Oxidative phenol-ethers

The hydroxyl groups can be alkylated with the usual alkylating agents. To obtain aryl ethers a reverse treatment is used, such as treatment of butynediol toluenesulfonate or dibromobutyne with a phenol (44). Alkylene oxides give ether alcohols (46). 

A carbonyl group cannot be protected as its ethylene ketal during the Birch reduction of an aromatic phenolic ether if one desires to regenerate the ketone and to retain the 1,4-dihydroaromatic system, since an enol ether is hydrolyzed by acid more rapidly than is an ethylene ketal. 1,4-Dihydro-estrone 3-methyl ether is usually prepared by the Birch reduction of estradiol 3-methyl ether followed by Oppenauer oxidation to reform the C-17 carbonyl function. However, the C-17 carbonyl group may be protected as its diethyl ketal and, following a Birch reduction of the A-ring, this ketal function may be hydrolyzed in preference to the 3-enol ether, provided carefully controlled conditions are employed. Conditions for such a selective hydrolysis are illustrated in Procedure 4. 

Oxidative reactions frequently represent a convenient preparative route to synthetic intermediates and end products This chapter includes oxidations of alkanes and cycloalkanes, alkenes and cycloalkenes, dienes, aromatic fluorocarbons, alcohols, phenols, ethers, aldehydes and ketones, carboxylic acids, nitrogen compounds, and organophosphorus, -sulfur, -selenium, -iodine, and -boron compounds... 

In the first of these, the key step in the synthetic sequence involves an oxidative phenol coupling reaction patterned after the biosynthesis of the natural product. Preparation of the moiety that is to become the aromatic ring starts by methyla-tion of phloroglucinol (5) with methanolic hydrogen chloride to give the dimethyl ether (6). Treatment of that intermediate with sulfuryl chloride introduces the chlorine atom needed in the final product (7). 

On oxidation it yields veratric acid melting at 179° to 180°, and by the action of bromine on the phenol-ether dissolved in absolute ether, a dibromide is obtained, which melts at 101° to 102°. It has the constitution—... 

On oxidation with permanganate of potassium, this phenol ether yields tetramethoxy benzoic acid, C H(OCH3)4COOH, melting at 87°. 

Oxidation of that compound with chromium trioxide in sulfuric acid leads cleanly to the desired ketone (67). Treatment with hydrobromic acid serves to demethylate the phenolic ether function (68). Direct... 

The conversion to quinones is of technical interest (Vit. E, K) starting from phenol ethers or naphthalines (Table 15, number 6) is compiled in Ref. [242]. Eor the oxidation to naphthoquinones, indirect methods proved to be superior [243]. 

Phenol ethers, like the parent phenols, are reactive substrates. Phenol ethers like anisole and phenetole are readily nitrated to their picryl ethers, 2,4,6-trinitroanisole and 2,4,6-trinitrophenetole respectively, on treatment with mixed acid composed of concentrated nitric and sulfuric acids at 0 °C. Such reactions are vigorous, prone to oxidative side-reactions, and pose a considerable safety risk. The direct nitration of 2,4-dinitrophenol ethers, obtained from the reaction of 2,4-dinitrochlorobenzene with alkoxides, provides a more practical route to picryl ethers on an industrial scale. ... 

Nonphenolic oxidative coupling of phenol ether derivatives using IBTA can also produce seven-membered N-containing heterocyclic compounds as exemplified by Eq. (45) [96JCS(CC)1481],... 

At least three methods have been found to be applicable to the solubilization of chemically modified wood. The first experiment (4) (Direct method) employed severe dissolution conditions. For example, in 20-150 min at 200-250°C, wood samples esterified by a series of aliphatic acids could be dissolved in benzyl ether, styrene oxide, phenol, resorcinol, ben-zaldehyde, aqueous phenol solutions, etc. For carboxymethylated, ally-lated and hydroxyethylated woods, the conditions provided for dissolution in phenol, resorcinol or their aqueous solutions, formalin, etc., by standing or stirring at 170°C for 30 to 60 min (5). 

Phenolic ethers, dealkylation of, 287 Phenols, nitrosation of, 394 Phenoxypropadiene, 11 3-Phenylamino-l-butyne, 97 Phenyl azide, 281-282 Phenylazoalkanes, 327 Phenylazodiphenylphosphine oxide, 328 Phenylazoethane, 308 Phenylazohydroperoxides, 331 2-Fhenylazo-l,3-indandione, 299 Phenylazo-l-naphthalene, 304, 311 PhenyIazo-2-naphthaIene, 304, 311 Phenylazonaphthalenes, 310... 

Oxidative coupling of phenols and phenol ethers.2 This reaction can be conducted with ferric chloride supported on silica gel. 

