反应详情

温度

25 °C

A modified procedure of Balli and Kersting procedure described in Balli, H. et al., Justis Liebigs Am. Chem. 1:647 (1961), was followed. A one liter three neck roundbottom flask was fitted with an over head stirrer and a reflux condenser connected to a gas scrubber. To the flask was added in order, phosphorus oxychloride (80 mL), phosphorus pentachloride (104.0 g, 0.5M) and 5,6-dichlorobenzimidazole-2-sulfonic acid (9) (66.8 g, 0.25M). The resulting mixture was carefully heated until an exothermic reaction occurred. The heat source was removed. When the reaction had subsided, the mixture was carefully heated to reflux. After all gas evolution had ceased (5 hr) the mixture was protected from moisture and allowed to cool to 25° C. The resulting thick slurry was carefully added to cold H2O (2.5 L) containing some ice. Ice was added as needed. The aqueous mixture was allowed to stand for 18 hr at 5° C. while the product precipitated. The pH of the mixture was adjusted to pH 8 with conc. NH4OH then acidffied to pH 3 with glacial AcOH. The solid was collected by filtration, washed with H2O, then dried on the filter. The material was dissolved in THF, treated with charcoal, then filtered through Celite. The solvent was removed under reduced pressure. The solid residue was dried at 60° C. under reduced pressure for 18 hr to yield 39.9 g (72%) of 2,5,6-trichlorobenzimidazole (5). MP: 212°-214° C. (eff. then solidifies). See Kawashima, E. et al., Nucleic Acid Chemistry: Improved and New Synthetic Procedures, Method and Techniques, eds. Townsend, L. B. et al., Wiley Interscience New York, N.Y., Part IV p. 96 (1991). TLC: Rf =0.89 (EtOAc; SiO2). Recrystallization from benzene-hexane raises the melting point to 223°-224° C.

1. temperatureThe resulting mixture was carefully heated until an exothermic reaction
2. customThe heat source was removed
3. temperaturethe mixture was carefully heated to reflux
4. custom(5 hr)
5. additionThe resulting thick slurry was carefully added to cold H2O (2.5 L)
6. additioncontaining some ice
7. additionIce was added
8. customprecipitated
9. filtrationThe solid was collected by filtration
10. washwashed with H2O
11. customdried on the filter
12. dissolutionThe material was dissolved in THF
13. additiontreated with charcoal
14. filtrationfiltered through Celite
15. customThe solvent was removed under reduced pressure
16. customThe solid residue was dried at 60° C. under reduced pressure for 18 hr