Acylation of toluene

A variety of other reactions such as acylation of toluene, anisole, and chlorobenzene to give selectively p-isomer, alkylations, etc. have been conducted with IL. 

Among the wide variety of organic reactions in which zeolites have been employed as catalysts, may be emphasized the transformations of aromatic hydrocarbons of importance in petrochemistry, and in the synthesis of intermediates for pharmaceutical or fragrance products.5 In particular, Friede 1-Crafts acylation and alkylation over zeolites have been widely used for the synthesis of fine chemicals.6 Insights into the mechanism of aromatic acylation over zeolites have been disclosed.7 The production of ethylbenzene from benzene and ethylene, catalyzed by HZSM-5 zeolite and developed by the Mobil-Badger Company, was the first commercialized industrial process for aromatic alkylation over zeolites.8 Other typical examples of zeolite-mediated Friedel-Crafts reactions are the regioselective formation of p-xylene by alkylation of toluene with methanol over HZSM-5,9 or the regioselective p-acylation of toluene with acetic anhydride over HBEA zeolites.10 In both transformations, the p-isomers are obtained in nearly quantitative yield. 

Seddon and coworkers studied the Friedel-Crafts acylations of toluene, chlorobenzene and anisole with acetyl chloride in [emim][Al2Cl7] and obtained excellent regioselectivities to the para isomer, Scheme 9. Similarly, the fragrance chemical, traseolide, was obtained in 99% yield as a single isomer. Scheme 10. It should be noted, however, that the question of product recovery from the reaction medium still needs to be addressed in these systems. 

In a kinetic study of the acylation of toluene, with p-xylene and the corresponding perdeutero compounds with aroyl triflates, correlation was found between the primary kinetic isotope effect and the ortho para ratio.35 Different conformations of the bent cr complexes36 for the two isomers resulted in a much higher rate of deprotonation and rearomatization for the para isomer. By appropriately selecting reaction conditions and thereby affecting the ratio of the two conformations, unusually high amounts of ortho products may be obtained.37,38... 

Further examples include the use of U4+ and U6+ salts, which are efficient catalysts under dry air,57 and the homogeneous complex [ReBr(CO)5], which catalyzes the acylation of toluene and m-xylene with various acid chorides.58... 

Numerous acylations mediated by zeolite materials were described since 1986, when the first results were reported.76 The acylation of toluene and p-xylene with C2—C20 alkanoic acids over Ce-exchanged NaY at 150°C in a batch reactor was reported. Shape selectivity was observed maximum activity was found for Ci2 and C 4 acids. Other studies showed that Br0nsted acid centers are involved in acylation77 and an electrophilic mechanism is operative.78 A comprehensive review2 of the subject is available and, therefore, only the more recent results are discussed here. 

In 2000, Dubac s group reported the microwave-assisted Friedel-Crafts acylation of slightly activated and deactivated arenes under solvent-free conditions with FeCl3 as catalyst. Here, for the acylation of toluene a 90% product yield is obtained after 5 min of irradiation and an overall reaction time of 30 min in the presence of only 5 mol% of FeCl3. A sequential MW irradiation at 300 W afforded the acylation of fluorobenzene with 2 -chlorobenzoyl chloride, with a surprisingly high yield of 92% of 2-chloro-4 -fluorobenzophenone (Scheme 6.11). 

The tertiary alcohol is an obvious place to disconnect. Rejecting the poor disconnection of one carbon atom 20a, we have a choice between 20b and 20c giving one of two ketones 23 or 24 and Grignard reagents made from one of two halides 22 or 25. We can easily make 22 and 24 by halogenation or Friedel-Crafts acylation of toluene. But what about 23 and 25 ... 

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. 

There are a number of synthetic routes available to access the benzhy-drols needed for this approach. The first published route to SNC80 used a Friedel-Crafts acylation of toluene with m-anisoyl chloride to yield a benzo-phenone, followed by sodium borohydride reduction of the ketone (after the three-step elaboration of the para-methyl group into the diethylcarboxamide, Scheme 3) [23,24],... 

