Borsche-Berkhout reaction

What is Borsche-Berkhout reaction?

The Borsche-Berkhout reaction, initially described in 1904 by Borsche and Berkhout, is a chemical process used for synthesizing 1,3-benzodioxanes from phenols and aldehydes in the presence of acidic substances like HCl and H2SO4. The resulting 1,3-benzodioxanes can then be oxidized to lactones and transformed into prodrugs of anti-inflammatory agents.

Borsche-Berkhout reaction
Borsche-Berkhout reaction

It has been observed that the stability of the dioxane system toward alkali solution decreases with the introduction of an electron-withdrawing group at position 8. For instance, in a 1% KOH solution, 6,8-dinitro-1,3-benzodioxane was readily cleaved into 2-hydroxy-3,5-dinitrobenzyl alcohol, whereas 6-nitro-1,3-benzodioxane remained stable even when boiled in a 25% aqueous alkali or alcoholic potassium ethoxide KOEt/EtOH.

A general application of the Borsche-Berkhout reaction is the synthesis of 1,3-benzodioxanes.

References

Borsche, W. and Berkhout, A.D. (1904), Ueber die Einwirkung von Formaldehyd auf p-Nitrophenole. [On the effect of formaldehyde on p-nitrophenols.] Justus Liebigs Ann. Chem., 330: 82-107. https://doi.org/10.1002/jlac.19043300107

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