Lewis acids catalytic Friedel-Crafts acylation

Against this background it is important that—quite fitting in this still new millennium— the first catalytic Friedel-Crafts acylations of (still relatively electron-rich) aromatic compounds were reported (Figure 5.35). Trifluoromethane sulfonates ( triflates ) of rare-earth metals, e. g., scandium(III)triflate, accomplish Friedel-Crafts acylations with amounts of as little as 1 mole percent. Something similar is true of the tris(trifluoromethanesulfonyl)-methides ( triflides ) of rare-earth metals. Unlike conventional Lewis acids, the cited rare-earth metal salts can form 1 1 complexes with the ketone produced, but these are so unstable that the Lewis acid can re-enter the reaction. Whether this works analogously for the third catalytic system of Figure 5.35 is unclear. 

As already underlined in the introduction to this book, catalytic homogeneous acylation reactions represent a remarkable improvement in the preparation of aromatic ketones because, in the conventional Lewis-acid-promoted reactions, formation of a stable complex between the ketone product and the catalyst implies that at least a stoichiometric amount of catalyst must be utilized. This drawback prompted a great number of studies aimed at setting up the experimental conditions to make catalytic Friedel-Crafts acylation reactions. Some positive results from fhe homogeneous catalytic Friedel-Crafts acylations are described here, with special attention to crucial economic and environmental advantages such as the recycling of expensive catalysts and the development of solvenf-free and highly selective synthetic processes. 

PoIysuIfonyIa.tlon, The polysulfonylation route to aromatic sulfone polymers was developed independendy by Minnesota Mining and Manufacturing (3M) and by Imperial Chemical Industries (ICI) at about the same time (81). In the polymerisation step, sulfone links are formed by reaction of an aromatic sulfonyl chloride with a second aromatic ring. The reaction is similar to the Friedel-Crafts acylation reaction. The key to development of sulfonylation as a polymerisation process was the discovery that, unlike the acylation reaction which requires equimolar amounts of aluminum chloride or other strong Lewis acids, sulfonylation can be accompHshed with only catalytic amounts of certain haUdes, eg, FeCl, SbCl, and InCl. The reaction is a typical electrophilic substitution by an arylsulfonium cation (eq. 13). 

Acidic chloroaluminate ionic liquids have already been described as both solvents and catalysts for reactions conventionally catalyzed by AICI3, such as catalytic Friedel-Crafts alkylation [35] or stoichiometric Friedel-Crafts acylation [36], in Section 5.1. In a very similar manner, Lewis-acidic transition metal complexes can form complex anions by reaction with organic halide salts. Seddon and co-workers, for example, patented a Friedel-Crafts acylation process based on an acidic chloro-ferrate ionic liquid catalyst [37]. 

In 2007, Womack et al. published the conversion of 2-aUcylcinnamyldehydes to 2-aLkylindanones via a catalytic intramolecular Friedel-Crafts reaction. In the presence of 5-10 mol% FeCls different in situ generated ( )-2-alkylcinnamaldehydes-derived dimethyl acetals cyclized to l-methoxy-2-aIkyl-7//-indenes in good to high yields (Scheme 6) [22]. The transformation corresponds to a formal intramolecular Friedel-Crafts acylation which is achieved with catalytic quantities of Lewis acid. This result is in strong contrast to traditional Friedel-Crafts acylations which require stoichiometric amounts of Lewis acid. 

Anthraquinone itself is traditionally available from the anthracene of coal tar by oxidation, often with chromic acid or nitric acid a more modern alternative method is that of air oxidation using vanadium(V) oxide as catalyst. Anthraquinone is also produced in the reaction of benzene with benzene-1,2-dicarboxylic anhydride (6.4 phthalic anhydride) using a Lewis acid catalyst, typically aluminium chloride. This Friedel-Crafts acylation gives o-benzoylbenzoic acid (6.5) which undergoes cyclodehydration when heated in concentrated sulphuric acid (Scheme 6.2). Phthalic anhydride is readily available from naphthalene or from 1,2-dimethylbenzene (o-xylene) by catalytic air oxidation. 

