Hydrazine hydrate (1:1) → 5-(But-3-enyl)-4-phenyl-3-p-tolyl-1H-pyrazole

HRID 1471892Notes

Reaction equation

HRID 1471892 reaction equation
[C:1]1([CH2:7][C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:27](Cl)(=O)[CH2:28][CH2:29][CH:30]=[CH2:31].O.[NH2:35][NH2:36]>C1(C)C=CC=CC=1.CC(O)=O.CCO>[CH2:28]([C:27]1[NH:36][N:35]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)[C:7]=1[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH2:29][CH:30]=[CH2:31]

Participants

8

Reactant 4

HCID 24654Hydrazine hydrate (1:1)HCID 2280161-(4-Methylphenyl)-2-phenylethan-1-oneHCID 2733832Lithium HexamethyldisilazideHCID 42284934-Pentenoyl chloride

Product 1

HCID 673853415-(But-3-enyl)-4-phenyl-3-p-tolyl-1H-pyrazoleYield 25.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

2-Phenyl-1-p-tolylethanone (1.0 g, 4.76 mmol) was dissolved in Toluene (20 mL). The reaction was cooled in an ice bath and then LiHMDS (4.76 mL, 4.76 mmol) was added slowly via syringe. The reaction was stirred at this temperature for 5 min and then pent-4-enoyl chloride (0.564 g, 4.76 mmol) was added. The reaction was warmed to room temperature and stirred at this temperature for 20 min. After this time EtOH (10 mL), AcOH (2 mL), and hydrazine hydrate (0.231 mL, 4.76 mmol) were added to the reaction. The reaction was heated to 80° C. and stirred at this temperature for an hour. After this time, the reaction was cooled and extracted (50 mL each of EtOAc and 1M NaOH). The aqueous layer was extracted again with EtOAc (50 mL). The combined organic layer was dried, concentrated, and the residue was purified by silica gel column chromatography to give the title compound (355 mg) as a colorless oil. LCMS m/z=289.0 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.22-2.32 (m, 5H), 2.55-2.69 (m, 2H), 4.86-5.02 (m, 2H), 5.75 (s, 1H), 6.99-7.24 (m, 6H), 7.25-7.31 (m, 1H), 7.33-7.39 (m, 2H), 12.74 (s, 1H).

Workup

  1. temperatureThe reaction was cooled in an ice bath
  2. stirringstirred at this temperature for 20 min
  3. temperatureThe reaction was heated to 80° C.
  4. stirringstirred at this temperature for an hour
  5. temperatureAfter this time, the reaction was cooled
  6. extractionextracted (50 mL each of EtOAc and 1M NaOH)
  7. extractionThe aqueous layer was extracted again with EtOAc (50 mL)
  8. customThe combined organic layer was dried
  9. concentrationconcentrated
  10. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-eb84adecd01840cda33ed6768b6dfe59
Source dataset
uspto-grants-2015_04
Patent number
US09012478B2

Reaction notes

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