Citric Acid → 4-Bromo-2,5-dimethylbenzaldehyde

HRID 1748749Notes

Reaction equation

HRID 1748749 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([Br:9])=[CH:4][C:3]=1[CH3:10].C([Mg]Cl)(C)C.C([Li])CCC.C(O)(=O)C[C:23](CC(O)=O)(C(O)=O)[OH:24]>C1COCC1.CN(C=O)C>[Br:9][C:5]1[C:6]([CH3:8])=[CH:7][C:2]([CH:23]=[O:24])=[C:3]([CH3:10])[CH:4]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 66175Benzene, 1,4-dibromo-2,5-dimethyl-HCID 178418339ButyllithiumHCID 178418918HCID 178418918, compound

Product 1

HCID 131191014-Bromo-2,5-dimethylbenzaldehydeYield 91%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

A solution of 1,4-dibromo-2,5-dimethylbenzene (5.0 g, 18.94 mmol, Aldrich) in anhydrous THF (20 mL) was cooled to about −10° C. Isopropyl magnesium chloride (3.95 mL, 2.0 M in THF, 7.9 mmol) was added. The mixture was allowed to stir at about −10° C. for about 0.25 h. Next n-butyl lithium (6.31 mL, 2.5 M in hexanes, 15.8 mmol) was added dropwise keeping the temperature at or below about 0° C. Once the addition was complete the reaction was stirred at about −10° C. for about 1 h. Next a solution of DMF in 10 mL anhydrous THF (20.52 mmol) was added dropwise keeping the temperature at or below about 0° C. The reaction was stirred at ambient temperature for about 3 hours. The reaction was poured into about 50 mL of about 5 M aqueous citric acid solution (exothermic) and stirred at room temperature for about 10 minutes. The layers were separated and the aqueous layer was extracted once with toluene (50 mL). The combined organic layers were washed with water (20 mL), then concentrated in vacuo. The residue was purified by column chromatography (SiO2, diethyl ether/petroleum ether 5:95) to give 4-bromo-2,5-dimethylbenzaldehyde (3.66 g, 17.18 mmol, 91%) as a pale crystalline solid: 1H-NMR (CDCl3, Bruker 400 MHz) δ 2.43 (3 H, s); 2.60 (3 H, s); 7.47 (1 H, s); 7.63 (1 H, s) 10.2 (1 H, s).

Workup

  1. custombelow about 0° C
  2. additionOnce the addition
  3. stirringwas stirred at about −10° C. for about 1 h
  4. custombelow about 0° C
  5. stirringThe reaction was stirred at ambient temperature for about 3 hours
  6. stirringstirred at room temperature for about 10 minutes
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted once with toluene (50 mL)
  9. washThe combined organic layers were washed with water (20 mL)
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by column chromatography (SiO2, diethyl ether/petroleum ether 5:95)

Sources & evidence

ORD record
ord-47bccb10356142899086a9a0d1f2ecbc
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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