An unusual transformation of 5-acyl-1,2,4-triazines into 3-pyridyl-1,2,4-triazines via tandem Stille cross-coupling/aza Diels-Alder reaction

A new route to 3-heteroaryl-1,2,4-triazines possessing a keto substituent at C-5 of the 1,2,4-triazine core using a Stille cross-coupling procedure and their unexpected ring transformation into pyridyltriazines as a result of enolization of an acyl group catalyzed by metal ions, are reported.     

Reactions of 1,2,4-triazines with nitromethide ion. A convenient method of preparation of 1,2,4-triazin-5-ylcarbaldehyde oximes and their synthetic applications

An efficient procedure for the preparation of 1,2,4-triazin-5-ylcarbaldehyde oximes 2a-f from 1,2,4-triazines 1a-f and nitromethide ion is described. The oximes 2c-d were converted into corresponding 5-cyano-1,2,4-triazines 6c-d . The latter compounds react easily with various nucleophiles to afford 5-substituted 1,2,4-triazines 7a-i and with 1-pyrrolidino-1-cyclohexene to form cyano derivative of 5,6,7,8-tetrahydroisoquinoline 9 .     

1,2,4-triazines in organic synthesis. 8. Intramolecular diels-alder reaction of 5-acyl-1,2,4-triazineoxime ethers. New route of synthesis of alkylhetarylketones

Intramolecular diene cycloaddition of 5-acyl-1,2,4-triazineoxime ethers involving a dienophile substituent in the 3-position of the triazine ring is studied. New alkylhetarylketones are synthesized by hydrolysis of the condensed N- and O-containing heterocyclic products. The starting materials are prepared by oxidation of 5-acetyl- and 5-butyryl-3-methylthio-1,2,4-triazineoxime ethers with KMnO₄ to the sulfonyl derviatives with subsequent replacement of the CH₃SO₂ group by sodium 3-butyn-1-oxide, 4-pentyn-1-oxide and o-cyanophenoxide.For Communication 7, see [1].Institute of Chemistry, Agricultural and Teachers University, Siedlce, 08–110, Poland.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 381–389, March, 1999.     

Synthesis and structure of 6-tert-butyl-5-triphenylgermyl-1,2,4-triazines

Russian Chemical Bulletin - 3-tert-Butyl-8-methyl-4-triphenylgermyl-1,4-dihydropyrazolo[5,1-c][1,2,4]triazine and...     

Synthesis and transformations of 3-azido-5-amino-1,2,4-triazines

The reaction of the tetrazolediazonium ion with malonic acid dinitrile and nitroacetonitrile leads to the formation of 3-azido-5-amino-1,2,4-triazine derivatives. According to the mass-spectrometric data and the results of X-ray diffraction analysis, the crystalline compounds exist in the amino form. The facile hydrolysis of the amino and azido groups to azauracils is an argument in favor of the existence of the imino form in solution.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 557–561, April, 1984.     

Synthesis and Structure of 5-Indolyl-6-thienyl-1,2,4-triazines

Acylation of indole and 2,5-dimethylthiophene with 2-(3-indolyl)-2-oxoacetyl chloride afforded the corresponding diketones. 1-(2,5-Dimethyl-3-thienyl)-2-(3-indolyl)ethanedione reacted with thiosemicarbazide under atmosperic and elevated pressure to give 6-(2,5-dimethyl-3-thienyl)-5-(3-indolyl)-2,3-dihydro-1,2,4-triazine-3-thione whose structure was studied in detail by the X-ray diffraction method. Reactions of 6-(2,5-dimethyl-3-thienyl)-5-(3-indolyl)-2,3-dihydro-1,2,4-triazine-3-thione with amines and hydrazine resulted in formation of fused triazolo- and tetrazolotriazines.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 6, 2005, pp. 895–902.Original Russian Text Copyright © 2005 by Krayushkin, Yarovenko, Sedishev, Zavarzin, Vorontsova, Starikova.Dedicated to Full Member of the Russian Academy of Sciences V.I. Minkin on his Jubilee     

1,2,4-triazines. III. A convenient synthesis of 1,2,4-triazines and their covalent hydration

A general synthesis of 1,2,4-triazines, from 3-methylthiotriazines is described. It has been shown that 1,2,4-triazines undergo covalent hydration across the N₄-C₅ bond.     

Preparation of new 1,2,4-triazines

Several 1,2,4-triazines were synthesized. ¹³C- and ¹⁵N-nmr spectroscopy was employed for structure determination.     

Nucleophilic substitution of 1,2,4-triazines

The reaction of 3-(methylthio)-5-carbethoxy-1,2,4-triazine (5) with ammonia was found to yield products from not only ammonia but also methanethiolate displacements. An account of the transformations and the products observed is given. The 3-position of 3,6-bis(methylthio)-5-carbamoyl-1,2,4-triazine (7) was shown to be more reactive than the 6-position toward nucleophilic substitution. Reduction at the 4,5 positions of triazine 5 occurred upon treatment with methanethiol under basic and neutral conditions.     

