Regioselective formylation of pyrazolo[3,4-b]pyridine and pyrazolo[1,5-a]pyrimidine systems using Vilsmeier-Haack conditions

Regioselective formylation behavior has been found in the reaction of pyrazolo[3,4-b]pyridines and pyrazolo[1,5-a]pyrimidines via Vilsmeier-Haack conditions. While the 4,5- and 6,7-dihydro derivatives afforded pyrazolo[3,4-b]pyridine-5-carbaldehydes and 4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarbaldehydes, respectively, the aromatic analogs rendered the pyrazolo[1,5-a]pyrimidine-3-carbaldehyde only, and no reaction took place at the pyrazolopyridine derivatives.     

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.     

A novel and convenient synthesis of thiazolo[3,2-a]pyrimidin-7-ones and pyrido[1,2-a]pyrimidin-2-ones using Vilsmeier reagent

A novel route for the synthesis of thiazolo[3,2-a]pyrimidin-7-ones and pyrido[1,2-a]pyrimidin-2-ones from acetylated 2aminothiazoles and 2-aminopyridines under Vilsmeier conditions has been developed.The plausible mechanism has also been proposed.     

Properties of 8-Cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridines

The alkylation, acylation, halogenation, nitration, oxidation, and hydrolysis reactions of 8-cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridine have been studied. It was found that the 6-halo derivatives add alcohol to give covalent solvates. X-ray analysis has been carried out on one of the solvates (6-chloro-8-cyano-7-ethoxy-5-phenyl-7-trifluoromethyl-1,2,3,7-tetrahydroimidazo[1,2-a]pyridine) as well as on 8-cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridine trifluoroacetate.     

Synthesis of 2,3-Dihydrothiazolo[3,2-a]pyrimidin-5-ones by a Michael-type Tandem Reaction

Summary. Although various thiazoles are known in literature for their biological and pharmacological properties only a few multi-step synthesis pathways for the preparation of thiazolo[3,2-a]pyrimidinones have been reported, which are tedious and time-consuming. An alternative synthesis pathway is described, which allows the preparation of 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-ones in a one-step process based on a Michael-type tandem reaction. By heating of 2-thiobarbituric acid with ethyl 4-bromocrotonate in ethanol at 60°C for 2 h, a 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-one was obtained in 73% yield, whereas carrying out the reaction at room temperature results in the formation of an unstable unsaturated ester. The structures of both, the α,β-unsaturated ester as well as the 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-one were confirmed by NMR spectroscopy. Additionally, the structure of the 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-one was investigated by single-crystal X-ray analysis. The described approach offers a significant improvement over previously reported synthesis pathways because it allows the simple preparation of 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-ones with good yields in a one-step reaction.     

Synthesis of trifluoromethyl-promoted functional pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-d][1,2,3,5]tetrazine-4(3H)-ones

Ethyl 5-amino-3-trifluoromethyl-1H-pyrazole-4-carboxylate (1) was efficiently synthesized via the condensation of ethyl cyanoacetate and trifluoroacetic anhydride, followed by chloridization and the condensation with aqueous hydrazine. Its unique reactivity was exploited for the synthesis of trifluoromethylated pyrazolo[1,5-a]pyrimidine (5) and pyrazolo[5,1-d][1,2,3,5]tetrazine-4(3H)-ones (8a-j). Among them, 5 was firstly found to be a novel fluorescent molecule that might be exploited as an attractive fluorophore for possessing many binding sites, and its fluorescence intensity was obviously stronger than its methyl analogue. 8 were found to be a new chemical class of potential monocotyledonous Echinochloa crus-galli L. Beauv inhibitors, and were more active than their methyl analogues.     

