Dihydro-1,2,4,5-tetrazines, tautomerism

There are manifold possibilities for tautomerism in partially saturated derivatives. As an example, dihydro-1,2,4,5-tetrazines have been formulated in the 1,2-, 1,4-, 1,6- and 3,6-dihydro structures, but the 1,4-dihydro structure is probably the most stable (see also Section 3.2.2.3.2). 

This procedure is also efficient for the synthesis of other fused tetrazoles, such as ethyl l,5-dihydro-5-oxo-7-phcnyl-8-(phenylsulfonyl)tetrazolo[ 1,5- pyridine-6-carboxy late <2000J(P1)3686>. At the same time, the unexpected azido-tetrazolo tautomerization and reversible tetrazolo transformation of 3,6-diazido-l,2,4,5-tetrazine are remarkable compared to all other polyazido heteroaromatic high-nitrogen C-N compounds <2005JA12537>. 

There are many possibilities for tautomerism in partially-saturated derivatives. Dihydropyridines can exist in several tautomeric forms, e.g., 37 and 38, of which the 1,4-dihydro isomers are usually the most stable. Similarly, dihydro-1,2,4,5-tetrazines have been formulated as the 1,2-, 1,4-, 1,6- and 3,6-dihydro structures but the 1,4-dihydro structure is probably the most stable. In contrast, 2/7-pyrans, e.g., 67, are more stable than 4/7-pyrans, e.g., 68. Of the five possible dihydropyrimidines most known derivatives have 1,2-, 1,4-, or 1,6-dihydro structures of which the 1,2-structure is calculated to be the most stable <1985AHC(38)1>. 

Tautomerism of tetrazines was investigated by ID 15N INADEQUATE.85 Dimethyl dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate can exist either in 1,2- (8) or... 

Much more is known about tetrahydro-l,2,4-tetrazines which can form tautomeric structures with more than one double bond in the ring. These include the tetrahydro-oxo(thioxo)-1,2,4-triazines and tetrahydro-dioxo(thioxo)-l,2,4-triazines, which, in the absence of a principal group of higher priority, are more usually named as dihydro-1,2,4-triazinones and dihydro-1,2,4-tri-azinethiones. Still better known are the tetrahydro-dioxo-l,2,4-triazines and their mono- and di-thiooxo analogues, because the 3,5-isomers [l,2,4-triazine-3,5(2//,4//)-diones, 1,2,4-triazine-3,5(2/7,4//)-dithiones, and dihydro-3/5-thioxo-l,2,4-triazin-5/3-ones] are aza-uracil derivatives. 

Investigations to elucidate the stereochemistry of the tetrazine cycloadditions are rendered more difficult because the initially formed Diels-Alder adduct is not isolable, but loses nitrogen extremely rapidly (Scheme 5) and the 4,5-dihydropyridazine derivative formed undergoes either a rapid tautomerization to the 1,4-dihydro isomer or a )6-elimination reaction to form aromatic compounds (Scheme 6). In both cases the stereochemical centers, by which the stereochemical course of the reaction could be followed, are destroyed. 

Reaction of alkylsulfanylchloroacetylenes 81 with 1,1-dimethylhydrazme 82 at room temperature afforded the corresponding 2,5-bis(alkylthiomethyl)-l,l,4.4-tetramethyl-l,4-dihydro-l,2,4,5-tetrazine-l,4-diium chlorides 85 in 67% and 80% yield. The reaction pathway is explained by initial formation of hydrazinium salt 83, which dimerizes into the tetrazinium salt 84. Tautomerization of the salt 84 leads to the product 85 (Scheme 21) <2005RJ01458>. 

The 1,2-1,4-dihydro tautomerism of a substituted dihydro-1,2,4,5-tetrazine derivative 41 was studied using N-enriched substances in several solvents (Scheme 5.32) [79]. The direct J( N, N) coupling constant of 12.2 Hz corresponds... 

---