Synthesis of 1,2,4,5-tetrazines, symmetrically and unsymmetrically 3,6-disubstituted by N-nucleophiles

6-R-3-(3,5-Dimethylpyrazol-1-yl)-1,2,4,5-tetrazines with aliphatic, cycloaliphatic, and aromatic amines, and also with NH-heterocycles undergo a nucleophilic substitution of the dimethylpyrazole moiety yielding symmetrically and unsymmetrically substituted 1,2,4,5-tetrazines. In the 3,6-diimidazolyl-and 3,6-dibenzotriazolyl derivatives reactions of nucleophilic substitution of the heterocyclic moiety also occur. In some cases an ipsosubstitution of amino, hydrazino, and azido groups is observed.     

Reactions of 1,2,4-Triazines with Nucleophiles. 6. Use of SNH Methodology for the Direct Introduction of Cyclic Diketone Residue into the 1,2,4-Triazine Ring FORENAME = D. N.

3-R-6-Phenyl-1,2,4-triazine 4-oxides react with cyclic -diketones (dimethylbarbituric acid, dimedone, and indan) in both acidic (substrate activation) and basic conditions (nucleophile activation) with formation of ^H-adducts, intermediates in the nucleophilic substitution of hydrogen (S_N ^H) in 3-R-5-Nu-4-hydroxy-6-phenyl-4,5-dihydro-1,2,4-triazines. Oxidative aromatisation of these intermediates or auto-aromatisation of acylated (benzoyl chloride) at the NOH -adducts with elimination of benzoic acid gave the corresponding substituted 1,2,4-triazine 4-oxides or 1,2,4-triazines.     

Acid-Base Properties and Prototropic Tautomerism of Isomeric 1,2,4-Triazin-3- and -5-ones

The acidity and basicity constants of isomeric phenyl(aryl)-1,2,4-triazin-3- and -5-ones in aqueous solution were determined by spectrophotometry: pK _a = 7.3–6.2; pK _BH+= 0.1 to –2.2. 1,2,4-Triazin-3-ones are weaker bases than the corresponding 1,2,4-triazin-5-ones. According to the AM1 calculations, the most thermodynamically favorable tautomer in the gas phase is the oxo form: namely, 2H-tautomers of the neutral bases and 2,4-H,H ⁺-tautomers of the conjugate acids.     

Synthesis of 7-Alkyl(aryl)-6-alkoxycarbonyl-5-fluoroalkyl-1,2,4-tri(tetr)azolo[1,5-a]pyrimidines

Fluorinated 3-oxo esters react with aldehydes and 3-amino-1,2,4-triazoles and 5-aminotetrazoles to give, respectively, 7-alkyl(aryl)-6-alkoxycarbonyl-5-fluoroalkyl-1,2,4-triazolo[1,5-a]pyrimidines and -tetra-zolo[1,5-a]pyrimidines. The same heterocyclic products can be obtained by reaction of 2-benzylidene-2-fluoroacyl esters with the corresponding aminoazoles.     

Direct introduction of heterocyclic units into porphyrin derivatives

In the reaction with quinazoline and 5-phenyl-1,2,4-triazin-5(2H)-one, 5,10,15,20-tetra(4-methoxyphenyl)porphyrin exhibits nucleophilic properties. In quinazoline excess, C—C coupling occurs at the C=N bond of azines and position 3 of the aryl ring to form 5,10,15,20-tetrakis(3-heteryl-4-methoxyphenyl)porphyrins. Monoheteryl-substituted porphyrin was obtained by the reaction of equimolar amounts of 5,10,15,20-tetra(4-methoxyphenyl)porphyrin and 5-phenyl-1,2,4-triazin-5(2H)-one.     

The formation of 1,2,4-triazolylimidazolidine-2,4-diones in reactions of 3-aryl-1,2,4-triazin-5(2H)-ones with alkylureas

Recyclization of the addition products of alkylureas to 3-aryl-1,2,4-triazin-5(2H)-ones affording 1,2,4-triazole derivatives was found to occur in Ac₂O.     

Three-component green synthesis of 6-ethoxycarbonyl-5-methyl-7-(thien-2-yl)-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine,a promising antituberculosis drug

Russian Chemical Bulletin - A new simple, technological, and environmentally friendly method for the catalyst-free synthesis in water of a promising antituberculosis drug,...     

Pericyclic reactions in the synthesis of new 5-aryl-5,6-dihydroquinolino[2,1-b]quinazolin-12-ones

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