146 Heterocycles with Ring-Junction Nitrogen (Bridgehead Nitrogen)
Imidazo[1,5-a]pyridines similarly undergo preferential lithiation at C-3, but when this is blocked by an ethylthio-
group, reaction is directed to C-5. This blocking/directing group is particularly useful as it is easily removed, revealing
the C-3-H.
1 , 2 ,3-Triazolo[1,5-a]pyridine and tetrazolo[1,5-a]pyridine can both exist in equilibrium with ring-open forms. For the
former, the ring-closed version is very dominant. Tetrazolopyridines can exist predominantly in either form, depending
on substituents – the parent is mainly the closed form but the 5-chloro-derivative is open.
Reaction of 1,2,3-triazolo[1,5-a]pyridines with electrophiles can take two courses, which may refl ect the reactivity of
the two tautomers: bromine and aqueous acid give 2-substituted pyridines, whereas acylation and nitration lead to
simple substitution of the bicyclic system.
Systems with extra nitrogen(s) in the six-membered ring have as a common feature ease of nucleophilic addition to the
six-membered ring, indeed some are so reactive that even exposure to moist air results in formation of a ‘covalent hydrate’.
Synthesis of indolizines and azaindolizines
Syntheses of imidazopyridines and some triazolopyridines are carried out mainly by two modes: cyclocondensation or
dipolar cycloaddition. The majority of routes start from pyridines or the higher azines.