Acetic anhydride anisole acetylation

The authors of this work were concerned chiefly with additions to alkenes, and evidence about the mechanism of aromatic nitration arises by analogy. Certain aspects of their work have been repeated to investigate whether the nitration of aromatic compounds shows the same phenomena ( 5-3-6). It was shown that solutions of acetyl nitrate in acetic anhydride were more powerful nitrating media for anisole and biphenyl than the corresponding solutions of nitric acid in which acetyl nitrate had not been formed furthermore, it appeared that the formation of acetyl nitrate was faster when 95-98% nitric acid was used than when 70 % nitric acid was used. 

Zeroth-order nitrations. The rates of nitration at 25 °C in solutions of acetyl nitrate (6xio —0-22 mol 1 ) in acetic anhydride of 0- and jw-xylene, and anisole and mesitylene were independent of the concentration and nature of the aromatic compound provided that... 

Acetoxylation and nitration. It has already been mentioned that 0- and m-xylene are acetoxylated as well as nitrated by solutions of acetyl nitrate in acetic anhydride. This occurs with some other homologues of benzene, and with methyl phenethyl ether,ii but not with anisole, mesitylene or naphthalene. Results are given in table 5.4. 

Other substituents which belong with this group have already been discussed. These include phenol, anisole and compounds related to it ( 5.3.4 the only kinetic data for anisole are for nitration at the encounter rate in sulphuric acid, and with acetyl nitrate in acetic anhydride see 2.5 and 5.3.3, respectively), and acetanilide ( 5.3.4). The cations PhSMe2+, PhSeMe2+, and PhaO+ have also been discussed ( 9.1.2). Amino groups are prevented from showing their character ( — 7 +717) in nitration because conditions enforce reaction through the protonated forms ( 9.1.2). 

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. 

It is generally admitted that over zeolites, acetylation of aromatic substrates with acetic anhydride (AA) is catalyzed by protonic acid sites. The direct participation of Lewis sites was excluded by using two BEA samples with similar protonic acidities, but with very different Lewis acidities indeed, these samples were shown to have quasi-similar activities. The currently accepted mechanism is shown in Figure 12.6 for the anisole acetylation example. The limiting step of the process is the attack of anisole molecules by acylium ions. 

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. 

The effects of added species. The rate of nitration of benzene, according to a rate law kinetically of the first order in the concentration of aromatic, was reduced by sodium nitrate, a concentration of io 3 mol l-1 of the latter retarding nitration by a factor of about 4.llc>28 Lithium nitrate anticatalysed the nitration and acetoxylation of o-xylene in solutions of acetyl nitrate in acetic anhydride. The presence of 6 x io-4 mol 1 1 of nitrate reduced the rate by a factor of 4, and modified the kinetic form of the nitration from a zeroth-order dependence on the concentration of aromatic towards a first-order dependence. However, the ratio of acetoxylation to nitration remained constant.146 Small concentrations of sodium nitrate similarly depressed the rate of nitration of anisole and again modified the reaction away from zeroth to first-order dependence on the concentration of the aromatic.116... 

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)... 

Figure 3.1 Acetylation at 373 K with acetic anhydride of a series of aromatic compounds over HBEA-15 zeolite. Conversion (XSUB) of anisole ( ), 2-methoxynaphthalene (x), m-xylene ( ), toluene ( ), 2-methylnaphthalene (o) and fluorobenzene (a) versus time. Reprinted from Journal of Catalysis, Vol. 230, Guidotti et al. Acetylation of aromatic compounds with H-BEA zeolite the influence of the substituents on the reactivity and on the catalyst stability, pp. 375-383, Copyright (2005), with permission from Elsevier...

