Friedel-Crafts acetylations, acetyl chloride

Synthesis of racemic naproxene Friedel-Crafts acylation (aluminum chloride - nitrobenzene) of p-naphthol methyl ether affords 2-acetyl-6-methoxy naphthalene, which, when treated with either dimethyl sulfonium or dimethylsulfoxonium methylide, gives 2-(6-methoxynaphthalen-2-yl)propylene oxide. Treatment of the latter with boron trifluoride etherate in tetrahydrofuran gives 2-(6-methoxynaphthalen-2-yl)propionaldehyde, which is oxidized using Jones reagent (4 M chromic acid) to yield the racemic 2-(6-methoxynaphthalen-2-yl)propionic acid. 

Electrophiles attack xanthene at C-2 and sometimes also at C-7 when conditions are sufficiently vigorous. Nitric acid simultaneously oxidizes xanthene to the xanthone and thus gives 2-nitroxanthone. Friedel-Crafts acetylation of xanthene gives either 2-acetyl- or 2,7-diacetylxanthene according to the temperature (0 or 18 °C) and the proportion of acetyl chloride (74BSF2963). 

Alkoxybenzo[6]thiophenes undergo electrophilic substitution in the 2-position. Thus, 6-ethoxybenzo[6]thiophene affords its 2-bromo, 2-formyl, and 2-acetyl derivatives on bromination, Vilsmeier-Haack formylation, and Friedel-Crafts acetylation, respectively,424 and 6-methoxybenzo[6]thiophene undergoes Friedel-Crafts reaction with /3-carbomethoxypropionyl chloride in the 2-position.618... 

Fe(cyclooctatetraene)(CO)3] reacts under Friedel-Crafts acetylation conditions (acetyl chloride/AlCb), but only low yields of the substituted product (24) are formed the major product being the bicyclic cation (25) (equation 12).36-38... 

Dihydroxyacetophenone (6) (cognate preparation in Expt 6.107), which cannot be prepared by a Friedel-Crafts acetylation of hydroquinone, is obtained in good yield when hydroquinone diacetate (5) is heated in the presence of 3.3 mol of aluminium chloride. 

Friedel Crafts acetylation of butadiene complex 56 proceeds smoothly to give a mixture of 1-acetyldienes 58 and 59 via the cationic 7r-allyl complex 57 [16]. Intramolecular Friedel-Crafts acylation with the acid chloride of the diene complex 60, promoted by deactivated AICI3 at 0 °C, gave the cyclopentanones. The (Z)-dienone complex 61 was the major product and the ( )-dienone 62 the minor one [17]. Acetylation of the 1,3-cyclohexadiene phosphine complex 63 proceeded easily at —78°C to give the rearranged complex 65 in 85% yield. Without phosphine coordination, poor results were obtained [18,19], In this reaction, the acetyl group at first coordinates to Fe, and attacks at the terminal carbon of the diene from the same... 

The effect of a Lewis acid on the o-nitro-(-aniline system is well illustrated by the unexpected result from the attempted Friedel-Crafts acetylation of these compounds. In 1926, van Romburgh and co-workers51,52 observed that the action of acetic anhydride and zinc chloride on the o-nitrodimethylaniline (111) did not give the acetylated product (112), but instead the benzimidazolone (113). Even more surprising was their alleged observation that the same reagents converted the diethyl compound (114) into the quinoxaline... 

The Friedel-Crafts acetylation of 3-phenylsydnone was accomplished with boron trifluoride etherate as catalyst. Formylation at C-4 by the Vilsmeier procedure occurred with 3-phenylsydnone. Mercuration is easily afforded with mercury(II) acetate or mer-cury(13) chloride and thioethers can be made directly with DMSO in acetyl chloride (74T409). At least one fused ring as in compound (35) has been made by a coupling reaction on the sydnone (34) at C-4 (79JCS(P2)175l). 

Aromatic ketones are important intermediates in the production of fine chemicals and pharmaceuticals1,2. Thus, the anti-rheumatic Naproxen is produced by the Friedel-Crafts acetylation of 2-methoxynaphthalene into 2-acetyl-6-methoxynaphthalene and subsequent Willgerodt-Kindler reaction. Commercial acylation processes involve over-stoechiometric amounts of metal chlorides (e g. AICI3) as catalysts and acid chlorides as acylating agents, which results in a substantial formation of by-products and in corrosion problems. This is why the substitution of these corrosive catalysts by solid acid catalysts and of acid chlorides by anhydrides or acids is particularly desirable. 

Free-ion attack is more likely for sterically hindered R. The ion CH3CO has been detected (by IR spectroscopy) in the liquid complex between acetyl chloride and aluminum chloride, and in polar solvents, such as nitrobenzene but in nonpolar solvents, such as chloroform, only the complex and not the free ion is present." In any event, 1 equivalent of catalyst certainly remains complexed to the product at the end of the reaction. When the reaction is performed with RCO+SbFg, no catalyst is required and the free ion" " (or ion pair) is undoubtedly the attacking entity." The use of LiC104 on the metal triflate-catalyzed Friedel-Crafts acylation of methoxy-naphthalene derivatives has been examined, and the presence of the lithium salt leads to acylation in the ring containing the methoxy unit, whereas reaction occurs in the other ring in the absence of lithium salts." Note that lithium perchlorate forms a complex with acetic anhydride, which can be used for the Friedel-Crafts acetylation of activated aromatic compounds." ... 

