1H-1,2,4-Triazole → 2-(1H-1,2,4-triazol-1-yl)Benzonitrile

HRID 1795272Notes

Reaction equation

HRID 1795272 reaction equation
F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]#[N:9].[NH:10]1[CH:14]=[N:13][CH:12]=[N:11]1.C(=O)([O-])[O-].[Cs+].[Cs+].[N:21]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[C:32]#[N:33])[CH:25]=[N:24][CH:23]=[N:22]1>CN(C=O)C.CCOC(C)=O>[N:21]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[C:32]#[N:33])[CH:25]=[N:24][CH:23]=[N:22]1.[N:10]1[N:11]=[CH:12][N:13]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[C:8]#[N:9])[CH:14]=1

Participants

8

Reactant 4

HCID 92571H-1,2,4-TriazoleHCID 10796Cesium carbonateHCID 678552-FluorobenzonitrileHCID 157121632-(1H-1,2,4-triazol-1-yl)Benzonitrile2×

Product 2

HCID 157121632-(1H-1,2,4-triazol-1-yl)BenzonitrileHCID 171749282-(1,2,4-Triazol-4-yl)cyanobenzene

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 2-fluorocyanobenzene (5.0 g, 41 mmol) in DMF (75 mL) was added 1,2,4-triazole (3.0 g, 43 mmol) and cesium carbonate (14 g, 43 mmol). The mixture was warmed to 50° C. and stirred under inert atmosphere for 18 h. The mixture was cooled to ambient temperature, diluted with an equal volume of EtOAc, filtered, and the filtrate solvents were removed under reduced pressure. The residue was partitioned between ether (50 mL) and water (100 mL). The undissolved solid was collected by suction filtration and dried under reduced pressure to give 4.6 g of a 10:1 mixture of 2-(1,2,4-triazol-1-yl)cyanobenzene (hplc retention time=2.29 min, 5% to 100% CH3CN in water containing 0.1% TFA, Zorbax C8, 4.6 mm ID×7.5 cm, 3.5 micron; TLC Rf=0.6, EtOAc) and 2-(1,2,4-triazol-4-yl)cyanobenzene (hplc retention time=1.91 min, 5% to 100% CH3CN in water containing 0.1% TFA, Zorbax C8, 4.6 mm ID×7.5 cm, 3.5 micron; TLC Rf=0.1, EtOAc). The mixture was separated by flash chromatography using a gradient elution of 0:100 to 5:95 MeOH:EtOAc to give 2-(1,2,4-triazol-1-yl)cyanobenzene (1H NMR (DMSO-d6) δ 9.19 (s, 1H), 8.37 (s, 1H), 8.10 (d, J=7.6 Hz, 1H), 7.96–7.87 (m, 2H), 7.71 (t, J=7.7 Hz, 1H); mass spec m/z=171 (M++H)) and 2-(1,2,4-triazol-4-yl)cyanobenzene (1H NMR (DMSO-d6) δ 9.03 (s, 2H), 8.13 (d, J=7.6 Hz, 1H), 7.93(t, J=7.8 Hz, 1H), 7.80 (d, J=7.8 Hz, 1H), 7.74 (t, J=7.7 Hz, 1H); mass spec m/z=171 (M++H)), both as white solids.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. filtrationfiltered
  3. customthe filtrate solvents were removed under reduced pressure
  4. customThe residue was partitioned between ether (50 mL) and water (100 mL)
  5. filtrationThe undissolved solid was collected by suction filtration
  6. customdried under reduced pressure
  7. customto give
  8. customThe mixture was separated by flash chromatography
  9. washa gradient elution of 0:100 to 5:95 MeOH

Sources & evidence

ORD record
ord-fc4e816d7fff49d399933697934e08f5
Source dataset
uspto-grants-2006_04
Patent number
US07026324B2

Reaction notes

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