4-methoxy Acetophenone With Zeolite Process

There are several means to maximize the yield in the desired monoalkylation product: high aromatic/ alkylation agent ratio, association of a transalkylation unit to the alkylation unit, and use of a shape selective zeolite as catalyst.

Figure 12.4 Ethylbenzene synthesis. Commercial processes. AlCl3 + HCl catalyst (1950): AlCl3 corrosivity and problems associated with safe handling and disposal. For one tonne of EB, consumption of 2-4 kg catalyst, 1 kg of HCl, and 5 kg of caustic solution with production of salts. Zeolite catalysts: (1) 1980 Mobil Badger vapor-phase process MFI (ZSM5) 370-420°C, 7-27 bar, B/CJ 5-20, WHSV 300-400 h"1, recycling of DEB, yield > 99.5%, cycle length: 1 year; high-energy efficiency. (2) 1995 EB Max liquid-phase process MWW (MCM22) 200°C, B/CJ 3.5, Yield > 99.9%, cycle length >3 years. Toward Cleaner Processes. AlCl3 was the first catalyst used for ethyl-benzene production, and nearly 40% of the ethylbenzene capacity still utilizes the AlCl3 process. There are serious problems due to the corrosivity of AlCl3 and to waste production (Figure.12.4). This has led most manufacturers to move toward zeolite catalyzed processes that do not present these inconveniencies. Figure 12.4 shows the significant improvements caused by the substitution of AlCl3 by the MFI zeolite (Mobil Badger process, 1980), and then by the MWW (MCM-22) zeolite (EB Max process, 1995). The Mobil Badger process operates in the vapor phase at a high temperature. One of the initial problems was the relatively fast deactivation of the MFI zeolite by coking with the need for frequent regenerations. This problem was solved in the second and third (1986, 1991) generations of processes, the cycle lengths passing from 60 days to more than one year. A very high ethylbenzene yield (>99.5%) can be obtained. Other advantages over the AlCl3 process were the recovery of practically all the heat of reaction (DH = "114 kJ.mol"1) as medium or low-pressure vapor, and the possibility to use dilute ethylene as feed. EB Max is a liquid-phase process. The MWW zeolite is very stable (cycle lengths > 3 years) and very selective to monoalkylate, which allows the process to use low feed ratios of benzene to ethylene. The undesired diethylbenzene products undergo transalkylation with benzene in an additional reactor operating either in liquid or in gas phase.21

Up to 10 years ago, cumene was essentially produced by isopropylation of benzene using solid phosphoric acid (SPA), actually phosphoric acid supported on kieselgur, or AlCl3 (for only a small number of plants). Small amounts of water have to be continuously fed to the reactor in order to maintain the desired level of activity; consequently, there is a continuous release of corrosive phosphoric acid. The other drawbacks of the SPA process deal with the disposal of the used catalyst as well as with the production of undesired bi- and triisopropyl benzenes (4-5 wt. %). Greener processes based on zeolite catalysts have been recently licensed by DOW (dealuminated mordenite), Enichem (BEA), and Mobil Badger (MWW). Higher cumene yields can be obtained owing to the attachment to the alkylation process of a transalkylation unit for converting the diisopropylbenzene by-product to cumene. Alkylation over the MWW Zeolite. The MWW (or MCM-22) zeolite developed by Mobil as catalyst for ethylbenzene and cumene production deserves particular attention. Indeed, this zeolite presents unique structural features (Figure 12.5). Its structure is constituted of three independent pore systems:21 large supercages (inner diameter of 7.1 A defined by a 12-member-ring [12-MR], height 18.2 A) each connected to six others through 10-MR apertures (4.0 A x 5.5 A), bidimensional sinusoidal channels (10-MR, 4.1 x 5.1 A),22 and large hemisupercages (7.1 A 0, 7.0 A) on the external surface?3

Acid sites were shown to be located in the three-pore system of protonated samples (HMWW), and methods were recently proposed for determining the distribution of these sites as well as their respective role in o-, m-, and p-xylene transformations.24 While xylene transformation was shown to occur in the three locations, benzene alkylation with ethylene was catalyzed by the acidic sites of the external hemicups only.25 Indeed, the activity for this reaction is completely suppressed by adding a base molecule (collidine) to the feed that is too bulky to enter the inner micropores. Moreover, adsorption experiments show that collidine does not influence the rate of ethylbenzene adsorption, so that the suppression of alkylation activity was not caused by pore mouth blocking.25

However, by using a model reaction (gas-phase toluene alkylation with propene) we have recently demonstrated26 that initially the protonic sites of the supercages catalyze the formation of heavy alkylaromatics, those of the sinusoidal channels, the transformation of the olefin through an oligomerization-cracking process, and the formation of a small amount of alkylaromatics. A large part of these alkylaromatics remain trapped within the inner micropores, causing a quasi-immediate blockage of their access by reactant molecules; this shows that only the protonic sites of the external hemicages seem to be active in ethylben-zene formation. The high selectivity of these sites to monoalkylates and their high

Mcm Structure
Figure 12.5 Pore structure of MCM22 (MWW).

stability are most likely due to the ease of desorption of product molecules from the large external hemicages.

