Dimethylformamide → 4-methyl-1H-benzimidazole-5-carbonitrile

HRID 475242Notes

Reaction equation

HRID 475242 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:5]2[NH:6][CH:7]=[N:8][C:4]=2[C:3]=1[CH3:11].[CH3:12][N:13](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Zn]>[CH3:11][C:3]1[C:4]2[N:8]=[CH:7][NH:6][C:5]=2[CH:9]=[CH:10][C:2]=1[C:12]#[N:13]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 592144445-Bromo-4-methyl-1H-benzo[d]imidazole

Product 1

HCID 451205504-methyl-1H-benzimidazole-5-carbonitrileYield 53%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
120 °C

Procedure

A mixture of 158 (21 g; 99 mmol), Zn(CN)2 (23.2 g; 198 mmol), Pd(dppf)Cl2 (6.4 g; 9.9 mmol) and zinc (258 mg; 4 mmol) in dry DMF (150 mL) under inert atmosphere was heated at 120° C. for 2 h. The reaction mixture was filtered through a pad of Celite® that was washed with EtOAc. The organics were washed with water, dried (MgSO4), filtered and evaporated in vacuo. The crude product was purified by SiO2 chromatography eluted with a DCM/MeOH gradient (0 to 10% MeOH) to afford 8.3 g (53%) of 4-methyl-1H-benzo[d]imidazole-5-carbonitrile (160) as a brown solid: MS (ESI) m/z=158 [M+1]+.

Workup

  1. filtrationThe reaction mixture was filtered through a pad of Celite® that
  2. washwas washed with EtOAc
  3. washThe organics were washed with water
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe crude product was purified by SiO2 chromatography
  8. washeluted with a DCM/MeOH gradient (0 to 10% MeOH)

Sources & evidence

ORD record
ord-b33e15483cc141048504e9b864486d02
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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