4-ETHYL-4H-1,2,4-TRIAZOLE-3-THIOL synthesis

Yield:27105-98-2 78%

Reaction Conditions:

with potassium carbonate in tetrahydrofuran;water at 50; for 5 h;

Steps:

3.2.4. General Procedure for the Synthesis of Thiones 5a-5n and 5ha-5hi

General procedure: A mixture of isothiocyanate 3a-3n or 3ha-3hi (90 mmol) and formic hydrazide (6.49 g, 108mmol) in THF (150 mL) was stirred at room temperature until the reaction completed as indicatedby TLC analysis, when a white slurry formed. The crystals were collected by vacuum filtration anddried in vacuo at room temperature to give the intermediate 4a-4n or 4ha-4hi, which was useddirectly in the next step without further purification and characterization. Thus, 4a-4n or 4ha-4hiwas dissolved in THF (150 mL; for 4a-4b) or DMF (150 mL; for 4c-4n and 4ha-4hi) followed byaddition of aqueous K2CO3 prepared by dissolving K2CO3 (12.44 g, 90 mmol) in a minimal amount ofwater, and the solution thus obtained was stirred at 50 °C until completion of the reaction asindicated by TLC analysis (typically within 5 h). On cooling to room temperature, for 4a-4b: the reaction mixture was directly concentrated on a rotary evaporator to remove THF, and the aqueousresidue was adjusted to pH 5-6 and further evaporated to dryness to give a residue, which waspurified by column chromatography to afford 5a-5b; for 4c-4n or 4ha-4hi: the reaction mixture waspoured into ice-water (300 mL), and the resulting mixture was adjusted to pH 5-6 with dilutedhydrochloric acid to give a white slurry. The white crystals were collected by vacuum filtration,washed with water and dried in vacuo to give the crude product 5c-5n or 5ha-5hi as a white solid,which was triturated with EtOAc/n-hexane to yield the pure product 5c-5n or 5ha-5hi. 4-Ethyl-2,3-dihydro-4H-1,2,4-triazoline-3-thione (5a): White solid; 8.08 g (78%); m.p. 169-171 °C.1H-NMR (DMSO-d6, 400 MHz) δ: 13.61 (brs, 1H), 8.38 (s, 1H), 3.42 (s, 3H). 13C-NMR (DMSO-d6, 100MHz) δ: 166.36, 142.60, 31.27.

References:

Cai, Wenqing;Wu, Jingwei;Liu, Wei;Xie, Yafei;Liu, Yuqiang;Zhang, Shuo;Xu, Weiren;Tang, Lida;Wang, Jianwu;Zhao, Guilong [Molecules,2018,vol. 23,# 2,art. no. 252]