Nucleophilic displacements neutral azoles

Halogen atoms in the 2-position of imidazoles, thiazoles and oxazoles can be replaced by the groups NHR, OR, SR, etc. The conditions required are more vigorous than those used, for example, for a- and y-halopyridines, but much less severe than those required for chlorobenzene. 

3-Chloro-5-arylisoxazoles undergo nucleophilic displacement with alkoxide ion. Halogen atoms in the 5-position of the isoxazole nucleus are readily displaced if an activating group is present in the 4-position 63AHC(2)365 . 

5-Halo-l-methyl-l,2,3-triazoles undergo substitution reactions with amines, but the 4-halo analogues do not. 5-Chloro-1,4,-diphenyl-1,2,3-triazole with sodium cyanide in DMSO gives the cyano derivative (63JCS2032). 1-Substituted 3-chloro- and 5-chloro-l,2,4-triazoles both react with amines. 

Reactivity of Five-membered Rings with Two or More Heteroatoms 

Halogen atoms at the 5-position of tetrazoles are reactive and easily replaced by nucleophiles. 5-Bromo-l-methyltetrazole is significantly more reactive than the 2-methyl isomer 77AHC(2i)323). 

---