Methyl 3-formyl-4-hydroxybenzoate

50-00-0

99-76-3

24589-99-9

The general procedure for the synthesis of methyl 3-formyl-4-hydroxybenzoate from formaldehyde and methyl nipagin was as follows: methyl 4-hydroxybenzoate (3.00 g, 19.7 mmol) and magnesium chloride (2.81 g, 29.5 mmol) were dissolved in 100 mL of acetonitrile and mixed by stirring. Subsequently, triethylamine (TEA, 10.3 mL, 73.9 mmol) was slowly added via syringe. Next, paraformaldehyde (12.0 g, 133 mmol) was added all at once and the reaction mixture was heated to reflux. After keeping the reaction stirred under reflux conditions for 24 hours, it was cooled to room temperature. Upon completion of the reaction, the reaction was quenched by addition of about 100 mL of 1N hydrochloric acid (HCl) and the mixture was poured into ethyl acetate (EtOAc). The organic and aqueous layers were separated and the organic layer was washed with saturated brine. The aqueous layer was back-extracted with ethyl acetate (EtOAc). All organic layers were combined, dried with anhydrous magnesium sulfate (MgSO4), filtered and concentrated in vacuum by rotary evaporator. The crude product was purified by fast column chromatography. Pure grades collected and confirmed by thin layer chromatography (TLC) were concentrated under vacuum to give 2.06 g (58% yield) of the target product, methyl 3-formyl-4-hydroxybenzoate. The structure of the product was confirmed by 1H NMR (400 MHz, DMSO-d6): δ 11.54 (s, 1H), 10.27 (s, 1H), 8.21 (d, J = 2.4 Hz, 1H), 8.03 (dd, J = 8.8, 2.4 Hz, 1H), 7.07 (d, J = 8.8 Hz, 1H), 3.79 (s, 3H).