112 1,2-Azoles and 1,3-Azoles
Organolithium, and in some cases Grignard, reagents are available from azole halides. The relative reactivities to
metal–halogen exchange, of halides at different positions, mirrors the C-H acidities discussed above. For example,
2,4-dibromothiazole gives the 2-lithio-derivative.
C-Deprotonation of oxazoles and isoxazoles
The deprotonation of oxazoles or isoxazoles needs to be considered separately. The complication is that the carbanions
produced can undergo ring-opening processes, the driving force for which can be traced to the greater electronega tivity
of oxygen. Thus base treatment of isoxazoles that have a hydrogen at C-3 leads inevitably to ring opening, with the
oxygen as the anionic leaving group, indeed this type of cleavage was fi rst recognised as long ago as 1891, when Claisen
found that 5-phenylisoxazole was cleaved by sodium ethoxide.
2-Lithiation of oxazoles can lead to open isonitrile-enolates, the existence of which can be demonstrated by trapping with
electrophiles. Signifi cantly, trapping the equilibrating mixture from isoxazole itself with triisopropylsilyl trifl ate produces
2-triisopropylsilyloxazole exclusively and this can then be utilised, via lithiation at C-5, the blocking 2-substituent being
fi nally removed with acid. 2-Zinc and 2-magnesium oxazoles exist in ring-closed form.