Acyl with arenes

Friedel-Crafts acylations of arenes with RCOCl or anhydrides (RC—O—CR) in the presence of AICI3 give good yields of ketones. 

Cross-linked polystyrene can be acylated with aliphatic and aromatic acyl halides in the presence of A1C13 (Friedel-Crafts acylation, Table 12.1). This reaction has mainly been used for the functionalization of polystyrene-based supports, and only rarely for the modification of support-bound substrates. Electron-rich arenes (Entry 3, Table 12.1) or heteroarenes, such as indoles (Entry 5, Table 15.7), undergo smooth Friedel-Crafts acylation without severe deterioration of the support. Suitable solvents for Friedel-Crafts acylations of cross-linked polystyrene are tetrachloroethene [1], DCE [2], CS2 [3,4], nitrobenzene [5,6], and CC14 [7]. As in the bromination of polystyrene, Friedel-Crafts acylations at high temperatures (e.g. DCE, 83 °C, 15 min [2]) can lead to partial dealkylation of phenyl groups and yield a soluble polymer. 

The reaction that occurs with arenes and acid anhydrides in the presence of aluminum chloride is Friedel-Crafts acylation. The methoxy group is the more powerful activating substituent, so acylation occurs para to it. 

A complex of SbCls and benzyltriethylammonium chloride, which is insensitive to air and moisture, catalyzes the Friedel-Crafts acylation of arenes with acyl chlorides and sulfonyl chlorides (Equation (36)).69 The Diels-Alder reaction of toluquinone with 1,3-dienes is catalyzed by SbCl5 with high regioselectivity (Equation (37)).70... 

As can be seen in the scheme below, a series of substituted 2-(2-aminothiazol-4-yl)-benzo[ ]furans with inhibitory activity for leukotriene B4 were made from benzofurans via acylation, followed by Hantzsch thiazole formation <070BC3083>. 2-Substituted benzo[ ]furans could also be generated via an aerobic oxidative coupling of 2-unsubstituted benzo[ ]furans with arenes through the palladium-catalyzed double C-H activation <07OL3137>. In addition, 2,3-diarylbenzo h I uran could be constructed by a palladium-catalyzed arylation of benzo[6]furan with an aryl chloride in the presence of a bulky, and electron-rich phosphine <07OL1449>. 

With arenes bearing a single resonance donor substituent (NR2, OMe, F), the addition is strongly preferred at the meta position, with small amounts of ortho substitution (0-10%). " The meta acylation of anisole, using a carbonyl anion equivalent as the nucleophile, illustrates the unique regioselectivity available with the Cr(CO)3 activation (equation 115). ... 

The mixed anhydrides can also be formed in situ by the reaction of acyl halides with arenes catalyzed by trifluorosulfonic aeid. ... 

Acylation of Water (Hydrolysis) with Imidothioates, Thioorthoesters and Ketene S,S-Acetals Acylation of Arenes and Carbanions under Formation of Carbon-Carbon Bonds... 

Friedel-Crafts acylation of arenes (c/. Volume 2, Chapter 3.1) can be achieved with 5-aryl or 5-n-alkyl chlorothioformates in good to moderate yields (equation 30). ... 

Moreover, the selenol esters can acylate reactive arenes and heteroaromatic compounds when cop-per(I) triflate is employed as the selenophilic metal cation. - The acylation of aromatics by use of the benzene complex of copper(I) triflate (43 Scheme 12) was complete within an hour at room temperature, with benzene as solvent, and the acylation products were obtained in high yields. Intramolecular acylation was examined successfully, as shown in equation (20). 

The A-Boc group is rapidly removed on reaction with AlClj under microwave irradiation. Friedel-Crafts reactions. Both alkylation and acylation of arenes can be performed without solvent, by thoroughly grinding the reagents in an agate mortar and pestle at room temperature. (This technique is also applicable to Beckmann rearrangement of oximes in nearly quantitative yields. )... 

Friedel-Crafts acylation. Electron-rich arenes undergo acylation with AcCl using Zn as promoter. 

