Methoxybenzenes, substitution

Bromination has been shown not to exhibit a primary kinetic isotope effect in the case of benzene, bromobenzene, toluene, or methoxybenzene. There are several examples of substrates which do show significant isotope effects, including substituted anisoles, JV,iV-dimethylanilines, and 1,3,5-trialkylbenzenes. The observation of isotope effects in highly substituted systems seems to be the result of steric factors that can operate in two ways. There may be resistance to the bromine taking up a position coplanar with adjacent substituents in the aromatization step. This would favor return of the ff-complex to reactants. In addition, the steric bulk of several substituents may hinder solvent or other base from assisting in the proton removal. Either factor would allow deprotonation to become rate-controlling. 

For the Birch reduction of mono-substituted aromatic substrates the substituents generally influence the course of the reduction process. Electron-donating substituents (e.g. alkyl or alkoxyl groups) lead to products with the substituent located at a double bond carbon center. The reduction of methoxybenzene (anisole) 7 yields 1-methoxycyclohexa-1,4-diene 8 ... 

The present method of preparation of 4,4 -dimethyl-l,l -biphenyl is that described by McKillop, Elsom, and Taylor 15 It has the particular advantages of high yield and manipulative simplicity and is, moreover, applicable to the synthesis of a variety of symmetrically substituted biaryls 3,3 - and 4,4 -Disubstituted and 3,3, 4,4 -tetrasubstituted 1,1 -biphenyls are readily piepared, but the reaction fails when applied to the synthesis of 2,2 -disubstituted-l,T biphenyls The submitters have effected the following conversions by the above procedure (starting aromatic bromide, product biphenyl, % yield) bromobenzene, biphenyl, 85,1 -bromo-4-methoxybenzene, 4,4 -dimethoxy-l, 1 -biphenyl, 99, 1 bromo 3 methylbenzene, 3,3 dimethyl-1,l -biphenyl, 85 4-bromo-l,2-dimethylbenzene, 3,3, 4,4 -tetramethyl-l,l -biphenyl, 76, l-bromo-4-chlorobenzene, 4,4 -dichloro-l,l -biphenyl, 73, l-bromo-4-fluorobenzene, 4,4 -difluoro-l,l -biphenyl, 73... 

In 1999, Ikeda et al. reported a new type of sulfur-oxazoline ligands with an axis-fixed or -unfixed biphenyl backbone prepared in good yields by coupling reactions of methoxybenzene derivatives substituted with a chiral oxazoline and a sulfur-containing Grignard reagent. These ligands were subsequently evaluated for the test palladium-catalysed asymmetric allylic alkylation... 

Iodination versus chlorination. Three distinct classes of halogenation reactions are observed with various substituted methoxybenzenes and IC1 when carried out under an identical set of conditions, i.e., exclusive iodination, exclusive chlorination, and mixed chlorination and iodination. For example, equimolar mixtures of anisole, 2,5-dimethyl-1,4-dimethoxybenzene and 1,4-dimethoxybenzene and iodine monochloride (kept in the dark) yield p-iodoanisole, chloro-2,5-dimethyl- 1,4-dimethoxybenzene, and a (4 6) mixture of chloro- and iododimethoxybenzene, respectively, in nearly quantitative yields,225 i.e.,... 

Ortho substitution also allows one to control other steps in the cycloaromatization cascade. For example, mira-molecular hydrogen-atom (H-atom) abstraction from the ortho-OCH3 group effectively intercepts the p-benzyne intermediate in the Bergman cycloaromatization of 2,3-diethynyl-l-methoxybenzene before this... 

Anodic nuclear substitution by methoxide or cyanide ions gives acceptable yields only for methoxybenzenes and methoxynaphthalenes. The nucleophile is attached to the point of highest positive charge density in the radical-cation and for many examples this leads to ipio-substitution. Oxidation of 1,4-dimethoxybenzene in methanol containing potassium hydroxide leads to the quinone diketal 8 [69]. The reaction is a general one for 1,4-dimethoxybenzenes [70, 71] and 1,4-... 

Anodic oxidation of methoxybenzenes in aqueous sulphuric acid also leads to loss of the methoxy substituent, this time through jju o-substitution on the radical-cation by water. Anisole and 4-niethoxyphenol are both converted to quinone [81]. The elimination of methanol is catalysed by protons by the mechanism illustrated in Scheme 6.8. Diphenyl derivatives have also been isolated from oxidation of some methoxybenzenes. They arise through the competitive reaction involving a... 

