Hydrochloric Acid → 4-Bromo-2,6-diethylbenzonitrile

HRID 1888421Notes

Reaction equation

HRID 1888421 reaction equation
[Br:1][C:2]1[CH:8]=[C:7]([CH2:9][CH3:10])[C:5](N)=[C:4]([CH2:11][CH3:12])[CH:3]=1.Cl.N([O-])=O.[Na+].C(=O)(O)[O-].[Na+].[Cu][C:24]#[N:25].[C-]#N.[K+]>O.C(Cl)Cl>[Br:1][C:2]1[CH:8]=[C:7]([CH2:9][CH3:10])[C:5]([C:24]#[N:25])=[C:4]([CH2:11][CH3:12])[CH:3]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 9032Potassium CyanideHCID 516892Sodium BicarbonateHCID 6114524-Bromo-2,6-diethylanilineHCID 23668193Sodium NitriteHCID 178418546HCID 178418546, compound

Product 1

HCID 532567634-Bromo-2,6-diethylbenzonitrileYield 88.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent4×HCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

4-Bromo-2,6-diethylaniline (4.80 g, 21.0 mmol) was suspended in a mixture of water (25 mL) and concentrated hydrochloric acid (8.0 mL) then sonicated for 10 minutes. The resultant suspension was cooled to 0° C. and a solution of sodium nitrite (1.60 g, 23.1 mmol) in water (5 mL) was slowly added, maintaining the reaction temperature below 5° C. After 30 minutes, the reaction mixture was neutralised by the careful addition of sodium bicarbonate, then the resultant suspension was added in aliquots to a solution of copper (I) cyanide (2.26 g, 25.2 mmol) and potassium cyanide (3.43 g, 52.6 mmol) in water (25 mL) at 70° C. After complete addition, heating at 70° C. was continued for 1 h then the reaction mixture was cooled to ambient temperature. Water and DCM were added then the organic phase was collected, dried over anhydrous sodium sulfate and concentrated in vacuo to afford a brown residue that was purified by flash chromatography (silica, 80 g column, ISCO, 0-10% ethyl acetate in cyclohexane) to afford the title compound as an off-white solid (4.43 g, 88%). 1H NMR (DMSO-D6, 300 MHz): 7.58 (s, 2H), 2.78 (q, J=7.6 Hz, 4H), 1.21 (t, J=7.6 Hz, 6H).

Workup

  1. customthen sonicated for 10 minutes
  2. temperaturemaintaining the reaction temperature below 5° C
  3. additionAfter complete addition
  4. waitwas continued for 1 h
  5. temperaturethe reaction mixture was cooled to ambient temperature
  6. customthe organic phase was collected
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customto afford a brown residue that
  10. customwas purified by flash chromatography (silica, 80 g column, ISCO, 0-10% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-9d685706cb2c4e2f988ab4d33ab10b21
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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