Synthesis Reference(s)
The Journal of Organic Chemistry, 55, p. 1585, 1990
DOI: 10.1021/jo00292a038
Synthesis
General procedure for the synthesis of 1-(4,5-dimethoxy-2-nitrophenyl)ethanone from 3,4-dimethoxyacetophenone: (1) Nitration step: a solution was prepared by dissolving 3,4-dimethoxyacetophenone (1,500 g) in 17% nitric acid (1,400 g) at 5 to 10 °C, followed by slow dropwise addition to a solution consisting of 67% nitric acid (8430 g) and sodium nitrite (18 g) (18 g). The titration process was controlled to be completed within 2 to 3 hours. After the dropwise addition, the reaction solution was continued to be stirred at 5 to 10°C for 1 to 2 hours. Cold water (7.5 L) was added to dilute the reaction mixture and stirred for 30 minutes. The reaction mixture was filtered and the filter cake was washed with water (30 L). The solid product obtained by filtration was re-suspended in water (7.5 L), neutralized with aqueous sodium bicarbonate to pH neutral, filtered again and washed with water (7 L). Finally, the product was dried under reduced pressure to afford 3,4-dimethoxy-6-nitroacetophenone (2164 g, 87.9% yield). The structure of the product was confirmed by 1H-NMR (400 MHz, CDCl3): δ 2.50 (s, 3H), 3.97 (s, 3H), 3.99 (s, 3H), 6.76 (s, 1H), 7.62 (s, 1H).
References
[1] Patent: EP1559715, 2005, A1. Location in patent: Page/Page column 17
[2] Heterocycles, 2016, vol. 92, # 10, p. 1882 - 1887
[3] Chemistry Letters, 2000, # 7, p. 712 - 713
[4] Patent: EP3205650, 2017, A1. Location in patent: Paragraph 0106; 0354; 0355
[5] Journal of Organic Chemistry, 1999, vol. 64, # 21, p. 7988 - 7995
