Carbon Dioxide → 3-Bromo-2-methylbenzoic Acid

HRID 564449Notes

Reaction equation

HRID 564449 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[C:3]=1[CH3:9].[C:10](=[O:12])=[O:11]>C1COCC1.[Li]C(C)(C)C>[Br:8][C:4]1[C:3]([CH3:9])=[C:2]([CH:7]=[CH:6][CH:5]=1)[C:10]([OH:12])=[O:11]

Participants

5

Reactant 2

HCID 280Carbon DioxideHCID 346812,6-Dibromotoluene

Product 1

HCID 27355903-Bromo-2-methylbenzoic AcidYield 63.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 178418306HCID 178418306, compoundSolvent

Procedure

To a solution of 1,3-dibromo-2-methylbenzene (6.57 g) in dry THF (100 mL), t-BuLi solution (1.5 M in pentane, 17 mL) was added dropwise at −80° C. After addition, the reaction mixture was stirred between −76˜−78° C. for 2 h. After the mixture was cooled to below −80° C., dry ice was added, and then warmed to room temperature naturally. Solvent was removed, 5% NaOH solution (40 mL) was added, washed with CH2Cl2 (10 mL×2). Then the aqueous layer was acidified with concentrated HCl to pH=1, extracted with EtOAc (100 mL×2). The combined organic phase was dried over anhydrous Na2SO4. After removing the solvent, the residue was purified by silica column chromatography, (eluted with petrol ether:EtOAc=8:1 to 1:1), to obtain 3.58 g of the product. Yield: 63.4%. 1H NMR (400 MHz, CDCl3): δ 2.73 (s, 3 H), 7.15 (t, J=8.0 Hz, 1 H), 7.77 (dd, J=8.0 Hz, J=1.2 Hz, 1 H), 7.94 (dd, J=8.0 Hz, J=1.2 Hz, 1 H).

Workup

  1. additionAfter addition
  2. temperatureAfter the mixture was cooled to below −80° C.
  3. customSolvent was removed
  4. addition5% NaOH solution (40 mL) was added
  5. washwashed with CH2Cl2 (10 mL×2)
  6. extractionextracted with EtOAc (100 mL×2)
  7. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
  8. customAfter removing the solvent
  9. customthe residue was purified by silica column chromatography, (eluted with petrol ether:EtOAc=8:1 to 1:1),

Sources & evidence

ORD record
ord-5459b2d9935144b2b9e146dbbea55e53
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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