General procedure for the synthesis of 2-chloro-3-cyanopyrazine from 2-cyanopyrazine: sulfonyl chloride (21.2 mL, 260.8 mmol) was slowly added to a solution of pyrazine-2-carbonitrile (6.90 g, 65.65 mmol) in toluene (48 mL) and DMF (5 mL) over 10 minutes. The reaction mixture was stirred in an ice bath for 30 minutes, followed by gradual warming to room temperature and continued stirring for 5 hours. After completion of the reaction, the toluene layer was decanted and the residual slightly reddish oily material was extracted three times with ether. The toluene and ether layers were combined, quenched with ice water and cooled in an ice bath. Subsequently, the combined organic layers were neutralized with solid NaHCO3, separated and the aqueous layer was further extracted with ether. All organic layers were combined, washed with water, dried over anhydrous Na2SO4, filtered and the solvent evaporated under reduced pressure to give the crude product 2-chloro-3-cyanopyrazine. The crude product was purified by silica gel column chromatography (eluent: 100% dichloromethane) to afford 3-chloropyrazine-2-carbonitrile (4.7 g, 51% yield) as a white powder. The product characterization data were as follows: Rf = 0.76 (dichloromethane); melting point 44-46 °C (literature value: 47-48 °C); IR (KBr) νmax (cm-1): 3088 (νCHar), 2242 (νCN), 1377 (νC=C), 1087 (νC-N); 1H NMR (400 MHz, DMSO-d6): δ 8.91 (d, 1H, J = 2.4 Hz, H-6), 8.88 (d, 1H, J = 2.4 Hz, H-5); 13C NMR (100 MHz, DMSO-d6): δ 150.67 (C-3), 147.97 (C-5), 144.26 (C-6), 129.87 (C-2), 114.66 (CN); MS (ESI) m/z (%): 140.3 (100) [M + H]+, 142.3 (40) [M + H + 2]+. Elemental analysis (C5H2ClN3) Calculated values: C, 43.04; H, 1.44; N, 30.11. Measured values: C, 43.18; H, 1.45; N, 30.16.