On the basis of these initial results, various rare earth metal triflates, including Sc(OTf)3, Hf(OTf)4 and Yb(OTf)3 were applied as catalysts [27-29]. Recently Beller and coworkers developed efficient Friedel-Crafts alkylations with catalytic amounts of Rh, W, Pd, Pt and Ir complexes [30] or FeCl3 [31-34] as Lewis acid catalysts. However, in the latter cases high catalyst loadings had to be applied. To overcome these major drawbacks, we decided to develop a Bi(III)-catalyzed Friedel-Crafts alkylation of arenes with benzyl alcohols. Although bismuth-catalyzed Friedel-Crafts acylations were well known at this time, Friedel-Crafts alkylations using benzyl alcohols had not been reported. 

A considerable difference between Friedel-Crafts alkylation and acylation is the amount of the Lewis acid necessary to induce the reaction. Friedel-Crafts alkylation requires the use of only catalytic amounts of the catalyst. Lewis acids, however, form complexes with the aromatic ketones, the products in Friedel-Crafts acylations, and the catalyst is thus continuously removed from the system as the reaction proceeds. To achieve complete conversion, therefore, it is necessary to use an equimolar amount of Lewis acid catalyst when the acylating agent is an acyl halide. Optimum yields can be obtained using a 1.1 molar excess of the catalyst. With... 

On the other hand, rare-earth trifluoromethanesulfonates (rare earth triflate, RE(OTf)3) have been found to work efficiently as Lewis acids even in aqueous media or in the presence of amines [4], A catalytic amount of RE(OTf)3 enables several synthetically useful reactions, for example aldol, Michael, allylation, Mannich, Diels-Alder reactions, etc., to proceed. It has also been demonstrated that a small amount of RE(OTf)3 is enough to complete the reactions and that RE(OTf)3 can easily be recovered from the reaction mixture and can be reused. A key to accomplishing the catalytic processes was assumed to be the equilibrium between Lewis acids and Lewis bases, for example water, carbonyl compounds, and amines, etc. A similar equilibrium was expected between Lewis adds and aromatic ketones, and, thus, RE(OTf)3-catalyzed Friedel-Crafts acylation was investigated [5]. 

It is well known that Friedel-Crafts acylation of aromatic compounds requires more than one equivalent of a Lewis acid relative to the substrate to bring the reaction to the completion, because the ketone produced deactivates the Lewis acid by complexation. Despite this, only 1 mol % TiCl(OTf)3 and 10 mol % TfOH in di-chloromethane or acetonitrile proved sufficient for the acylation shown in Eq. (175) this is, therefore, a catalytic Friedel-Crafts reaction [434]. The high regioselectivity obtained is also useful. 

The catalytic activity of ZrCk in acylation [11] and alkylation reactions [12] has been studied for more than half a century and compared with that of AICI3. More recently it has been found that Zr(OTf)4 and Hf(OTf)4 is sometimes an efficient catalyst in Friedel-Crafts acylation reactions [13], although the characteristics of the zirconium Lewis acid in this classical reaction, and the scope of the reaction, have not yet been extensively studied. 

New C—C bonds to arenes can be made by Friedel-Crafts reactions. Friedel-Crafts alkylations are traditionally executed with an alkyl chloride and catalytic AICI3 or an alkene and a strong Brpnsted or Lewis acid the key electrophilic species is a carbocation. Friedel-Crafts acylations are usually executed with an acyl chloride and an excess of AICI3 the key electrophilic species is an acylium ion (RC=0+). In the Bischler-Napieralski reaction, intramolecular attack on a nitrilium ion (RC=NR) occurs. 

