Acylation Hoesch

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). 

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

The synthetic importance of the Houben-Hoesch reaction is even more limited by the fact that aryl ketones are also available by application of the Friedel-Crafts acylation reaction. 

Friedel-Crafts acylation with nitriles and HCl is called the Hoesch or the Houben-... 

Hoesch reaction. 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 BCls. Acylation in the case of amines is regioselectively ortho. Monohydric phenols, however, generally do not give ketones " but are attacked at the oxygen to produce imino esters. Many nitriles... 

Acylation of aromatic rings with nitriles (Hoesch)... 

Acylation with Nitriles. The Hoesch Reaction Acylation or Acyl-de-hydrogenation... 

Pyrroles and furans also undergo the Gattermann aldehyde synthesis with HC1 and HCN, furan gives furfuraldehyde and 2-methylindole gives 2-methylindole-3-carboxaldehyde. The Houben-Hoesch ketone synthesis is also applicable to the preparation of acyl derivatives of furans and pyrroles, e.g. ethyl 2,4-dimethylpyrrole-3-carboxylate with MeCN and HC1 yields (81). 

Various intramolecular reactions are widely used to prepare this type of heterocycle. Intramolecular acylation has been used frequently (84AHC(37)i). Houben-Hoesch cyclization of I -(3-cyanoethylpyrrole (4a) gives l-oxo-2,3-dihydropyrrolizine (5a). The methyl group in (4b) selectively activates C-2 so that only the isomer (5b) is formed (66JA1305). 

Intramolecular acylation has been used frequently. Houben-Hoesch cyclization of 1 -/ -cyanoethylpyrrole (2a) gives l-oxo-2,3-dihydropyrrolizine (3a).9-17 Difficulties occur because polymerization of the nitrile (2a) can be a side reaction. Addition of boron trifluoride [3a (33%)]11 or its ethyl ether complex [3a (60-80%)]15 has been recommended. Treatment of nitrile 2a with a molten aluminum chloride-potassium chloride-sodium chloride mixture yields 70% of ketone 3a but the experimental conditions are highly critical.13 A reproducible procedure that is based mainly on Clemo s specification9,10 gave 22% of ketone 3a.17 Purification of 3a should be carried out in an efficient fume hood because it appears to induce analgesia.1 ... 

The intramolecular acylation of 2-aryloxybenzonitriles allowed the synthesis of molecules with dixanthone skeleton.363 The procedure, in fact, is an intramolecular Houben-Hoesch reaction364 to afford the intermediate bisiminium salts [Eq. (5.144)] which, after hydrolysis, gave the final diketo products. 

Phenolic ketones may be prepared by the Hoesch acylation reaction, which may be regarded as an extension of the Gattermann aldehyde synthesis (Section 6.10.1, p. 990). The procedure involves reaction of a nitrile with a phenol (or phenolic ether) in the presence of zinc chloride and hydrogen chloride best results are usually obtained with polyhydric phenols or their ethers, as for example in the preparation of phloroacetophenone (Expt 6.125). The formation of phenolic ketones by means of the Fries rearrangement of phenolic esters with aluminium chloride is discussed on p. 976. 

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 Phenol acylation 162 Huang Mnlon 426 Hubert 232, 299... 

In the laboratory of D.W. Cameron the total synthesis of the azaanthraquinone natural product bosttycoidin was undertaken using the Minisci reaction and the intramolecular Houben-Hoesch reaction as the key steps. It is worth noting that the synthesis of specific di- and trihydroxyazaanthraquinones by the Friedel-Crafts acylation is very limited due to the lack of orientational specificity and the lack of reactivity of pyridine derivatives in acylation reactions. 

Acylations with Nitriles. With particularly reactive aromatic nuclei such as phenols, a Friedel-Crafts type reaction may be effected with nitriles in the presence of an acid catalyst such as hydrogen chloride, aluminum chloride, or zinc chloride. The reaction is usually called the IIouben-Hoesch synthesis.700 When hydrogen cyanide is employed, the process leads to aromatic aldehydes even with a number of aromatic... 

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. 

---