The Importance of Directing Effects in Synthesis

When designing a multistep synthesis involving electrophilic aromatic substitution, we must keep in mind the directing and activating effects of the groups involved. Consider, for example, the bromination and nitration of benzene to make bromonitroben-zene. If we brominate first and then nitrate, we will get a mixture of the ortho and para isomers. 

This is because the bromine atom in bromobenzene is ortho,para directing. On the other hand, if we nitrate first and then brominate, we will get mainly the meta isomer because the nitro group is meta directing. 

The sequence in which we carry out the reactions of bromination and nitration is therefore very important. It determines which type of product is formed. 

PROBLEM 4.16 Devise a synthesis for each of the following, starting with benzene  

PROBLEM 4.17 Explain why it is not possible to prepare m-bromochlorobenzene or p-nitrobenzenesulfonic acid by carrying out two successive electrophilic aromatic substitutions. 

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