Regioselectivity in electrophilic aromatic substitution

The choice between ortho/para and meta substitution when an electrophile attacks a benzene ring (Chapter 21) is also a matter of regioselectivity. We shall discuss all these examples in further detail in this chapter, and extend these ideas to new reactions as well. 

We start with electrophilic aromatic substitution. It was established in Chapter 21 that an electron-donating substituent favours ortho/para and an electron-withdrawing substituent favours meta substitution. Although meta substitution is usually slower than ortho/para substitution (because electron-withdrawing groups deactivate the ring), it usually gives the meta product alone. 

Most reactions of benzene rings with electron-donating substituents give ortho/para mixtures and, if the substituent is very electron-donating, may lead to both ortho and para substitution in the same molecule. Control in favour of the para product can usually be achieved by reducing the reactivity of the substituent and increasing its size. 

Of course, if the para position is blocked, ortho substitution is the only option, and we will come back to the idea of blocking substituents shortly. But there is a general way of directing electrophiles to the ortho position using activation by metallation. 

Making organometallics by deprotonating aromatic rings orthoiithiation 

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Would you expect the substituent —N(CH3)3 to more closel resemble —NfCHj), or —NO, in its effect on rate and regioselectivity in electrophilic aromatic substitution Why ... 

How substituents control rate and regioselectivity in electrophilic aromatic substitution results from their effect on carbocation stability. An electron-releasing substituent stabilizes the cyclohexadienyl cation intermediates corresponding to ortho and para attack more than meta. 

Regioselectivity in electrophilic aromatic substitution and in radical substitution. 

Predicting regioselectivity in electrophilic aromatic substitution where directing effects are more subtle. 

Representative Electrophilic Aromatic Substitution Reactions of Benzene 457 Mechanistic Principles of Electrophilic Aromatic Substitution 458 Nitration of Benzene 459 Sulfonation of Benzene 461 Halogenation of Benzene 462 Biosynthetic Halogenation 464 Friedel-Crafts Alkylation of Benzene Friedel-Crafts Acylation of Benzene Synthesis of Alkylbenzenes by Acylation-Reduction 469 Rate and Regioselectivity in Electrophilic Aromatic Substitution 470 Rate and Regioselectivity in the Nitration ofToluene 472... 

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