Toluene acylation carboxylic acids

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. 

Treatment of salicylic hydrazide in toluene with a single carbon insertion unit, such as carboxylic acid anhydride, acid chloride, and orthoester, in the presence of an equimolecular amount of methanesulfonic acid gave the l,3,4-benzoxadiazepin-5-ones (530) (43-68% yield), via the O-acylation intermediates (529) (92S929). 

Our pioneering work in 1986[1] has shown that acid zeolites are efficient catalysts in the Friedel-Crafts acylation of toluene and xylene with carboxylic acids and constitutes a breakthrough in environmentally friendly fine chemistry replacing the conventional AICI3 method by a heterogeneous catalysts. Since this initial study, a tremendous amount of work has been performed in this area[2] and particularly, in recent years, the acetylation reaction, which is a field of research with large potential for the production of fine chemicals, has been intensively investigated. 

Chiche, B., Finiels, A., Gauthier, C., Geneste, P., Graille, J. and Pioch, D. Friedel-Crafts acylation of toluene and /7-xylene with carboxylic acids catalyzed by zeolites. J. Org. Chem., 1986, 51, 2128-2130. 

Initial studies showed that Ru3(CO)i2 and [Ru(CO)2(02CCH3)]n were able to promote the addition of carboxylic acids to diphenylacetylene at 145 °C in toluene [29, 30]. Subsequently, a number of catalytic systems based on ruthenium catalysts have been discovered, and these have made possible - under mild conditions - the Markovnikov addition of carboxylic acids to terminal alkynes according to Scheme 8.14 to produce enol esters used as acylating reagents. 

N-Acyloxazolidin-2-ones. A convenient A-acylation of heterocycles is performed by heating a carboxylic acid with PivCl and triethylamine in toluene. 

Due to the attractivity of this method several groups have developed onium salt supported versions of classical reactions. For example, starting from hydroxyl derived imidazolium salts, formation of supported acrylates with acryloyl chloride followed by reaction with diene in refluxing toluene afforded Diels Alder adduct in good yields (>65%). After saponification, products are isolated without further purification [127], Alternatively, starting from carboxylic acid derived imidazolium salts, acyl chloride formation with thionyl chloride in acetonitrile, followed by reaction with 4-aminophenol led to supported N-arylamide. Williamson alkylation using NaOH as a base and subsequent cleavage from the onium salt support under acidic condition (HCI/I I2()/ AcOH) allowed for isolation of various alkoxy substituted anilines with >98% purity... 

Attempts to condense the quinolizine (73.4) with methyl propynoate in boiling tenzene or toluene containing palladium-charcoal failed, but when nitrobenzene was used, moderate-to-good yields of the pyridoquinolizine were obtained. Formation of a 4 oxo- or 4-chloro-pyridine ring from a carboxylic acid (or ester) or an acyl chloride respectively Is well documented (see pp. 378-381, and Section II.3 of this chapter) in this particular example, a fused... 

A number of protic acids have been used to catalyze acylation reactions. It is assumed that the reactions involve the generation of acylium ions. Polymeric reagents such as Nafion-H have been used for example 2-fluorobenzoyl chloride and toluene give the benzophenone derivatives with an ortho.para ratio of 4 81. ° A zeolite-catalyzed acylation (equation 6) has been reported to afford 4-dodecenoyltol-uene in 96% yield but the yields are low with short chain carboxylic acids. Early examples of the use of trifluoroacetic and perchloric acids reported good yields of products. Some more recent examples are shown in equations (7) to (9). Phosphoric and polyphosphoric acids have been used together with carboxylic acids (equation 10),anhydrides and acylureas (equation 11). °... 

Pioneering and extensive work in this field was realized in 1985 [8] by use of exchanged Ce Y-zeolite as the catalyst for the Friedel-Crafts acylation of toluene (Eq. 3) and xylene with carboxylic acids. Different aspects of this initial work are of interest. Firstly, it shows that the mild acidity of zeolites is sufficient to effect the reaction, and, secondly, it shows that this reaction can be conducted with carboxylic acids and not the corresponding acid chlorides. Only the more lipophilic acids were found reactive whereas no acetylation occurs with acetic acid. The reaction with toluene (Table 1) is extremely para selective and more selective than a conventional aluminum chloride homogeneous process. The different reactivities reported in this paper are essentially because of differences between preferential adsorption of the substrates on the catalyst and not their intrinsic activity. 

In a series of valuable studies, the activity of various cation-exchanged Y zeolites in the acylation of toluene and xylenes with aliphatic carboxylic acids was investigated In a model reaction between toluene and octanoic acid, the activity of rare earth-, transition metal-, and alkaline earth-cation-exchanged Y zeolites was considered. CeY zeolite exhibits the highest activity (3 yield = 75%) in the para-acylation (Scheme 4.3) in agreement with the results published in an early study qj., contrary, unmodified Y zeolite shows a lower activity (3 yield < 40%), and transition metal and alkaline-earth-exchanged Y are nearly inactive. 

Figure 4.4 Dependence of the yield in toluene acylation with linear carboxylic acids on the chain length in the presence of CeY.

Acylation of toluene with carboxylic acids can be performed with metal-clay-exchanged catalysts. A series of exchanged montmorillonites was studied in the model acylation of toluene with dodecanoic acid. Best results are achieved with AIKIO (60% yield of the three isomers). 

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. 

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. 

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