Friedel Crafts with carboxylic anhydrides

In the Friedel-Crafts acylation, carboxylic acid chlorides and carboxylic acid anhydrides are activated with stoichiometric amounts of A1C13 (Section 5.2.7). However, this activation is only possible in the presence of very weak nucleophiles such as aromatic compounds. Stronger nucleophiles would react with the A1C13 instead of the carboxylic acid derivative. If one wants to acylate such stronger nucleophiles—for example, alcohols or amines—with car-... 

Izumi, J. and Mukaiyama, T. 1996. The catalytic Friedel-Crafts acylation reaction of aromatic compounds with carboxylic anhydrides using combined catalysts system of titanium(IV) chloride tris(trifluoromethanesulfonate) and trifluoromethanesulfonic acid. Chem. Lett. 739-740. 

Friedel-Crafts acylation (Section 12 7) An electrophilic aro matic substitution in which an aromatic compound reacts with an acyl chloride or a carboxylic acid anhydride in the presence of aluminum chlonde An acyl group becomes bonded to the nng... 

Diaryl sulfones can be formed by treatment of aromatic compounds with aryl sulfonyl chlorides and a Friedel-Crafts catalyst. This reaction is analogous to Friedel-Crafts acylation with carboxylic acid halides (11-14). In a better procedure, the aromatic compound is treated with an aryl sulfonic acid and P2O5 in polypho-sphoric acid. Still another method uses an arylsulfonic trifluoromethanesulfonic anhydride (ArS020S02CF3) (generated in situ from ArS02Br and CF3S03Ag) without a catalyst. ... 

Friedel-Crafts acylation can be carried out with cyclic anhydrides, in which case the product contains a carboxyl group in the side chain. When succinic... 

An alternative route to anthraquinone, which involves Friedel-Crafts acylation, is illustrated in Scheme 4.3. This route uses benzene and phthalic anhydride as starting materials. In the presence of aluminium(m) chloride, a Lewis acid catalyst, these compounds react to form 2-benzoyl-benzene-1-carboxylic acid, 74. The intermediate 74 is then heated with concentrated sulfuric acid under which conditions cyclisation to anthraquinone 52 takes place. Both stages of this reaction sequence involve Friedel-Crafts acylation reactions. In the first stage the reaction is inter-molecular, while the second step in which cyclisation takes place, involves an intramolecular reaction. In contrast to the oxidation route, the Friedel-Crafts route offers considerable versatility. A range of substituted... 

Almost every major structural class discussed to date has featured at least one nonsteroidal antiinflammatory carboxylic acid. It is thus perhaps not surprising to find a dibenzoheterocycle serving as the nucleus for one of these agents, furobufen (34). Straightforward Friedel-Crafts acylation of dibenzo-furan (33) with succinic anhydride affords a mixture of 2- and 3-acylated products, with the latter predominating. The mixture is esterified with methanol, and the methyl ester of the 3-isomer is separated by fractional crystallization. Hydrolysis back to the... 

Acyl-transfer reactions are some of the most important conversions in organic chemistry and biochemistry. Recent work has shown that adjacent cationic groups can also activate amides in acyl-transfer reactions. Friedel-Crafts acylations are known to proceed well with carboxylic acids, acid chlorides (and other halides), and acid anhydrides, but there are virtually no examples of acylations with simple amides.19 During studies related to unsaturated amides, we observed a cyclization reaction that is essentially an intramolecular acyl-transfer reaction involving an amide (eq 15). The indanone product is formed by a cyclization involving the dicationic species (40). To examine this further, the related amides 41 and 42 were studied in superacid promoted conversions (eqs 16-17). It was found that amide 42 leads to the indanone product while 41... 

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). 

Several other heterohelicenes resist this reaction even when the Friedel-Crafts catalyst (A1C13) is exchanged for FSOjH, 90% HjSO, 40% HF and other strong acids. Some dehydroheterohelicenes have been used to prepare heterocirculenes by a Diels-Alder reaction with maleic anhydride and subsequent hydrolysis and removal of the carboxylic acid groups167). 

