Synthesis
The general procedure for the synthesis of 5,6-dichloropyrazine-2,3-dicarbonitrile from 5,6-dioxo-1,4,5,6-tetrahydropyrazine-2,3-dicarbonitrile is shown in Figure 13. The reaction should be carried out in a fume hood. A magnetically stirred slurry consisting of 8.10 g (0.050 mol) of 5,6-dioxo-1,4,5,6-tetrahydropyrazine-2,3-dicarbonitrile, 4.0 mL of dimethylformamide, and 160 mL of thionyl chloride is heated in a 500 mL round-bottomed flask equipped with 24/40 milled glass fittings under a high efficiency reflux condenser and nitrogen atmosphere. At the beginning of the reaction, the release of SO2 and HCl gas was observed at about 62°C. After about 3.5 h, the solid was completely dissolved and the temperature was raised to 70°C. Upon completion of the reaction, the reaction mixture was cooled to room temperature and subsequently placed in a dry ice/acetone bath to -65°C. The cooled slurry was rapidly filtered through a sintered-glass filter to collect the crystals formed under nitrogen protection. The solids were washed with two 50 mL portions of cold ether and air dried to give 7 g (70% yield) of 2,3-dichloro-5,6-dicyanopyrazine with a melting point of 180-182°C. If the product is darker, it can be carbonated and recrystallized by carbon treatment in 50 mL of chloroform to give 5.5 g of purified product.
References
[1] Journal of Heterocyclic Chemistry, 1986, vol. 23, p. 1419 - 1421
[2] Patent: US8742107, 2014, B1. Location in patent: Page/Page column 4; 5
[3] Acta Chemica Scandinavica, 1996, vol. 50, # 12, p. 1153 - 1156
[4] Tetrahedron Letters, 2012, vol. 53, # 25, p. 3126 - 3130