Friedel-Crafts acylation. Aluminum chloride-mediated acetylation of arenes in the analogous ionic liquid l-methyl-3-ethylimidazolium chloride occurs at room temperature. 

Acyl halides bearing a-hydrogen atoms, and acetyl chloride in particular, have limited stability in the presence of strong Lewis acids. Elimination of proton from the acylium ion leads to the ketene. This intermediate undergoes ready Friedel-Crafts acylation, acetyl chloride eventually forming the diacetylace-tylium ion, ° which is a poor acylating agent. For this reason, excessive reaction temperatures and times should be avoided in Friedel-Crafts acetylations. 

Ci2H10O, Mr 170.21, 6pi.7kPa 171-173 °C, df 1.171, ng° 1.6752, has been identified in some essential oils. It smells like orange blossom and is a colorless crystalline solid (mp 56 °C). It is usually prepared by Friedel-Crafts acetylation of naphthalene (with acetyl chloride, acetic anhydride, etc.) in the presence of aluminum chloride. In polar solvents (e.g., nitrobenzene), the percentage of the simultaneously formed a isomer is lower. Methyl P-naphthyl ketone is used in eau de cologne, soap perfumes, and detergents. It is a good fixative. 

The use of these parameters RY, BA and BA, was illustrated utilizing the production of phenone via the Friedel-Craft acetylation. The basic balance sheet (material balance) is shown in Figure 11. The values of BA and BA, were calculated from the complete reaction equation (Figure 12). (AICI3 and 3 H2O are included as primary raw materials.) The following value was determined for the stoichiometric or relative yield (calculated on benzoyl chloride as main educt) ... 

Lanthanide bis(trifluoromethylsulfonyl)amides Ln[N(S02CF3)2] catalyse the acetylation of anisole by acetic anhydride in good yield with easy catalyst recovery. The Friedel-Crafts acetylation of (3-bromopropyl)benzene by acetyl chloride to form p-(3-bromopropyl)acetophenone together with a little of the 3-chloro analogue has been studied. The acylation of phenol by acetic acid has been subject to... 

Also obtained by Friedel-Crafts acetylation of 4-bromopyrogaUol trimethyl ether with acetyl chloride in the presence of aluminium chloride in carbon disulfide, then treatment of the compound obtained (partly demethylated) with dimethyl sulfate in the presence of sodium hydroxide [3833]. 

Friedel-Crafts Acetylation. Arenes undergo acetylation to afford aryl methyl ketones on treatment with acetyl chloride (AcCl) together with a Lewis acid, usually aluminum chlorides. This reaction, known as the Friedel-Crafts acetylation, is valuable as a preparative method because a single positional isomer is produced from arenes that possess multiple unsubstituted electron-rich positions in many instances. 

A particularly impressive green example (Real Life 3-1) of this effect is achieved in the Friedel-Crafts acetylation of (2-methylpropyl)benzene with acetic anhydride, in an industrial approach to an ibuprofen intermediate (Chapter Opening see also Exercise 16-10). Here, a porous zeolite catalyst (see Section 3-3) provides not only the acidic surface sites necessary for the reaction to proceed, but also an environment that enhances para selectivity. This process avoids the use of the corrosive acetyl chloride and AICI3 reagents and with it the formation of the toxic HCl by-product of the classical Friedel-Crafts acetylation. Instead, the by-product is acetic acid, itself a valuable commodity. 

TTie true ketones, in which the >CO group is in the side chain, the most common examples being acetophenone or methyl phenyl ketone, C HjCOCH, and benzophenone or diphenyl ketone, C HjCOC(Hj. These ketones are usually prepared by a modification of the Friedel-Crafts reaction, an aromatic hydrocarbon being treated with an acyl chloride (either aliphatic or aromatic) in the presence of aluminium chloride. Thus benzene reacts with acetyl chloride... 

The p-methylacetophenone is readily prepared by the Friedel-Crafts reaction cf. p. 254), toluene being treated with acetyl chloride in the presence of alumfnium chloride. The toluene is employed in considerable excess so that it... 

The ketones are readily prepared, for example, acetophenone from benzene, acetyl chloride (or acetic anhydride) and aluminium chloride by the Friedel and Crafts reaction ethyl benzyl ketones by passing a mixture of phenylacetic acid and propionic acid over thoria at 450° and n-propyl- p-phenylethylketone by circulating a mixture of hydrocinnamic acid and n-butyric acid over thoria (for further details, see under Aromatic Ketones, Sections IV,136, IV,137 and IV,141). 

Acetamido-4-methylthiazole does not react with acetyl chloride in the Friedel-Crafts reaction (172. 407, 449). 

---