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Chapter-5
Synthesis of highly substituted pyrroles
Pyrrole is extremely weak base because the lone pair of electrons on the
nitrogen atom involved in the cyclic delocalization and is, therefore, less available for
protonation. Moreover, pyrrole is a weaker base than pyridine and even than aniline in
which lone pair on the nitrogen atom is involved in the resonance and not essentially
contributes to the aromatic sexlet. The protonation of pyrrole at nitrogen or C 2 or C 3
atom of the ring reduces its basicity and destroys its aromaticity. However, C- and N-
alkyl substituents enhance the basicity of pyrrole but the electron withdrawing
substituents on the ring make pyrrole a weaker base. 1-11
5.2 Various synthetic approaches for highly substituted pyrroles.
Pyrroles are generally synthesized by the cyclization reactions involving
nucleophilic-electrophilic interactions. This is the most widely used method and
involves the cyclizative condensation of α-aminoketones or α-amino-β-keto
esters(three atom fragment with nucleophilic nitrogen and electrophilic carbonyl
carbon) with β-diketones or β-ketoesters (two atom fragment with electrophilic
carbonyl carbon and a nucleophilic carbon) with the formation of N-C 2 and C 3 -C 4
bonds (Figure-2).
Figure-2
The reaction of α-aminoketones with alkynes proceeds with the nucleophilic
addition of amino group to the electrophilic carbon of alkyne with the formation of
enamine intermediate which on intramolecular cyclization provides pyrroles involving
nucleophilc (β-carbon of the enamine intermediate)-electrophilic (carbonyl carbon)
interaction with the formation of C 3 -C 4 bond (Figure-3). 12
Figure-3
Department of Chemistry, Saurashtra University, Rajkot-360005 159