Houben-Hoesch reaction, aluminum chloride

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 ... 

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. 

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... 

Imidoyl chlorides are also intermediates in the Gattermann aldehyde synthesis and in the Houben-Hoesch ketone synthesis. The former reaction uses hydrocyanic acid, hydrogen chloride, and aluminum chloride as the catalyst, while in the latter reaction nitriles, hydrogen chloride, and zinc chloride are used. Hoesch in 1915 assumed that the nitriles combine with hydrogen chloride to form imidoyl chlorides, which undergo electrophilic substitution reaction with a wide variety of substrates. Stephen verified Hoesch s hypothesis by reacting phenylbenzimidoyl chloride with resorcinol, and he obtained the intermediate anil CLIX, which can be hydrolyzed to the corresponding ketone (CLX). 

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