Carboni-Lindsey reaction

What is Carboni-Lindsey reaction?

In 1959, Carboni and Lindsey reported the Carboni-Lindsey reaction which involves the reaction of tetrazines with various unsaturated compounds, including dienes, acetylenes, and aliphatic and aromatic olefins, resulting in the formation of 3,6-disubstituted pyridazines and the release of nitrogen. This reaction likely occurs through the 1,4-addition of the -C=N-N=C- diene system of the tetrazine to a suitable olefinic or acetylenic dienophile, followed by a rapid retro-Diels-Alder reaction, leading to the final product and the loss of nitrogen, N2.

Carboni-Lindsey reaction - general reaction scheme
Carboni-Lindsey reaction

Carboni-Lindsey reaction can be controlled by lowering the temperature or using diluents such as ether or benzene. The reaction is considered to be driven by a HOMO (dienophile)-LUMO (diene) interaction, meaning that the reaction occurs more easily with complementarily inverse electron demand of diene/dienophile substituent effects. Specifically, dienophiles with electron-releasing substituents facilitate the reaction, while those with electron-attracting groups slow it down. The reaction is typically complete when the characteristic red or violet-red tetrazine color disappears, and nitrogen evolution stops.

References

R. A. Carboni and R. V. Lindsey Jr.
Reactions of Tetrazines with Unsaturated Compounds. A New Synthesis of Pyridazines
Journal of the American Chemical Society 1959 81 (16), 4342-4346
DOI: 10.1021/ja01525a060

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