Benzyl Bromide → 3-Benzyloxy-5-hydroxybenzonitrile

HRID 415028Notes

Reaction equation

HRID 415028 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([OH:10])[CH:9]=1)[C:5]#[N:6].C([O-])([O-])=O.[K+].[K+].[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CC#N>[CH2:17]([O:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([OH:10])[CH:9]=1)[C:5]#[N:6])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 879523,5-Dihydroxybenzonitrile

Product 1

HCID 219043673-Benzyloxy-5-hydroxybenzonitrileYield 29.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of 3,5-dihydroxybenzonitrile (1.08 g, 8 mmol) and K2CO3 (1.104 g, 8 mmol) in CH3CN (50 mL), benzyl bromide (1.438 g, 8 mmol) was added. The mixture was heated to reflux for 2 hours. Solvent was evaporated under vacuum. The residue was treated with EtOAc (200 mL) and 1M HCl (200 mL). The organic layer was washed, dried, and evaporated in vacuo. The residue was chromatographed (gradient, Hexanes-CH2Cl2-MeOH) to give 3-benzyloxy-5-hydroxybenzonitrile (529 mg, 29%), 3,5-dibenzyloxybenzonitryl (784 mg, 31%) and 256 mg (23.7 mg, 24%) of the starting material. The product 3-benzyloxy-5-hydroxybenzonitrile had: MP 144-145° C.; 1H NMR δ 9.15 (s, 1H, OH), 7.47 (d, 2H, J=7.0 Hz, 2′ and 6′), 7.40 (ddd, 2H, J=7.0, 7.0, 2.0 Hz, 3′ and 5′), 7.34 (dd, 1H, J=7.7 and 2.1 Hz, 4′), 6.89 (dd, 1H, J=1.5 Hz, 4), 6.78 (d, 2H, J=1.8 Hz), 5.16 (s, 2H).

Workup

  1. additionwas added
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 2 hours
  4. customSolvent was evaporated under vacuum
  5. additionThe residue was treated with EtOAc (200 mL) and 1M HCl (200 mL)
  6. washThe organic layer was washed
  7. customdried
  8. customevaporated in vacuo
  9. customThe residue was chromatographed (gradient, Hexanes-CH2Cl2-MeOH)

Sources & evidence

ORD record
ord-dcb1bfa9037b440c93b07cfa6440fe34
Source dataset
uspto-grants-2012_01
Patent number
US08088768B2

Reaction notes

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