8-Hydroxyquinoline → 3-(4-nitrophenyl)-1-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazole

HRID 520216Notes

Reaction equation

HRID 520216 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]=[CH:13][NH:12][N:11]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].Br[C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+].OC1C=CC=C2C=1N=CC=C2>CN(C=O)C.O.[Cu]I>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[N:14]=[CH:13][N:12]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)[N:11]=2)=[CH:8][CH:9]=1)([O-:3])=[O:2]

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 178526551HCID 178526551, compound

Product 1

HCID 904164163-(4-nitrophenyl)-1-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazoleYield 63%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
140 °C

Procedure

A mixture of 3-(4-nitrophenyl)-1H-1,2,4-triazole (20.0 g, 105 mmol), 1-bromo-4-(trifluoromethyl)benzene (28.0 g, 124 mmol), cesium carbonate (68.4 g, 210 mmol), copper(I) iodide (2.59 g, 13.6 mmol), and 8-hydroxyquinoline (1.80 g, 12.4 mmol) in N,N′-dimethylformamide/water (9:1, 142 mL) under nitrogen was heated to 140° C. for 18 hours. The reaction was cooled to room temperature (about 22° C.) and quenched with ammonium hydroxide (10 mL). The reaction mixture was extracted with ethyl acetate. The organic layer was separated and washed with water (3×100 mL) and brine (300 mL). The organic layer was separated and dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography (silica gel) using 0-65% ethyl acetate/petroleum ether as eluent provided the title compound as a white solid (22.0 g, 63%): 1H NMR (300 MHz, CDCl3) δ 8.72 (s, 1H), 8.42-8.34 (m, 4H), 7.94 (d, J=8.7 Hz, 2H), 7.84 (d, J=8.5 Hz, 2H); ESIMS m/z 335 ([M+H]+).

Workup

  1. temperatureThe reaction was cooled to room temperature (about 22° C.)
  2. customquenched with ammonium hydroxide (10 mL)
  3. extractionThe reaction mixture was extracted with ethyl acetate
  4. customThe organic layer was separated
  5. washwashed with water (3×100 mL) and brine (300 mL)
  6. customThe organic layer was separated
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by flash column chromatography (silica gel)

Sources & evidence

ORD record
ord-4477215d73ac409f882529d84c6d83b8
Source dataset
uspto-grants-2016_05
Patent number
US09326516B2

Reaction notes

Loading…