反应详情

A solution of 3-nitrobenzoylchloride (25 g, 134 mmol), malononitrile (9.74 g, 147 mmol) and THF (140 mL) was cooled to 0° C. DIPEA (59 mL, 335 mmol) was added dropwise and the reaction was allowed to warm to room temperature and proceed for 2 hours. Afterwards, dimethylsulfate (38 mL, 399 mmol) was added and the temperature was raised to 70° C. for 4 hours. Next, the reaction mixture was brought to room temperature and allowed to proceed for an additional 12 hours. EtOAc (200 mL) was added to the reaction mixture in addition to brine (200 mL). The organic and aqueous layers were separated and the aqueous layer was extracted with EtOAc (4×25 mL). The combined organic layers were dried with MgSO4 and concentrated in vacuo. The material was purified over a silica column using chloroform:hexane (90:10) initially and eluted with pure chloroform. After concentrating the fractions containing the product, a yellow oil was triturated with diethyl ether to yield a solid (11.3 g, 37% yield): 1H NMR (400 MHz, DMSO) δ 8.63 (s, 1H), 8.51 (d, J=7.7, 1H), 8.16 (d, J=7.7, 1H), 7.94 (t, J=7.8, 1H), 3.93 (s, 3H); 13C NMR (100 MHz, DMSO) δ 183.66, 147.82, 135.23, 131.00, 129.55, 127.15, 124.08, 113.31, 111.87, 66.71, 61.87; [M+H]− calculated for C11H7N3O3 228.0, found 214.10 (product appears to hydrolyze during LC/MS analysis).

1. temperaturethe temperature was raised to 70° C. for 4 hours
2. customwas brought to room temperature
3. waitto proceed for an additional 12 hours
4. customThe organic and aqueous layers were separated
5. extractionthe aqueous layer was extracted with EtOAc (4×25 mL)
6. dry with materialThe combined organic layers were dried with MgSO4
7. concentrationconcentrated in vacuo
8. customThe material was purified over a silica column
9. washeluted with pure chloroform
10. concentrationAfter concentrating the fractions
11. additioncontaining the product
12. customa yellow oil was triturated with diethyl ether