Iodine → 2,3,4-trifluoro-5-iodobenzoic acid

HRID 910821Notes

Reaction equation

HRID 910821 reaction equation
CC(OC(C)=O)=O.OS(O)(=O)=O.[I:13]I.[F:15][C:16]1[C:24]([F:25])=[C:23]([F:26])[CH:22]=[CH:21][C:17]=1[C:18]([OH:20])=[O:19]>O=[Mn]=O.C(Cl)Cl.CC(O)=O>[F:15][C:16]1[C:24]([F:25])=[C:23]([F:26])[C:22]([I:13])=[CH:21][C:17]=1[C:18]([OH:20])=[O:19]

Participants

8

Reactant 4

HCID 807Iodine3×HCID 1118Sulfuric AcidHCID 7918Acetic AnhydrideHCID 3029322,3,4-Trifluorobenzoic acid

Product 1

HCID 111094122,3,4-trifluoro-5-iodobenzoic acidYield 232.1%

Reagents, catalysts & solvents 3

HCID 14801Manganese dioxideCatalyst3×HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

AcOH (1.2 L) and Ac2O (0.63 L) were added to a 5 L flask. H2SO4 (1.6 L) was then added to the same flask while cooling with ice to prevent the temperature from exceeding 40° C. Next, I2 (70 g), activated MnO2 (70 g) and 2,3,4-trifluorobenzoic acid (120 g, 0.68 mol) were added in solid form while stirring at room temperature. While stirring the resulting dark purple suspension at 50° C., I2 (70 g) and activated MnO2 (70 g) were added after 2 to 3 hours, and I2 (33 g) and activated MnO2 (37 g) were further added after 4 to 6 hours. After 24 hours, the reaction mixture was added to ice water (2 L). The purple organic layer obtained by extraction three times with CH2Cl2 (1.6 L, 1.0 L, 1.0 L) was washed twice with 0.2N Na2S2O3 aqueous solution (2.0 L, 1.0 L), resulting in alteration of the organic layer color to pale yellow. The organic layer was washed four times with 1.0 L of water to remove the AcOH, yielding a non-cloudy transparent organic layer. After removing water in the organic layer with Na2SO4 (1.3 kg), the solvent was removed by distillation to yield 192 g of 2,3,4-trifluoro-5-iodobenzoic acid (0.64 mol, 94%, purity: 99 LC area % (UV peak area % in LC)) as white powders. If necessary, rinsing may be performed with a mixed solvent of ethanol and hexane (EtOAc: hexane=1:9 (v/v)).

Workup

  1. temperaturewhile cooling with ice
  2. customfrom exceeding 40° C
  3. stirringWhile stirring the resulting dark purple suspension at 50° C.
  4. washwas washed twice with 0.2N Na2S2O3 aqueous solution (2.0 L, 1.0 L)
  5. customresulting in alteration of the organic layer color to pale yellow
  6. washThe organic layer was washed four times with 1.0 L of water
  7. customto remove the AcOH
  8. customyielding a non-cloudy transparent organic layer
  9. customAfter removing water in the organic layer with Na2SO4 (1.3 kg)
  10. customthe solvent was removed by distillation

Sources & evidence

ORD record
ord-615ab72dc1794caf9eb40dffc683fa7b
Source dataset
uspto-grants-2011_09
Patent number
US08022247B2

Reaction notes

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