24.9 Acylation of Phenol SAMPLE SOLUTION (a) The ring that bears the hydroxyl group is much more reactive than the other ring. In electrophilic aromatic substitution reactions of ings that bear several substituents, it is the most activating substituent that con- trols the orientation. bromination occurs para to the hydroxyl group H3C H3C OH CH 3-Benzyl-2, 6-dimethy 3-Benzyl-4-bromo-2, 6-dimethylphenol (isolated in 100% yield) The aromatic ring of a phenol, like that of an arylamine, is seen as an electron- rich functional unit and is capable of a variety of reactions. In some cases, however, it is the hydroxyl oxygen that reacts instead. An example of this kind of chemical reac- tivity is described in the following section 24.9 ACYLATION OF PHENOLS Acylating agents, such as acyl chlorides and carboxylic acid anhydrides, can react with phenols either at the aromatic ring(C-acylation) or at the hydroxyl oxygen(O-acyla -OH or RCOCR Phenol Aryl ketone Aryl ester (product of C-acylation As shown in the sixth entry of Table 24. 4, C-acylation of phenols is observed under the customary conditions of the Friedel-Crafts reaction(treatment with an acyl chloride or acid anhydride in the presence of aluminum chloride). In the absence of aluminum chloride, however, O-acylation occurs instead. OH+CH3(CH2)6CCl—> OC(CH2)6CH3+ HCI Phenol Octanoyl chloride Phenyl octanoate Hydrogen (95%) The O-acylation of phenols with carboxylic acid anhydrides can be conveniently catalyzed in either of two ways. One method involves converting the acid anhydride to a more powerful acylating agent by protonation of one of its carbonyl oxygens. Addi tion of a few drops of sulfuric acid is usually sufficient OH+ CH;COCCH3so→>F -OCCH+ ChaCON A p-Fluorophenyl acetate Acetic (81%) Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
SAMPLE SOLUTION (a) The ring that bears the hydroxyl group is much more reactive than the other ring. In electrophilic aromatic substitution reactions of rings that bear several substituents, it is the most activating substituent that controls the orientation. Bromination occurs para to the hydroxyl group. The aromatic ring of a phenol, like that of an arylamine, is seen as an electronrich functional unit and is capable of a variety of reactions. In some cases, however, it is the hydroxyl oxygen that reacts instead. An example of this kind of chemical reactivity is described in the following section. 24.9 ACYLATION OF PHENOLS Acylating agents, such as acyl chlorides and carboxylic acid anhydrides, can react with phenols either at the aromatic ring (C-acylation) or at the hydroxyl oxygen (O-acylation): As shown in the sixth entry of Table 24.4, C-acylation of phenols is observed under the customary conditions of the Friedel–Crafts reaction (treatment with an acyl chloride or acid anhydride in the presence of aluminum chloride). In the absence of aluminum chloride, however, O-acylation occurs instead. The O-acylation of phenols with carboxylic acid anhydrides can be conveniently catalyzed in either of two ways. One method involves converting the acid anhydride to a more powerful acylating agent by protonation of one of its carbonyl oxygens. Addition of a few drops of sulfuric acid is usually sufficient. F OH p-Fluorophenol CH3COCCH3 O O Acetic anhydride CH3COH O Acetic acid F OCCH3 O p-Fluorophenyl acetate (81%) H2SO4 OH Phenol CH3(CH2)6CCl O Octanoyl chloride HCl Hydrogen chloride OC(CH2)6CH3 O Phenyl octanoate (95%) RCCl or RCOCR O X O X O X OH Phenol RC O OH Aryl ketone (product of C-acylation) or OCR O Aryl ester (product of O-acylation) Br2 CHCl3, 0°C CH2 H3C CH3 OH 3-Benzyl-2,6-dimethylphenol H3C CH2 CH3 OH Br 3-Benzyl-4-bromo-2,6-dimethylphenol (isolated in 100% yield) 24.9 Acylation of Phenols 949 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER TWENTY-FoUR Phenols TABLE 24. 4 Electrophilic Aromatic Substitution Reactions of Phenols action and comments Specific example Halogenation Bromination and chlorination of phe- OH nols occur readily even in the absence of a catalyst. Substitution occurs primarily at the position para to CICH the hydroxyl group. When the para position is HBr blocked, ortho substitution is observed. Phenol Bromine Nitration Phenols are nitrated on treatment with a OH dilute solution of nitric acid in either water or acetic acid. It is not necessary to use mixtures of nitric and sulfuric acids, because of the high reactivity of phe- p-Cresol 4-Methyl-2-nitrophenol Nitrosation On acidification of aqueous solutions of N=O sodium nitrite the nitrosonium ion N=o: )is O formed, which is a weak electrophile and attacks the strongly activated ring of a phenol. the product is a nitroso phenol -Naphthol 1-Nitroso-2-naphthol Sulfonation Heating a phenol with concentrated OH sulfuric acid causes sulfonation of the ring HaC CH3 H3C. CH3 .6 Dimethylphenol dimethyibenenesuit acid (69%) Friedel-Crafts alkylation Alcohols in combination OH with acids serve as sources of carbocations Attack of a carbocation on the electron-rich ring of a phe- nol brings about its alkylation +(CH3)3COH o-Cresol tert-Butyl alcohol 63%) (Continued) Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
950 CHAPTER TWENTY-FOUR Phenols TABLE 24.4 Electrophilic Aromatic Substitution Reactions of Phenols Reaction and comments Halogenation Bromination and chlorination of phenols occur readily even in the absence of a catalyst. Substitution occurs primarily at the position para to the hydroxyl group. When the para position is blocked, ortho substitution is observed. Nitration Phenols are nitrated on treatment with a dilute solution of nitric acid in either water or acetic acid. It is not necessary to use mixtures of nitric and sulfuric acids, because of the high reactivity of phenols. Nitrosation On acidification of aqueous solutions of sodium nitrite, the nitrosonium ion (:NPO :) is formed, which is a weak electrophile and attacks the strongly activated ring of a phenol. The product is a nitroso phenol. Sulfonation Heating a phenol with concentrated sulfuric acid causes sulfonation of the ring. Friedel-Crafts alkylation Alcohols in combination with acids serve as sources of carbocations. Attack of a carbocation on the electron-rich ring of a phenol brings about its alkylation. (Continued) Specific example OH Phenol OH Br p-Bromophenol (93%) ClCH2CH2Cl 0°C Br2 Bromine HBr Hydrogen bromide OH CH3 p-Cresol OH NO2 CH3 4-Methyl-2-nitrophenol (73–77%) HNO3 acetic acid 5°C OH H3C CH3 2,6-Dimethylphenol OH CH3 SO3H H3C 4-Hydroxy-3,5- dimethylbenzenesulfonic acid (69%) H2SO4 100°C OH 2-Naphthol 1-Nitroso-2-naphthol (99%) N O OH NaNO2 H2SO4, H2O 0°C OH CH3 o-Cresol OH CH3 C(CH3)3 4-tert-Butyl-2- methylphenol (63%) H3PO4 60°C (CH3)3COH tert-Butyl alcohol Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website