Synthesis of Substituted 5,6-Dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines

A one-pot synthetic approach to the novel 5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines by thermal cyclization of 4-acylhydrazino-2,3-dihydro-1H-1,5-benzodiazepines is described.     

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 4-Amino-6-R-4,5-dihydro-3-phenacylthio-1,2,4-triazin-5-ones and 8H-3-R-7-Aryl-1,2,4-triazino[3,4-b][1,3,4]thiadiazin-4-ones

A study was carried out on the reaction of 4-amino-6-R-2,3,4,5-tetrahydro-3-thioxo-1,2,4-triazin-5-ones with halo ketones in alkaline media to yield 4-amino-6-R-4,5-dihydro-3-phenacylthio-1,2,4-triazin-5-ones, which then convert to 8H-3-R-7-aryl-1,2,4-triazino[3,4-b][1,3,4]thiadiazin-4-ones.     

Unexpected Direction of Iodocyclization of 3-Allylthio-5-phenyl-4H-1,2,4-triazole

The reaction of 3-allylthio-5-phenyl-4H-1,2,4-triazole with iodine to give a mixture of 5,6-dihydro-5-iodomethyl-3-phenyl[1,3]thiazolo[2,3-c][1,2,4]triazole, 6,7-dihydro-6-iodo-3-phenyl-5H-[1,2,4]triazolo[3,4-b][1,3]thiazine, 5,6-dihydro-6-iodomethyl-2-phenyl[1,3]thiazolo[3,2-b][1,2,4]triazole, and 6,7-dihydro-6-iodo-2-phenyl-5H-[1,2,4]triazolo[5,1-b][1,3]thiazine has been studied. The structure of the products obtained was established using ¹H NMR spectroscopy of their dehydriodination products.     

Aminolysis 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

We have established that the products of aminolysis of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo-[5,1-b][1,3]thiazin-7-ones in boiling ethanol are 3-R-3-(5-aryl-4H-1,2,4-triazol-3-ylsulfanyl)-propanamides, and at 180°C–210°C (depending on the structure of the substituent R): 3-phenyl-4,5-dihydro-1H-1,2,4-triazoline-5-thione and 3-arylacrylamides or 3-(3-aryl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)propanamides. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1587–1592, October, 2005.     

Novel One-Pot Multicomponent Synthesis of Substituted 2,3-Dihydro-2-(6-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)phthalazine-1,4-diones and Substituted 3-[3-(N′-Benzylidene-hydrazino)-7H-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazin-6-yl]-4-hydroxy-6-methyl-pyran-2-ones

A one-pot procedure has been developed for the synthesis of substituted 2,3-dihydro-2-(6-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7H-[1,2,4]triazolo[3,4-b] [1,3,4]thiadiazin-3-yl)phthalazine-1,4-diones by reaction of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and phthalic anhydrides in acetic acid medium. Similarly, a one-pot, three-component synthetic procedure has been developed for substituted 3-[3-(N¹-benzylidene-hydrazino)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-yl]-4-hydroxy-6-methyl-pyran-2-ones from 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and various aromatic aldehydes in absolute ethanol and a few drops of glacial acetic acid.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

2-R-5-Ar(Het)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones

A novel method for synthesis of 2-R-5-Ar(Het)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by condensation of 3-R-4,5-dihydro-1H-1,2,4-triazole-5-thiones with 3-aryl(heteryl)-2-propenoyl chlorides is proposed.     

TheSemmler-Wolff aromatization andSchmidt reaction applied to some pyrido[2′,3′:3,4]pyrazolo[5,1-c][1,2,4]benzotriazines

Pyrido[2,3:3,4]pyrazolo[5,1-c][1,2,4]benzotriazin-4(1H)ones were transformed via their oximes in aSemmler-Wolff aromatization process in the tetracyclic heteroaromatic amines4 or bySchmidt reaction into a mixture of the same amine4 and a ring enlarged lactam3. Syntheses of some halo pyrazolo[3,4-b]pyridines and a photochemical transformation of 3-azidopyrazolo[3,4-b]pyridine are also described.

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Über dieSemmler-Wolff- undSchmidt-Reaktion einiger Pyrido[2,3:3,4]pyrazolo[5,1-c][1,2,4]benzotriazine

Zusammenfassung Pyrido[23:3,4]pyrazolo[5,1-c][1,2,4]benzotriazin-4(1H)one werden über Oxime in einerSemmler-Wolff-Reaktion in die tetracyklischen aromatischen Amine4 umgewandelt. In einerSchmidt-Reaktion wurden dieselben Ketone in ein Gemisch aus Amin4 und Lactam3 übergeführt. Synthesen von halogensubstituierten Pyrazolo[3,4-b]pyridinen und photochemische Umwandlung von 3-Azidopyrazolo[3,4-b]pyridin werden beschrieben.

