Hydrochloric Acid → 4'-Methoxy-3-phenylpropiophenone

HRID 556029Notes

Reaction equation

HRID 556029 reaction equation
[C:1]1([CH2:7][CH2:8][C:9](Cl)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Al+3].[Cl-].[Cl-].[Cl-].Cl>ClCCl.O>[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([C:9](=[O:10])[CH2:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7519AnisoleHCID 64801Benzenepropanoyl chlorideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 2455544'-Methoxy-3-phenylpropiophenone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a 500 ml three-necked flask provided with a mechanical agitator and a thermometer were added a solution of 22.4 g (133.2 mmol) in theoretical amount of 3-phenylpropionyl chloride which was prepared in the step 1, dissolved in 100 ml dichloromethane, 14.4 g (205.9 mmol) methylphenyl ether and 150 ml dichloromethane, the mixture was cooled in an ice salt bath to lower than −5° C., while maintaining the inside temperature at −5° C. to −10° C., 17.8 g (133.2 mmol) anhydrous AlCl3 was added portionwise, upon the completion of addition. The mixture was stirred at this temperature for 1 hour and then at room temperature for 1 hour, the resultant was poured under stirring into a mixture of 100 g ice, 100 g water and 40 ml concentrated hydrochloric acid, the organic layer was separated, and the aqueous layer was extracted with dichloromethane twice ×20 ml, the organic layers were combined and washed with saturated brine, then with saturated aqueous sodium bicarbonate solution, and then with saturated brine until neutrality, dried over anhydrous magnesium sulfate, filtrated and concentrated under a reduced pressure to obtain a crude product, which was recrystallized with petroleum ether and ethyl acetate (2:1) to obtain a 23.5 g product, the mother liquid was concentrated and recrystallized to obtain a 3.3 g product in a yield of 83.7% in total, mp: 96-97□. 1H-NMR (CDCl3, 400 MHz) δ: 3.05 (2H, t, J=8.16 Hz), 3.25 (2H, t, J=8.16 Hz), 3.86 (3H, s, OCH3), 6.92 (2H, d, J=9.00 Hz, ArH), 7.18˜7.32 (5H, m, ArH), 7.94 (2H, d, J=9.00 Hz, ArH); EI-MS m/e (%): 240.1 (M+, 37), 135 (100).

Workup

  1. customTo a 500 ml three-necked flask provided with a mechanical agitator
  2. customwas prepared in the step 1
  3. temperaturewhile maintaining the inside temperature at −5° C. to −10° C.
  4. waitat room temperature for 1 hour
  5. additionthe resultant was poured
  6. customthe organic layer was separated
  7. extractionthe aqueous layer was extracted with dichloromethane twice ×20 ml
  8. washwashed with saturated brine
  9. dry with materialwith saturated aqueous sodium bicarbonate solution, and then with saturated brine until neutrality, dried over anhydrous magnesium sulfate
  10. filtrationfiltrated
  11. concentrationconcentrated under a reduced pressure
  12. customto obtain a crude product, which
  13. customwas recrystallized with petroleum ether and ethyl acetate (2:1)

Sources & evidence

ORD record
ord-285b51b0e8ec4107a435fce619d898b4
Source dataset
uspto-grants-2011_11
Patent number
US08053581B2

Reaction notes

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