Phenols from aryl ketones

The Dakin Reaction allows the preparation of phenols from aryl aldehydes or aryl ketones via oxidation with hydrogen peroxide in the presence of base. The aryl formate or alkanoate formed as an intermediate is subsequently saponified to yield the substituted phenol product. 

This reaction was initially reported by Dakin in 1909. It is the preparation of phenols from aryl aldehydes or aryl ketones involving the oxidation of corresponding aromatic compounds by hydrogen peroxide in the presence of a base and subsequent hydrolysis of the aryl formate or alkylcarboxylate intermediates. Therefore, this reaction is generally known as the Dakin reaction. It has been reported that the para-or ortho- substituents (such as OH, NH2) on aryl aldehydes or aryl ketones will facilitate this reaction, especially for the ortho OH group, which accelerates the reaction via the formation of an intfamolecular hydrogen bonding. ... 

This reaction has general applications in the synthesis of phenols from aryl aldehydes or aryl ketones. 

The HOPG (highly oriented pyrolytic graphite) carbon electrode chemically modified with (5[-phenylalanine at the basal surface led to 2% ee in the reduction of 4-acetylpyridine [377]. A cathode modified with a chiral poly(pyrrole) reduced 4-methylbenzophenone or acetophenone in DMF/LiBr and phenol as proton donor to 1-phenylethanol with up to 17% ee [382]. Alkyl aryl ketones have been reduced to the corresponding alcohols at a Hg cathode in DMF/water in the presence of (1R,2S)-A,A-dimethylephedrinium tetrafluorobo-rate (DET), producing (5 )-l-phenylethanol with 55% ee from acetophenone. Cyclovoltammetry supports an enantioselective protonation of the intermediate (PhCOH(CH3)) [383]. 

The Fries rearrangement used for the preparation of aryl ketones from phenolic esters is now one of the most significant reactions in the synthetic chemistry of aromatic compounds, both in the classical version (equation 99) and in the newest modifications (see Section IV.D.3). 

Arylbismuth 671, 673 Arylboronic acid 671, 673 Arylbutenes, formation of 613 Aryl-2-cyclohexenones 653 Aryl ethers—see also AUyl aryl ethers. Diaryl ethers. Phenyl ethers, Propargyl aryl ethers formation from calixarenes 1387 Aryl haUdes, as phenol precursors 396, 397 Ai-Arylhydroxylamines, isomerization of 801-805 oxidation of 419 3-Arylindoles, synthesis of 1236 Aryl ketones, oxidation of 424, 425 Aryloxylium cations 179 Asatone, synthesis of 1178, 1179 Ash, from incineration of municipal waste, phenoUc compounds in 938 Aspersitin, synthesis of 1327, 1328 Aspirin 10, 11... 

A range of imines derived from trifluoromethyl aryl ketones have been converted into heterocyclic products via intramolecular cyclization with loss of the CF3 group. For example, o-aminoimine (15), when treated with strong base, cyclizes to benzimidazole (16), with loss of trifluoromethyl anion. The corresponding o-phenols yield benzoxazoles, and examples using an external amine lead to aziridines. 

Many organic compounds are also prepared by hydrolysis of the appropriate halides. Alcohols can be prepared by hydrolysis of alkyl halides (though yields are often poor due to the formation of considerable amounts of olefins and polyolefins) phenols are prepared from aryl halides under pressure, in the presence of concentrated base (Samuel and Scheinmann, private communication), aromatic aldehydes and ketones from gem-dihalides (Doering and Dorfman, 1953), and aromatic acids from trihalides (Ponticorvo and Rittenberg, 1954). 

Another synthesis of the cortisol side chain from a C17-keto-steroid is shown in Figure 20. Treatment of a C3-protected steroid 3,3-ethanedyidimercapto-androst-4-ene-ll,17-dione [112743-82-5] (144) with a tnhaloacetate, 2inc, and a Lewis acid produces (145). Addition of a phenol and potassium carbonate to (145) in refluxing butanone yields the aryl vinyl ether (146). Concomitant reduction of the C20-ester and the Cll-ketone of (146) with lithium aluminum hydride forms (147). Deprotection of the C3-thioketal, followed by treatment of (148) with y /(7-chlotopetben2oic acid, produces epoxide (149). Hydrolysis of (149) under acidic conditions yields cortisol (29) (181). 

Sulphuric acid (concentrated). Widely used in desiccators. Suitable for drying bromine, saturated hydrocarbons, alkyl and aryl halides. Also suitable for drying the following gases hydrogen, nitrogen, carbon dioxide, carbon monoxide, chlorine, methane and paraffins. Unsuitable for alcohols, bases, ketones or phenols. Also available with an indicator (a cobalt salt, blue when dry and pink when wet) under the name Sicacide (from Merck) for desiccators. 

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