O-Cresol → ((4-Hydroxy-3-methylphenyl)sulfanyl)formonitrile

Temperature

0 °C

To a 500 ml three-necked flask were added sequentially with agitation o-cresol (15 g, 138.7 mmol), sodium thiocyanate (NaSCN, 34 g, 419.3 mmol), sodium bromide (NaBr, 16 g, 155.5 mmol) and methanol (200 ml). The mixture was cooled to 0° C., and then a solution of bromine (8.6 ml, 167 mmol) in methanol (30 ml) was added dropwise thereinto. After 1 hour of stirring at 0° C., the mixture was warmed up to room temperature and then stirred for another 4 hours at room temperature. After the reaction was completed, a 200 ml saturated aqueous solution of sodium bicarbonate (NaHCO3) was added to the reaction mixture and stirred for 10 min. The mixture was extracted with ethyl acetate (2×500 ml). The combined organic layer was dried over anhydrous magnesium sulfate, filtrated, concentrated under reduced pressure to give yellow oil. Silica gel column chromatography purification (silica-gel H: 300-400 mesh; petroleum ether/ethyl acetate=8:1 v/v) was performed to yield 3-methyl-4-hydroxy-phenyl thiocyanic acid as a white solid (16 g, yield: 69.8%).

1. temperaturethe mixture was warmed up to room temperature
2. stirringstirred for another 4 hours at room temperature
3. stirringstirred for 10 min
4. extractionThe mixture was extracted with ethyl acetate (2×500 ml)
5. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
6. filtrationfiltrated
7. concentrationconcentrated under reduced pressure
8. customto give yellow oil
9. customSilica gel column chromatography purification (silica-gel H: 300-400 mesh; petroleum ether/ethyl acetate=8:1 v/v)

ORD record

ord-7a98d82f58164f7d9a1cbb1c275b2a20

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08822519B2