Electrophilic Attack on C-Substituted Benzenes

In addition to electrophilic attack on the pyrrole ring in indole, there is the possibility for additions to the fused benzene ring. First examine the highest-occupied molecular orbital (HOMO) of indole. Which atoms contribute the most What should be the favored position for electrophilic attack Next, compare the energies of the various protonated forms of indole (C protonated only). These serve as models for adducts formed upon electrophilic addition. Which carbon on the pyrrole ring (C2 or C3) is favored for protonation Is this the same as the preference in pyrrole itself (see Chapter 15, Problem 2)1 If not, try to explain why not. Which of the carbons on the benzene ring is most susceptible to protonation Rationalize your result based on what you know about the reactivity of substituted benzenes toward electrophiles. Are any of the benzene carbons as reactive as the most reactive pyrrole carbon Explain. 

Probtom 11.12 (a) Draw enthalpy-reaction diagrams for the first step of electrophilic attack on benzene, toluene (meia and para) and nitrobenzene (meta and para). Assume all ground states have the same energy, (b) Where would the para and meta substitution curves for C HjCI lie on this diagram ... 

Polycyclic aromatic hydrocarbons undergo electrophilic aromatic substitution when treated with the same reagents that react with benzene In general polycyclic aromatic hydrocarbons are more reactive than benzene Most lack the symmetry of benzene how ever and mixtures of products may be formed even on monosubstitution Among poly cyclic aromatic hydrocarbons we will discuss only naphthalene and that only briefly Two sites are available for substitution m naphthalene C 1 and C 2 C 1 being normally the preferred site of electrophilic attack... 

In benzimidazole (2), electrophilic substitution occurs most readily in the fused benzene ring, commonly at C-5 a second substituent usually enters at C-6, although in all cases groups already present on the molecules can substantially modify the usual orientation of substitution. Thus, in benzimidazoles, a strongly electron-releasing group at C-5 will direct subsequent attack to C-4 electron-withdrawing substituents lead to subsequent attack at C-4 or C-6. Increased reactivity is achieved if the molecules can be induced to react in their anionic forms. ... 

In early phenol alkylation studies 61), we noticed that alkylation of phenol with ethylene occurred at 204°C, a temperature much higher than that required for ethylation of the much less nucleophilic benzene nucleus (121°C) under similar conditions. Superficially, at least, this appears to violate the classical laws of electrophilic substitution (24). Closer examination of this system 62, 64), however, showed that phenol, at moderately low temperatures, was specifically adsorbed at sites active for alkylation, thus hindering adsorption of ethylene at these same sites, and preventing generation of the electrophile necessary for attack on the phenyl nucleus. That is, alkylation by a Rideal-type mechanism see Scheme 5) cannot occur until temperatures high enough to desorb phenol from the active sites—and allow ethylene to compete for adsorption— are obtained. In such systems, alkylation can be facilitated by imposition of pressure (in the case of ethylene), or use of more polar or higher... 

The position of electrophilic substitution of quinolones and isoquinolones depends upon the pH of the reaction medium. Each type protonates on carbonyl oxygen so reactions in strongly acidic media involve attack on this cation the contrast can be illustrated by the nitration of 4-quinolone at different acid strengths. The balance between benzene ring and unprotonated heterocyclic ring selectivity is small, for example 2-quinolone chlorinates preferentially, as a neutral molecule, at C-6, and only secondly at C-3. 

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