Step 2: Synthesis of 2,5-dichloropyrazine
To a stirred solution of 5-chloropyrazin-2-amine (1 g, 7.751 mmol) in concentrated hydrochloric acid (10 mL), an aqueous solution of sodium nitrite (1.1 g, 15.89 mmol) was slowly added at -10 °C, and the addition process lasted for 1 hour. After addition, the reaction mixture was stirred at 0 °C for 1 h, and then brought to room temperature and continued stirring for 2 h. The reaction was carried out by thin layer chromatography (TLC). The reaction process was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the reaction mixture was neutralized with 50% sodium hydroxide (NaOH) solution and subsequently extracted with dichloromethane (DCM). The organic layers were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The crude product was purified by column chromatography on silica gel (100-200 mesh) to afford 2,5-dichloropyrazine (0.59 g, 15% yield) as a colorless oil using hexane solution containing 2% ethyl acetate as eluent. Mass spectrum (MS): 184.1 [M-1].
