Toluene → 2-[4-(Hydroxymethyl)phenyl]benzonitrile

HRID 1047656Notes

Reaction equation

HRID 1047656 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([C:15]#[N:16])=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:5][CH:4]=1.C1(C)C=CC=CC=1.C([O-])(=[O:26])C.[K+].[OH-].[Na+]>O>[OH:26][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([C:15]#[N:16])=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 1140Toluene2×HCID 14798Sodium HydroxideHCID 517044Potassium AcetateHCID 15019124'-(Bromomethyl)-2-cyanobiphenyl

Product 1

HCID 13938962-[4-(Hydroxymethyl)phenyl]benzonitrile

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
90 °C

Procedure

A 750 ml flask is charged with 54.4 g (0.2 mol) of 4′-bromomethyl-biphenyl-2-carbonitrile and 250 ml of toluene. To this suspension is added a solution of 30 g (0.3 mol) of potassium acetate in 15 ml of water. The heterogeneous mixture is heated up to an internal temperature of 90° C. to become a clear biphasic solution. After 12 hours at an internal temperature of 90° C. the conversion to the OAc derivative is complete. The biphasic mixture is cooled down to internal temperature of about 50° C. followed by addition of 150 ml NaOH (2N). The mixture is heated up to an internal temperature of ca. 70° C. (extern. temp. 80° C.). After 5 hours at this temperature the PTC saponification is complete (100% conversion, HPLC). Additional 150 ml toluene is added and the warm reaction solution (ca. 50° C.) is washed three times with 50 ml of hot water until the pH is around 7. The toluene phase is evaporated under reduced pressure and the resulting crystalline residue is dried at 50° C. over 24 hours in vacuum to give the white crystalline product with 98% purity (HPLC) and a water content of 0.23%.

Workup

  1. temperatureThe biphasic mixture is cooled down to internal temperature of about 50° C.
  2. temperatureThe mixture is heated up to an internal temperature of ca. 70° C. (extern. temp. 80° C.)
  3. customthe warm reaction solution (ca. 50° C.)
  4. washis washed three times with 50 ml of hot water until the pH is around 7
  5. customThe toluene phase is evaporated under reduced pressure
  6. customthe resulting crystalline residue is dried at 50° C. over 24 hours in vacuum
  7. customto give the white crystalline product with 98% purity (HPLC)

Sources & evidence

ORD record
ord-d398485ff99e4dd791d5776049fa8c45
Source dataset
uspto-grants-2013_10
Patent number
US08569528B2

Reaction notes

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