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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, photochemical ...
in which a nitrile
In organic chemistry, a nitrile is any organic compound that has a functional group. The prefix '' cyano-'' is used interchangeably with the term ''nitrile'' in industrial literature. Nitriles are found in many useful compounds, including me ...
reacts with an arene compound to form an aryl ketone
In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double b ...
. The reaction is a type of Friedel-Crafts acylation with hydrogen chloride
The compound hydrogen chloride has the chemical formula and as such is a hydrogen halide. At room temperature, it is a colourless gas, which forms white fumes of hydrochloric acid upon contact with atmospheric water vapor. Hydrogen chlorid ...
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 sp ...
catalyst
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
.
The synthesis of 2,4,6-Trihydroxyacetophenone (THAP) from phloroglucinol
Phloroglucinol is an organic compound with the formula C6H3(OH)3. It is a colorless solid. It is used in the synthesis of pharmaceuticals and explosives. Phloroglucinol is one of three isomeric benzenetriols. The other two isomers are hydroxyqu ...
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 charged, have an atom that carrie ...
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 severa ...
''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 *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
Buflomedil, sold under the brand name Loftyl, is a vasoactive drug used to treat claudication or the symptoms of peripheral arterial disease. It is currently not approved by the Food and Drug Administration (FDA) for use in the United States.
T ...
''.
References
{{Reflist Substitution reactions Name reactions