Acylium electrophile

The electrophile in a Friedel-Crafts acylation reaction is an acyl cation (also referred to as an acylium ion) Acyl cations are stabilized by resonance The acyl cation derived from propanoyl chloride is represented by the two resonance forms... 

Friedel-Crafts acylation of aromatic compounds (Section 12 7) Acyl chlorides and carboxylic acid anhydrides acylate aromatic rings in the presence of alumi num chloride The reaction is electrophil ic aromatic substitution in which acylium ions are generated and attack the ring... 

Oxidative Ring Closure Reactions 4.03.4.1.1 C—N bond formation N—N bond formation C—S bond formation N—S bond formation O—C bond formation O—N bond formation S—S, S—Se and Se—Se bond formation Electrophilic Ring Closures via Acylium Ions and Related Intermediates Ring Closures via Intramolecular Alkylations... 

Electrophilic Ring Closures via Acylium Ions and Related Intermediates... 

The mesomeric anion (157 Scheme 10) reacts readily with electrophilic reagents such as alkyl or acyl halides at N-2, C-4 and the exocyclic oxygen atom. The percentages of the different products formed are controlled by the HSAB principle. The acylium ion (hard) attacks preferentially at oxygen (hard), whilst the softer alkylating agents attack the nitrogen atom. 

Friedel-Crafts acylation usually involves the reaction of an acyl halide, a Lewis acid catalyst, and the aromatic substrate. Several species may function as the active electrophile, depending on the reactivity of the aromatic compound. For activated aromatics, the electrophile can be a discrete positively charged acylium ion or the complex formed... 

This provides unequivocal evidence that the acylium ion can act as the active electrophile. 

The activation energies were computed to 3.0 (toward 183), 0.3 (toward 182), and 21.8 kcal/mol (toward 184) at the B3-LYP/6-31G level, and thus the mechanism leading to 182 is the preferred one. The transition states of all three reactions belong to concerted but asynchronous reaction paths. The transacetalization of 177 with acylium cations results in the formation of the thermodynamically stabilized 187 (Scheme 121) [97JCS(P2)2105]. 186 is less stable than 187, and 185 is destabilized by 32.5 kcal/mol. Moreover, transacetalization of 177 with sulfinyl cations is not a general reaction. Further computational studies on dioxanes cover electrophilic additions to methylenedioxanes [98JCS(P2)1129] and the influence... 

The reaction is initiated by formation of a donor-acceptor complex 4 from acyl chloride 2, which is thereby activated, and the Lewis acid, e.g. aluminum trichloride. Complex 4 can dissociate into the acylium ion 5 and the aluminum tetrachloride anion 4 as well as 5 can act as an electrophile in a reaction with the aromatic substrate ... 

Depending on the specific reaction conditions, complex 4 as well as acylium ion 5 have been identified as intermediates with a sterically demanding substituent R, and in polar solvents the acylium ion species 5 is formed preferentially. The electrophilic agent 5 reacts with the aromatic substrate, e.g. benzene 1, to give an intermediate cr-complex—the cyclohexadienyl cation 6. By loss of a proton from intermediate 6 the aromatic system is restored, and an arylketone is formed that is coordinated with the carbonyl oxygen to the Lewis acid. Since a Lewis-acid molecule that is coordinated to a product molecule is no longer available to catalyze the acylation reaction, the catalyst has to be employed in equimolar quantity. The product-Lewis acid complex 7 has to be cleaved by a hydrolytic workup in order to isolate the pure aryl ketone 3. 

The Lewis acid complex 4 can cleave into an ion-pair that is held together by the solvent cage, and that consists of an acylium ion and a Lewis acid-bound phenolate. A fr-complex 6 is then formed, which further reacts via electrophilic aromatic substitution in the ortho- or para-position ... 

Ether cleavage can also be effected by reaction with acetic anhydride and Lewis acids such as BF3, FeCl3, and MgBr2.97 Mechanistic investigations point to acylium ions generated from the anhydride and Lewis acid as the reactive electrophile. 

These reactions probably involve acylium ions as the electrophiles. 

As in the alkylation reaction, the reactive intermediate in Friedel-Crafts acylation can be a dissociated acylium ion or a complex of the acid chloride and Lewis acyl.49 Recent mechanistic studies have indicated that with benzene and slightly deactivated derivatives, it is the protonated acylium ion that is the kinetically dominant electrophile.50... 

The cleavage of C5-C4 and formation of C5-C3 suggests that we have a 1,2-alkyl migration of C5 from C4 to a cationic C3. Then the electrons in the C2-C3 bond can move to form a new n bond between C3 and C4, leaving a stabilized acylium ion at C2. After addition of H2O to the acylium ion, an acid-catalyzed electrophilic addition of the resultant carboxylic acid to the alkene occurs to give the final product. 

The acylium ion is now our electrophile, and aromatic substitution proceeds in the predicted manner. 

Now the electrophilic attack of the aromatic system onto the acylium cation. The product is para substituted, so go for that site of attack. We then need removal of a proton, and chloride is the obvious base, but since this is complexed as AlC, we need the latter to decompose to chloride and AICI3. 

Friedel-Crafts reactions are electrophilic substitution reactions in which the electrophile is a Ccirbocation or an acylium ion. The removal of a halide ion from an alkyl halide is the means of generating the ceirbocation. An acylium ion is created by removing a chloride ion from an acid chloride (R-CO-Cl). Both of these processes require a Lewis acid as a catalyst. The most commonly used Lewis acid is aluminum chloride. 

A Friedel-Crafts acylation is a synthetic method that avoids the problem of rearrangement of the cation. Figure 7-10 illustrates the generation of the electrophile (the acylium ion) from an acid chloride. The presence of resonance stabilizes the acylium ion, and that reduces the possibility of rearrangement. 

Regioselectivity in Friedel-Crafts acylations can be quite sensitive to the reaction solvent and other procedural variables.45 In general, para attack predominates for alkylbenzenes.46 The percentage of ortho attack increases with the electrophilicity of the acylium ion, and as much as 50% ortho product is observed with the formylium and... 

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