Synthesis
The general procedure for the synthesis of 3,4-dihydroxy-5-nitrobenzaldehyde from 5-nitrovanillin was as follows: iodine (2.095 g), aluminum powder (0.368 g) and acetonitrile (40 mL) were added to a 100 mL aubergine flask, heated to reflux, and stirred for 2 hr until the violet-red color of the iodine disappeared completely. Subsequently, pyridine (1.597 g) and 5-nitrovanillin (0.986 g) were added and the reaction was continued for 18 hours. After completion of the reaction, the mixture was cooled to room temperature and then acidified by adding 2 mol/L dilute hydrochloric acid (10 mL) to the reaction solution. The reaction mixture was extracted with ethyl acetate (50 mL x 3), the organic phases were combined and dried with anhydrous sodium sulfate. The filtrate was concentrated to dryness by rotary evaporator to remove the solvent. Finally, the residue was purified by fast column chromatography (mobile phase of ethyl acetate to petroleum ether 1:3, v/v) to afford the target product 3,4-dihydroxy-5-nitrobenzaldehyde (yellow solid, 0.650 g, 71% yield).
References
[1] Journal of Medicinal Chemistry, 2018, vol. 61, # 5, p. 1969 - 1989
[2] Journal of Organic Chemistry, 2000, vol. 65, # 23, p. 8001 - 8010
[3] Journal of the American Chemical Society, 2000, vol. 122, # 44, p. 10781 - 10787
[4] Organic Letters, 2008, vol. 10, # 7, p. 1369 - 1372
[5] Patent: WO2016/199943, 2016, A1. Location in patent: Paragraph 0402
