Electrophilic aromatic substitution, acylation mechanism

The mechanism for that step is closely related to that of the Friedel-Crafts acylation. Upon subsequent hydrolysis the o-substituted Lewis acid-coordinated phenolate 7 is converted to the free o-acylphenol 2. By an analogous route, involving an electrophilic aromatic substitution para to the phenolate oxygen, the corresponding para-acylphenol is formed. 

A review of solvent properties of, and organic reactivity in, ionic liquids demonstrates the relatively small number of quantitative studies of electrophilic aromatic substitution in these media.3 Studies mentioned in the review indicate conventional polar mechanisms. 1-Methylpyrrole reacts with acyl chlorides in the ionic liquid 1-butylpyridinium tetrafluoroborate to form the corresponding 2-acylpyrrole in the presence of a catalytic amount of ytterbium(III) trifluoromethanesulfonate.4 The ionic liquid-catalyst system is recyclable. Chloroindate(III) ionic liquids5 are catalytic media for the acylation, using acid chlorides and anhydrides, of naphthalene, benzene, and various substituted benzenes at 80-120 °C. Again the ionic liquid is recyclable. 

Aromatic compounds react mainly by electrophilic aromatic substitution, in which one or more ring hydrogens are replaced by various electrophiles. Typical reactions are chlorination, bromination, nitration, sulfonation, alkylation, and acylation (the last two are Friedel-Crafts reactions). The mechanism involves two steps addition of the electrophile to a ring carbon, to produce an intermediate benzenonium ion, followed by proton loss to again achieve the (now substituted) aromatic system. 

Acylation Mechanisms of Electrophilic Aromatic Substitution (page 696) ElectrophilicAromatic Substitution Reactions (page 699)... 

The reaction presented in this problem is known as a Friedel-Crafts acylation. Technically, this example belongs to a class of reactions referred to as electrophilic aromatic substitutions. Furthermore, the actual mechanism associated with this reaction, utilizing Lewis acid reagents as catalysts, proceeds through initial formation of an electrophilic acyl cation followed by reaction with an aromatic ring acting as a nucleophile. This mechanism, shown below, reflects distinct parallels to standard addition-elimination reaction mechanisms warranting introduction at this time. 

Please note that while the Friedel-Crafts acylation reaction is presented in discussions of addition-elimination reaction mechanisms, this reaction is actually an electrophilic aromatic substitution reaction. The correct mechanisms for a Freidel-Crafts acylation was presented in the solution for Problem 6 (h) from Chapter 7. 

The mechanism of Friedel-Crafts acylation (shown next) resembles that for alkylation, except that the electrophile is a resonance-stabilized acylium ion. The acylium ion reacts with benzene or an activated benzene derivative via an electrophilic aromatic substitution to form an acylbenzene. 

Predict products and propose mechanisms for the common electrophilic aromatic substitutions halogenation, nitration, sulfonation, and Friedel-Crafts alkylation and acylation. Problems 17-44, 47, 48, 51, 59, G4, and 70... 

Draw a mechanism for the acylation of anisole by propionyl chloride. Recall that Friedel-Crafts acylation involves an acylium ion as the electrophile in electrophilic aromatic substitution. 

In Friedel-Crafts acylation, the Lewis acid AICI3 ionizes the carbon-halogen bond of the acid chloride, thus forming a positively charged carbon electrophile called an acylium ion, which is resonance stabilized (Mechanism 18.7). The po.sitively charged carbon atom of the acylium ion then goes on to react with benzene in the two-step mechanism of electrophilic aromatic substitution. 

Benzene s aromaticity causes it to undergo electrophilic aromatic substitution reactions. The electrophilic addition reactions characteristic of alkenes and dienes would lead to much less stable nonaromatic addition products. The most common electrophilic aromatic substitution reactions are halogenation, nitration, sulfonation, and Friedel-Crafts acylation and alkylation. Once the electrophile is generated, all electrophilic aromatic substitution reactions take place by the same two-step mechanism (1) The aromatic compound reacts with an electrophile, forming a carbocation intermediate and (2) a base pulls off a proton from the carbon that... 

