1,2-Azoles and 1,3-Azoles 113Palladium(0)-catalysed reactions
Extensive use has been made of palladium(0)-catalysed cross-couplings of the azoles, particularly involving halogen,
boron and tin derivatives of thiazole, imidazole and pyrazole, but stannanes are particularly useful at the 2-position of
1,3-azoles due to their much greater stability compared with boronic acids. The selection below is illustrative of this.
1,3-Azolium ylides
One special aspect of 1,3-azole chemistry is the acidity of the C-2-hydrogen of 1,3-azolium salts. At room temperature,
in neutral or weakly basic solution, all three 1,3-azoles undergo a rapid C-2-H exchange, the relative rates being in the
order: imidazole oxazole thiazole. The mechanism for this special process involves, fi rstly, formation of a concen-
tration of protonic salt, then C-2-H deprotonation of the salt, producing an ylide, to the structure of which a carbene
form is an important resonance contributor. Note that these species are overall neutral. It follows that quaternary salts
of 1-alkylimidazoles and of oxazole and thiazole also undergo regioselective C-2-H exchange. For the azolium salts,
the relative rates of exchange via this ylide mechanism, are: oxazolium thiazolium N-methylimidazolium, in a
ratio of about 10^5 :10^3 :1 (see pages 161–162 for the involvement of thiazolium ylides in the mechanism of action of
thiamine (vitamin B 1 )).