Tetrazine is a compound that consists of a six-membered aromatic ring containing four nitrogen atoms with the molecular formula C2H2N4. The name tetrazine is used in the nomenclature of derivatives of this compound. Three core-ring isomers exist: 1,2,3,4-tetrazines, 1,2,3,5-tetrazines, and 1,2,4,5-tetrazines, also known as v-tetrazines, as-tetrazines and s-tetrazines respectively.

1,2,3,4-Tetrazines 1,2,3,4-Tetrazines are often isolated fused to an aromatic ring system and are stabilized as the dioxide derivatives.Churakov AM, Tartakovsky VA. Progress in 1,2,3,4-tetrazine chemistry. Chem Rev. 2004 May;104(5):2601-16.

1,2,4,5-Tetrazines 1,2,4,5-Tetrazines have been well studied and myriad 3,6-disubstituted 1,2,4,5-tetrazines are known.(see United States Patent 6645325) These materials are of use in the area of energetic chemistry.

Heavily substituted tetrazines form the verdazyls, a family of stable radicals.

Protected tetrazines are strong acetylene acceptors in Diels-Alder equilibria. For example, dipyridinyl 1,2,4,5-tetrazine abstracts acetylene from norbornadiene to cyclopentadiene and a pyridazine: 1,2,4,5-tetrazines are widely used in bioorthogonal chemistry as part of inverse electron demand diels alder (IEDDA) reactions due to their biocompaibility and the degree of orthogonality they provide to other commonly used reactions such as click chemistry (CuAAC or SPAAC).

With norbornadiene fused to an arene the reaction stops at an intermediary stage.π-Bond Screening in Benzonorbornadienes: The Role of 7-Substituents in Governing the Facial Selectivity for the Diels-Alder Reaction of Benzonorbornadienes with 3,6-Di(2-pyridyl)-s-Tetrazine. Ronald N. Warrener and Peter A. Harrison Molecules 2001, 6, 353–369 Online Article

1,2,3,5-Tetrazines 1,2,3,5-Tetrazines are comparatively less explored than the other two isomers, but some general synthetic routes are known.Wu ZC, Boger DL. 1,2,3,5-Tetrazines: A General Synthesis, Cycloaddition Scope, and Fundamental Reactivity Patterns. J Org Chem. 2022 Dec 16;87(24):16829-16846.

See also

6-membered rings with one nitrogen atom: pyridine 6-membered rings with two nitrogen atoms: diazines 6-membered rings with three nitrogen atoms: triazines 6-membered rings with five nitrogen atoms: pentazine 6-membered rings with six nitrogen atoms: hexazine

References