138 Heterocycles with More than Two Heteroatoms: Higher Azoles (5-Membered) and Higher Azines (6-Membered)
Of the oxa- and thia-compounds with more than two nitrogens, only derivatives of 1,2,3,4-thiatriazoles are well
defi ned, but even here only 5-aryl and 5-amino compounds are reasonably stable; some compounds, such as the
5-chloro and the 5-thiol, are dangerously explosive. The source of this instability is an easy loss of sulfur and molecu-
lar nitrogen as can be seen by inspection of the structure. Mesoionic 1,2,3,4-oxatriazoles (azasydnones) are relatively
stable, and indeed are the only stable 1,2,3,4-oxatriazoles, probably because there is no low energy possibility for these
isomers to lose nitrogen. (The presence of two contiguous unsubstituted nitrogen atoms can allow easy extrusion of
nitrogen gas, however in the azasydnone this direct elimination of N 2 is blocked by the presence of methyl on the
central nitrogen.)
Nucleophilic substitution at carbon
Owing to the highly electron-defi cient nature of these rings, electrophilic substitution on carbon is rare but, conversely,
nucleophilic displacements proceed readily. There are large differences in relative reactivity, which are rather diffi cult
to predict on simple examination, but some experimental data are available.
C-Metallation of higher azoles (containing O/S)
Lithiation occurs readily and can be used for manipulation of substituents, but ring-opening and other side
reactions are common. Some systems, such as 1,2,5-oxadiazole, are decomposed even by weak bases. In the thia-
compounds, direct attack on S can also occur, particularly with organolithium reagents, leading to fragmentation
of the ring.
Ring synthesis
Some syntheses of oxa- and thiadiazoles follow the condensation–cyclisation approaches used for simpler azoles, but
oxidative cyclisations may be required when a sulfur–nitrogen bond is required.