Whereas the Friedel-Crafts alkylations require only catalytic quantities of the Lewis acidic AICI3 catalyst, Friedel-Crafts acylations of phenols require excess Lewis acids, due to the complex formation of the Lewis acids with the hydroxyl group . Boron trifluoride-phosphoryl chloride, in stoichiometric amounts, is used for the Fridel-Crafts reaction of phenol with /3,/S-dimethylacrylic acid to give the acrylophenone. ... 

Phenols are C-acylated either by electrophilic substitution under acidic conditions or by nucleophilic acylation under basic conditions. Advances in the chemistry of strong acids and Lewis acids provided novel aspects to catalytic Fries rearrangement and Friedel-Crafts acylation. Effenberger and Gutermann used a catalytic amount of... 

Bismuth(lll) salts such as BiCls, BiBrj, Bi(OCOR)3, and Bi (OTf), [166] have been widely used as Lewis acid catalysts to mediate C-C bond formation. Bi (OTf) 3, Bi2O3, and BiCl, catalyze Friedel-Crafts acylation with acyl chlorides or acid anhydrides [167]. Both electron-rich and electron-deficient arenes are acylated in high yields under catalysis by Bi(OTf)3 (Scheme 14.82). Under microwave irradiation the catalytic activity of BiX3 (X = C1, OTf) in the acylation of aromatic ethers is enhanced [168]. The N-acyl group of p-substituted anilides migrates to the ortho position of the aromatic nucleus under BiCls catalysis [169]. Treatment of 2,3-dichloroanisole with the ethyl glyoxylate polymer in the presence of a catalytic amount of Bi(OTf)3 affords an a,a-diarylacetic acid ester quantitatively (Scheme 14.83) [170]. 

To resolve the effluent problem, much work has been performed investigating the conditions or catalysts that enable the Friedel-Crafts acylation to be performed with catalytic quantities of Lewis acid. 

The Friedel-Crafts acylation with catalytic quantities of Lewis acid requires a knowledge of the equilibria (2) and (5). 

Hard Lewis acid chloroaluminate ionic liquids show intense catalytic activity in the Friedel-Crafts acylation reaction however, they suffer from the same issues as anhydrous aluminum chloride. i Of particular interest to these reactions, aluminum chloride may be replaced by indium trichloride to form chloroindate(III) ionic liquids. The advantage of using indium trichloride compared with aluminum chloride is represented by its hydrolytic stability and reduced oxophilicity. Chloroindate(III) ionic liquids are synthesized by mixing l-butyl-3-methylimidazolium chloride [C4mim]Cl with anhydrous indium trichloride at 80°C. In the benzoyla-tion of anisole with benzoic anhydride (BAN) at 80°C, the best yield of... 

Late-transition metal salts have been utilized as catalysts to promote Friedel-Crafts acylation of arenes and heteroarenes with anhydrides. A mismatch between their soft metal center and the hard carbonyl oxygen atoms of the products avoids the formation of a kinetically inert complex and results in catalytic turnovers. Although late-transition metal salts exhibit, a priori, rather poor Lewis acidity, sufficient reactivity can be gained by rendering them cationic. The acylation of variously substituted... 

The preparation and use of indium trichloride, gallium trichloride, and zinc chloride supported on MCM-41 as Lewis acids in the Friedel-Crafts acylation of aromatics with acyl chlorides was investigated. The support itself shows no catalytic activity in the benzoylation of benzene with BC, whereas the highest activity is showed by the supported indium trichloride. The order for acylation activity of the supported metal chloride (indium trichloride > gallium trichloride zinc chloride) is quite similar to that of the redox potential of the metals [E , +/, (-0.34 V) > E°Ga /Ga ( 0.53 V) > E 2n +/zn ( 0.74 V)] and confirms a possible relationship between the redox potential and the catalytic activity of the supported metal chloride. The reaction can be efficiently applied to a variety of aromatic compounds, including toluene, para-xylene, mesitylene, anisole, and 2-MN (70%-90% yield), confirming the moisture insensitivity of the catalyst. ... 

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