Electrophilic aromatic substitution reaction resonance effects

The effect that substituents already present have on electrophilic aromatic substitution reactions represents an area of structure-reactivity relationships that has been under study since about 1870. The classification of substituents as activating and ortfto-para-directing or deactivating and mete-directing has been known since those early studies. A basic understanding of these substituent effects became possible when ideas about electronic interactions and resonance theory were... 

In order to understand these resonance effects, let us begin by recalling the effect of the amino group on electrophilic aromatic substitution reactions. The amino group is not only a powerful activating group, it is also a powerful ortho—para director. We saw earlier (Section 15.10D) that aniline reacts with bromine in aqueous solution at room temperature and in the absence of a catalyst to yield a product in which both ortho positions and the para position are substituted. 

There were two schools of thought concerning attempts to extend Hammett s treatment of substituent effects to electrophilic substitutions. It was felt by some that the effects of substituents in electrophilic aromatic substitutions were particularly susceptible to the specific demands of the reagent, and that the variability of the polarizibility effects, or direct resonance interactions, would render impossible any attempted correlation using a two-parameter equation. - o This view was not universally accepted, for Pearson, Baxter and Martin suggested that, by choosing a different model reaction, in which the direct resonance effects of substituents participated, an equation, formally similar to Hammett s equation, might be devised to correlate the rates of electrophilic aromatic and electrophilic side chain reactions. We shall now consider attempts which have been made to do this. 

Resonance effects are the primary influence on orientation and reactivity in electrophilic substitution. The common activating groups in electrophilic aromatic substitution, in approximate order of decreasing effectiveness, are —NR2, —NHR, —NH2, —OH, —OR, —NO, —NHCOR, —OCOR, alkyls, —F, —Cl, —Br, —1, aryls, —CH2COOH, and —CH=CH—COOH. Activating groups are ortho- and para-directing. Mixtures of ortho- and para-isomers are frequently produced the exact proportions are usually a function of steric effects and reaction conditions. 

We will address this issue further in Chapter 10, where the polar effects of the substituents on both the c and n electrons will be considered. For the case of electrophilic aromatic substitution, where the energetics of interaction of an approaching electrophile with the 7t system determines both the rate of reaction and position of substitution, simple resonance arguments are extremely useful. 

Probably the most important development of the past decade was the introduction by Brown and co-workers of a set of substituent constants,ct+, derived from the solvolysis of cumyl chlorides and presumably applicable to reaction series in which a delocalization of a positive charge from the reaction site into the aromatic nucleus is important in the transition state or, in other words, where the importance of resonance structures placing a positive charge on the substituent - -M effect) changes substantially between the initial and transition (or final) states. These ct+-values have found wide application, not only in the particular side-chain reactions for which they were designed, but equally in electrophilic nuclear substitution reactions. Although such a scale was first proposed by Pearson et al. under the label of and by Deno et Brown s systematic work made the scale definitive. 

The effect of a substituent on the aromatic substitution reaction is similar to its effect on electrophilic side chain reactions, but not precisely parallel. Thus the Hammett relationship using the usual sigma or substituent constants gives considerable scatter when applied to aromatic substitution. The scatter is probably due to an increased importance of resonance effects in the nuclear substitution reaction as compared with the side chain reactions. 

The effect of monofluorination on alkene or aromatic reactivity toward electrophiles is more difficult to predict Although a-fluonne stabilizes a carbocation relative to hydrogen, its opposing inductive effect makes olefins and aromatics more electron deficient. Fluorine therefore is activating only for electrophilic reactions with very late transition states where its resonance stabilization is maximized The faster rate of addition of trifluoroacetic acid and sulfuric acid to 2-fluoropropene vs propene is an example [775,116], but cases of such enhanced fluoroalkene reactivity in solution are quite rare [127] By contrast, there are many examples where the ortho-para-dueeting fluorine substituent is also activating in electrophilic aromatic substitutions [128]... 

There are similarities between nucleophilic aromatic substitution (SnAt) and its more usual counterpart, electrophilic aromatic substitution. Each involves the formation of a resonance-stabilized intermediate, and each involves a temporary loss of aromaticity that is regained in the final step of the reaction. But the similarities are only so deep. The electrophilic reaction involves cationic intermediates the nucleophilic involves anionic intermediates. Use the differing effects of a nitro group, strongly deactivating in the electrophilic substitution and strongly activating in the nucleophilic substitution, to keep the two mechanisms distinct in your mind. 

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