1,2,4-Triazines VIII. The synthesis of 1,2,4-triazino[2,3-e]pyrazolo[1,5-a]-1,3,5-triazines and 1,2,4-triazino[4,3-e]pyrazolo[],5-a] -1,3,5-triaziness

Substituted 2,5-dihydro-3[3-methyI(or phenyl)-5-aminopyrazolyl]-1,2,4-triazin-5-ones reacted with orthoesters to yield exclusively 1,2,4-triazino[2,3-e]pyrazolo[1,5-a]-1,3,5-triazin-5-ones. The structure elucidation was supported by independent synthesis of the isomeric 1,2,3-triazino-[4,3-e]pyrazolo[1,5-α]-1,3,5-triazin-7-one as well as by spectroscopical methods.     

Condensed imidazo-1,2,4-azines. 15. Reaction of 1,2-diaminobenzimidazole with 5-phenyl-2,3-dihydrofuran-2,3-dione

The reaction of 1,2-diaminobenzimidazole with 5-phenyl-2,3-dihydrofuran-2,3-dione in acetic acid gave a mixture of 2-benzoylmethyl-1,2,4-triazino [2,3-a]-benzimidazol-4H-3-one and 3-benzoylmethyl-1,2,4-triazino[2,3-a]benzimidazol-1H-2-one, the intramolecular cyclization of which gave isomeric 2-phenylfuro-[5,4-e]- and 2-phenylfuro[4,5-e]-1,2,4-triazino[2,3-a]benzimidazoles. Only the corresponding furo[4,5-e]-1,2,4-triazino[2,3-a]benzimidazole was isolated when the reaction was carried out in sulfuric acid.See [1] for Communication 14.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 533–535, April, 1987.     

Tautomerism of 1,2,4-triazino[2,3-a]benzimidazol-5(4)H-3-ones

Studies by X-ray diffraction and quantum chemical methods demonstrated that 1,2,4-triazino[2,3-a]benzimidazol-5(4)H-3-ones exist in the condensed state primarily in the 5H-tautomeric form, whereas these compounds exist, most likely, predominantly as 4H tautomers in the gas phase. The low-barrier tautomerism of 1,2,4-triazino[2,3-a]benzimidazol-5(4)H-3-ones occurs through the intermediate formation of hydrogen-bonded cyclic dimers followed by the concerted two-proton transfer. N-Alkylation of both the electroneutral and N-anionic forms of 2-methyl-1,2,4-triazino[2,3-a]benzimidazol-5(4)H-3-one affords predominantly N(4)-alkyl derivatives. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 475–483, March, 2006.     

Synthesis of 1,2,4-triazolo[4,3-a]quinoline-9-, 1,2,3,4-tetrazolo[4,3-a]quinoline-9 and 1,2,4-triazino[4,3-a]quinoline-10-carboxylic acids from 2-chloro- and 2-hydrazinocinchoninic acids

Treatment of 2-chlorocinchoninic acid with hydrazine gives 2-hydrazinocinchoninic acid and with aroylhydrazines to give 1,2,4-triazolo[4,3-a]quinoline-9-carboxylic acids. These are also prepared by the action of benzoyl chloride or the carboxylic acid on 2-hydrazinocinchoninic acid. With pyruvic acid the latter gives 3-methyl-4-oxo-1,2,4-triazino[4,3-a]quinoline-10-carboxylic acid and with nitrous acid gives 1,2,3,4-tetrazolo[4,3-a]quinoline-9-carboxylic acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1227–1229, September, 1991.     

Triazino-1,2,4-[4,5-a] indoles IV. Etude des triazinoindolethiones

The 1,2-dihy dro-1,2,4-triazino[4,5-a] indole-1-thiones 2 and 3 obtained by sulphurization of the 1,2-dihydro-1,2,4-triazino-[4,5-a] indol-1-ones 1 and 4 with phosphorus pentasulphide are intermediate products in the synthesis of 1,2,4-triazino[4,5-a]-indolc 10 and 4-methyl-1,2,4 omdp;e 19. The thiolactam-thiolactim tautomerism was studied using the ir and nmr spectra and allowed N. and S.substitutions. The methylation with dimethyl sulphate afforded mixtures of N. and S. methyl derivatives which were separated by chromatographic analysis and identified by |21|0H nmr and unequivocal synthesis.     

