Nitrogen → 4-[1-(1H-imidazol-1-yl)ethyl]-Benzonitrile

HRID 579773Notes

Reaction equation

HRID 579773 reaction equation
C([Li])CCC.[N:6]#N.[CH:8]([NH:11][CH:12](C)C)([CH3:10])C.N1C=CN=[C:16]1[CH2:20][C:21]1[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=1>O1CCCC1>[N:11]1([CH:20]([C:21]2[CH:22]=[CH:23][C:24]([C:25]#[N:26])=[CH:27][CH:28]=2)[CH3:16])[CH:8]=[CH:10][N:6]=[CH:12]1

Participants

6

Reactant 4

HCID 947NitrogenHCID 7912DiisopropylamineHCID 111481024-(1-Imidazolylmethyl)benzonitrileHCID 178418339Butyllithium

Product 1

HCID 142311584-[1-(1H-imidazol-1-yl)ethyl]-Benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of n-butyl lithium (25 mL of 2.1M reagent in hexane, 0.0525 mole) is added dropwise in an N2 atmosphere to a solution of di-isopropylamine (5.6 g) in tetrahydrofuran (100 mL) which is maintained at -20°. This cold solution is then added dropwise to a solution of 4-(1-imidazolylmethyl)benzonitrile (9.15 g) in tetrahydrofuran (250 mL) which is maintained at -50° during addition and for 30 minutes subsequently. The reaction mixture is then cooled to -70° for 30 minutes and then without external cooling for 10 hours. The reaction is quenched by addition of water (300 mL) and extracted with diethyl ether (3×100 mL). The combined ether extracts are extracted with 3N hydrochloric acid (3×60 mL) and the acid extracts are made basic (pH 9) with 6N sodium hydroxide. The crude product is extracted into ether (3×60 mL), and after drying (MgSO4) and solvent evaporation, 4-[1-(1-imidazolyl)ethyl]benzonitrile is obtained. The crude material is dissolved in acetone and treated with ethereal HCl to afford the hydrochloride salt, m.p. 184°-186°.

Workup

  1. temperatureis maintained at -20°
  2. temperatureis maintained at -50° during addition and for 30 minutes subsequently
  3. temperatureThe reaction mixture is then cooled to -70° for 30 minutes
  4. temperaturewithout external cooling for 10 hours
  5. customThe reaction is quenched by addition of water (300 mL)
  6. extractionextracted with diethyl ether (3×100 mL)
  7. extractionThe combined ether extracts are extracted with 3N hydrochloric acid (3×60 mL)
  8. extractionThe crude product is extracted into ether (3×60 mL)
  9. customafter drying
  10. custom(MgSO4) and solvent evaporation

Sources & evidence

ORD record
ord-e496c09f562047b69e1a18ad8b6eb36d
Source dataset
uspto-grants-1988_06
Patent number
US04749713

Reaction notes

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