2-Methoxyphenols, oxidative coupling

The previous examples have invariably involved the 4-position but where this is substituted as in the case of 4-methoxyphenol, oxidative coupling can take place at the 2-position probably via an intermediate phenoxide ion without... 

Although permanganate ions are not generally used to effect oxidative coupling of phenols, it has been shown that, in the presence of a catalyst in an organic solvent, 2-methoxyphenols are coupled oxidatively under very mild conditions to produce the dimeric products (>50%) [48], Unsaturated substituents are not oxidized under the mild conditions. 

These compounds contain a furan ring fused to a benzene moiety in the 2,3-position. This synthesis was also described by Flynn et al. [73] and is shown in Scheme 25 involved the coupling of 2-iodo-5-methoxyphenol 104, 4-methoxyphenylethyne 105 to form the intermediate o-alkynylphenolate 106. Aryl iodide 107 was added to the phenolate in DMSO with heat. Oxidative addition, palladium(II)-induced cyclization and reductive elimination resulted in the product 108 with an 88% yield. 

The voltammetric response of curcumin and carthamin must, in principle, be dominated by the oxidation of the phenol and/or methoxyphenol groups (see Scheme 2.2). The electrochemistry of methoxyphenols has claimed considerable attention because of their applications in organic synthesis [159-163]. As studied by Quideau et al., in aprotic media, 2-methoxyphenols are oxidized in two successive steps into cyclohexadienone derivatives [163], whereas a-(2)- and a-(4-methoxyphenoxy) alkanoic acids undergo electrochemically induced spirolac-tonization to develop synthetically useful orthoquinone bis- and monoketals. In the presence of methanol, the electrochemical pathway involves an initial one-electron loss, followed by proton loss, to form a monoketal radical. This undergoes a subsequent electron and proton loss coupled with the addition of alcohol to form an orthoquinone monoketal. The formal electrode potential for the second electron transfer... 

On controlled electrolysis (+880 mV vi. SCE 2 Fmol ) in MeOH, 2,6-dibromo-4-methoxyphenol (50) underwent 2e oxidation, followed by nucleophilic capture with MeOH to afford 2,6-dibromo-4,4-dimethoxy-2,5-cyclohexadien-l-one (51) in quantitative yield. 50 was also electrolyzed at a less positive potential (+440 mV ca 1 Fmor ) in MeOH containing AcOH-AcONHt to give two dienones (52 and 53) in 32 and 55% yields, respectively, as shown in Scheme 10. Herein, these products must be formed by C—O and C—C couphngs with bromine substitution, respectively. Therefore, the selective formation of 2e oxidation products or radical coupling dimers depends on the choice of the solvent. 

Oxidative cross-coupling has been effected moderately selectively. For example, by the addition of aluminium chloride in nitromethane to a nitromethane solution of 4-methylphenol and 4-methoxyphenol under nitrogen followed by gradual treatment with with dichlorodicyano-1,4-benzoquinone and reaction at ambient... 

Oxidative dimerisation of 4-methoxyphenol has been mentioned in the previous chapter. 4-Methylphenol in bromobenzene containing caesium carbonate, the only effective base for the reaction, was mixed with 10mole% of a rhodium complex at ambient temperature. Heating of the mixture at 90X for 24 hours afforded a 51% yield of the coupled product, 2,2 -dihydroxy-5,5 -dimethylbiphenyl (ref. 73). The yield was improved by the addition of 2.2 moles of water. 

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