Quinolines and Isoquinolines 67Oxygen substituents
Quinolines and isoquinolines with hydroxyl groups on the benzene rings are normal phenols. Oxygen at the isoquino-
line-1-position and the quinoline-2- or -4-positions takes the carbonyl tautomeric form; the reactions of isoquinolin-
1-one and the quinolones strictly parallel those of pyridones, for example conversion into halides by reaction with
phosphorus halides.
N-Oxides
Like the N-oxide of pyridine, those of quinoline and isoquinoline are versatile synthetic reagents, their reactivity being
closely similar to that of their monocyclic counterpart, and for this reason we give just a couple of typical examples
using isoquinoline N-oxide. Each transformation involves initial interaction of an electrophile with the oxygen to give
an isoquinolinium salt, which adds a nucleophile, at C-1, the fi nal product resulting from a 1,2-elimination and thus
re-formation of the aromatic system.
Ring synthesis – disconnections
In order to discuss ring synthesis, we need to consider quinoline and isoquinoline separately. The important routes to
quinolines all start with an aniline. Isoquinolines can be made from 2-arylethanamines or from aryl aldehydes. The
new bonds formed in the processes are shown.
Synthesis of quinolines from anilines
(1,2- and 4,4a-bonds made)
Anilines react with 1,3-dicarbonyl compounds very effi ciently to give -arylamino-enones; these can be cyclised with
acid involving electrophilic attack on the benzene ring; fi nal loss of water produces the aromatic quinoline – the
Combes synthesis. If one of the carbonyl groups is that of an ester, then a quinolone results.