Heterocyclic Chemistry at a Glance, Second Edition. John A. Joule and Keith Mills.
© 2013 John Wiley & Sons, Ltd. Published 2013 by John Wiley & Sons, Ltd.
Electrophilic substitution at carbon
Pyrroles do not react with electrophiles by addition at nitrogen (a direct contrast with pyridines) – the nitrogen elec-
tron pair is involved in the aromatic sextet and addition of an electrophile to the nitrogen would produce a high-energy
non-aromatic species.
Pyrroles readily undergo electrophilic C-substitution, preferentially at an -position but also, and only slightly less
rapidly, at a -position. Pyrroles are attacked by electrophiles much more easily than benzene – about 10^5 times more
rapidly. Both of these aspects are nicely illustrated by the nitration of pyrrole, which requires only a weakly electrophilic
nitrating agent (AcONO 2 ) and a low temperature to produce a mixture of 2- and 3-nitropyrroles, favouring the former.
The tetra-iodination of pyrrole, again under mild conditions, is another good illustration of the high reactivity of pyr-
role towards even weak electrophiles.
Positional selectivity and the high reactivity can both be explained by a consideration of the mesomeric contribu-
tors to the intermediates (and, by implication, the transition states that lead to them) for electrophilic substitution.
Intermediate cations from both - and -attack are well stabilised, however the delocalisation, involving donation
of electron density from the heteroatom, is greater in the intermediate from -attack, as illustrated by the number
of low energy resonance contributors (three) compared with the -intermediate (two). Note that the carbon-
carbon double bond in the intermediate for -attack is not, and cannot become, involved in delocalisation of the
charge.
The balance in positional selectivity can be tipped to by the presence of bulky groups on nitrogen, which sterically
impede reaction at -positions. For example, 1-(tri-isopropylsilyl)pyrrole (TIPS-pyrrole) is attacked exclusively at a