Direct tri-0-alkylation of calix[4]arenes has been reported to lead to the syn/syn isomer using bases such as BaO, BaO/Ba(OH)2 or CaH2 in DMF " . The tribenzoate of the p-unsubstituted calix[4]arene, one of the first examples of selectively derivatized calix[4]arenes, was obtained as the anti-syn isomer (benzoyl chloride/pyridine) , while the tribenzoate of 2a obtained in toluene with iV-methylimidazole as base (70% yield) was described as the syn-syn isomer, assuming a partial cone conformation with an inverted phenol ring . Both tris(3,5-dinitrobenzoates) of 2a were obtained by acylation with 3,5-dinitrobenzoyl chloride/l-methylimidazole. While 95% of the syn-syn isomer was formed in acetonitrile, 70% of the anti-syn isomer was obtained in chloroform . 

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]. 

Benzoylation under Friedel-Crafts acylation is an important process for the preparation of many industrially valuable chemicals. However, like the acetylation, the use of conventional Lewis acids, for example, AICI3, ZnCl2, and so on, in the homogeneous Friedel-Crafts acylation of arenes entails problems of materials due to corrosion work up and effluent issues. Thus, for benzoylation, as with acetylation, the use of heterogeneous catalysts seems to be an interesting alternative technique to the homogeneous reaction. 

The acylation of arenes with succinic and phthalic anhydrides in a chloroaluminate ionic liquid gives the corresponding ketoacids in good yields (50%-95%). The system follows a fypical elecfrophilic behavior, and lower yields are achieved with election-poor aromatics. ... 

Different patents have been registered concerning the preparation of specific aryl ketones by Friedel-Crafts acylation of convenient aromatic substrates in the presence of variable amounts of both Bronsted and Lewis acids. As an example, a large number of aryl ketones was efficiently synthesized through acylation of arenes with acyl chlorides in methylene chloride and in the presence of a mixture of aluminum chloride and lithium chloride as the catalyst. Some synthetic results are reported in Table 2.3. 

Galli, C. 1979. Acylation of arenes and heteroarenes with in situ generated acyl trifluoroacetates. Synthesis 303-304. 

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... 

Ytterbium(lll) tris(perfluoroalkanesulfonyl)methides 34 are effective catalysts (10% mol) for the Friedel-Crafts acylation of arenes with anhydrides. Compounds 34 can be prepared as described in Scheme 3.7. Trimethylsilylmethyl lithium 31 is reacted with commercially available per-fluoroalkanesulfonyl fluorides, giving intermediates 32 that can similarly produce tris-perfluoroalkanesulfonyl derivatives 33. These compounds are converted into the catalysts 34 by reaction with ytterbium oxide. It is shown that the highly fluorinated catalyst (34, Ri = C5F13, = C8F17) (10% mol)... 

Bromopentacarbonylrhenium(I) [ReBr(CO)5] promotes the Friedel-Crafts acylation of arenes with acyl chlorides. Toluene rmdergoes benzoy-lation with BC in the presence of the rhenium-based catalyst (0.1% mol), affording a mixture of ortho-, meta-, and para-methylbenzophenones in 91% yield (11 4 85 molar ratio). The yield decreases to 72% when using the same catalyst in a lower amount (0.01% mol). The process can be applied to different acyl chlorides, giving the corresponding ketones a satisfactory to high yield (Table 3.17). 

Thanks to their low cost and easy availability, many metal-exchanged clays have been patented as efficient solid catalysts in Friedel-Crafts acylation reactions. A great number of arylketones is prepared by electrophilic acylation of arenes with anhydrides in the presence of ion-exchanged clays at 150°C-250°C. Thus, for example, aluminum-enriched mica promotes the reaction of BAN with mcto-xylene at reflux for 4 h in 99% yield. 

The Fries rearrangement of phenyl- and 1-naphthyl esters can be efficiently performed in the presence of hafnium triflate. The method is based on the one previously described for the Friedel-Crafts acylation of arenes with acyl chlorides. The reaction occurs in toluene-nitromethane mixtures at 100°C for 6 h. Several examples of this Fries isomerization with synthetic application are reported in Table 5.5. In all cases, complete regioselectivity is obtained, and 2-acylated phenol or naphthol derivatives are isolated in good yields. 

Friedel-Crafts acylation. Using the AgC104-SiCl4 combination as catalyst, the acylation of arenes with free carboxylic acids and an aroic anhydride proceeds via the mixed anhydrides. 

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