Heterocycles with More than Two Heteroatoms: Higher Azoles (5-Membered) and Higher Azines (6-Membered) 135C-Metallation
1-Alkylated 1,2,3- and 1,2,4-triazoles lithiate readily at C-5, but the lithio-compound from the 1,2,3-isomer decom-
poses on warming to room temperature; the lithiated 1,2,4-isomer is signifi cantly more stable. The lithio-compound
from a 1-substituted tetrazole decomposes above 50 °C. However, all react normally with electrophiles while low
temperatures are maintained.
Palladium(0)-catalysed reactions
There are only a few examples of organometallics derived from higher azoles being used in cross-coupling reactions,
particularly zinc and tin derivatives; the reverse coupling using the haloazole as substrate is more generally applicable.
Ring synthesis
1,2,3-Triazoles are usually prepared via a cycloaddition of an azide to an alkyne or its equivalent; for example, in
the example below vinyl acetate is used as a higher boiling equivalent of ethyne. (Caution: All azides are potentially
explosive but the risk varies greatly – low molecular weight alkyl azides and hydrazoic acid are particularly dangerous.
Trimethylsilyl azide and aryl azides are safer.)
This triazole ring synthesis is often referred to as a ‘Click reaction’ on account of its effi ciency, reliability and general
applicability, especially for the purpose of linking (clicking together) two moieties. (The term ‘Click reaction’ originally
referred to any highly effi cient and reliable general reaction that can be used for linking moieties.)