反应详情

Part A: To a stirred solution of 106 g (500 mmol) of 2,4,6-trichlorophenyl hydrazine in 600 mL of absolute ethanol was added 48.1 mL (530 mmol) of isobutyraldehyde. The solution was stirred 2 h at RT and concentrated under reduced pressure to afford an oil. The crude oil was dissolved in 450 mL of dry DMF and cooled to 0° C. This solution was treated with 94.3 g (530 mmol) of NBS in four portions over 10 min. The solution was stirred 1 h at 0° C. and poured onto ice. The mixture was diluted with water and extracted with 800 mL of ether. The organic extract was washed twice with water and once with brine, dried (MgSO4), and concentrated under reduced pressure to afford an oil. In a separate flask, 44.3 g (670 mmol) of malononitrile in 140 mL of EtOH was cooled to 0° C. and treated with 252 mL (670 mmol) of 2.66 M NaOEt in EtOH over 6 min. This solution was added in four portions over 5 min. to a rapidly stirred solution of the crude bromohydrazone in 350 mL of absolute EtOH. Using a heat pistol, this solution was maintained at reflux for 10 min. further. The reaction was cooled, quenched with 5% aq. HOAc, and extracted twice with ether. The combined organic extracts were washed (brine), dried (MgSO4) and filtered over activated charcoal and celite, and concentrated under reduced pressure. The product was chromatographed on silica gel (gradient elution with 1:3 ether-hexanes and 2:1 ether-CH2Cl2) to afford 93.5 g (57%) of 5-amino-4-cyano-3-isopropyl-1-(2,4,6-trichlorophenyl)pyrazole as a white solid. 1H NMR (CDCl3, 300 MHz) δ 7.51(s, 2H); 4.28(br. s, 2H); 3.05(septet, 1H, J=7.0 Hz); 1.36(d, 6H, J=7.0 Hz).

1. concentrationconcentrated under reduced pressure
2. customto afford an oil
3. temperaturecooled to 0° C
4. stirringThe solution was stirred 1 h at 0° C.
5. additionpoured onto ice
6. extractionextracted with 800 mL of ether
7. extractionThe organic extract
8. washwas washed twice with water and once with brine
9. dry with materialdried (MgSO4)
10. concentrationconcentrated under reduced pressure
11. customto afford an oil
12. temperaturethis solution was maintained
13. temperatureat reflux for 10 min. further
14. temperatureThe reaction was cooled
15. customquenched with 5% aq. HOAc
16. extractionextracted twice with ether
17. washThe combined organic extracts were washed (brine)
18. dry with materialdried (MgSO4)
19. filtrationfiltered over activated charcoal and celite
20. concentrationconcentrated under reduced pressure
21. customThe product was chromatographed on silica gel (gradient elution with 1:3 ether-hexanes and 2:1 ether-CH2Cl2)