Uses
2,6-Dichloro-3-nitrobenzoic acid may be used in the preparation of 9-chloro-2-methoxy-6-nitro-5,10-dihydrobenzo[b][1,5]naphthyridin-10-one, required for the synthesis of potential DNA-binding antitumor agents. It may be used in the preparation of 2-(aminoalkyl)-5-nitropyrazolo [3,4,5-kl] acridines.
Synthesis
Step a: Synthesis of 2,6-dichloro-3-nitrobenzoic acid
2,6-Dichlorobenzoic acid (10 g, 52 mmol) was added to a pre-stirred mixture of nitric acid (15 mL) and sulfuric acid (30 mL) and reacted at 55 °C for 30 min, followed by continued stirring at room temperature for 30 min. Upon completion of the reaction, the reaction mixture was slowly poured into ice-cold water (1 L) and the precipitated solid was filtered and dried to afford 2,6-dichloro-3-nitrobenzoic acid (9 g). The filtrate was extracted with ethyl acetate (2 x 200 mL), the organic layers were combined, dried over anhydrous sodium sulfate and concentrated to dryness to give the additional product (2 g). The total yield was 11 g in 88% yield.
1H NMR (400 MHz, MeOH-d4): δ 7.98 (d, J=8.8 Hz, 1H), 7.67 (d, J=8.8 Hz, 1H).
References
[1] Journal of Medicinal Chemistry, 2011, vol. 54, # 19, p. 6597 - 6611
[2] Patent: WO2012/160464, 2012, A1. Location in patent: Page/Page column 79
[3] Patent: US2014/155398, 2014, A1. Location in patent: Paragraph 0474
[4] Chemische Berichte, 1987, vol. 120, p. 803 - 810
[5] Chemische Berichte, 1937, vol. 70, p. 1526,1531
