Friedel-Crafts reaction, fine chemical

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. 

In addition to large-scale industrial applications, solid acids, such as amorphous silica-alumina, zeolites, heteropoly acids, and sulfated zirconia, are also versatile catalysts in various hydrocarbon transformations. Zeolites are useful catalysts in fine-chemical production (Friedel-Crafts reactions, heterosubstitution).165-168 Heteropoly compounds have already found industrial application in Japan, for example, in the manufacture of butanols through the hydration of butenes.169 These are water tolerant, versatile solid-phase catalysts and may be used in both acidic and oxidation processes, and operate as bifunctional catalysts in combination with noble metals.158,170-174 Sulfated zirconia and its modified versions are promising candidates for industrial processes if the problem of deactivation/reactivation is solved.175-178... 

A monograph by Sheldon and van Bekkum gives a detailed treatment of heterogeneous catalytic processes applied in the fine-chemical industry.179 Clay materials proved to be extremely useful catalysts in organic chemistry.180,181 A particular example is clayzic,161,182 a highly active catalyst in various Friedel-Crafts reactions. 

The Friedel-Crafts reaction and the related Fries rearrangement of aromatics are the most important methods in organic chemistry for synthesizing aromatic ketones, which are of interest in the synthesis of numerous fine chemicals such as drugs, fragrances, dyes and pesticides. 

As mentioned earlier, supercritical fluids have a broad potential for application in new processes. In recent years a number of publications reviewed the role of supercritical fluids in technical applications [9-16], and more industrial applications of sc-fluids were established in the synthesis of fine chemicals. In a variety of reactions such as hydrogenations, hydroformylations and Friedel-Crafts reactions, the advantageous use of sc-fluids as solvents has been demonstrated with respect to yield, selectivities, and no work-up procedure [17]. 

Since initiation with conventional Friedel-Crafts halides cannot be controlled, the fine-tuning of reactions becomes extremely cumbersome. In contrast, by the use of alkylaluminum compounds elementary events (initiation, termination, transfer) become controllable and thus molecular engineering becomes possible. Indeed, by elucidating the mechanism of initiation etc., a large variety of new materials, i.e., block3, graft4-6 bigraft7 copolymers, have been synthesized and some of their physical-chemical properties determined. 

Friedel-Crafts acylation is widely used for the production of aromatic ketones applied as intermediates in both fine chemicals and pharmaceutical industries. The reaction is carried out by using conventional homogenous catalysts, which represents significant technical and environmental problems. The present work reports the results obtained in the Friedel-Crafts acylation of aromatic substrates (anisole and 2-methoxynaphthalene) catalyzed by Beta zeolite obtained by crystallization of silanized seeds. This material exhibits hierarchical porosity and enhanced textural properties. For the anisole acylation, the catalytic activity over the conventional Beta zeolite is slightly higher than with the modified Beta material, probably due to the relatively small size of this substrate and the weaker acidity of the last sample. However, the opposite occurred in the acylation of a bulky substrate (2-methoxynaphthalene), with the modified Beta showing a higher conversion. This result is interpreted due to the presence of a hierarchical porosity in this material, which favors the accessibility to the active sites. 

The Friedel-Crafts acylation of aromatic compounds is an important synthesis route to aromatic ketones in the production of fine and specialty chemicals. Industrially this is performed by reaction of an aromatic compound with a carboxylic acid or derivative e.g. acid anhydride in the presence of an acid catalyst. Commonly, either Lewis acids e.g. AICI3, strong mineral acids or solid acids e.g. zeolites, clays are used as catalysts however, in many cases this gives rise to substantial waste and corrosion difficulties. High reaction temperatures are often required which may lead to diminished product yields as a result of byproduct formation. Several studies detail the use of zeolites for this reaction (1). 

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. 

Aromatic ketones are important intermediates in the production of fine chemicals and pharmaceuticals1,2. Thus, the anti-rheumatic Naproxen is produced by the Friedel-Crafts acetylation of 2-methoxynaphthalene into 2-acetyl-6-methoxynaphthalene and subsequent Willgerodt-Kindler reaction. Commercial acylation processes involve over-stoechiometric amounts of metal chlorides (e g. AICI3) as catalysts and acid chlorides as acylating agents, which results in a substantial formation of by-products and in corrosion problems. This is why the substitution of these corrosive catalysts by solid acid catalysts and of acid chlorides by anhydrides or acids is particularly desirable. 

