Hydrochloric Acid → 1,3,4-Thiadiazol-2-amine, 5-(trifluoromethyl)-

Temperature

20 °C

A three-liter reaction flask fitted with a mechanical stirrer, heating mantle, dropping funnel, thermometer and water-cooled condenser connected to a caustic trap was charged with 228 g (2.5 mole) of thiosemicarbazide, 1260 ml of 1,4-dioxane and 285.1 g (2.5 mole, 193 ml) of trifluoroacetic acid. The dropping funnel contained 383.8 g (2.5 mole, 229 ml) of phosphorus oxychloride which was added to the reaction flask over a period of 30 minutes. The resulting thick slurry was heated slowly to reflux with rapid evolution of hydrogen chloride gas. The slurry thinned with separation of the product as a heavy syrup. Total reflux time required about four hours until the gas evolution ceased. The dioxane was decanted and then 1700 ml of water was added to the residue. The mixture was cooled to 20° C. and made basic with 50% sodium hydroxide (~225 ml) to pH 9. The slurry was cooled to 10° C. and collected on a filter funnel. The cake was washed with cold water and dried in the oven. There was obtained 305 g, Mp 219°-220.5°, yield 72.1%. The proton NMR recorded in Me2SO-d6 consisted of a peak at 7.9∂ (NH2) with respect to tetramethylsilane.

1. customA three-liter reaction flask
2. customfitted with a mechanical stirrer
3. temperatureheating mantle
4. customconnected to a caustic trap
5. additionwas added to the reaction flask over a period of 30 minutes
6. temperatureThe resulting thick slurry was heated slowly
7. customThe slurry thinned with separation of the product as a heavy syrup
8. customabout four hours
9. customThe dioxane was decanted
10. addition1700 ml of water was added to the residue
11. temperatureThe slurry was cooled to 10° C.
12. customcollected on a filter funnel
13. washThe cake was washed with cold water
14. customdried in the oven
15. customThere was obtained 305 g, Mp 219°-220.5°, yield 72.1%

ORD record

ord-30360a46193442d78be991fd81c5b0ca

Source dataset

uspto-grants-1981_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04264616