Water → HCID 22414788, compound

HRID 2260172Notes

Reaction equation

HRID 2260172 reaction equation
[CH3:1][C:2]([CH3:7])=[CH:3][C:4](Cl)=[O:5].[C:8]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([CH3:21])([CH3:20])[CH3:19])[C:13]=1[OH:22])([CH3:11])([CH3:10])[CH3:9].O.C(Cl)[Cl:25]>Cl[Ti](Cl)(Cl)Cl>[C:18]([C:14]1[CH:15]=[C:16]([C:4](=[O:5])[CH2:3][C:2]([Cl:25])([CH3:7])[CH3:1])[CH:17]=[C:12]([C:8]([CH3:11])([CH3:10])[CH3:9])[C:13]=1[OH:22])([CH3:21])([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 962WaterHCID 6344Dichloromethane2×HCID 314052,6-Di-tert-butylphenolHCID 1023943-Methyl-2-butenoyl chloride

Product 1

HCID 22414788HCID 22414788, compound

Reagents, catalysts & solvents 1

HCID 24193Titanium TetrachlorideCatalyst

Procedure

In a 1 L round bottom flask, equipped with internal thermometer, magnetic stirrer and septum inlet, is placed a solution of 3,3-dimethylacryloylchloride (Aldrich Chemical Co.) (18.4 mL, 0.166 mol) in CH2Cl2) 150 mL). The stirred solution is cooled in a salt-ice bath, while TiCl4 (18.2 mL, 0.20 mol, 1.2 eq) is added dropwise via canula at a rate such that the reaction mixture does not warm above 0° C. The solution is stirred for 10 minutes after addition is complete, and then a solution of 2,6-di-tert-butylphenol (Aldrich Chemical Co.) (34.0 g, 0.166 mol, 1.0 eq) in CH2Cl2 (100 mL) is added dropwise via addition funnel. Again, the rate of addition is adjusted to maintain the reaction temperature below 0° C. The cold bath is removed, and the mixture is allowed to stir at ambient temperature for 3 hours. TLC analysis (EtOAc:hexane, 1:9) indicates the reaction to be complete. H2O (100 mL) is added, and the organic phase is separated, washed with additional H2O (2×100 mL), dried over MgSO4, filtered, and evaporated to a dark oil (49.0 g). At this stage, the reaction mixture consists of a mixture of the desired p-chloroketone and the intermediate α,β-unsaturated ketone. The oil is taken up in 1M HCl-saturated Et2O (150 mL), and stirred at ambient temperature overnight. The reaction is then extracted with H2O (3×100 mL), dried over MgSO4, filtered, and evaporated to a viscous dark oil. The crude product is crystallized from pentane to give 1-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-chloro-3-methyl-butan-1-one as a white solid, mp 101°-2° C.

Workup

  1. customIn a 1 L round bottom flask, equipped with internal thermometer, magnetic stirrer and septum inlet
  2. additionis added dropwise via canula at a rate such that the reaction mixture
  3. temperaturedoes not warm above 0° C
  4. additionafter addition
  5. additionAgain, the rate of addition
  6. temperatureto maintain the reaction temperature below 0° C
  7. customThe cold bath is removed
  8. stirringto stir at ambient temperature for 3 hours
  9. customthe reaction
  10. customthe organic phase is separated
  11. washwashed with additional H2O (2×100 mL)
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. customevaporated to a dark oil (49.0 g)
  15. additionAt this stage, the reaction mixture consists of a mixture of the desired p-chloroketone
  16. stirringstirred at ambient temperature overnight
  17. extractionThe reaction is then extracted with H2O (3×100 mL)
  18. dry with materialdried over MgSO4
  19. filtrationfiltered
  20. customevaporated to a viscous dark oil
  21. customThe crude product is crystallized from pentane

Sources & evidence

ORD record
ord-4dd6f08f05904427a6889a9d4f965c93
Source dataset
uspto-grants-1995_12
Patent number
US05476876

Reaction notes

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