1,2-Dichloroethane → 3-Nitro-4-(trifluoromethyl)benzoic acid

HRID 257574

Reaction equation

HRID 257574 reaction equation
[N+:1]([C:4]1[CH:9]=[C:8](C)[CH:7]=[CH:6][C:5]=1[C:11]([F:14])([F:13])[F:12])([O-:3])=[O:2].ClCCCl.Cl[O-].[Na+].[OH-].[Na+].[C:24]([O-:27])(O)=[O:25].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.[Ru](Cl)(Cl)Cl>[N+:1]([C:4]1[CH:9]=[C:8]([CH:7]=[CH:6][C:5]=1[C:11]([F:12])([F:13])[F:14])[C:24]([OH:27])=[O:25])([O-:3])=[O:2]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 14798Sodium Hydroxide2×HCID 516892Sodium BicarbonateHCID 197831564-Methyl-2-nitro-1-(trifluoromethyl)benzeneHCID 23665760Sodium Hypochlorite3×

Product 1

HCID 27790153-Nitro-4-(trifluoromethyl)benzoic acidYield 49%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6093376Ruthenium trichloride hydrateCatalyst

Conditions

Temperature
45 °C

Procedure

To a rapidly stirred mixture of 1.00 g (4.88 mmol) of 2-nitro-4-methylbenzotrifluoride (from Step A), 236 mg (0.732 mmol) of tetra-n-butylammonium bromide, 51 mg (0.244 mmol) of ruthenium trichloride hydrate, and 2 mL of 1,2-dichloroethane were added five 5.8 -mL (approximately 22 mmol) portions of 13% sodium hypochlorite solution (aqueous, approx. 3.8M) while monitoring and adjusting the pH. With each addition of sodium hypochlorite solution, 5N NaOH was added as necessary to maintain the pH between 8.5 and 10.5, and the next portion of sodium hypochlorite was added only when the pH was stable for about 5 minutes. The entire addition required approximately 2 hours, and the final pH was 10.3. After being stirred overnight at 45° C., the 2-phase mixture was cooled and separated. The aqueous phase was acidified to pH 3 by addition of 20% sulfuric acid and extracted 3× with ethyl acetate. The combined organic extracts were washed with H2O (3×), then with brine, and dried over anhydrous Na2SO4. The residue obtained upon concentration was taken up in 5% NaHCO3 (aqueous) adjusted to pH 9 with 5% NaOH. The aqueous phase was washed twice with methylene chloride and then with ether. Next, the water phase was acidified with 20% sulfuric acid and extracted with ethyl acetate as above to yield 563 mg (49%) of the title compound as an off-white solid, mp 156°-158° C.; TLC in 1:1 hexane-EtOAc (at origin); mass spectrum (EI) m/e 235 (M+). 200 MHz 1H NMR (CD3OD) δ7.87 (d, J=8 Hz, 1H), 8.31 (d, J=8 Hz, 1H), 8.45 (s, 1H).

Workup

  1. additionwas added as necessary
  2. temperatureto maintain the pH between 8.5 and 10.5
  3. additionThe entire addition required approximately 2 hours
  4. temperaturethe 2-phase mixture was cooled
  5. customseparated
  6. additionThe aqueous phase was acidified to pH 3 by addition of 20% sulfuric acid
  7. extractionextracted 3× with ethyl acetate
  8. washThe combined organic extracts were washed with H2O (3×)
  9. dry with materialwith brine, and dried over anhydrous Na2SO4
  10. customThe residue obtained upon concentration
  11. washThe aqueous phase was washed twice with methylene chloride
  12. extractionextracted with ethyl acetate as above

Sources & evidence

ORD record
ord-68c384858fbc45a39c79ce8447993645
Source dataset
uspto-grants-1993_11
Patent number
US05262412

Linked notes

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