Malononitrile → 2-((1-Benzyl-1H-pyrazol-4-yl)(hydroxy)methylene)malononitrile

HRID 64302Notes

Reaction equation

HRID 64302 reaction equation
[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]([OH:15])=O)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:16](#[N:20])[CH2:17][C:18]#[N:19].CCN(C(C)C)C(C)C>O=S(Cl)Cl.C1COCC1.C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]([OH:15])=[C:17]([C:16]#[N:20])[C:18]#[N:19])[CH:10]=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 8010MalononitrileHCID 81531DiisopropylethylamineHCID 64838761-Benzyl-1H-pyrazole-4-carboxylic acid

Product 1

HCID 1176683522-((1-Benzyl-1H-pyrazol-4-yl)(hydroxy)methylene)malononitrileYield 827.3%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 1-benzyl-1H-pyrazole-4-carboxylic acid (25.0 g, 123.8 mmol) in SOCl2 (250 mL) was heated to reflux for 3 hr. The mixture was concentrated in vacuum to give the intermediate, which was used in the next step without further purification. To a solution of propanedinitrile (8.2 g, 12.8 mmol), DIEA (32.0 g, 247.6 mmol) in THF (250 mL) was added dropwise a solution of intermediate in toluene (250 mL) at 0-5° C. over 1 hr. The resultant mixture was allowed to warm to RT and stirred for 16 hr. The reaction was quenched with water (500 mL) and extracted with EA (500 mL×3), The organic layers were washed with 3 N HCl (500 mL), brine (500 mL×3), dried over Na2SO4 and concentrated to give the crude product (26.5 g, 85.0%) as a yellow solid. MS (ESI) m/e [M+1]+ 250.9.

Workup

  1. temperatureto reflux for 3 hr
  2. concentrationThe mixture was concentrated in vacuum
  3. customto give the intermediate, which
  4. customwas used in the next step without further purification
  5. customThe reaction was quenched with water (500 mL)
  6. extractionextracted with EA (500 mL×3)
  7. washThe organic layers were washed with 3 N HCl (500 mL), brine (500 mL×3)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-11938f5d5aed4cc8b635534f4c9e7be2
Source dataset
uspto-grants-2016_09
Patent number
US09447106B2

Reaction notes

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