As was emphasized in the introduction, the main cause of the significant waste production in the Fine Chemicals Industry (5 > 50 kg/kg product (1)) is the large use of homogeneous reactions carried out stoichiometrically or by using stoichiometric amounts of catalysts (e.g. A1C13 in Friedel Crafts acylation). The examples presented in this chapter show that cleaner, more simple and more economic processes using solid catalysts, especially zeolites, can be substituted for these... 

Another catalytic methodology that is widely used for C-C bond formation is the Heck and related coupling reactions [86, 87]. The Heck reaction [88] involves the palladium-catalysed arylation of olefinic double bonds (Fig. 1.31) and provides an alternative to Friedel-Crafts alkylations or acylations for attaching carbon fragments to aromatic rings. The reaction has broad scope and is currently being widely applied in the pharmaceutical and fine chemical industries. For example, Albemarle has developed a new process for the synthesis of the anti-in-... 

Stephan, M. S., De Vries, J. G. Homogeneous catalysis for fine chemicals The Heck reaction as a clean alternative for Friedel-Crafts... 

Besides only as green reaction media, ionic liquids as dual green solvents and catalysts are also widely used in acylation reactions, especially C-acylation. Benzophenone and its derivatives are important fine chemicals or intermediates in dyes, pharmaceuticals, and other chemical industries. Li et al. have studied the Friedel-Crafts acylation reactions using ionic liquids like BMlMCl-FeClj, BMIMCI-AICI3, and BMIMCl-ZnCl as dual catalyst-solvent to synthesize benzophenone and its derivatives. They found that BMIMCl-FeCl3 showed much higher catalytic activity than that observed for the other two ionic liquids, and in conventional organic... 

Research to develop new specific catalysts for fine chemicals must be applicable to a range of products and cannot be limited to only one compound. Furthermore, since development time is limited, the chemical feasibility of the reaction must be demonstrated in advance. Since synthesis of fine chemicals has not been fully studied up to now, there is a unique opportunity to review classical organic chemistry and to find and develop new selective catalysts for key reactions. Since the reactions must be general careful choice of reactions to investigate is key to success. We have demonstrated that for important reactions such as Friedel-Crafts, Carbonylation, Reductions and oxidations, it is possible to develop new catalysts for the selective synthesis of fine chemicals. 

The Friedel-Crafts acylation is an important reaction in the synthesis of many fine chemicals (e. g. pharmaceuticals, fragrances, and agrochemicals). In syntheses of... 

Solid-acid catalysts have now found successful large-scale application in heterogeneous Friedel-Crafts type reactions, especially for the production of bulk chemicals. This field is now rapidly expanding to the area of fine chemicals. 

Maximum effort has been directed toward the use of solid acid catalysts. In fact, heterogeneous catalysts can be easily separated from the reaction mixture and reused they are generally not corrosive and do not produce problematic side products. Different classes of materials have been studied and utilized as heterogeneous catalysts for Friedel-Crafts acylations these include zeolites (acid treated), metal oxides, and heteropoly acids already utilized in hydrocarbon reactions. Moreover, the application of clays, perfluorinated resinsulfonic acids, and supported (fluoro) sulfonic acids, mainly exploited in the production of fine chemicals, are the subject of intensive studies in this area. 

Owing to the great interest in the argument, minireviews have been published on the use of solid catalysts in Friedel-Crafts acylation. Kouwen-hoven and van Bekkum, in a chapter of the Handbook of Heterogeneous Catalysis, faced the basic problem of the use of zeolites in the reaction. A further essential overview of the same argument was reported by Metivier in Fine Chemicals through Heterogeneous Catalysis Furthermore, Bezouhanova described the synthetic aspects of the zeolite-catalyzed preparation of aromatic ketones. ... 

Acylation of aromatic compounds is a widely used reaction for the production of fine chemicals. The classic methodology for acylation is Friedel-Crafts, this uses stoichiometric amounts of Lewis acids, such as metal halides, but some Bronsted acids, such as polyphosphoric and sulphuric acid, can also be used as catalysts. Moreover, the reaction is carried out homogeneously and the catalyst must be destroyed to obtain the final products, generating a great amount of corrosive and toxic waste. 

A number of reactions relevant to fine chemicals manufacture can be catalyzed by superacids, for example, dehydration of carboxamides to nitriles, Friedel-Crafts alkylation and acylation, Fisher indole synthesis of coumarins, isomerization of limonene, condensation of hydroquinone with aniline, and esterification in general (Hino and Arata, 1980, 1985 Joshi and Rajadhyaksha, 1980 Rajadhyak-sha and Chaudhari, 1987 Kumbhar and Yadav, 1989 Rajadhyaksha and Joshi, 1991 Kumbhar et al., 1994). Two particularly important reactions are described here. 

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