反应详情

温度

-15 °C

To a cooled (-15° C.) and stirred suspension of 4-(imidazol-1-yl)aniline, dihydrochloride (20 g, 86.2 mmol) in concentrated hydrochloric acid (100 ml) was added dropwise, over 1 hour, a solution of sodium nitrite (6.25 g, 90.6 mmol) in water (40 ml). After a further 10 minutes of stirring at -12° C., the mixture was quickly filtered to remove a solid, and the filtrate was added portionwise to a cooled (-20° C.) and stirred solution of tin (II) chloride dihydrate (100 g) in concentrated hydrochloric acid (50 ml) at such a rate as to maintain the internal temperature below -10° C. (15 minutes). The mixture was allowed to warm to 5° C. over 30 minutes, and the solid was collected and washed with diethyl ether (4×100 ml). The above solid was suspended in water (200 ml) and basified with 4N sodium hydroxide solution and extracted with ethyl acetate (5×500 ml). The combined organic solutions were dried (Na2SO4) and filtered. The filtrate was vigorously stirred while hydrogen chloride was being bubbled through the solution until a deep red mixture was obtained. Stirring was continued for a further 20 minutes to give a cream solid which was collected by filtration and dried over phosphorus pentoxide-potassium hydroxide under high vacuum to leave 12.7 g (60%) of the title compound; δH (360 MHz, DMSO-d6) 7.20 (2H, d, J=9.0 Hz), 7.73 (2H, d, J=9.0 Hz), 7.91 (1H, t, J=1.5 Hz), 8.23 (1H, t, J=1.7 Hz), 9.71 (1H, t, J=1.3 Hz).

1. additionwas added dropwise, over 1 hour
2. stirringAfter a further 10 minutes of stirring at -12° C.
3. filtrationthe mixture was quickly filtered
4. customto remove a solid
5. additionthe filtrate was added portionwise to
6. temperaturea cooled (-20° C.)
7. stirringstirred solution of tin (II) chloride dihydrate (100 g) in concentrated hydrochloric acid (50 ml) at such a rate as
8. temperatureto maintain the internal temperature below -10° C. (15 minutes)
9. temperatureto warm to 5° C. over 30 minutes
10. customthe solid was collected
11. washwashed with diethyl ether (4×100 ml)
12. extractionextracted with ethyl acetate (5×500 ml)
13. dry with materialThe combined organic solutions were dried (Na2SO4)
14. filtrationfiltered
15. stirringThe filtrate was vigorously stirred while hydrogen chloride
16. customwas being bubbled through the solution until a deep red mixture
17. customwas obtained
18. stirringStirring
19. customto give a cream solid which
20. filtrationwas collected by filtration
21. dry with materialdried over phosphorus pentoxide-potassium hydroxide under high vacuum