Halogen atoms in the 4- and 5-positions of thiazoles exhibit different reactivities depending on the nucleophile: with methoxide ion in methanol the reactivity sequence is 5-chlorothiazole > 2-chlorothiazole > 4-chlorothiazole. In contrast, with thiophenoxide ion or piperidine in methanol, the sequence 2 > 4 > 5 is observed. With the series of alkoxide ions methoxide, ethoxide, isopropoxide and t-butoxide in the corresponding alcohol, the reactivity ratios of 4-chlorothiazole versus 2-chlorothiazole are: 0.07, 0.6, 4, 42. The nucleophilic reactivity of 2-halogenothiazoles is strongly affected by substituents: 2-chloro-5-nitrothiazole is more reactive than 2-chlorothiazole by a factor of 10.
