Heterocycles with Ring-Junction Nitrogen (Bridgehead Nitrogen) 149isoelectronic analogue (2.2.2)azacyclazine both behave as aromatic molecules, whereas (3.3.3)cyclazine (12 electrons)
is unstable and highly reactive. The hexaaza(3.3.3)cyclazine is very stable (due to perturbation of the orbitals).
(A synthesis of a (3,2,2)cyclazine from indolizine is shown above on page 144.)
Exercises
- Which indolizines would be formed from the following combinations: (i) 2-picoline with (a) BrCH 2 COMe–
NaHCO 3 and (b) MeCHBrCHO–NaHCO 3? (ii) What would be the products if the 2-picoline was replaced
by 2-aminopyridine? - Deduce the structures of intermediates and fi nal product in the following sequence: 5-methoxy-2-methyl-
pyridine reacted with KNH 2 – i-AmONO → C 7 H 8 N 2 O 2 then this with Zn–AcOH → C 7 H 10 N 2 O, and fi nally
this with HCO 2 Me–PPE (polyphosphate ester) → C 8 H 8 N 2 O. - Imidazo[1,5-a]pyridine, on reaction with aqueous HNO 2 gave 3-(pyridin-2-yl)-1,2,4-oxadiazole. Suggest a
mechanism. What product would be obtained by reaction of indolizine with nitrous acid? - Give the structures of the bicyclic compounds formed by the following reactions: (i) 2-hydrazinothiazole
with nitrous acid ( C 3 H 2 N 4 S; and (ii) 2-aminothiazole with BrCH 2 COPh→ C 11 H 8 N 2 S. - Suggest a structure for the fi nal, monocyclic product of the following sequence: quinolizinium bromide
with LiAlH 4 and then H 2 –Pd giving C 9 H 13 N. - What are the structures of the intermediates in the following synthesis of the quinolizinium cation?
2-Methylpyridine was reacted with LDA, then EtO(CH 2 ) 2 CH=O to give C 11 H 17 NO 2 , which was heated with
HI (→ C 9 H 12 NO I); this salt was then heated with Ac 2 O (→ C 9 H 10 N I) and this fi nally heated with
Pd–C to afford quinolizinium iodide.