反应详情

温度

90 °C

A 3-neck 22 L flask equipped with a temperature probe with a chart recorder, mechanical stirrer, a Dean-Stark apparatus and a reflux condenser is charged with 4,6-dihydroxy nicotinic acid (88 %, 2.0 Kg, 12.81 mol), phosphoric acid (85%, 6 L, 103.15 mol). The off gases from the condenser are scrubbed by bubbling into 50% aqueous NaOH. The suspension is heated until a sufficient amount of water has been removed (about 1.2 L) , i.e., dehydration of the phosphoric acid. Without the dehydration of the phosphoric acid, the carboxylation does not occur. For the internal temperature to reach 210° C.±5° C, a mantle temperature of 290° C is applied over an elapsed time of 3.5 hours. After being stirred for 4-5 hours at that temperature, the disappearance of the starting material is confirmed by HPLC. The reaction mixture is then allowed to cool down to a temperature of less than 100° C., at which point acetic acid (6 L, 104.81 mol) is added and the temperature is maintained at 90° C. To this mixture is added nitric acid (485 mL, 12.11 mol) at a constant rate (5-6 mL/minute) until HPLC shows no more 4,6-dihydroxy nicotinic acid present. Water (6 L, 333.3 mol) is then added to the reaction and heating is stopped. A yellow solid starts appearing at a temperature of less than 80° C. and is allowed to precipitate with stirring overnight. Filtration in a scintered glass funnel (course porosity) yields a yellow solid which is then washed with 2.5 L of isopropyl alcohol. The resulting cake is air-dried for 48 hours and then put in a drying oven under vacuum (20 in. Hg with a air bleed) at 50° C. for 3 days. 2,4-dihydroxy-3-nitropyridine (1.050 Kg) is obtained in 60% yield.

1. customA 3-neck 22 L flask equipped with a temperature probe with a chart recorder, mechanical stirrer
2. customby bubbling into 50% aqueous NaOH
3. temperatureThe suspension is heated until a sufficient amount of water
4. customhas been removed (about 1.2 L) , i.e., dehydration of the phosphoric acid
5. customto reach 210° C.±5° C
6. customa mantle temperature of 290° C
7. customis applied over an elapsed time of 3.5 hours
8. additionis added
9. temperatureheating
10. customappearing at a temperature of less than 80° C.
11. customto precipitate
12. stirringwith stirring overnight
13. filtrationFiltration in a scintered glass funnel (course porosity)
14. customyields a yellow solid which
15. washis then washed with 2.5 L of isopropyl alcohol
16. customThe resulting cake is air-dried for 48 hours
17. customput in a drying oven under vacuum
18. waitHg with a air bleed) at 50° C. for 3 days