Dimethylformamide → 1-Methyl-5-(p-tolyl)-1H-pyrazole-4-carbaldehyde

Participants

Reaction Steps

N,N-Dimethylformamide (300 mL) was cooled to 0° C. and treated with phosphorus oxychloride (80 g, 0.52 mol). After completion of the addition, the resulting mixture was warmed to room temperature and stirred for 1 hour. 5-(4-Methylphenyl)-1-methyl-1H-pyrazole (C2) (30.0 g, 174 mmol) was added and the reaction mixture was heated to 120° C. and stirred overnight. The mixture was cooled to room temperature and concentrated in vacuo. The residue was poured into ice-water (700 mL), then adjusted to a pH of approximately 8 with saturated aqueous sodium carbonate solution. The resulting mixture was extracted with dichloromethane (4×300 mL); the combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by silica gel chromatography (Gradient: 1:100 to 1:30 ethyl acetate in petroleum ether) afforded the product as a yellow solid. Yield: 28.2 g, 141 mmol, 81%. 1H NMR (400 MHz, CDCl3) δ 2.46 (s, 3H), 3.81 (s, 3H), 7.33 (br AB quartet, JAB=8 Hz, ΔνAB=17 Hz, 4H), 8.04 (s, 1H), 9.60 (s, 1H).

Provenance & Evidence