Acetanilide → 2-methyl-1-phenyl-1H-benzimidazole

HRID 1028366Notes

Reaction equation

HRID 1028366 reaction equation
I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-])=O.[C:11]1([NH:17][C:18](=O)[CH3:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CNCCN.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I.[Fe]>[CH3:19][C:18]1[N:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:2]=2)[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:17]=1

Participants

8

Reactant 4

HCID 904AcetanilideHCID 8014N-MethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 69115o-Iodonitrobenzene

Product 1

HCID 6394272-methyl-1-phenyl-1H-benzimidazoleYield 78.7%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A reaction tube containing 2-iodonitrobenzene (125 mg, 0.5 mmol), N-phenylacetamide (81 mg, 0.6 mmol), CuI (4.8 mg, 0.025 mmol), N-methylethylenediamine (4.4 μL, 0.05 mmol), potassium phosphate (212 mg, 1 mmol) in dry toluene (3 mL) was purged with dry argon for 3 min. Then the mixture was heated at 100° C. for 18 h. After cooling, the reaction was hydrolyzed with 3 mL of water and filtered through a Varian cartridge Chem Elut 12198007, rinsing with ethyl acetate. The crude mixture was dissolved in 10 mL of glacial acetic acid and refluxed for 30 min in the presence of iron powder (279 mg, 5 mmol). The acid was removed under reduced pressure and the residue was suspended in saturated sodium bicarbonate solution and extracted with ethyl acetate. The obtained crude was purified by preparative HPLC, affording the title compound as a yellow solid (82 mg, 78% yield). mp 46-48° C. 1H NMR δ 2.63 (m, 3 H), 7.32 (d, J=Hz, 1 H), 7.47 (t, J=Hz, 1 H), 7.53 (t, J=Hz, 1 H), 7.66-7.72 (m, 5 H), 7.88 (d, J=7.2 Hz, 2 H); 13C NMR δ 12.6, 111.8, 115.1, 125.3, 127.1, 130.2, 130.3, 132.9, 133.8, 152.2, 158.3. HRMS (FAB): cal. for C14H13N2 [M+H+]: 209.1079; found: 209.1072. The same reaction was also performed on 25 mmol scale, obtaining the final product in 75% yield (3.9 g). The same product was obtained from 2-bromonitrobenzene (101 mg, 0.5 mmol) in 80% yield (83 mg).

Workup

  1. customwas purged with dry argon for 3 min
  2. temperatureAfter cooling
  3. filtrationfiltered through a Varian cartridge Chem Elut 12198007
  4. washrinsing with ethyl acetate
  5. dissolutionThe crude mixture was dissolved in 10 mL of glacial acetic acid
  6. customThe acid was removed under reduced pressure
  7. extractionextracted with ethyl acetate
  8. customThe obtained crude
  9. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-e0082c3c19b6471a8840ee0d183340c5
Source dataset
uspto-grants-2014_05
Patent number
US08735586B2

Reaction notes

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