Friedel benzoylation

Prepared by the dehydration of benzamide. Hydrolysed by dilute acids and alkalis to benzoic acid. Good solvent. benzopheDone,C]3HioO,PhC(0)Ph. Colourless rhombic prisms, m.p. 49 C, b.p. 306°C. Characteristic smell. It is prepared by the action of benzoyl chloride upon benzene in the presence of aluminium chloride (Friedel-Crafts reaction) or by the oxidation of di-phenylmethane. It is much used in perfumery. Forms a kelyl with sodium. 

Hydroxy-4-methylthiazole failed to react when submitted to Friedel-Crafts benzoylation conditions (349) on the other hand, it reacted normally in Gattermann and in Reimer-Tiemann formylation reactions, affording the 5-formyl derivative (348). 4-Methylthiazole is insufficiently activated and fails to react under the same conditions. 2,4-Dimethylthiazole undergoes perfluoroalkylation when heated at 200° for 8 hr in a sealed tube with perfluoropropyl iodide and sodium acetate (116) (358). 

Friedel-Crafts acylation of benzene with benzoyl chloride (CgH5CCl) (j) Nitration of the product from part (1)... 

Benzophenone is produced by the oxidation of diphenylmethane (350). This free from chlorine (FCC) route is favored for perfume uses. The Friedel-Crafts reaction of benzene and benzoyl chloride in the presence of aluminum chloride is also possible this reaction may proceed in the absence of catalyst at a temperature of 370°C and pressure of 1.4 MPa (351). 

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

Benzoyl chloride is an important benzoylating agent. In this use the benzoyl radical is introduced into alcohols, phenols, amines, and other compounds through the Friedel-Crafts reaction and the Schotten-Baumaim reaction. Other significant uses are in the production of benzoyl peroxide [94-56-0], benzophenone [119-61-9], and in derivatives employed in the fields of dyes, resins, perfumes, pharmaceuticals, and as polymerization catalysts. 

Thiophene is also readily acylated under both Friedel-Crafts and Vilsmeier-Haack conditions and similarly to pyrrole and furan gives 2-acylated products. An almost quantitative conversion of thiophene into its 2-benzoyl derivative is obtained by reaction with 2-benzoyloxypyridine and trifluoroacetic acid. The attempted preparation of 2-benzoylthiophene under standard Friedel-Crafts conditions, however, failed (80S139). 

The oxygen atom in these molecules can in many cases be dispensed with as well substitution of sulfur for nitrogen affords a molecule whose salient biologic properties are those of a sedative and tranquilizer. Friedel-Crafts acylation of the n-butyl ether of thiophenol with benzoyl chloride gives the corresponding benzophenone. Reduction of the ketone (15) followed by... 

Friedel-Crafts alkylations and acylations of N-arylamides also proceed normally. For example, benzoylation of acetanilide (iV-acetylaniline) under Friedel-Crafts conditions gives 4-aminobenzophenone in 80% yield after hydrolysis. 

Unlike alkylation, Friedel-Crafts acylation has been generally considered to be irreversible, but a number of instances of electrofugal acyl groups have been reported, especially where there are two ortho substituents, for example the hydro-de-benzoylation of 42. ... 

Because activated 4-0-trimethylsilylated-2, 3, 5 -0-acyluridines such as 3 are also obtained as reactive intermediates in the Friedel-Crafts-catalyzed silyl-Hilbert-Johnson reaction [59, 59 a] of persilylated uracils or 6-azauracils such as 227 with sugars such as l-0-acetyl-2,3,5-tri-0-benzoyl-/9-D-ribofuranose 228 in the presence of SnCl4, treatment of the reactive intermediate 229 with a large excess of pyrrolidine neutralizes the SnCLi. used and aminates 229 to afford the protected 6-aza-cytidine 230, although in 57% yield only [49, 59] (Scheme 4.20). 

Olah et al. (1999) have been able to realize selective cyclisation of o-benzoyl benzoic acid to anthraquinone using dichlorobenzene as a solvent and Nafion-H as a catalyst. This may lead to avoidance of the Friedel-Crafts reaction using a stoichiometric amount of aluminium chloride and resulting in a lot of wa,ste. Many other examples of similar reactions have been reported. 

Friedel-Crafts reaction with benzoyl chloride... 

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... 

Sometimes acylium ions lose carbon monoxide to generate an ordinary carbonium ion. It will be recalled that free acyl radicals exhibit similar behavior at high temperatures. Whether or not the loss of carbon monoxide takes place seems to depend on the stability of the resulting carbonium ion and on the speed with which the acylium ion is removed by competing reactions. Thus no decarbonylation is observed in Friedel-Crafts reactions of benzoyl chloride, the phenyl cation being rather unstable. But attempts to make pivaloyl benzene by the Friedel-Crafts reaction produce tert-butyl benzene instead. With compound XLIV cyclization competes with decarbonylation, but this competition is not successful in the case of compound XLV in which the ring is deactivated.263... 

Benzophenones are usually attached as a complete photophore. Apart from the standard chemical techniques, new C-C coupling procedures extend the synthetic repertoire. However, in some cases direct benzoylation (e.g., Friedel-Crafts acylation) of aromatic or heteroaromatic rings can provide an easy access to BP or BP-like photophores (Scheme 4D) [38,39]. 

