1,2,4,5-Tetrazines 1,2-dihydro— from

Another method for the preparation of the 1,2,4,5-tetrazine system from a diazo compound was reported by Staudinger and Meyer (19HCA619). They reacted diaryldiazomethanes (321) with triethylphosphine and isolated the phosphazines (322). In moist benzene or chloroform these compounds were transformed into 3,3,6,6-tetraaryl-l,2,3,6-tetrahydro-1,2,4,5-tetrazines (323). This result was only obtained when triethylphosphine was used. The intermediate formation of hydrazones seems unlikely, since these compounds are stable and do not dimerize. A reaction which has a certain similarity to the above was reported by Merrill and Shechter (75TL4527). They obtained 3,6-diphenyl-l,4-dihydro-l,2,4,5-tetrazine (80) when the phosphazine (324) was hydrolyzed. 

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. 

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... 

Methyl 3-acyl-l-diphenylmethyleneamino-4,5-dioxo-4,5-dihydro-l//-pyrrole-2-carboxylates 489 are formed from 488 and oxalyl chloride in good yields. Preparative thermolysis of these compounds at 130-140°C gives mixtures of dipyrazolo[l,2- l,2- [l,2,4,5]tetrazines 491 as major products and pyrazoles 492 as minor hydrolytic by-products. The intermediacy of mesoionic compound 490 is expected (Scheme 83) <2004T5319>. 

Coordination complexes derived from 3,6-di(2-pyridyl)-l,4-dihydro-l,2,4,5-tetrazines (DPDHT) and trimethylgallium have been described <98CJC1800>. 

Dihydro-1,2,4,5-tetrazines (552) can be prepared from PhCN and N2H4. 

Reaction of benzyne with arsabenzene affords l,4-etheno-l,4-dihydro-l-arsanaphthalene (192) from which an etheno bridge can be removed with 3,6-di(2-pyridyl)-l,2,4,5-tetrazine (184) to afford, via the polycyclic intermediate (193), the arsanaphthalene (194) (79CC880). 

Interaction of 1,3,5-triazine (241) with hydrazine affords 1,2-diformylhydrazine dihy-drazone (242) which is a light-sensitive compound which turns pink, especially in the presence of air. The color is attributed to the formation of 1,2,4,5-tetrazine (38) but due to its high volatility the tetrazine could not be isolated. Heating (242) for two hours with acetic anhydride again affords an unisolated red, volatile product formulated as (38), and 1,2-diacetyl-l,2-dihydro-1,2,4,5-tetrazine (243). Since compound (242) is prepared from hydrazine and (241) this preparation is in the final analysis a [2+ 1+ 2 + 1] method (57JA2839). 

The use of ammonia or amines instead of sodium hydroxide for the dimerization of ethyl diazoacetate leads to the formation of dihydro-1,2,4,5-tetrazine-3,6-dicarboxamides. The products isolated were formulated either as l,2-dihydro-l,2,4,5-tetrazine derivatives (314), as l,6-dihydro-l,2,4,5-tetrazine derivatives (315), or as mixtures of both. The dimerization is usually run in alcoholic solution at temperatures from cold to 100 °C (78HC 33)1075, pp. 1157, 1158, 76G1). 

Dihydropyridazines are obtained from 1,4-dicarbonyl compounds and hydrazine (Section III,B) or from the reaction of sym-tetrazines and simple ethylenic compounds (Section III,H). There are also a few special reactions, such as that between a tetrahydrofuran and phenylhydrazine, or from a 1,4,5,6-tetrahydropyridazine derivative. The 1,4-dihydro structure has been found to be correct, rather than the 1,6-dihydro structure, postulated earlier for some of these reduced pyridazines (Section III,H). 1,4-Dihydropyridazines can be reduced or oxidized easily and acid treatment of l-tosyl-1,4-dihydropyridazine causes rearrangement to 1-tosylaminopyrrole. ... 

Treatment of O-benzylated ribono(arabino)-1,4-lactone oxime methanesulfonate 24 with NH3 in MeOH gave the crystalline 1,4-dihydro-1,2,4,5-tetrazines 25, (15)-eiythritol-l-yl isomer fiom the ribono and (l/ )-isomer from the arabino derivative <03HCA1488>. 

