The Hoesch reaction or Houben–Hoesch reaction is an organic reaction in which a nitrile reacts with an arene compound to form an aryl ketone. The reaction is a type of Friedel-Crafts acylation with hydrogen chloride and a Lewis acid catalyst.

The synthesis of 2,4,6-Trihydroxyacetophenone (THAP) from phloroglucinol is representative:^[1] If two-equivalents are added, 2,4-Diacetylphloroglucinol is the product.

An imine can be isolated as an intermediate reaction product. The attacking electrophile is possibly^[2] a species of the type R-C⁺=NHCl⁻. The arene must be electron-rich i.e. phenol or aniline type. A related reaction is the Gattermann reaction in which hydrocyanic acid not a nitrile is used.

The reaction is named after Kurt Hoesch^[3] and Josef Houben^[4] who reported about this new reaction type in respectively 1915 and 1926.

Mechanism

The mechanism of the reaction involves two steps. The first step is a nucleophilic addition to the nitrile with the aid of a polarizing Lewis acid, forming an imine, which is later hydrolyzed during the aqueous workup to yield the final aryl ketone.

See also

• Stephen aldehyde synthesis
• Gattermann reaction
• Hoesch reaction is demonstrated for Buflomedil.

References