterocyclic sytems with a γ-unsubstituted pyridine ring (pyrazolo[3,4-b]quinoline, acridine, and pyrimido[4,5-b]quinoline). Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 244-251, February, 2009.