A regioselective approach to 5-substituted-3-amino-1,2,4-triazines

Nucleophilic displacement of readily available alpha,alpha-dibromoketones with excess morpholine gave the corresponding ketoaminals, which upon condensation with aminoguanidine in MeOH in the presence of AcOH afforded 5-substituted-3-amino-1,2,4-triazines in >95% regioselectivity and 45-76% isolated yield. [reaction: see text]     

Triazine chemistry VIII. 2,5-dihydro-5-oxo-1,2,4-triazines

2,5-Dihydro-5-oxo-1,2,4-triazine and some of its alkylated derivatives have been prepared. Nmr spectroscopic analysis has established that the 2,5-dihydro-5-oxo tautomers are preferred over the 4,5-dihydro-5-oxo ones. This preference, and the behavior of 1,2,4-triazines in some other chemical reactions has been interpreted in terms of electron-electron repulsions between the lone pairs of electrons of N₁ and N₂ in this ring system.     

Synthesis of pyridines from 1,2,4-triazines under high pressure

A procedure has been proposed for the synthesis of pyridines from 1,2,4-triazine derivatives and bicyclo[2.2.1]hepta-2,5-diene under high pressure in the presence of lithium perchlorate as catalyst.     

1,2,4-Triazines. XII. Syntheses of 5-carboxarnido-1,2,4-triazines via an addition-oxidation reaction

5-Unsubstituted 1,2,4-triazines, when treated with potassium cyanide suspended in moist dioxane afford 5-carhoxamido as well as 5,5′ -bi-1,2,4-triazinyl derivatives. A probable reaction sequence is described.     

New possibilities of 1,2,4-triazines functionalization: first examples of synthesis and structure of boron-containing 1,2,4-triazines

By oxidation of 3-thioderivatives of 1,2,4-triazine 1a,b 3-alkylsulfonic derivatives 2a,b were obtained. Interaction of the sulfonic derivative 2a with indole leads to 3-oxo-5-indolyl-5-phenyl-as-triazine 4. The sulfone 2a reacts with 1-ethyl-2,6-dimethylquinolinium iodide to give 3-(1-ethyl-6-methyl-1,2-dihydroquinoline-2-methylene)-5-phenyl-1,2,4-triazine 5. The 3-morpholino- 3 and 3-thioderivatives 6, 7a,b of as-triazine were obtained by interaction of the sulfone 2 with morpholine and organic boron-containing thiols. The crystal structure of boron-containing derivative of as-triazine 7b was investigated by X-ray analysis.     

Spatial structure of 3-acyl-2-methylindole oximes

It has been established on the basis of the results of ¹H and ¹³C NMR, UV, and IR spectroscopy that 3-acyl-2-methylindole oximes each exist in the form of a mixture of two isomers with a predominance of syn-s-trans form. The proportion of the anti form rises (to 25–35%) with an increase in the volume of the alkyl radical in the oxime grouping.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 65–68, January, 1984.     

Preparation of some substituted 1,2,4-triazines

By nitrosating 6-R-1,2,4-triazine-3,5-diones(thiones) the corresponding 4-nitroso derivatives are obtained. On reacting methyl iodide with 3-thio-4-nitroso-6-R-1, 2,4-triazin-5-ones their methyl analogs are obtained. The influence of structural factors on the course of the reactions has been examined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 400–402, March, 1986.     

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.     

Biologically active azolo-1,2,4-triazines and azolopyrimidines

The review presents current data on the methods of synthesis and biological activity of purine-isosteric azolo-annulated 1,2,4-triazines and pyrimidines with a bridgehead nitrogen atom, which are among the most promising classes of biologically active compounds.     

Synthesis of substituted 2,3,4,5-tetrahydro-1,2,4-triazines from nitroformaldehyde arylhydrazones

2,3,4,5-Tetrahydro-1,2,4-triazines were obtained by condensation of nitroformaldehyde arylhydrazones with aldehydes and ammonia or primary amines.     

Synthetic and spectroscopic study of 5-amino-2-acyl-1,2,4-thiadiazolin-3-ones

5-Amino-2-acyl-1,2,4-thiadiazolin-3-ones 2–1 can be synthesized from 5-amino-2H-1,2,4-thiadiazolin-3-one ( 1–1 ) via a selective acylation with an acid anhydride in pyridine. The ¹H nmr spectral characteristics of 5-amino-2-acyl-1,2,4-thiadiazolin-3-ones 2–1 is in particular, compared with 5-amino-2H-1,2,4-thiadiazolin-3-one ( 1–1 ) and 5-amino-2-alkyl-1,2,4-thiadiazolin-3-ones 1–2, 1–3 . The 5-amino group of 2–1 appeared as two peaks in its ¹H nmr spectrum, which merged to a single peak at a higher temperature, while those of compound 1–1, 1–2 and 1–3 appear only as a single peak. The restricted rotation of the C(5)-N(5) (at amino) bond of 5-amino-2-acetyl-1,2,4-thiadiazolin-3-one (2a-1) is about 14.5 Kcal/mol.