Dimethylformamide → 2,5-Dimethoxy-3,4,6-trimethylbenzaldehyde

HRID 1021186Notes

Reaction equation

HRID 1021186 reaction equation
Br[C:2]1[C:7]([CH3:8])=[C:6]([O:9][CH3:10])[C:5]([CH3:11])=[C:4]([CH3:12])[C:3]=1[O:13][CH3:14].[Li]CCCC.CN([CH:23]=[O:24])C>C1C=CC=CC=1>[CH3:14][O:13][C:3]1[C:4]([CH3:12])=[C:5]([CH3:11])[C:6]([O:9][CH3:10])=[C:7]([CH3:8])[C:2]=1[CH:23]=[O:24]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 2973651-Bromo-2,5-dimethoxy-3,4,6-trimethylbenzeneHCID 178418339Butyllithium

Product 1

HCID 27526052,5-Dimethoxy-3,4,6-trimethylbenzaldehydeYield 112%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

1-Bromo-2,5-dimethoxy-3,4,6-trimethylbenzene from Step 1 (5 g, 19.3 mmol, 1 equiv.) was dissolved in benzene (2×20 mL) and the solvent removed in vacuo to remove residual water. The dry solid was dissolved in toluene (100 mL) and the resulting solution cooled in an ice-water bath. To the colorless solution was added n-BuLi (1.6 M in hexanes, 16 mL, 26.9 mmol, 1.4 equiv.) dropwise over 1 min. After 2 min stirring, the resulting aryllithium species was quenched with DMF (7 mL, 90 mmol, 4.5 equiv.). Following an additional 30 min, excess base was quenched with 1 M aqueous citric acid (20 mL), and the mixture diluted in ethyl acetate (100 mL). The organics were removed, rinsed with brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give 4.5 g 2,5-dimethoxy-3,4,6-trimethylbenzaldehyde as an orange solid, which was used without further purification. 1H NMR (CDCl3, 400 MHz) 10.5 (s, 1H), 3.79 (s, 3H), 3.63 (s, 3H), 2.55 (s, 3H), 2.31 (s, 3H), 2.23 (s, 3H) ppm.

Workup

  1. customthe solvent removed in vacuo
  2. customto remove residual water
  3. dissolutionThe dry solid was dissolved in toluene (100 mL)
  4. temperaturethe resulting solution cooled in an ice-water bath
  5. waitFollowing an additional 30 min
  6. customexcess base was quenched with 1 M aqueous citric acid (20 mL)
  7. additionthe mixture diluted in ethyl acetate (100 mL)
  8. customThe organics were removed
  9. washrinsed with brine (30 mL)
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9a9802f5f0d34fcba1a1acf0b9a62ddc
Source dataset
uspto-grants-2014_05
Patent number
US08716527B2

Reaction notes

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