Electrophilic aromatic substitution reactions direct protonation

If the other reactant is an electrophile and a strong Lewis acid or proton acid is present, then the aromatic ring acts as the nucleophile and the reaction is one of the electrophilic aromatic substitution reactions listed in Table 17.2. Do not forget to consider the directive and rate effects of substituents on the aromatic ring. 

The overall reaction is the substitution of an electrophile (E+) for a proton (H+) on the aromatic ring electrophilic aromatic substitution. This class of reactions includes substitutions by a wide variety of electrophilic reagents. Because it enables us to introduce functional groups directly onto the aromatic ring, electrophilic aromatic substitution is the most important method for synthesis of substituted aromatic compounds. 

In bromination (Mechanism 18.2), the Lewis acid FeBr3 reacts with Br2 to form a Lewis acid-base complex that weakens and polarizes the Br- Br bond, making it more electrophilic. This reaction is Step [1] of the mechanism for the bromination of benzene. The remaining two steps follow directly from the general mechanism for electrophilic aromatic substitution addition of the electrophile (Br in this case) forms a resonance-stabilized carbocation, and loss of a proton regenerates the aromatic ring. 

In another study, Arkin and Hazer modified the PHA-Cl into quaternary ammonium salts, thiosulfate moieties and phenyl derivatives. In addition, they cross-linked the modified PHA-Cl with benzene by electrophilic aromatic substitution using a Friedel-Crafts reaction. The random composition of PHA-Cl was calculated from its H NMR spectrum by comparing the relative peak areas of the methine protons on the polymer backbone. Hence, increased chlorination of the methyl protons caused the peak of methine protons to be moved further downfield. In addition, the PHA-Cl mole fractions were calculated by comparing the peak areas of protons on chlorinated a-carbons and protons on p-carbons. Samsuddin et al. ° described a process for the direct fluorination of PHBHHx at elevated pressure in the... 

From a theoretical point of view, the key issue has been the basic nature of the metalation step, where the R groups moves from a R -H bond to a M-R bond. C-H activation is very common in organic chemistry as it allows the formation of functionalized hydrocarbons. Different mechanisms had been proposed for this metalation step, including electrophilic aromatic substitution, a-bond metathesis, oxidative addition/reductiveelimination and Heck-like insertion. Theoretical studies have facilitated narrowing the mechanistic possibilities to two main options oxidative addition/reductive elimination and proton abstraction by a base. In the oxidative addition/reductive elimination process the metal is inserted in the C-H bond with formal increase in the oxidation state of the metal, and the hydride leaves the metal coordination sphere of the metal afterwards. In the proton abstraction mechanism, the metal does not interact directly with the proton, which is captured by a base, with simultaneous formal creation of a carbanion that binds to the metal center. The mechanism of the reaction will depend on the presence of a base able to abstract the proton and of the existence of an energetically accessible oxidation state for the metal. 

Therefore, it is justifiable to assume that the protonation of CO is extremely difficult compared to that of the aromatic substrates involved in the formylation reactions vide supra) and that the equilibria involved should rather be to the left for equation 2.18 and right for equation 2.20. This would render the concentration of reacting species in the proposed electrophilic aromatic substitution extremely low and be expected to result in almost no reaction a result in direct contrast to experimental observations. 

This awareness in a short time led to new homolytic aromatic substitutions, characterized by high selectivity and versatility. Further developments along these lines can be expected, especially as regards reactions of nucleophilic radicals with protonated heteroaromatic bases, owing to the intrinsic interest of these reactions and to the fact that classical direct ionic substitution (electrophilic and nucleophilic) has several limitations in this class of compound and does not always offer alternative synthetic solutions. Homolytic substitution in heterocyclic compounds can no longer be considered the Cinderella of substitution reactions. 

It is shown that the MP2(/c)/6-31G7//fF/6-31G + ZPE (HF/6-31G ) model reproduces very well the experimental proton affinities in a large number of substituted benzenes and naphthalenes. Extensive applications of this model revealed that the proton affinity of polysubstituted aromatics followed a simple additivity rule, which have been rationalized by the ISA (independent substituent approximation) model. Performance of this model is surprisingly good. Applications of proton affinities, obtained by the transparent and intuitively appealing ISA model, in interpreting directional ability of substituents in the electrophilic substitution reactions of aromatics are briefly discussed. 

The second pathway for electrophilic substitution requires coordination of the C—H bond to a Lewis acidic metal center, which depletes electron density of the C—H moiety and enhances its acidity and, hence, increases the propensity toward proton transfer. This reaction can occur with both aromatic substrates and alkanes. It is known that the coordination of dihydrogen can substantially increase the acidity of H2 4 and it is reasonable to assume that a similar effect can occur through metal coordination of C—H bonds, particularly with highly Lewis acidic metals. Although the pK values of hydrocarbons coordinated to metal centers have not been directly measured, the acidity of intramolecular agostic bonds has been reported.2... 

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