Aromatic substitution in phenols

Now we will examine some reactions that occur with phenols, but not with alcohols. Phenols undergo electrophilic aromatic substitution under very mild conditions because the hydroxyl group is strongly ring activating. For example, phenol can be nitrated with dilute aqueous nitric acid. 

Phenol is also brominated rapidly with bromine in water, to produce 2,4,6-tribromophenol. 

Draw the intermediate in electrophilic aromatic substitution para to a hydroxyl group, and show how the intermediate benzenonium ion is stabilized by the hydroxyl group. 

An unshared electron pair on the oxygen atom helps to delocalize the positive charge. 

PROBLEM 7.20 Explain why phenoxide ion undergoes electrophilic aromatic substitution even more easily than does phenol. 

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Phenol and anisole are among the commonly encountered benzene derivatives listed in Table 11.1. Electrophilic aromatic substitution in phenol is discussed in more detail in Section 24.8. 

A hydroxyl group is a very powerful activating substituent, and electrophilic aromatic substitution in phenols occurs far- faster, and under milder conditions, than in benzene. The first entry in Table 24.4, for exfflnple, shows the monobromination of phenol in high yield at low temperature and in the absence of any catalyst. In this case, the reaction was carried out in the nonpolar- solvent 1,2-dichloroethane. In polar- solvents such as water it is difficult to limit the bromination of phenols to monosubstitution. In the following exfflnple, all three positions that are ortho or para to the hydroxyl undergo rapid substitution ... 

Many of the properties of phenols reflect the polarization implied by the contributing structures. The hydroxyl oxygen is less basic, and the hydroxyl proton more acidic, in phenols than in alcohols. Electrophilic aromatic substitution in phenols is much faster than in benzene, indicating that the ring, especially at the positions ortho and para to the hydroxyl group, is relatively electron-rich. ... 

The Lewis acid complex 4 can cleave into an ion-pair that is held together by the solvent cage, and that consists of an acylium ion and a Lewis acid-bound phenolate. A fr-complex 6 is then formed, which further reacts via electrophilic aromatic substitution in the ortho- or para-position ... 

Diazonium coupling reactions are typical electrophilic aromatic substitutions in which the positively charged diazonium ion is the electrophile that reacts with the electron-rich, ring of a phenol or arylamine. Reaction usually occurs at the para position, although ortho reaction can take place if the para position is blocked. 

The kinetics of polycondensation hy nucleophilic aromatic substitution in highly polar solvents and solvent mixtures to yield linear, high molecular weight aromatic polyethers were measured. The basic reaction studied was between a di-phenoxide salt and a dihaloaromatic compound. The role of steric and inductive effects was elucidated on the basis of the kinetics determined for model compounds. The polymerization rate of the dipotassium salt of various bis-phenols with 4,4 -dichlorodiphenylsulfone in methyl sulfoxide solvent follows second-order kinetics. The rate constant at the monomer stage was found to be greater than the rate constant at the dimer and subsequent polymerization stages. 

We shall return to reactions of phenols and phenyl ethers when we consider directing effects in electrophilic aromatic substitution in other reactions and in Friedel-Crafts reactions in particular. 

Diazonium Coupling Reactions. The union of a diazonium ion with a phenol or an amine is known as a diazonium coupling reaction. The process appears to be an example of aromatic substitution in which the reactive species are the diazonium cation and phenoxide ion or the substituted aniline molecule 9... 

The reaction of phenol with FITS reagents led to a mixture of ortho-, meta- and para-perfluoroalkylphenols, formed by electrophilic aromatic substitution. In the case of the relatively hindered electron-rich phenols, a different outcome was observed 0-perfluoroalkylation was observed together with the C-perfluoroalkylation products. At high temperature, the amount of the 0-substituted product became predominant. ... 

Proton-deuteron exchange reactions are most easily studied by n.m.r. Examples are the exchange of aromatic protons in phenols under alkaline conditions, exchange of the a-protons in methoxy-acetone in aqueous solution, exchange of NH protons in triethyl-ammonium ion, exchange of the nuclear protons of hydroxy-indoles in deuterium oxide under mildly basic conditions and exchange of aromatic protons of substituted benzophenones in deutero-sulphuric acid. ... 

Along with reactive aryl and alkenyl radicals, acyl radicals-readily generated from the corresponding acylselenides-undergo efficient homolytic aromatic substitutions in the presence of tin hydride or (Me3Si)3SiH [47]. Arenes, as well as heteroarenes, can be used as acceptors. As an example, the highly efficient radical transformation of acylselenide 20 to heteroarene 21, which readily isomerizes to phenol 22 is depicted in Scheme 13.6 ]48]. 

Scheme 8.42. Electrophilic aromatic substitution of phenol with an acyl group. The acylation of phenol with acetyl chloride (CH3COCI) in the presence of aluminum trichloride (AICI3) can apparently occur via a direct addition of the aluminum trichloride complexed acetyl chloride (in competition with O-acylation) or by a subsequent rearrangement of O-acylated phenol. The former is presented in the upper portion of the scheme, while the latter is shown in the lower portion.

Kolbe Reaction The phenoxide ion is even more susceptible to electrophilic aromatic substitution than phenol itself. (Why ) Use is made of the high reactivity of the phenoxide ring in a reaction called the Kolbe reaction. In the Kolbe reaction carbon dioxide acts as the electrophile. 

Substituted dibenzofurans 4 can be prepared in a one-pot two-step procedure of o-bromophenols 1 with 2- or 4-acceptor-substituted fluorobenzenes 2 in the presence of K2CO3, consisting ofa nucleophiHc aromatic substitution by phenolate ( 3) followed by Pd-catalyzed intramolecular aryl-aryl coupling (3 —> 4) [57] ... 

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