Ethylenimine derivatives of some 1,2,4-triazines

The first 3-ethylenimino-1,2,4-triazines ( 9 ) have been synthesized from the corresponding 3-(β-chloroethyl)amino-1,2,4-triazines ( 8 ). In addition some 2,3-dihydroimidazo[1,2-b]-1,2,4-triazines and imidazo[1,2-b]-1,2,4-triazines were obtained. The stability, properties and potential therapeutic value of these compounds are discussed.     

Heterocyclic nitro compounds. 28. 1-(Oxoalkyl)-3-nitro-5-r-1,2,4-triazoles in reactions with hydrazine and hydroxylamine

The reaction of 1-(oxoalkyl)-3-nitro-5-R-1,2,4-triazoles with hydroxylainine and hydrazine takes place at the keto group to give azines and oximes (R = H, CH₃), with reduction of the nitro group (R = NO₂, hydroxylamine), or with participation of both reaction centers with annelation and conversion to triazolo[3,2-c]-1,2,4-triazines and -1,2,4-triazepines, depending on the character of the substituent in the 5 position of the triazole ring and the type of reagent.See [1] for Communication 27.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1113–1117, August, 1982.     

Nitroazines. 9. Characteristic features of nucleophilic substitution of the nitro group in dihydroazolo[5,1-c] [1,2,4]triazines

The reaction of 6-nitro-7-oxo-4,7-dihydroazolo[5,1-c]-1,2,4-triazines with O-, N-, and S-nucleophiles leads to the corresponding 6-substituted compounds. In the reaction of 2,4-dimethyl-6-nitro-7-oxo-4,7-dihydro-1,2,4-triazolo[5,1-c][1,2,4]triazine with hydrazine hydrate, 3-methyl-5-(N-methylamino)-1,2,4-triazole is formed.Article 8, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 253–257, February, 1989.     

3,4,5,6-Tetrafluoro-1,2-dehydrobenzene in reactions with 1,2,4-triazines

Tetrafluoro-substituted aryne, 3,4,5,6-tetrafluoro-1,2-dehydrobenzene, has been generated in situ from 2-amino-3,4,5,6-tetrafluorobenzoic acid, and its reactivity in reactions with 1,2,4-triazines as dienes has been studied. In these reactions, the corresponding azine ring transformation products, i.e., 1,2,3,4-tetrafluoro-10-(1H-1,2,3-triazol-1-yl)pyrido[1,2-a]indoles, have been obtained, in the case of triazines activated by the presence of electron-withdrawing groups, such as 6-aryl-3-(2-pyridyl)-5-cyano-1,2,4-triazines. The crystal structure of the obtained products was confirmed by X-ray diffraction analysis.     

Reaction of N-cyanoformimidates with some heterocyclic compounds. A new synthesis of 5-azaadenine and related compounds

3-Amino-1,2,4-triazoles and 2-aminobenzimidazole were reacted with N-cyanoimidates to give 5-amino-1,2,4-triazolo[2,3-a]-1,3,5-triazines (5-azaadenines) and 4-aminobenzimidazo[1,2-a]-1,3,5-triazines, respectively. The structures of the compounds obtained were confirmed through the comparison with some of the possible isomers prepared by independant methods.     

Ring transformation of 1,5-benzoxazepines into spirobenzoxazoles. Synthesis of pyrazolo[1′,5′:3,4][1,2,4]triazino-[5,6-b][1,5]benzoxazepines and spiro[benzoxazole-2′(3′H),4(1H)-pyrazolo[5,1-c][1,2,4]triazines]

The reactions of the 3-substituted 4-amino-8-ethoxycarbonyl[5,1-c][1,2,4]triazines 1 and 2 with o-amino-phenol hydrochloride gave the pyrazolo[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzoxazepines 5 and 8 . The alkylation of 5 with methyl iodide and isopropyl iodide afforded the 6-alkoxylpyrazolo[1′,5′:3,4][1,2,4]triazino-[5,6-b][1,5]benzoxazepines 6a and 6b , respectively. Refluxing of 5, 6a, 6b and 8 in hydrochloric acid/acetic acid resulted in ring transformation to produce the spiro[benzoxazole-2′(3′H),4(1H)pyrazolo[5,1-c][1,2,4]-triazines] 7a, 7b and 9 . The screening data of the above compounds was described.     

