2,4-Dihydroxybenzaldehyde → 2,4-Dihydroxybenzonitrile

Participants

Reaction Conditions

Reaction Steps

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)).

Provenance & Evidence