Acetic Acid → 2,4-Diamino-3-fluoro-5-nitrobenzoic acid

HRID 391267Notes

Reaction equation

HRID 391267 reaction equation
F[C:2]1[C:10]([F:11])=[C:9](F)[C:8]([N+:13]([O-:15])=[O:14])=[CH:7][C:3]=1[C:4](O)=O.[OH-:16].[NH4+:17].[OH2:18].C(O)(=O)C.C[N:24]1CCCC1=O>>[NH2:17][C:2]1[C:10]([F:11])=[C:9]([NH2:24])[C:8]([N+:13]([O-:15])=[O:14])=[CH:7][C:3]=1[C:4]([OH:18])=[O:16]

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 962WaterHCID 13387N-methyl-2-pyrrolidoneHCID 14923Ammonium Hydroxide2×HCID 158712412,3,4-Trifluoro-5-nitrobenzoic acid

Product 1

HCID 593654992,4-Diamino-3-fluoro-5-nitrobenzoic acidYield 86%

Conditions

Temperature
85 °C

Procedure

A suspension of 2,3,4-trifluoro-5-nitrobenzoic acid (1) (5 g) and ammonium hydroxide (7.7 grams, 25 wt % NH3 in H2O, 4.9 equivalents) in N-methylpyrrolidinone (12.5 mL) was heated at 80-90° C. in a sealed reactor. During the reaction the mixture became homogeneous and the pressure rose to 0.4 bar. After 1.75 hours, HPLC analysis showed incomplete conversion and a further charge of ammonium hydroxide (2 g, 25 wt % NH3 in H2O) was added, followed by heating at 80-90° C. in the sealed reactor for an additional 1.5 hours. After this time HPLC analysis indicated >99% conversion and the mixture was allowed to cool to room temperature overnight. The contents of the reactor were then added to water (100 mL), producing a homogeneous, brown solution with a pH of 9.4. Acetic acid was then added to the mixture until the pH was 6. After cooling to 0° C. the product was isolated by filtration and washed with a mixture of water (10 mL) and MeOH (10 mL), then dried in a vacuum oven at 50° C., to provide 4.4 g (86% yield) of 2,4-diamino-3-fluoro-5-nitrobenzoic acid (2) (HPLC purity 99.7 a %). 1H NMR (400 MHz, d6 DMSO) δ 7.27 (2H, br s, NH2), 7.31 (2H, br s, NH2), 8.46, (1H, s, Ar—H), 13.10 (1H, br, CO2H). 13C NMR (100 MHz, d6 DMSO) δ 102 (C), 123 (C), 127 (CH), 136 (d, J 229, CF), 138 (C), 143 (CF), 168 (C═O).

Workup

  1. customDuring the reaction the mixture
  2. additionwas added
  3. temperatureby heating at 80-90° C. in the sealed reactor for an additional 1.5 hours
  4. temperatureto cool to room temperature overnight
  5. customproducing a homogeneous, brown solution with a pH of 9.4
  6. temperatureAfter cooling to 0° C. the product
  7. customwas isolated by filtration
  8. washwashed with a mixture of water (10 mL) and MeOH (10 mL)
  9. customdried in a vacuum oven at 50° C.

Sources & evidence

ORD record
ord-428da38c91d947e0bf100d01ba47f5db
Source dataset
uspto-grants-2013_02
Patent number
US08383832B2

Reaction notes

Loading…