p-Toluenesulfonic acid → 5,6-Dichloro-1,2-dimethylbenzimidazole

HRID 1020889노트

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HRID 1020889 반응식
[C:1](OCC)(OCC)(OCC)C.ClC1C(Cl)=CC(N)=C(N)C=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[Cl:33][C:34]1[C:43]([Cl:44])=[CH:42][C:37]2[N:38]=[C:39]([CH3:41])[NH:40][C:36]=2[CH:35]=1.[OH-].[K+].IC>C1(C)C=CC=CC=1.CC(C)=O>[Cl:44][C:43]1[C:34]([Cl:33])=[CH:35][C:36]2[N:40]([CH3:1])[C:39]([CH3:41])=[N:38][C:37]=2[CH:42]=1

참가 물질

9

반응물 6

HCID 6101p-Toluenesulfonic acidHCID 6328Methyl iodideHCID 14797Potassium HydroxideHCID 66221Triethyl orthoacetateHCID 792974,5-Dichloro-1,2-phenylenediamineHCID 6083195,6-Dichloro-2-methylbenzimidazole

생성물 1

HCID 8407155,6-Dichloro-1,2-dimethylbenzimidazole수율 90.6%

시약·촉매·용매 2

HCID 180Acetone용매HCID 1140Toluene용매

실험 절차

Triethyl orthoacetate (4.6 g, 1 eq) was added drop wise to a refluxing mixture of 4,5-dichloro-1,2-phenylenediamine (5 g, 1 eq) and a catalytic amount of p-toluenesulfonic acid in toluene (40 mL). The mixture was refluxed for 3 hrs and 5.7 g black solid was collected after evaporation of the solvents under reduced pressure and used directly in the following step without further purification. ESI-MS (m/z) calcd (found): 200.0 (201.1) for [M+H]+. To the crude 5,6-dichloro-2-methyl-benzoimidazole (5.7 g, 1 eq) (see FIG. 9) and grinded potassium hydroxide (4.8 g, 3 eq) in acetone (50 mL) was added iodomethane (5.2 g, 1.4 eq) drop wise and the mixture was stirred overnight. The solvent was evaporated under reduced pressure and the residue was partitioned between dichloromethane (200 mL) and water (200 mL). The aqueous phase was washed two times with dichloromethane (200 mL) and the combined organic phase was dried over Na2SO4 and evaporated to dryness. The crude product was recrystallized from ethyl acetate. 5.5 g product was collected as pale flakes with 90.6% yield for two steps. 1H NMR: (CDCl3) 2.55 (s, 3H), 3.63 (s, 3H), 7.28 (s, 1H), 7.68 (s, 1H). 13C NMR: (CDCl3): 13.82, 30.05, 110.20, 120.00, 125.58, 125.75, 134.97, 141.83, 153.93. ESI-MS (m/z) calcd (found): 214.0 (215.1) for [M+H]+.

후처리

  1. temperatureThe mixture was refluxed for 3 hrs
  2. custom5.7 g black solid was collected
  3. customafter evaporation of the solvents under reduced pressure
  4. customused directly in the following step without further purification
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was partitioned between dichloromethane (200 mL) and water (200 mL)
  7. washThe aqueous phase was washed two times with dichloromethane (200 mL)
  8. dry with materialthe combined organic phase was dried over Na2SO4
  9. customevaporated to dryness
  10. customThe crude product was recrystallized from ethyl acetate
  11. custom5.5 g product was collected as pale flakes with 90.6% yield for two steps

출처 및 근거

ORD 기록
ord-9cef2a8d488442fa99a9ac317b2aae81
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08716491B2

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