p-Bromopropiophenone → 4-Propanoylbenzonitrile

HRID 218078

Reaction equation

HRID 218078 reaction equation
[CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([C:10]#[N:11])=[CH:6][CH:5]=1)=[O:3].[CH3:12]CC(C1C=CC(Br)=CC=1)=O>CN(C=O)C.[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:12][CH2:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([C:10]#[N:11])=[CH:6][CH:5]=1)=[O:3]

Participants

6

Reactant 2

HCID 66312p-BromopropiophenoneHCID 740444'-Cyanoacetophenone

Product 1

HCID 107732464-PropanoylbenzonitrileYield 89%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

As described for the preparation of 4-cyanoacetophenone (Synth. Commun 1994, 887-890), a mixture of 4-bromopropiophenone (5.65 g, 26.4 mmol), Zn(CN)2 (1.80 g, 15.3 mmol), and Pd(PPh3)4 (2.95 g, 2.6 mmol) was refluxed at 80° C. in deoxygenated DMF (35 mL, stored over 4 Å molecular sieves, bubbled with Ar before use) for 18 h. The mixture was partitioned between toluene (100 mL) and 2N NH4OH (100 mL). The organic phase was extracted with 2N NH4OH (100 mL), washed with saturated aqueous NaCl (2×100 mL), dried, and concentrated in vacuo. A 10 mmol scale reaction was done similarly and the crude products were combined. Flash chromatography (330 g silica, 6/1 petroleum ether-EtOAc) afforded the desired compound as a white solid (5.17 g, 89%).

Workup

  1. customThe mixture was partitioned between toluene (100 mL) and 2N NH4OH (100 mL)
  2. extractionThe organic phase was extracted with 2N NH4OH (100 mL)
  3. washwashed with saturated aqueous NaCl (2×100 mL)
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customA 10 mmol scale reaction

Sources & evidence

ORD record
ord-91fe3a169e2d4fd0960a76262063508a
Source dataset
uspto-grants-2012_06
Patent number
US08198283B2

Linked notes

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