Acetic anhydride Friedel-Crafts reaction with

Acetic anhydride can be used to synthesize methyl ketones in Friedel-Crafts reactions. For example, benzene [71-43-2] can be acetylated to furnish acetophenone [98-86-2]. Ketones can be converted to their enol acetates and aldehydes to their alkyUdene diacetates. Acetaldehyde reacts with acetic anhydride to yield ethyhdene diacetate [542-10-9] (18) ... 

Although all four tocopherols have been synthesized as their all-rac forms, the commercially significant form of tocopherol is i7//-n7i a-tocopheryl acetate. The commercial processes ia use are based on the work reported by several groups ia 1938 (15—17). These processes utilize a Friedel-Crafts-type condensation of 2,3,5-trimethylhydroquinone with either phytol (16), a phytyl haUde (7,16,17), or phytadiene (7). The principal synthesis (Fig. 3) ia current commercial use iavolves condensation of 2,3,5-trimethylhydroquiQone (13) with synthetic isophytol (14) ia an iaert solvent, such as benzene or hexane, with an acid catalyst, such as ziac chloride, boron trifluoride, or orthoboric acid/oxaUc acid (7,8,18) to give the all-rac-acetate ester (15b) by reaction with acetic anhydride. Purification of tocopheryl acetate is readily accompHshed by high vacuum molecular distillation and rectification (<1 mm Hg) to achieve the required USP standard. 

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 sequence requires first simple A-acetylation with acetic anhydride. This product is then the substrate for the Friedel-Crafts reaction. The acylium cation is generated from acetyl chloride and aluminium chloride. 

Attempts to prepare a monoketone also failed with 10-ethyl- and 10-phenylphenothiazine. There is evidence, derived primarily from UV spectra, that 2,7-diketones are the products when 3,10-dialkyl-phenothiazines undergo Friedel-Crafts acylation. The best yields of diketones are obtained, as expected, when a 1 2 molar ratio of AICI3 and acetic anhydride is used, because the catalyst is involved here only in the generation of the electrophilic agent of the Friedel-Crafts reaction, unlike with the 10-acyl derivatives where it also forms a complex lO-acylphenothiazine-AlCls. ... 

It is a general rule that imidazoles and benzimidazoles are resistant to Friedel-Crafts reactions. This is not surprising since such basic compounds must be markedly deactivated in the presence of Lewis acids. Imidazolin-2-ones appear to be an exception and apparently possess sufficient activation to react. Reactions between imidazoles and Af-methylfor-manilide and phosphoryl chloride are also unproductive. With 4,5-diphenylimidazole, phenyl isocyanate at 80 °C gives products of both N- and C-substitution, but in boiling nitrobenzene only the latter (86) is formed. 2-Methyl-4-phenylimidazole gives (87) under the same conditions, and 1,3-diphenylimidazolium perchlorate is transformed by potassium t-butoxide into a ylide which reacts at C-2 with phenyl isothiocyanate. Sufficient activation is present in l-methyl-2-phenyl-4-phenylaminoimidazole for it to react by substitution at C-5 with acetic anhydride (71JOC3368). 

Ref 5). Insol in w but miscible with all common org solvents. According to Kirk Othmer(Ref 2), it was first prepd in 1857 by Friedel by distn of a mizt of Ca benzoate and Ca acetate. Commercially,acetophenone is prepxl by the Friedel—Crafts reaction usr ing benz,Al chloride and acetic anhydride. 

Chromic acid in hot glacial acetic acid oxidizes anthracene quantitatively to antlmaquinone in a very smooth reaction, but the method is too expensive for coxnmercial application in competition with synthetic anthraquinone made from cheap phthalic anhydride and benzene by means of the Friedel-Crafts reaction Prior to the development of the present methods of phthalic anhydride manufacture, the process was used extensively for anthraquinone production in Europe. The method has been recommended for anthracene analysis. 

Mekonnen and Crank also found the same reaction dichotomy in Friedel-Crafts reactions of 622 (X = O) with acid chlorides or acid anhydrides. In general, acylation of 622 (X = O, R = CH3) with acetic anhydride or benzoyl chloride/ pyridine afforded the corresponding 2-(acylamino)-4-methyloxazole 630a and 630b (Scheme 1.174). However, low-temperature acetylation or aroylation of 622 (X = O, R = CH3) in the presence of two equivalents of AICI3 produced a 5-acyl-2-amino-4-methyloxazole 631 in low to modest yield. The authors reported that AICI3 was the most effective Lewis acid (SnCLj and TiCL) and that the reaction required two equivalents of Lewis acid. Selected examples are shown in Table 1.48. 

Thiophene is the least reactive of the three because the p orbital of the lone pair of electrons on sulfur that conjugates with the ring is a 3p orbital rather than the 2p orbital of N or O, so overlap with the 2p orbitals on carbon is less good. Both furan and thiophene undergo more or less normal Friedel-Crafts reactions, although the less reactive anhydrides (here acetic anhydride, AC2O) are used instead of acid chlorides, and weaker Lewis acids than AICI3 are preferred. 

Friedel-Crafts acylation involves the direct introduction of an acyl group on the aromatic rings. This reaction, when carried out using corrosive and liquid catalysts, poses tedious workup and separation problems. An effort to minimize such limitations was made by Alizadeh et al. (2007), who reported a Friedel-Crafts reaction involving the treatment of acetic anhydride with aromatic compounds in the presence of SSA as a reusable, nontoxic, and heterogeneous catalyst (Scheme 5.44). 

The A-heterocyclic carbene precursor 49 is a photo-switchable catalyst for amidation reactions. The synthesis of this catalyst begins with two Friedel-Crafts reactions firstly, 2-melhyl-5-phenylthiophene was 3-acetylated with acetic anhydride using SnCLj, then product ketone oxidised to a glyoxal by SeOa- The glyoxal itself was used as acylating agent to react with 2-methyl-5-phenylthiophene with the assistance of SnCLj. After several further steps, the salt 49 was obtained (Scheme 51) [69]. 

Friedel-Crafts Reactions. Aluminum trifluoromethanesulfonate has been used for the Friedel-Crafts alkylation reaction of toluene with isopropyl and tert-butyl chlorides (eq 1), and for the acylation of benzene and toluene with acetyl and benzoyl chlorides in low to moderate yields. Intramolecular Friedel-Crafts acylation of an aromatic compound with Meldrum s acid has also been reported using catalytic amounts of Al(OTf)3. Acylation of 2-methoxynaphthalene with acetic anhydride has been reported using Al(OTf)3 and lithium perchlorate as an additive to afford the corresponding 6-acetylated adduct in 83% yield. Effective acylation of arenes with carboxylic acids has also been disclosed using polystyrene-supported Al(OTf)3. ... 

Sb(0S02CF3)3 has been reported as Lewis catalyst for reactions requiring traces of water. Benzoylation of toluene, acylation of m-xylene, and sulfonylation of toluene were examples demonstrating its role in Friedel-Crafts reactions [26]. Also, catalytic amount of Sb(OTf)3 catalyzed the reaction of 2-methoxynaphthalene with acetic anhydride in nitromethane-lithium perchlorate to afford 2-acetyl-6-methoxynaphthalene, a well-known intermediate for the synthesis of naproxen, in a high yield [27]. 

Y(OTf)3, as all other metal triflates, is able to catalyze Friedel-Crafts reactions in the presence of water. But it may also exhibit activity in more particular Friedel-Crafts reactions. For example, it showed activity in the acetylation at the 4-position of 3-phenylsydnone (Equation (8.25)) with acetic anhydride using either acetonitrile or acetic anhydride, in excess, as solvent [53]. 

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