Study of the prototropic tautomerism in the 1,2,4-triazino[2,3-a]benzimidazol-(4h)-3-one system

The peri-prototropic tautomerism of 1,2,4-triazino[2,3-a]benzimidazol-(4H)-3-one in the gas and liquid phases was studied by IR and PMR spectroscopy, high-efficiency liquid chromatography, mass spectrometry, and photoionization. Analytical criteria were found for the fixed tautomeric forms of this compound, which permitted us to evaluate the nature of the methylation reaction carried out by different methods.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 937–943, July, 1992.     

Research on imidazo[1,2-a]benzimidazole derivatives. 22. Synthesis of 2,3-dihydroimidazo[1,2-a]benzimidazoles starting from 2-imino-3-(2-hydroxyethyl)benzimidazolines

A -elimination reaction with the formation of 2-imino-3-vinylbenzimidazolines occurs simultaneously with intramolecular alkylation and the formation of an imidazoline ring in the action of alcoholic alkali on 2-imino-3-(2-chloroethyl) benzimidazolines. The thermolysis of 3-chlorethyl-substituted imines without a solvent or in an inert solvent leads exclusively to 2,3-dihydroimidazo[1,2-a] benzimidazoles. An attempt to obtain the latter directly from 2-imino-3-(2-hydroxyethyl) benzimidazolines by the action of a mixture of thionyl chloride and acetic anhydride on them also leads to ambiguous results.See [1] for communication 21.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 918–925, July, 1986.     

Synthesis of 4-and 5-substituted 2-methyl-and 2-(2-carboxyethyl)-1,2,4-triazino-[2,3-a]benzimidazol-4(5)H-3-ones

Condensation of 2-alkylamino-1-aminobenzimidazoles and quaternary 1,2-diamino-3R-benzimidazolium salts with pyruvate and α-ketoglutaric acid has given 4-and 5-substituted 2-methyl-and 2-(2-carboxyethyl)-1,2,4-triazino[2,3-a]benzimidazol-4(5)H-3-ones. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 738–747, May, 2006.     

Condensed imidazo-1,2,4-triazines. 29. Synthesis of 3-amino-1,2,4-triazino[2,3-f]xanthines and their spectral properties

The reaction of substituted 3-chloro-1,2,4-triazino[2,3-f]theophyllins with secondary amines gives new water-soluble active media for dye lasers. The luminescence and generation characteristics of these compounds were studied. These properties were found to depend on the lactam-lactim tautomerism of 1,2,4-triazino[2,3-f]theophyllin-4H-3-ones.For Communication 28, see [1].Kherson Industrial University, Kherson 325008, Ukraine. A. N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, Moscow 117071. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 551–554, April, 1998.     

Synthesis of 1,2,4-triazolo[4,3-c]-, tetrazolo[1,5-c]-, and 1,2,4-triazino[5,6-c]pyrano[4'3':4,5]pyrrolo-[3,2-e]pyrimidine derivatives

4-Hydrazinopyrano[4',3':4,5]pyrrolo[2,3-d]pyrimidines served as precursors in the synthesis of new heterocyclic systems, namely, 1,2,4-triazolo[4,3-c]-, tetrazolo[1,5-c]-, and 1,2,4-triazino[5,6-c] pyrano[4',3':4,5]-pyrrolo[3,2-e]pyrimidines.A. L. Mndzhoyan Institute of Fine Organic Chemistry, National Academy of Sciences of the Republic of Armenia, 375014 Yerevan. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 700-703, May, 1995. Original article submitted January 10, 1995; revision submitted April 20, 1995.     