Synthesis of new heteroaromatic systems: Naphth[2,1-e]imidazo[5,1-c]-1,2,4-triazines and benz[e]imidazo-[5,1-c]-1,2,4-triazines

Cyclization of azo compounds, synthesized from 5-diazoimidazoles and 2-naphthol or p-substituted phenols, into naphth[2,1-e]imidazo[5,1-c]-1,2,4-triazines and benz[e]imidazo[5,1-c]-1,2,4-triazines occurs only in the presence of p-toluenesulfonic acid. Imidazo[4,5-d]-1,2,3-triazines are also formed in this reaction when an amide substituent is present in the imidazole ring.Ural State Technical University, Ekaterinburg 620002, Russia: e-mail: mokr@htf.ustu.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 540–546, April, 2000.     

Synthesis and photolysis of 3-tert-butyl-4-oxy(mercapto)-1,4-dihydropyrazolo[5,1-c][1,2,4]triazines

Russian Chemical Bulletin - Reactions of 3-tert-butyl- or 3,4-di-tert-butyl-substituted 8-methylpyrazolo[5,1-c][1,2,4]-triazines with trifluoroacetic anhydride afforded...     

Synthesis of 5-azaadenine derivatives from N-(1,2,4-triazol-5-yl)amidines

A method is proposed for the synthesis of N-substituted 5-azaadenines. The condensation of N-(1,2,4-triazol-5-yl)amidines with trichloroacetonitrile gives trichloromethyl derivatives of 1,2,4-triazolo[1,5-a]-1,3,5-triazines, which are converted by the action of primary or secondary amines into N-alkylamino- or N,N-dialkylamino-1,2,4-triazolo-[1,5-a]-1,3,5-triazines (5-azaadenines).Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 241–243, January, 1991.     

Chichibabin-type condensation of cyclic ketones with 3-R-1,2,4-triazin-5(4H)-ones

Reactions between substituted 1,2,4-triazines and ketones were investigated. General procedures for one-pot synthesis of hydrogenated derivatives of such polycyclic systems as benzo[c][1,2,4]triazino[1,6-a][2]azecine, [1,2,4]triazino[1,6-f]phenantridine, and dicyclopenta[b,d]pyrido[1,2-f][1,2,4]triazine are described.     

The mass spectra of 1,2,4-triazines and related compounds

The mass spectra of monocyclic 1,2,4-triazines and 1,2,4-triazines fused to a pyrazole ring through a bridgehead nitrogen have been investigated: fragmentation pathways were elucidated by the use of metastable ions and high resolution mass measurements. The spectra of the monocyclic 1,2,4-triazines indicate that loss of nitrogen from the molecular ions is a relatively unimportant feature. The decomposition modes of the bicyclic pyrazolo[3,2-c]-as-triazines are sensitive to the nature of the substituent in the triazine ring.     

Condensed as-triazines. Synthesis of 7-aryl-8H-[1,4]thiazino[2,3-e]-1,2,4-triazin-3(2H)-one

Ring closure of 6-amino-3-oxo-as-triazine-5-thione with α-haloketones provides the thiazino[2,3-e]-1,2,4-triazines which dehydrate via an unusual pathway to give 7-aryl-8H[1,4]thiazino[2,3-e]-1,2,4-triazin-3(2H)-ones.     

Synthesis of thieno[2,3-e]-1,2,4-triazines

3-Methylmercapto-5-oxo-6-vinyl- and 2-methyl-3-mercapto-5-oxo-6-vinyl-2,5-dihydro-1,2,4-triazines were readily converted into the corresponding thieno[2,3-e]-1,2,4-triazine in one step by the action of phosphorus pentasulfide in pyridine. 4-Methyl-3-mercapto-5-oxo-4,5-dihydro-1,2,4-triazine is only converted into the 5-thioxo analog and no thiophene ring product was obtained under the same conditions. Thieno[2,3-e]-1,2,4-triazines were also more efficiently obtained by the action of phosphorus petnasulfide in pyridine on the appropriate 6-acylmethyl-3-mercapto-5-oxo-2,5-dihydro-1,2,4-triazine.     

Polysubstituted 2,3-dihydrofuro[2,3-b]pyridines and 3,4-dihydro-2H-pyrano[2,3-b]pyridines via microwave-activated inverse electron demand Diels-Alder reactions

Polysubstituted 2,3-dihydrofuro[2,3-b]pyridines and 3,4-dihydro-2H-pyrano[2,3-b]pyridines have been synthesized from 1,2,4-triazines using the inverse electron Diels-Alder reaction. For this purpose, 3-methylsulfanyl-1,2,4-triazines were reacted with several nucleophiles allowing the formation of appropriately substituted alkynes to undergo the intramolecular inverse electron demand Diels-Alder reaction. Sealed-tube microwave activation of the cycloaddition reaction has proved to be very efficient and allowed shorter reaction times. This strategy enabled an efficient synthesis of 3-hydroxy-2,3-dihydrofuro[2,3-b]pyridines and 4-hydroxy-3,4-dihydro-2H-pyrano[2,3-b]pyridines with several points of diversity on the bicyclic scaffold.     

