Synthesis and some reactions of hexahydro-1,2,4-triazine-3,6-dione

The synthesis of hexahydro-1,2,4-triazine-3,6-dione by hydrogenolysis of 1,2-dibenzylhexahydro-1,2,4-triazine-3,6-dione is reported. Ring contraction of the former dione to 3-amino-2,4-imidazolidinedione is discussed. The preparation of the 1- and 2-benzyl derivatives of hexahydro-1,2,4-triazine-3,6-dione and their conversion to the unsubstituted product are also described.     

UV photoelectron spectra of 5- and 6-azauracil

The He(I) photoelectron spectra of 5-azauracil (1,3,5-triazine-2,4(1H,3H)-dione) and 6-azauracil (1,2,4-triazine-3, 5(2H,4H)-dione) are presented. The spectra are assigned by using INDO/S calculations and comparison arguments with uracil. The first ionization energy in the title compounds is higher than in the usual nucleic acid bases.     

Diethylamine and triethylamine as sources of the dienophile component in the reverse azadiene synthesis with dimethylpyrimido[4,5-e]- and-[5,4-e]-1,2,4-triazinediones and 1,2,4,5-tetrazines

Diethylamine (DEA) and triethylamine (TEA) can function as sources for the two-carbon component in the reverse azadiene synthesis. Reaction of 5,7-dimethylpyrimido[4,5-e]-1,2,4-triazine-6,8-dione, 6,8-dimethylpyrimido-[5,4-e]-1,2,4-triazine-5,7-dione, or 1,2,4,5-tetrazine with an excess of DEA or TEA gives, respectively, the pyrido[2,3-d]pyrimidine-2,4-dione,pyrido[3,2-d]pyrimidine-2,4-dione, or pyridazine. The presence of an oxidant (atmospheric oxygen, MnO₂, or an electron-acceptor solvent) is required for the reaction to occur. Reaction of 5,7-dimethylpyrimido[4,5-e]-1,2,4-triazinedione with piperidine, morpholine, or under certain conditions DEA, results in opening of the triazine ring to give uracils with an amidine group in the 6-position.For preliminary communication, see [1, 2].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1545–1558, November, 1990.     

Synthesis of 1,3-dialkylpyrazolo [1,5-a]-1,3,5-triazine-2,4-diones isomers of 1,3-dialkylxanthines

The synthesis of a new series of alkylxanthine analogs containing a bridgehead nitrogen atom is reported. 1,3-Dialkylpyrazolo[1,5-a]-1,3,5-triazine-2,4-diones, were prepared by the treatment of 3-methylpyrazolo[1,5-a]-1,3,5-triazine-2,4-dione (3) with the corresponding alkyl iodide. Similarly, the reaction of 3-methyl-7-phenylpyrazolo[1,5-a]-1,3,5-dialkyl-7-phenylpyrazolo[1,5-a]-1,3,5-triazine-2,4-diones. The starting materials, 3 and 17 , were prepared via the reaction of an appropriate 3-aminopyrazole with ethoxycarbonyl isothiocyanate. Several 8-bromo derivatives were prepared by direct bromination of the 1,3-dialkylpyrazolo[1,5-a]-1,3,5-triazine-2,4-diones.     

Pyrimidines. XXXIII. Synthesis and properties of new fervenulin derivatives

A series of new 3-substituted fervenulin (6,8-dimethylpyrimido[5,4-c]-1,2,4-triazine-5,7-dione) ( 1 ) derivatives have been synthesized by modifying the 3-alkyl- and aralkyl side-chains. Brominations of 3-methyl -15 , 3-ethyl -16- and 3-benzylfervenulin ( 17 ) led to mono- and dibromo derivatives 22, 23, 25–27 , which are prone to various nucleophilic displacement reactions 24, 28–35 . Periodate oxidation and ozonolysis, respectively, of 3-styrylfervenulin ( 20 ) afforded fervenulin-3-carboxaldehyde ( 36 ) which was transformed to a folic acid analog ( 39 ). Potassium permanganate oxidation of 3-alkylfervenulins 15–19 afforded only ring-contraction to 3-alkyl-5,7-dimethylimidazo[4,5-e]-1,2,4-triazin-6-ones 42–46 which are also formed as mixtures with its 2,4a-dihydro derivatives 47–50 on treatment with ethanolic sodium hydroxide. Fervenulin-3-carboxylic acid ( 55 ) can be converted to the corresponding acid chloride 58 which reacts with amines to fervenulin-3-carboxamides 59, 64–67 and/or 2,4a-dihydro-5, 7 -dimethylimidazo[4,5-e]-1,2,4-triazin-6-one-biscarboxamides 60–64 .     