A very simple synthesis of coumestrol (228) has been described by Kappe and coworkers (Scheme 46) (74ZN(B)292). It is based upon dehydrogenation of 4-hydroxy-3-phenyl-coumarins to coumestans (720PP233). A number of 2 -hydroxy 3-phenylcoumarins were oxidized with lead tetraacetate to the corresponding coumestans 3-(l-acetoxy-4-methoxy-2-oxo-3,5-cyclohexadienyl)coumarins were obtained as by-products (76BCJ1955). Coumes-tan itself (226) has been obtained by photolysis of the phenol ether (232), which is in turn available from 4-hydroxycoumarin (229) and (diacetoxyiodo)benzene (Scheme 47) (78CB3857) via an iodonium ylide (231). 

Oxidative phenolic coupling.1 A new hiomimetic approach to morphine alkaloids involves oxidative intramolecular coupling of the reticuline derivative 1 to a salutaridine derivative 2 with VOCl3 in ether.1 If the reaction is conducted in CH2C12 2 is obtained in markedly lower yield and the undesired aporphine 3 is formed as a major product. The dienone 2 has been converted into 2-hydroxycodeine (4). 

Kita and Tohma found that exposure of p-substituted phenol ethers to [bis(tri-fluoroacetoxy)iodo]benzene 12 in the presence of some nucleophiles in polar, less nucleophilic solvents results in direct nucleophilic aromatic substitution [Eq. (84)] [156]. Involvement of a single-electron transfer (SET) from phenol ethers to A3-iodane 12 generating arene cation radicals was suggested by the detailed UV-vis and ESR studies. SET was involved in the oxidative biaryl coupling of phenol ethers by 12 in the presence of BF3-Et20 [157]. 

The use of hypervalent iodine reagents in carbon-carbon bond forming reactions is summarized with particular emphasis on applications in organic synthesis. The most important recent methods involve the radical decarboxylative alkylation of organic substrates with [bis(acyloxy)iodo]arenes, spirocyclization of para- and ortho-substituted phenols, the intramolecular oxidative coupling of phenol ethers, and the reactions of iodonium salts and ylides. A significant recent research activity is centered in the area of the transition metal-mediated coupling reactions of the alkenyl-, aryl-, and alkynyliodonium salts. 

Oxidative Cyclization of Substituted Phenols and Phenol Ethers. . 103... 

Intramolecular oxidative cyclizations in the appropriately substituted phenols and phenol ethers provide a powerful tool for the construction of various practically important polycyclic systems. Especially interesting and synthetically useful is the oxidation of the p-substituted phenols 12 with [bis(acyloxy)iodo]-arenes in the presence of an appropriate external or internal nucleophile (Nu) leading to the respective spiro dienones 15 according to Scheme 6. It is assumed that this reaction proceeds via concerted addition-elimination in the intermediate product 13, or via phenoxenium ions 14 [18 - 21]. The recently reported lack of chirality induction in the phenolic oxidation in the presence of dibenzoyltar-taric acid supports the hypothesis that of mechanism proceeding via phenoxenium ions 14 [18]. The o-substituted phenols can be oxidized similarly with the formation of the respective 2,4-cyclohexadienone derivatives. 

The oxidation of phenol ethers 26 by [bis(trifluoroacetoxy)iodo]benzene in the presence of external or internal nucleophiles affords products of nucleophilic substitution 28 via the intermediate formation of the cation radical intermediate 27 according to Scheme 12 [21,27 - 30]. 

In the intermolecular mode, this reaction has been utilized for the preparation of products 28 from various nucleophiles, including C-nucleophiles (e. g. (3-dicarbonyl compounds). A similar reaction in the intramolecular mode provides a powerful synthetic tool for the preparation of various polycyclic compounds via oxidative biaryl coupling [21,27 - 30]. Several examples of these C-C bond forming reactions are shown in Schemes 13-15. Specifically, various dibenzoheterocyclic compounds 30 have been prepared by the oxidation of phenol ether derivatives 29 with [bis(trifluoroacetoxy)iodo]benzene in the presence of BF3-etherate in dichloromethane (Scheme 13) [27-29]. 

Under similar conditions, the phenanthro-fused thiazoles, isoxazoles and pyrimidines 32 (Scheme 14) can be prepared by oxidative coupling of the respective phenol ethers 31 [31,32]. 

Similar para-quinone derivatives can be obtained by oxidative demethyla-tions of phenol ethers which can be performed in water. Either [bis(trifluo-roacetoxy)iodo]benzene 4 or the polymer-supported reagent 19 can be used for the generation of para-quinones 38 from 1,4-dimethoxybenzene derivatives of type 39, Scheme 19 [93]. 

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