Sulfuric Acid → 5-(2-Chlorophenyl)cyclohexane-1,3-dione

HRID 1700524Notes

Reaction equation

HRID 1700524 reaction equation
[O-:1][CH2:2][CH3:3].[Na+].C(OCC)(=O)CC(OCC)=O.[Cl:16][C:17]1[CH:27]=[CH:26][CH:25]=[CH:24][C:18]=1[CH:19]=[CH:20][C:21](=[O:23])[CH3:22].[OH-].[Na+].S(=O)(=O)(O)O>C(O)C.C(OCC)(=O)C>[Cl:16][C:17]1[CH:27]=[CH:26][CH:25]=[CH:24][C:18]=1[CH:19]1[CH2:3][C:2](=[O:1])[CH2:22][C:21](=[O:23])[CH2:20]1

Participants

8

Reactant 5

HCID 1118Sulfuric AcidHCID 7761Diethyl MalonateHCID 14798Sodium HydroxideHCID 1407602-ChlorobenzylideneacetoneHCID 2723922Sodium ethoxide

Product 1

HCID 8753605-(2-Chlorophenyl)cyclohexane-1,3-dione

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 20% sodium ethoxide in ethanol (170.1 g) was added diethyl malonate (80.1 g) at room temperature (immediately precipitated material was observed), and then a solution of crude 2-chlorobenzalacetone (94.6 g) in ethanol (40 ml). The mixture was stirred at 90° C. for 2 hours, cooled at room temperature and under-ice-cooling (for 1 hour). Precipitated materials were filtered and washed with ethyl acetate and isopropylether to give crude ethyl 6-(2-chlorophenyl)-2-hydroxy-4-oxo-2-cyclohexene-1-carboxylate monosodium salt (151.0 g) as pale yellow powder. To said powder was added 2 M sodium hydroxide (350 ml), and the mixture was stirred at 100° C. for 2 hours and cooled. To the mixture was added 2.5 M sulfuric acid (350 ml) for 15 minutes, and the mixture was stirred at 100° C. for 2 hours and cooled. To the mixture was added ethyl acetate (1.4 l), and the mixture was subjected to extraction. The ethyl acetate layer was washed with brine, dried (anhydrous magnesium sulfate), and ethyl acetate was evaporated under reduced pressure. Precipitated crystals were washed with ethyl acetate-isopropylether (1:4) and isopropylether to give 5-(2-chlorophenyl)cyclohexane-1,3-dione (82.1 g) as colorless crystals.

Workup

  1. temperaturecooled at room temperature
  2. temperatureunder-ice-cooling (for 1 hour)
  3. filtrationPrecipitated materials were filtered
  4. washwashed with ethyl acetate and isopropylether
  5. customto give crude ethyl 6-(2-chlorophenyl)-2-hydroxy-4-oxo-2-cyclohexene-1-carboxylate monosodium salt (151.0 g) as pale yellow powder
  6. stirringthe mixture was stirred at 100° C. for 2 hours
  7. temperaturecooled
  8. stirringthe mixture was stirred at 100° C. for 2 hours
  9. temperaturecooled
  10. extractionthe mixture was subjected to extraction
  11. washThe ethyl acetate layer was washed with brine
  12. dry with materialdried (anhydrous magnesium sulfate), and ethyl acetate
  13. customwas evaporated under reduced pressure
  14. customPrecipitated crystals
  15. washwere washed with ethyl acetate-isopropylether (1:4) and isopropylether

Sources & evidence

ORD record
ord-6dcfcada7b9d4a898c54fb9e6d63421c
Source dataset
uspto-grants-2002_02
Patent number
US06350749B1

Reaction notes

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