Solid Phase Synthesis of 4H-Pyrimido[2,1-b] Benzothiazol-4-ones from Resin-Bound Cyclic Malonic Ester

The solid phase synthesis of 4H-pyrimido[2,1-6] benzothizaol-4-ones has been reported.     

Reaction of 2-alkylthio-6-amino-pyrimidin-4(3H)-ones with ethyl bromopyruvate. Synthesis of furo-[2,3-<Emphasis Type="Italic">d</Emphasis>]-pyrimidine and furo[3,2-<Emphasis Type="Italic">e</Emphasis>]imidazo-[1,2-<Emphasis Type="Italic">c</Emphasis>]pyrimidine carboxylates

Reaction of 2-alkylthio-6-aminopyrimidin-4(3H)-ones with ethyl bromopyruvate to give ethyl 2-alkyl-thio-4-aminofuro[2,3-d]pyrimidine-5-carboxylates has been shown to proceed under neutral or acidic conditions. The obtained furo[2,3-d]pyrimidines underwent further cyclocondensation reaction with ethyl bromopyruvate to afford diethyl 5-alkylthiofuro[3,2-e]imidazo[1,2-c]pyrimidine-2,9-dicarboxy-lates. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 440–443, March, 2009.     

Synthesis and antimicrobial activity of 2<Emphasis Type="Italic">H</Emphasis>-pyrimido[2,1-<Emphasis Type="Italic">b</Emphasis>]benzothiazol-2-ones

4-Phenyl-2H-pyrimido[2,1-b]benzothiazol-2-ones have been synthesized in quantitative yields by the reaction of 2-aminobenzothiazoles with alkynoic acid. The antimicrobial activity of the synthesized compounds was tested against bacterial species, Bacillus coagulans, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa. The synthesized compounds have shown significant activity against microorganisms which can be correlated with the fused heterocyclic systems.     

Synthesis of 2-Aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-Aryl-2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones

The reaction of 2-mercaptobenzimidazole, 5-ethoxy-2-mercaptobenzimidazole, and 2-mercaptoimidazoline with cinnamoyl chloride, its derivatives, and heteroanalogs was studied. Convenient methods were found for the synthesis of 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-aryl-2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones.     

Synthesis of 6-substituted 5,6,7,8-tetrahydropyrimido[4,5-<Emphasis Type="Italic">d</Emphasis>]pyrimidine-2,4-diones and 2-thioxo-5,6,7,8-tetrahydropyrimido[4,5-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4-ones

Three-component reactions of 6-aminouracils and 6-aminothiouracils with formaldehyde and primary amines gave 6-alkyl-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidine-2,4-diones and 6-alkyl-2-thioxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-ones. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1512–1515, July, 2008.     

An efficient <Emphasis Type="Italic">Mannich</Emphasis>-type synthesis of <Emphasis Type="Italic">bis</Emphasis>(pyrido[2,1-<Emphasis Type="Italic">b</Emphasis>][1,3,5]thiadiazin-7-yl)-methanes

Morpholinium 3-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-thiolate upon treatment with primary amines and a formaldehyde excess under mild conditions produces bis(pyrido[2,1-b][1,3,5]thiadiazin-7-yl)methane derivatives in good yields (67–87%). Correspondence: Victor V. Dotsenko, State Enterprise “Luganskstandartmetrology”, 91021 Lugansk, Ukraine.     

Synthesis of diarylazolo[<Emphasis Type="Italic">a</Emphasis>]pyridines from [(<Emphasis Type="Italic">Z</Emphasis>)-2,4-diaryl-4-oxo-2-butenyl]azolium salts

A method for the synthesis of derivatives of [1, 3]thiazolo[3,2-a]pyridines, pyrido[2,1-b][1, 3]benzo-thiazole, [1, 3, 4]thiadiazolo[3,2-a]pyridine, and [1, 2, 4]triazolo[4,3-a]pyridine, which includes base initiated cyclization of quaternary azolium salts, formed by the interaction of (Z)-1,3-diaryl-4-bromo-2-buten-1-ones with 1-alkyl-1H-1,2,4-triazoles, 4-methyl-1,3-thiazole, 1,3-benzothiazole, and N-phenyl-1,3,4-thiadiazole-2-amine. Derivatives of 2-chloroimidazo[1,2-a]pyridine were obtained when 5-chloro-1-methyl-1H-imidazole was used.     

Synthesis of pyrazolo[4,3-<Emphasis Type="Italic">e</Emphasis>][1,2,4]triazolo[4,3-<Emphasis Type="Italic">c</Emphasis>]pyrimidines

Starting from 1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones, a synthesis pathway to the tricyclic pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines is described. Reaction of 1,5-dihydro-4H-pyrazolo[3,4-d] pyrimidin-4-ones with phosphoryl chloride afforded the corresponding 4-chloro-1H-pyrazolo[3,4-d]pyrimidines. Treatment of these compounds with hydrazine hydrate at reflux temperature gave the hydrazino derivatives, which were subsequently cyclized to the titled compounds on heating with orthoesters in ethanol. Correspondence: Abolghasem Davoodnia, Department of Chemistry, School of Sciences, Islamic Azad University, Mashhad Branch, Mashhad 91735-413, Iran.     

