4-Hydroxybenzaldehyde → HCID 14018450, compound

Temperature

70 °C

A 2.5 l sulfonation flask equipped with stirrer, thermometer, reflux condenser, addition funnel and bubble counter connected to an argon flask is charged with 92.2 g Mg turnings, (4.0 mol) and 150 ml THF. After the system has been flushed with argon one iodine crystal is added followed by 30 drops of a solution of 192.6 g vinyl bromide (1.8 mol) in 300 ml THF. Using an oil bath, the reaction flask is heated to 70° C. and one drop of bromine is added. After ignition of the Grignard-reaction the oil bath is removed and the vinyl bromide-THF solution is added steadily at ambient temperature over a period of 6 hours. Stirring is continued for another 30 minutes and the cloudy, black-grey mixture obtained is cooled to 0° with an ice bath. After dilution with 600 ml THF, a solution of 61.05 g 4-hydroxy-benzaldehyde (0.5 mol) in 150 ml THF is added under efficient cooling (ice bath) over a period of 30 minutes. The thick, but stirrable suspension obtained is stirred at room temperature overnight and then cooled to 0° C. Under vigorous stirring a solution of 133.7 g NH4Cl (2.5 mol) in 350 ml H2O is added very carefully over a period of 1.5 hours. suspension obtained is stirred for another 1.5 hours, the precipitated solids are separated by filtration and the reaction vessel is rinsed several times with a total of 600 ml MTBE. The combined organic layers are washed 2× with 500 ml water, 2× with 500 ml aq. NaHSO3 (10%), 2× with 500 ml H2O, 1× with 500 ml saturated. NaHCO3 and 2× with 500 ml brine/water ca 2:1. Each aqueous phase is extracted 1× with 500 ml MTBE, the combined organic phases are dried over MgSO4 and concentrated in vacuo. The crude product is purified by flash chromatography (silica gel 60, Merck Flash; 30 cm column with 7.5 cm diameter; solvent: hexane/MTBE 1:1) to give 56.0 g (75%) 4-(1-hydroxyallyl)-phenol in the form of a yellowish, viscous oil that slowly crystallizes.

1. customA 2.5 l sulfonation flask equipped with stirrer
2. temperaturethermometer, reflux
3. additioncondenser, addition funnel
4. custombubble counter
5. customconnected to an argon flask
6. customAfter the system has been flushed with argon one iodine crystal
7. additionis added
8. customAfter ignition of the Grignard-reaction the oil bath
9. customis removed
10. additionthe vinyl bromide-THF solution is added steadily at ambient temperature over a period of 6 hours
11. customthe cloudy, black-grey mixture obtained
12. temperatureis cooled to 0° with an ice bath
13. temperatureunder efficient cooling (ice bath) over a period of 30 minutes
14. customThe thick, but stirrable suspension obtained
15. stirringis stirred at room temperature overnight
16. temperaturecooled to 0° C
17. additionis added very carefully over a period of 1.5 hours
18. customsuspension obtained
19. stirringis stirred for another 1.5 hours
20. customthe precipitated solids are separated by filtration
21. washthe reaction vessel is rinsed several times with a total of 600 ml MTBE
22. washThe combined organic layers are washed 2× with 500 ml water, 2× with 500 ml aq. NaHSO3 (10%), 2× with 500 ml H2O, 1× with 500 ml saturated
23. extractionEach aqueous phase is extracted 1× with 500 ml MTBE
24. dry with materialthe combined organic phases are dried over MgSO4
25. concentrationconcentrated in vacuo
26. customThe crude product is purified by flash chromatography (silica gel 60, Merck Flash; 30 cm column with 7.5 cm diameter; solvent: hexane/MTBE 1:1)

ORD record

ord-e10079b5a8164f8b85b603aca6f7f9e9

Source dataset

uspto-grants-2003_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06504048B1