Parallel solid-phase synthesis of 2-imino-4-oxo-1,3,5-triazino[1,2-a]benzimidazoles via tandem aza-Wittig/heterocumulene-mediated annulation reaction

The parallel synthesis of a large number of 2-imino-4-oxo-1,3,5-triazino[1,2-a]benzimidazole derivatives via a solid-phase 1,3,5-triazino-annulation reaction is described. The solid-phase approach involves the in situ generation of iminophosphorane derivatives derived from resin-bound 2-aminobenzimidazoles employing Mitsunobu conditions. The subsequent Aza-Wittig reaction of the iminophosphoranes with isocyanates leads to highly reactive carbodiimides, which undergo an intramolecular heterocyclization reaction to form tetrasubstituted 2-imino-4-oxo-1,3,5-triazino[1,2-a]benzimidazoles in high yields (74-94%) and good purity (>80%).     

One-pot synthesis of imidazo[1,2-b]pyrazole,imidazo[1,2-b]-1,2,4-triazole,imidazo[1,2-a]pyridine,imidazo[1,2-a]pyrimidine,imidazo[1,2-a]benzimidazole,and 1,2,4-triazolo[4,3-a]benzimidazole derivatives

Hydrazonoyl bromides 1a-c react with 5-amino-3-phenyl-1H-pyrazole, 5-amino-1H-1,2,4-triazole, 2-aminopyridine, and 2-aminobenzimidazole to afford the corresponding imidazol[1,2-b]pyrazoles 10, imidazo[1,2-b]-1,2,4-triazoles 11, imidazo[1,2-a]pyridines 16, imidazo[1,2-a]pyrimidines 17, and imidazo[1,2-a]benzimidazoles 20, respectively. Compounds 1a-c reacted also with 2-methylthiobenzimidazole to give 1,2,4-triazolo[4,3-a]benzimidazole derivatives 21. © 1997 John Wiley & Sons, Inc.     

Synthesis and transformations of 2,3-dioxo-2,3-dihydroimidazo [1,2-a]-benzimidazole derivatives

9-(H)Alkyl-2,3-dioxo-2,3-dihydroimidazo[1,2-a]benzimidazoles were synthesized by the action of oxalyl chloride on 2-amino-1(H)alkylbenzimidazoles and subsequent cyclization of the resulting 2-amino-1-(H)alkyl-3-chlorooxalylbenzimidazolium chlorides in the presence of triethylamine. The behavior of the synthesized benzimidazoles with respect to the action of alkalis, lithium aluminum hydride, and ethylmagnesium bromide was studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1391–1395, October, 1976.     

Synthesis of pyrazolo[1′,5′:1,2]-1,3,5-triazino[5,6-a]benzimidazoles

The synthesis of a new class of tetracyclic bridgehead heterocycle pyrazolo[1′,5′:1,2]-1,3,5-triazino[5,6-a] benzimidazoles is reported. The key intermediate 2-(3-aminopyrazol-2-yl)benzimidazoles were prepared by the reaction of 2-hydrazinobenzimidazole with an appropriate reagent such as ethyl ethoxymethylenecyanoacetate, ethoxymethylenemalononitrile, β-cyanoacetophenone or α-formylphenylacetonitrile. The treatment of these key intermediates with triethylorthoesters afforded the corresponding pyrazolo[1′,5′:1,2]-1,3,5-triazino[5,6-a]benzimidazoles.     

Efficient electrosynthesis of 1,2,4-triazino[3,4-b]-1,3,4-thiadiazine derivatives

Electrochemical oxidation of catechols 1a-d has been studied in the presence of 4-amino-6-methyl-1,2,4-triazine-3-thion-5-one 3 as a nucleophile in aqueous solutions, using cyclic voltammetry and controlled-potential coulometry, leading to the efficient synthesis of 1,2,4-triazino[3,4-b]-1,3,4-thiadiazines.     

