反应详情

500 mg (2.473 mmol) of 5-hydroxypsoralen and 893 mg (4.088 mmol) of 4-iodo-1-chlorobutane were stirred at 25° C. in 30 ml of anhydrous acetone in the presence of an excess (2.0 g) of anhydrous potassium carbonate for 28 hours. The progress of the reaction was monitored by thin layer chromatography. After 28 hours the reaction mixture was concentrated under reduced pressure and distilled off the solvent almost completely. The oily residue was cooled and diluted with water. The aqueous solution was then acidified with concentrated hydrochloric acid to pH 1. The slurry was stirred for 15-20 min and filtered. The solids were washed with water to neutral pH and dried. The dried solids were suspended in petroleum ether, filtered and dried under vacuum. To the solids were added 400 mg (5.875 mmol) of pyrazole, 2.0 g anhydrous potassium carbonate, catalytic amounts of potassium iodide, 30 ml of 2-butanone and the reaction mixture was refluxed for 50 hours. After 50 hours the reaction mixture was concentrated under vacuum. The residue was diluted with water and acidified to pH 1 with concentrated hydrochloric acid. The separated oily organic layer was extracted with 3×50 ml of dichloromethane. The dichloromethane layer was then washed with 0.75% aqueous sodium hydroxide to separate the un-reacted 5-hydroxypsoralen followed by washing with acidic water. The dichloromethane layer was dried over anhydrous sodium sulfate and concentrated. The residue was dissolved in an acetone-methanol mixture, treated with charcoal and re-crystallized from an ethyl acetate-petroleum ether (20:80) mixture.

1. concentrationAfter 28 hours the reaction mixture was concentrated under reduced pressure
2. distillationdistilled off the solvent almost completely
3. temperatureThe oily residue was cooled
4. additiondiluted with water
5. filtrationfiltered
6. washThe solids were washed with water to neutral pH
7. customdried
8. filtrationfiltered
9. customdried under vacuum
10. temperaturethe reaction mixture was refluxed for 50 hours
11. concentrationAfter 50 hours the reaction mixture was concentrated under vacuum
12. additionThe residue was diluted with water
13. extractionThe separated oily organic layer was extracted with 3×50 ml of dichloromethane
14. washThe dichloromethane layer was then washed with 0.75% aqueous sodium hydroxide
15. customto separate the un-reacted 5-hydroxypsoralen
16. washby washing with acidic water
17. dry with materialThe dichloromethane layer was dried over anhydrous sodium sulfate
18. concentrationconcentrated
19. dissolutionThe residue was dissolved in an acetone-methanol mixture
20. additiontreated with charcoal
21. customre-crystallized from an ethyl acetate-petroleum ether (20:80) mixture