Electrophilic substitution substituted benzene

In compounds with a fused benzene ring, electrophilic substitution on carbon usually occurs in the benzenoid ring in preference to the heterocyclic ring. Frequently the orientation of substitution in these compounds parallels that in naphthalene. Conditions are often similar to those used for benzene itself. The actual position attacked varies compare formulae (341)-(346) where the orientation is shown for nitration sulfonation is usually similar for reasons which are not well understood. 

Evidently S, is a measure of intramolecular selectivity because it involves a ratio, the contribution of the benzene substitution rate disappears, and the selectivity factor expresses the selectivity of the reagent X in Eq. (7-83) for the para position relative to the meta position. Each individual partial rate factor, on the other hand, is expressive of an inteimolecular selectivity thus p is a measure of the selectivity of the reagent for the para position in CgHsY relative to benzene. It was observed that Eq. (7-85), where Cmc is a constant, is satisfied for a large number of electrophilic substitutions of toluene. 

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. 

Another drawback to the use of amino-substituted benzenes in electrophilic aromatic substitution reactions is that Friedel-Crafts reactions are not successful (Section 16.3). The amino group forms an acid-base complex with the AICI3 catalyst, which prevents further reaction from occurring. Both drawbacks can be overcome, however, b3 carrying out electrophilic aromatic substitution reactions on the corresponding amide rather than on the free amine. 

Indole has a nonbasic, pyrrole-like nitrogen and undergoes electrophilic substitution more easily than benzene. Substitution occurs at C3 of the electron-rich pyrrole ring, rather than on the benzene ring. 

Documenting the lack of an effect can be just as important as the presence of one. Consider the nitration of benzene, an electrophilic substitution process. The use of... 

The frontier orbital theory was developed for electrophilic aromatic substitution (Chapter Elements of a Chemical Orbital Theory by Inagaki in this volume). Application is successful to the ortho-para orientation (Scheme 23a) for the benzenes substituted with electron donating groups. The ortho and para positions have larger HOMO amplitudes. The meta orientation (Scheme 23b) for the electron accepting groups is under control of both HOMO and the next HOMO [25]. 

Benzene is unusually stable and it is the delocalised electrons that account for this stability. The presence of the delocalised electrons also explains why benzene does not undergo addition reactions. Addition reactions would disrupt the electron delocalisation and so reduce the stability of the ring. Substitution reactions, on the other hand, can occur without any such disruption and the stability of the benzene ring is maintained. The delocalised electrons in the % molecular orbital make benzene susceptible to attack by electrophiles (electron pair acceptors). As a result, benzene undergoes electrophilic substitution reactions and some of these are outlined at the top of the next page. Note that the electrophiles are shown in red, the reagents in blue and the reaction names in green. 

When substituted benzene undergoes electrophilic attack, groups already on the ring affect the reactivity of the benzene ring as weU as the orientation of the reachon. A summary of these effects of substituents on reachvity and orienta-hon of electrophihc substituhon of substituted benzene is presented below. 

Toluene, like benzene, undergoes electrophilic substitutions, where the substitutions take place in ortho and para positions. As the —CH3 group is an activating group, the reaction rate is much faster than usually observed with benzene. For example, the nitration of toluene produces ortho-nitro-toluene (61%) and para-nitrotoluene (39%). 

Pyrrole, furan and thiophene undergo electrophilic substitution reactions. However, the reactivity of this reaction varies significantly among these heterocycles. The ease of electrophilic substitution is usually furan > pyrrole > thiophene > benzene. Clearly, all three heterocycles are more reactive than benzene towards electrophilic substitution. Electrophilic substitution generally occurs at C-2, i.e. the position next to the hetero-atom. 

Electrophilic substitutions Pyridine s electron-withdrawing nitrogen causes the ring carbons to have significantly less electron density than the ring carbons of benzene. Thus, pyridine is less reactive than benzene towards electrophilic aromatic substitution. However, pyridine undergoes some electrophilic substitution reactions under drastic conditions, e.g. high temperature, and the yields of these reactions are usually quite low. The main substitution takes place at C-3. 