     

Study of the Products of Iodocyclization of 4-Allyl-5-phenyl-1,2,4-triazole-3-thione

The interaction of 4-allyl-5-phenyl-1,2,4-triazole-3-thione with iodine proceeds with the formation of a mixture of 6-iodomethyl-3-phenyl-5,6-dihydrothiazolo[2,3-c]-1,2,4-triazole and 6-iodo-3-phenyl-6,7-dihydro-5H-1,2,4-triazolo[3,4-b]-1,3-thiazine. The structures of the cyclization products obtained were established on the basis of the ¹H NMR spectra of their dehydroiodinated derivatives. 6-Methyl-3-phenylthiazolo[2,3-c]-1,2,4-triazole, 3-phenyl-5H-1,2,4-triazolo[3,4-b]-1,3-thiazine, and 3-phenyl-7H-1,2,4-triazolo[3,4-b]-1,3-thiazine are formed on eliminating HI from the cyclization products.     

Cyclocondensation of 2-Amino-1,3,4-thiadiazoles with β-Sulfonylvinyltrifluoromethyldiols

A series of CF₃-containing 6,7-dihydro-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-ols was obtained by the interaction of 2-amino-1,3,4-thiadiazoles with -sulfonylvinyltrifluoromethyldiols and their stereochemistry was established. The structure of 5-(phenylsulfonyl)-7-(trifluoromethyl)-6,7-dihydro-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-ol was confirmed by X-ray crystallography.     

Synthesis,Antibacterial, and Antifungal Activities of Imidazo[2,1-c][1,2,4]triazoles and 1,2,4-Triazolo[4,3-a]pyrimidinones

A straightforward method has been developed for the synthesis of 1-phenyl-imidazo [2,1-c][1,2,4]triazole derivatives 5a–j and 1-phenyl-[1,2,4]triazolo[4,3-a]pyrimidinones derivatives 6a–g starting from 5-amino-1-phenyl[1,2,4]triazole and p-toluenesulfonic acid (PTSA). This methodology affords a number of 1-phenyl-imidazo [2,1-c][1,2,4]triazoles 5a–j and 1-phenyl-[1,2,4]triazolo[4,3-a]pyrimidinones 6a–g in reasonable yields and short reaction times. The structures of all new compounds were elucidated using infrared, ¹H and ¹³C NMR, and high-resolution mass spectrometry. Some of the newly synthesized compounds were screened for their antimicrobial activity.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications ^® for the following free supplemental resource(s): Full experimental and spectral details.]     

Synthesis and molecular structure of 2,4,8a-triaryl-6-methylperhydro[1,3,2]dioxaborinino[5,4-c]pyridines

Condensation of arylboronic acids with 4-hydroxy-3-(-hydroxybenzyl)-1-methyl-4-phenylpiperidine afforded 2,4,8a-triarylperhydro[1,3,2]dioxaborinino[5,4-c]pyridines. The molecular structure of 6-methyl-2,4,8a-triphenylperhydro[1,3,2]dioxaborinino[5,4-c]pyridine was established by X-ray diffraction analysis.     

2-R-7-methyl[1,2,4]triazolo[2,3-a]pyrimidines: synthesis and structures

Reactions of 5-R-3-amino-1,2,4-triazoles with ethoxymethylideneacetylacetone and ethyl ethoxymethylideneacetoacetate proceeded regioselectively, giving 2-R-7-methyl[1,2,4]triazolo[2,3-a]-pyrimidines in good yields. The compounds obtained were characterized by elemental analysis, ¹H NMR spectroscopy, and X-ray diffraction analysis (for ethyl 2-ethylthio-7-methyl[1,2,4]triazolo[2,3-a]pyrimidine-6-carboxylate). The frontier orbitals, the molecular electrostatic potential, and the geometries of the reagent molecules were calculated by the DFT method (B3LYP/6-31G**). Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1244–1248, June, 2008.     