Intramolecular cyclization of 5-aryl-3-arylamino-4-benzoyl-1h-3-pyrrolin-2-ones to pyrrolo[3,4-<Emphasis Type="Italic">b</Emphasis>]quinolines

It has been shown that 5-aryl-3-arylamino-4-benzoyl-1H-3-pyrrolin-2-ones cyclize in the presence of conc. H₂SO₄ to give pyrrolo[3,4-b]quinolines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1543–1545, October, 2004.     

Reaction of 2-Aryl-5-R-5,6-dihydro-7H-[1,2,4]-triazolo[5,1-<Emphasis Type="Italic">b</Emphasis>][1,3]thiazin-7-ones with Aryl Bromomethyl Ketones and Benzyl Bromide

The products of the reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with aryl bromomethyl ketones are 2-aryl-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones and aryl methyl ketones or 2,5-diaryl[1,3]thiazolo[3,2-b][1,2,4]triazoles and 3-phenyl-2-propenoic acid, depending on the structure of R. The reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with benzyl bromide yields 5-aryl-3-benzylthio-4H-1,2,4-triazoles and 3-aryl-2-propenoyl bromide. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 905–909, June, 2005.     

Synthesis of Sulfur Heterocycles by Thio-<Emphasis Type="Italic">Claisen</Emphasis> Rearrangement

Summary. 7-Chloro-4-hydroxydithiocoumarin was alkylated with allylic halides under phase transfer catalysis condition in the presence of TBAB or BTEAC in chloroform-aqueous NaOH (1%) at room temperature. 2,3-Dichloroprop-2-ene on similar treatment with 7-chloro-4-hydroxydithiocoumarin afforded 2-methylthieno[2,3-b]thiochromen-4-one in 65% yield. The S-alkylated thiochromen-4-ones were then refluxed in quinoline to give 7-chloro-2,3-dihydrothieno[2,3-b]thiochromen-4-ones or 7-chloro-2,3,4-trihydrothiopyrano[2,3-b]thiochromen-5-ones or 7-chloro-2,3-dihydro-3-vinylthieno[2,3-b]thiochromen-4-one.     

Interaction of 3-amino-2-(isoxazol-3-yl)-4-methoxymethyl-6-methyl-thieno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridine with Raney nickel

3-Amino-2-(isoxazol-3-yl)-4-methoxymethyl-6-methylthieno[2,3-b]pyridine was synthesized by the reaction of 2(1H)-thioxopyridine-3-carbonitrile with 3-chloromethylisoxazole in the presence of two equivalents of KOH. Boiling of 3-amino-2-(isoxazol-3-yl)-4-methoxymethyl-6-meth-ylthieno[2,3-b]pyridine with Raney nickel results in 4-aminothieno[2,3-b;4,5-b′]dipyridine or 5-(4-amino-2-pyridyl)pyridine depending on the reaction conditions. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 669–670, March, 2008.     

Reaction of 2-methoxy-1,3,2-dioxaphosphorino[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-4(4<Emphasis Type="Italic">H</Emphasis>)-one with hexafluoroacetone

The reaction of the di-O-trimethylsilyl derivative of 2-hydroxynicotinic acid with methyl phosphodichloridite afforded 2-methoxy-1,3,2-dioxaphosphorino[4,5-b]pyridin-4(4H )-one. The NMR spectrkscopic data suggest that the reaction of the latter with hexafluoroacetone produces unstable 2-methoxy-2,5-dioxo-4,4-bis(trifluoromethyl)-4,5-dihydro-1,3,2-dioxaphosphepino[4,5-b]pyridine, which is readily transformed into 9-methyl-2,5-dioxo-4,4- bis(trifluoromethyl)-4,5-dihydro-1,3,2-dioxaphosphepino[4,5-b]pyrid-9-inium-2-oate. The structure of the hydrolysis product of the latter, viz., 1-methyl-3-(2-hydroxy-3,3,3-trifluoro-2- trifluoromethylpropanoyl)pyridin-2-one, was established by X-ray diffraction analysis.Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1640–1646, August, 2004.     

