Catalyst phenol acylation

The intermediate N-acylpyridinium salt is highly stabilized by the electron donating ability of the dimethylamino group. The increased stability of the N-acylpyridinium ion has been postulated to lead to increased separation of the ion pair resulting in an easier attack by the nucleophile with general base catalysis provided by the loosely bound carboxylate anion. Dialkylamino-pyridines have been shown to be excellent catalysts for acylation (of amines, alcohols, phenols, enolates), tritylation, silylation, lactonization, phosphonylation, and carbomylation and as transfer agents of cyano, arylsulfonyl, and arylsulfinyl groups (lj-3 ). 

Advantage can be drawn from the positive effect of phenol on PA transformation into p-HAP to improve the yield and selectivity of p-HAP production.[82 84] Thus, with a HBEA zeolite the yield and selectivity for p-HAP passes from ca. 5 and 28 % respectively with cumene solvent to 24 and 60% with phenol as a solvent .[84] Again sulfolane was shown to have a very positive effect on the selectivity for p-HAP and limits the catalyst deactivation. To explain these observations as well as the effect of P and PA concentrations on the reaction rates, it was proposed that sulfolane plays two independent roles in phenol acylation solvation of acylium ion intermediates and competition with P and PA for adsorption on the acid sites.1831... 

A kinetic study of the acylation of phenol with phenyl acetate was carried out in liquid phase at 160°C over HBEA zeolite samples, sulfolane or dodecane being used as solvents. The initial rates of hydroxyacetophenone (HAP) production were similar in both solvents. However the catalyst deactivation was faster in dodecane, most likely because of the faster formation of heavy reaction products such as bisphenol A derivatives. Moreover, sulfolane had a very positive effect on p-HAP formation and a negative one on o-HAP formation. To explain these observations as well as the influence of phenol and phenyl acetate concentrations on the rates of 0- and p-HAP formation it is proposed that sulfolane plays two independent roles in phenol acylation solvation of acylium ions intermediates and competition with phenyl acetate and phenol for adsorption on the acid sites. Donor substituents of phenyl acetate have a positive effect on the rate of anisole acylation, provided however there are no diffusion limitations in the zeolite pores. 

Phenol acylation with acetic anhydride over MFI catalysts is also very o-HAP selective, although with this acylating agent o-HAP would result from direct C-acylation of phenol rather than secondary transformation of phenyl acetate [21]. 

The whole argument is organized in four sections stoichiometric acylations, catalytic homogeneous acylations, catalytic heterogeneous acylations, and phenol acylations. It is structured according to the role played by the catalyst in the activation of reagents as well as in the different modes of regioselectivity encountered in the acylation of arenes, aromatic ethers, and phenols. 

Results from the literature suggest that direct phenol acylation and the Fries rearrangement are frequently competitive processes and difficult to characterize by the mechanistic point of view. Consequently, in Section 5.1, we include the synthetic process where the phenol substrate, the acylating agent, and the catalyst are mixed together in the starting reaction mixture aside from the specific reaction mechanism, whereas in Section 5.2 we include reactions involving phenyl esters. 

Sfudies on phenol acylation wifh acefic acid (AAC) over ZSM-5 zeolife confirm thaf fhe reacfion is very complicafed. The reacfion is carried ouf in a flow reactor charged wifh the zeolite catalyst at 280°C. The main... 

Studies on catalyst deactivation during phenol acylation with PA in the presence of BEA zeolite were performed by recovering the organic material entrapped into the zeolite following two methodologies ... 

While the first process represents a positive event because acetoxyaceto-phenones are convertible into HAPs and can give further intermolecular phenol acylation affording both ortho- and para-HAP, the second process produces ketene, which, being highly reactive, represents the most important source of coke responsible for heterogeneous catalyst deactivation. 

Transacylation. Alcohols and amines are acylated with an ester using Ini, as catalyst. Selective acylation of primary alcohols (vs. secondary alcohols and phenols) and amines (vs. secondary amines and primary alcohols) is possible. 

