Acylation of phenol

TABLE 22.3 Electrophil ic Aromatic Substitution Reactions of Phenols (Continued) 

Reaction with arenediazonium salts Adding a phenol to a solution of a diazonium salt formed from a primary aromatic amine leads to formation of an azo compound. The reaction is carried out at a pH such that a significant portion of the phenol is present as its phenoxide ion. The diazonium ion acts as an electrophile toward the strongly activated ring of the phenoxide ion. 

Each of the following reactions has been reported in the chemical literature and gives a single organic product in high yield. Identify the product in each case. 

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 

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 reactivity is described in the following section. 

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 (0-acyla-tion)  

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. 

---

The preference for O acylation of phenols arises because these reactions are kmetically controlled O acylation is faster than C acylation The C acyl isomers are more stable how ever and it is known that aluminum chloride is a very effective catalyst for the conversion of aryl esters to aryl ketones This isomerization is called the Fries rearrangement... 

Thus ring acylation of phenols is observed under Friedel-Crafts conditions because the presence of aluminum chloride causes that reaction to be subject to thermodynamic (equi librium) control... 

Catalytic amounts of I fCl4-AgC104 and Hf(OTf)4 are used for activation of acid halides and acid anhydrides for Friedel -Crafts acylation (Scheme 42) 178 the reactions of both reactive and unreactive aromatic substrates proceed smoothly in the presence of Hf(OTf)4. Furthermore, the Fries rearrangement179,180 and direct C-acylation of phenolic compounds181,182 take place using Hf(OTf)4. Formation of esters and Mannich-type reactions and allylation of imines have been also reported.152... 

Acid-catalyzed acylation of phenols as well as phenolic ethers using nitriles. 

NENCKI REACTION. The ring acylation of phenols with acids in the presence of zinc chloride, or the modification of the Friedel-Crafls alkylarioii-acylaliun procedure by substitution of ferric chloride for aluminum chloride. 

As reported in the literature, the acylation of aromatic hydrocarbons can be carried out by using zeolites as catalysts and carboxylic acids or acyl chlorides as acylating agents. Thus toluene can be acylated by carboxylic acids in the liquid phase in the presence of cation exchanged Y-zeolites (ref. 1). The acylation of phenol or phenol derivatives is also reported. The acylation of anisole by carboxylic acids and acyl chlorides was obtained in the presence of various zeolites in the liquid phase (ref. 2). The acylation of phenol by acetic acid was also carried out with silicalite (ref. 3) or HZSM5 (ref. 4). The para isomer has been generally favoured except in the latter case in which ortho-hydroxyacetophenone was obtained preferentially. One possible explanation for the high ortho-selectivity in the case of the acylation of phenol by acetic acid is that phenylacetate could be an intermediate from which ortho-hydroxyacetophenone would be formed intramolecularly. 

Figure 3.6 Yields, X (%) of phenyl acetate, PA ( ), o-hydroxyacetophenone, o-HAP (o) and p-hydroxyacetophenone, p-HAP ( ) as a function of the conversion of phenol, Xp (%), in an equimolar mixture with acetic acid over HMFI at 553 K. Reprinted from Journal of Molecular Catalysis, Vol. 93, Neves et al., Acylation of phenol with acetic acid over a HZSM-5 zeolite, reaction scheme, pp. 169-179, Copyright (1994), with permission from Elsevier...

Zeolites H-BEA and H-Y were found to be the most active catalysts, however all catalysts readily form the phenyl benzoate (Table 4.1). In the conditions of the reaction, the formation of phenyl benzoate (PB) occurs rapidly via O-acylation of phenol. Direct C-alkylation of phenol with benzoic anhydride (B) and Fries rearrangement of phenyl benzoate results in the formation of 2- and 4-hydroxy-benzophenones (2-HPB and 4-HPB) (Scheme 4.3). 

The Friedel-Crafts acylation of phenols proceeds via initial esterification followed by Fries rearrangement of the resulting aryl ester to afford the hydroxyaryl... 

Schotteii Baumanii). The acylation of phenols without a basic solvent is promoted by small amounts of sulfuric acid or stannic chloride. Care must be exercised to prevent rearrangement of the phenolic ester to a phenolic ketone (Fries reaction, method 209). 

HOUBEN HOESCH Phenol Ai Synthesis of ketones (or aldehydes) by acylation of phenols with nitnles (or ortho formates)... 

Hf(OTf)4 catalyzes the Fries rearrangement (Eq. 17) [22]. Direct acylation of phenols is also possible by treatment with acid chloride to give orf/io-acylated product (Eq. 18). A crossover experiment showed that the reaction involves direct C-acylation and the rearrangement of the in situ-formed ester [22]. 

Although phenolic ketones can be made by direct acylation of phenols, they are more often prepared in two steps by means of the Fries rearrangement (Sec. 24.9). 

The same resins have been used for C-acylation of phenols with anhydrides, probably via O-acylation and Fries rearrangement." However, yields are low even with 1,3-dihydroxybenzenes. 

Phenol readily couples with diazonium salts to yield coloured compounds. The latter can be nsed for the photometric detection of phenol as in the case of diazotized 4-nitroaniline. Sahcylic acid (2-hydroxybenzoic acid) can be prodnced by the Kolbe-Schmitt reaction (stndied by the density functional method ) from sodinm phenolate and carbon dioxide, whereas potassium phenolate gives the para compound. Alkylation and acylation of phenol can be carried out with aluminium chloride as catalyst methyl groups can also be introduced by the Mannich reaction. Diaryl ethers can only be produced under extreme conditions. 

Regioselective direct acylation of phenol and naphthol derivatives with acid chlorides was achieved by using hafnium triflate, Hf(OTf)4 (5 to 20 mol%), as a catalyst (equations 40 and 41) 5. 

The Hf(OTf)4, is also effective in the ortho-acylation of phenols using carboxylic acids instead of the acid chlorides, although somewhat lower yields are obtained and larger amounts of the catalyst are required (equations 42 and 43). ... 

Similarly, scandium triflate (Sc(OTf)3), zirconium triflate (Zr(OTf)4) and titanium chloro(tris)triflate (TiCl(OTf)3) were also used for the orf/zo-acylation of phenols and 1-naphthols using acid chlorides . ... 

By using suitable protecting groups, meta-acylation of phenols and ansioles was made possible using acetyl chloride and aluminium chloride . 

---