Sulfuric Acid → Propionyl Acetophenone

HRID 2300599Notes

Reaction equation

HRID 2300599 reaction equation
[H-].[Na+].[C:3]([O:7]CC)(=O)[CH2:4][CH3:5].[C:10]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)(=[O:12])[CH3:11].OS(O)(=O)=O>C1COCC1.CCO.C1OCCOC2C(=CC=CC=2)OCCOCCOC2C(=CC=CC=2)OC1>[C:13]1([C:10](=[O:12])[CH2:11][C:3](=[O:7])[CH2:4][CH3:5])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 7410AcetophenoneHCID 7749Ethyl PropionateHCID 24758Sodium hydride

Product 1

HCID 21408Propionyl AcetophenoneYield 90.8%

Reagents, catalysts & solvents 3

HCID 702EthanolCatalystHCID 26541Dibenzo-18-crown-6CatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

The title compound was prepared according to Popio, V. V. et al. Synthesis (March 1991), pp 195-197. To a stirred suspension of NaH (1.2 g, 50 mmol) and ethyl propionate (5.73 mL. 50 mmol) in 20 mL THF at 20° C. was added EtOH (2 drops), acetophenone (3.0 g, 25 mmol) in 20 mL of THF, and dibenzo-18-crown-6 (150 mg, 0.4 mmol) in 20 mL of THF. Stirred for 30 min, then at reflux for 1 hr. Cooled (0° C.), then added 25 mL of 10% H2SO4 solution and the aqueous was extracted with Et2O. The organics were washed with H2O, aqueous Na2CO3, and brine. The solution was dried over Na2SO4 and concentrated. Purification by silica gel chromatography (1% to 10% EtOAc in hexanes) gave 4.0 g of Intermediate 16 as a thin oil. 1H NMR indicated an ˜10:1 mixture of tautomers favoring the enol form: 1H NMR (400 MHz, CDCl3, enol form) δ7.87 (m, 2H), 7.52-7.4 (m, 3H), 6.17 (s, 1H), 2.47 (q, 2H, J=7.5), 1.21 (t, 3H, J=7.5)

Workup

  1. customThe title compound was prepared
  2. customet al. Synthesis (March 1991), pp 195-197
  3. temperatureat reflux for 1 hr
  4. extractionthe aqueous was extracted with Et2O
  5. washThe organics were washed with H2O, aqueous Na2CO3, and brine
  6. dry with materialThe solution was dried over Na2SO4
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (1% to 10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-732c85f600d84e1fb015889f89e1d748
Source dataset
uspto-grants-2002_12
Patent number
US06498174B1

Reaction notes

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