Synthetic Approach to 6-Benzoyl-2H-[1,2,4]triazine-3,5-dione and 6-Benzyl-5-thioxo-3,4-dihydro-2H-[1,2,4]triazin-3-one and Studies on Their Transformation to Fused[1,2,4]triazine Systems

Reaction of phenylpyruvic acid with semicarbazide afforded 6-benzyl-2H-[1,2,4]triazine-3,5-dione ( 1 ) which upon oxidation with potassium dichromate furnished 6-benzoyl-2H-[1,2,4]triazine-3,5-dione ( 2 ) in good yield. Constructing pyrazolo[3,4-e][1,2,4]triazine system ( 4 ) was achieved by reacting 2 with arylhydrazines in ethanolic solution. However treatment of 2 with the less reactive heteroarylhydrazines gave only the corresponding hydrazones ( 3 ). Attempt for constructing 1,2,4,5,10-pentaaza-dibenzo[a,d]cyclohept-3-one ( 7 ) from 2 was failed and (benzoimidazol-2-yl) [1,2,4] triazine derivative ( 6 ) was the only product. Reaction of 1 with phosphorus pentasulphide afforded compounds 8 and 9 . Compound 8 was transformed to the hydrazino compound 14 , which led to the construction of triazolo[4,3-d] [1,2,4]triazine system. Thus compounds 15 and 16 were obtained by reacting 14 with carbon disulfide or acetic anhydride respectively. Attempt to couple 8 with chloroacetic acid failed, while it's known isomer 10 led to the formation of thiazolo [2,3-c] [1,2,4]triazine derivative ( 13 ). Simple theoretical calculation using AM1 and PM3 semiempirical Hamitonian provided rational ways to correlate the reactivity with structure proposed.     

Fluoroalkyl-containing lithium β-diketonates in the synthesis of 1,2,4-triazolo[1,5-a]pyrimidines

Cyclocondensation of fluorine-containing lithium -diketonates with 3-amino-1,2,4-triazoles afforded 7-fluoromethyl-1,2,4-triazolo[1,5-a]pyrimidines.     

Regioselective Synthesis of 2-Substituted [1,2,4]Triazolo[5,1-b][1,3]thiazin-7-ones by Heteropolyacids

2-Substituted [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones 3 were synthesized via regioselective cyclization of 4H-[1,2,4]triazol-3-ylsulfanyl-acrylic acids 2 in the presence of catalytic amounts of heteropolyacids at room temperature in very good yields and rates.     

2-Methylthio-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidin-5- and -7-Ones

The cyclocondensation of methylcinnamates and arylidene derivatives of Meldrums acid with 3-amino-5-methylthio-1,2,4-triazole in DMF gives 2-methylthio-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]-pyrimidin-5-ones. The reaction involving arylidene derivatives of Meldrums acid or its synthetic equivalents in ethyl acetate with a catalytic amount of pyridine gives a mixture of 2-methylthio-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]pyrimidin-5- and -7-ones.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 246–251, February, 2005.     

Synthesis of New Imidazo[4,5-b]pyridine Derivatives

New imidazo[4,5-b]pyridine derivatives with various substituents in the 2-position (,-unsaturated ketones, imines, ²-pyrazolines, pyrimidines, 1,2,3,4-tetrahydropyrimidines) and derivatives of the new pyrido[3',2':4,5]imidazo[1,2-d][1,2,4]triazine ring system were synthesized. Biological data for selected compounds are presented.     

Condensed Thienopyrimidines. 14. Synthesis of 10H-Thiopyrano[4',3':4',5']thieno[2',3':4,5]pyrimido[2,3-c]-1,2,4-triazines

Reaction of a substituted 2-aminothienothiopyran with methyl(phenyl) isothiocyanate, intramolecular cyclization of the obtained N'-methyl(phenyl) thioureido derivatives, and work up of the cyclization products with hydrazine hydrate gave 2-hydrazinodihydrothiopyranothienopyrimidines. Treatment of the latter with pyruvic acid gave the novel 10H-thiopyrano[4',3':4',5']thieno[2',3':4,5]pyrimido[2,3-c]-1,2,4-triazines.     

Bromination of Substituted 5H-Imidazo[1,2-b]-1,2,4-triazepin-4-ones and -thiones

The reactions of substituted 5H-imidazo[1,2-b]-1,2,4-triazepin-4-ones and -thiones with bromine and N-bromosuccinimide have been studied. Derivatives of 3- and 8-bromo-, 3,8-dibromoimidazo[1,2-b]-1,2,4-triazepine and 5H-2-bromomethyl-3-methyl-7,8-diphenylimidazo[1,2-b]-1,2,4-triazepin-4-one are formed, depending on the degree of substitution, the nature of the brominating agent, and the reaction conditions.