Synthesis of 2,8-disubstituted 1,2,4-triazolo[5,1-i]purines

This paper describes the preparation of 2-aryl-8-fluorobenzyl-1,2,4-triazolo[5,1-i]purines 2 , starting from 2-aryl-7,8-diamino-1,2,4-triazolo[1,5-c]pyrimidines 9 . Our synthetic procedure represents the first example of a feasible approach for the synthesis of 2,8-disubstituted triazolo[5,1-i]purines. New syntheses of 5-amino-3-arylpyrimido[5,4-e]1,2,4-triazines 12 and 8-fluorobenzyl-6-hydrazinopurines 15 are also reported.     

Aminovinyl ketones and aminovinyl esters as CCN building blocks for the synthesis of 1H-pyrrolo[3,2-e]1,2,4-triazines

5,6-Unsubstituted-3-aryl-1,2,4-triazines were found to react with aminovinyl ketones and aminovinyl esters in acetic anhydride to form derivatives of 3a,4,7,7a-tetrahydro-1H-pyrrolo[3,2-e]1,2,4-triazines in good yields.     

Photochemistry of phenyl-substituted 1,2,4-thiadiazoles. 15N-labeling studies

Irradiation of 5-phenyl-1,2,4-thiadiazole (6) resulted in the formation of benzonitrile (5), 3-phenyl-1,2,4-thiadiazole (4), phenyl- and diphenyl-1,3,5-triazines (7 and 8), and a trace quantity of diphenyl-1,2,4-thiadiazole (9). The formation of 4,5, 7, and 8 can be explained in terms of photoinduced electrocyclic ring closure resulting in the formation of an intermediate 4-phenyl-1,3-diaza-5-thiabicyclo[2.1.0]pentene. 15N-labeling experiments revealed that sulfur can undergo sigmatropic shifts around all four sides of the diazetine ring. Thus, irradiation of 6-4-15N led to the formation of 6-2-15N and an equimolar mixture of 4-2-15N and 4-4-15N. The thiabicyclo[2.1.0]pentene intermediate is also suggested to undergo sulfur elimination resulting in the formation of phenyldiazacyclobutadiene, which can undergo complete fragmentation to benzonitrile or [4+2] cycloaddition leading to unstable tricyclic adducts, the suggested precursors of the 1,3,5-triazine products 7 and 8. The observed 15N distribution in 7 and 8 is consistent with this mechanism. Irradiation of 4 led only to the formation of 5. 15N-labeling experiments show that 4 does not undergo electrocyclic ring closure but reacts exclusively by photofragmentation of the thiadiazole ring.     

Annelation of the thiazole ring to 1,2,4-triazines by tandem AN—AN or SN H—SN H reactions

The reactions of 3-aryl-1,2,4-triazines with aromatic thioamides and 4-arylthiosemicarbazides in acetic anhydride at room temperature afforded cyclic products of the tandem nucleophilic addition reactions, viz., tetrahydrothiazolo[4,5-e]-annelated 1,2,4-triazines, in good yields. The latter underwent aromatization in the presence of potassium permanganate.     

Synthesis of 3-amino-5H-pyrrolo[2,3-e]-1,2,4-triazines by Sonogashira/copper(I)-catalyzed heteroannulation

A Sonogashira/copper(I)-catalyzed heteroannulation sequence was developed to convert 3,5-diamino-6-chloro-1,2,4-triazines to the corresponding 3-amino-5H-pyrrolo[2,3-e]-1,2,4-triazine derivatives in good yields.     

Reaction of 4-Amino-3-methylthio-5-oxo-6-R-4,5-dihydro-1,2,4-triazines with Sulfonylacetic Acid Nitriles

The reactions of 4-amino-3-methylthio-5-oxo-6-R-4,5-dihydro-1,2,4-triazines with arylsulfonylacetonitriles and with dinitriles of sulfonyldiacetic acid and methylenebis(sulfonylacetic) acid have been studied. 7-Amino-3-R-8-(R'-sulfonyl)-1,4-dihydropyrazolo[5,1-c][1,2,4]triazin-4-ones have been synthesized and these are the first representatives of geminal sulfones in which the heterocyclic ring is bound directly to the sulfur atoms of the sulfonyl groups.