Limitations on Electrophilic Substitution Reactions with Substituted Benzenes

10 Limitations on Electrophilic Substitution Reactions with Substituted Benzenes 

Although electrophilic aromatic substitution worics well with most substituted benzenes, halogena-tion and the Friedel-Crafts reactions have some additional limitations that must be kept in mind. 

Monosubstitution of H by Br occurs with Br2 alone without added catalyst to form a mixture of ortho and para products. 

Friedel-Crafts reactions are the most difficult electrophilic aromatic substitution reactions to carry out in the laboratory. For example, they do not occur when the benzene ring is substituted with NO2 (a strong deactivator) or with NH2, NHR, or NR2 (strong activators). 

A benzene ring deactivated by a strong electron-withdrawing group—that is, any of the meta directors—is not electron rich enough to undergo Friedel-Crafts reactions. 

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Limitations on electrophilic substitution reactions with substituted benzenes... 

Successively, Friedel and Crafts studied the generality and the limitations of the new synthetic method. They found that the reaction could be successfully applied to a large number of aromatic compounds, as well as alkyl and acyl chlorides or anhydrides in the presence of chlorides of certain metals such as aluminum, zinc, and iron. A mechanistic hypothesis was postulated on the basis of the possible existence of an intermediate compound 3 formed between benzene and aluminum chloride (Scheme 1.2). This intermediate would react with the electrophilic reagent, giving the substitution product and restoring the catalyst. 

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