Substitution, electrophilic resonance interaction

The best-known equation of the type mentioned is, of course, Hammett s equation. It correlates, with considerable precision, rate and equilibrium constants for a large number of reactions occurring in the side chains of m- and p-substituted aromatic compounds, but fails badly for electrophilic substitution into the aromatic ring (except at wi-positions) and for certain reactions in side chains in which there is considerable mesomeric interaction between the side chain and the ring during the course of reaction. This failure arises because Hammett s original model reaction (the ionization of substituted benzoic acids) does not take account of the direct resonance interactions between a substituent and the site of reaction. This sort of interaction in the electrophilic substitutions of anisole is depicted in the following resonance structures, which show the transition state to be stabilized by direct resonance with the substituent ... 

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. 

The more extensive problem of correlating substituent effects in electrophilic substitution by a two-parameter equation has been examined by Brown and his co-workers. In order to define a new set of substituent constants. Brown chose as a model reaction the solvolysis of substituted dimethylphenylcarbinyl chlorides in 90% aq. acetone. In the case ofp-substituted compounds, the transition state, represented by the following resonance structures, is stabilized by direct resonance interaction between the substituent and the site of reaction. 

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. 

Reactions that occur with the development of an electron deficiency, such as aromatic electrophilic substitutions, are best correlated by substituent constants based on a more appropriate defining reaction than the ionization of benzoic acids. Brown and Okamoto adopted the rates of solvolysis of substituted phenyldimeth-ylcarbinyl chlorides (r-cumyl chlorides) in 90% aqueous acetone at 25°C to define electrophilic substituent constants symbolized o-. Their procedure was to establish a conventional Hammett plot of log (.k/k°) against (t for 16 /wcra-substituted r-cumyl chlorides, because meta substituents cannot undergo significant direct resonance interaction with the reaction site. The resulting p value of —4.54 was then used in a modified Hammett equation. 

One solution for this problem, the most optimistic, suggested the existence of three independent sets of o--constants. The first set, the Hammett constants, would be applicable to side-chain reactions in which resonance interactions between the substituent and the side-chain were either small or insignificant. The second set, the w-constants, would apply to side-chain reactions of phenols and anilines and nucleophilic aromatic substitution reactions in which a negative charge was introduced in the aromatic nucleus (Miller, 1956). A third set, the c7+-constants, would apply to electrophilic substitution and electrophilic side-chain reactions for which resonance interactions between the reaction site and the substituent were important. 

Initially, a series of monoamic acids was prepared in chloroform from substituted phthalic anhydrides and 4-fluoroaniline (Figure 17.4). These syntheses resulted in nearly quantitative yields of crystalline amic acids, which precipitated from the chloroform solvent when cooled. The spectra were measured on these compounds Table 17.1 summarizes the data and indicates in each case which isomer was preferentially formed in chloroform from similar carbon peak heights. Most of the results followed the expected trend as die electron-withdrawing capability of any substituent increased, the carbon wilh which dial substituent could interact by resonance became more electrophilic and was subsequently attacked preferentially by 4-FA. For example, in 4-nitrophthalic... 

In 3-phenylpropenenitrile, the -CN group interacts with the ring through the n electrons of the side chain. Resonance forms show that -CN deactivates the ring toward electrophilic substitution, and substitution occurs at the meta position. 

When two or more significant resonance structures may be written for a molecule, it will be stabilized with respect to the basic structure. As a result, the energy required to reach the transition state will be increased unless there are corresponding interactions in the transition state. The latter will be the case for electrophilic substitution on anisole. 

Naphthalene undergoes electrophilic aromatic substitution at C-1 more easily than at C-2. There is a smaller loss of resonance energy in forming the intermediate for reaction at C-1 and reaction takes place more rapidly at this centre. However, the products of aromatic substitution at C-1 suffer interactions with C-8 (peri interactions) and are less stable than the corresponding products of substitution at C-2. Hence those aromatic substitution reactions that are carried out under conditions that allow equilibration between isomers (thermodynamic control) lead to substitution ai C-2, but reactions that are carried out under conditions... 

The intermediates, formed by electrophilic reaction at the ortho or para positions, are not as stable as the intermediate formed by reaction at the meta position because, for ortho and para attack, one of the three resonance forms has positive charge on the carbon bearing the positively charged sulfur of the sulfonic acid group. For example, for the intermediate resulting from reaction at the para position we can draw three resonance forms. Of these 4-69-2 is particularly unstable because of the destabilizing effect of two centers of positive charge in close proximity. Because the intermediate involved in meta substitution lacks this unfavorable interaction, it is more stable and meta substitution is favored. 

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