Electrophilic aromatic substitution, acylation rearrangements

Solid acid catalysts are, in principle, applicable to a plethora of acid-promoted processes in organic synthesis [27-29]. These include various electrophilic aromatic substitutions, e.g. nitrations, and Friedel-Crafts alkylations and acylations, and numerous rearrangement reactions such as the Beckmann and Fries rearrangements. 

Pertinent examples of zeolite-catalyzed reactions in organic synthesis include Friedel-Crafts alkylations and acylations and other electrophilic aromatic substitutions, additions and eliminations, cyclizations, rearrangements and isomeriza-tions, and condensations. 

Scheme 8.42. Electrophilic aromatic substitution of phenol with an acyl group. The acylation of phenol with acetyl chloride (CH3COCI) in the presence of aluminum trichloride (AICI3) can apparently occur via a direct addition of the aluminum trichloride complexed acetyl chloride (in competition with O-acylation) or by a subsequent rearrangement of O-acylated phenol. The former is presented in the upper portion of the scheme, while the latter is shown in the lower portion.

A Friedel-Crafts alkylation is an electrophilic aromatic substitution reaction that attaches a carbon-carbon bond to the ring.The electrophile is R, which will add to the aromatic ring to produce a cyclohexadienyl cation. Aromaticity is regained when that intermediate cyclohexadienyl cation is deprotonated. That s all there is to it—all the rest is details. Remember to watch out for rearrangements, because this Friedel-Crafts alkylation is especially prone to them. In the Friedel-Crafts acylation, an acid chloride is used to generate the acylium ion which is the reactive electrophile. No rearrangements are observed in Friedel-Crafts acylation. 

In Summary The problems of Friedel-Crafts alkylation (multiple substitution and carboca-tion rearrangements) are avoided in Friedel-Crafts acylations, in which an acyl halide or carboxylic acid anhydride is the reaction partner, in the presence of a Lewis acid. The intermediate acylium cations undergo electrophilic aromatic substitution to yield the corresponding aromatic ketones. 

Bronsted Acids. Sulfuric acid (H2SO4) is an inexpensive, easy to handle protic acid used widely as catalyst in hydrolysis, hydration and dehydration, elimination, substitution, and rearrangements. It also catalyzes aromatic electrophilic substitutions mostly Friedel-Crafts acylations and alkylations (22). A very important application of sulfuric acid is its use in commercial isoalkane-alkene alkylation technologies. These commercial processes are still based on the use of sulfuric acid (and hydrogen fluoride) catalysts (23). 

The experiments in Sections 15.2 and 15.3 illustrate the Friedel-Crafts alkylation and acylation of aromatic hydrocarbons, respectively. A complication of Friedel-Crafts reactions is apparent in the alkylation experiment, wherein rearrangements of the carbo-cations generated from the alkyl halide provide mixtures of substitution products. The acylation reaction of Section 15.3 provides an example of how a combination of electronic and steric effects can affect the orientation of electrophilic attack on an aromatic ring. 

Acylation reactions generally do not suffer from these limitations, and can be conducted using acid chlorides or anhydrides as the electrophilic reagents. Since the introduction of a carbonyl group onto the aromatic ring in an acylation reaction deactivates the ring, the problem of multiple substitution is avoided. The acyUum cation, since it is resonance stabilized, is unlikely to rearrange. 

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,... 

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