Friedel-Crafts reaction, fine chemical synthesis

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. 

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]. 

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). 

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-... 

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... 

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. 

Even though the catalytic systens described iu the preceding sections provide greater practicality than stoichiometric systens, their application in industrial synthesis is not widespread. However, in more recent times, 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 (HPAs) already utilized in the hydrocarbon reactions [24]. Moreover, the application of clays, perfluorinated resin-sulfonic acids, and supported (fluoro) sulfonic acids, mainly exploited in the production of fine chemicals, is the subject of intensive studies in this area. 

D. Baudry-Barbier studied the catalytic properties of Sc, La and Nd modified KIO clays in Friedel-Crafts acylations of anisole with benzoyl chloride for yielding 4-methoxybenzophenone, and found La modified KIO clay exhibited the best catalytic activity for acylations of anisole. In comparison with the acid catalyzed reactions using liquid acids, the solid acid catalyzed process was non-polluting and also the final work-up didn t require any aqueous treatment, which exhibited wide prospect for the clean synthesis of building block and fine chemicals [195]. 

---