Pyrazine N-oxide

Synthesis

General procedure 1: Diazine oxidation; Pyrazine (1 eq.) and mCPBA (1 eq.) were dissolved in DCM (0.2 M). The reaction mixture was stirred at room temperature for 16 hours. PPh3 (0.5 eq.) was then added to quench the unreacted peracid and stirring was continued for 4 hours. After completion of the reaction, the solvent was removed by concentration under reduced pressure and the residue was purified by silica gel column chromatography. The synthesis of pyrazine-N-oxide was carried out according to the general procedure 1 using 100% EtOAc as the initial eluent, followed by switching to 20% MeOH/EtOAc mixed solvent in a gradient elution to give a white solid product in 88% yield. The product was characterized as follows: 1H NMR (300 MHz, CDCl3, 293 K, TMS): δ 8.50 (2H, d, J = 3.9 Hz), 8.14 (2H, d, J = 4.8 Hz); 13C NMR (75 MHz, CDCl3, 293 K, TMS): 147.8, 134.0; HRMS (ESI) m/z calculated for C4H4N2O [M]+: 96.0324, found: 96.0295; mp: 103.2-104.5 °C; IR (νmax/cm-1): 3120, 3088, 1595, 861, 847, 838; Rf (20% MeOH/EtOAc): 0.3.

Purification Methods

If the sample contains pyrazine-1-oxide, then place it in a Soxhlet extractor and extract it with hot pet ether (b 60-68o) in which the mono-oxide is soluble. Collect the dioxide from the thimble and recrystallise it from MeOH. It is dried in vacuo. It has at 1270cm-1 . [Koelsch & Gumprecht J Org Chem 23 1605 1958.]

References

[1] Organic Letters, 2017, vol. 19, # 18, p. 4707 - 4709
[2] Organic Letters, 2018, vol. 20, # 8, p. 2346 - 2350
[3] Angewandte Chemie - International Edition, 2006, vol. 45, # 46, p. 7781 - 7786
[4] Patent: US2008/132698, 2008, A1. Location in patent: Page/Page column 17-18
[5] Chemical Communications, 2015, vol. 51, # 12, p. 2425 - 2428