Electrophilic aromatic substitution, acylation arenes

Remember from Section 12.16 that it is the more activating substituent that determines the regioselectivity of electrophilic aromatic substitution when an arene bears two different substituents. Methoxy is a strongly activating substituent fluorine is slightly deactivating. Friedel-Crafts acylation takes place at the position para to the methoxy group. 

This electrophilic aromatic substitution allows the synthesis of monoacylated products from the reaction between arenes and acyl chlorides or anhydrides. The products are deactivated, and do not undergo a second substitution. Normally, a stoichiometric amount of the Lewis acid catalyst is required, because both the substrate and the product form complexes. 

This Lewis acid-catalyzed electrophilic aromatic substitution allows the synthesis of alkylated products via the reaction of arenes with alkyl halides or alkenes. Since alkyl substituents activate the arene substrate, polyalkylation may occur. A valuable, two-step alternative is Friedel-Crafts Acylation followed by a carbonyl reduction. 

Electrophilic aromatic substitution reactions are a very important class of chemical reactions that allow the introduction of substituents on to arenes by replacing a hydrogen atom covalently bonded to the aromatic ring structure by an electrophile. The most common reactions of this type are aromatic nitrations, halogenations, Friedel-Crafts alkylations and acylations, formylations, sulfonations, azo couplings and carboxylations - to name just a few. 

The Friedel-Crafts reaction involves an electrophilic aromatic substitution that facilitates the alkylation or acylation of arenes (135) and heterocyclic compounds catalyzed by acidic catalysts. Zinc oxide has been found to be an effective catalyst for the Friedel-Crafts acylation of activated and nonactivated aromatic compounds (135) (Hosseini-Sarvari and Sharghi 2004) under solvent-free and room temperature conditions (Scheme 9.44). The catalyst provides a large surface area for the reaction. This Friedel-Crafts reaction is a safe and environmentally benign method which requires simple workup, mild reaction conditions and a short reaction time. 

In the preceding section, benzene reacted with cations to form substituted benzene derivatives. The cations of interest include Br+, C1+, the nitronium ion, and sulfur trioxide or sulfuric acid, which react as electrophiles. In principle, benzene may react with any cation, including carbocations, once that cation is formed. Carbocations are generated by several different methods they react with nucleophiles, as described for reactions of alkenes with acids such as HX (Chapter 10, Section 10.2) and for S l reactions (Chapter 11, Section 11.4). If benzene reacts with a carbocation, a new carbon-carbon bond is formed, and electrophilic aromatic substitution will give an arene. The reaction of benzene and its derivatives with carbocations is generically called the Friedel-Crafts reaction, after the work of French chemist Charles Friedel (France 1832-1899) and his American protege, James M. Crafts (1839-1917). The reaction takes two fundamental forms Friedel-Crafts alkylation and Friedel-Crafts acylation. Both variations will be discussed, beginning with the alkylation reaction. 

Several important reactions of arenols involve aromatic substitution of arenolate ions with carbon electrophiles. In a sense, these reactions are alkylation and acylation reactions as discussed for arenes (Sections 22-4E and 22-4F). In another sense, they are alkylation and acylation reactions of enolate anions and therefore could give rise to products by C- and O-alkyla-tion, or C- and O-acylation (Section 17-4). Thus ... 

Nevertheless, such reactions catalyzed by zeolites have been discussed in the review of 2001 (1) isomerization (double-bond shift, isomerization of tricyclic molecules, like synthesis of adamantane, isomerization of terpenes, diverse rearrangements, conversion of aldehydes into ketones), (2) electrophilic substitution in arenes (alkylation of aromatics, including the synthesis of linear alkylbenzenes, alkylation and acylation of phenols, heteroarenes and amines, aromatics nitration and halogenation), (3) cyclization, including the formation of heterocycles, Diels-Alder reaction, (4) nucleophilic substitution and addition,... 

Study of the reactivity of aromatic C-H bonds in the presence of transition metal compounds began in the 1960s despite the quite early discovery of Friedel-Crafts alkylation and acylation reactions with Lewis acid catalysts. In 1967, we reported Pd(II)-mediated coupling of arenes with olefins in acetic acid under reflux [1], The reaction involves the electrophilic substitution of aromatic C-H bonds by a Pd(II) species, as shown in Scheme 2, and this is one of the earliest examples of aromatic C-H bond activation by transition metal compounds. Al-... 

The electrophile is usually produced by the reaction between a catalyst and a compound containing a potential electrophile (Eq. 15.3). The second-order nature of the reaction arises from the step shown in Equation 15.4 in which one molecule each of arene and electrophile react to give a cationic intermediate. The formation of this cation is the rate-determining step (rds) in the overall reaction the subsequent deprotonation of the cation (Eq. 15.5) is fast. The bimolecular nature of the transition state for the rate-limiting step and the fact that an electrophile is involved in attacking the aromatic substrate classifies the reaction as S 2 (Substitution Electrophilic Bimolecular). Experiments involving four different such reactions are given in this chapter Friedel-Crafts alkylation and acylation, nitration, and bromination. 

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