Acetyl chloride, Friedel-Crafts reaction

Preparation by reaction of acetyl chloride on 3-chloro-phenol with aluminium chloride (Friedel-Crafts reaction) [1958]. 

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... 

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

Acetophenone. Acetophenone [98-86-2] (methyl phenyl ketone) is a colorless Hquid that forms laminar crystals at low temperature (mp 20°C). It has a characteristic sweet orange blossom odor, and is soluble in alcohols and ethers. It is found in nature in oil of casatoreum, obtained from beavers oil of labdanum, recovered from plants and in buds of balsam poplar. It can be prepared by the Friedel-Crafts reaction (qv) of acetyl chloride with benzene in the presence of aluminum chloride however, this route is of Htde commercial significance. 

Aromaticity of 2,4,6-tri-fert-butylphenylphosphole (17d) was also revealed in chemical reactions phosphole 17d could undergo aromatic electrophilic substitution. In reaction with acetyl chloride, a mixture of 2-, 4-, and 5-acetyl phospholes (23a, 24a, and 25a, respectively), as well as a diacetyl derivative (26a) were formed (Scheme 6) [39], Interestingly, the most crowded 2-acetyl derivative (23a) was the main product of the Friedel-Crafts reaction. A similar situation was observed for 3-methylpyrrol [46],... 

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. 

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. 

Interestingly, treating (>/4-cyclooctatetraene)Fe(CO)3 with acetyl chloride under Friedel-Crafts reaction conditions yielded unexpectedly222-223 the (>/2,>/3-8-e.x0-acetyl bicy-clo[3.2.1]octadienylium)Fe(CO)3 cation complex, presumably by rearrangement of the intermediate bicyclo[5.1.0]octadienylium isomer (Scheme 8). The structure of the rearranged cation was confirmed from the X-ray crystal structure and from the typical 1,3-cr.ji-allylic products obtained upon nucleophilic reaction with LiAlD4 and NaCN. The nucleophilic reaction of the more bulky iodide occurs, however, on the metal. 

This yield of acetophenone is 10% better than that obtained in the ordinary Friedel-Crafts reaction. A similar method can be applied to the preparation of p-tolyl-methyl-ketone, 20 gms. (1 mol.) of dry toluene, 2 gms. of aluminium powder, 35 gms. of mercuric chloride, and 17 gms. (1 msl.) of acetyl chloride being used. The yield is 45% theoretical (13 gms.). The ketone is obtained as a low-melting solid, B.P. 224°. 

Tetrahydrobenzo[ ]thiophene behaves like thiophene in electrophilic substitution reactions. Thus, it is formylated with a mixture of vV-methylformanilide and phosphorus oxychloride,436 iodinated in the presence of mercuric oxide,193 and brominated by V-bromosuccinimide,193 all in the 2-position in Friedel-Crafts reactions with acetyl chloride,194-436 propionyl chloride,436 succinic... 

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... 

Phenone is produced by the acetylation of benzyl chloride with o-xylene via a Friedel-Crafts reaction. Table 1.1 presents the elements of the material balance. Calculate the efficiency of raw materials. 

Friedel-Crafts reaction of -acetylphenoxazine in carbon disulfide with a large excess of acetyl chloride and aluminum chloride yielded 2,8-diacetylphenoxazine (28), which proved to be identical with the diacetylphenoxazine which was formed by oxidation of 2,8-diethyl-phenoxazine with potassium permanganate (see Section IV,E).61... 

In the case of Friedel-Crafts reactions, mild conditions are essential, since binaphthyls are formed under vigorous conditions. Reaction with acetyl chloride in tetrachloroethane in the presence of aluminium chloride gives 1-acetylnaphthalene (Scheme 12.5), although in nitrobenzene the 2-acetyl derivative 11 is the major product. Attack at the less hindered 2-position is preferred in the latter case because of the larger size of the solvated acylating species. 

Olefinic ketones have been obtained from the reaction of acyl chlorides or anhydrides with olefins using the conditions of the Friedel-Crafts reaction. The intermediate chloro ketones are oftentimes stable and must be treated with sodium bicarbonate or dimethylaniline to complete the de-hydrohalogenation. In this manner, 1-acetyl-1-cyclohexene (62%) ° and 1-butyryl-1-cyclohexene (60%) are prepared. 

For the preparation of unsymmetrical ferrocenes, two ways by which only mono-substituted derivatives are produced have been suggested. One route starts from iron tetracarbonyl and a substituted cyclopenta-diene the other from monocyclopentadienyl iron dicarbonyl bromide, which on treatment with a substituted cyclopentadienyl lithium is finally converted into the corresponding mono-substituted ferrocene. Experience shows the first method to be more suitable for the preparation of aryl, and the latter method for the preparation of alkyl, derivatives (57). Corresponding work already carried out on substitution in Ru(C5H6)2 and Os CsH5)2 has also been fruitful. It is found that in the Friedel-Crafts reaction with acetyl or benzoyl chloride there is a distinct predominance of mono- over disubstitution as the atomic weight of the central atom increases (47, 72). 

Chloroform is useful as solvent for Friedel-Crafts reactions not only because It dissolves the aluminum chloride-acetyl chloride complex but also because it hai an orienting effect. Thus the reaction of naphthalene with 2 equivalents each of... 

In a brief preliminary note Heine, Cottle, and Van Mater reported comparative results showing that zirconium tetrachloride is generally superior to aluminum chloride for the Friedel-Crafts p-acetylation of toluene with acetyl chloride. However, the results were less consistent with ZrCl, than with AICI3. Gore and Hoskins studied the Friedel-Crafts reaction of benzoyl chloride with anthracene in ethylene dichloride at 0° in the presence of 14 different catalysts. The best yields of very pure 9-benzoylanthracene were with zirconium tetrachloride (97% yield after lihrs.) and with aluminum chloride (86% yield after U hrs., 99% yield after 99 hrs.). 

Friedel-Crafts reaction. A type of reaction involving anhydrous aluminum chloride and similar metallic halides as catalysts, discovered in 1877 by Charles Friedel, a French chemist (1832-1899), and James Mason Crafts, an American chemist (1830-1917), during joint research in France it has been developed since then for many important industrial uses, exemplified by the condensation of ethyl chloride and benzene to form ethylbenzene and the manufacture of acetophenone from acetyl chloride and benzene. The name is now applied to a wide variety of acid-catalyzed organic reactions. 

If the electrophile also benefits from Lewis acid catalysis, as in the aliphatic Friedel-Crafts reaction, good yields of products are generally found. The anion of the allyl phosphonate 192 can be silylated to give the vinyl silane 193 and this reacts in turn with the classical combination of acetyl chloride and A1C13 to give the enone -194 that can be used in HWE reactions to make dienones46 (chapter 15). 

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