Hoesch ketone synthesis

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). 

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). 

The Hoesch ketone synthesis also functions well in the pyrrole series s, 28, 33 ketones resulting from reaction with a variety of reagents R.CN R = Me, CH2GI, G02Et, GN, -GH2GN) in the presence of ethereal hydrogen chloride. Orientation follows the same rules as in the Gattermann reaction. 2,3,4-Trimethylpyrrole is said not to react with acetonitrile in the Hoesch synthesis. 

The ketone synthesis of Houhen and Hoesch, which is based on the principle of the Gattermann reaction, proceeds very smoothly and gives very favourable results, especially in the case of polyhydric phenols. In this synthesis nitriles are used. Here it is the iminochlorides R—C=NH which are converted into ketimines and then into ketones, a... 

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

Hoesch synthesis A variation of the Gattermann synthesis of hydroxy-aldehydes, this reaction has been widely applied to the synthesis of anthocyanidins. It consists of the condensation of polyhydric phenols with nitriles by the action of hydrochloric acid (with or without ZnCl2 as a catalyst). This gives an iminehydrochloride which on hydrolysis with water gives the hydroxy-ketone. 

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

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 ... 

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. 

Hoesch, K. A new synthesis of aromatic ketones. I. Preparation of some phenol ketones. Ber. 1915,48, 1122-1133. 

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. 

As long as the nucleophilic partner is substituted with electron-donating substituents, the Houben-Hoesch reaction has broad scope. This is most directly illustrated by the work of Parmar and co-workers who used Houben-Hoesch conditions for the synthesis of a large number of benzyl phenyl ketones. ... 

Hao and colleagues disclosed a rapid total synthesis of ( )-tr onoliimine A via a Strecker/Houben-Hoesch sequence.The three-component Strecker-type reaction of 169, 170, and TMSCN was found to be effectively promoted by TMSOTf to furnish intermediate 171 this intermediate was unstable in basic or neutral environments and thus was treated directly with triflic acid at room temperature to effect the Houben-Hoesch cyclization and give ketone 172. Finally, the addition of hydrazine triggered deprotection of the amine and subsequent cyclization to furnish 173 (130L528). 

The benzyl ketones required for this synthesis are usually prepared by a Hoesch reaction between a benzyl cyanide and a mono- or poly-hydric phenol. When the benzyl cyanide is labelled with isotopic carbon at the nitrile group, it is possible to prepare a C-4 labelled chromone [80] which may be useful in further metabolic studies (Figures 2.3). 

Another approach to the synthesis of the dihydrobenzofurancarboxylic acid 1 is outlined in Scheme 4. The key reaction in this alternative is the Houben-Hoesch reaction on methyl-4-amino-2-methoxy-5-chloro benzoate 10. Houben-Hoesch reaction on anilines, giving exclusively ortho amino ketones has been described by Sugasawa.[i3] Under these reaction conditions, the ether function is demethylated to provide the keto-phenol 11. Compound 11 can then be cyclized under very mild conditions to the furanone 12 which, after reduction... 

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... 

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