The Friedel-Crafts Acylation of Benzene

Two electrophilic substitution reactions bear the names of chemists Charles Friedel and James Crafts. Friedel-Crcfts acylation places an acyl group on a benzene ring, and Friedel-Crafts alkylation places an alkyl group on a benzene ring. 

An acyl chloride or an acid anhydride is used as the source of the acyl group needed for a Friedel-Crafts acylation. 

The electrophile (an acylium ion) required for the reaction is formed by the reaction of an acyl chloride (or an acid anhydride) with AICI3, a Lewis acid. Oxygen and carbon share 

Because the product of a Friedel-Crafts acylation contains a carbonyl group that can complex with AICI3, Friedel-Crafts acylations must be carried out with more than one equivalent of AICI3. When the reaction is over, water is added to the reaction mixture to liberate the product from the complex. 

The synthesis of benzaldehyde from benzene poses a problem because formyl chloride, the acyl halide required for the reaction, is unstable and must be generated in situ. The Gatterman-Koch reaction uses a high-pressure mixture of carbon monoxide and HCl to generate formyl chloride and an aluminum chloride-cuprous chloride catalyst for the acylation. 

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In-situ IR-spectroscopic characterization of the Friedel-Crafts acylation of benzene in ionic liquids derived from AICI3 and FeCl3 showed that the mechanism of the reaction in ionic liquids was the same as that in 1,2-dichloroethane (128). The immobilization of ferric chloride-containing ionic liquid onto solid supports (e.g., silica and carbon) however failed to catalyze the acylation reaction, because leaching was a serious problem. When the reaction was carried out with gas-phase reactants, catalyst deactivation was observed. 

Phenyl heptyl ketone has been prepared by the Friedel-Crafts acylation of benzene with octanoyl chloride.6 It is also a product of the thermal decomposition of the mixed ferrous salts of benzoic and octanoic acids.7... 

Strategy To identify the carboxylic acid chloride used in the Friedel-Crafts acylation of benzene, break the bond between benzene and the ketone carbon and replace it with a -Cl. 

In the Friedel-Crafts acylation of benzene, the above procedure gave only poor yield, whereas a new catalyst system, Hf(OTf)4 and CF3SO3H, was found to catalyze the reaction of even deactivated benzenes, e.g. chlorobenzene and fluorobenzene (Eq. 13) [20]. 

In the presence of a stoichiometric amount of SbCls, Friedel-Crafts acylation proceeds with acyl hahdes and acid anhydrides [47], SbCls also promotes the Fries rearrangement of phenyl acetates [48], The electrophilic acylation of fluoro-olefins with acetyl fluoride or benzoyl fluoride is promoted by SbFs in liquid SOy [49], The Friedel-Crafts acylation of benzene and electron-rich arenes is successfully catalyzed by SbCl5-AgClO4 [50], SbCl, Ar.BCl [51], SbCl5-LiClO4 [52], or CaCI, AgSbFg [53] (Scheme 14,19), Acyl chlorides, acid anhydrides, and acyl enolates are used as sources of acyl groups. 

Hydroxy-3-methylanthranil is methylated normally with methyl iodide and sodium carbonate to give the 7-methoxy derivative.135 Anthranil carboxylic acids are converted into their acid chlorides by thionyl chloride,208 and their methyl esters by diazomethane.169 The acid chloride of 5-chloro-3-phenylanthranil-6-carboxylic acid participates in the Friedel-Crafts acylation of benzene to give 6-benzoyl-5-chloro-3-phenylanthranil (67%).208... 

The remaining steps in the Friedel-Crafts acylation of benzene are the following ... 

Scheme 9.137. A representation of the Friedel-Crafts acylation of benzene (CeHe) by butane-1,4-dioic anhydride (succinic anhydride) in the presence of an aluminum trichloride (AICI3) catalyst. Generation of the 4-phenyl-4-oxobutanoic acid and hydrolysis of the catalyst are shown as the last step.

Devise a synthesis of each of the following compounds starting from the Friedel—Crafts acylation of benzene. 

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