Synthesis of 5-Phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridines

Syntheses are reported for a series of 2-alkylamino-6-phenyl-4-trifluoromethylpyridines. The reaction of 3-cyano-2-(hydroxyalkylamino)-6-phenyl-4-trifluoromethylpyridines with thionyl chloride gave the corresponding 2-(chloroalkylamino)pyridines, 8-cyano-5-phenyl-7-trifluoromethyl-2,3-dihydro-imidazo[1,2-a]pyridines, and 9-cyano-6-phenyl-8-trifluoromethyl-2,3,4-trihydropyrido[1,2-a]-pyrimidines. X-ray diffraction structural analysis was used to study 8-cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridine.     

Imidazo[1,5-a]- and Thiazolo[3,4-a]quinoxalines Based on 3-(a-Thiocyanobenzyl)quinoxalin-2(1H)-one

When 3-(a-thiocyanobenzyl-2(1H)-one is heated, competing processes of [a]-annelation of the imidazole or thiazole rings occurs with formation of imidazo[1,5-a]- and thiazolo[3,4-a]quinoxalin-4(5H)-ones.     

Some chemical properties of 2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-one and 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones

We have studied the reaction of 2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-one and 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones with amines, alkylating reagents, and hydrogen peroxide. We have shown that the presence of an aryl substituent at the 2 position of [1,3-thiazino[3,2-a]benzimidazol-4-ones has a substantial effect on the direction of the reactions. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 445–452, March, 2006.     

A new synthesis for 1,2,4-triazolo[1,5-a]-pyridines and 1,2,4-triazolo[1,5-a]isoquinolines

Summary Condensation of cyano acid hydrazide1 with cyclopentanone in refluxing ethanolic piperidine yields hydrazone2. With mixtures of aliphatic aldehydes and different active methylene reagents,2 reacts to 1,2,4-triazolo[1,5-a]pyridines (8a–f). Compound2 also reacts with arylidenes9a–g to give triazolopyridines10a–g. Reaction of2 with aromatic aldehydes affords compounds13a–c. Diazotation of2 with aryldiazonium chloride in ethanol at 0 °C leads to the azo adducts15a–d. The thieno-1,2,4-triazolopyridine16 is obtained by reaction of8a with elementary sulfur.16 undergoes cycloaddition with -nitrostyrene, maleic anhydride, N-arylmalemide, and acrylonitrile yielding the isoquinolines21–24. All new compounds have been characterized by their IR,¹H NMR, and mass spectra.

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Ein neuer Syntheseweg für 1,2,4-Triazolo[1,5-a]pyridine und 1,2,4-Triazolo[1,5-a]isochinoline

Zusammenfassung Kondensation des Cyanohydrazids1 mit Cyclopentanon in ethanolischem Piperidin bei Rückflußtemperatur ergibt das Hydrazon2. Mit Gemischen aus aliphatischen Aldehyden und verschiedenen Verbindungen mit aktiven Methylengruppen reagiert2 zu 1,2,4-Triazolo[1,5-a]pyridinen (8a–f). Verbindung2 reagiert außerdem mit den Arylidenen9a–g zu den Triazolopyridinen10a–g. Umsetzung von2 mit aromatischen Aldehyden führt zu den Verbindungen13a–c. Diazotierung von2 mit Aryldiazoniumchloriden in Ethanol bei 0°C ergibt die Azoaddukte15a–d. Das Thieno-1,2,4-triazolylpyridin16 erhält man durch Reaktion von8a mit elementarem Schwefel.16 geht it -Nitrostyrol, Maleinsäureanhydrid, N-Arylmaleimid und Acrylnitril eine Cycloaddition zu den Isochinolinen21–24 ein. Alle neuen Verbindungen wurden durch ihre IR-,¹H-NMR- und Massenspektren charakterisiert.

     

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.     

Formylation of Furyl-substituted Imidazo[1,2-a]pyridine, Imidazo[1,2-a]pyrimidine and Imidazo[2,1-b]thiazole

Vilsmeier formylation of 2-(2-furyl)-substituted imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrimidine, and also 6-(2-furyl)imidazo[2,1-b]thiazole with 1 mole of reagent occurs at the free position of the imidazole ring, while with an excess of the reagent it also occurs at the position 5 of the furyl group.     