Two years after the discovery of the first asymmetric Br0nsted acid-catalyzed Friedel-Crafts alkylation, the You group extended this transformation to the use of indoles as heteroaromatic nucleophiles (Scheme 11). iV-Sulfonylated aldimines 28 are activated with the help of catalytic amounts of BINOL phosphate (5)-3k (10 mol%, R = 1-naphthyl) for the reaction with unprotected indoles 29 to provide 3-indolyl amines 30 in good yields (56-94%) together with excellent enantioselec-tivities (58 to >99% ee) [21], Antilla and coworkers demonstrated that A-benzoyl-protected aldimines can be employed as electrophiles for the addition of iV-benzylated indoles with similar efficiencies [22]. Both protocols tolerate several aryl imines and a variety of substituents at the indole moiety. In addition, one example of the use of an aliphatic imine (56%, 58% ee) was presented. 

Moreover, phosphoric acid (5)-3r (5 mol%, R = SiPhj) bearing a bulky triphe-nylsilyl group turned out to be a suitable catalyst for the asymmetric Friedel-Crafts alkylation of iV-alkyl pyrroles 31 with M-benzoyl-protected aldimines 32 (Scheme 12) [23]. 2-Pyrrolyl amines 33 were obtained in high yields (66-97%) and moderate to high enantioselectivities (42 to >99% ee). 

Hardacre et al. report the Friedel-Crafts benzoylation of anisole with benzoic anhydride to yield 4-methoxybenzophenone with various ILs and zeolite catalysts (USY, HZSM-5, H-beta, and H-mordenite). The rates of reaction were found to be significantly higher using ionic liquids compared with organic solvents.Continuous-flow studies of successful ionic liquid systems indicate that the bulk of the catalysis is due to the formation of an acid via the ion exchange of the cation with the protons of the zeolite as shown in the following reaction. Scheme 8. 

The acylation of dibenzofuran is carried out under the usual Friedel-Crafts conditions with an acid chloride or an acid anhydride in the presence of aluminum chloride. Dibenzofuran on treatment with 2-trifluoromethane-sulfonyloxypyridine and benzoic acid in boiling trifluoroacetic acid produces the 2-benzoyl derivative in 75% yield. The species responsible for benzoyla-tion is probably a mixed anhydride of trifluoromethanesulfonic acid and benzoic acid. Dibenzofuran on treatment with 2-benzoyloxypyridine and trifluoroacetic acid also produces the 2-benzoyl compound (21%). The kinetics of the acetylation of dibenzofuran with acetyl chloride and aluminum chloride in nitroethane at 25"C have been studied. Only the 2-acetyl compound was detected by the methods used. The rate obtained is in general agreement with the studies mentioned previously. The rate of acetylation of diphenyl ether relative to toluene was 138 (+ 16), whereas that of dibenzofuran was 5.9 ( 0.3). In contrast, the benzoylation of dibenzofuran with benzoyl chloride in the presence of aluminum chloride in nitrobenzene at... 

A -Acylamino aromatic ketones 790 can be prepared by arylation of saturated oxazolones in the presence of Lewis acids. Cyclodehydration of 790 leads to 2,5-diaryloxazoles 791. For example, saturated 5(4//)-oxazolones 789 from 7/-benzoyl-alanine or A-benzoylvaline undergo Friedel-Crafts arylation to afford substituted A-benzoylphenacylamines 790. In the presence of POCI3, 790 cyclizes to produce 5-aryl-2-phenyloxazoles 791 (Scheme 7.241). ... 

The data clearly indicate that the only primary product was phenylbenzoate, while all the other compounds formed by consecutive reactions upon the ester. Therefore, the scheme of reaction is that one summarized in Figure 3. The formation of the ester as the only primary product represents one important difference with respect to the Friedel-Crafts benzoylation of phenol with benzoylchloride or benzyltrichloride, catalyzed by AICI3. In the latter case, in fact, the product of para-C-acylation (p-hydroxybenzophenone) is the main product of reaction this is due to the fact that AICI3 coordinates with the 0 atom of the hydroxy group in phenol, and makes it less available for the ester formation, due to both electronic and steric reasons. 

Friedel-Crafts acylation fails with quinoline, isoquinoline, acridine and many derivatives. However, when sufficient activation is present substitution can result. For example, 8-methoxyquinoline (28) in the presence of aluminum chloride and acetyl or benzoyl chloride gives the 5-acetyl and 5-benzoyl derivatives in 25% and 35% yields respectively. 

When (190) was subjected to a Friedel-Crafts reaction with benzoyl chloride, the result was an analog of coralyne with a phenyl rather than a methyl group at position 8. Kametani et al. (74YZ478) have carried out a parallel study using the Vilsmeier-Haack reaction to produce norcoralyne. 

Rhodium acetylacetonate differed considerably from the other metal chelates in the acetylation reaction (26). Under the same conditions that had given extensive acetylation of the cobalt and chromium acetylacetonates, the rhodium chelate reacted very slowly and formed only a small amount of the monoacetylated compound (XX). Fortunately, the hydrolytic stability of rhodium acetylacetonate is such that the Friedel-Crafts reaction can be carried out under vigorous conditions that would rapidly degrade the chromium and cobalt chelates. Thus treatment of rhodium acetylacetonate with acetyl chloride and aluminum chloride in dichloroethane afforded the mono- and diacetylated chelates (XX and XXI). No triacetylated chelate was isolated from this reaction. In a similar manner butyryl-and benzoyl-substituted rhodium chelates (XXIII and XXIV) have been prepared. These and other experiments indicate that the rhodium acetylacetonate ring is less reactive than the cobalt or chromium rings. 

The monomers described so far have all been prepared by starting with 4-bromobenzocyclobutene, 2. A different approach to the preparation of monomers begins with the parent hydrocarbon benzocyclobutene 1 by carrying out electrophilic aromatic substitution reactions [36]. Benzocyclobutene readily undergoes a Friedel-Crafts benzoylation reaction with a variety of substituted acid chlorides (Fig. 7). 

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