3-CHLORO-2,5-DIMETHYLPYRAZINE

6890-37-5

95-89-6

General procedure for the synthesis of 3-chloro-2,5-dimethylpyrazine from 2,5-dimethylpyrazine 1-oxide: 2,5-dimethylpyrazine 1-oxide (7,15.0 g, 121 mmol) and phosphorous trichloride (POCl3, 55.1 g, 360 mmol) were mixed, and the mixture was stirred and heated for 30 min at 60 °C. (Note: Caution is required during handling, as there have been reports of explosions during mixing). Upon completion of the reaction, the mixture was cooled to room temperature and subsequently poured in batches into ice water. The pH was adjusted to alkaline with 20% aqueous sodium hydroxide (NaOH) and then extracted with ether (Et2O). The organic phase was washed sequentially with water and saturated saline, dried over anhydrous magnesium sulfate (MgSO4) and concentrated under reduced pressure. Distillation of the residue gave 12.2 g (71% yield) of 3-chloro-2,5-dimethylpyrazine as a light yellow oil with a boiling point of 98-100 °C/40 Torr. Its infrared spectrum (νmax, membrane method) showed characteristic absorption peaks: 3045 (w), 2999 (w), 2962 (w), 2925 (w), 1567 (w), 1519 ( w), 1454 (s), 1377 (m), 1329 (s), 1313 (s), 1248 (m), 1168 (m), 1088 (s), 968 (m), 456 (m) cm-1. NMR hydrogen spectrum (δH, CDCl3): 2.49 (3H, s), 2.59 (3H, s), 8.23 (1H, s); NMR carbon spectrum (δC, CDCl3): 21.2,22.3,142.1,148.3,150.1,151.7.