General procedure for the synthesis of 2-amino-5-bromo-1,3,4-thiadiazole from 2-amino-1,3,4-thiadiazole:
1. A solution of 2-amino-1,3,4-thiadiazole (5 g, 48.45 mmol) in methanol (70 mL) was added to a reaction flask.
2. Sodium bicarbonate (8.14 g, 96.90 mmol) and bromine (2.5 mL, 48.45 mmol) were added sequentially.
3. The reaction mixture was stirred at room temperature until the complete disappearance of the ingredients was demonstrated by thin layer chromatography (TLC) monitoring (about 30-40 minutes).
4. After completion of the reaction, the solvent was removed by rotary evaporator under reduced pressure.
5. The crude product was ground with a solvent mixture of methanol-ether (1:1, v/v) to give 2-amino-5-bromo-[1,3,4]thiadiazole as a white solid.
6. The mother liquor containing a small amount of product was purified by fast column chromatography using dichloromethane-methanol (99:1, v/v) as eluent.
7. The product was confirmed by nuclear magnetic resonance hydrogen spectroscopy (1H NMR, 300 MHz, DMSO-d6): δ 7.52 (br s, 2H).
8. Mass spectrometry (ES+) analysis showed m/z 181 ([M+H]+, calculated value: 180.0).
Yield: 99%.