Ortho-methoxyphenols

A similar substitution pattern can be obtained by applying a thermal protocol as well [75]. Ortho-methoxyphenol 131 has been synthesised in good yields by warming the cyclobutene-containing 1,3,5-metallatriene 130 in tetra-hydrofuran (Scheme 55). 

Explain why Is ortho nltrophenol more addle than ortho methoxyphenol ... 

After 72 h at room temperature with a substrate catalyst ratio (R) of 10, the reaction mixture was methylated with dimethylsulphate and potassium carbonate and analyzed by GLC-MS. Veratric acid methyl ester 4 and 1,2-dimethoxybenzene 22 were recognized, indicating that the oxidation reaction mixture contained vanillic acid methyl ester 6 and ortho-methoxyphenol 20. Also, 3,4-dimethoxyacetophenone 21 was found, indicating the presence of 3-methoxy-4-hydroxyacetophenone 19 in the oxidation reaction mixture. 

The second P-0-4 dimer submitted to reaction with dioxygen (10 bar) at room temperature in the presence of Co(II) salen as the catalyst was l-(3,4-dimethoxyphenyl)-(2-methoxyphenoxy)ethane-l-ol 23, also prepared according to Landucci (22). In the same reaction conditions, again, veratric add methyl ester 4 was recognized after methylation, derived from vanillic acid methyl ester 6 present in the oxidation reaction mixture. The other component of the methylated mixture was 1,2-dimethoxy-benzene 22, derived from ortho-methoxyphenol 20. 

With 4-methoxyphenols, the phenoxyl formed is further stabilized by delocalization of the unpaired electron to the p-type orbital of the methoxyl oxygen (105 -106). This interaction is allowed in vitamin E and in compound 103 but prohibited in compound 104 because the former two compounds exist in conformation 107 and the latter in conformation 108. In conformation 108, due to the methyl groups in ortho position, the methoxyl group is twisted out of the plane of the aromatic ring and the delocalization of the methoxyl oxygen electron pair is consequently prohibited. 

This pK a is higher than would be anticipated for ortho- and meta- substituted phenols since the o meth-oxyphenol has a pK a of 9.98, m-methoxyphenol a pK a of 9.65 and resorcinol a pK a of F.81 (13). A molecular model of the drug shows that the free rotation of the phenolic hydrogen is hindered by the A -hydrogen and can explain a9-tetrahydrocannabinol s higher pK a. Of course, if solvated dimers, trimers, etc., exist with hydrophobic bonding, the observed pK a could be a hybrid pK a for a solution of such polymers. 

Fluorinated aromatic substrates have been used in the synthesis of fluorinated biaryl derivatives via S l reactions650. Substrates YC6H4Br (Y = F, CF3 or OCF3) were treated with the anions from 2,4-di-ter/-butylphenol, 2,6-di-tert-butylphenol, / ara-methoxyphenol, / 0ra-(trifluoromethoxy)phenol and 2-naphthol leading to the biaryls YC6H4—ArOH by C-arylation at the carbon atom ortho to the deprotonated hydroxyl group (C-l in 2-naphthol), but at the para carbon atom in 2,6-di-terr-butylphenol. 

Now the tosylation—under the usual conditions—followed by the nucleophilic aromatic substitution (Chapter 23). The leaving group is ortho to two electron-withdrawing groups, and so the substitution pattern is right for nucleophilic aromatic substitution. The nucleophile is 4-methoxyphenol, deprotonated by pyridine. 

Lutskii (1280, 1277, see C.A. 49, 15324h) shows that in/ramolecularly H bonded substances have lower surface tensions than do the isomers that have interaction between molecules. For example, at 131 C the surface tensions of o-, m-, and / -methoxyphenol are 28.8, 33.6, and 34.2 dynes/cm. For the three dimethoxyphenols, the values are all 26 0.5 dynes/cm. This same ortho effect on surface tension (as well as on viscosity, density, and boiling point) is illustrated with many types of compounds in the papers quoted. 

Various other routes produce Reissert-type ring-closure precursors. For example, the palladium-catalysed coupling, in the presence of a methoxyphenol additive, of ort/to-halo-nitroarenes with methyl ketones, followed by titanium trichloride reduction of the products, leads directly to 3-unsubstituted indoles. More obviously, ortho-halo trifluoroacetanilides can be coupled with p-keto esters or amides, the base incorporated in the mixture leading to hydrolysis and closure to the indole. ... 

The conversion of the o-methoxyphenol to the methylenedioxy group may occur late in the biosynthetic pathway. Tritiated norpluviine is converted to tritiated lycorine by the Deanna Durbin daffodil. This transformation not only demonstrates the conversion of an o-methoxyphenol to the methylenedioxy group but also indicates that the C-2 hydroxyl group of lycorine is derived by allylic oxidation of either norpluviine or caranine. This late-stage hydroxylation was suspected when it was found that hydroxynorbelladine (CCXXVIII R,Ri,R2,Rs = H OH instead of H ortho to RgO) was incorporated into lycorine with extremely low efficiency. 

The antioxidant activity of phenol is also increased by the presence of additional hydroxyl group in the ortho or para positions. An example of such an antioxidant is TBHQ. The effectiveness of 1,2-dihydroxybenzene derivatives is attributed to a phenoxyl radical stabilised by an intramolecular hydrogen bond (11-8). The activity of 2-methoxyphenol is lower, because the generated radical cannot be stabihsed by a hydrogen bond. The antioxidant activity of 1,2-and 1,4-dihydroxybenzene is partly caused by the fact that the semi-quinone radical can be further oxidised to the corresponding o-quinone orp-quinone, respectively, by reaction with another lipid radical (Figure 11.7) or may disproportionate to the corresponding quinone and hydroquinone. 

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