Azirine Explained

Azirines are three-membered heterocyclic unsaturated (i.e. they contain a double bond) compounds containing a nitrogen atom and related to the saturated analogue aziridine.[1] They are highly reactive yet have been reported in a few natural products such as Dysidazirine. There are two isomers of azirine: 1H-Azirines with a carbon-carbon double bond are not stable and rearrange to the tautomeric 2H-azirine, a compound with a carbon-nitrogen double bond. 2H-Azirines can be considered strained imines and are isolable.

Preparation

2H-Azirine is most often obtained by the thermolysis of vinyl azides.[2] During this reaction, a nitrene is formed as an intermediate. Alternatively, they can be obtained by oxidation of the corresponding aziridine.Azirine can be generated during photolysis of isoxazole.[3] Due to the weak N-O bond, the isoxazole ring tends to collapse under UV irradiation, rearranging to azirine. [4]

Substituted azirines can be produced via the Neber rearrangement.

Reactions

Photolysis of azirines (under 300 nm) is a very efficient way to generate nitrile ylides. These nitrile ylides are dipolar compounds and can be trapped by a variety of dipolarophiles to yield heterocyclic compounds, e.g. pyrrolines.

The strained ring system also undergoes reactions that favor ring opening and can act as a nucleophile or an electrophile.

Azirines readily hydrolyse to give aminoketones which are themselves susceptible to self-condensation.

See also

Notes and References

  1. Teresa M. V. D. Pinho e Melo and Antonio M. d’A. Rocha Gonsalves. Current Organic Synthesis. 1. 3. 2004. 275–292. Exploiting 2-Halo-2H-Azirine Chemistry. 10.2174/1570179043366729. dead. https://web.archive.org/web/20060928104209/http://bentham.org/cos/contabs/cos1-3.htm. 2006-09-28 .
  2. 2H-Azirines as synthetic tools in organic chemistry. Palacios F, Ochoa de Retana AM, Martinez de Marigorta E, de los Santos JM. Eur. J. Org. Chem.. 2001. 2401–2414. 10.1002/1099-0690(200107)2001:13<2401::AID-EJOC2401>3.0.CO;2-U. 2001. 13.
  3. Edwin F. Ullman. Photochemical Transposition of Ring Atoms in Five-Membered Heterocycles. The Photorearrangement of 3,5-Diphenylisoxazole . J. Am. Chem. Soc. . 88 . 8 . 1844–1845 . 1966. 10.1021/ja00960a066 .
  4. Cheng, K. . Qi, J. . Ren, X. . Zhang, J. . Li, H. . Xiao, H. . Wang, R. . Liu, Z. . Meng, L . Ma, N. . Sun, H.. Developing Isoxazole as a Native Photo-Cross-Linker for Photoaffinity Labeling and Chemoproteomics. . Angew. Chem. Int. Ed. . 61 . 47 . e202209947 . 2022. 10.1002/anie.202209947 .