4-Hydroxybenzaldehyde → 6-(4-Formylphenoxy)nicotinonitrile

Participants

Reaction Steps

Combine 4-Hydroxybenzaldehyde (8.0 g, 65.5 mmol), 6-Chloronicotinonitrile (9.07 g, 65.5 mmol), powdered K2CO3 (13.6 g, 98.3 mmol), and DMA/Toluene (80/240 mL) in a 500 mL RB flask equipped with a stir, reflux condenser and a Dean Stark Trap. Reflux the reaction mixture for several hours under a Nitrogen atmosphere then cool to room temperature and quench with sat NH4Cl (aq). Add Ethyl acetate to extract the product and wash several times with water and then brine. Dry the organic layer over Na2SO4. Concentrate and flash chromatograph using 2:1 Hexanes:Ethyl acetate to give 13.2 g (88% yield) of the title compound: 1H NMR (500 MHz, CDCl3); 7.1 (1H, d), 7.3-7.4 (2H, m), 7.9-8.0 (3H, m), 8.5 (1H, d), 10.0 (1H, s); MS m/z 225 (M+1).

Provenance & Evidence