反应详情

To a stirred suspension of 4-amino-2-nitrobenzoic acid (9.895 g, 54.326 mmol) in water (17 ml) was added concentrated H2SO4 (12 ml). The resulting homogenous solution was cooled in an ice bath and additional water (10 ml) added to aid stirring. Crushed ice (50 ml) was added followed by the drop-wise addition of NaNO2 (4.124 g, 59.759 mmol) in water (9 ml). The temperature was kept below 5° C. during the addition and then stirred for 1.25 h at 0° C. The reaction mixture was quenched by adding urea (6 g), stirred for 10 minutes at 0° C., filtered and the filtrate added drop-wise into a boiling solution of concentrated H2SO4 (39 ml) and water (27 ml). After the addition, the entire mixture was refluxed for 3 hours then cooled. The reaction mixture was extracted with ethyl acetate (6×50 ml) and the combined organics washed with brine, filtered and concentrated to a small volume which was then purified by flash chromatography on silica. The first column was eluted with ethyl acetate and 20% MeOH/EtOAc. The second column was eluted with 10% MeOH/CHCl3 and the third column was eluted with 60% EtOAc/Hexane. The purification process gave 4-hydroxy-2-nitrobenzoic acid (5.331 g, 29.112 mmol, 54%) as an orange solid, dec. 232-236° C. 1H NMR (DMSO-d6) δ 7.05 (dd, 1H), 7.15 (s, 1H), 7.78 (d, 1H) 11.10 (s, 1H), 13.38 (s, 1H); mass spectrum [ES(−)], m/z 182 (M−H)−.

1. temperatureThe resulting homogenous solution was cooled in an ice bath
2. additionThe temperature was kept below 5° C. during the addition
3. stirringstirred for 1.25 h at 0° C
4. customThe reaction mixture was quenched
5. additionby adding urea (6 g)
6. stirringstirred for 10 minutes at 0° C.
7. filtrationfiltered
8. additionthe filtrate added drop-wise into a boiling solution of concentrated H2SO4 (39 ml) and water (27 ml)
9. additionAfter the addition
10. temperaturethe entire mixture was refluxed for 3 hours
11. temperaturethen cooled
12. extractionThe reaction mixture was extracted with ethyl acetate (6×50 ml)
13. washthe combined organics washed with brine
14. filtrationfiltered
15. concentrationconcentrated to a small volume which
16. customwas then purified by flash chromatography on silica
17. washThe first column was eluted with ethyl acetate and 20% MeOH/EtOAc
18. washThe second column was eluted with 10% MeOH/CHCl3
19. washthe third column was eluted with 60% EtOAc/Hexane