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.
Introduction
In addition to the biologically important purines and major benzo-fused heterocycles such as indole, many other
aromatic bicyclic and polycyclic fused heterocyclic ring systems are known. The most important of these other ring
systems are those containing a ring-junction nitrogen (a bridgehead nitrogen) – that is, where a nitrogen is common
to both rings. These compounds, although rare in nature, have great signifi cance in applied chemistry, particularly
medicines. Only bicyclic combinations of fi ve- and six-membered rings are considered here, although other combina-
tions are possible and known.
Of the parent systems that have a ring-junction nitrogen as the only heteroatom, only indolizine has a neutral, fully
conjugated aromatic ten-electron -system, comprising four pairs of electrons from the four double bonds and the
lone pair from the nitrogen, much as in indole. 4H-Quinolizine is not aromatic because there is a saturated carbon
interrupting the conjugation, but the cation, quinolizinium, derived formally by loss of hydride from quinolizine, does
have an aromatic ten-electron -system. 4-Quinolizinone is similarly a ten-electron -system as illustrated by the
polarised resonance contributor.
Pyrrolizine, which is already aromatic as a pyrrole, can only achieve a bicyclic aromatic ten-electron -system by
conversion into its conjugate anion. However, and more interestingly, replacing the saturated carbon by a heteroatom,
which contributes a lone pair to the -system, gives stable aromatic compounds isoelectronic with the anion.
In all these systems, replacement of carbon by nitrogen does not disrupt the aromaticity, as can be seen in the benzene–
pyridine relationship. This feature leads to a wide range of interesting heterocyclic systems (the azaindolizines), illustrated
above by pyrrolo[1,2-a]pyrazine and imidazo[1,2-a]pyridine.