Chloroacetyl chloride → 2-(chloromethyl)-1-propyl-1H-benzo[d]imidazole-5-carbonitrile

HRID 1594040Notes

Reaction equation

HRID 1594040 reaction equation
[Cl:1][CH2:2][C:3](Cl)=O.ClCC(=N)OCC.[NH2:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][C:21]=1[NH:22][CH2:23][CH2:24][CH3:25])[C:17]#[N:18].C(N(CC)CC)C>C(OCC)(=O)C.O.C(O)(=O)C>[CH2:23]([N:22]1[C:21]2[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][C:14]=2[N:13]=[C:3]1[CH2:2][Cl:1])[CH2:24][CH3:25]

Participants

8

Reactant 4

HCID 6577Chloroacetyl chloride2×HCID 8471TriethylamineHCID 193264Ethyl chloroacetimidateHCID 223802993-Amino-4-(propylamino)benzonitrile

Product 1

HCID 223800642-(chloromethyl)-1-propyl-1H-benzo[d]imidazole-5-carbonitrile

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Alternatively, chloroacetylchloride rather than ethyl chloroacetimidate can by used: To a solution of 3-amino-4-n-propylaminobenzonitrile (5.15 g, 29.4 mmol) and triethylamine (4.51 mL) in ethyl acetate (52 mL) at room temperature, chloroacetyl chloride (2.57 mL) is added slowly. After stirring the reaction mixture for 30 minutes at room temperature, acetic acid (5 mL) is added and the reaction mixture heated to reflux. After heating for 20 h, the reaction mixture is cooled to room temperature and diluted with water (50 mL). The organic solution is washed twice with 1.0 M sodium hydroxide (2×50 mL), then washed with an aqueous solution of 0.25 M KH2PO4 (50 mL), followed by brine (50 mL). The organic layer is dried (sodium sulfate), concentrated in vacuo, and the solid recrystallized by heating in ethyl acetate (20 mL), adding hexane (40 mL) and cooling to room temperature with stirring to afford 1-n-Propyl-2-chloromethyl-5-cyanobenzimidazole as brown crystals. 1H NMR (CDCl3): δ 8.08 (d, J=0.8 Hz, 1H), 7.57 (dd, J=1.65, 8.52 Hz, 1H), 7.45 (d, J=8.24 Hz, 1H), 7.26 (s, 1H), 4.84 (s, 2H) 4.24 (t, J=7.6 Hz, 2H), 1.94 (pentet, J=7.4. 7.6 Hz, 2H) 1.03 (t, J=7.4 Hz, 3H).

Workup

  1. temperaturethe reaction mixture heated to reflux
  2. temperatureAfter heating for 20 h
  3. temperaturethe reaction mixture is cooled to room temperature
  4. washThe organic solution is washed twice with 1.0 M sodium hydroxide (2×50 mL)
  5. washwashed with an aqueous solution of 0.25 M KH2PO4 (50 mL)
  6. dry with materialThe organic layer is dried (sodium sulfate)
  7. concentrationconcentrated in vacuo
  8. customthe solid recrystallized
  9. temperatureby heating in ethyl acetate (20 mL)
  10. additionadding hexane (40 mL)
  11. temperaturecooling to room temperature
  12. stirringwith stirring

Sources & evidence

ORD record
ord-d28fd60610f64dc090eb24f170a44b65
Source dataset
uspto-grants-2007_11
Patent number
US07300945B2

Reaction notes

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