Synthesis
General procedure for the synthesis of 2-iodopyrazine from 2-chloropyrazine: a reaction mixture of 2-chloropyrazine (7.5 mL, 83 mmol), NaI (30.3 g, 202 mmol), HOAc (9.6 mL, 168 mmol) and H2SO4 (0.5 mL) in MeCN (105 mL) was heated and refluxed for 4.5 hours. Upon completion of the reaction, the solvent was removed under reduced pressure and water (120 mL) was added. The solution was alkalized with saturated NaHCO3 solution and extracted with dichloromethane (DCM) (2 x 125 mL). The DCM layers were combined, washed sequentially with saturated Na2S2O3 solution and brine, and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure to give the crude 2-iodopyrazine as an oil (12.33 g, 20% yield, 71% purity).1H NMR analysis showed that the crude contained less than about 10 mol% of 2-chloropyrazine. Following the same procedure, another batch of 2-chloropyrazine (50 g, 437 mmol) was converted to the crude 2-iodopyrazine (~65 g). The two crude batches were combined and distilled under reduced pressure (ca. 0.75 Torr, boiling point 47 °C) to give 64 g of pure 2-iodopyrazine (60% yield).1H-NMR (CDCl3, 300 MHz) δ 8.40 (dd, J = 1.8, 2.4 Hz, 1H), 8.51 (d, J = 2.4 Hz, 1H), 8.87 (d, J = 1.5 Hz, 1H).
References
[1] Tetrahedron, 1998, vol. 54, # 33, p. 9701 - 9710
[2] Patent: WO2009/114313, 2009, A2. Location in patent: Page/Page column 15
