Benzoylation of phenols

The Environmentally Benign, Liquid-phase Benzoylation of Phenol Catalyzed by H-p Zeolite. 

The data clearly indicate that the only primary product was phenylbenzoate, while all the other compounds formed by consecutive reactions upon the ester. Therefore, the scheme of reaction is that one summarized in Figure 3. The formation of the ester as the only primary product represents one important difference with respect to the Friedel-Crafts benzoylation of phenol with benzoylchloride or benzyltrichloride, catalyzed by AICI3. In the latter case, in fact, the product of para-C-acylation (p-hydroxybenzophenone) is the main product of reaction this is due to the fact that AICI3 coordinates with the 0 atom of the hydroxy group in phenol, and makes it less available for the ester formation, due to both electronic and steric reasons. 

Table 4.1 Benzoylation of phenol with benzoic anhydride over various zeolites and A1C13...

Dewar, M. J. S., Hart, L. S. Aromatic rearrangements in the benzene series. I. Fries rearrangement of phenyl benzoate the benzoylation of phenol. Tetrahedron 1970, 26, 973-1000. 

The reaction rate was shown to be related to the accessibility of the acid sites-H-MFI zeolite was practically inactive and Nafion was the most active catalyst. With all the catalysts, not only the desired p-hydroxybenzophenone (/ -HBP) product but also j3-benzoxybenzophenone (p-BXBP) and o-hydroxybenzophenone (o-HBP) were formed. The para products result from benzoylation of phenol (formed by hydrolysis of PB) or of PB and o-HBP from the intramolecular rearrangement of PB. The selectivity to p-HBP can, therefore, be significantly improved by adding phenol to the reactant mixture [4]. Unfortunately, thermodynamic limitations arising from the low polarity of the medium employed (even with very polar solvents such as sulfolane) seems to preclude the use of a solid acid for the production of diphenol monomers from diphenyl benzoate [4]. 

Benzotrichloride and BC are, however, efficiently utilized for small-scale hydroxybenzophenone synthesis. Thus benzoylation of phenol can be simply performed by stirring at 120°C for 5 h an equimolecular mixture of phenol and benzotrichloride in the presence of ZSM-5 in 1,2-dichloro-ethane. 4-Hydroxybenzophenone is obtained in 80% yield, whereas by using BC under the same reaction conditions, the same product is isolated in 67% yield. 

Acetylation—Replacement of bromine by hydrogen s. 13, 272 Benzoylation of phenols ArOH ArOBz... 

Dissolve 5 g. of phenol in 75 ml. of 10 per cent, sodium hydroxide solution contained in a wide-mouthed reagent bottle or conical flask of about 200 ml. capacity. Add 11 g. (9 ml.) of redistilled benzoyl chloride, cork the vessel securely, and shake the mixture vigorously for 15-20 minutes. At the end of this period the reaction is usually practically complete and a sohd product is obtained. Filter oflf the soUd ester with suction, break up any lumps on the filter, wash thoroughly with water and drain well. RecrystaUise the crude ester from rectified (or methylated) spirit use a quantity of hot solvent approximately twice the minimum volume required for complete solution in order to ensure that the ester does not separate until the temperature of the solution has fallen below the melting point of phenyl benzoate. Filter the hot solution, if necessary, through a hot water funnel or through a Buchner funnel preheated by the filtration of some boiling solvent. Colourless crystals of phenyl benzoate, m.p. 69°, are thus obtained. The yield is 8 g. 

Because phenols are weak acids, they can be freed from neutral impurities by dissolution in aqueous N sodium hydroxide and extraction with a solvent such as diethyl ether, or by steam distillation to remove the non-acidic material. The phenol is recovered by acidification of the aqueous phase with 2N sulfuric acid, and either extracted with ether or steam distilled. In the second case the phenol is extracted from the steam distillate after saturating it with sodium chloride (salting out). A solvent is necessary when large quantities of liquid phenols are purified. The phenol is fractionated by distillation under reduced pressure, preferably in an atmosphere of nitrogen to minimise oxidation. Solid phenols can be crystallised from toluene, petroleum ether or a mixture of these solvents, and can be sublimed under vacuum. Purification can also be effected by fractional crystallisation or zone refining. For further purification of phenols via their acetyl or benzoyl derivatives (vide supra). 

