Benzyl Bromide → 3-Benzyloxy-5-hydroxybenzonitrile

HRID 1174810Notes

Reaction equation

HRID 1174810 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-39b038d65e364f08b9c66bba2df21b18
Source dataset
uspto-grants-2010_11
Patent number
US07838542B2

Reaction notes

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