3-[(Dimethylamino)methyl]-4-hydroxy-5-methoxybenzenecarbaldehyde

Synthesis

To a stirred solution of aqueous formaldehyde (37% w/w, 37.5 mmol, 2.8 mL) and aqueous dimethylamine (40% w/w, 37.5 mmol, 4.8 mL) in ethanol (25 mL) was added 4-hydroxy-3-methoxybenzaldehyde (vanillin, 25 mmol, 3.883 g). The reaction mixture was stirred and heated to reflux for 45 minutes, followed by continued stirring at room temperature overnight. Upon completion of the reaction, the precipitated milky white solid was separated by filtration under reduced pressure, washed with ice-cold acetone and dried under vacuum at room temperature to afford 3-((dimethylamino)methyl)-4-hydroxy-5-methoxybenzaldehyde as an off-white solid. Yield: 75% (3.910 g); Melting point: 140-142°C (literature value: 139-141°C, see reference [43j]); 1H NMR (400 MHz, CDCl3) δ (ppm): 10.6 (1H, broad single peak, OH), 9.77 (1H, single peak, CHO), 7.34 (1H, single peak, ArH). 7.15 (1H, single peak, ArH), 3.94 (3H, single peak, OCH3), 3.76 (2H, single peak, CH2), 2.38 (6H, single peak, 2×CH3); 13C NMR (100 MHz, CDCl3) δ (ppm): 190.7, 154.5, 148.6, 128.1, 125.3, 121.4. 109.8, 62.2, 56.0, 44.3.

References

[1] Tetrahedron Letters, 2010, vol. 51, # 15, p. 1979 - 1981
[2] Synthetic Communications, 1983, vol. 13, # 8, p. 677 - 684
[3] Patent: WO2016/80853, 2016, A1. Location in patent: Paragraph 00310; 00311
[4] Patent: CN105418601, 2016, A. Location in patent: Paragraph 0271; 0272, 0273
[5] Bulletin of the Chemical Society of Japan, 1956, vol. 29, p. 265,269