Benzoylation reactions of phenols (33, 97) and naphthols (20, 98-100) can be accomplished very efficiently by heating with benzoyl chloride (101) under-... 

Brackmann R, G Fuchs (1993) Enzymes of anaerobic metabolism of phenolic compounds 4-hydroxy benzoyl-CoA reductase (dehydroxylating) from a denitrifying Pseudomonas sp. Eur J Biochem 213 563-571. 

Method of Preparation Add 20 mL of 5% sodium hydroxide to about 1 g of phenol in a conical flask followed by the drop-wise addition of 2 mL of benzoyl chloride with vigorous shaking / sonication, after stoppering the flask securely in between the each addition of the reagent. Cool the mixture throughout the addition and shake further for 5-10 min after the final addition of benzoyl chloride. Filter the product, wash with water and recrystallise in alcohol. 

In other reactions also the OH-group of the phenols shows itself to be more reactive than that of the aliphatic alcohols. Phenols, but not alcohols, react easily with diazomethane. With other alkylating agents also, such as alkyl halides, and dialkyl sulphates, the phenols react even in aqueous alkaline solution whilst the alcohols do not react under such conditions. Benzoyl derivatives, most of which crystallise readily, are excellently adapted for the characterisation of phenols (Schotten-Baumann reaction). 

A kinetic smdy of the acylation of ethylenediamine with benzoyl chloride (110) in water-dioxane mixtures at pH 5-7 showed that the reaction involves mainly benzoylation of the monoprotonated form of ethylenediamine. Stopped-flow FT-IR spectroscopy has been used to study the amine-catalysed reactions of benzoyl chloride (110) with either butanol or phenol in dichloromethane at 0 °C. A large isotope effect was observed for butanol versus butanol-O-d, which is consistent with a general-base-catalysed mechanism. An overall reaction order of three and a negligible isotope effect for phenol versus phenol- /6 were observed and are consistent with either a base- or nucleophilic-catalysed mechanism. Mechanistic studies of the aminolysis of substituted phenylacetyl chlorides (111) in acetonitrile at —15 °C have revealed that reactions with anilines point to an associative iSN2 pathway. ... 

Uses Preparation of sodium and butyl benzoates, benzoyl chloride, phenol, caprolactum, and esters for perfume and flavor industry plasticizers manufacture of alkyl resins preservative for food, fats, and fatty oils seasoning tobacco dentifrices standard in analytical chemistry antifungal agent synthetic resins and coatings pharmaceutical and cosmetic preparations plasticizer manufacturing (to modify resins such as polyvinyl chloride, polyvinyl acetate, phenol-formaldehyde). 

Cyclohexanol and cyclohexanone are made by the air oxidation of cyclohexane (81%) with a cobalt(II) naphthenate or acetate or benzoyl peroxide catalyst at 125-160°C and 50-250 psi. Also used in the manufacture of this mixture is the hydrogenation of phenol at elevated temperatures and pressures, in either the liquid or vapor phase (19%). The ratio of alcohol to ketone varies with the conditions and catalysts. 

The reaction of phenol benzoylation catalyzed by a H-P zeolite (Si/Al ratio 75) has been studied, with the aim of determining the reaction scheme. The only primary product was phenylbenzoate, which then reacted consecutively to yield o- and p-hydroxybenzophenone and benzoylphenylbenzoate isomers, via both intermolecular and intramolecular mechanisms. 

This does not occur in the case of catalyst and reactants here described. With Bronsted-type catalysis, the reaction between the benzoyl cation, Ph-C" =0, and the hydroxy group in phenol is quicker than the electrophilic substitution in the ring. This hypothesis has been also confirmed by running the reaction between anisole and benzoic acid in this case the prevailing products were (4-methoxy)phenylmethanone (the product of para-C-benzoylation) and methylbenzoate (obtained by esterification between anisole and benzoic acid, with the co-production of phenol), with minor amounts of phenylbenzoate, phenol, 2-methylphenol and 4-methylphenol. Therefore, when the 0 atom is not available for the esterification due to the presence of the substituent, the direct C-acylation becomes the more favored reaction. 

---