6-p-Halophenyl-3-pyrid-4-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles (2a～2c) were synthesized by a composite catalyst of phase transfer catalysts tetrabutylammonium bromide (TBAB) and (4-dimethylaminopyridine (DMAP) via cyclo-condensation of 4-amino-5-pyridin-4-yl-s-triazole-3-thiol (1) with para halogenated benzoic acids in the presence of POCl₃ in high yields, and the following nucleophilic substitution of halogen at phenyl ring with substituted piperazine under catalysis of PEG-600 gave the corresponding free bases 3a～3c successfully. Among them, mono substituted piperazine free base 3a was reacted with functionalized halides to give corresponding bis-substituted piperazine derivatives 6-[4-(4-substituted piperazin-1-yl)phenyl]-3-pyrid-4-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 4a～4g. These yielded piperazine free bases were treated with hydrochloride to the respective HCl salts. The structures of new compounds synthesized were characterized by elemental analysis and spectral data, and their in vitro antibacterial activity and structure-activity relationships were also evaluated.

Key words: s-triazole, s-triazolothiadiazole, piperazine, antibacterial activity, structure-activity relationship (SAR)