Synthesis
Procedure: a solid mixture of formylhydrazine (6.0 g, 0.1 mol; Aldrich) and thiopropionamide (8.92 g, 0.1 mol; TCI) was heated in an oil bath at 150 °C with stirring and under nitrogen protection for 2 hours. After completion of the reaction, it was cooled to room temperature and allowed to stand overnight. The solid reaction mixture was suspended in 20% EtOAc/CH2Cl2 mixed solvent, filtered to remove insoluble solids and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography with a gradient elution of 50-80% EtOAc/CH2Cl2 to remove the by-products, followed by 10% MeOH/CH2Cl2, and the target product, 3-ethyl-1H-1,2,4-triazole, 5.4 g (0.056 mol, 56% yield), was collected as a white solid. Mass spectrum (ESI-) m/z 96 ([M-H]-); 1H NMR (CDCl3) δ 1.37 (3H, t, J = 7.5 Hz), 2.88 (2H, q, J = 7.5 Hz), 8.06 (1H, s, 5-H), 9.4 (1H, br, NH). Ref: Vanek, T.; Velkova, V.; Gut, Jiri Coll. Czech. Chem. Commun. 1985, 49, 2492.
References
[1] Patent: US2004/110785, 2004, A1. Location in patent: Page 221-222
[2] Journal of Medicinal Chemistry, 2018, vol. 61, # 14, p. 6308 - 6327