Solvent-free reaction between acenaphthoquinone, various benzils and ammonium acetate: synthesis of 9,10-diaryl-7H-benzo[d,e]imidazo[2,1-a]isoquinolin-7-ones

A simple synthesis of benzo[d,e]imidazo[2,1-a]isoquinolines is described. Heating a mixture of acenaphthoquinone, a benzil, and ammonium acetate under solvent-free conditions afforded 9,10-diaryl-7H-benzo[d,e]imidazo[2,1-a]isoquinolin-7-ones in good to excellent yields.     

Expeditious synthesis of 5,6,7,8-tetrahydro-imidazo[1,2-a]pyrimidin-2-ones and 3,4,6,7,8,9-hexahydro-pyrimido[1,2-a]pyrimidin-2-ones

A convenient synthesis of new 5,6,7,8-tetrahydro-imidazo[1,2-a]pyrimidin-2-ones and 3,4,6,7,8,9-hexahydro-pyrimido[1,2-a]pyrimidin-2-ones from the Baylis-Hillman adducts of acrylonitrile and their derivatives is described. A common strategy employed to achieve the syntheses of title compounds involved generation of diamines from different Baylis-Hillman derivatives followed by treatment with cyanogen bromide at reflux temperature to trigger a double intramolecular cyclization.     

Synthesis of N-Alkylated Derivatives of Pyrazolo[1,5-a]pyrimidine and Their Reaction with Methylamine

With the object of studying the factors influencing the course of enamine rearrangements, we have carried out the N-alkylation of alkyl- and aryl-substituted pyrazolo[1,5-a]pyrimidines. Using the NOEDIF NMR spectroscopic method for the cases of 5,7-dimethyl-2-phenyl- and 2,5,7-triphenylpyrazolo[1,5-a]pyrimidines it was found that addition of the alkyl group occurs at the N₍₄₎ atom of the pyrimidine fragment in the pyrazolo[1,5-a]pyrimidine. It was shown that, when reacting with an alcoholic solution of methylamine, the 5,7-dimethyl-2-phenyl- and 2,5,7-triphenylpyrazolo[1,5-a]pyrimidine iodomethylates undergo decomposition to give 5-methylamino-3-phenylpyrazole and 5-(1,3-diphenyl-3-methylamino-2-propenylid-1-ene)amino-3-phenylpyrazole.     

Benzannulation of 5-methyl-7-phenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine with chalcones and their synthetic equivalents as a method for the synthesis of tetrazolo[5,1-b]quinazolines

Derivatives of tetrahydrotetrazolo[5,1-b]quinazolines were synthesized by the reactions of 5-methyl-7-phenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine with α,β-unsaturated carbonyl compounds and their synthetic equivalents in methanol in the presence of sodium methoxide. The spontaneous or specifically target oxidation of these derivatives gives rise to aromatic tetrazoloquinazolines. The reaction pathways and mechanisms were discussed. The structures of the resulting compounds were confirmed by IR and ¹H NMR spectroscopy, mass spectrometry, and elemental analysis. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1971–1976, September, 2008.     

Synthesis and chemical transformations of partially hydrogenated [1,2,4]triazolo[5,1-b]quinazolines

The reaction of 5-methyl-7-phenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine with α,β-unsaturated carbonyl compounds in MeOH in the presence of MeONa affords partially hydrogenated aryl-substituted [1,2,4]triazolo[5,1-b]quinazolines. Hydrolysis, oxidation, reduction, and alkylation of 5,6,8-triphenyl-5,6,7,10-tetrahydro[1,2,4]triazolo[5,1-b]quinazoline were studied. The structure of one oxidation product, viz., 7-hydroxy-5,6,8-triphenyl-6,7-dihydro[1,2,4]triazolo[5,1-b]quinazoline, was established by X-ray diffraction. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 335—340, February, 2006.