Phenol electrophilic halogenation

The hydroxyl group is a strongly activating, ortho- and para-directing substituent in electrophilic aromatic substitution reactions (Section 16.4). As a result, phenols are highly reactive substrates for electrophilic halogenation, nitration, sulfonation, and lTiedel-Crafts reactions. 

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... 

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). ... 

A number of S Ar reactions have also been developed in which the electrophile is generated by an oxidative process. For example, She and coworkers recently used a (diacetoxyiodo)benzene-promoted phenol oxidation to generate the cationic species (24) that undergoes cychzation to the natural product— gymnothehgnan N (25, Scheme 1.7) [15]. Other oxidative synthetic methods have been developed for electrophilic halogenation [16], aminations [17], and nitrations [18]. 

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. 

Reactions. -Hydroxybenzoic acid undergoes the typical reactions of the carboxyl and hydroxyl moieties. When heated above its melting point, it decomposes almost completely into phenol and carbon dioxide. It reacts with electrophilic reagents in the predicted manner and does not undergo the Friedel-Crafts reaction. Nitration, halogenation, and sulfonation afford the 3-substituted products. Heating -hydroxybenzoic acid with 8 IV-nitric acid results in a 95% yield of picric acid. In a similar fashion, treatment with chlorine water yields 2,4,6-trichlorophenol (50). 

The reacting species is a rather weak electrophile and, therefore, only particularly reactive aromatics are suitable substrates. Consequently, the reaction is restricted for polyhydric phenols and their ethers, and reactive heterocycles. With strong acidic systems, such as AICI3 in halogenated benzene solvents, alkylben-zenes can react at more elevated temperatures (>50°C). Trichloroacetonitrile works also well with nonactivated aromatics. The 12 chloroimine, the protonated nitrile (13), or the nitrile coordinated with the Lewis acid are possible involved electrophiles. 

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