Hydrochloric Acid → 5-Bromo-2-isopropyl-4-methoxy-benzaldehyde

HRID 81740Notes

Reaction equation

HRID 81740 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:11][CH3:12].[Br:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=1[CH:22]([CH3:24])[CH3:23].Cl[CH:26](Cl)[O:27]C.Cl>ClCCCl.Cl[Ti](Cl)(Cl)Cl>[Br:1][C:2]1[C:3]([O:11][CH3:12])=[CH:4][C:5]([CH:8]([CH3:10])[CH3:9])=[C:6]([CH:7]=1)[CH:17]=[O:20].[Br:13][C:14]1[C:15]([CH:22]([CH3:24])[CH3:23])=[CH:16][C:17]([O:20][CH3:21])=[C:18]([CH:19]=1)[CH:26]=[O:27]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 21004Methane, dichloromethoxy-HCID 117464064-Bromo-3-isopropylanisoleHCID 231138811-Bromo-4-isopropyl-2-methoxybenzene

Product 2

HCID 595985355-Bromo-2-isopropyl-4-methoxy-benzaldehydeHCID 595985875-Bromo-4-isopropyl-2-methoxy-benzaldehyde

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 1-bromo-4-isopropyl-2-methoxy-benzene and 1-bromo-2-isopropyl-4-methoxy-benzene from step 2 (6.621 g, 28.9 mmol) in 100 mL 1,2 dichloroethane was added TiCl4 (6.3 mL, 57.8 mmol) at 0° C. After 10 minutes, dichloromethoxymethane (Cl2CHOMe) (2.6 mL, 28.9 mmol) was added and the mixture was warmed to reflux. After 3 hours the mixture was cooled poured over ice and acidified with 50 mL 2 M HCl. The resulting slurry was extracted with CH2Cl2, and washed with brine. The combined organics were dried over MgSO4, filtered and concentrated in vacuo to give a dark-green oil. Purification via flash chromatography (96:4 hexane/ethyl acetate) afforded 5-bromo-2-isopropyl-4-methoxy-benzaldehyde and 5-bromo-4-isopropyl-2-methoxy-benzaldehyde (2.876 g, 39%, 6.621 g, 72%) as a 1:1 mixture of inseparable isomers in the form of an orange oil, which was used directly in step 4.

Workup

  1. temperaturethe mixture was warmed to reflux
  2. temperatureAfter 3 hours the mixture was cooled
  3. additionpoured over ice
  4. extractionThe resulting slurry was extracted with CH2Cl2
  5. washwashed with brine
  6. dry with materialThe combined organics were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a dark-green oil
  10. customPurification via flash chromatography (96:4 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-a5e65a8085e24d8d99edb0f74c25b2fc
Source dataset
uspto-grants-2014_09
Patent number
US08846705B2

Reaction notes

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