Reactivity of Five-membered Rings with One Heteroatom

Reactivity of Five-membered Rings with One Heteroatom 

We first consider the different types of reactivity of which five-membered heteroaromatic rings with one heteroatom are capable. We compare and contrast the effects of the different heteroatoms and compare these compounds with analogous aliphatic and benzenoid derivatives. All these reactions are considered later in this chapter in more detail. 

Electrophilic attack at ring heteroatoms is rare for the neutral compounds, although examples are known for thiophenes and selenophenes. However, pyrrole anions undergo easy reaction with electrophiles at both C and N atoms. 

The most important reactions involve electrophilic attack on ring carbon atoms, a wide variety of which are known for pyrroles, -furans and thiophenes. Most frequently, such electrophilic attack is followed by proton loss, resulting in overall substitution. 

Nucleophilic attack on neutral pyrroles, furans and thiophenes without strongly electron-withdrawing substituents is restricted to deprotonation at N or C atoms. However, the cations formed by electrophilic attack on pyrrole, furan and thiophene rings react readily with weak nucleophiles, resulting in overall addition or ring-opening reactions. 

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The reactivity of five-membered rings with one heteroatom to electrophilic reagents has been quantitatively compared in a variety of substitution reactions. Table 2 shows the rates of substitution compared to thiophene for formylation by phosgene and iV,AT-dimethylfor-mamide, acetylation by acetic anhydride and tin(IV) chloride, and trifluoroacetylation with trifluoroacetic anhydride (71AHC(13)235). 

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