Phenols electrophilic substitution

Beside being acidic, a significant industrial chemical property of phenol is the extremely high reactivity of its ring toward electrophilic substitution. If steric conditions permit, the substitution leads first to the formation of the 2- or 4-mono derivative, then to the 2,4- or 2,6-diderivative, and finally to the 2,4,6-triderivative. The halogenation of phenol produces mono-, di-, and tribal ophenols. 

Other typical electrophilic aromatic substitution reactions—nitration (second entr-y), sul-fonation (fourth entry), and Friedel-Crafts alkylation and acylation (fifth and sixth entries)—take place readily and are synthetically useful. Phenols also undergo electrophilic substitution reactions that are limited to only the most active aromatic compounds these include nitrosation (third entry) and coupling with diazonium salts (seventh entry). 

An 5-(l-m-nitrophenyl-2-benzoyl)ethyl thioether was used to protect thio-phenols during electrophilic substitution reactions of the benzene ring. ... 

The acid-catalyzed reaction occurs by an electrophilic substitution where formaldehyde is the electrophile. Condensation between the methylol groups and the benzene rings results in the formation of methylene bridges. Usually, the ratio of formaldehyde to phenol is kept less than unity to produce a linear fusible polymer in the first stage. Crosslinking of the formed polymer can occur by adding more formaldehyde and a small amount of hexamethylene tetramine (hexamine. 

Certain groups attached to an aromatic ring can donate electrons into its delocalized molecular orbitals. Examples of these electron-donating substituents include —NH2 and —OH. Electrophilic substitution of benzene is much faster when an electron-donating substituent is present. For example, the nitration of phenol, C6H5OH, proceeds so quickly that it requires no catalyst. Moreover, when the products are analyzed, the only products are found to be 2-nitrophenol (ortho-nitrophenol, 37) and 4-nitrophenol (pnra-mtrophcnol, 38 . 

Long before their theories were supported by computations, organic chemists found a way to use resonance structures to explain the product distribution in electrophilic substitution. Thus, the Lewis structure for phenol is regarded as a resonance hybrid of the following structures ... 

The Ar-O-R aromatic ethers can give rise to reactions of electrophilic substitution that can be dangerous not only because of the reagents nature but also the activation effect due to the active oxygen. The activation mechanism can be described in the same way as for phenols. 

The literature on basic- and acid-catalyzed alkylation of phenol and of its derivatives is wide [1,2], since this class of reactions finds industrial application for the synthesis of several intermediates 2-methylphenol as a monomer for the synthesis of epoxy cresol novolac resin 2,5-dimethylphenol as an intermediate for the synthesis of antiseptics, dyes and antioxidants 2,6-dimethylphenol used for the manufacture of polyphenylenoxide resins, and 2,3,6-trimethylphenol as a starting material for the synthesis of vitamin E. The nature of the products obtained in phenol methylation is affected by the surface characteristics of the catalyst, since catalysts having acid features address the electrophilic substitution in the ortho and para positions with respect to the hydroxy group (steric effects in confined environments may however affect the ortho/para-C-alkylation ratio), while with basic catalysts the ortho positions become the... 

The difference in position of attack on primary and secondary aromatic amines, compared with phenols, probably reflects the relative electron-density of the various positions in the former compounds exerting the controlling influence for, in contrast to a number of other aromatic electrophilic substitution reactions, diazo coupling is sensitive to relatively small differences in electron density (reflecting the rather low ability as an electrophile of PhN2 ). Similar differences in electron-density do of course occur in phenols but here control over the position of attack is exerted more by the relative strengths of the bonds formed in the two products in the two alternative coupled products derivable from amines, this latter difference is much less marked. 

The synthesized CPMV-alkyne 42 was subjected to the CuAAC reaction with 38. Due to the strong fluorescence of the cycloaddition product 43 as low as 0.5 nM, it could be detected without the interference of starting materials. TMV was initially subjected to an electrophilic substitution reaction at the ortho-position of the phenol ring of tyrosine-139 residues with diazonium salts to insert the alkyne functionality, giving derivative 44 [100]. The sequential CuAAC reaction was achieved with greatest efficiency yielding compound 45, and it was found that the TMV remained intact and stable throughout the reaction. 

This principle of formation proved to be general for quinocyclopropenes of type 61a ( phenylogous cyclopropenones )- The required p-hydroxy-phenyl cyclopropenium cations were available by electrophilic substitution of phenolic components (preferentially 2,6-disubstituted) and heterosubstituted cyclopropenium cations (75 and 109), as the representative examples 11099 11176 112and 113 show ... 

Tyrosine may be targeted specifically for modification through its phenolate anion by acylation, through electrophilic reactions such as the addition of iodine or diazonium ions, and by Mannich condensation reactions. The electrophilic substitution reactions on tyrosine s ring all occur at the ortho position to the —OH group (Figure 1.11). Most of these reactions proceed effectively only when tyrosine s ring is ionized to the phenolate anion form. 

The rhodium-catalyzed arylation of phenols with aryl halides occurs in the presence of phosphinites [PR2(OAr)] as a co-catalyst (Equation (59)).66 The phosphorus atom coordinates to the rhodium atom to facilitate the electrophilic substitution with the rhodium(m) species at the ortho-pos i on. 

Chlorination and chloramination of a widely used antibacterial additive, triclo-san, which is used in many household personal care products, results in the formation of chloroform, 5,6-dichloro-2-(2,4-dichlorophenoxy)phenol, 4,5-dichloro-2-(2,4-dichlorophenoxy)phenol, 4,5,6-trichloro-2-(2,4-dichlorophenoxy)phenol, 2, 4-dichlorophenol, and 2,4,6-trichlorophenol [119]. The reaction of triclosan with monochloramine is slow, however, compared to chlorine [120]. The chlorophenox-yphenols are formed via bimolecular electrophilic substitution of triclosan. 

In phenols, the reactions that take place on the aromatic ring are electrophilic substitution reactions (Unit 13, Class XI). The -OH group attached to the benzene ring activates it towards electrophilic substitution. Also, it directs the incoming group to ortho and para positions in the ring as these positions become eiectron rich due to the resonance effect caused by -OH group. The resonance structures are shown under acidity of phenols. 

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