Quinolines and Isoquinolines 65‘Reissert compounds’ are formed when quinoline or isoquinoline is reacted with an acid chloride, usually benzoyl
chloride, in the presence of cyanide – here, it is the cyanide that adds as a nucleophile, generating isolable and stable
adducts. Various uses have been devised for Reissert compounds: our example shows that the nitrile-bearing carbon
carries an acidifi ed C-hydrogen, which can be removed with a strong base, the resulting carbanion alkylated, hydrolytic
conditions then producing overall a C-1-alkylated heterocycle.
The salt that results from N-arylation of isoquinoline with 2,4-dinitrochlorobenzene (cf. pages 13–14), and is known
as Zincke’s salt, easily adds primary amines at C-1. These adducts undergo a ring-opening–ring-closing sequence –
the acronym ‘ANRORC’ (Addition Nucleophilic Ring Opening Ring Closing) is usually used for such sequences – to
regenerate an isoquinolinium salt, but in which the attacking primary amine nitrogen is now the isoquinolinium
nitrogen and 2,4-dinitroaniline has been expelled.
C-Metallated quinolines and isoquinolines
Direct deprotonation of quinolines/isoquinolines has only been carried out with ortho assistance (DoM).
Quinolines with a directing group at C-3 are lithiated at C-4, not C-2. Metal–halogen exchange processes can be
used to produce organometallic nucleophiles from halides located on either the benzene ring or on the heterocyclic
ring, but the maintenance of a low temperature is essential to avoid the type of facilitated nucleophilic addition
discussed above.
Palladium(0)-catalysed reactions
Boronic acid and stannane derivatives at all positions of the heterocyclic ring of quinoline and isoquinoline are known
and take part in cross-coupling reactions. Two typical examples are shown. Positional selectivity can be seen when
a dihalide is used for the coupling, for example, in 1,3-dichloroisoquinoline, reaction takes place at C-1. Similarly,
2,4-dichloroquinoline reacts fi rst at C-2.