Formaldehyde → 4-Fluoro-2-hydroxybenzaldehyde

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of magnesium methoxide (13 g, 150 mmol, 6% in methanol) in methanol (50 mL) was added 3-fluorophenol (22.4 g, 200 mmol). The solution was heated to reflux, approximately half the methanol distilled off, toluene (300 mL) added, and the reaction heated with azeotropic removal of solvent until the temperature of the distillate reached 95 ° C.. A slurry of paraformaldehyde powder (22 g, 720 mmol) in toluene (20 mL) was added in small portions over 1 hour to the reaction with concurrent removal of volatile materials by distillation. Stirring was continued at 95 ° C. for 1 hour, cooled to 25 ° C., the reaction quenched by slow addition to 10% sulfuric acid and stirred at 30-40 ° C. for 2 hours. The layers were separated and the aqueous portion extracted with toluene (2×50 mL). The combined organic layers were washed with 10% sulfuric acid, water, dried with sodium sulfate, filtered and solvent evaporated. The resulting yellow oil was purified by flash chromatography over silica gel eluting with hexane:ethyl acetate (5: 1) to provide 9.7 g of the title compound as a white solid.

Provenance & Evidence