Quinoliziniums and Related Systems

The quinolizinium ion occurs naturally only rarely, for example as a fused ylide in the alkaloid sempervirine, however there are hundreds of indole alkaloids which have the same tetracyclic system, but with the quinolizine at an octahydro-level, in addition, many simpler quinolizidine alkaloids, such as lupinine, are known. Amongst synthetic compounds the anti-asthma drug Pemirolast is an aza-analogue. 

Practically all the reactions of quinolizinium ion are similar to those of pyridinium salts, thus it is resistant to electrophilic attack but readily undergoes nucleophilic addition, the initial adducts undergoing spontaneous electrocyclic ring opening to afford, finally, 2-substituted pyridines, however the susceptibility of the cation to nucleophiles is not extreme - like simpler pyridinium salts it is stable to boiling water. 

Quinazolones can be made to undergo electrophilic substitution, at C-l/C-3, there being a clear analogy with the reactivity of pyridones. 

Quinolizine derivatives are usually prepared by cyclisations onto the nitrogen in a precursor pyridine.  

Some are so susceptible to nucleophilic addition that they form hydrates  

Ring synthesis of such molecules can proceed from diazines using methods analogous to those described for the synthesis of azolopyridines from pyridines, but generally they are more easily obtained from a five-membered precursor. 

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