Hydrochloric Acid → Phenol

Temperature

5 °C

3-hydroxythiophenol was then prepared by charging a dry 12 L jacketed flask purged with nitrogen, with sulfur powder (52.1 g, 1.6 mol) and THF (585 mL). The mixture was cooled to 5° C. with stirring followed by addition of the above Grignard solution via a Teflon transfer line by applying N2 pressure. The rate of the Grignard reaction was adjusted so that the reaction temperature could be kept below 15° C. The Grignard flask was rinsed with THF (2×234 mL) and the rinsed solution was added to the reaction mixture. The reaction mixture was allowed to warm to room temperature and stirred until a negative Gilman test was obtained. To the resultant mixture was then added 10% aqueous HCl (1158 g) in one portion. The pot temperature rose to 50° C. The reaction was stirred for one additional hour while cooling to room temperature. The bottom aqueous layer was drained off from the top THF layer and was treated with a solution of KOH (508 g) and Na2S2O5 (212.7 g) in water (1740 mL). The resultant mixture was heated at reflux for two hours. The THF layer was separated and concentrated. The residue was combined with the aqueous layer, which was washed with butyl methyl ether (2×1170 mL). The aqueous phase was acidified to pH 1 with concentrated HCl. The resultant mixture was then extracted with t-butyl methyl ether three times (1560, 1170 and 780 mL) and the combined organic layer was washed with brine (780 mL). Removal of the solvent under reduced pressure while keeping the water bath temperature less than 30° C. afforded the crude product (181.6 g) as a slightly yellow liquid. Vacuum distillation using a Vigruex distilling column gave phenol (16 g), 3-hydroxythiophenol (135.7 g) and a high boiling point residue (29.9 g). The yield of the desired product was 53%, and purity was greater than 99%, as determined by GC.

1. customThe rate of the Grignard reaction
2. customcould be kept below 15° C
3. washThe Grignard flask was rinsed with THF (2×234 mL)
4. additionthe rinsed solution was added to the reaction mixture
5. temperatureto warm to room temperature
6. stirringstirred until a negative Gilman test
7. customwas obtained
8. customrose to 50° C
9. stirringThe reaction was stirred for one additional hour
10. temperaturewhile cooling to room temperature
11. temperatureat reflux for two hours
12. customThe THF layer was separated
13. concentrationconcentrated
14. washwas washed with butyl methyl ether (2×1170 mL)
15. extractionThe resultant mixture was then extracted with t-butyl methyl ether three times (1560, 1170 and 780 mL)
16. washthe combined organic layer was washed with brine (780 mL)
17. customRemoval of the solvent under reduced pressure
18. customthe water bath temperature less than 30° C.
19. customafforded the crude product (181.6 g) as a slightly yellow liquid
20. distillationVacuum distillation
21. distillationdistilling column

ORD record

ord-067b3c7e70ea4a8185e18d6d2be2b035

Source dataset

uspto-grants-2000_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06054623