Tolazoline → 1-(2,4-Dichlorophenyl)methyl-4,5-dihydro-2-phenylmethylimidazole

HRID 543302Notes

Reaction equation

HRID 543302 reaction equation
[CH:1]1[CH:2]=[CH:3][C:4]([CH2:7][C:8]2[NH:12][CH2:11][CH2:10][N:9]=2)=[CH:5][CH:6]=1.[H-].[Na+].[Cl:15][C:16]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:17]=1[CH2:18]Cl>CN(C)C=O>[Cl:15][C:16]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:17]=1[CH2:18][N:9]1[CH2:10][CH2:11][N:12]=[C:8]1[CH2:7][C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1

Participants

5

Reactant 3

HCID 5504TolazolineHCID 72122,4-Dichlorobenzyl chlorideHCID 24758Sodium hydride

Product 1

HCID 138511211-(2,4-Dichlorophenyl)methyl-4,5-dihydro-2-phenylmethylimidazoleYield 50.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
65 °C

Procedure

Tolazoline (16 g, 0.1 mol) in dimethylformamide (40 ml) was added dropwise to a suspension of sodium hydride (80% dispersion in mineral oil, 3 g, 0.1 mol) in dimethylformamide (40 ml) under a nitrogen atmosphere. After stirring at 20° C. for 30 minutes and at 65° C. for an additional 30 minutes, a solution of 2,4-dichlorobenzyl chloride (19.5 g, 0.1 mol) in dimethylformamide was added dropwise to the reaction mixture over a period of 2.5 hours. The mixture was heated to 80°-90° C. for 5 hours, cooled and concentrated under reduced pressure. Water was added to the residue and the resulting mixture was extracted with ethyl acetate. The organic phase was separated, washed with brine and dried over anhydrous magnesium sulphate. The solvent was removed under reduced pressure yielding a residue which was chromatographed on silica gel eluting with ammonia/methanol/ethyl acetate (3:12:85) to yield as a colorless oil, 1-(2,4-dichlorophenylmethyl)-4,5-dihydro-2-phenylmethylimidazole (16 g). Treatment of the oil with ethereal hydrogen chloride yielded the hydrochloride salt of 1-(2,4-dichlorophenylmethyl)-4,5-dihydro-2-phenylmethyl imidazole m.p. 185°-189° C. (Found C, 56.75; H, 4.91; N, 7.71. C17H17Cl3N2.1/4H2O requires C, 56.70; H, 5.58; N, 7.77) having the formula ##STR22##

Workup

  1. temperatureThe mixture was heated to 80°-90° C. for 5 hours
  2. temperaturecooled
  3. concentrationconcentrated under reduced pressure
  4. additionWater was added to the residue
  5. extractionthe resulting mixture was extracted with ethyl acetate
  6. customThe organic phase was separated
  7. washwashed with brine
  8. dry with materialdried over anhydrous magnesium sulphate
  9. customThe solvent was removed under reduced pressure
  10. customyielding a residue which
  11. customwas chromatographed on silica gel eluting with ammonia/methanol/ethyl acetate (3:12:85)

Sources & evidence

ORD record
ord-61aab923db8445a480b39ad39af5817c
Source dataset
uspto-grants-1987_04
Patent number
US04661602

Reaction notes

Loading…