Hydrochloric Acid → 4-Chloro-2-sulfanylbenzoic acid

Temperature

0 °C

To a cooled mixture of concentrated hydrochloric acid (6 mL) and ice (10 g) was added slowly a solution of 2-amino-4-chlorobenzoic acid (4 g, 23.3 mmol), sodium hydroxide (0.94 g, 23.5 mmol) and sodium nitrite (1.6 g, 23.3 mmol) in water (30 mL) in an ice bath. The resulting mixture was stirred at 0° C. for 1 hour. A solution of potassium ethoxymethanedithioate (20.8 g, 65.2 mmol) in water (40 mL) in a beaker was heated to 65° C. The cold diazonium salt solution was added slowly to the above hot solution while evolution of gas was observed. After the addition the mixture was cooled to room temperature and acidified to about pH 3 with an aqueous solution of hydrochloric acid (4 N). The aqueous phase was decanted from the resulting semisolid and the sludge was dissolved in 10% aqueous sodium hydroxide (20 mL). The solution was heated for 2 hours at 100° C. followed by addition of sodium hydrosulfite (2 g). The resulting mixture was heated with stirring at 100° C. for an additional 10 minutes, then cooled to room temperature and filtered through a pad of celite. The filtrate was acidified to about pH 4 with concentrated hydrochloric acid. The formed solid was collected by filtration, washed with water, and dissolved in methanol (10 mL) and diethyl ether (150 mL). The solution was dried over sodium sulfate and concentrated in vacuo to afford 2.8 g of 4-chloro-2-sulfanylbenzoic acid as a yellow solid (yield was 63%).

1. additionAfter the addition the mixture
2. temperaturewas cooled to room temperature
3. customThe aqueous phase was decanted from the resulting semisolid
4. dissolutionthe sludge was dissolved in 10% aqueous sodium hydroxide (20 mL)
5. temperatureThe solution was heated for 2 hours at 100° C.
6. additionfollowed by addition of sodium hydrosulfite (2 g)
7. temperatureThe resulting mixture was heated
8. stirringwith stirring at 100° C. for an additional 10 minutes
9. temperaturecooled to room temperature
10. filtrationfiltered through a pad of celite
11. filtrationThe formed solid was collected by filtration
12. washwashed with water
13. dissolutiondissolved in methanol (10 mL)
14. dry with materialThe solution was dried over sodium sulfate
15. concentrationconcentrated in vacuo

ORD record

ord-e1cf195e67af4b788419ef51a854179f

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08871756B2