反应详情

To a solution containing 1-formyl-4-(2-hydroxyethyl)piperazine (1.58 g, 10 mmol), 2-mercaptobenzimidazole (5.56 g, 37 mmol), and triphenylphosphine (9.26 g, 35.3 mmol) in dimethylformamide (100 mL), diethyl azodicarboxylate (5.19 g, 29.8 mmol) was added dropwise over 5 minutes with ice-cooling and stirring under argon. The mixture was stirred for 80 minutes at room temperature, and then water (2 mL) was added to the mixture so as to deactivate the reagent. The reaction mixture was concentrated under reduced pressure, and chloroform (200 mL) was added to the residue. Insoluble material was removed through filtration, and the filtrate was concentrated under reduced pressure. 2N Hydrochloric acid (20 mL) and ethyl acetate (100 mL) were added to the residue, and the liquid was partitioned. The organic layer was extracted with 2N hydrochloric acid (20 mL×2). The aqueous extract and the aqueous layer were combined, and the mixture was washed with chloroform (50 mL×2) . The pH of the mixture was adjusted to about 9 through addition of potassium carbonate, followed by extraction with chloroform (50 mL×3), washing the organic layer with saturated brine, drying over sodium sulfate anhydrate, and removing the solvent. The thus-formed crude product was crystallized from acetone-diethyl ether, thereby yielding 2.19 g of 1-formyl-4-[2-(benzimidazol-2-ylthio)ethyl]piperazine (yield: 76%) as a colorless crystalline powder. The crystallization mother liquor was concentrated under reduced pressure, and the residue was purified through silica gel column chromatography (eluent: chloroform:methanol=50:1 to 20:1), thereby yielding 0.42 g of 1-formyl-4-[2-(benzimidazol-2-ylthio)ethyl]piperazine (yield: 14%) as a colorless crystalline powder. The overall yield was 90%.

1. additionwas added dropwise over 5 minutes with ice-
2. temperaturecooling
3. stirringThe mixture was stirred for 80 minutes at room temperature
4. concentrationThe reaction mixture was concentrated under reduced pressure, and chloroform (200 mL)
5. additionwas added to the residue
6. customInsoluble material was removed through filtration
7. concentrationthe filtrate was concentrated under reduced pressure
8. addition2N Hydrochloric acid (20 mL) and ethyl acetate (100 mL) were added to the residue
9. customthe liquid was partitioned
10. extractionThe organic layer was extracted with 2N hydrochloric acid (20 mL×2)
11. extractionThe aqueous extract
12. washthe mixture was washed with chloroform (50 mL×2)
13. additionThe pH of the mixture was adjusted to about 9 through addition of potassium carbonate
14. extractionfollowed by extraction with chloroform (50 mL×3)
15. washwashing the organic layer with saturated brine
16. dry with materialdrying over sodium sulfate anhydrate
17. customremoving the solvent
18. customThe thus-formed crude product
19. customwas crystallized from acetone-diethyl ether