The basic nucleophilic poly(iV-alkylacrylamide)-immobilized catalyst 95 was prepared from the active estercopolymer 94 according to the chemistry shown in Eq. 37 [131]. This polymercontained a ca. 8 mol% loading of an analog of ATjAT-dimethylaminopyridine, anucleophilic catalyst that others had immobilized on insoluble cross-linked resins previously. This soluble version was shown to be effective as a catalyst for acylation of hindered alcohols and phenols (Eqs. 38 and 39). This catalyst contained an azo dye as a marker, which facilitated analysis of the phase separation of the polymer-immobilized catalyst. 

Tetrasubstituted guanidines catalyse the methylation of phenols using dimethylcarbonate. When DBU is used as catalyst, the reaction temperature is lower. Methylation of acids has also been accomplished. TBD has been demonstrated to be an excellent catalyst for acyl transfer and transesterification reactions. Vinyl acetate with TBD forms AT-acetyl TBD that hy adding benzyl alcohol results in formation of the corresponding acetate and regeneration of the TBD. TBD has also heen used for the ring-opening polymerisation of cyclic esters. ... 

Hosseini-Sarvari, M. and Sharghi, H. 2004. A simple, economical and efficient Friedel-Crafts acylation reaction over zinc oxide (ZnO) as anew catalyst. J. Org. Chem. 69 6953-6956. Hosseini-Sarvari, M. and Sharghi, H. 2005. Zinc oxide (ZnO) as a new, highly efficient, and reusable catalyst for acylation of alcohols, phenols and amines under solvent free conditions. Tetrahedron 61 10903-10907. 

The remaining discussion is organized in three sections dealing, respectively, with the use of homogeneous catalysts, heterogeneous catalysts, and direct phenol acylation. Each section contains various subtopics based on the nature and role of each class of catalysts. 

Solid acid catalysts such as clays and zeolites are also utilized for phenol acylation however, these processes suffer from catalyst deactivation problems and lack C-selectivity. In the acylation of phenol with acetic anhydride, HZSM-5 zeolite shows a very high ort/io-selectivity (48% o-HAP yield, <1% p-HAP yield), although phenyl acetate is isolated in only approximately 20% yield [115]. The SAR value has a remarkable influence on the selectivity of the process when the reaction is carried out in the presence of HZSM-5(30), HZSM-5(150), and HZSM-5(280) zeolites, the o-HAP yields are 42,40, and 15%, respectively, whereas the O-acylation is noticeably increased. These results mean that C-acylation requires higher Brpnsted acidity and that lower acidity leads to phenyl acetate formation. It must be noted that the reaction performed with an amorphous aluminosilicate acid catalyst gives mostly phenyl acetate without isomer selectivity. These results suggest that the C-acylation of phenol occurs in the channels of zeolites and not on the external surface. 

Esterifications. Pyridine is a widely used catalyst for acylation reactions. Acetylation reactions are effectively carried out in the presence of hexachlorocyclophosphazatriene and pyridine. Acetylation of phenols by acetic anhydride in carbon tetrachloride is also catalyzed by pyridine. In the absence of the pyridine catalyst, at 0 °C and 25 °C, no acylation of the phenols is observed (eq 21). ... 

These catalysts have been tested in a variety of reactions such as acylation of alcohols and alkylation of phenols and naphthols [71,72,96,100,101,108]. The encapsulated triflate derivatives, and particularly the immobilized Lewis acid r rr-butyldimethylsilyltri-fluoromethanesulfonate, are very active catalysts in acylation of 2-methoxynaphthalene with acetic anhydride. In solvent-free conditions, the TOF is much higher than the values reported in literature for other heterogeneous catalysts. Moreover, leaching can be completely avoided when the solvent is omitted. The major product was in all cases the 1-acetylated methoxynaphthalene the isomerization to the 6-isomer was negligible even at high conversions. 

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... 

Sulfonated styrene—divinylbensene cross-linked polymers have been appHed in many of the previously mentioned reactions and also in the acylation of thiophene with acetic anhydride and acetyl chloride (209). Resins of this type (Dowex 50, Amherljte IR-112, and Permutit Q) are particularly effective catalysts in the alkylation of phenols with olefins (such as propylene, isobutylene, diisobutylene), alkyl haUdes, and alcohols (210) (see Ion exchange). Superacids. 

