Sulfuric Acid → Phthalonitrile

Toluene (100 ml) and dimethylacetamide (0.25 mol) were added to Compound B (17.5 g, 0.114 mol), and then to the resultant mixture was added dropwise thionyl chloride (25 ml) under reflux over 10 minutes. The mixture was refluxed under heating for additional 1 hour, and then concentrated under reduced pressure, to thereby obtain a viscous liquid. Separately, dimethylacetamide (10 ml) and acetonitrile (100 ml) were added to diethoxyethylamine (38.0 g, 0.235 mol), and to the resultant mixture the aforesaid viscous liquid was added dropwise over 15 minutes under stirring at 10° C. to 15° C. The mixture was stirred for additional 30 minutes, and was poured into water (100 ml) and ethyl acetate (100 ml), to thereby separate the ethyl acetate layer. The ethyl acetate layer was washed twice with water (100 ml). The ethyl acetate layer was dried with magnesium sulfate, and ethyl acetate was distilled off under reduced pressure, to thereby obtain a pale yellow viscous liquid of C. To this pale yellow viscous liquid of C, were added water (50 ml), ethanol (200 ml), and zinc powder (12 g), and to the resultant mixture was added, dropwise, a solution containing sulfuric acid (10 ml) diluted with water (40 ml) under reflux by heating, over 20 minutes. The mixture was stirred under heating for additional 30 minutes, and then cooled, and an insoluble substance was separated through filtration. To the thus-obtained solution, were added a saturated brine (50 ml) and ethyl acetate (100 ml), to thereby separate the ethyl acetate layer. The ethyl acetate layer was washed twice with water (100 ml). The ethyl acetate layer was dried with magnesium sulfate, and then the ethyl acetate was distilled off under reduced pressure, to thereby obtain a pale yellow viscous liquid of D. Separately, 3-nitrophthalonitrile (19.7 g, 0.113 mol), dimethylacetamide (70 ml), and potassium carbonate (15 g, 0.108 mol) were stirred at 20° C. to 25° C. under a stream of nitrogen, and to the resultant mixture was added the aforesaid pale yellow viscous liquid of D over 10 minutes. The mixture was stirred for additional 30 minute, and was then poured into water (300 ml) under stirring. The thus-precipitated crystals were filtered, and sufficiently washed with water. The thus-obtained crystals were recrystallized from methanol (70 ml). The precipitated crystals were filtered, washed with cold methanol (30 ml), and dried, to thereby obtain white crystals of Phthalonitrile compound 140 (35.0 g, yield 72.6%).

1. temperatureunder reflux over 10 minutes
2. temperatureThe mixture was refluxed
3. temperatureunder heating for additional 1 hour
4. concentrationconcentrated under reduced pressure
5. customto thereby obtain a viscous liquid
6. stirringThe mixture was stirred for additional 30 minutes
7. customto thereby separate the ethyl acetate layer
8. washThe ethyl acetate layer was washed twice with water (100 ml)
9. dry with materialThe ethyl acetate layer was dried with magnesium sulfate, and ethyl acetate
10. distillationwas distilled off under reduced pressure
11. customto thereby obtain a pale yellow viscous liquid of C
12. temperatureunder reflux
13. temperatureby heating, over 20 minutes
14. stirringThe mixture was stirred
15. temperatureunder heating for additional 30 minutes
16. temperaturecooled
17. customan insoluble substance was separated through filtration
18. additionTo the thus-obtained solution, were added a saturated brine (50 ml) and ethyl acetate (100 ml)
19. customto thereby separate the ethyl acetate layer
20. washThe ethyl acetate layer was washed twice with water (100 ml)
21. dry with materialThe ethyl acetate layer was dried with magnesium sulfate
22. distillationthe ethyl acetate was distilled off under reduced pressure
23. customto thereby obtain a pale yellow viscous liquid of D
24. stirringThe mixture was stirred for additional 30 minute
25. stirringunder stirring
26. filtrationThe thus-precipitated crystals were filtered
27. washsufficiently washed with water
28. customThe thus-obtained crystals were recrystallized from methanol (70 ml)
29. filtrationThe precipitated crystals were filtered
30. washwashed with cold methanol (30 ml)
31. customdried

ORD record

ord-d03314924fe74edf8a2c9a650800c5ab

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08703935B2