Synthesis and Reactions of 4-Oxiranylmethylfuro[3,2-b]pyrroles and Their Benzo Derivatives

Methyl 4-oxiranylmethyl-4H-furo[3,2-b]pyrrole-5-carboxylates 2a-c and methyl 1-oxiranylmethyl-1H-benzo[4,5]furo[3,2-b]pyrrole-2-carboxylate (2d) were prepared by reaction of the appropriate starting compounds 1a-d with excess chloromethyloxirane. The compounds 2a-d undergo oxirane ring opening by heterocyclic amines (morpholine, pyrrolidine, piperidine or 4-methylpiperazine) giving N-2-hydroxy-3-heteroaminopropyl-substituted compounds 3a-f or substituted 4,5-dihydrofuro[2',3':4,5]pyrrolo[2,1-c][1,4]oxazin-8-ones 4a-e.     

Synthesis of 3-Aroylmethylene-1,6,7,11b-tetrahydro-2H-pyrazino-[2,1-<Emphasis Type="Italic">a</Emphasis>]isoquinolin-4-ones

The reaction of substituted methyl aroylpyruvates with 1-aminomethyl-1,2,3,4-tetrahydroisoquinoline dihydrochloride in the presence of AcOH gives 3-aroylmethylene-1,6,7,11b-tetrahydro-2H-pyrazino[2,1-a]isoquinolin-4-ones whose structures have been confirmed by IR, ¹H NMR, and mass spectrometry. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1218–1221, August, 2005.     

The Synthesis of Cyclopenta[<Emphasis Type="Italic">c</Emphasis>]pyridine (2-Pyrindene) Derivatives

Summary. Ethyl 2-(N-morpholinyl)cyclopent-1-ene-1-carboxylate reacted smoothly with cyanothioacetamide to give morpholinium 4-cyano-1-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[c]pyridine-3-thiolate; the former when treated with N-benzyl-α-chloroacetamide gave either a S-alkyl derivative or cyclopenta[d]thieno[2,3-b]pyridine, depending on the reaction conditions. Under Mannich-type aminomethylation with primary amines and formaldehyde the above thiolate afforded derivatives of the previously unknown heterocyclic system, cyclopenta[g]pyrido[2,1-b][1,3,5]thiadiazine in 81–90% yields. Victor P. Litvinov, was Deceased Victor P. Litvinov, This paper is dedicated to the blessed memory of our colleague, Prof. Victor Petrovich Litvinov (Dec 24, 1932–Feb 26, 2007)     

Facile synthesis of 2-(substituted amino)-4<Emphasis Type="Italic">H</Emphasis>-thieno[3,2-<Emphasis Type="Italic">e</Emphasis>]-1,3-thiazin-4-ones

Interaction between 2,5-dichlorothiophene-3-carbonyl isothiocyanate, accessible via 2,5-dichlorothiophene-3-carbonyl chloride, and model heterocyclic amines produced the respective 2,5-dichloro-N-(substituted aminocarbonothioyl)thiophene-3-carboxamides. Upon heating, the deprotonated form of the latter underwent intramolecular cyclization to deliver the corresponding 2-(substituted amino)-4H-thieno[3,2-e]-1,3-thiazin-4-ones. The structures of these new bicyclic derivatives and their acyclic precursors are based on microanalytical and spectral (IR, MS, and NMR) data. Correspondence: Rajab Abu-El-Halawa, Chemistry Department, Faculty of Science, Al al-Bayt University, Mafraq, Jordan.     

On the reduction of 1-aryl-2-oxo-1,2,3,6-tetra-hydro[1,4]diazepino[6,5-<Emphasis Type="Italic">b</Emphasis>]indole 4-oxides

Electrochemical reduction of 1-aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole 4-oxides, 2-oxo-1-phenyl-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole, and 2-oxo-1-phenyl-1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole was studied. The results obtained were compared with previous data for the reduction of 4-oxides with formamidinesulfinic acid.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2715–2718, December, 2004.     

Synthesis of imidazo[4,5-<Emphasis Type="Italic">a</Emphasis>]acridones and imidazo[4,5-<Emphasis Type="Italic">a</Emphasis>]acridines as potential antibacterial agents

Abstract  New imidazo[4,5-a]acridone derivatives were synthesized from the rearrangement of 3H-imidazo[4′,5′:3,4]benzo[c]isoxazoles. New imidazo[4,5-a]acridines were obtained from the reaction of imidazo[4,5-a]acridones in boiling POCl₃. All of these compounds exhibited antimicrobial activities comparable to streptomycin as reference drug. Graphical abstract        

Azolo[5,1-<Emphasis Type="Italic">c</Emphasis>]-1,2,4-triazines as a new class of antiviral compounds

Synthetic methods, reactivity, and the properties of a new class of antiviral compounds, pyrazolo-, imidazo-, 1,2,4-triazolo[5,1-c]-1,2,4-triazinones, tetrazolo[5,1-b]-1,2,4-triazinones, and azoloannulated amino-1,2,4-triazines having structural similarity with biogenic purines and capable of mimicking them in metabolic processes are considered. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 967–995, May, 2008.