HOUBEN - HOESCH Phenol acylation

HOUBEN - HOESCH Phenol Acylation Synthesis ol ketones (or aldehydes) by acylation ol phenols with nitriles (or ortho formates)... 

HOUBEN - HOESCH Phenol acylation 162 Huang Mnlon 426 Hubert 232, 299... 

HOUBEN HOESCH Phenol acylation 162 Huang Minion 426 Hubert 232,299 HOekel 34... 

Friedel-Crafts acylation using nittiles (other than HCN) and HCI is an extension of the Gattermann reaction, and is called the Houben-Hoesch reaction (120—122). These reactions give ketones and are usually appHcable to only activated aromatics, such as phenols and phenoHc ethers. The protonated nittile, ie, the nitrilium ion, acts as the electrophilic species in these reactions. Nonactivated ben2ene can also be acylated with the nittiles under superacidic conditions 95% trifluoromethanesulfonic acid containing 5% SbF (Hg > —18) (119). A dicationic diprotonated nittile intermediate was suggested for these reactions, based on the fact that the reactions do not proceed under less acidic conditions. The significance of dicationic superelectrophiles in Friedel-Crafts reactions has been discussed (123,124). 

Friedel-Crafts acylation with nitriles and HC1 is called the Hoesch or the Houben-Hoesch reaction,354 In most cases, a Lewis acid is necessary zinc chloride is the most common. The reaction is generally useful only with phenols, phenolic ethers, and some reactive heterocyclic compounds, e.g., pyrrole, but it can be extended to aromatic amines by the use of BCly.355 Acylation in the case of amines is regioselectively ortho. Monohydric phenols, however, generally do not give ketones354 but are attacked at the oxygen to produce imino esters. 

Highly activated aromatic compounds such as dihydric phenols can be acylated by reaction with an aliphatic nitrile in the presence of a Lewis acid, usually zinc chloride, and hydrogen chloride (Scheme 6.24). The Houben-Hoesch reaction is a variation of the Gattermann formylation and proceeds via an iminium salt, which is isolated and subsequently hydrolysed. 

Houben-Hoesch reaction. Synthesis of acyl-phenols from phenols or phenolic ethers by the action of organic nitriles in the presence of hydrochloric acid and aluminum chloride as catalyst. 

The metal-template effect is also exploited as a powerful tool to achieve highly selective phenol ort/io-acylation with trichloroacetonitrile according to a typical Houben-Hoesch reaction [111]. The best catalyst is boron chloride, which, by reacting with phenols in 1,2-dichloroethane, produces dichlorophenoxyboron derivatives, the reactive species responsible for the activation of trichloroacetonitrile as well as for the ort/jo-regioselective attack. By using zinc chloride and acetic anhydride without any solvent, an equimolecular mixture of 2- and 4-hydroxyacetophenone (36 and 40% yield, respectively) is produced, excluding any remarkable metal-template effect in the ZnClj-based system. 

Aliphatic nitriles react slowly with phenols and phenyl ethers in the presence of trifluoromethanesulphonic acid to give ketones after hydrolysis, in a variation of the Houben-Hoesch reaction. The crystalline complex of copper(i) triflate and benzene induces the acylation of aromatic substrates with selenol esters, affording a transition-metal mediated version of the Friedel-Crafts reaction. Aromatic carboxylic acids can be converted into symmetrical diaryl ketones in good yield by treatment of their 5-(2-pyridyl)thioesters with bis-(l,5-cyclo-octadiene)nickel [equation (15)]. In contrast to other methods for preparing symmetrical aromatic ketones, this method allows their preparation from a single starting material. 

Several name reactions are promoted by AICI3. For example, the Darzens-Nenitzescu reaction is simply the acylation of alkenes. The Ferrario reaction generates phenoxathiins from diphenyl ethers (eq 19) The rearrangement of acyloxy aromatic systems is known as the Fries rearrangement (eq 20). Aryl aldehydes are produced by the Gatterman aldehyde synthesis (eq 21). The initial step of the Haworth phenanthrene synthesis makes use of a Friedel-Crafts acylation. The acylation of phenolic cort tounds is called the Houben-Hoesch reaction (eq 22). The Leuckart amide s)oithesis generates aryl amides from isocyanates (eq 23). ... 

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