1,2,4,5-Tetrazines 1,2-dihydro

Oxidation of a solution of 3-alkyl(aryl)-l,2,4,5-tetrazines in liquid ammonia with permanganate proved to be an excellent route for preparing 6-amino-l,2,4,5-tetrazines (Scheme 30) (81JHC123). The covalent a-adduct, i.e., amino-dihydro-1,2,4,5-tetrazine, is intermediate, as proved by NMR spectroscopy. Based on model studies of 3-phenyl-1,6-dihydro-1,2,4,5-tetrazine, this non-isolable amino-dihydro-1,2,4,5-tetrazine has been characterized as having a homotetrazole structure A (Scheme 30) (81JOC3805). 

Dissolving 3-aryl(alkyl)-1,2,4,5-tetrazines (21) in liquid ammonia or primary aliphatic amines at — 35°C to — 40°C, followed by addition of potassium permanganate, gives 6-alkylamino-3-aryl-(alkyl)-1,2,4,5-tetrazines (23) in reasonable to excellent yields. This shows that, under the reaction conditions, addition of A-nucleophiles to the tetrazine ring must have occurred (Scheme 1) <8 JHC123>. The presumption of a 1,6-dihydro intermediate (22) rests on the experimental result that tetrazines can be transformed by sodium borohydride into the isolable 1,6-dihydro-1,2,4,5-tetrazines, which can be considered as neutral homoaromatic systems <8UOC2i38>. 

Diphenyl-l,2,4,5-tetrazin wird beim Erhitzen mit Salzsaure oder ethanolischer Kalilauge zu 2,5-Diphenyl-J, 3,4-oxadiazol und 3,6-Diphenyl-],4-dihydro-tetrazin umgewandelt558. Fiihrt man diese Reaktion mit Peressigsaure und Natriumacetat bei 50-60 durch, so erhalt man meist ausschliefilich 2,5-Diaryl-l, 3,4-oxadiazole559 ... 

Heating compound (244) for several minutes with copper(II) sulfate in pyridine led to the isolation of 3,6-diphenyl-l,2,4,5-tetrazine (51). The mechanism of this reaction seems to be cyclization of (244) to give the intermediate (245) which eliminates prussic acid, affording the dihydro tetrazine (80), which is oxidized by copper (II) sulfate (60AC(R)277). 

Dihydrazide-dihydro-tetrazine. See 3,6-Bis (hydrazide)-l,2-dihydro-l,2,4-tetrazine in Vol 2,p B143-R... 

Tetrazine-3,6-dicarboxylic acid, 1,6-dihydro-diethyl ester... 

Like lV-methyl-2-phenylbenzothiazoliiim iodide (76KGS635), the salt 19 reacts with hydrazine hydrate to give 3,6-diphenyl-l,2-dihydro-l,2,4,5-tetrazine and di(o-lV-methylaminophenyl) ditelluride (92MI1). 

Oxidation of the 2//-4a,7-dihydro derivative 15, the inverse electron-demand [4+2] Diels-Alder cycloadduct of ethyl 1 /7-azepine-l -carboxylate and dimethyl l,2,4,5-tetrazine-3,6-dicar-boxylate, with tetrachloro-l,4-bcnzoquinone furnishes the pyridazino[4.5-r/]azepine 16.112... 

The isomeric pyridazino[4,5-6]azepine 19 is obtained directly during the decomplexation of the [4 + 2] adduct 17 formed from tricarbonyl(ethyl +17/-azepine-l-carboxylate)iron and 1,2,4,5-tetrazine-3,6-dicarboxylate, with trimethylamine A-oxide.113 Surprisingly, decomplexation of adduct 17 with tetrachloro-l,2-benzoquinone yields only the dihydro derivative 18 (71 %), aromatization of which is achieved in high yield with trimethylamine A-oxide in refluxing benzene. 

Several dihydrotetrazine materials have been promoted as oxygen scavengers, including 3,6-dimethyl,1-2-dihydro,1,2,4,5-tetrazine, and the diethyl- and diphenyl-derivatives. 3,6-Dimethyl,1-2-dihydro,1,2,4,5-tetrazine is a six-sided ring with a formula H3C-CN2C-CH3NHNH its MW equals 102. Its basic reaction with oxygen is shown here ... 

Regarding the series of hetero aromatic pentacyclic compounds with three heteroatoms, an accelerated synthesis of 3,5-disubstituted 4-amino-1,2,4-triazoles 66 under microwave irradiation has been reported by thermic rearrangement of dihydro-1,2,4,5 tetrazine 65 (Scheme 22). This product was obtained by reaction of aromatic nitriles with hydrazine under microwave irradiation [53]. The main limitation of the method is that exclusively symmetrically 3,5-disubstituted (aromatic) triazoles can be obtained. 

Nitrilimines react with hydrazones of aliphatic aldehydes and ketones to yield addition products 9 which cyclise when treated with palladium charcoal at room temperature to give 1,6-dihydro-j-tetrazines 10 <96JCR(S)174>. 

Amino-1,2,4-triazole has been obtained from orthoformic ester and hydrazine hydrate in a sealed tube at 120° 1 by heating formylhydrazine at 150-210° 2-3-4 by heating N,N -diformyl-hydrazine at 160° 5 by decarboxylation of 4-amino-1,2,4-tria-zoldicarboxylic acid 6 by fusion of l,2-dihydro-l,2,4,5-tetrazine 6 and by heating l,2-dihydro-l,2,4,5-tetrazinedicarboxylic add above its melting point.4-6-7... 

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