4-METHYL-5-(TRIFLUOROMETHYL)-1,2,4-TRIAZOLIN-3(2H)-THIONE synthesis

Yield:-

Reaction Conditions:

with sodium hydroxide in waterReflux;

Steps:

General procedure: The appropriate thiosemicarbazide derivative (1.0 equiv) was suspended thereafter in 1M aq. NaOH solution (1mL/mmol). The mixture was heated at reflux temperature until the starting thiosemicarbazide derivative was no longer detectable by TLC (n-heptane/EtOAc 1:1 or CHCl₃:MeOH 10:1). After completion of the reaction, the mixture was cooled to 5°C and neutralized with 1M aq. HCl solution to pH~6-7. The precipitated product was filtered off, washed with water (2×1mL/mmol) and dried in a vacuum desiccator over P₂O₅/KOH (average yield: 65-95%). Only in few cases the resulting 1,2,4-triazole-3-thiol had to be purified via flash chromatography (gradient EtOAc/n-heptane).

References:

Frackenpohl, Jens;Schneider, Linn;Decker, Luka J.B.;Dittgen, Jan;Fenkl, Franz;Fischer, Christian;Franke, Jana;Freigang, Joerg;Getachew, Rahel;Gonzalez Fernandez-Nino, Susana M.;Helmke, Hendrik;Hills, Martin J.;Hohmann, Sabine;Kleemann, Jochen;Kurowski, Karoline;Lange, Gudrun;Luemmen, Peter;Meyering, Nicole;Poree, Fabien;Schmutzler, Dirk;Wrede, Sebastian [Bioorganic and Medicinal Chemistry,2019,vol. 27,# 24,art. no. 115142]