Steric effects electrophilic aromatic substitution

We cannot, then, expect this approach to understanding chemical reactivity to explain everything. We should bear in mind its limitations, particularly when dealing with subjects like ortho/para ratios in aromatic electrophilic substitution, where steric effects are well known to be important. Likewise solvent effects (which usually make themselves felt in the entropy of activation term) are also well known to be part of the explanation of the principal of hard and soft acids and bases. Some mention of all these factors will be made again in the course of this book. Arguments based on the interaction of frontier orbitals are powerful, as we shall see, but they must not be taken so far that we forget these very important limitations. 

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. 

The substituent effects in aromatic electrophilic substitution are dominated by resonance effects. In other systems, stereoelectronic effects or steric effects might be more important. Whatever the nature of the substituent effects, the Hammond postulate insists diat structural discussion of transition states in terms of reactants, intermediates, or products is valid only when their structures and energies are similar. 

Now that we have determined that the intermediate in electrophilic aromatic substitution is usually a a complex (see, however, p. 394), let us return to a consideration of Reaction 7.76. Two factors probably combine to cause the observed isotope effect and base catalysis. First, the strong electron-donating groups stabilize the intermediate 76 (Equation 7.77) and make departure of the proton more difficult than proton loss in many other electrophilic substitutions. [Remember, however, that k1 < k2 (see p. 386).] Second, steric interactions between the large diazonium group and the nearby substituents increase the rate... 

The effect of the o-c-Pr group in electrophilic aromatic substitution is anomalous Thus in nitration high o, p-product ratios were obtained (2.0-4.7), whereas in halogenation the ratios are much lower. It was found in aromatic detritiation, a reaction suggested to be free of steric effects that the ratio of partial rate factors for /p//o for cyclopropyl was 9, and this was interpreted that the high fraction of o-nitration was a peculiarity of this particular reaction and not a general effect of the cyclopropyl group. ... 

The substituent effects in aromatic electrophilic substitution are dominated by resonance effects. In other systems, stereoelectronic or steric effects might be more... 

The directing effects associated with electrophilic aromatic substitution play no role in directed metalation. Likewise, steric effects are not very important. It is common, for example, for metalation to occur at C-2 of a 1,3-disubstituted benzene. 

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