反应详情

温度

142.5 °C

A 22 L round bottom flask was fitted with a thermocouple, mechanical stirrer and a Dean-Stark trap which was connected to a nitrogen bubbler. The vessel was purged with nitrogen and then 4,5,6-trichloropicolinate (2547 g, 10.07 mol), pyridinium p-toluene sulfonate (PPTS; 130 g, 0.52 mol), benzyl alcohol (2249 g, 20.8 mol) and xylenes (10278 g) were added. Stirring was started, and the pot was heated to 140 to 145° C. The xylenes/water azeotrope was collected in the Dean-Stark trap over about 5 h. The total amount of distillate collected was 4750 g (415 g was water). After the water stopped distilling overhead, a reactor sample was taken and analyzed by high-performance liquid chromatography (HPLC) to ensure less than 1.5 area % of starting carboxylic acid remained. The reaction was allowed to cool to room temperature and stirred overnight. Xylenes (4000 g) were removed by vacuum distillation. The solution was cooled to 85-100° C. and then vacuum transferred to a 30 L jacketed crystallization vessel that had been fitted with a mechanical stirrer and thermocouple. The vacuum was released with nitrogen and a nitrogen bubbler was placed on the crystallization vessel. To the xylene solution was added isopropyl alcohol (IPA; 6200 g) over about 15 minutes (min). The resulting slurry was allowed to cool slowly to room temperature and then cooled further to 5° C. The solid was collected by filtration, and the cake was washed with cold (5-10° C.) IPA (3731 g). The solid was dried in air to a constant weight providing white crystals (2765 g, gas chromatography (GC) internal standard purity 96.5%, 84.3%).

1. customA 22 L round bottom flask was fitted with a thermocouple, mechanical stirrer
2. customThe vessel was purged with nitrogen
3. customThe xylenes/water azeotrope was collected in the Dean-Stark trap over about 5 h
4. distillationThe total amount of distillate collected
5. distillationAfter the water stopped distilling overhead
6. customa reactor sample was taken
7. temperatureto cool to room temperature
8. stirringstirred overnight
9. customXylenes (4000 g) were removed by vacuum distillation
10. temperatureThe solution was cooled to 85-100° C.
11. customcrystallization vessel that
12. customhad been fitted with a mechanical stirrer
13. additionTo the xylene solution was added isopropyl alcohol (IPA; 6200 g) over about 15 minutes (min)
14. temperatureto cool slowly to room temperature
15. temperaturecooled further to 5° C
16. filtrationThe solid was collected by filtration
17. washthe cake was washed with cold (5-10° C.) IPA (3731 g)
18. customThe solid was dried in air to a constant weight
19. customproviding white crystals (2765 g, gas chromatography (GC) internal standard purity 96.5%, 84.3%)