Electrophilic substitution, aromatic kinetic control

Seemingly anomalous effects of substituents are known, but such effects may be due to equilibrium control. One example is the aluminum chloride-catalyzed alkylation of benzene, which leads to the formation of a 1,3,5-trialkylbenzene in preference to the expected 1,2,4-isomer (see Section 22-4E). The preferred reaction occurs particularly readily because alkylation is reversible and because alkylation is one of the least selective of the electrophilic aromatic substitutions (considerable meta isomer is formed even under conditions where kinetic control is dominant). Equilibrium control, which favors the 1,3,5-product rather than the less stable 1,2,4-product, becomes most evident when the reaction time, the reaction temperature, and aluminum chloride concentration are increased. Another source of anomalous substituent effects is discussed in the next section. 

The text points out that C-l of naphthalene is more reactive than C-2 toward electrophilic aromatic substitution. Thus, of the two possible products of sulfonation, naphthalene-1-sulfonic acid should be formed faster and should be the major product under conditions of kinetic control. Since the problem states that the product under conditions of thermodynamic control is the other isomer, naphthalene-2-sulfonic acid is the major product at elevated temperature. 

First, it is important to note that most aromatic electrophilic substitution reactions are under kinetic, and not thermodynamic, control. This is because most of the reactions are irreversible, and the remainder are usually stopped before equilibrium is reached. In a kinetically controlled reaction, the distribution of products (or product spread), i.e. the ratio of the various products formed, is determined not by the thermodynamic stabilities of the products, but by the activation energy barrier that controls the rate determining step. In a two-step reaction, it is a reasonable assumption that the transition state of the rate determining step is close in energy to that of the intermediate, which in this case is the Wheland intermediate and so by invoking the Hammond postulate, one may assume that they have similar geometries. 

Aromatic electrophilic substitution reactions are under kinetic, and not thermodynamic, control. This is because many of the reactions are irreversible, and the remainder are usually stopped before equilibrium is reached. 

Electrophilic substitution of aromatic (and heteroaromatic) molecules proceeds via a two-step sequence, initial addition (of EF) giving a positively charged intermediate (a o-complex, or Wheland intermediate), then elimination (normally of H ), of which the former is usually the slower (rate-determining) step. Under most circumstances such substitutions are irreversible and the product ratio is determined by kinetic control. 

On the whole the effect of substituents on the relative stability of isomeric arenium ions (for details see Sect. IV, 1) is described in the same terms as those used to explain the influence of substituents on the orientation and relative rates of electrophilic aromatic substitution. However, the isomeric composition of electrophilic substitution products is often controlled by kinetic factors while the equilibrium composition of isomeric arenium ions formed in aromatic compound protonation is determined by thermodynamic equilibrium. Therefore, no quantitative agreement may be observed between the relative hydrogen substitution rates at different positions of this compound and the ratio of equilibrium concentrations of the respective arenium ions formed in protonating the same compound even under identical conditions (cf. Sect. IV, 7). 

It can be demonstrated that the reactions are kinetically controlled. It is therefore the value that holds the key to the connection between the rate effects and the substituent s directing effects. But to discuss AG satisfactorily, we must know something about the reaction mechanism and the nature of the competing transition states. Electrophilic aromatic substitution will be discussed in detail in Chapter 10. 

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