Hydrogen Bromide → 4-Bromo-5-fluoro-2-nitrotoluene

HRID 844206Notes

Reaction equation

HRID 844206 reaction equation
N([O-])=O.[Na+].[F:5][C:6]1[CH:12]=[C:11]([CH3:13])[C:10]([N+:14]([O-:16])=[O:15])=[CH:9][C:7]=1N.[BrH:17]>O.[Cu]Br>[Br:17][C:7]1[CH:9]=[C:10]([N+:14]([O-:16])=[O:15])[C:11]([CH3:13])=[CH:12][C:6]=1[F:5]

Participants

6

Reactant 3

HCID 260Hydrogen Bromide2×HCID 120999472-Fluoro-4-methyl-5-nitroanilineHCID 23668193Sodium Nitrite

Product 1

HCID 27793654-Bromo-5-fluoro-2-nitrotolueneYield 50%

Reagents, catalysts & solvents 2

HCID 24593copper(I) bromideCatalystHCID 962WaterSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of sodium nitrite (7.6 g, 110 mmol) in water (30 mL) was added dropwise over 15 min to a stirred suspension of 2-fluoro-4-methyl-5-nitroaniline (17 g, 100 mmol) in hydrobromic acid, (48%, 150 mL) and water (30 mL) at 0° C. The mixture was stirred at 0° C. for 15 min then added portionwise over 10 min to a stirred suspension of copper(I)bromide (16.5 g, 112 mmol) in hydrobromic acid (48%, 50 mL) and water (90 mL) at 0° C. The mixture was stirred at 0° C. for 30 min then warmed to room temperature and stirred for 3 h. The mixture was poured onto ice-water (500 mL) and extracted with ethyl acetate (3×). The combined organic extracts were washed with saturated aqueous sodium bicarbonate solution, dried (magnesium sulfate), concentrated in vacuo and purified by column chromatography [SiO2; heptane-ethyl acetate (19:1)] to give the product (11.8 g, 50%) as an off-white solid: IR νmax (nujol)/cm−1 2925, 2855, 1571, 1523, 1478, 1349, 1264, 1103, 895, 671 and 589; NMR δH (400 MHz, CDCl3) 8.27 (1H, d, J 6.5), 7.10 (1H, d, J 9.1), 2.60 (3H, s).

Workup

  1. stirringThe mixture was stirred at 0° C. for 30 min
  2. temperaturethen warmed to room temperature
  3. stirringstirred for 3 h
  4. additionThe mixture was poured onto ice-water (500 mL)
  5. extractionextracted with ethyl acetate (3×)
  6. washThe combined organic extracts were washed with saturated aqueous sodium bicarbonate solution
  7. dry with materialdried (magnesium sulfate)
  8. concentrationconcentrated in vacuo
  9. custompurified by column chromatography [SiO2; heptane-ethyl acetate (19:1)]

Sources & evidence

ORD record
ord-e60dbfc952ee44e0b4ed138fefcc60c4
Source dataset
uspto-grants-2002_04
Patent number
US06380238B1

Reaction notes

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