The Reaction Intermediate or Sigma-Complex Approach

Pankratov in 2000 computed relative a-complex energies for nitration, which he referred to as cationic localization energies, for a large number of monosubstituted benzenes by the use of the semiempirical PM3 method [91]. Good linear relationships were found for predicting the positional selectivity from the a-complex energies. However, different scaling factors were needed for the different positions, that is, the ortho, meta, and para positions. 

In this chapter, we have reviewed the current mechanistic understanding of the S Ar reaction based on experimental and theoretical studies. The nitration reaction often proceeds via the formation of two consecutive x-complexes before the appearance of the o-complex. The first complex involves the coordination of an oxygen to the aromatic ring center, whereas the second complex, which seems to be present in all nitrations, has the N-atom of the nitronium ion coordinated to one of the ring C-atoms. In the gas phase, the nitration may have a contribution from a SET, and this contribution increases with the activation tendency of the aromatic substrate. The solution reaction lacks a driving force for SET, and the rate-determining step is the transformation of the C-atom coordinated x-complex into the o-complex. This step has a very early transition state corresponding to a loosely bound x-complex. The deprotonation of the o-complex is fast in the presence of water. 

The uncatalyzed halogenation with molecular chlorine as the electrophile proceeds via a C-atom coordinated x-complex before the formation of the o-complex. In solution, the latter has a Cl—Cl bond that is nearly dissociated. The rate-determining transition state is similar in structure to the o-complex. Deprotonation of the o-complex is easily facilitated even by a weak base, but the process requires the leaving of the Cl formed fiorn the electrophile to occur before the abstraction of the proton. 

Other SgAr reactions are less well studied by theoretical methods, and kinetic measurements indicate that the mechanisms often are complex. In the case of sulfonation, both theory and experiments show that the reaction is second order in the electrophile and first order in the nucleophile in a nonpolar environment, whereas a polar solvent promotes a traditional second-order SgAr mechanism. 

Reaction indices have been frequently used to analyze and predict positional selectivity of S Ar reactions. The average local ionization energy, 7(r), seems to have the best predictive power for this reaction type among the commonly used descriptors. Local minima in /(r) reflect both the positional selectivity for S Ar and the relative reactivity in aromatic and heteroaromatic systems. The 7(r) approach generally has quantitative predictive capacity for nitrations and halogenation, but it has problems for systems where steric hindrance is of key importance for the regioselectivity. 

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