Reaction of 5-substituted-2-amino-2-oxazolines with ethoxycarbonyl isocyanate. A route to 2,3,6,7-tetrahydro-4H-oxazolo[3,2-a]-1,3,5-triazine-2,4-diones

The reaction of 2-amino-2-oxazolines with ethoxycarbonyl isocyanate was investigated in order to access to fused 1,3,5-triazine-2,4-diones with a potential 5-HT₂ antagonist activity. The reaction leads to 2,3,6,7-tetrahydro-4H-oxazolo[3,2-a]-1,3,5-triazine-2,4-diones and to 1-carbethoxy-3-(2-iminooxazolidine)ureas. During the carbamoylation the regioselectivity seems to be related to the strong nucleophilic character of the endo nitrogen atom of 2-amino-2-oxazolines. The structures of two compounds were studied by X-ray crystallography. N-Substituted compounds have been prepared by alkylation of the 2,3,6,7-tetrahydro-7-phenoxymethyl-4H-oxazolo[3,2-a]-1,3,5-triazine-2,4-dione.     

Biological perspective of a triazine derivative with isatin/chalcone/acridone: DFT and docking investigations

Structural Chemistry - The article highlights insights into biological activity using computational methods in products of 1,3,5-triazine-2,4-diamine with 1H-indole-2,3-dione...     

Biomimetic oxidation of metribuzin with hydrogen peroxide catalyzed by 5,10,15,20-tetraarylporphyrinatoiron(III) chlorides

The biomimetic oxidation of metribuzin, a pre- and post-emergence herbicide with hydrogen peroxide catalyzed by 5,10,15,20-tetraarylporphyrinatoiron(III) chlorides [TAPFe(III)Cl], has been studied yielding 6-t-butyl-3-methylthio-1,2,4-triazine-5(4H)-one, 4-amino-6-t-butyl-3,5(2H,4H)-dione and 6-t-butyl-1,2,4-triazin-3,5(2H,4H)-dione under various reaction conditions.     

1,2,4-三嗪类化合物的研究(Ⅸ)——3-氧代-2,3-二氢-6-甲硫基吡唑[3,4-e]并-1,2,4-三嗪的合成及其化学性质

研究了3-氧代-2,3-二氢-6-甲硫基吡唑[3,4-e]并-1,2,4-三嗪的合成及其对酸、碱的不稳定性、对胺的取代反应以及关键性中间体-3,5-二甲硫基-1,24-三嗪-6-羧酸乙酯的亲核性取代反应活性。     

A New Route to Substituted Pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones and Facile Extension to 5,7(6H,8H) Isomers

A new route to substituted pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones is outlined. The synthesis proceeds via pre-formed hydrazone intermediates, which are then condensed with an activated chlorouracil to build up the entire molecular framework, followed by a reductive ring closure to provide the parent series. The route has been extended to the isomeric pyrimido[5,4-e]-1,2,4-triazine-5,7(6H,8H)-dione class via the use of methylhydrazine as hydrazine surrogate, followed by regiospecific alkylation of the N(8)-H pyrimidotriazinediones with a range of alkyl and alkaryl substituents. This new methodology permits the generation of a wide range of compounds with variable substitution at the N(1), C(3), and N(8) positions for a heterocyclic scaffold with demonstrated pharmacological activity.     

Intramolecular cyclization of hydrazides of (2-alkylthio-3,4-dihydro-6-methyl-4-oxo-3-pyrimidml)acetic acids to 1,2,3,4-tetrahydropyrimido[2,1-c]-1,2,4-triazine-3,6-diones

A method has been developed for the synthesis of 1,2,3,4-tetrahydropyrimido[2, 1-c]-1,2,4-triazine-3,6-diones by intramolecullar cyclization of hydrazides of (2-alkylthio-3,4-dihydro-6-methyl-4-oxo-3-pyrimidinyl)acetic acids in benzylamine.Vilnius University, Vilnius 2734. Translated Born Khimiya Geterotsiklicheskikh Soedinenii, No, 7, pp. 967–970, July, 1994. Original article submitted April 4, 1994.     

Diastereoselective reactions in glycine templates containing an ent-ardeemin fragment

Self-consistent reaction field solvation models derived from SCF-MO calculations are shown to be reliable in modeling the diastereoselectivity of the reactions of the anion and cation derived from (4S)-2,4-dimethyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-dione (1) at C(1) with electrophiles and nucleophiles, respectively. The found anti/syn ratio of compound 8, which is a seco-ent-ardeemin analogue obtained by alkylation of 1 with gramine methiodide, confirms this computational model. A close similarity between the calculated geometry of the piperazine ring in the anti isomers of 1,2,4-trialkyl derivatives and that deduced from their (1)H NMR (solution) and X-ray data has been also established.     

