70 Quinolines and Isoquinolines
Synthesis of isoquinolines from ortho-alkynyl aryl-aldehydes
or corresponding imines (2,3-bond made)
Electrophile-promoted closure of ortho-alkynyl arylaldehyde t-butylimines, with loss of the N-substituent, generates
isoquinolines carrying the electrophile at C-4. The example below shows how this approach can also be used to pro-
duce naphthyridines, in the case shown, a 1,6-naphthyridine.
If, instead of an imine, the aldehyde oxime is used, the result is formation of an isoquinoline N-oxide.
Even simpler, and also for the synthesis of naphthyridines, each of the isomeric ortho-alkynyl pyridinyl aldehydes will
react with ammonia to produce a naphthyridine (or with hydroxylamine to give a naphthyridine N-oxide), possibly,
but not necessarily, via the imine, as shown.
Exercises
- What are the structures of the high-yield mono-nitration products: (i) C 10 H 8 N 2 O 3 from 6-methoxyquinoline;
(ii) C 10 H 8 N 2 O 3 from 7-methoxyisoquinoline; and (iii) C 16 H 12 N 2 O 2 from 1-benzylisoquinoline? - What is the structure of the product C 16 H 16 ClNO 4 from 1,3-dichloroisoquinoline and NaCH(CO 2 Et) 2?
- Deduce a structure for the product C 15 H 18 N 2 OS, formed on treatment of 2-(t-BuCONH)-quinoline succes-
sively with three equivalents of n-BuLi and then dimethyl disulfi de (MeSSMe). - What reactants would combine to produce: (i) 6-methoxyquinoline; (ii) 6-methoxy-2,4-diethylquinoline;
and (iii) 7-methoxyisoquinoline? - Deduce the structure of the quinoline that is formed by the following sequence: isatin (page 94) is hydrolysed
with NaOH to give C 8 H 6 NNaO 3. This is then reacted with dimedone (5,5-dimethylcyclohexane-1,3-dione)
to produce C 16 H 15 NO 3.