Acetoacetic Acid → 2-Acetylpyridine-4-carbonitrile

HRID 931176Notes

Reaction equation

HRID 931176 reaction equation
[C:1](#[N:8])[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.S(OOS([O-])(=O)=O)([O-])(=O)=O.[NH4+].[NH4+].S(=O)(=O)(O)O.[O:26]=[C:27](C)[CH2:28]C(O)=O.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.O.[N+]([O-])([O-])=O.[Ag+]>[C:27]([C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][N:5]=1)[C:1]#[N:8])(=[O:26])[CH3:28]

Participants

9

Reactant 5

HCID 96Acetoacetic AcidHCID 1118Sulfuric AcidHCID 75064-CyanopyridineHCID 10340Sodium CarbonateHCID 62648Ammonium Persulfate

Product 1

HCID 104644602-Acetylpyridine-4-carbonitrileYield 71.9%

Reagents, catalysts & solvents 3

HCID 24470Silver NitrateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of isonicotinonitrile (52 g, 0.5 mol) in dichloromethane (1300 mL) and water (1100 mL) were added ammonium persulfate ((NH4)2S2O8) (170 g, 0.75 mol), silver nitrate (6.8 g, 0.04 mol) and aqueous sulfuric acid (40 mL, 98% sulfuric acid in 400 mL). A solution of 3-oxo-butyric acid (110 g, 1.25 mol) in dichloromethane (100 mL) was added dropwise while keeping the mixture refluxing. The reaction mixture was refluxed for 2 h. The resulting mixture was basified to pH˜8-9 using sodium carbonate powder. The mixture was filtered and the filtrate was extracted with dichloromethane (500 mL×3). The combined organics were dried over sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethanol to afford 2-acetylisonicotinonitrile (52.0 g, 71.9%).

Workup

  1. temperaturerefluxing
  2. temperatureThe reaction mixture was refluxed for 2 h
  3. filtrationThe mixture was filtered
  4. extractionthe filtrate was extracted with dichloromethane (500 mL×3)
  5. dry with materialThe combined organics were dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was recrystallized from ethanol

Sources & evidence

ORD record
ord-026b558df57d49be8331a8e3ada41600
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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