Attack on Substituted Aromatic Rings

The rates of attack of radicals on aromatic rings correlate with ionisation potential, with localisation energy and with superdelocalisability (see page 130), a picture reminiscent of the situation in aromatic electrophilic substitution. As in that field, there are evidently a number of related factors affecting reactivity. Frontier orbitals provide useful explanations for a number of observations in the field. 

The partial rate factors of Table 7.1 show that a phenyl radical reacts with nitrobenzene and anisole faster than it does with benzene. This can readily be explained if the energy levels come out, as they plausibly might, in the order shown in Fig. 7.3. 

With anisole, the SOMO/HOMO interaction (B) is strong, and with nitrobenzene the SOMO/LUMO interaction (A) is strong, but with benzene neither is stronger than the other. Product development control can also explain this, since the radicals produced by attack on nitrobenzene and anisole will be more stabilised than that produced by attack on benzene. However, this cannot be the explanation for another trend which can be seen in Table 7.1, namely that a p-nitrophenyl radical reacts faster with anisole and benzene than it does with nitrobenzene. This is readily explained if the SOMO of the p-nitrophenyl radical is lower in energy than that of the phenyl radical, making the SOMO/HOMO interactions (C and D) strong with the former pair. 

In hydrogen atom abstractions, alkyl radicals change, as the degree of substitution increases, from being mildly electrophilic (the methyl radical) to being mildly nucleophilic (the ferf-butyl radical). In addition reactions to pyridinium cations, the Minisci reaction, they are all relatively nucleophilic, as shown by their 

The more substituted radicals continue to be measurably the more nucleophilic. The relative rates with which the various alkyl radicals react with the 4-cyan-opyridinium cation (7.33, Y = CN) and the 4-methoxypyridinium cation (7.33, Y = OMe) are given in Table 7.2. The LUMO of the former will obviously be lower than that of the latter. The most selective radical is the ferf-butyl, which reacts 350000 times more rapidly with the cyano compound than with the methoxy. This is because the ferf-butyl radical has the highest-energy SOMO, which interacts (B in Fig. 7.4) very well with the LUMO of the 4-cyanopyridi-nium ion, and not nearly so well (A) with the LUMO of the 4-methoxypyridinium ion. At the other end of the scale, the methyl radical has the lowest-energy SOMO, and hence the difference between the interactions C and D in Fig. 7.4 is not so great as for the corresponding interactions (A and B) of the ferf-butyl radical. Therefore, it is the least selective radical, reacting only 50 times more rapidly with the cyano compound than with the methoxy. 

The most vexed subject in this field is the site of radical attack on substituted aromatic rings. Some react cleanly where we should expect them to. Phenyl radicals add to naphthalene 7.63, to anthracene 7.641017 and to thiophene 7.65,1018 with the regioselectivity shown in the diagrams. In all three cases, the frontier orbitals are clearly in favour of this order of reactivity we should note that, because of the symmetry in these systems, both HOMO and LUMO have the same absolute values for the coefficients, so there is no ambiguity here as to which to take. 

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Draw resonance forms for the sigma complexes resulting from electrophilic attack on substituted aromatic rings. Explain which substituents are activating and which are deactivating, and show why they are ortho, para-directing, or meta-allowing. Problems 17-47,48, 54, 57, 50, and 64... 

The most vexed subject in this field is the site of radical attack on substituted aromatic rings. Some react cleanly where we should expect them to. Phenyl radicals add to naphthalene (399), to anthracene (400)323 and to thiophene... 

The reactivity of allenyl ketones is also manifested in the Hg(II)-catalyzed ipso substitution that converts 54 to spirodione 55 (Eq. 13.17) [19]. The reaction presumably involves activation of the allene by Hg(II), followed by intramolecular electrophilic attack on the aromatic ring. Hydrolytic cleavage of the metal from the intermediate product of the reaction, followed by rearrangement leads to the observed spirocyclic dione. 

Note The thallium functional group is believed to proceed via an electrophilic substitution mechanism. However, the position of attack on the aromatic ring by the Tl group is not as predictable as it was for other electrophiles. For -R, -Q and -OR. the Tl attacks almost exclusively the para position. However, for groups such 0 O... 

Here, once again, the cyclising step involves electrophilic attack on the aromatic ring so the method works best for activated rings, and meto-substituted-aryl ethanamides give exclusively 6-substituted isoquinolines. 

These observations support the electrophilic mechanism for substitution. If the reaction rate depends on electrophilic (that is, electron-seeking) attack on the aromatic ring, then substituents that donate electrons to the ring will increase its electron density and, hence, speed up the reaction substituents that withdraw electrons from the ring will decrease electron density in the ring and therefore slow down the reaction. This reactivity pattern is exactly what is observed, not only with nitration, but also with all electrophilic aromatic substitution reactions. 

The experiments in Sections 15.2 and 15.3 illustrate the Friedel-Crafts alkylation and acylation of aromatic hydrocarbons, respectively. A complication of Friedel-Crafts reactions is apparent in the alkylation experiment, wherein rearrangements of the carbo-cations generated from the alkyl halide provide mixtures of substitution products. The acylation reaction of Section 15.3 provides an example of how a combination of electronic and steric effects can affect the orientation of electrophilic attack on an aromatic ring. 

Since heteroaromatic compounds sometimes exhibit interesting physical properties and biological activities, construction of substituted heteroaromatics has drawn some attention. Heteroaromatics can be divided into two major categories. One is the tt-electron-sufhcient heteroaromatics, such as pyrrole, indole, furan, and thiophene those easily react with electrophiles. The other is the 7r-electron-deficient heteroaromatics, such as pyridine, quinoline, and isoquinoline those have the tendency to accept the nucleophilic attack on the aromatic ring. Reflecting the electronic nature of heteroaromatics, the TT-electron-deflcient ones are usually used as the electrophiles.t The rr-electron-sufficient heteroaromatics having simple structures, such as 2-iodofuran and 2-iodothio-phene, have also been utilized as the electrophiles. Not only the electronic nature of the heteroaromatics but also coordination of the heteroatom to the palladium complexes influence catalytic activity. This is another reason why the couphng reaction did not proceed efficiently in some cases. 

In Chapter 3, it was mentioned that positive ions can form addition complexes with 7T systems. Since the initial step of electrophilic substitution involves attack by a positive ion on an aromatic ring, it has been suggested that such a complex, called a % complex (represented as 10), is formed first and then is converted to the arenium ion 11. Stable solutions of arenium ions or 7t complexes (e.g., with Br2, l2> picric... 

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