Beirut reaction

What is Beirut reaction?

Haddadin and Issodorides first reported this reaction in 1965. The Beirut reaction involves the synthesis of quinoxaline-1,4-dioxides through the cycloaddition of benzofuroxan (i.e., benzofurazan N-oxide) with dienes, α,β-unsaturated ketones, enamines, or enolates.

Despite the authors’ discovery, the reaction is not named after them, but instead is referred to as the Beirut reaction after the city where the inventors conducted their initial work.

Beirut reaction
Beirut reaction
  • R1 = alkyl, aryl, etc.
  • R2 = acyl, alkyl, aryl, CO2R, CONH2, CONHR, CN, etc.
  • X = NRR’, O (see list of acronyms)

The Beirut reaction works well with ketones, 4β-diketones, 5β-ketoesters, 5bβ-ketonitrile, 1,3-dinitrile, and β-ketoamides, and corresponding enolates can be easily obtained with the use of a weak base like triethylamine. Additionally, phenolic enolates derived from phenol, resorcinol, hydroquinone, or benzoquinone can also undergo a similar dehydrative condensation with benzofuroxan under mild conditions (e.g., NaOH/H2O, H2O, MeOH/RNH2, SiO2/MeCN at room temperature) to yield phenazine N,N-dioxide derivatives.

References

Makhluf J. Haddadin, Costas H. Issidorides
Enamines with isobenzofuroxan: a novel synthesis of quinoxaline-di-n-oxides,
Tetrahedron Letters, 6, (36) 3253-3256 (1965)
DOI: 10.1016/S0040-4039(01)89222-4

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