Helferich condensation

What is Helferich condensation?

The Helferich condensation, also known as the Helferich and Schmitz-Hillebrecht fusion or Helferich and Schmitz-Hillebrecht synthesis, was initially reported in 1933 by Helferich and Schmitz-Hillebrecht. The reaction involves the direct synthesis of acetylated phenyl glycosides through the fusion of monosaccharide pentaacetate and phenol with an acidic catalyst.

Helferich condensation - general reaction scheme - Helferich - Schmitz-Hillebrecht fusion - Helferich and Schmitz-Hillebrecht synthesis
Helferich condensation

The α-anomer is produced when the reaction occurs in the presence of fused ZnCl2, whereas the β-anomer is formed when p-toluenesulfuric acid is present. While carrying out the condensation under vacuum has led to improvements in the reaction, releasing acetic acid immediately from the reaction system, even higher yields can be obtained in the presence of acetic acid and acetic anhydride compared to the original procedure.

It is important to note that the reaction is not suitable for less common or harder to obtain phenols like tetrahydrocannabinol, and in such cases, a high yield of glycosylation occurs in benzene solution with moist phosphorus oxychloride.

References

Helferich, B. and Schmitz-Hillebrecht, E. (1933), Eine neue Methode zur Synthese von Glykosiden der Phenole1). [A new method for the synthesis of glycosides of phenols1).] Ber. dtsch. Chem. Ges. A/B, 66: 378-383. https://doi.org/10.1002/cber.19330660313

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