The SHMO orbitals of pyrrole, pyridine, and pyridinium are shown in Figure 11.6. The HOMO of pyrrole is the same as that of butadiene. Thus pyrrole is more reactive than benzene toward electrophilic attack. Attack, leading to substitution, occurs mainly at the... 

Electrophilic substitution usually occurs preferentially in the aryl group. In compounds containing both an aryl group and a fused benzene ring, electrophiles usually attack the aryl group exclusively. 

Thiophene is far more reactive than benzene in electrophilic substitution reactions. Reaction with bromine in acetic acid has been calculated to be 1.76 x 109 times faster than with benzene (72IJS(C)(7)6l). This comparison should, of course, be treated with circumspection in view of the fact that the experimental conditions are not really comparable. Benzene in the absence of catalysts is scarcely attacked by bromine in acetic acid. More pertinent is the reactivity sequence for this bromination among five-membered aromatic heterocycles, the relative rates being in the order 1 (thiophene) and 120 (furan) or, for trifluoroacetylation, 1 (thiophene), 140 (furan), 5.3 xlO7 (pyrrole) (B-72MI31300, 72IJS(C)(7)6l). Among the five-membered heteroaromatics, thiophene is definitely the least reactive. 

The SHMO orbitals of pyrrole, pyridine, and pyridinium are shown in Figure 11.6. The HOMO of pyrrole is the same as that of butadiene. Thus pyrrole is more reactive than benzene toward electrophilic attack. Attack, leading to substitution, occurs mainly at the 2- and 5-positions where the electron density of the HOMO is concentrated. In the case of pyridine (Figure 11.6b), the HOMO is not the n orbital, but the nonbonded MO, wn, which would be situated at approximately a - 0.5 //. Thus, it is not pyridine but pyridinium (Figure 11.6c) which undergoes electrophilic attack and substitution. The reactivity is much less than that of benzene, although this could not be deduced directly from the SHMO calculation. Neither does the calculation suggest the reason that electrophilic substitution occurs mainly at the 3- and 5-positions, since the n HOMO is... 

A quantitative description of the reactivity of monosubstituted benzenes to electrophilic substitution based on considerations of inductive effect parameters and con-jugative effect parameters from the 13 C chemical shifts of the aromatic compounds has been proposed.3 MO calculations on the proton migration in the ipso adducts formed in the reaction of CH3+ and SiH3+ with benzene have been described.4 With SiH3+ the ipso adduct is the most stable of possible isomers, whereas for CH3+ the >ara-protonated isomer is the most stable. 

Explain why pyridine is less reactive than benzene in electrophilic aromatic substitution reactions. 

Donor-substituted benzenes and electrophiles should produce mixtures of para- and orf/zo-disubstituted aromatic compounds, in which the /zara-disubstituted product is formed in a greater amount. Only traces of the /neto-disubstitution product are expected, even though a donor-substituted benzene is substituted faster at the meta-C atom than benzene itself at any of its C atoms. 

It is agreed that attack of an electrophilic reagent is directed towards the most reactive centers of a core with high electron density. These centers are carbon atoms in the ortho- and /j ra-positions of the benzene substituted if a substituting group is an electron donor, and in the meta-positions if a substituting group is an electron acceptor. 

When a substituted benzene is nitrated, the substituent on the ring has an effect on the rate of the reaction. In addition, the N02+ electrophile can attach ortho, meta, or para to the substituent. For example, when toluene is nitrated, it is found to react 17 times faster than benzene. Substitution occurs primarily ortho and para to the methyl group. 

Nitrobenzene is about 100,000 times less reactive than benzene toward electrophilic aromatic substitution. For example, nitration of nitrobenzene requires concentrated nitric and sulfuric acids at temperatures above 100 °C. Nitration proceeds slowly, giving the meta isomer as the major product. 

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