Benzoylation of anisole

The short reaction time (1 min, 160 °C) in the benzoylation of anisole was probably a result of large temperature gradients rather than a nonthermal microwave effect. 

Hardacre et al. report the Friedel-Crafts benzoylation of anisole with benzoic anhydride to yield 4-methoxybenzophenone with various ILs and zeolite catalysts (USY, HZSM-5, H-beta, and H-mordenite). The rates of reaction were found to be significantly higher using ionic liquids compared with organic solvents.Continuous-flow studies of successful ionic liquid systems indicate that the bulk of the catalysis is due to the formation of an acid via the ion exchange of the cation with the protons of the zeolite as shown in the following reaction. Scheme 8. 

The formation of 4-methoxybenzophenone by the benzoylation of anisole with benzoic anhydride is shown in Scheme 4.1. 

Hardacre, C., Katdare, S. P., Milroy, D., Nancarrow, P., Rooney D. W. and Thompson, J. M. A catalytic and mechanistic study of the Friedel-Crafts benzoylation of anisole using zeolites in ionic liquids, J. Catal., 2004, 227, 44-52. 

Scheme 9.22 Solvent and catalyst effects in the benzoylation of anisole...

Table 14.5 Benzoylation of anisole with benzoyl chloride catalyzed with several zeolites.

Table 14.5 shows the results obtained for several zeolites in the reaction of benzoylation of anisole with benzoyl chloride. 

As far as catalysis of acylation is concerned, BiCl3 has been little studied. Two references report the use of this salt for the acetylation of toluene (ref. 38) and for the benzoylation of anisole (ref. 39), with average results for the latter, but poor for toluene. More recently, Le Roux and al. showed that BiCl3-metallic iodide systems efficiently catalyze the acylation reaction of enoxysilanes and allylsilanes for which they represent the first known catalysts (refs. 30b, 40). 

Eventhough, selectivity was found to be very high in all cases, the activity was low. It appears obvious from these experiments that the benzoylation of anisole is independent on the pore sizes of the zeolites. 

The same catalyst (10% mol) can be utilized in the benzoylation of anisole by benzoyl chloride (BC), showing yield improvement when performed in combination with microwave irradiation. The BC conversion is 95% (with ortho/para isomer ratio 0.06) after 1 min irradiation at 165°C and 300 W power. The reaction can be applied to different activated arenes, giving products in high yields and showing the characteristics of an economical energy-saving process able to perform clean reactions in reduced time. A further advantage is the avoidance of the solvent since the aromatic substrate can replace it. 

In the benzoylation of anisole with BC, the copper(II) triflate/[bmim] [BFJ is recycled three times after washing with diethyl ether, affording the methoxy-substituted BPs in 86%, 79%, and 65% yield with an ortho/para ratio of 0.04 for all runs. The lowering of the catalyst efficiency is assumed to be due to the production of hydrogen chloride, possibly leading to the formation of an increasing amount of copper dichloride, which is inactive under these conditions. 

Benzoylation of anisole with BC at the para-position is performed in the presence of a catalytic amount of iron(III) oxide (85% yield) lower yields of 4-halobenzophenones are achieved with the weakly deactivated chlorobenzene (33%), bromobenzene (31%), and iodobenzene (30%). However, taking into account the possible leaching of active iron trichloride produced by the reaction of iron(III) oxide with hydrogen chloride, the contribution of the homogeneous iron-based Lewis acid form is strongly suspected. 

Zinc oxide, an inexpensive and commercially available inorganic solid, can be utilized as an efficient catalyst in the Friedel-Crafts acylation of activated and unactivated aromatic compounds with acyl chlorides at room temperature for 5 to 120 min (Table 4.14). Acylation is claimed to occur exclusively at the para-position of the monosubstituted aromatic compounds. The catalyst can be recovered and reused, after washing with methylene chloride, for at least two further cycles, showing quite similar high yield (-90%) in the model benzoylation of anisole. Mechanistically, it seems that zinc chloride can be the true catalyst, generated in situ by the reaction of zinc oxide with hydrogen chloride. 

Table 4.17 Activity of different catalysts in the benzoylation of anisole with BC in nitrobenzene at 150°C for 22 h...

Some occasional information is available concerning the reusability of the SZ catalyst in the benzoylation of anisole with BAN. The catalyst is effectively utilized for a second cycle, but more drastic experimental conditions are needed to achieve a yield comparable to that of the first run. Moreover, detailed spectroscopic analysis of the utilized catalyst confirms that, during the reaction, carbonaceous deposits are formed on the surface, and the number of the available acid surface sites decreases. 

Similar good resulfs can be obfained in the benzoylation of anisole wifh BC. Af 110°C, an 80% conversion of fhe acyl chloride is achieved after 2 h wifh CsPWKlO (20% loading), para-methoxybenzophenone being fhe sole producf obfained. The catalyst can be efficiently reused three times. 

Benzoylation of anisole over borate zirconia solid acid catalyst. Catal. Commun. 3 411-416. 

Trunschke, A., Deutsch, J., Muller, D., Lieske, H., Quaschning, V., and Kemnitz, E. 2002. Nature of surface deposits on sulphated zirconia used as catalyst in the benzoylation of anisole. Catal. Lett. 83 271-279. 

Yadav, G. D., Asthana, N. S., and Kamble, V. S. 2003. Cesium-substituted dodecatungstophosphoric acid on K-10 clay for benzoylation of anisole with benzoyl chloride. /. Catal. 217 88-99. 

The feasabihty of using metal triflates as Lewis catalysts for different aromatic acetylations in non-chloroaluminate ILs such as [BMIM][BF4] has also been demonstrated. The faster rates were obtained with copper(II) triflate for the benzoylation of anisole but triflates are restricted to activated substrates [13]. 

Friedel-Crafts Acylation, Alkylation, and Related Reactions. While a stoichiometric amount of AICI3 is needed in Friedel-Crafts acylations, a small amount of Sc(OTf)3 smoothly catalyzes the same reaction. In the acetylation of thioanisole and o- or m-dimethoxybenzene, a single acetylated product is formed in an excellent yield. In the benzoylation of anisole, both benzoic anhydride and benzoyl chloride are effective, while benzoic anhydride gives a slightly higher yield. Addition of lithium perchlorate (LiC104) as a cocatalyst improves the yield dramatically (eq 13). ... 

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