Benzyl Bromide → 3-Benzyloxy-5-hydroxybenzonitrile

HRID 500416Notes

Reaction equation

HRID 500416 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-d123c472ba7542d2a0a6819e9625cef5
Source dataset
uspto-grants-2010_08
Patent number
US07772216B2

Reaction notes

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