Acetylation of anisole

Smith et al. (1998) have reported selective para acetylation of anisole, phenetole, and diphenyl ether with carboxylic anhydrides at 100 °C, in the presence of catalytic quantities of zeolites H-beta. The zeolite can be recovered and recycled to give essentially the same yield as that given by fresh zeolite. 

The acetylation over protonic zeolites of aromatic substrates with acetic anhydride was widely investigated. Essentially HFAU, HBEA, and HMFI were used as catalysts, most of the reactions being carried out in batch reactors, often in the presence of solvent. Owing to the deactivation effect of the acetyl group, acetylation is limited to monoacetylated products. As could be expected in electrophilic substitution, the reactivity of the aromatic substrates is strongly influenced by the substituents, for example, anisole > m-xylene > toluene > fluorobenzene. Moreover, with the poorly activated substrates (m-xylene, toluene, and fluoroben-zene) there is a quasi-immediate inhibition of the reaction. It is not the case with activated substrates such as anisole and more generally aromatic ethers. It is why we have chosen the acetylation of anisole and 2-methoxynaphtalene as an example. 

Figure 12.7 Acetylation of anisole. Characteristics of the old (AICI3) and new (HBEA)...

In the field of fine chemical synthesis there is an urgent need to substitute the cleaner technologies for the old polluting ones. It is hoped that the large economic and environmental benefits brought by the recently developed catalysis processes—acetylation of anisole and of veratrole, Beckmann rearrangement, and so forth—will initiate great strides in this field. 

Amorphous and mesostructured Zr02 solid catalysts impregnated with various amounts of triflic acid were tested in the acylation of biphenyl356,357 and toluene358 (with benzoyl chloride and para-toluyl chloride, respectively, nitrobenzene solvent, 170°C and 130°C). All catalysts exhibited lower activity when compared with neat triflic acid. The mesoporous catalysts, however, showed complete selectivity in the formation of para-benzoylbiphenyl. A triflic acid-silica catalyst, in turn, prepared using an aminopropyl-modified silica, showed good characteristics in the solvent-less acetylation of anisole and 2-methoxynaphthalene with acetic anhydride.359,360 The activity of 1,1,2,2-tetrafluoroethanesulfonic acid, either neat or embedded in silica, was found to be similar to that of triflic acid in the acetylation of anisole.196... 

In 2001, Holderich s group [37] presented 1-methyl-3-butylimidazolium chlor-oferrate (Fe-IL) in addition to Al-IL and Sn-IL as a catalyst for Friedel-Crafts acylations. In the acetylation of anisole with acetic anhydride, full conversion of the acylating agent was observed using Fe-IL. The immobilization of these catalysts, however, led to some serious problems such as catalyst leaching. 

In the Sc(0Tf)3-LiC104-system, wider substrate scope was observed as is shown in Table 8. Each acylation reaction in the Table gave a single acylation product and formation of other isomers was not observed. Acetylation of anisole (1) resulted in excellent yield of the product (entry 1). Mesitylene (3) and xylenes were transformed to 2,4,6-trimethylacetophenone and dimethylacetophenones, respectively, in moderate yields (entries 2-5). It is noteworthy that toluene was acylated by the Sc(0Tf)3-LiC104 system to give 4-methylacetophenone in 48 % yield (entry 6) but the acylation did not proceed in the absence of LiC104. Furthermore, recovery and reuse of the RE(0Tf)3-LiC104 system were performed successfully. As shown in Table 9, the yields of 6 in the second and third uses of the catalyst system were almost the same as that in the first use. 

Figure 2.5 Relative occupancy (%) of the intracrystalline volume of a H-BEA zeolite during the transformation of a 2 1 molar anisole - acetic anhydride mixture in a batch reactor, assuming no adsorption of acetic acid and full occupancy of the micropores. Anisole ( ), acetic anhydride (o) and 4-methoxyacetophenone (x). Reprinted from Journal of Catalysis, Vol. 187, Derouane et al., Zeolite catalysts as solid solvents in Fine Chemicals synthesis 1. Catalyst deactivation in the Friedel-Crafts acetylation of anisole, pp. 209-218, copyright (1999), with permission from Elsevier...

Table 3.1 Liquid phase acetylation of anisole and derivatives (S) with acetic anhydride (AA) over zeolite catalysts. Batch reactors were employed except in References [6] and [9] (fixed bed reactor)... 

During the first 2h of reaction, a decrease in AcOH conversion (from 48 to 43 %) for benzene acetylation at 523 K with an increase in selectivity to the monoacetylated product (from 80 to 90%) can be observed. The only problem involves the low catalyst activity 1.5 mmolh 1g 1 of acetophenone, which corresponds to a TOF value of 2.2 h-1. This means that less than 0.2 g of this acetylated arene can be produced per hour and per gram of catalyst under the operating conditions (i.e. 10 times less than in the liquid phase acetylation of anisole with AA). The kinetic study of the reaction shows an increase in the selectivity with the substrate/acetic acid ratio, but no increase in yield, an increase in acetic acid conversion with the reaction temperature with a significant decrease in selectivity due to a greater formation of diacetylated products.[62,63] HFAU and RE-FAU zeolites do... 

Derouane, E. G., Dillon, C. J., Bethell, D., Derouane Abd-Hamid, S. B. Zeolite catalysts as solid solvents in fine chemicals synthesis-1. Catalyst deactivation in the Friedel-Crafts acetylation of anisole, J. Catal., 1999, 187, 209-218. 

Fig. 14.2 Acetylation of anisole at 90°C in a fixed bed reactor. Ratio between the initial conversion of anisole and the maximum conversion which can be obtained vs. the inverse of the weight hourly space velocity (WHSV) for anisole...

