8-Hydroxyquinoline → 1-[4-nitro-3-(propan-2-yloxy)phenyl]-1H-1,2,4-triazole

HRID 518818Notes

Reaction equation

HRID 518818 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH:12]([CH3:14])[CH3:13])[CH:3]=1.N1C=[CH:18][N:17]=[N:16]1.C(=O)([O-])[O-].[K+].[K+].OC1C=CC=C2C=1[N:35]=[CH:34]C=C2.[NH4+].[OH-]>CS(C)=O.[Cu]I.C(OCC)(=O)C.O>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([N:17]2[CH:18]=[N:35][CH:34]=[N:16]2)=[CH:3][C:4]=1[O:11][CH:12]([CH3:14])[CH3:13])([O-:10])=[O:9]

Participants

10

Reactant 5

HCID 19238-HydroxyquinolineHCID 11430Potassium CarbonateHCID 14923Ammonium HydroxideHCID 226243214-Bromo-2-isopropoxy-1-nitro-benzeneHCID 178418936HCID 178418936, compound

Product 1

HCID 830131781-[4-nitro-3-(propan-2-yloxy)phenyl]-1H-1,2,4-triazoleYield 483.8%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1 g of 4-bromo-1-nitro-2-(propan-2-yloxy)benzene, 319 mg of triazole, 110 mg of copper (I) iodide, 585 mg of potassium carbonate and 84 mg of 8-hydroxyquinoline in 8 ml of DMSO is stirred overnight at ambient temperature and then heated at 120° C. for 3 hours. The reaction medium is poured into 10 ml of an aqueous 25% NH4OH solution, 40 ml of water and 10 ml of ethyl acetate. The mixture is stirred for 30 minutes at ambient temperature and then the two phases are separated. The aqueous phase is washed with twice 40 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and evaporated. Purification is carried out by flash chromatography on silica gel (40-63 μm), elution being carried out with a mixture of dichloromethane and acetone (100/0 to 95/5). 695 mg of 1-[4-nitro-3-(propan-2-yloxy)phenyl]-1H-1,2,4-triazole are obtained in the form of a beige solid. 965 mg of ammonium formate and 172 mg of Pd/C (10%) are added to a solution of 691 mg of 1-[4-nitro-3-(propan-2-yloxy)phenyl]-1H-1,2,4-triazole in 14 ml of methanol. The reaction medium is microwave-heated at 80° C. for 5 minutes. The mixture is filtered on Clarcel, and the Clarcel is rinsed with methanol. The filtrate is concentrated under reduced pressure. The residue is taken up with 20 ml of ethyl acetate, 2 ml of water and 8 ml of a saturated aqueous sodium chloride solution. The two phases are separated and the aqueous phase is washed with 3 times 10 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and evaporated, so as to give 589 mg of 2-(propan-2-yloxy)-4-(1H-1,2,4-triazol-1-yl)aniline in the form of a brown oil.

Workup

  1. temperatureheated at 120° C. for 3 hours
  2. stirringThe mixture is stirred for 30 minutes at ambient temperature
  3. customthe two phases are separated
  4. washThe aqueous phase is washed with twice 40 ml of ethyl acetate
  5. dry with materialThe combined organic phases are dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customPurification
  9. washis carried out by flash chromatography on silica gel (40-63 μm), elution
  10. additionbeing carried out with a mixture of dichloromethane and acetone (100/0 to 95/5)

Sources & evidence

ORD record
ord-867d5d38e1054ba1957bf49f24bd04aa
Source dataset
uspto-grants-2015_08
Patent number
US09115140B2

Reaction notes

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