Acylation of aromatics ethers

Friedel-Crafts acylation of aromatic ethers has been performed in the presence of a variety of metal chlorides and oxides (FeCl3, ZnCl2, A1C13, Fe203, Fe304, etc.) but without temperature control [52], Scheme 10.8. 

Polyphosphoric acid has also been used to effect both acylation of aromatic ethers and subsequent ring closure (74IJC474). 

Also, Marquie and co-workers have conducted Friedel-Crafts reactions on a large laboratory scale via a continuous flow process126. They reported the acylation of aromatic ethers and sulphonylation of mesitylene, isolating up to 300 g and 250 g of product, respectively (Schemes 9.13 and 9.14). 

The acylation of aromatic ethers by acyl chlorides is highly regioselective in the presence of 10 mol% Sml3.53 Some aromatic compounds are efficiently acylated by acid anhydrides catalysed by niobium pentachloride with silver perchlorate.54 Arenes of a range of reactivity are acylated by acetic anhydride in a fluorous biphasic system catalysed by Hfps SCLCgFn L (1 mol%)55 The catalyst is easily recoverable and can usually be used again without decrease in activity. 

In zeolite-catalysed acylation of aromatic ethers, zeolites have two advantages with respect to benzene and alkylbenzene acylation ... 

Acylation of aromatic ethers yields the corresponding keto ethers. Typical examples are found in the conversion of anisole with aluminum chloride and appropriate acyl halide to p-methoxybutyrophenone (85%) and p-methoxyphenyl benzyl ketone (84%). Mild catalysts like iodine and phosphorus pentoxide are also effective. 

Ranu, B. C., Ghosh, K., Jana, U. Simple and Improved Procedure for Regioselective Acylation of Aromatic Ethers with Carboxylic Acids on the Solid Surface of Alumina in the Presence of Trifluoroacetic Anhydride. J. Org. Chem. 1996, 61, 9546-9547. 

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]. 

Friedel-Crafts Acylation of Aromatic Ethers Using Zeolites... 

An impressive number of papers and books has been published and numerous patents have been registered on the aq lation of aromatic compounds over solid catalysts. Recently Sartori and Maggi [1] have written an excellent review with 267 references on the use of solid catalysts in Friedel-Crafts acylation. In one section of this review, namely acylation of aromatic ethers or thioethers, the authors report work on acylation by solid catalysts such as zeolites, clays, metal oxides, acid-treated metal oxides, heteropolyacids or Nafion. When examining in details these results, it appeared very difficult for us to build upon these experimental results as the reaction conditions differ drastically from one paper to the next. This prompted us to reinvestigate the scope and limitations of the Friedel-Crafts acylation using heterogeneous solids as catalysts, trying as much as we could to rationalize the observed effects. 

Speciality and fine chemicals Chapter 14, Friedel-Crafts acylation of aromatic ethers Chapter 15, the production of nicotinates Chapter 16, production of intermediate for resmethrins. 

Acylation of Aromatic Ethers. A simple and improved procedure for regioselec-tive acylation of aromatic ethers with carboxylic acids on alumina in the presence of trifluoroacetic anhydride has been described by Ranu et al. [Eq. (21)]... 

Other recent works concerning the catalytic acylation of aromatic ethers concern ... 

BISMUTH HU) SALTS IN THE FRIEDEL-CRAFTS ACYLATION OF AROMATIC ETHERS... 

Table 3.5 Acylation of aromatic ethers with anhydrides in the presence of titanium(IV) monochlorotriflate-triflic acid mixture...

Table 3.16 Aluminum-hydrogensulfate-promoted acylation of aromatic ethers with acetic and propionic anhydrides...

A high para-selectivity is also observed in the acylation of aromatic ethers with propanoic anhydride, carried out with the same catalyst. The 4-methoxypropiophenone is isolated with 99% selectivity after a 2 h reaction at 150°C. 

Acylation of aromatic ethers with acid anhydrides in the presence of cation-exchanged clays. Appl. Catal. A Gen. 171 155-160. 

Friedel-Crafts acylation. An improved procedure for the acylation of aromatic ethers is to carry it out with acids in the presence of (CFjCOljO on an alumina surface. 

Friedel-Crafts acylation of aromatic ethers Solvent-free benzoylation of aromatic ethers has been performed under the action of microwave irradiation in the presence of a metallic catalyst, FeCla being one of the most efficient [163], With careful control of the temperature and other conditions, nonthermal microwave effects have not been observed either in terms of yield or isomeric ratios of the obtained products (Eq. 79) ... 

The Friedel-Crafts acylation of aromatic ethers has attracted considerable interest in organic synthesis and in industrial chemistry because of the widespread application of the corresponding ketones as valuable intermediates in fine chemistry [39-43]. An example is the selective acetylation of 2-methoxynaphthalene at the carbon in position 6 owing to the great interest in 2-methoxy-6-acetylnaphthalene, an intermediate in the preparation of the anti-inflammatory drug (S)-Naproxen [44,45]. 

The regioselective acylation of aromatic ethers with carboxylic acids (aromatic ether/carboxylic acid ratio =1) can be pafonned with an equimolecular mixture of trifluoroacetic anhydride adsorbed on the surface of alumina without any solvent [77]. The process can be applied, with nearly quantitative yields, to anisole and the three isomeric dimethoxybenzenes by using carboxylic acids. The authors outline that in the case of anisole, the acylation selectively occurs at the para position to the methoxy group. The reaction requires a large amount of alumina and trifluoroacetic anhydride, and consequently, it can only be appUed at the laboratory scale. The intervention of a mixed carboxyhc acidArifluoroacetic acid mixed anhydride intermediate is presumed. 

---