Friedel-Crafts Reactions in Organic Synthesis

significant advances of Friedel-Crafts reaction have appeared, including the developments of new catalysis and methods for the efficient intermolecular and intramolecular reactions. Some recent examples will be accounted for in the following section, with an emphasis on the control of diastereoselectivity and enantioselectivity. 

SCHEME 10.20 Calcium-catalyzed intennolecular Friedel-Crafts alkylation with Jt-activated alcohols. 

SCHEME 10.21 Calcium-catalyzed intramolecular Friedel-Crafts alkylation with alcohols. 

SCHEME 10.23 Diastereoselective intennolecular Friedel-Crafts alkylation via chiral a-branched benzyUc carbocations. 

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Friedel-Crafts alkylations are among the most important reactions in organic synthesis. Solid acid catalysts have advantages in ease of product recovery, reduced waste streams, and reduction in corrosion and toxicity. In the past, people have used (pillared) clays (18), heteropolyacids (19) and zeohtes (20) for Friedel-Craft alkylations, with mixed success. Problems included poor catalyst stabihty and low activity. Benzylation of benzene using benzyl chloride is interesting for the preparation of substitutes of polychlorobenzene in the apphcation of dielectrics. The performance of Si-TUD-1 with different heteroatoms (Fe, Ga, Sn and Ti) was evaluated, and different levels of Fe inside Si-TUD-1 (denoted Fei, Fe2, Fes and Feio) were evaluated (21). The synthesis procedure of these materials was described in detail elsewhere (22). 

Heaney H (1991) The bimolecular aromatic Friedel-Crafts reaction. In Trost BM, Fleming I (eds) Comprehensive organic synthesis, vol 2. Pergamon, Oxford, p 733... 

S. C. Eyley, The Aliphatic Friedel-Crafts Reaction, in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 2, 707, Pergamon Press, Oxford, 1991. 

Pertinent examples of zeolite-catalyzed reactions in organic synthesis include Friedel-Crafts alkylations and acylations and other electrophilic aromatic substitutions, additions and eliminations, cyclizations, rearrangements and isomeriza-tions, and condensations. 

Introduction. The object of this and of the two following experiments is to illustrate the application of the Friedel-Crafts reaction to the synthesis of organic compounds. In the present experiment the preparation of aromatic hydrocarbons will be considered. 

The Friedel-Crafts reaction is an important reaction in organic synthesis and is widely used for the substitution of a side chain in an aromatic ring with AICI3 as catalyst. The reaction between benzene and phthalic anhydride, which constitutes a step in the preparation of anthraquinone, is one such reaction. We give below the chemist s and the chemical engineer s ways of looking at this reaction (see Rose, 1981, for a detailed discussion). ... 

Friedel-Crafts (FC) reaction is one of the most fundamental carbon-carbon bond-forming reactions in organic synthesis [243]. The reaction can be promoted by the presence of a Lewis acid, generally used in more than a stoichiometric amount to prevent the promoter deactivation by complexation to the ketone products. In spite of this thumb rule, a catalytic version of the FC reaction was developed using only 1 mol% TiCl(OTf)3 and 10 mol% TfOH in dichloromethane or acetonitrile, providing the acylated aromatic compounds with high regioselectivity [244] (Scheme 14.104). 

Asymmetric synthesis of organofluorine compounds is an important issue in pharmaceutical chemistry 1,2) and optoelectronic material science 3,4). In particular, asymmetric catalysis of carbon-carbon bond-forming reactions is the most attractive method, because the carbon skeleton of chiral organofluorine molecules can be constructed at the time of asymmetric induction 5-10). The Friedel-Crafts (F-C) reaction is one of the most fundamental carbon-carbon bondforming reactions in organic synthesis 11-14). However, its application to catalytic asymmetric synthesis has been quite limited (diastereoselective 25-22, enantioselective 23-25, stereospecific 2d,2. Herein, we report the catalytic... 

Stamatoff and Wittmann reported a synthesis of a 2-(4-phenoxyphenyl)hexa-duoroisopropanol in the presence of HF and an organic solvent via a Friedel-Crafts reaction, as shown in Scheme 6.29.231 The resulting polymer could be compression molded at 330-350°C. It also exhibited excellent thermostability and mechanical properties. 

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 is one of the most important and versatile tools for the formation of carbon-carbon bonds in the synthesis of substituted aromatic and heteroaromatic compounds present in numerous natural products and drugs. Catalytic asymmetric variants using either metal complexes or organic molecules attracted considerable attention over the last few years. 

Regarding acylation reactions, acylation of alcohols produces esters and acylation of amines produces amides Both of these transformations are illustrated in Figure 8.2. These, in addition to the introduction of acyl groups adjacent to carbonyls (Scheme 8.11), only hint at the breadth of related acylation reactions available and useful in organic synthesis. One additional reaction is the Friedel-Crafts acylation illustrated in Scheme 8.12. Through this transformation, extended functionalization of aryl groups becomes accessible. 

Solid acid catalysts are, in principle, applicable to a plethora of acid-promoted processes in organic synthesis [27-29]. These include various electrophilic aromatic substitutions, e.g. nitrations, and Friedel-Crafts alkylations and acylations, and numerous rearrangement reactions such as the Beckmann and Fries rearrangements. 

HPAs, however, is their solubility in polar solvents or reactants, such as water or ethanol, which severely limits their application as recyclable solid acid catalysts in the liquid phase. Nonetheless, they exhibit high thermal stability and have been applied in a variety of vapor phase processes for the production of petrochemicals, e.g. olefin hydration and reaction of acetic acid with ethylene [100, 101]. In order to overcome the problem of solubility in polar media, HPAs have been immobilized by occlusion in a silica matrix using the sol-gel technique [101]. For example, silica-occluded H3PW1204o was used as an insoluble solid acid catalyst in several liquid phase reactions such as ester hydrolysis, esterification, hydration and Friedel-Crafts alkylations [101]. HPAs have also been widely applied as catalysts in organic synthesis [102]. 

Owing to its powerful Lewis acidity, BF3 is an effective reagent in organic synthesis, for example, promoting the conversion of alcohols and acids to esters, the polymerization of olefins and olefin oxides, and acylations and alkylations (in a manner similar to Friedel-Crafts processes). Mechanistic studies of some reactions of the latter type, such as the ethylation of benzene by QH5F, have shown that the BF3 functions as a scavenger for HF via the formation of HBF4 and thus participates stoichiometrically rather than catalytically. 

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