Fluorescence was observed for the TMB family such as 3,5-dimethoxyphenol, l,3-dihydroxy-5-methoxybenzene (5-methoxyresorcinol), l-acetoxy-3,5-dimethoxyben-zene, and l,3,5-trimethoxy-2-methylbenzene. These results indicated that complete symmetry of the substitution on O atoms is not necessary to observe fluorescence from the TMB family, and that the variation of parent molecules of fluorescent radical cation is possibly performed [153]. Fluorescence was also detected from hexamethxybenzene as an example of pseudo-Dgh molecules. The discussion of the symmetry has been described here on the fluorescence from fluorobenzenes in the vapor-phase or noble gas matrices. 

The genus Pimpinella (Apiaceae) produces rare phenylpropanoids with an unusual substitution pattern at the phenyl ring the (1 )-propenyl-2-hydroxy-5-methoxybenzene skeleton of these compounds... 

A series of oxygenated 2-hydroxy-2 -methoxybenzophenones has been prepared by the Friedel-Crafts acylation of various methoxybenzenes with substituted benzoyl chlorides. 

Explain the nature of this reaction. What is likely to be the substituting agent What products would you expect from trifluoroperoxyethanoic acid and fluorobenzene Would fluorobenzene be more, or less, reactive than methoxybenzene ... 

Kinetic and DFT studies have found that the rapid cycloaromatization of 2,3-diethynyl-l-methoxybenzene compared with 1,2-diethynylbenzene can be attributed to intramolecular hydrogen abstraction by the p-bcnzyne diradical intermediate from the OMe substituent. This has been shown to render the cyclization effectively irreversible by leading to a more stable diradical, and may have significant implications for the action of therapeutic enediynes.57 In general, the Bergman cycloaromatizations of 1-substituted 2,3-diethynylbenzenes have been found to be highly sensitive to the nature of the ortho-substituent, but the measurements and even the relative trends... 

Ohashi, M., Tanaka, Y., and Yamada, S. (1977) The [2 + 2]cycloaddition vs substitution in photochemical reactions of methoxybenzene-acrylonitrile systems. Tetrahedron Letters, 18, 3629-3632. 

Redox potential is a catalytically relevant property of heme peroxidases, as in theory, sets the limit for the oxidative ability of the enzyme. An inverse correlation was found between the activity and the redox potential of methoxybenzenes and methoxy-substituted benzyl alcohols for lignin peroxidase (LiP) and horseradish peroxidase (HRP) [42, 43]. These enzymes were able to catalyze the oxidation of methoxybenzenes with redox potential as high as 1.45 V and 1.12 V, respectively [42]. In the case of methoxy-substituted benzyl alcohols, the maximum substrate redox potential was 1.39 V for both enzymes [43]. This type of correlation has allowed ranking enzymes from the more oxidant to the less oxidant. The inverse... 

Similar reactions with 1,4-dihydroxybenzene and para-substituted methoxybenzenes did not produce the expected diaryl tellurium dichlorides1. 

Difunctional compounds will have 3 values larger than either of the mono-substituted compounds. For example, for benzaldehyde 3 = 0.23 and for methoxybenzene 3 = 0.15, but the 3 value for methoxybenzaldehyde will be larger than 0.23 by an increment which depends upon the difference between values (A 3) of the mono substituted compounds as follows ... 

Pichat et al. [119] previously reported an increase in the apparent first order rate constant with increasing hydrophobicity of a series of chlorophe-nols. In a follow up study of meta and para substituted methoxybenzenes no simple correlation was observed between the hydrophobicity (Kow) of the compound and the first order rate constant for the photocatalytic decomposition process [120]. They proposed this discrepancy was possibly due to an interaction between adsorbate molecules resulting from van der Waals forces. 

Methoxybenzene (anisole), 1,2-dimethoxybenzene, and similar aromatic ethers react with S2CI2 in dry ether or benzene at 0-20 °C within several days to give a mixtnre of bisarylsulfanes R2S with n = 1-3 (eqnation 29). Anisole is substituted in the para position. ... 

The (difluoroiodo)arene reagents can be synthesized by anodic oxidation of 4-substituted iodo-benzenes.230 l-(Difluoroiodo)-4-methoxybenzene is used as a fluorinating agent for 1.3-dithio-lanes without isolation and purification. The electrolytic solution is simply mixed with a solution of the dithiolane. The electrolytic cell is depicted in Figure 2. 

We have seen in Chapter 2 that electrophilic attack of methoxybenzene gives a mixture of the 2- and 4-isomers. The significance of the orthometallation process is the ease with which the 2-substituted compound can be obtained exclusively through reaction of the organolithi-um product with a variety of electrophiles (Scheme 10.4). 

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