反应详情

温度

10 °C

3-Thiophenecarboxyalic acid ethyl ester (1.98 g) was dissolved in acetonitrile (30 ml), and sulfuryl chloride (1.5 ml) was added under ice-cooling. The mixture was stirred at 10° C. for 30 minutes, and then 10% aqueous sodium thiosulfate (100 ml) was added. The resulting mixture was stirred at room temperature for 2 hours, and then extracted with diethyl ether. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a mixture of 5-chloro-3-thiophenecarboxylic acid ethyl ester and 2,5-dichloro-3-thiophenecarboxylic acid ethyl ester. This mixture was dissolved in a mixture of ethanol (15 ml) and tetrahydrofuran (15 ml), and 1N aqueous sodium hydroxide (20 ml) was added. The resulting mixture was stirred at room temperature, and then washed with diethyl ether. The aqueous layer was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give a mixture of 5-chloro-3-thiophenecarboxylic acid and 2,5-dichloro-3-thiophenecarboxylic acid (1.7 g). This mixture was suspended in toluene (15 ml), and oxalyl chloride (1.56 ml) was added dropwise. Further, N,N-dimethylformamide (1 drop) was added, and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduce pressure, and the concentrate was dissolved in ethyl acetate (10 ml). The resulting solution was added dropwise to a mixture of 25% aqueous ammonia (16 ml) and ethyl acetate (70 ml) with stirring under ice- cooling. The resulting mixture was stirred at room temperature for 10 minutes, and the organic layer was collected. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 5-chloro-3-thiophenecarboxamide (0.76 g).

1. temperaturecooling
2. stirringThe resulting mixture was stirred at room temperature for 2 hours
3. extractionextracted with diethyl ether
4. washThe extract was washed with saturated aqueous sodium chloride solution
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. customto give
8. additionwas added
9. stirringThe resulting mixture was stirred at room temperature
10. washwashed with diethyl ether
11. extractionextracted with ethyl acetate
12. dry with materialThe extract was dried over anhydrous magnesium sulfate
13. concentrationconcentrated under reduced pressure
14. customto give
15. stirringthe reaction mixture was stirred at room temperature for 1 hour
16. concentrationThe reaction mixture was concentrated
17. dissolutionthe concentrate was dissolved in ethyl acetate (10 ml)
18. additionThe resulting solution was added dropwise to a mixture of 25% aqueous ammonia (16 ml) and ethyl acetate (70 ml)
19. stirringwith stirring under ice-
20. temperaturecooling
21. stirringThe resulting mixture was stirred at room temperature for 10 minutes
22. customthe organic layer was collected
23. extractionThe aqueous layer was extracted with ethyl acetate
24. dry with materialdried over anhydrous magnesium sulfate
25. concentrationconcentrated under reduced pressure
26. customThe residue was purified by silica gel column chromatography