Reactions of aroylpyruvic acids withS-methylisothiosemicarbazide hydroiodide and studies of the crystal structures of the reaction products

The reactions ofp-chlorobenzoyl- and benzoylpyruvic acids withS-methylisothiosemicarbazide hydroiodide gave 3-methylthio-6-(p-chlorophenacyl)-2,5-dihydro-1,2,4-triazin-5-one and 6-phenacyl-2,3,4,5-tetrahydro-1,2,4-triazine-3,5,-dione, respectively. The molecular and crystal structures of the compounds synthesized were studied by X-ray diffraction analysis. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 704–708, April, 1998.     

Synthesis of a new bridgehead nitrogen heterocyclic system. Pyrrolo [2,1-f]-1,2,4-triazine derivatives

1-Ureidopyrroles of type 6a,b prepared by the general method previously described (2), readily cyclized under basic conditions giving pyrrolo [2,1-f]-1,2,4-triazine-2,4(1H, 3H)dione derivatives.     

Synthesis of New Thiazolo[3,2-b][1,2,4]triazole Derivatives and Preliminary Evaluation of Their Biological Activity

Russian Journal of General Chemistry - Heterocyclization of 3-[(1H-1,2,4-triazol-3-yl)thio]pentane-2,4-dione afforded 1-(6-methylthiazolo[3,2-b][1,2,4]-triazol-5-yl)ethan-1-one, the reactions of...     

Synthesis of 8,10-dimethyl-1,10b-dihydro[1,3,5]triazino-[2,1-a]isoindole-2,4,6(3H)-trione by Direct arylation of 1,3,5-triazine-2,4(1H,3H)-dione

Direct arylation of 1,3,5-triazine-2,4(1H,3H)-dione with mesitylene afforded a novel fused heterocyclic system, 8,10-dimethyl-1,10b-dihydro[1,3,5]triazino[2,1-a]isoindole-2,4,6(3H)-trione.     

α-Thioureidoalkylation of 4-alkyl- and 4-phenylthiosemicarbazides

Previously unknown 1,3-dialkyl-4,5-bis[4-alkyl(phenyl)thiosemicarbazido]imidazolidine-2-thiones and 4,5,7-trialkylperhydroimidazo[4,5-e]-1,2,4-triazine-3,6-dithiones have been synthesized by the α-thio-ureidoalkylation of 4-alkyl(phenyl)thiosemicarbazides using 1,3-dialkyl-4,5-dihydroxyimidazolidine-2-thiones.     

Über die Herstellung von substituierten 2,3,4,5-Tetrahydro-1,2,4-triazin-6-carbonitrilen und einige ihrer Abwandlungsreaktionen

Preparation of substituted 2,3,4,5-Tetrahydro-1,2,4-triazine-6-carbonitriles and some of its Derivatives. The synthesis of 4-substituted 2-aryl-2,3,4,5-tetrahydro-5-imino-3-oxo-1,2,4-triazine-6-carbonitriles ( 3 ), 2-aryl-2,3,4,5-tetrahydro-3, 5-dioxo-1,2,4-triazine-6-carbonitriles ( 4 ) and some 3-thioxo-derivatives thereof by a novel approach is described. In addition some possibilities for the derivatisation of these compounds are given.     

Synthesis of pyrido[2,3-d]pyrimidine-2,4-diones from pyrimido-[4,5-e]-1,2,4-triazine-6,8-diones by reversed azadiene synthesis

It was shown that pyrimido[4,5-e]-1,2,4-triazine-6,8-diones enter the reversed azadiene synthesis reaction with ketones and vinyl ethyl ether in the presence of diethylamine or boron trifluoride etherate, and also with enamines. As a result of the reaction, pyrido[2,3-d]pyrimidine-2,4-diones are formed in good yield. Pyrimido[5,4-e]-1,2,4-triazine-5,7-diones do not undergo such reactions with acetone. The reasons for the unique behavior of the isomeric pyrimidotriazinediones in the reaction with acetone are discussed.For a preliminary communication, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 224–233, February, 1990.     

Synthesis of bridged heterocycles from <Emphasis Type="Italic">cis</Emphasis>-pyrrolidine-2,4-dicarboxylic acids: I. 3,6-Diazabicyclo[3.2.1]octanes

cis-5-Arylpyrrolidine-2,4-dicarboxylic acid monoamides undergo thermal intramolecular condensation with formation of bicyclic imides having a 3,6-diazabicyclo[3.2.1]octane skeleton. The use of copper(I) cyanide as catalyst ensures high yields of 3,6-diazabicyclo[3.2.1]octane-2,4-diones substituted at the 3-, 5-, 6-, and 7-positions. (1R*,5R*,7S*)-7-(4-Chlorophenyl)-5,6-dimethyl-3,6-diazabicyclo[3.2.1]octane-2,4-dione was found to inhibit thrombin in a buffer solution at a millimolar concentration.