Houben-Hoesch reaction

What is Houben-Hoesch reaction?

This reaction was first reported by Hoesch in 1915 and was extended subsequently by
Houben in 1926. The Houben-Hoesch reaction is also referred to as the Hoesch synthesis, Houben-Hoesch condensationHouben-Hoesch acylation, Houben-Hoesch synthesis, or Hoesch reaction. Moreover, the intramolecular version of such reaction is also known as the Houben-Hoesch cyclization.

This Houben-Hoesch reaction involves the production of acylphenols from either phenols or phenolic ethers. This is achieved through the use of organic nitriles, with the addition of hydrochloric acid and aluminum chloride serving as catalysts.

Houben-Hoesch reaction
Houben-Hoesch reaction

The Houben-Hoesch reaction is a method of acylating electron-rich aromatics, including multi-hydroxy phenols, their ethereal derivatives, and certain heterocyclic compounds, using organic nitriles. The reaction proceeds via the intermediate formation of ketimines and requires the presence of either hydrochloric acid, Lewis acid, or both as catalysts.

Several acidic catalysts can be employed in this reaction, such as ZnCl2, AlCl3, the combination of BCl3 and AlCl3, numerous superacids, and even cation-exchange resin (Amberlite IR-120). It has been noted that simple phenol does not readily undergo acylation, instead producing a salt of iminomethyl phenyl ether. However, ortho-acylation of phenol from nitriles can be achieved using the BCl3 and AlCl3 catalyst combination.

The true acylation species in this reaction has been identified as dications, specifically carbocations destabilized by an iminium cation group. The reaction has also been adapted using a palladium-catalyzed approach, which is suitable for both intermolecular and intramolecular acylation of less electron-rich arenes.