1.2.3- Triazines, fused oxidation

Azine approach. The fused uracil (58) has been prepared from 5-amino-l,3,6-trimethyl-uracil diazotization of the latter yields a fused triazine A-oxide (57), which has its triazine ring transformed into an isoxazole ring by tin(II) chloride treatment (62USP3056781). 

In addition to the above, a number of other heterocyclic compounds, for example, 2-aroylbenzofurans, 1,3-benzoxathioles, dihydropyrans, 1,4-benzoxazines, hydantoin derivatives, piperazine-2,5-diones, thioethenes, 1-arylbenzimidazoles, benzofuran-1-oxides, piperazinones, thiazoles, 5-thiacyclohexanecarboxaldehyde, pyrroles, triazines, fused napthoquinone derivatives and P-lactams have been synthesised using PTC technique." ... 

N-Oxidation of 3-azido-l,2,4-triazines at either N-l or N-2 destabilizes the bicyclic compounds so that only the monocyclic azide tautomers (59, 60) are observed (77JHC1221). 3-Azido-l,2,4-benzotriazine was also found to exist as the azido tautomer (61b) in solution, but in the crystalline state it favoured the tetrazolo[5,l-c][l,2,4]benzotriazine structure (61a) (73JHC575). In DMSO the third isomer, the tetrazolo[l,5-b ]-fused compound (61c), was detected in small amount (10%) by 13C NMR spectroscopy (79JOC1823). Solvent and... 

The dominant influence of secondary orbital interactions is observed in the reaction of the cyclopenta[e][l,2,4]triazine ester (415) witl the two enamines (416) and (417). In the first case the fused pyridine (418) was obtained directly in the latter the dihydropyridine (419) was isolated, and aromatized, by iV-oxidation and Cope elimination, to (420) <82CB2807>. 

Azole approach. Cyclization of the thiazolo oxime (424) with acid catalysis gives the fused pyridazine 7-oxide (425) in which the oxide bond is cleaved in the usual way by the reaction with phosphorus bromide (69JCS(C)227o). Fused 1,2,4-triazines can be constructed from appropriately substituted thiazole-2-hydrazones as shown for (426) (79MI42901). 

With a-di ketones 1- and 2-amino- and 1,2- and 1,5-diaminoimidazoles condense to give fused-ring heterocycles, with initial attack at the C-amino function. An N-amino group can be removed by treatment with nitrous acid. Oxidation of quaternary salts of 1-aminoimidazoles gives azoimidazolium salts, while manganese dioxide converts 1,2-di-aminoimidazoles into triazoles and triazines (see Section IV,D). 

Simple uncharged six-membered aromatic heterocycles cannot contain a divalent heteroatom. The azines are numbered to indicate the relative positions of the nitrogen atoms. 1,2,3,4-Tetrazine, pentazine and hexazine are unknown, however, a number of fused 1,2,3,4-tetrazines, primarily A -oxides and A -aryl quaternary salts, are known, but of monocycUc compounds, only a few di-A -oxides have been prepared. Of the other systems, 1,2,3,5-tetrazine is unknown, although theoretically it could be moderately stable, but fused derivatives include the drug temozolomide (see 33.7). Derivatives of 1,3,5-triazine are very well known and available in large quantities, indeed they are amongst the oldest known heterocycles the trioxy-compound ( cyanuric acid ) was first prepared in 1776 by Scheele by the pyrolysis of uric acid. 

The dominant influence of secondary orbital interactions is apparent in the reaction of methyl cyclopenta[e]-l,2,4-triazine-3-carboxylate with enamines from 3,4-dihydronaphthalen-1 (2//)-or -2(l/f)-ones. In the case of the 3,4-dihydronaphthalen-2-amine the fused pyridine 24 is obtained directly using the 3,4-dihydronaphthalen-l-amine the dihydropyridine is isolated, but can be oxidized to give the aromatic pyridine 25 derivative via a Cope elimination.403... 

New fused tetrazoloazines that have been reported include tetrazolo[5,l-a]isoquinolines,665 tetrazolo[5, l-6]benzothiazoles,666 and tetrazolopyridines.667 Reactions of fused tetrazoloazines, or the azido isomers, that have been reported include hydrolytic cleavage of the pyrimidine ring of tetrazolopyrimidines,66 pyrolysis of 3-azido-pyridazine 2-oxides,66 and photolysis of azido-l,3,5-triazine.670 Dipole moments of 3-azido-1,2,4-triazole derivatives have also been reported.671... 

Amino-3-hydrazino-5-mercapto-l,2,4-triazine (Purpald ) 402 is a well-established reagent for qualitative and quantitative detection of aldehydes. In the presence of an aldehyde or ketone, Purpald is transformed into a fused tetrahydrotetrazine intermediate 403. However, only with aldehydes, further oxidation of 403 takes place to give a deeply purple colored [l,2,4]triazolo[4,3-. ][l,2,4,5]tetrazine-3-thiol 404 (Scheme 95) <2000ALD28>. 

Reaction of heterocycles with a hydrazine residue at the a-position with sugars gave the respective hydrazones whose oxidative heterocyclization gave the 1,2,4-triazolo ring fused to the heterocycle. A variety of fused heterocycles such as pyridines, quinolines, triazines, and fused ring systems were prepared as acycHc nucleosides [2-5,109-111]. 

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