Triethylamine → Sulfamic acid 4-(2H-1,2,4-triazol-2-yl)phenyl ester hydrochloride

Participants

Reaction Steps

4-(1H-1,2,4-triazol-1-yl)phenol (5.0 g, 0.031 mole) was suspended in methylene chloride (30 ml) and sulfamoyl chloride (7.13 g, 0.062 mole) added to the stirring mixture. Triethylamine (6.27 g, 0.062 mole) was added dropwise while maintaining the temperature between 25°-30° C. After the addition was complete the reaction was stirred for several hours at room temperature. An aliquot was removed and injected onto an High Pressure Liquid Chromatography diol column (10% methanol in ethyl acetate) which indicated reaction had not gone to completion. The reaction was treated with an additional 0.031 mole of sulfamoyl chloride and triethylamine. The reaction stirred overnight at room temperature and was worked up after 1H NMR indicated reaction had gone to completion. The solvent was evaporated and the residue partitioned between ethyl acetate/acetonitrile (1:1)/aqueous sodium hydroxide, sodium bicarbonate (1:1). The organic layer was evaporated and the base isolated as an off-white powder (4.78 g, 64%). The crystals were dissolved in hot isopropyl alcohol, cooled and the mixture filtered. The filtrate containing the base was evaporated to a residue, dissolved in methanol and a solution of anhydrous HCl/isopropyl alcohol added. White crystals fell out of solution as more isopropyl alcohol was added and methanol removed. The crystals were filtered, dried and analyzed (0.80 g, 0.0029 mole, 9%, mp 169°-173° C.).

Provenance & Evidence