CHAPTER TWENTY-FoUR Phenols of arene oxide intermediates formed by the enzyme-catalyzed reaction between an aro- matic ring and molecular oxygen R+0=R一mR Arene Arene oxide Phenol In plants, phenol biosynthesis proceeds by building the aromatic ring from carbohydrate precursors that already contain the required hydroxyl group 24.8 REACTIONS OF PHENOLS: ELECTROPHILIC AROMATIC SUBSTITUTION In most of their reactions phenols behave as nucleophiles, and the reagents that act on them are electrophiles. Either the hydroxyl oxygen or the aromatic ring may be the site of nucleophilic reactivity in a phenol. Reactions that take place on the ring lead to elec trophilic aromatic substitution; Table 24.4(p. 950) summarizes the behavior of phenols in reactions of this type A hydroxyl group is a very powerful activating substituent, and electrophilic aro- matic substitution in phenols occurs far faster, and under milder conditions, than in ben- zene. The first entry in Table 24. 4, for example, shows the monobromination of phenol in high yield at low temperature and in the absence of any catalyst. In this case, the reac- tion was carried out in the nonpolar solvent 1, 2-dichloroethane. In polar solvents such s water it is difficult to limit the bromination of phenols to monosubstitution. In the fol- lowing example, all three positions that are ortho or para to the hydroxyl undergo rapid 2, 4, 6-Tribromo-3- Hydrogen Other typical electrophilic aromatic substitution reactions---nitration(second entry), sul fomation(fourth entry), and Friedel-Crafts alkylation and acylation(fifth and sixth entries)take place readily and are synthetically useful. Phenols also undergo elec- trophilic substitution reactions that are limited to only the most active aromatic com- pounds; these include nitrosation(third entry) and coupling with diazonium salts(sev enth entry) PROBLEM 24.6 Each of the following reactions has been reported in the chem ical literature and gives a single organic product in high yield. Identify the prod- uct in each case (a)3-Benzyl-2, 6-dimethylphenol treated with bromine in chloroform (b)4-Bromo-2-methylphenol treated with 2-methylpropene and sulfuric acid (c)2-lsopropyl-5-methylphenol (thymol)treated with sodium nitrite and dilute hydrochloric acid d)p-Cresol treated with propanoyl chloride and aluminum chloride Back Forward Main MenuToc Study Guide ToC Student o MHHE Websiteof arene oxide intermediates formed by the enzyme-catalyzed reaction between an aro￾matic ring and molecular oxygen: In plants, phenol biosynthesis proceeds by building the aromatic ring from carbohydrate precursors that already contain the required hydroxyl group. 24.8 REACTIONS OF PHENOLS: ELECTROPHILIC AROMATIC SUBSTITUTION In most of their reactions phenols behave as nucleophiles, and the reagents that act on them are electrophiles. Either the hydroxyl oxygen or the aromatic ring may be the site of nucleophilic reactivity in a phenol. Reactions that take place on the ring lead to elec￾trophilic aromatic substitution; Table 24.4 (p. 950) summarizes the behavior of phenols in reactions of this type. A hydroxyl group is a very powerful activating substituent, and electrophilic aro￾matic substitution in phenols occurs far faster, and under milder conditions, than in ben￾zene. The first entry in Table 24.4, for example, shows the monobromination of phenol in high yield at low temperature and in the absence of any catalyst. In this case, the reac￾tion 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 fol￾lowing example, all three positions that are ortho or para to the hydroxyl undergo rapid substitution: Other typical electrophilic aromatic substitution reactions—nitration (second entry), sul￾fonation (fourth entry), and Friedel–Crafts alkylation and acylation (fifth and sixth entries)—take place readily and are synthetically useful. Phenols also undergo elec￾trophilic substitution reactions that are limited to only the most active aromatic com￾pounds; these include nitrosation (third entry) and coupling with diazonium salts (sev￾enth entry). PROBLEM 24.6 Each of the following reactions has been reported in the chem￾ical literature and gives a single organic product in high yield. Identify the prod￾uct in each case. (a) 3-Benzyl-2,6-dimethylphenol treated with bromine in chloroform (b) 4-Bromo-2-methylphenol treated with 2-methylpropene and sulfuric acid (c) 2-Isopropyl-5-methylphenol (thymol) treated with sodium nitrite and dilute hydrochloric acid (d) p-Cresol treated with propanoyl chloride and aluminum chloride H2O 25°C OH F m-Fluorophenol 3Br2 Bromine Br OH F Br Br 2,4,6-Tribromo-3- fluorophenol (95%) 3HBr Hydrogen bromide enzyme R Arene O2 R O Arene oxide HO R Phenol 948 CHAPTER TWENTY-FOUR Phenols Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website