In choosing the Key Mechanisms, I ve used two major criteria. If the mechanism is one of the fundamental mechanisms that make up the longer, more complex mechanisms, then it must be a Key Mechanism. Examples are S l, 5 2, El, E2, nucleophilic acyl substitution, electrophilic aromatic substitution, and so forth. The other criterion is more subjective. If the mechanism is one of the ones I routinely expect students to do on exams, then it is a Key Mechanism. Examples are formation of imines and acetals, aldol and Claisen condensations, and so oa If you feel I have left one out or included one that should not be a Key Mechanism, please let me know. 

Isotope effects are also useful in providing insight into other aspects of the mechanisms of individual electrophilic aromatic substitution processes. In particular, since primary isotope effects are expected only when the breakdown of the rate-determining, the observation of a substantial kn/ko points to rate-determining deprotonation. Some typical isotope effects are summarized in Table 9.7. While isotope effects are rarely observed for nitration and halogenation, Friedel-Crafts acylation, sulfonation, nitrosation, and diazo coupling provide examples in which the rate of proton abstraction can control the rate of substitution. 

The Stolle reaction is thought to occur via a typical mechanism for amide formation from an amine and acid chloride, followed by Friedel-Crafts alkylation or acylation. No definitive mechanistic work has been performed on this reaction, but incorporating the mechnistic understandings of two steps provides a firm basis for understanding the mechanism of this reaction. Formation of the mono-amide from oxalyl chloride and aniline provides intermediate 4, which in the presence of AICI3 undergoes intramolecular electrophilic aromatic substitution to the desired 2,3-dioxindole (isatin) 7 via intermediates 5 and 6. 

A Friedel-Crafts acylation is an electrophilic aromatic substitution in which the electrophile (E ) is an acylium ion. There are other methods of forming acylium ions, such as treatment of an anhydride with a Lewis acid. The resulting acylium ion can also be attacked by a benzene ring, resulting in acylation of the aromatic ring. With this in mind, draw the mechanism of the following transformation ... 

Benzene undergoes electrophilic aromatic substitution with anhydrides, compounds having the general structure (RC0)20, in a reaction that resembles Friedel-Crafts acylation. Draw a stepwise mechanism for the reaction of benzene with glutaric anhydride in the presence of AICI3. 

Gallium(lll) oxide supported on MCM-41 mesoporous silica shows high catalytic activity with little or no moisture sensitivity in the acylation of aromatics wifh acyl chlorides. The cafalysf is utilized in 1,2-dichloro-ethane af 80°C for 3 h wifh differenf aromatic compounds, and aromatic as well as aliphatic acyl chlorides, giving ketones in 54%-82% yield. The activity order of fhe aromatic subsfrafes is benzene (43% yield) < toluene (50% yield) < mesifylene (71% yield) < anisole (79% yield), in agreement with the electrophilic substitution trend previously observed. This acylation reaction follows a probable redox mechanism similar to thaf described in Scheme 4.26. ... 

With this purpose, several different types of solid acid catalysts have been investigated for the acylation of aromatics, but the best performances have been obtained with medium-pore and large-pore zeolites (3-9). In general, however, the use of acylating agents other then halides, e.g., anhydrides or acids, is limited to the transformation of aromatic substrates highly activated towards electrophilic substitution. In a previous work (10), we investigated the benzoylation of resorcinol (1,3-dihydroxybenzene), catalyzed by acid clays. It was found that the reaction mechanism consists of the direct 0-benzoylation with formation of resorcinol monobenzoate, while no primary formation of the product of C-benzoylation (2,4-dihydroxybenzophenone) occurred. The latter product formed exclusively by... 

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