Quinolines and Isoquinolines 63Exceptionally, and via a different mechanism, some substitutions in the pyridine ring of quinoline and isoquinoline are
known, notably bromination and nitration. These rest on the ability of the bicyclic systems (in contrast to monocyclic
pyridine) to add successively an electrophile at the nitrogen and then a nucleophile, forming an adduct; the adduct
contains an enamine unit and the electrophilic step involves attack at the -position of the enamine unit.
Electron-releasing substituents on the heterocyclic ring can permit substitution in that ring: an interesting case is
the nitration of quinolin-4-one where, depending on the strength of acid used, substitution of the heterocyclic ring
occurs on the neutral molecule but nitration in the benzene ring must involve the O-protonated species, that is, the
4-hydroxy-1H-quinolinium cation.
Nucleophilic substitution
Recalling that pyridine is susceptible to addition of nucleophiles at the - and -positions and that benzene compounds
are not normally attacked by nucleophiles, it follows that it is only the heterocyclic ring in quinoline/isoquinoline which
is subject to nucleophilic substitution. In quinoline, there is one - and one -type position, C-2 and C-4; of the two
-type positions in isoquinoline, reaction at the 1-position is much the more favoured one.
Substitution of hydrogen
As the intermediates for nucleophilic addition to the heterocyclic ring still contain a complete benzene ring, with its asso-
ciated resonance stabilisation,nucleophilic addition is easier in these bicyclic systems than in pyridines – less resonance