Nitriles Houben-Hoesch synthesis

REACTIONS USING NITRILES — THE HOUBEN-HOESCH SYNTHESIS... 

REACTIONS USING NITRILES —THE HOUBEN-HOESCH SYNTHESIS 747... 

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

The synthesis of 11-hydroxy O-methylsterigmatocystin (HOMST) was carried out in the laboratory of C.A. Townsend by utilizing the alkyinitrilium ion variant of the Houben-Hoesch reaction The alkyinitrilium salt was prepared by reacting the aryl nitrile with 2-chloropropene in the presence of SbCIs. Next, the phenol was added in a 2.5 1 excess. Alkaline hydrolysis then afforded the xanthone, which was subsequently converted to HOMST in few more steps. 

Houben-Hoesch reaction Synthesis of aromatic ketones from activated aromatic compounds (e.g. phenols) and nitriles. 216... 

Bigi, F., Maggi, R., Sartori, G., Casnati, G., Bocelli, G. Template Houben-Hoesch reaction on metal phenolates. Synthesis of aromatic ketones, nitriles and amides. Crystal structure of dichloro[2-(1-imino-2,2,2-trichloroethyl)-4-methoxyphenoxido-0,N]boron. Gazz. Chim. Ital. 

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. 

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). 

For a complete description of the synthetic utility of the Houben-Hoesch reaction as it applies to other aromatic systems, as well as some mechanistic discussions, the reader is directed to two reviews on the subject. Due to the diminished electrophilic reactivity of nitriles compared to other carboxylic acid derivatives as well as the broad number of Friedel-Crafts substrates, most Houben-Hoesch pyrrole acylation reactions are conducted intramolecularly. However, an impressive intermolecular example was delineated by Chang and co-workers in efforts directed toward the synthesis of novel 2-[5-aroylpyrrolo]alkanoic acids, for evaluation of their potential analgesic and anti-inflammatory activities. Treatment of substituted pyrrole 4 and 3-cyanopyridine (5) with acid in dry chloroform resulted in the preparation of 6 in good yield. 

Prof. Hao s synthesis commenced with the copper(I) chloride-catalyzed oxidation of the tryptamine derivative to afford ketone 42 [74], A three-component Strecker-type reaction was designed to react the ketone 42 with tryptamine and TMSCN to finish the first ring closure. After examining a series of both Lewis acid and Bronsted acids, the authors found a catalytic amount of TMSOTf promoted the transformation and afforded nitrile intermediate 43, which is ready for the Houben-Hoesch-type cyclization [75]. Treatment by TfOH (trifluoromethanesulfonic acid) [76] in DCM and the... 

---