5-Cyano-l,2,4-triazines

The list of relatively simple 1,2,4-triazines for which the X-ray data have been obtained involves 3-amino-l,2,4-triazin-5(2//)-one <2002MI723> and a great number of phenyl derivatives 3,6-diphenyl-5-cyano-l,2,4-triazine <2002RJOC744>,... 

Cross-coupling reactions of 1,2,4-triazines are less common due to rather poor availability of suitable substituted 1,2,4-triazine derivatives. Nevertheless, they attract attention from researchers resulting in development of new synthetic methods for 1,2,4-triazine functionalization. Thus, the synthesis of novel substituted 1,2,4-triazines 33 and 34 containing thiophene and furan rings using palladium-catalyzed cross-coupling reactions of 3-alkylsulfanyl- or 5-cyano-l,2,4-triazine 35, 36 was described (14T4697). 

The reaction of oxepin and 2,7-dimethyloxepin with dimethyl 3-cyano-l,2,4-triazine-5,6-dicarb-oxylate takes the same course as the cycloaddition to the tetrazine. Two different addition products 11a and 12 are obtained in the case of oxepin, whereas dimethyloxepin yields only the [4 + 2] adduct lib.235... 

The reaction of 5,6-diphenyl-3-cyano-l,2,4-triazine with hydrazine gives the amidrazone which, with 1,2-diketones, yields 3,3 -bistriazinyls 74 <95MI03 96CA(124)86945>. 

Dimethyl 3-cyano-l,2,4-triazine-5,6-dicarboxylate (445) reacts with formaldehyde dimethylhydrazone (446) via a [4 + 2] cycloaddition to give the dihydropyrimidine (447) in very low yield (82CZ100). 

When bicyclopropylidene was treated in the same way only trimers of the initially formed 8,9-diazadispiro[2.0.2.4]deca-7,9-diene were isolated.The cycloaddition reaction of the unsym-metrical dimethyl 3-cyano-l, 2,4-triazine-5,6-dicarboxylate with methylenecyclopropane was re-gioselective. The primary product was the 2-cyanospiro-3,4-dihydropyridine system (with C3 as spirocenter) which hydrolyzed readily upon chromatography. Dimethyl 4-oxo-5-aza-spiro[2.5]oct-5-ene-6,7-dicarboxylate was isolated as a stable product in 8%> yield. ... 

Amino-2H-l,4-benzoxazines. o-Aminophenoxyacetonitrile treated at room temp, with Na-methoxide in methanol, and refluxed 0.5 hr. under Ng 3-amino-2H-1,4-benzoxazine. Y 78%. M. Mazharuddin and G. Thyagarajan, Chem. Ind. 1971, 178 5-amino-l,2,4-triazines from l-cyano-4-amino-2,3-diaza-l,3-butadienes s. V. Uchytilova, P. Fiedler, and J. Gut, Coll. 57, 2221 (1972). 

The pyrazolo-fused pyrimido[4,5-< ]-l,2,4-triazine 35 was synthesized using the 5-amino-6-cyano triazine 131 (Scheme 21) as the precursor. Reaction with phosgeniminium chloride gave the amide halide intermediate 132 which in turn produced the pyrimido[4,5-< ]-l,2,4-triazine 35 upon treatment with gaseous hydrogen chloride <1996T3037>. 

A practical synthesis of 2//-pyrimido[4,5-e]ll,2,4]triazin-3-ylidenecyanamides 106 has been developed. The key step is the coupling reaction of an aryldiazonium salt with l-cyano-3-(2,6-dioxo-l,2,3,6-tetrahydropyrimidin-4-ylamino)-2-methylisothiourea 105, obtained from uracil 104, followed by an intramolecular cyclization <04TL931ft>. 

The presence of electron-withdrawing groups in the 1,2,4-triazine ring facilitates the cycloaddition reaction. Indeed, ethyl 3-(2-pyridinyl)-l,2,4-triazin-6-carboxylates 170 or 6-cyano-1,2,4-triazines 171 and 172 react with 2,5-norbornadiene on reflux in ethanol or benzene (Scheme 94) <200382400, 2003TL693, 2003JOC2882, 2005TL6111>. 

Cyano-l,2,3-tris(difluoroamino)propane, 1428a Cyanuric acid, see 2,4,6-Trihydroxy-1,3,5-triazine, 1115 Cyanuric chloride, see 2,4,6-Trichloro-1,3,5-triazine, 1035 Cyclo-o%o-butadiynyl-2,3-dioxocyclobutenylidene, see Oligo(octacarbondioxide), 3103 f Cyclobutane, 1575... 

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