Activating substituents, and electrophilic aromatic substitution

The hydroxyl group of a phenol is a strongly activating substituent and electrophilic aromatic substitution occurs readily m phenol and its deriv atives Typical examples were presented m Table 24 4... 

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 ... 

A Summary of Substituent Effects in Aromatic Substitution A summary of the activating and directing effects of substituents in electrophilic aromatic substitution is shown in Table 16.2. 

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. 

In an analogous reaction, where anisole (0.5 mole), chloromethyl ether (0.1 mole), and REX catalyst (2 gm) were stirred for 14 hours at room temperature, a 28% yield of a mixture of 2,2 -dimethoxydiphenyl-methane, 2,4 -dimethoxydiphenylmethane, and 4,4 -dimethoxydi-phenylmethane in the ratio of 1 5.7 5.4 was obtained. No 1 1 adduct (chloromethyl- or methoxymethylanisole) was observed. The lower reaction temperatures required with anisole reflect the activating effect of an electron-donating substituent in electrophilic aromatic substitution. 

If acetoxylation were a conventional electrophilic substitution it is hard to understand why it is not more generally observed in nitration in acetic anhydride. The acetoxylating species is supposed to be very much more selective than the nitrating species, and therefore compared with the situation in (say) toluene in which the ratio of acetoxylation to nitration is small, the introduction of activating substituents into the aromatic nucleus should lead to an increase in the importance of acetoxylation relative to nitration. This is, in fact, observed in the limited range of the alkylbenzenes, although the apparently severe steric requirement of the acetoxylation species is a complicating feature. The failure to observe acetoxylation in the reactions of compounds more reactive than 2-xylene has been attributed to the incursion of another mechan-104... 

Why IS there such a marked difference between methyl and trifluoromethyl substituents m their influence on electrophilic aromatic substitution s Methyl is activating and ortho para directing trifluoromethyl is deactivating and meta directing The first point to remember is that the regioselectivity of substitution is set once the cyclohexadienyl cation intermediate is formed If we can explain why... 

Table 12.2 summarizes orientation and rate effects in electrophilic aromatic substitution reactions for a variety of frequently encountered substituents. It is arianged in order of decreasing activating power the most strongly activating substituents are at the top, the most strongly deactivating substituents are at the bottom. The main features of the table can be summarized as follows ... 

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