Carboxylic acids anisole acylation

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. 

In our study of the acylation of anisole with carboxylic acids [24], and the Nafion-silica composite as the catalyst, no leaching was detected during reaction conditions. This was also not observed in the study of Botella et al. [22] in the alkylation of 2-butene by isobutane. 

Acylation of anisole with carboxylic acids, in particular with octanoic acid, is described to be carried out over variously activated HBEA zeolites [51, 52]. Activation of the zeolite by treatment with oxalic acid after steaming results in a significant decrease of the surface area (from 670 to 500mVg) and an increase of the bulk SAR (from 13 to 51). This provides an increase in activity and selectivity in fact, HBEA itself exhibits an activity, defined as the initial apparent first-order constant k, of 0.031/g j h and a selectivity toward compound 17 (R = C. Hjj) of 80% at 50% conversion, whereas a great activity increase ( =0.121/g -h) and a selectivity improvement... 

Cs2.5 for the acylation. Anisole and /j-xylene are acylated with benzoic anhydride and acetic anhydride in the presence of Cs2.5 without the dissolution of this catalyst. Carboxylic acids are much less reactive as acylating agents than the corresponding anhydrides because of the liberation of water. But when the water is removed, the acylation proceeds smoothly 214). Although the reaction of benzene with acetic acid is attractive in prospect, there is no report of heteropoly compounds as catalysts for this reaction. 

The selective acylating action of a mixed anhydride of two carboxylic acids was first correctly diagnosed by B hal, who showed that, in the acylation of an alcohol by a mixed anhydride, there preponderates (in the product) the ester formed from the acid having the smaller number of carbon atoms. The formation, from a mixture of acetic anhydride and either mono-, di-, or tri-chloroacetic acid, of an acetylating agent sufficiently powerful to effect p-acetylation of anisole was later demonstrated by Unger. ... 

Anisole has also been acylated with aliphatic or aromatic carboxylic acids, with 92-95.6% selectivity at... 

Table 4.12 Anisole acylation with different carboxylic acids catalyzed by zeolite ZSM-5...

Anisole can be acylated with carboxylic acids over ZSM-5 catalyst. The reaction is carried out in a batch reactor under reflux for 2 d. Table 4.12 shows fhe resulfs obfained utilizing carboxylic acids with different chain length. Prom propanoic acid to stearic acid, the conversion decreases from 92% to 1%, showing a trend opposite to that observed with REY zeolites. This behavior can be ascribed to the small micropore size of ZSM-5, in which the formation of large molecules is difficulf (for penfanoic to octanoic acid) or impossible (for longer-chain carboxylic acids). The poor conversion of AAC can be affribufable to the low reflux temperature. 

The mesoporous aluminosilicate AlMCM-41-type material, prepared from BEA zeolite seeds, can be utilized as catalyst in the acylation of anisole with acyl chloride with the aim of improving the transport of the reactants, especially for the relatively hindered molecules such as octanoyl chloride. The catalyst shows good activity, being para-octanoyl anisole obtained in 90% yield after 1 h. As commonly observed, the use of carboxylic acid as acylating agent results in a slower process (-20% yield after 26 h) due to its lower electrophilicity and the production of water that inhibits the active sites of the zeolite, as previously observed by Beers et al. ... 

More interestingly, carboxylic acids can be employed in the acylation of aromatic compounds. The acylation of toluene and anisole with C2-C42 aliphatic carboxylic acids can be carried out with CsPW, affording the corresponding products in 41%-71% yield. These solid acids are superior in activity to the conventional acid catalysts such as sulfuric acid and zeolites, and can be reused after a simple workup, albeit with reduced activity. 

In studies on the acylation of anisole with octanoic acid, it is observed that carboxylic acids, when present in large amounts, adsorb so strongly on the catalyst surface that the aromatic substrates have no chance to react. ... 

Corma, A., Climent, M. J., Garda, E., and Primo, J. 1989. Design of synthetic zeolites as catalysts in organic reactions. Acylation of anisole by acyl chlorides or carboxylic acids over acid zeolites. Appl. Catal. 49 109-123. 

Kaur, J. and Kozhevnikov, I. V. 2002. Efficient acylation of toluene and anisole with aliphatic carboxylic acids catalysed by heteropoly salt CsjgHQ 5PW12O40. Chem. Commun. 2508-2509. 

Recently, it was demonstrated that the acylation of toluene and anisole with C2 -Cl 2 aliphatic carboxylic acids in liquid phase is efficiently catalysed by Cs2,5Ho,5[PWi204o]. The acylation of toluene was carried out at a molar ratio PhMe/RCOOH = 50 and 110 C in the presence of ca. 10 wt% Cs2.5Ho.5[PWi204o] (Table... 

The acylation of anisole with C2 - C12 acids was carried out under the same conditions as that of toluene, except a shorter reaction time (5 h). The acylated anisole formed as the major product para/ortho = 59 1 - 96 1 and no meta isomers) together with esterification products - methyl esters of carboxylic acids and phenol. No phenyl esters formed. The selectivity to esters increases from acetic to dodecanoic acid, reaching 40% for the latter. The acylation of anisole, in contrast to that of toluene, is most efficient with C2 - C6 acids, giving a 62 - 65% yield of acylated products and only 2 - 6% of methyl esters. 

The regioselective acylation of aromatic ethers with carboxylic acids (aromatic ether/carboxylic acid ratio =1) can be pafonned with an equimolecular mixture of trifluoroacetic anhydride adsorbed on the surface of alumina without any solvent [77]. The process can be applied, with nearly quantitative yields, to anisole and the three isomeric dimethoxybenzenes by using carboxylic acids. The authors outline that in the case of anisole, the acylation selectively occurs at the para position to the methoxy group. The reaction requires a large amount of alumina and trifluoroacetic anhydride, and consequently, it can only be appUed at the laboratory scale. The intervention of a mixed carboxyhc acidArifluoroacetic acid mixed anhydride intermediate is presumed. 

From a theoretical point of view, the products more easily produced in the acylation of anisole are fhe ortho- and para-acylanisoles and phenyl carboxylic esfer 32. The selectivity of ZSM-5 zeolife toward para-acylanisole 31 increases from 0.5 wifh AAC to 60% with propanoic acid and finally reaches 80% wifh bufanoic acid. In addition, at low temperature (120°C), the reaction affords producf 32 with a selectivity higher than 70%, whereas the maximum selectivity toward ketone 31 is achieved by carrying out the process at 150°C. This means that the activation energy of the O-acylation reaction is lower than that of C-acylation. 

Anisole, implicated in the preceding paragraph, can be the cause of an additional side reaction, another electrophilic substitution catalyzed by strong acids. To wit, the side chain carboxyl group of glutamyl residues participates in the Friedel-Crafts acylation of the scavenger and yields a stable ketone ... 

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