As would be expected, high rate accelerations can result when reactions proceeding through ionic intermediates, e.g. carbocations, are performed in ionic liquids. For example, Seddon and coworkers [100] studied the Friedel-Crafts acylation of toluene, chlorobenzene (Fig. 7.30) and anisole with acetyl chloride in [emi-m][Al2Cl7], whereby the ionic liquid is acting both as solvent and catalyst. They ob-... 

The Friedel-Crafts acylation of toluene, chlorotol-uene, and anisole with acetyl chloride in [emim] [C1]/A1C13 gives excellent regioselectivities to the... 

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. 

Table 1. Acylation of toluene with different acids over Ce -exchanged Y zeolite (150 °C, 48 h).

If the acylation of toluene with acetic acid depicted above [8] failed, use of the more active acyl chlorides instead of acids and La-exchanged Y-zeolite leads to the para-acylated product [20],... 

Table 3.17 Bromopentacarbonylrhenium(I)-catalyzed acylation of toluene and anisole with acyl chlorides...

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 4.2 Dependence of the degree of sodium ion exchanged by cerium ion on the activity of Y zeolite in the acylation of toluene by octanoic acid at 200°C.

Some synthetic results merit underlining, such as the high-yield and para-selectivity values observed in the acylation of toluene with octanoic, dodecanoic, and palmitic acids that reach values of 75% yield with 94% para-selectivity, 96% yield with 94% para-selectivity, and 80% yield with 99% para-selectivity, respectivelyi ... 

Several BEA zeolites have been tested as catalysts for the liquid-phase acylation of toluene with AAN (Table 4.7). [S]-Named zeolites are hydro-thermally prepared using amorphous silica as the silicon source, whereas [T]-named zeolites are prepared by using tetraethylorthosilicate (TEOS) as the silicon source with different SAR. The acylation process represents a very selective route to 4-methylacetophenone 18 small amounts of ortho- and mete-methylacetophenone 19 and 20 are produced in less than 2% of the total yield of the acetylated products. For the [S]-type BEA zeolites, the acidity values are in good agreement with the catalytic activity, following the order [S]-BEA(32) > [S]-BEA(26) > [S]-BEA(54) [S]-BEA(76). In the [T]-BEA series, the catalytic activity decreases when the SAR increases, regardless of the increase of hydrophobicity. The conclusion is that low SAR lead to better yields in acetophenones (APs). However, the poisoning... 

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). 

In an early study, it was shown that SZ calcined at 650°C was cata-lytically active in the acylation of toluene with acetic and benzoic acids... 

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. 

Botella, R, Corma, A., Lopez-Nieto, J. M., Valencia, S., and Jacquot, R. 2000. Acylation of toluene with acetic anhydride over Beta zeolites influence of reaction conditions and physicochemical properties of the catalyst. /. Catal. 195 161-168. 

Sheemol, V. N., Tyagi, B., and Jasra, R. V. 2004. Acylation of toluene using rare earth cation exchanged zeolite (3 as solid acid catalyst. J. Mol. Catal. A Chem. 215 201-208. 

Hino, M. and Arata, K. 1985. Acylation of toluene with acetic and benzoic acids catalysed by a solid superacid in a heterogeneous system. /. Chem. Soc., Chem. Commun. 112-113. 

Arata, K., Nakamura, H., and Shouji, M. 2000. Friedel-Crafts acylation of toluene catalyzed by solid superacids. Appl. Catal. A Gen. 197 213-219. 

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. 

Gauthier et al. (1989) studied the activity of various cation-exchanged Y-type zeolites in the acylation of toluene with octanoic acid, obtaining selectivities to the para isomer of 94% at 75% yield of acylated product. The most efficient catalysts were rare-earth-exchanged zeolites (70% exchange), the following order of activity being observed Cr3+, Zr4+ < M2+, Cu2+, Co2+ <11 < Pr3+, La3+, Gd3+, Yb3+, Ce3+. 

In contrast to anisole, the acylation of toluene with HPA is far less efficient than that with H-Beta. These results can be explained by the well-known strong affinity of bulk HPA towards polar oxygenates, which would lead to the preferential adsorption of acetic anhydride on HPA, blocking access for toluene to the catalyst surface. It appears that the hydrophobic zeolites with high Si/Al ratios less strongly differentiate the adsorption than the hydrophilic HPA and, therefore, are more suitable catalysts for the acylation of nonpolar aromatics like toluene. 

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