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

HRID 1020889Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1020889
[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

Komponenten

9

Edukt 6

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

Produkt 1

HCID 8407155,6-Dichloro-1,2-dimethylbenzimidazoleAusbeute 90,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 180AcetoneLösungsmittelHCID 1140TolueneLösungsmittel

Versuchsvorschrift

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]+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-9cef2a8d488442fa99a9ac317b2aae81
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08716491B2

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