Reaktion #51745

Reaktionsgleichung

N,N-dimethylthiocarbamoyl chloride

KOH

dimethylthiocarbamoyl chloride THF

KOH

5-tert-butyl-4-hydroxy-2-methylbenzaldehyde

5-tert-Butyl-4-hydroxy-2-methylbenzaldehyde

→

title compound

Dimethylthiocarbamic acid O-(2-tert-butyl-4-formyl-5-methylphenyl)ester

Lösungsmittel

THF

water

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto remove the THF
2. 2
   workup.DISTILLATIONduring this distillation
3. 3
   Temperaturwhile maintaining the pH range between 12.0 and 11.6
4. 4
   Sonstigebetween 23° C. to 25° C
5. 5
   workup.DISTILLATIONThe distillation
6. 6
   workup.ADDITIONafter all the dimethylthiocarbamoyl chloride solution had been added
7. 7
   workup.WAITwas continued for another 90 minutes, during which time
8. 8
   workup.ADDITIONA solution of EtOAc (150 mL) and heptane (150 mL) was added to the reaction mixture
9. 9
   workup.STIRRINGafter stirring
10. 10
    Sonstigethe layers were separated
11. 11
    Extraktionthe aqueous layer extracted with 1:1 heptane
12. 12
    ExtraktionThe combined organic extracts were extracted with 10% KOH (2×100 mL) and water (2×90 mL)
13. 13
    Einengenconcentrated
14. 14
    workup.ADDITIONThe residue was diluted with MeOH (120 mL)
15. 15
    workup.ADDITIONH2O (20 mL) was added
16. 16
    TemperaturThe solution was cooled to room temperature
17. 17
    workup.ADDITION50% NaOH (170 mg) was added
18. 18
    Einengenthe solution was concentrated
19. 19
    workup.DISSOLUTIONThis residue was redissolved in MeOH (120 mL) at 50° C.
20. 20
    workup.ADDITIONH2O (15 mL) was added
21. 21
    TemperaturThe solution was cooled slowly to −5° C. with the addition of dimethylthiocarbamic acid O-(2-tert-butyl-4-formyl-5-methyl-phenyl)ester seed crystals
22. 22
    Sonstigecrystallization
23. 23
    FiltrationThe mixture was filtered
24. 24
    Waschenthe solid washed with 4:1 MeOH

Vorschrift

Ten percent KOH (80 mL) was added to a mixture of 5-tert-butyl-4-hydroxy-2-methylbenzaldehyde (Example T; 99.0 g, 515 mmol) in water (180 mL) and THF (135 mL.) The mixture was treated with a solution of N,N-dimethylthiocarbamoyl chloride (86.1 g) in THF (108 mL) over a 2-hour period with simultaneous addition of 10% KOH in order to hold the pH of the reaction mixture between 12.0 and 12.3. After approximately 70% of the dimethylthiocarbamoyl chloride-THF solution had been added, vacuum was applied to the reaction mixture to remove the THF; during this distillation, the simultaneous additions of 10% KOH and the dimethylthiocarbamoyl chloride-THF solution were continued while maintaining the pH range between 12.0 and 11.6 and the reaction temperature between 23° C. to 25° C. The distillation was continued for 10 minutes after all the dimethylthiocarbamoyl chloride solution had been added. Stirring at ambient pressure and temperature was continued for another 90 minutes, during which time the pH was stable between 11.6 and 11.75. A solution of EtOAc (150 mL) and heptane (150 mL) was added to the reaction mixture, and after stirring and settling, the layers were separated and the aqueous layer extracted with 1:1 heptane:EtOAc. The combined organic extracts were extracted with 10% KOH (2×100 mL) and water (2×90 mL) and concentrated. The residue was diluted with MeOH (120 mL). The solution was warmed to 45° C. and H2O (20 mL) was added. The solution was cooled to room temperature, 50% NaOH (170 mg) was added, and the solution was concentrated. This residue was redissolved in MeOH (120 mL) at 50° C. and H2O (15 mL) was added. The solution was cooled slowly to −5° C. with the addition of dimethylthiocarbamic acid O-(2-tert-butyl-4-formyl-5-methyl-phenyl)ester seed crystals to promote crystallization. The mixture was filtered and the solid washed with 4:1 MeOH:H2O to give the title compound, mp 80-81° C.

Quelle