1,2,4,5-Tetrazine synthesis

Scheme 2 a One-pot Lewis acid-promoted asymmetric tetrazine synthesis and corresponding functionalized tetrazine derivatives, b Alkenyl-1,2,4,5-tetrazine synthesis by a cascade elimination-... 

Tetrazines, synthesis and properties 84MI18 78HC(33,1)1. s-Tetrazines, cycloaddition reactions of 81 KGS 1462. Tetrazines, synthesis from hydrazines 84H(22)1821. Verdazyl radicals, vibrational spectra of 84UK1959. 

Many detailed procedures for the synthesis of specific compounds can be extracted from the schemes presented above and the corresponding literature of these contributions. A review describes tetrazine synthesis using carboxylic iminoesters <95RCR317>. 

General methods for the preparation of 1,2,4,5-tetraoxanes Key structures for the development of peroxidic antimalarial agents 12KGS60. Reactions oftetrazines with dienophiles 12KGS1237. 1,2,4,5-Tetrazines and azolo[l,2,4,5]tetrazines Synthesis and reactions with nucleophiles 13KGS75. 

The only recorded synthesis of this type from a pyridazine involves the [4 + 2] cycloaddition of the lactim ether (374) with l,2,4,5-tetrazine-3,6-dicarboxylic ester, which proceeds with loss of nitrogen and methanol from the intermediate adduct to give the pyrido[2,3-t/]pyridazine (375) (77AP936). 

Boger developed his pyridine synthesis out of a need to eonstruet a pentasubstituted pyridine in an approach to the formal total synthesis of antitumor antibiotic streptonigrin 44. The requisite triazine 48 was produeed by using this methodology in an iterative sense with two different aza-heteroeyeles. Reaetion of thioamidate 46 with tetrazine 47, in a eyeloaddition/eyeloreversion sequenee, afforded 1,2,4-triaziene 48. Exposure of enamine 49 to 48 resulted in the formation of 50. This compound was elaborated into a eompound that intereepted Kende s synthesis of 44. ... 

There is only one reported synthesis of a bcnzannulated 1,2,4-triazocine system. 2-Phenylbenz-azete (1), which can be generated from 4-phenyl-l,2,3-benzotriazine by pyrolysis, is reacted with tetrazine 2 to give a [4 + 2] adduct, which loses nitrogen and finally results in the eight-membered-ring derivative after valence isomerization.2... 

---