Rhodia is operating an industrial process for acetylation of anisole into paramethoxyacetophenone (pMAP) (18) which is a precursor of Parsol used for sun... 

The present catalyst was examined in a more reactive acetylation, the acetylation of anisole with acetic anhydride. A quantitative yield of methoxyacetophenone was obtained under the reaction conditions, showing how reactive anisole is in comparison with toluene-demonstrating the effect an oxygen has on reactivity. Several papers concerning the Eriedel-Crafts reaction of anisole have been published [212-216], but studies of the reaction of toluene or even benzene are desired. The difference in reactivity between anisole and toluene is close to 100 °C in terms of the reaction temperature. 

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. ... 

Eor the acetylation of anisole by acetic anhydride, the zeolite H BE A is the better catalyst, but in an industrial process the separation of this catalyst for recycling is a key issue and it has to be taken into account. Indeed, the filtration rate of HBEA, especially after reaction is too slow and this operation is not industrially and economically viable. 

Table 1 Acetylation of Anisole with Acetic Anhydride Using Various Heterogeneous Catalysts (8 h, 90°C)...

The latter possibility has been suggested by Iqbal in the case of the Co11 catalyzed acetylation of anisole by acetylchloride (ref. 31). However, no experimental support of the mechanism has been provided so far. Oxidation and electrophilic attack can be competitive pathways or oxidation can be a common pathway for both dimerization and trifluoroacetylation. 

C9H10O2, My 150.18, d41 1.0818, ng1 1.5470, occurs in anise oil. It forms white crystals (mp 38 °C) with a sweet odor, reminiscent of hawthorn. 4-Methoxyacetophe-none is prepared by Friedel-Crafts acetylation of anisole. A modem process uses fl-zeolites as Friedel-Crafts catalysts in combination with a continuous flow technology. 4-Methoxyacetophenone is used in soap perfumes [178a], [178b]. 

Table 2. Acetylation of anisole with acetic anhydride and different heterogeneous catalysts (8 h. 90 °C).

Kouwenhoven s group [10] also worked on acetylation of anisole with various zeolites and found that Yip has particularly high activity, irrespective of the silica to alumina ratio of the zeolite. Systematic work was then performed in Rhodia [11] to try to rationalize the observed effects. Results obtained using the same reaction conditions changing only the catalyst are depicted in Table 2. 

Table 5. Acetylation of anisole with phenylacetyl chloride using Nafion-based materials.

Para-acetylation of anisole with AAN is performed in the presence of ytterbium triflate (20% mol). The reaction proceeds smoothly even when the catalyst is employed in a small amount (5% mol), and the desired acylation product is obtained in 79% yield. Several substituted benzenes are subjected to ytterbium-triflate-catalyzed acetylation. Though acetylation of benzene does not occur, introduction of a methylthio or dimethylamino group on the aromatic ring gives the acylation products in high yields. The presence of a methyl group is less effective, and mete-xylene is acy-lated to 2,4-dimethylacetophenone in only 25% yield. Ytterbium triflate can be recovered from the aqueous layer by simple extraction and reused for two additional runs in the model acetylation of anisole, affording para-acetylanisole with almost the same yield as in the first use. 

Experimental conditions were developed that require the use of indium(lll) triflate (1% mol) in the acetylation of anisole with AAN in combination with silver perchlorate in acetonitrile at 50°C. 3 The reaction gives para-methoxyacetophenone in 82% yield, and better results, namely, 96% yield, can be achieved by increasing the lithium perchlorate amount (from 25% to 100%) in nitromethane at 50°C for 1 h. The catalytic system is highly effective for the acetylation of electron-rich aromatic and... 

However, species resulting from AAN self-condensation, such as compounds 24,25, and 26, are also present (Figure 4.5). These compounds do not appear in the acetylation of anisole and 2-MN, which shows only a limited decrease in the reaction rate with the reaction time. On the other hand, they play a more significant role than aromatic ketones in the inhibition of the acetylation reaction and are the major products retained in the zeolite during the acetylation of fluorobenzene, which occurs very slowly and with a significant decrease in the reaction rate. 

Synthetically valuable methods for the efficient acylation of aryl ethers with anhydrides over different BEA zeolites under batch conditions are also reported. Significant results are summarized in Table 4.9. The reaction can be performed without solvent, and the catalyst can be reused in the acetylation of anisole with unchanged activity for three further cycles after recovery and regeneration by heating in air at 550°C for 3 h. ... 

Catalyst deactivation in the Friedel-Crafts acetylation of anisole. /. Gatal. 187 209-218. 

Derouane, E. G., Schmidt, L, Lachas, H., and Christensen, C. J. H. 2004. Improved performance of nano-size H-BE A zeolite catalysts for the Friedel-Crafts acetylation of anisole by acetic anhydride. Gatal. Lett. 95 13-17. 

Rohan, D., Canaff, C., Fromentin, E., and Guisnet, M. 1998. Acetylation of anisole by acetic anhydride over a HBEA zeolite—origin of deactivation of the catalyst. /. Catal. 177 296-305. 

Lanthanide bis(trifluoromethylsulfonyl)amides Ln[N(S02CF3)2] catalyse the acetylation of anisole by acetic anhydride in good yield with easy catalyst recovery. The Friedel-Crafts acetylation of (3-bromopropyl)benzene by acetyl chloride to form p-(3-bromopropyl)acetophenone together with a little of the 3-chloro analogue has been studied. The acylation of phenol by acetic acid has been subject to... 

Table 3.1 Benzoylation/acetylation of anisole, i-propylatior of benzene and dismutation of CCI2F2 over host/guest catalysts (Data taken from [13] by permission of Elsevier Publishers)...

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