Electrophilic substitution of phenols

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 ... 

Benzylic cations have also been implicated in the formation of phenol-formaldehyde polymers. The synthesis of phenol-formaldehyde polymers, including the involvement of carbocations, has been reviewed [39], The involvement of benzylic cations in this reaction sequence is shown in Fig. 14. The first step of the acid-catalyzed reaction is the formation of a hydroxymethyl carbocation. Electrophilic substitution of phenol produces an o- or p-hydroxymethylphenol 91. Rapid protonation of the hydroxymethyl, followed by loss of H20, results in the formation of benzylic... 

Okajima T (2001) Ab initio MO investigation on the reactivity for electrophilic substitution of phenolic with oxirane and aziridine, as the model compounds of binding site of mutagen. J Mol Struct (THEOCHEM) 536 73-82... 

PhS(0)(0Ph)Me + RLi and LiX - PhSOCH X + PhSO Me]/ or reduction with homologation (with RjCuLi and LiX)/ Standard sulphinylation procedures reported include electrophilic substitution of phenols with ArSOCl and AlClj and the preparation of optically active sulphoxides from resolved (—)-menthyl sulphinates with ( )-l-alkenylmagnesium bromides or arylthiomethyl- or arylsulphonylmethyl-lithium compounds/ A practical route to 1-alkenyl sulphoxides uses non-activated alkynes and sulphenic acids, generated in situ from the thermolysis of 2-cyanoethyl phenyl sulphoxides/ ... 

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 . 

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. 

Condensations with carbonyl compounds phenol-formaldehyde resins. Acid or base catalyzes electrophilic substitution of carbonyl compounds in ortho and para positions of phenols to form phenol alcohols (Lederer-Manasse reaction). 

Phenols undergo electrophilic substitutions. In phenol, the substitutions take place in ortho and para positions. As the —OH group is an activating group, the reaction rate is much faster than usually observed with benzene. For example, the bromination of phenol produces ort/io-bromophenol (12%) and para-bromophenol (88%). 

Phenolic derivatives were prepared and then converted into thioether analogs using ethanedithol followed by oxidation of this intermediate to the disulfide. Phenolic resins were prepared by electrophilic substitution of allyl phenol derivatives with formaldehyde and then flee radically copolymerizing with ethanedithol. Epoxidation was performed using epichlarohydrine. 

The unusual wiefa-bromination of phenols and their methyl ethers [9] under superacid conditions is quite expected because O-protonation inverts polarity of all the nuclear carbon atoms. This reaction is reminiscent of the better known electrophilic substitutions of aniline in acidic media. 

Electrophilic substitution is much easier than in benzene. Thiophene reacts about as readily as mesitylene pyrrole and furan react as readily as phenol or even resorcinol. Electrophilic substitution of heterocycles has been reviewed (86HC(44/2)l), (90AHC(47)87), and the following conclusions were reached ... 

Generally, electrophilic halogenation of phenols leads to the corresponding ortho-and para-substituted products. The synthesis of meta-substituted products is considered difficult.474,555... 

If the phosphorotropic rearrangement is combined with selective electrophilic substitution of free phenolic units (e.g. bromination) and hydrolysis of ester or phosphate groups a variety of inherently chiral calixarenes becomes available,130 as demonstrated by the examples in Figure 15. 

It is not known yet whether the 1,2-dithiolium salts are sufficiently electrophilic to attack even benzene derivatives containing less efficient electron-donating groups. In any case trithionium salts, with their already weaker electrophilic character, are unable to substitute phenols70 recently, substitution of phenolate has been reported.98b... 

Contrary to the easy synthesis of alkylated phenols, e.g. via the electrophilic alkylations of phenols using alkyl halides, alkenes or other alkyl derivatives, there is no universal method for the preparation of arylated phenols. Radical or other arylation procedures usually lead to a mixture of difficult to separate isomers. Aryl-substituted phenols have, therefore, to be prepared by special routes. 

Similarly, electrogenerated MeS and PhS may afford [298] electrophilic substitution with phenols and ethers (Scheme 66). The addition of such electrophiles onto acetylenic bonds was also reported [297]. 

Electrophilic reactions of phenols a variety of substituted isatins and phenols. 

The electrophilic halogenation of phenols give rise to mixtures of ortho- and para-substituted phenols. Phenols are more reactive than aUcylaromatics in these reactions due to the enhanced resonance stabilization of the carbocationic intermediates (equation 72). However, in superacidic solutions, the oxygen protonation of the phenols leads to the deactivated substrate for halogenation and meta-halo products are obtained (equation 73). ... 

Electrophilic substitutions of 3-hydroxypyridine take place at C-2, for example nitration, Mannich substitution and iodination. " Its phenol-like character is nicely illustrated by efhcient 2,4,6-tribromination with Af-bromosuccinimide. 2-Methoxypyridine brominates at C-5 and 4-methoxypyridine at C-3. ... 

A striking difference between pyridines and their A-oxides is the susceptibility of the latter to electrophilic nitration. This can be understood in terms of mesomeric release from the oxide oxygen, and is parallel to electron release by oxygen and hence increased reactivity towards electrophilic substitution in phenols and phenoxides. One can find support for this rationalisation by a comparison of the dipole moments of trimethylamine and its A-oxide, on the one hand, and pyridine and its A-oxide, on the other the difference... 

As the ipso effect is sometimes ineffective with strong-electron donating groups, advantage of the possible electrophilic substitution of the allylsilane intermediate was taken to perform the acylation of phenols in the meta position according to Scheme 6 (refs. 15 - 17) ... 

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