12.2.3 Fine Chemicals Synthesis

Significant advances remain to be accomplished to make the fine chemical processes environmentally friendly: indeed, the so-called environmental factor27 that is, the ratio between the amounts of waste and product, is still between 5 and 50, that is, 50 to 500 times greater than in refining and petrochemicals. Of course, this is because the fine chemicals synthesis requires a significant number of chemical and separation steps, but also because most of the chemical steps are carried out in batch reactors in homogeneous phase, either stoichiometrically or by using acid catalysts such as H2SO4 or AlCl3. These acids, which are not reusable, have to be neutralized, which generates a large amount of valueless salts.

There is an urgent need to substitute cleaner technologies, such as those based on heterogeneous catalysis, for these polluting technologies. Indeed, solid catalysts such as zeolites offer many advantages, in particular, easy recovery of reaction products, safe handling, easy setup of continuous processes, and regenerability. Here we show that acid zeolites that, due to their shape-selective properties and the easy tailoring of their active sites and porosity, are the major catalysts in refining and petrochemicals should play a significant role in fine chemical synthesis in the near future.

However, some characteristics of the reactant and product (and solvent) molecules used in the reactions of fine chemical synthesis have to be considered: their large size, their low thermal stability, and their polarity. The small size of the micropores limits the use of zeolites to the synthesis of relatively small molecules; solutions to overstep this limitation have been found with the development of larger (mesoporous) molecular sieves and of nanocrystallite zeolites, the reaction then occurring on the large external surface. The low thermal stability of the molecules leads to operation at a low temperature, often in the liquid phase. Last, as will be shown in the first example (Section, the differences in polarity between reactant(s), product(s), and solvent molecules have to be considered for optimizing both the zeolite catalyst and the operating conditions. Acetylation of Arenes with Acetic Anhydride. Arylketones are generally prepared by acylation of aromatics or by the related Fries rearrangement. These ketones are important intermediates in the synthesis of fragrances of the musk type and of pharmaceuticals such as paracetamol, ibuprofen, and S-naproxen.28 Acylation processes are often carried out in the liquid phase by using batch reactors with corrosive metal chlorides, such as AlCl3 as catalysts and acid chlorides as acylating agents. A characteristic of this reaction is the formation of a stable 1:1 molar adduct with the catalyst, which generates serious environmental problems: use of more than a stoichiometric amount of the "catalyst," necessary hydrolysis of the adduct for recovering the desired ketone with ocho

destruction of the catalyst, and production of a large amount of HCl (more than 4 mol per mol of ketone produced) with corrosion problems and final production of valueless salts. All that makes the substitution of AlCl3 by acid zeolites highly desirable, and also that of acetyl chloride by acetic anhydride or acetic acid.

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, acety-lation 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.29 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.30 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.

Whatever the zeolite, 4-methoxyacetophenone is largely predominant (>98%), which indicates that this selective formation is not due to shape-selectivity effects, but is a characteristic of the reaction. In contrast, the selectivity of

Anisole Acetylation

2-methylnaphtalene (2-MN) acetylation depends very much on the zeolite employed: over FAU zeolites, acetylation of 2-MN occurs very selectively at the very active C1 position with formation of 1-acetyl-2 methoxynaphtalene (1-AMN), whereas with other large-pore zeolites with smaller-pore apertures (BEA, MTW, ITQ7), the desired 2-acetyl-6-methoxynaphtalene product, 2-AMN (precursor of the anti-inflammatory S-naproxen), also appears as a primary product. Moreover, at long reaction times, 1-AMN isomerizes into 2-AMN. This isomerization is much faster in the presence of 2-MN than in its absence, causing the following intermolecular (transacetylation) mechanism to be proposed:31

2-MN + 1-AMN -► 2-AMN + 2-MN

The location of 2-MN acetylation over HBEA zeolites was largely debated. Some authors claimed that the bulkier isomer (1-AMN) could be formed only on the external surface, and the linear one (2-AMN) both within the micropores and on the external surface, while other than that both isomers were essentially formed within the micropores. The second proposal seems to be more likely; indeed, adsorption experiments showed that 1-AMN could enter the micropores of HBEA and even those of MFI, a medium-pore zeolite.32

Kinetic studies of the acetylation of several arylethers were carried out over HBEA zeolites. The main conclusion is that the rate and stability of the reactions are determined by the competition between reactant(s) and product(s) molecules for adsorption within the zeolite micropores.28 This competition shows that the autoinhibition of arene acetylation, that is, the inhibition by the acetylated products, and also by the very polar acetic acid product is generally observed. This effect is much more pronounced with hydrophobic substrates such as methyl and fluoro aromatics than with hydrophilic substrates because of the larger difference in polarities between substrate and product molecules.

