Nitric Acid → 2,3,4-Trifluoro-5-nitrobenzoic acid

HRID 1665837Notes

Reaction equation

HRID 1665837 reaction equation
[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[C:14]([F:15])=[C:13]([F:16])[CH:12]=[CH:11][C:7]=1[C:8]([OH:10])=[O:9].O>OS(O)(=O)=O>[F:5][C:6]1[C:14]([F:15])=[C:13]([F:16])[C:12]([N+:1]([O-:4])=[O:2])=[CH:11][C:7]=1[C:8]([OH:10])=[O:9]

Participants

5

Reactant 3

HCID 944Nitric Acid2×HCID 962WaterHCID 3029322,3,4-Trifluorobenzoic acid

Product 1

HCID 158712412,3,4-Trifluoro-5-nitrobenzoic acidYield 75%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent2×

Procedure

Fuming HNO3 90% (549.0 g, 7.84 mol corrected for 90% wt, 1.26 equiv.) was added to 2.0 L (3.35 kg) of concentrated H2SO4 over 18 minutes with stirring. The solution of HNO3 was then added to a mixture of 2,3,4-trifluorobenzoic acid (1094 g, 6.21 mol, 1 equiv.) in 3.3 L (5.85 kg) of concentrated H2SO4 in a second flask with ice-water bath cooling over an hour. Upon complete addition, the reaction mixture was allowed to warm to room temperature. After 5 hours, the reaction was complete by HPLC and the reaction mixture (brown solution) was poured over 10 minutes into a mechanically stirred mixture of 10.6 kg of distilled water and 11.8 kg of ice. The yellow slurry was cooled to 14° C., stirred for 2 hours and then filtered. The cake was rinsed with 4.0 L of distilled water and then with 5 L of heptane. The wet cake was oven-dried overnight. The crude solids (1.791 kg) were then stirred in 16 L of distilled water (9 vol.), filtered and oven-dried at 55° C. under high vacuum overnight to yield 1035.9 g (75%) of compound 2 as a yellowish solid. HPLC was 98 a % (220 nm) and 100% (254 nm). 1H NMR (400 MHz, d6 DMSO) δ 8.44 (1H, apparent dt, J 1.9, 7, Ar—H). 19F NMR (376 MHz, d6 DMSO) δ −153.9, −131.5, −120.9. 13C NMR (100 MHz, d6 DMSO) δ 117 (C, m), 124 (CH, b s), 134 (C, s), 141 (C—F, dt, J 251, 10), 148 (C—F, dd, J 265, 13), 154 (C—F, dd, J 265, 10), 163 (COOH). IR νmax/cm−1 3108 (br), 1712, 1555, 1345, 1082. MS APCI (−) m/z 220 (M−1) detected.

Workup

  1. temperaturecooling over an hour
  2. additionUpon complete addition
  3. temperatureThe yellow slurry was cooled to 14° C.
  4. stirringstirred for 2 hours
  5. filtrationfiltered
  6. washThe cake was rinsed with 4.0 L of distilled water
  7. customThe wet cake was oven-dried overnight
  8. stirringThe crude solids (1.791 kg) were then stirred in 16 L of distilled water (9 vol.)
  9. filtrationfiltered
  10. customoven-dried at 55° C. under high vacuum overnight

Sources & evidence

ORD record
ord-23e744ef84144527b8907fc20707f925
Source dataset
uspto-grants-2011_10
Patent number
US08039637B2

Reaction notes

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