2,4-Dihydroxybenzaldehyde → 2,4-Dihydroxybenzonitrile

Temperature

33 °C

In a double walled reactor 50.0 g (0.362 mol, 1.0 meq) 2,4-dihydroxybenzaldehyde were added to 180 mL formic acid, which resulted in a brown suspension at room temperature. Then 45.8 g (0.673 mol, 1.8 meq) sodium formate were added over 2 min, and the temperature increased to 33° C. After the temperature decreased to 30° C., 35.6 g (0.217 mol, 1.2 meq) hydroxyl ammonium sulfate were added during 3 min to give a thick brown suspension which became a brown solution after stirring 10 min at 30-32° C. While heating the mixture to 100° C., crystallization occurred at 38° C. and stirring was interrupted. At 70° C. the reaction mixture became a thin suspension, which was easy to stir. This reaction mixture was stirred for 2 hours at 100° C. The color turned dark brown. TLC (silica gel 60 F254, acetone:n-hexane:water 20:20:1) showed an almost complete reaction. Formic acid (170 mL) was evaporated under reduced pressure (60° C., 10 mbar). The solid dark brown residue was stirred with 400 mL MTBE at 40° C. for 1 hour (incomplete dissolution). The insoluble residue (62.5 g) was filtered and washed two times each with 50 mL MTBE. To the mother liquor 10 g activated carbon (Norit CA 5) were added and this mixture was refluxed for 1 hour and filtered at 40° C. by Celite Super Hyflow (washing with 2×50 mL portions of MTBE). The MTBE-mother liquor was washed three times each with 100 mL water. After removing the water from this MTBE solution with azeotropic distillation (water separator) it was concentrated under reduced pressure to 20% of the starting volume and 500 mL toluene were added. Then the MTBE was distilled off under reduced pressure. During this process a brown residue began to precipitate, which was filtered. The toluene mother liquor was concentrated to 150 mL and 2,4-dihydroxybenzonitrile precipitated, which was filtered and washed two times each with 30 mL toluene. The pale tan product was dried under reduced pressure (45° C., 20 mbar). The reaction yielded 34.5 g of 2,4-dihydroxybenzonitrile (70.5%, purity 97% (HPLC)).

1. customresulted in a brown suspension at room temperature
2. customdecreased to 30° C.
3. customto give a thick brown suspension which
4. temperatureWhile heating the mixture to 100° C.
5. customcrystallization
6. customoccurred at 38° C.
7. stirringstirring
8. customAt 70° C.
9. stirringto stir
10. stirringThis reaction mixture was stirred for 2 hours at 100° C
11. customan almost complete reaction
12. customFormic acid (170 mL) was evaporated under reduced pressure (60° C., 10 mbar)
13. stirringThe solid dark brown residue was stirred with 400 mL MTBE at 40° C. for 1 hour
14. dissolution(incomplete dissolution)
15. filtrationThe insoluble residue (62.5 g) was filtered
16. washwashed two times each with 50 mL MTBE
17. additionTo the mother liquor 10 g activated carbon (Norit CA 5) were added
18. temperaturethis mixture was refluxed for 1 hour
19. filtrationfiltered at 40° C. by Celite Super Hyflow (washing with 2×50 mL portions of MTBE)
20. washThe MTBE-mother liquor was washed three times each with 100 mL water
21. customAfter removing the water from this MTBE solution
22. distillationwith azeotropic distillation (water separator) it
23. concentrationwas concentrated under reduced pressure to 20% of the starting volume and 500 mL toluene
24. additionwere added
25. distillationThen the MTBE was distilled off under reduced pressure
26. customto precipitate
27. filtrationwhich was filtered
28. concentrationThe toluene mother liquor was concentrated to 150 mL and 2,4-dihydroxybenzonitrile
29. customprecipitated
30. filtrationwhich was filtered
31. washwashed two times each with 30 mL toluene
32. customThe pale tan product was dried under reduced pressure (45° C., 20 mbar)

ORD record

ord-698918c3b6c84fd28c7244d4e1aebcd9

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06875883B2