Proton acids can be used as catalysts when the reagent is a carboxylic acid. The mixed carboxylic sulfonic anhydrides RCOOSO2CF3 are extremely reactive acylating agents and can smoothly acylate benzene without a catalyst.265 With active substrates (e.g., aryl ethers, fused-ring systems, thiophenes), Friedel-Crafts acylation can be carried out with very small amounts of catalyst, often just a trace, or even sometimes with no catalyst at all. Ferric chloride, iodine, zinc chloride, and iron are the most common catalysts when the reactions is carried out in this manner.266... 

Friedel-Crafts acylation can be carried out with cyclic anhydrides,272 in which case the product contains a carboxyl group in the side chain. When succinic anhydride is used, the product is ArCOCH2CH2COOH. This can be reduced (9-37) to A1CH2CH2CFLCOOH, which can then be cyclized by an internal Friedel-Crafts acylation. The total process is called the Haworth reaction 173... 

New Soluble Catalysts. Trifluoromethansulfonic acid (triflic acid, TfOH)42 and acyl triflates, that is mixed anhydrides of carboxylic acids and triflic acid,43 44 were first reported to be effective for Friedel-Crafts acylation in 1972. Significantly lower yields (<30%) were obtained with other Brpnsted acids. High activities were also observed for perfluorobutanesulfonic acid.37... 

Friedel-Crafts Acylation, The Friedel-Crafts acylation procedure is the most important method for preparing aromatic ketones and their derivatives. Acetyl chloride (acetic anhydride) reacts with benzene in the presence of aluminum chloride or acid catalysts to produce acetophenone [98-86-2], CgHgO (1-phenylethanone). Benzene can also be condensed with dicarboxylic acid anhydrides to yield benzoyl derivatives of carboxylic acids. These benzoyl derivatives are often used for constructing polycyclic molecules (Haworth reaction). For example, benzene reacts with succinic anhydride in the presence of aluminum chloride to produce p-benzoylpropionic acid [2051-95-8] which is converted into a-tetralone [529-34-0] (30). 

The acylation of thiophenes has been reviewed (86HC(44/3)309). The best catalyst for the Friedel-Crafts acylation of thiophene, using free carboxylic acids, appears to be 2-(trifhioromethylsulfonyloxy)pyridine (84) in conjunction with TFA. 2-Acylthiophene is formed in quantitative yield, without any evidence of the thiophene dimerizing. The reaction might be mediated by the mixed anhydride (85) (Scheme 15) (88BCJ455) (cf. (84CHEC-(4)74l)). 

B is correct. Scheme 1, step 1 shows an anhydride reacting with an aromatic ring in the presence of A1C1- to form a carboxylic acid and a ketone. This reaction has the same form. This is a Friedel-Crafts reaction. 

Although Friedel-Crafts acylation is well known with carboxylic acids, anhydrides, and acid halides, there are virtually no reports of Friedel-Crafts acylations being done with amides.63 These results demonstrate the application of distonic superelectrophiles to accomplish such a difficult... 

A total synthesis of dihydrolycorine (85), y-lycorane (87) and 8-lyco-rane (92), has been achieved starting from the indanone carboxylic acid 77. This, in turn, was obtained, like the tetralone ester 76, from the known anhydride (75) via Friedel-Crafts cyclization of the monomethyl esters obtained from 75 by treatment with 1 mole of methanol. Reduction of the methyl ester of 77 (LiAlH4), followed by Mn02 oxidation,... 

In a third microreactor, the anion of 4-ferf-butyl l-ethyl-2-(diethox-yphosphoryl)succinate was prepared in situ using sodium ethoxide 237 (in EtOH) and the Wittig-Horner olefination with benzaldehyde 116 performed using a residence time of 47 min to afford (E)-ferf-butyl-l-ethyl-2-benzylidenesuccinate 238 in excellent selectivity (89% yield). In a fourth reactor, the acid-catalyzed (TFA 239) ferf-butyl ester deprotection was achieved using a residence time of 5 min at 34 °C and employing DCM as the reaction solvent to afford (E)-3-(ethoxycarbonyl)-4-phenylbut-3-enoic acid 246 in 82% yield. The deprotection was subsequently followed by a Friedel-Crafts acylation, using triethylamine 14 and acetic anhydride 37, to afford 4-acetoxy-naphthalene-2-carboxylic acid ethyl ester 241 in quantitative yield when conducted at 130 °C (residence time = 47 min). 

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