Ketones Friedel-Crafts acylation

Formation of ketones. Friedel-Crafts acylation. Discussed in Sec. 19.6. 

Conversion to ketones (Friedel—Crafts acylation, Sections 15.7—15.9) ... 

Synthesis of Aromatic Ketones (Friedel-Crafts Acylation)... 

Friedel-Crafts acylation using nittiles (other than HCN) and HCI is an extension of the Gattermann reaction, and is called the Houben-Hoesch reaction (120—122). These reactions give ketones and are usually appHcable to only activated aromatics, such as phenols and phenoHc ethers. The protonated nittile, ie, the nitrilium ion, acts as the electrophilic species in these reactions. Nonactivated ben2ene can also be acylated with the nittiles under superacidic conditions 95% trifluoromethanesulfonic acid containing 5% SbF (Hg > —18) (119). A dicationic diprotonated nittile intermediate was suggested for these reactions, based on the fact that the reactions do not proceed under less acidic conditions. The significance of dicationic superelectrophiles in Friedel-Crafts reactions has been discussed (123,124). 

Ketone formation can also be avoided if one of the functional acyl halogens ia phosgene is blocked. Carbamyl chlorides, readily obtained by the reaction of phosgene with ammonia or amines, are suitable reagents for the preparation of amides ia direct Friedel-Crafts acylation of aromatics. The resulting amides can be hydroly2ed to the corresponding acids (134) ... 

Intramolecular Friedel-Crafts acylations of olefins also give cycHc a,P-unsaturated cycHc ketones. Cyclopropane fused bicyclo[5.3.0]octenones, thus obtained, were used in the preparation of the marine sesquiterpenes, africanol [53823-07-7] and dactjlol [58542-75-9] (174). 

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). 

Each of the compounds indicated undergoes an intramolecular Friedel-Crafts acylation reaction to yield a cyclic ketone. Write the structure of the expected product in each case. 

The most important method for the synthesis of aromatic ketones 3 is the Friedel-Crafts acylation. An aromatic substrate 1 is treated with an acyl chloride 2 in the presence of a Lewis-acid catalyst, to yield an acylated aromatic compound. Closely related reactions are methods for the formylation, as well as an alkylation procedure for aromatic compounds, which is also named after Friedel and Crafts. 

The synthetic importance of the Houben-Hoesch reaction is even more limited by the fact that aryl ketones are also available by application of the Friedel-Crafts acylation reaction. 

While the Friedel-Crafts acylation is a general method for the preparation of aryl ketones, and of wide scope, there is no equivalently versatile reaction for the preparation of aryl aldehydes. There are various formylation procedures known, each of limited scope. In addition to the reactions outlined above, there is the Vdsmeier reaction, the Reimer-Tiemann reaction, and the Rieche formylation reaction The latter is the reaction of aromatic compounds with 1,1-dichloromethyl ether as formylating agent in the presence of a Lewis acid catalyst. This procedure has recently gained much importance. 

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... 

Reaction of the potassium salt of salicylaldehyde with chlo-roacetone affords first the corresponding phenolic ether aldol cyclization of the aldehyde with the ketonic side chain affords the benzofuran (1). Reduction of the carbonyl group by means of the Wolf-Kischner reaction affords 2-ethyl-benzofuran. Friedel-Crafts acylation with anisoyl chloride proceeds on the remaining unsubstituted position on the furan ring (2). The methyl ether is then cleaved by means of pyridine hydrochloride (3). lodina-tion of the phenol is accomplished by means of an alkaline solution of iodine and potassium iodide. There is thus obtained benziodarone (4)... 

A closet member of this little group, revelation of whose i(>al nature requires metabolic transformation of an acetylenic linkage to an acetic acid moiety, is fl uretofen (14). The .ynthesis begins by Friedel-Crafts acylation of 2-fluorobi-phenyl (11) with acetic acid to give ketone 1. Heating with... 

Friedel-Crafts acylation of fluorobenzene with thiophene-l-carboxylic acid gives the ketone 7. Nitration proceeds ortho to the fluoro group to give the intermediate Nucleophilic displacement by means of... 

Friedel-Crafts acylation reactions usually involve the interaction of an aromatic compound with an acyl halide or anhydride in the presence of a catalyst, to form a carbon-carbon bond [74, 75]. As the product of an acylation reaction is less reactive than its starting material, monoacylation usually occurs. The catalyst in the reaction is not a true catalyst, as it is often (but not always) required in stoichiometric quantities. For Friedel-Crafts acylation reactions in chloroaluminate(III) ionic liquids or molten salts, the ketone product of an acylation reaction forms a strong complex with the ionic liquid, and separation of the product from the ionic liquid can be extremely difficult. The products are usually isolated by quenching the ionic liquid in water. Current research is moving towards finding genuine catalysts for this reaction, some of which are described in this section. 

The Friedel-Crafts acylation reaction has also been performed in iron(III) chloride ionic liquids, by Seddon and co-workers [96]. An example is the acetylation of benzene (Scheme 5.1-66). Ionic liquids of the type [EMIM]Cl/FeCl3 (0.50 < X(FeCl3) < 0.62) are good acylation catalysts, with the added benefit that the ketone product of the reaction can be separated from the ionic liquid by solvent extraction, provided that X(FeCl3) is in the range 0.51-0.55. 

I Aryl ketones are prepared by Friedel-Crafts acylation of an aromatic ring with an acid chloride in the presence of AICI3 catalyst (Section 16.3). 

Intramolecular Friedel-Crafts acylation of diaryl ketones Oxidation of phenols or aromatic amines Oxidation of aromatic hydrocarbons... 

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