反应详情

温度

85 °C

A solution of N-(2,4-dichlorophenyl)-N′-methyl-urea (12.0 g, 54.8 mmol) in acetic anhydride (100 mL) was treated with cyanoacetic acid (5.6 g, 65.8 mmol). The reaction mixture was heated at 85° C. for 2.5 h. Additional cyanoacetic acid (0.90 g, 11.0 mmol) was added and the reaction mixture was stirred for 45 min. A third portion of cyanoacetic acid (0.45 g, 5.5 mmol) was added and the reaction mixture was stirred for 30 min. Excess acetic anhydride was distilled off under reduced pressure at a temperature not higher than 70° C. The residue was treated with 20% aqueous sodium hydroxide (95 mL) in portions. During the addition a spontaneous increase in temperature (65–70° C.) occurred. The reaction mixture was heated at 60° C. for 1 h during which time the product precipitated. The reaction mixture was then cooled to 0° C. The precipitate was collected on a Buchner funnel, washed with cold water, and dried at 55° C. under vacuum. The crude product was triturated in hot toluene (stirred for 1 h at 110° C.), and the solid was immediately collected on a Buchner funnel then dried under vacuum to afford a pale yellow solid (8.46 g, 54% yield): mp 249–251° C.; 1H NMR (300 MHz, DMSO-d6) δ 7.89 (d, J=1.8 Hz, 1H), 7.59 (d, J=1.8 Hz, 2H), 6.44 (s br, 1H), 4.79 (s, 1H), 3.09 (s, 3H); LRMS (APCI) m/e 286.0 [(M+H)+, calcd for C11H10N3O2Cl2 286.0].

1. stirringthe reaction mixture was stirred for 30 min
2. distillationExcess acetic anhydride was distilled off under reduced pressure at a temperature not higher than 70° C
3. additionThe residue was treated with 20% aqueous sodium hydroxide (95 mL) in portions
4. additionDuring the addition
5. temperaturea spontaneous increase in temperature (65–70° C.)
6. temperatureThe reaction mixture was heated at 60° C. for 1 h during which time the product
7. customprecipitated
8. temperatureThe reaction mixture was then cooled to 0° C
9. customThe precipitate was collected on a Buchner funnel
10. washwashed with cold water
11. customdried at 55° C. under vacuum
12. customThe crude product was triturated in hot toluene (stirred for 1 h at 110° C.)
13. customthe solid was immediately collected on a Buchner funnel
14. customthen dried under vacuum