Synthesis of 1-and 7-substituted 2,3-dihydro-1h-pyrrolo[1,2-a]benzimidazoles

Cyclization of 5-substituted 2-(-chloroalkyl)benzimidazoles in the presence of sodium ethoxide gave some benzene-and pyrroldine-ring-substituted 2,3-dihydro-1H-pyrrolo[1,2-a]-benzimidazoles.Translated from Khimiya Geterotsklicheskikh Soedinenii, No.8, pp.1137–1139, August, 1974.     

1,2,4-Triazino[4,3-c]- and [2,3-c]quinazolines

This paper describes the reactions of 2-o-aminophenyl-1,4,5,6-tetrahydro-1-methyl-1,2,4-triazine with a variety of reagents to give substituted 1,2,4-triazino[4,3-c]quinazolines or 1,2,4-triazino[2,3-c]quinazolines. Certain representative compounds of these two new heterocyclic systems were characterized by the tlc, ir, nmr, mass spectra, and identified by unequivacol synthesis.     

Synthesis of 2-substituted cinchoninic acid amides and their cyclization into 1,2,4-triazolo[4,3-α]-quinoline-9-and 1,2,4-triazino[4,3-a]quinoline-10-carboxylic acid amides

Substituted amides of 2-hydrazino- and 2-ethylhydrazinocinchoninic acids react with pyruvic acid and its ethyl ester to give amides of 3-methyl-4-oxo-1,2,4-triazino[4,3-a]quinoline-10-carboxylic acid. On reaction with aromatic aldehydes they are converted into amides of 2-ethyl-3-phenyl-2,3-dihydro-1,2,4-triazolo[4,3-a]quinoline-9-carboxylic acid, or, in the case of unsubstituted hydrazines, into amides of 2-arylidene-hydrazinocinchoninic acid, which was oxidized to substituted 1,2,4-triazolo[4,3-a]quinolines.Perm Pharmaceutical Academy, Perm 614600. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 701–705, May, 1977.     

Novel triazinium-imidothioate zwitterions: intermediates in the reaction of [1,3,4]thiadiazolo[2,3-d][1,2,4]triazolo[1,5-a][1,3,5]triazinium cations with amines

Starting with bis([1,3,4]thiadiazolo)[1,3,5]triazinium halides 1, a novel class of heterocyclic compounds, the [1,3,4]thiadiazolo[2,3-d][1,2,4]triazolo[1,5-a][1,3,5]triazinium halides 5 were prepared. The reaction between 5 and primary or secondary amines 6 yielded highly substituted guanidines 8 and fused tricyclic bis([1,2,4]triazolo)[1,5-a:1′,5′-d][1,3,5]triazinium halides 9. The formation of the reactive triazinium-imidothioate zwitterions 7, which is controlled by the influence of negative hyperconjugation, was proven by NMR data and the X-ray structure of 7c. The subsequent ring-closure/ring-opening steps can be understood in terms of an S_N(ANRORC) process accompanied by intramolecular proton-transfer reactions. The zwitterions 7 were reacted with EtI forming cationic derivatives 10 or hydrolyzed at pH 6-7 to give novel heterocyclic ethanethioamides 11.     

Condensed Imidazo-1,2,4-azines. 31. Synthesis and Chemical Transformations of Substituted 1,2,4-Triazepino[2,3-a]benzimidazoles

By reaction of 1,2-diaminobenzimidazole with 1,3-diketones, acetoacetic ester and its derivatives, we have synthesized substituted 1,2,4-triazepino[2,3-a]benzimidazole and 5H-1,2,4-triazepino[2,3-a]benzimidazol-4-one. By reaction of 5H-2-methyl-1,2,4-triazepino[2,3-a]benzimidazol-4-one with aromatic aldehydes or phenyldiazonium chloride, we have obtained 3-arylidene(phenylazo) derivatives of this compound, and by reaction with P₂S₅ we have obtained 5H-2-methyl-1,2,4-triazepino[2,3-a]benzimidazole-4-thione. We have shown that when reacted with ammonia, primary or secondary amines, the latter forms 4-amino-substituted 2-methyl-1,2,4-triazepino[2,3-a]benzimidazole.