Various solutions to limit the negative effect of the polarity of the acetylated products were proposed:

• Choice of operating conditions favoring the adsorption of the reactant molecules and the desorption of the product molecules; fixed-bed reactor instead of batch reactor, high molar substrate/ acylating agent ratio, low conversion, high temperature, use of solvents with adequate polarities.

Acetoanisole Parsol

Acetoanisole Parsol






Chemical + Physical Steps



Aqueous effluents (t/t anisole)



Effluent composition (wt %)

h2o ai3+

68.7 5

99 0







Figure 12.7 Acetylation of anisole. Characteristics of the old (AlCl3) and new (HBEA) technologies.

Figure 12.7 Acetylation of anisole. Characteristics of the old (AlCl3) and new (HBEA) technologies.

• Adequate choice and adjustment of the zeolite characteristics, small path of diffusion (small crystallites, mesopores), good balance between hydrophobi-city and acidity.

Industrial processes were developed by Rhodia33 for the selective acetylation of anisole into 4-methylacetophenone and veratrole into 3,4-dimethoxyacetophenone, which are, respectively, precursors of Parsol, used for sun protection, and of Verbu-tin, a synergist for insecticides. In both cases, the substitution of the new technology (fixed-bed reactor, HBEA or HFAU zeolites as catalysts, acetic anhydride as acylating agent) for the old technology (batch reactor, AlCl3 as catalyst, and acet-ylchloride as acylating agent) constitutes a major environmental and economical breakthrough. The main improvements brought about by the new process of anisole acetylation are presented in Figure 12.7: this process is much simple, the consumption of water much smaller, and lower amounts of organic compounds and no mineral compounds in the aqueous effluents.28 One-Pot Multistep Synthesis of Ketones on Bifunctional Zeolite

Catalysts. One-pot multistep reactions constitute an elegant and efficient way to decrease the number of chemical and separation steps, hence, to develop greener synthesis processes. Bifunctional metal-acidic or metal-basic zeolite catalysts, which can be prepared easily with the desired properties (e.g., distribution of the different types of active sites, characteristics of the diffusion path) are good candidates for these reactions.

A widely studied example is the synthesis of various ketones or aldehydes, such as methylisobutylketone from acetone, cyclohexylcyclohexanone from cyclo-hexanone, 1,3-diphenylbutan-1-one from acetophenone, 2-ethylhexanal from n-butyraldehyde. Thus methyl isobutyl ketone (MIBK), which is used as a solvent for ink and lacquers, was previously prepared through the three-step catalytic process: base catalyzed production of diacetone alcohol (DA) by acetone aldoliza-tion, acid dehydration of DA into mesityl oxide (MO), then hydrogenation of MO on a Pd catalyst (Figure 12.8). Since acetone aldolization also occurs by acid catalysis, it is possible to synthesize MIBK in one apparent step by combining the acidic and hydrogenation functions. Most of the studies were carried out in the gas phase by using fixed-bed reactors.

The best yield and selectivity to MIBK were obtained with PdMFI:34 28 and 98% at 453 K or PdCsMFI:35 35 and 82%. Pd supported over large pore zeolites such as HFAU are much less selective. The main by-products are propane and 2-methylpentane resulting from three-step bifunctional catalytic transformations of acetone and methylisobutylketone, respectively (C=O hydrogenation, dehydration, and C=C hydrogenation).36 This is why Pd, which is known to be more selective for the desired hydrogenation of the C=C bond than for the hydrogenation of the C=O bond, is generally chosen. Diisobutyl ketone (DIBK) may also be formed from acetone and MIBK through a bifunctional scheme similar to the one involved in MIBK formation.36 The significance of the secondary reactions of MIBK (methylpentane and DIBK formation) can be significantly reduced by an adequate choice of the zeolite pore structure (preferentially tridimensional, to facilitate the desorption of MIBK) and of the crystallite size.

Pd supported overlarge-pore tridimensional acidic zeolites such as HFAU are the more active and selective catalysts for the synthesis of bulkier ketones. Thus, in a 0.2% Pd-HFAU catalyst, yield and selectivity from cyclohexanone of 23 and 75% can be obtained in cyclohexylcyclohexanone synthesis.37 Furthermore, the synthesis of aldehydes can only be made selective by joining the hydrogenating metallic sites (Pd) to basic sites (instead of acidic sites). Thus, 2-ethylhexanal, which is a component of perfumes and fragrances, can be synthesized with high yield and selectivity (64 and 91%, respectively) on a PdKX zeolite.38 Much lower yields and selectivities are obtained over nonzeolitic materials, such as Pd/MgO.

2 CHg C CHg -«- CHg 0 GH2 C CHg -^ C—OH 0 CHg -^ CH CH2 C CHg

3 DA


9 catalysts CH3X 9

Figure 12.8 Synthesis of methyl isobutyl ketone (MIBK) from acetone.

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  • ANDI
    How to make ethylbenzene process greener?
    8 years ago
  • eetu
    How the acylium ion formed from acetic acid and aceticanhydride?
    8 years ago
  • Kibra
    Is 4 methoxyacetophenone formation?
    8 years ago

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