Hoesch reaction

Houben–Hoesch reaction
Named after Josef Houben
Kurt Hoesch
Reaction type Coupling 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.

The synthesis of 2,4,6-Trihydroxyacetophenone (THAP) from phloroglucinol is representative:[1]

An imine is 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.

Listed Examples

  1. If instead of acetonitrile, propionitrile is used, then Flopropione is the species formed.
  2. Genistein Patent WO 2006111289 . The whole process can be adapted, e.g. to Quercetin by reiterating the requisite permutations.
  3. Viminol uses a modified Hoesch reaction, in which chloroacetonitrile is used instead.
  4. Resorcinol is used to make Resacetophenone;[5] protection of the alcohols with benzoyl esters, and conversion to liquiritigenin, or 7-hydroxyflavone, which can then be converted to Flavodilol, & recordil.

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 ed.), New York: Wiley, ISBN 0-471-85472-7
  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
  5. ↑ http://canov.jergym.cz/mechanic/pravidl2/hoe/h.htm
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