Hoesch reaction

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
Hoesch reaction example, 1-(2,4,6-trihydroxyphenyl)ethanone from phloroglucinol

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.

Hoesch reaction mechanism
Hoesch reaction mechanism

See also

References
  1. Gulati, K. C.; Seth, S. R.; Venkataraman, K. (1935). "Phloroacetophenone". Organic Syntheses. 15: 70. doi:10.15227/orgsyn.015.0070.
  2. March, Jerry (1985), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 3rd edition, New York: Wiley, p. 732, ISBN 9780471854722, OCLC 642506595
  3. Eine neue Synthese aromatischer Ketone. I. Darstellung einiger Phenol-ketone Berichte der deutschen chemischen Gesellschaft Volume 48, Issue 1, Date: Januar–Juni 1915, Pages: 1122–1133 Kurt Hoesch doi:10.1002/cber.191504801156
  4. Über die Kern-Kondensation von Phenolen und Phenol-äthern mit Nitrilen zu Phenol- und Phenol-äther-Ketimiden und -Ketonen (I.) Berichte der deutschen chemischen Gesellschaft (A and B Series) Volume 59, Issue 11, Date: 8. Dezember 1926, Pages: 2878–2891 J. Houben doi:10.1002/cber.19260591135
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