Anisole acetylation, which was one of the main reactions investigated, was first shown to be catalysed by zeolite ten years ago by Bayer (13), which was confirmed by Harvey et al. (14), then by Rhodia (15). Large pore zeolites and especially those with a tridimensional pore structure such as HBEA and HFAU were found to be the most active at 80°C, in a batch reactor with an anisole/acetic anhydride molar ratio of 5 and after 6 hours reaction, the yield in methoxyacetophenone (MAP) was close to 70% with HBEA and HFAU zeolites, to 30% with HMOR and 12% with HMFI. With all the zeolites and also with clays and heteropolyacids, the selectivity to the para-isomer was greater than 98%, which indicates that this high selectivity is not due to shape selective effects but rather to the reaction mechanism (electrophilic substitution). The lower conversion observed with HMOR can be related to the monodimensional pore system of this zeolite which is very sensitive to blockage by heavy secondary products. Furthermore, limitations in the desorption of methoxyacetophenone from the narrow pores of HMFI are probably responsible for the low activity of this intermediate pore size zeolite. 

Fig. 14.1 Reaction of an equimolar mixture of anisole and acetic anhydride (35 mmol of each) on 100 mg of HBEA10 at 60°C in a batch reactor. Influence of the addition of p-methoxyacetophenone (p-MAP) in the reactant mixture (1.5 mmol) on anisole acetylation...

Tables 14.1 and 14.2 show the dramatic improvement brought by the substitution of the old technology with AICI3 catalyst and acetylchloride as acylating agent in a batch reactor by the new technology with a HBEA zeolite catalyst, acetic anhydride as acylating agent in a fixed bed reactor (12). The fixed bed reactor process constitutes a major break-through in anisole acetylation.

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. ... 

Catalytic acylation of electron-rich aromatics is achieved with a combination of InCls and silver perchlorate (Scheme 8.114) [157]. Acetic anhydride, acetyl chloride and isopropenyl acetate serve as satisfactory acyl donors. By using an InCl3-impreg-nated Si-MCM-41 catalyst at low concentration, acylation of aromatic compounds (benzene, toluene, p-xylene, mesitylene, anisole, naphthalene, methylnaphfhalene, and methoxynaphfhalene) by acyl chlorides (benzoyl chloride, phenylacetyl chloride, propionyl chloride, or butyryl chloride) can be accomplished rapidly (3 h) at 80 °C in high yield, even in the presence of moisture in the aromatic substrate or solvent (dichloroethane) (Scheme 8.115) [158], In(OTf) j is an efficient catalyst in the sulfonylation of both activated and deactivated aromatic compounds (Scheme 8.116) [159]. 

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. 

To start our investigations, we examined the conversion of 2,3-dimethyl-2-butene (1) into 3,3,4-trimethyl-4-penten-2-one (2) as a model reaction (eq. 1). The choice of acetic anhydride as the acetylating agent was made in the light of related studies on the acylation of aryl ethers. Our work in this field had shown that acetic anhydride was the most effective reagent for the Friedel-Crafts acylation of anisole in the presence of Hp zeolite. A lower degree of conversion was achieved with acetyl chloride, while hardly any reaction occurred with ethyl acetate or acetic acid [6]. 

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

The acetylation of alcohols and phenols with acetic anhydride and HSZ-360 zeolite at 60oC used no solvent. The acetate of 1-dodecanol was obtained in 98% yield, and the acetate from 1 naphthol in 100% yield.183 The acylation of anisole with acetic anhydride at 100oC without solvent using zeolite H-/8 gave 4-methoxyacetophenone (6.30) in 98%yield.184 The catalyst could be recovered, regenerated, and reused with no decrease in yield. These reactions show that not all zeolites are used at high temperatures in the vapor phase. 

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

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. 

Thus, the Rhodia company developed and applied an industrial process for fhe acylation of anisole with acetic anhydride over BEA zeolite to selectively give para-acetylanisole. Furthermore, the reaction of isobutyl-benzene with the same acylating agent leads with high yield and selectivity to para-acetyl isobutylbenzene, which is an intermediate in the synthesis of ibuprofen, an important anti-inflammatory drug. ... 

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