Hydrogen Bromide → 5-Bromo-2-methylbenzonitrile

HRID 1921319Notes

Reaction equation

HRID 1921319 reaction equation
S(=O)(=O)(O)O.N([O-])=O.[Na+].N[C:11]1[CH:12]=[CH:13][C:14]([CH3:19])=[C:15]([CH:18]=1)[C:16]#[N:17].[BrH:20]>C(O)(=O)C>[Br:20][C:11]1[CH:12]=[CH:13][C:14]([CH3:19])=[C:15]([CH:18]=1)[C:16]#[N:17]

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 1118Sulfuric AcidHCID 27353655-Amino-2-methylbenzonitrileHCID 23668193Sodium Nitrite

Product 1

HCID 129940045-Bromo-2-methylbenzonitrile

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
30 °C

Procedure

Conc. sulfuric acid (60 mL) is added to sodium nitrite (5.75 g, 83.4 mmol). The temperature rises to 70° C. and solution is effected. After cooling to 20-40° C., the above solution is added dropwise to a mechanically stirred solution of 5-amino-2-methylbenzonitrile (10.0 g, 75.8 mmol) in acetic acid (150 mL). The temperature is maintained at 20-40° C. throughout the addition. The reaction mixture is cooled to 16-20° C. and a solution of cuprous bromide (24 g, 167 mmol) in conc. hydrobromic acid (150 mL) is added keeping the temperature between 16-20° C. After 45 min, the reaction mixture is poured onto ice (500 g) and the solids are collected by filtration then dissolved in dichloromethane (600 mL), washed with brine, dried, filtered and concentrated to give 5-bromo-2-methylbenzonitrile (see also, Dressler, J. et al. EP 0 594 019) (11.5 g, 77%) as a brown solid. 1H NMR (CDCl3, δ ppm): 7.72 (1H, s), 7.60 (1H, dd), 7.20 (1H, dd), 2.50 (3H, s).

Workup

  1. customrises to 70° C.
  2. temperatureThe temperature is maintained at 20-40° C. throughout the addition
  3. temperatureThe reaction mixture is cooled to 16-20° C.
  4. custombetween 16-20° C
  5. additionthe reaction mixture is poured onto ice (500 g)
  6. filtrationthe solids are collected by filtration
  7. dissolutionthen dissolved in dichloromethane (600 mL)
  8. washwashed with brine
  9. customdried
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-d45d7a38b171400bba0a815bed629587
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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