Electrophilic aromatic substitution reactions cationic electrophile formation

Keep in mind that the mechanisms of electrophilic aromatic substitution reactions are all very similar. After the formation of the electrophile, attack of the electrophile on the aromatic ring occurs to give a resonance-stabilized cation intermediate.The last step of the mechanism is proton transfer to a base to regenerate the aromatic ring. The base in nitration is water, which was generated in the formation of the electrophile. 

There are similarities between nucleophilic aromatic substitution (SnAt) and its more usual counterpart, electrophilic aromatic substitution. Each involves the formation of a resonance-stabilized intermediate, and each involves a temporary loss of aromaticity that is regained in the final step of the reaction. But the similarities are only so deep. The electrophilic reaction involves cationic intermediates the nucleophilic involves anionic intermediates. Use the differing effects of a nitro group, strongly deactivating in the electrophilic substitution and strongly activating in the nucleophilic substitution, to keep the two mechanisms distinct in your mind. 

As mentioned above, ferrocene is amenable to electrophilic substitution reactions and acts like a typical activated electron-rich aromatic system such as anisole, with the limitation that the electrophile must not be a strong oxidizing agent, which would lead to the formation of ferrocenium cations instead. Formation of the CT-complex intermediate 2 usually occurs by exo-attack of the electrophile (from the direction remote to the Fe center. Fig. 3) [14], but in certain cases can also proceed by precoordination of the electrophile to the Fe center (endo attack) [15]. 

Step (1) is reminiscent of electrophilic addition to an alkene. Aromatic substitution differs in that the intermediate carbocation (a benzenonium ion) loses a cation (most often to give the substitution product, rather than adding a nucleophile to give the addition product. The benzenonium ion is a specific example of an arenonium ion, formed by electrophilic attack on an arene (Section 11.4). It is also called a sigma complex, because it arises by formation of a o-bond between E and the ring. See Fig. 11-1 for a typical enthalpy-reaction curve for the nitration of an arene. 

For non-electrophilic strong oxidants, the reaction with an alkane typically follows an outer-sphere ET mechanism. Photoexcited aromatic compounds are among the most powerful outer-sphere oxidants (e.g., the oxidation potential of the excited singlet state of 1,2,4,5-tetracyanobenzene (TCB) is 3.44 V relative to the SCE) [14, 15]. Photoexcited TCB (TCB ) can generate radical cations even from straight-chain alkanes through an SET oxidation. The reaction involves formation of ion-radical pairs between the alkane radical cation and the reduced oxidant (Eq. 5). Proton loss from the radical cation to the solvent (Eq. 6) is followed by aromatic substitution (Eq. 7) to form alkylaromatic compounds. 

By theoretical calculations (B3LYP/6-31G ) four reaction pathways were investigated formation of endo or egzo product with initial bond formation to C2 or C3 in indole. For each mechanism theoretical 13C KIE were analysed and the best agreement of theoretical and experimental KIEs was found for the reaction involving the intermediacy of the radical cation 11, resulting from electrophilic aromatic substitution of indole at C3 by cyclohexadiene in the rate-limiting step ... 

We suggest that electron transfer and electrophilic substitutions are, in general, competing processes in arene oxidations. Whether the product is formed from the radical cation (electron transfer) or from the aryl-metal species (electrophilic substitution) is dependent on the nature of both the metal oxidant and the aromatic substrate. With hard metal ions, such as Co(III), Mn(III), and Ce(IV),289 reaction via electron transfer is preferred because of the low stability of the arylmetal bond. With soft metal ions, such as Pb(IV) and Tl(III), and Pd(II) (see later), reaction via an arylmetal intermediate is predominant (more stable arylmetal bond). For the latter group of oxidants, electron transfer becomes important only with electron-rich arenes that form radical cations more readily. In accordance with this postulate, the oxidation of several electron-rich arenes by lead(IV)281 289 and thallium(III)287 in TFA involve radical cation formation via electron transfer. Indeed, electrophilic aromatic substitutions, in general, may involve initial charge transfer, and the role of radical cations as discrete intermediates may depend on how fast any subsequent steps involving bond formation takes place. 

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. 

Hydroarylation can also be mediated by Au(I) and Au(III) (Scheme 33) (384). In the case of aryl substituted alkynes, the Au(III) Ji complex undergoes electrophilic aromatic substitution with the electron-rich arene to give aLkenyl-Au(III) complex, which is immediately protonated by the H generated upon C C bond formation. For the Au(I)-catalyzed hydroarylation, the cationic gold complex k coordinates the alkyne, with subsequent nucleophilic attack by the arene from the opposite face leading to an alkenyl-gold complex, which is protonated to the desired products. The nature of the reaction causes the regioselectivity of this reaction to be sensitive to electronic rather than steric factors. 

The previous sections leave no doubts that aromatic compounds, react with positively charged electrophiles to form a-complexes-arenium ions. But are they the primary intermediates It is not by accident that the problem of preliminary formation of radical cations has arisen. Its statement is an attempts to explain the orientational peculiarities of electrophilic aromatic substitution of hydrogen. The widespread view that the orientation in the reactions of aromatic compounds with electrophiles is dictated by the relative stabilities of the cr-complexes explains but a part of the accumulated material. In the first place this refers to the meta- and para-orienting effects of electron-releasing substituents in benzene in terms of the QCT -approach and to that of the relative reactivity of various aromatic substrates... 

We begin with the fact that the rate of electrophilic aromatic substitution is determined by the slowest step in the mechanism, which, in almost every reaction of an electrophile with the aromatic ring, is attack of the electrophile on the ring to give a resonance-stabilized cation intermediate. Thus, we must determine which of the alternative carbocation intermediates (that for ortho-para substitution or that for meta substitution) is the more stable. That is, we need to show which of the alternative cationic intermediates has the lower activation energy for its formation. 

By far the most important reaction in this chapter is electrophilic aromatic substitution by a variety of electrophiles (E ). This reaction involves the initial formation of a resonance-stabilized, but not aromatic, cyclohexadienyl cation. Deprotonation regenerates an aromatic system (Fig. 14.119). 

The complex that is formed can dissociate to form a cation (n-tr-complex) and an iodide anion, with the iodide ion reacting with the excess iodine molecules that are present. In addition the decomposition of the n-cr-complex can lead to the formation of highly reactive iodine cations, which can initiate further reactions — e.g. oxidations or electrophilic substitutions of aromatic systems [11, 13]. 

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