Tetrazine

Related molecular formulas
C2H4N4
CN4 C2H2N4 C3H4N4
C2N4
C2HN3 C2H3N5
Structure of 1,2,3,4-tetrazine
Structure of 1,2,4,5-tetrazine

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.

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. These materials are of use[vague] in the area of energetic chemistry.[citation needed]

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).

reaction of norbornadiene with 3,6-di-2-pyridyl-1,2,4,5-tetrazine

With norbornadiene fused to an arene the reaction stops at an intermediary stage.

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.

See also

References

  1. ↑ Alvarez-Builla, Julio; Jose Vaquero, Juan; Barluenga, José (2011). Modern Heterocyclic Chemistry. Wiley-VCH. p. 1778. ISBN 978-3527332014.
  2. ↑ Churakov AM, Tartakovsky VA. Progress in 1,2,3,4-tetrazine chemistry. Chem Rev. 2004 May;104(5):2601-16. doi:10.1021/cr020094q PMID 15137801
  3. ↑ (see United States Patent 6645325)
  4. ↑ Hicks, Robin G. (2010). "Verdazyls and related radicals containing the hydrazyl [R2N–NR] group". In Hicks, Robin G. (ed.). Stable Radicals. Wiley. pp. 246–264. ISBN 978-0-470-77083-2.
  5. ↑
    • Dalkılıç, Erdin, and Arif Daştan. "Synthesis of cyclopentadiene derivatives by retro-Diels–Alder reaction of norbornadiene derivatives." Tetrahedron 71.13 (2015): 1966-1970.
    • Dalkılıç, Erdin, et al. "Novel and versatile protocol for the preparation of functionalized benzocyclotrimers." Tetrahedron Letters 50.17 (2009): 1989-1991.
  6. ↑ Saracoglu, Nurullah (May 2007). "Recent advances and applications in 1,2,4,5-tetrazine chemistry". Tetrahedron. 63 (20): 4199–4236. doi:10.1016/j.tet.2007.02.051. ISSN 0040-4020.
  7. ↑ Bird, Robert E.; Lemmel, Steven A.; Yu, Xiang; Zhou, Qiongqiong Angela (2021-12-15). "Bioorthogonal Chemistry and Its Applications". Bioconjugate Chemistry. 32 (12): 2457–2479. doi:10.1021/acs.bioconjchem.1c00461. ISSN 1043-1802.
  8. ↑ 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
  9. ↑ 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. doi:10.1021/acs.joc.2c02687 PMID 36461931