Reaction of nitrilimines 26 with 1-substituted-1-methylhydrazines 27 yielded the acyclic adducts 28. Thermal cyclization of adducts gave tetrahydro-l,2,4,5-tetrazines 29 in 70-80% yields. Dihydro-1,2,4,5-tetrazines 30 were obtained (22-25% yield) upon elimination of formaldehyde from tetrahydrotetrazines 29a <03SC1245>. 

The formation of dihydro or tetrahydrotetrazine intermediates in Pellizzari type reactions carried out at high temperatures has long been suspected. The conversion of diphenyl-tetrazine (275) into 3,5-diphenyltriazole (276) by reduction (62LA(654)146) occurs in two stages (Scheme 121). Formation of the aminotriazole (277) may be interpreted as an intramolecular leacylation of the amidrazone analogue derived from (275) followed by reductive cleavage of N(4)—NH2. The conversion of (275) into (276) with ethanolic alkali also is consistent with the known lability of N(4)—NH2. 

Synthetically, compound 152 was prepared by the Friedel-Crafts procedure from furan-3,4-dicarbonyl chloride and a tetralin derivative (85JCR (S)338). 1,4-Dihydro-l,4-epoxy-5,8-naphthoquinone, when treated with 3,6-di(2-pyridyl)-l,2,4,5-tetrazine, yielded the quinone 153 (75JCS(P1)1339) derivatives of 153 are also known (74CC1034). The parent compound (153) is a stable derivative of the unstable isobenzofuran. Finally, 3-acetyl-2-furyl-1,4-benzo- (or -naphtho-) quinones are isomerized photochemically in aprotic solvents into the quionones 154 (66HCA1806). 

Indoles have been prepared from reactions of o-aminophenylketones with reactive , or stable " arsonium ylides. Oxo-stabilized ylides reacted with 2-chloro-oximes to give trans-5-acyl-A -isoxazolines, and isoxazoles have been obtained from reactive arsonium ylides and a-isonitrosoketones, and from triphenylarsonium methylide and nitrile oxides The latter ylide reacts similarly with nitrile imines to give pyrazoles. With triphenylarsonium benzylides and benzoylylides,benzene diazonium salts give 1,3,4,6-substituted 1,4-dihydro-1,2,4,5-tetrazines in a reaction in which initial coupling of the reagents is followed by a dimerisation. ... 

The submitters employed, without purification, thionyl chloride obtained from Fisher Scientific Company. The procedure should be performed in a well-ventilated hood since thionyl chloride Is a lachrymator. The yield of dimethyl ester was found to be lower in instances when the thienyl chloride-methanol solution was not allowed to stir (30 min, -30°C) prior to the addition of dihydro-1,2,4,5-tetrazine-3,6-dicarboxylic acid. 

Reaction of 1,2,4,5-tetrazines with aliphatic aldehyde dimethylhydrazones affords a bicyclic intermediate which eliminates nitrogen to yield 9. However, elimination of an amine from dihydro-1,2,4-triazin-4-amine 9 to give the aromatic 1,2,4-triazine has not been reported.199-200... 

Diacylhydrazines 1 or dichloro-substituted azines 3 are cyclized with hydrazine to give the dihydro-1,2,4,5-tetrazines 4 which are converted to 1,2,4,5-tetrazines 5 by oxidation with the usual oxidation agents.4 5 27,165 - 168 The use of the dichloro azines 3 (see Houben-Weyl, Vol. 10/2, p 164) appears to be the better method. Since 3 can be prepared either from 1 or... 

Liberating the acid from the disodium salt with H2S04 decreases the yield of this step considerably. Dimethyl t,4-Dihydro-i,2,4J-tetrazine-3,6-dicarboxylate (2b) ... 

Thermal or photochemical elimination of nitrogen from tetrazoles 1 affords nitrile imines 8 (see Houben-Weyl, Vol E8d, p774ff) which dimerize to give 1,4-dihydro-l,2,4,5-tetrazines 9 which are oxidized under the reaction conditions to 1,2,4,5-tetrazines 10 (when R2 = H).175-179... 

---