HOUBEN-HOESCH

To explain the experimentally observed high reactivity of HCN and alkyl nitriles under snperacidic condition, Shndo found that in the Gat-terman and Houben-Hoesch reactions, diprotonated HCN (or nitriles) are involved as the de facto reagents (HC N H2, RC N H2). 

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)... 

An analogous reaction is the Houben-Hoesch reaction,(sometimes called the Hoesch reaction) using nitriles 7 to give aryl ketones 8. This reaction also is catalyzed by Lewis acids often zinc chloride or aluminum chloride is used. The Houben-Hoesch reaction is limited to phenols—e.g. resorcinol 6—phenolic ethers and certain electron-rich aromatic heterocycles ... 

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. 

Houben-Hoesch reaction, 12 179 Household appliances, virtual two-way SMA devices in, 22 348 Household laundering, 4 45-46 detersive systems for, <5 413t Household products emulsion use in, 10 129 organic esters in, 10 518-519 Household uses, sodium sulfates in,... 

Houben-Hoesch synthesis orgchem Condensation of cyanides with polyhydric phenols in the presence of hydrogen chloride and zinc chloride to yield phenolic ketones. hit-ban harsh sin-tha-sas ... 

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. 

A method for the preparation of 1-hydroxypyrrolizidine was published by Adams et al.7i Cyclization of 1 -(/ -cyanoethyl)pyrrole under the conditions of the Houben-Hoesch reaction gave rise to l-oxo-3/f-l,2-dihydropyrrolo(l,2-a)pyrrole (123) (cf. refe. 48 and 73), which can be converted into 1-hydroxypyrrolizidine by either direct hydrogenation over rhodium on alumina or hydrogenation of the corresponding hydroxy derivative 124. This route has some interest as a potential... 

The Houben-Hoesch Reaction refers specifically to phenols as substrates, where the reaction is generally most useful. 

More recent studies with superacidic systems (TfOH, TfOH—SbF5), used also in the Gattermann reaction, indicated that strong acids significantly increase reactivities of benzene with benzonitrile.33 104 It is concluded that the superelectrophilic 14 dication formed as a results of protonation of 13 is the reactive species in the Houben-Hoesch reaction. 

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 ... 

Friedel-Crafts reactions have found application to form the 1,2-bond of pyrrolizines. Treatment of anhydride 78 with aluminum chloride gave 93% of acid 79, which on heating in the presence of copper gave a 91% yield of 2,3-benzo-1 H-pyrrolizin-1 -one (17).55 Benzopyrrolizinones (81) have been obtained from acid chlorides (80) by a similar route.56,57 Houben-Hoesch cyclization of nitrile 82 gave 2,3-benzo-lf/-pyrrolizin-l-one (17) in a reaction that resembles the formation of 17 from 16a.58... 

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