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The Hoesch reaction or Houben–Hoesch reaction is an
organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, mechanistic organ ...
in which a nitrile
In organic chemistry, a nitrile is any organic compound that has a functional group. The name of the compound is composed of a base, which includes the carbon of the , suffixed with "nitrile", so for example is called " propionitrile" (or pr ...
reacts with an arene compound
Aromatic compounds or arenes are organic compounds "with a chemistry typified by benzene" and "cyclically conjugated."
The word "aromatic" originates from the past grouping of molecules based on odor, before their general chemical properties were ...
to form an aryl ketone
In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
. The reaction is a type of Friedel–Crafts acylation with hydrogen chloride
The Chemical compound, compound hydrogen chloride has the chemical formula and as such is a hydrogen halide. At room temperature, it is a colorless gas, which forms white fumes of hydrochloric acid upon contact with atmospheric water vapor. Hyd ...
and a Lewis acid
A Lewis acid (named for the American physical chemist Gilbert N. Lewis) is a chemical species that contains an empty orbital which is capable of accepting an electron pair from a Lewis base to form a Lewis adduct. A Lewis base, then, is any ...
catalyst
Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...
.
The synthesis of 2,4,6-Trihydroxyacetophenone
2,4,6-Trihydroxyacetophenone (THAP) is a chemical compound that is a derivative of phloroglucinol.
In an animal model, THAP was reported to enhance cholesterol 7 alpha-hydroxylase (CYP7A1) activity.
THAP is also used as a matrix in matrix-assis ...
(THAP) from phloroglucinol
Phloroglucinol is an organic compound with the formula C6H3(OH)3. It is a colorless solid. It is used in the organic synthesis, synthesis of pharmaceuticals and explosives. Phloroglucinol is one of three isomeric benzenetriols. The other two isom ...
is representative: If two-equivalents are added, 2,4-Diacetylphloroglucinol is the product.
:
An imine
In organic chemistry, an imine ( or ) is a functional group or organic compound containing a carbon–nitrogen double bond (). The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bon ...
can be isolated as an intermediate reaction product. The attacking electrophile
In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively Electric charge, charged, have an ...
is possibly 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
The Gattermann reaction (also known as the Gattermann formylation and the Gattermann salicylaldehyde synthesis) is a chemical reaction in which aromatic compounds are formylated by a mixture of hydrogen cyanide (HCN) and hydrogen chloride (HCl) ...
in which hydrocyanic acid not a nitrile is used.
The reaction is named after Kurt Hoesch and Josef Houben
Heinrich Hubert Maria Josef Houben (27 October 1875, in Waldfeucht (Rheinland) Germany – 28 June 1940, in Tübingen) was a German chemist. He made achievements within ketone synthesis, terpenes, and camphor studies. After being wounded several ...
''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
''Chemische Berichte'' (usually abbreviated as ''Ber.'' or ''Chem. Ber.'') was a German-language scientific journal of all disciplines of chemistry founded in 1868. It was one of the oldest scientific journals in chemistry, until it merged with ' ...
(A and B Series) Volume 59, Issue 11, Date: 8. Dezember 1926, Pages: 2878–2891 J. Houben 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
Stephen aldehyde synthesis, a named reaction in chemistry, was invented by Henry Stephen (chemist), Henry Stephen (Order of the British Empire, OBE/Member of the Order of the British Empire, MBE). This reaction involves the preparation of aldehyde ...
* Gattermann reaction
The Gattermann reaction (also known as the Gattermann formylation and the Gattermann salicylaldehyde synthesis) is a chemical reaction in which aromatic compounds are formylated by a mixture of hydrogen cyanide (HCN) and hydrogen chloride (HCl) ...
*Hoesch reaction is demonstrated for '' Buflomedil'' & Linderatin & Viminol
Viminol (marketed under the brandname Dividol) is an opioid analgesic developed by a team at the drug company Zambon in the 1960s. Viminol is based on the α-pyrryl-2-aminoethanol structure, unlike any other class of opioids.
Viminol has both an ...
.
References
{{Reflist Substitution reactions Name reactions