Several methods are available to supplement the phenol alkylations described above. Primary alkylphenols can be produced using the more traditional Friedel-Crafts reaction. Thus an -butylphenol can be synthesized direcdy from a butyl haUde, phenol, and mild Lewis acid catalyst. Alternatively, butyryl chloride can be used to acylate phenol producing a butyrophenone. Reduction with hydrazine (a Wolff-Kishner reduction) generates butylphenol. 

Sc(OTf)3, AcOH, p-nitrobenzoic anhydride or Sc(OTf)3, AC2O, 66- >95% yield. The lower yields are obtained with allylic alcohols propargylic alcohols give higher yields. Phenols are effectively acylated with this catalyst, but at a much slower rate than simple aliphatic alco-hols. The method was shown to be superior to most other methods for macrolactonization with minimum diolide formation. 

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a 8 2 mechanism. As with 10-8, the mechanism can be S l or tetrahedral. Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 10-9). The reaction is of wide scope, and many functional groups do not interfere. A base is frequently added to combine with the HX formed. When aqueous alkali is used, this is called the Schotten-Baumann procedure, but pyridine is also frequently used. Both R and R may be primary, secondary, or tertiary alkyl or aryl. Enolic esters can also be prepared by this method, though C-acylation competes in these cases. In difficult cases, especially with hindered acids or tertiary R, the alkoxide can be used instead of the alcohol. Activated alumina has also been used as a catalyst, for tertiary R. Thallium salts of phenols give very high yields of phenolic esters. Phase-transfer catalysis has been used for hindered phenols. Zinc has been used to couple... 

The scope of this reaction is similar to that of 10-21. Though anhydrides are somewhat less reactive than acyl halides, they are often used to prepare carboxylic esters. Acids, Lewis acids, and bases are often used as catalysts—most often, pyridine. Catalysis by pyridine is of the nucleophilic type (see 10-9). 4-(A,A-Dimethylamino)pyridine is a better catalyst than pyridine and can be used in cases where pyridine fails. " Nonbasic catalysts are cobalt(II) chloride " and TaCls—Si02. " Formic anhydride is not a stable compound but esters of formic acid can be prepared by treating alcohols " or phenols " with acetic-formic anhydride. Cyclic anhydrides give monoesterified dicarboxylic acids, for example,... 

Sulfonic esters are most frequently prepared by treatment of the corresponding halides with alcohols in the presence of a base. The method is much used for the conversion of alcohols to tosylates, brosylates, and similar sulfonic esters. Both R and R may be alkyl or aryl. The base is often pyridine, which functions as a nucleophilic catalyst, as in the similar alcoholysis of carboxylic acyl halides (10-21). Primary alcohols react the most rapidly, and it is often possible to sulfonate selectively a primary OH group in a molecule that also contains secondary or tertiary OH groups. The reaction with sulfonamides has been much less frequently used and is limited to N,N-disubstituted sulfonamides that is, R" may not be hydrogen. However, within these limits it is a useful reaction. The nucleophile in this case is actually R 0 . However, R" may be hydrogen (as well as alkyl) if the nucleophile is a phenol, so that the product is RS020Ar. Acidic catalysts are used in this case. Sulfonic acids have been converted directly to sulfonates by treatment with triethyl or trimethyl orthoformate HC(OR)3, without catalyst or solvent and with a trialkyl phosphite P(OR)3. ... 

The exact mechanism has still not been completely worked out. Opinions have been expressed that it is completely intermolecular, completely intramolecular, and partially inter- and intramolecular. " One way to decide between inter- and intramolecular processes is to run the reaction of the phenolic ester in the presence of another aromatic compound, say, toluene. If some of the toluene is acylated, the reaction must be, at least in part, interraolecular. If the toluene is not acylated, the presumption is that the reaction is intramolecular, though this is not certain, for it may be that the toluene is not attacked because it is less active than the other. A number of such experiments (called crossover experiments) have been carried out sometimes crossover products have been found and sometimes not. As in 11-14, an initial complex (40) is formed between the substrate and the catalyst, so that a catalyst/substrate molar ratio of at least 1 1 is required. 

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