Hoesch reaction
Chemical reaction
From Wikipedia, the free encyclopedia
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.
| Houben–Hoesch reaction | |
|---|---|
| Named after | Josef Houben Kurt Hoesch |
| Reaction type | Coupling reaction |
The synthesis of 2,4,6-Trihydroxyacetophenone (THAP) from phloroglucinol is representative:[1] If two-equivalents are added, 2,4-Diacetylphloroglucinol is the product.
Hoesch reaction example, 1-(2,4,6-trihydroxyphenyl)ethanone from phloroglucinol
ethanone_from_phloroglucinol.png)
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.
Applications
- Hoesch reaction is demonstrated for Buflomedil, Flopropione, Linderatin, Leptospermone, Viminol, & meta-Phloretin (novel artificial sweetener compound).[5]
- Hoesch reaction with isovaleronitrile could in theory be used for the first step in the synthesis of Humulone & Lupulone, although in practice a Friedel-Crafts reaction with isovaleric acid was performed.