5-Nitroindole-2-carboxylic acid

16732-57-3

16730-20-4

General procedure for the synthesis of 5-nitroindole-2-carboxylic acid from ethyl 5-nitroindole-2-carboxylate: lithium hydroxide monohydrate (LiOH-H2O, 1.06 g, 46.2 mmol, 2.1 eq.) was added to ethyl 5-nitro-1H-indole-2-carboxylate (II, 5.15 g, 22 mmol, 1 eq.) in a suspension of a mixed solvent (180 mL) in a 1:1:2 ratio of tetrahydrofuran (THF), methanol (MeOH) and water (H2O) in a solvent mixture (180 mL) with a ratio of 1:1:2. The reaction mixture rapidly changed to a dark yellow color and was stirred continuously at 25 °C. After 30 min, the reactants were completely dissolved and the reaction was fully converted after 6 h. The reaction mixture was cooled to 0 °C and the reaction mixture was then converted to a dark yellow color with constant stirring. The reaction mixture was cooled to 0 °C and the pH was adjusted to 5 with 2N hydrochloric acid (HCl) to terminate the reaction. Subsequently, the organic volatiles were removed by evaporation under reduced pressure and filtered to give a white precipitate, which was dried to give the target product 5-nitroindole-2-carboxylic acid (III). The yield was 4.53 g (quantitative yield) in small scale experiments. In a 50 g scale reaction, the same procedure was followed to give 42.2 g of compound III in 96% yield. The product was analyzed by liquid chromatography-mass spectrometry (LCMS, HPLC method 2) and showed m/z 205 [MH]- (retention time 2.58 min). Nuclear magnetic resonance hydrogen spectroscopy (1H NMR, 400 MHz, DMSO-d6) data were as follows: δ 2.59 (dd, J = 15.91, 5.67 Hz, 1H), 2.82 (dd, J = 15.97, 8.29 Hz, 1H), 3.58 (dd, J = 12.86, 5.67 Hz, 1H), 3.89 (dd, J = 13.35 , 4.08 Hz, 1H), 5.17-5.23 (m, 1H), 7.36 (s, 1H), 7.80 (d, J = 9.15 Hz, 1H), 8.15 (dd, J = 9.15, 2.32 Hz, 1H), 8.27 (d, J = 5.12 Hz, 1H), 8.72 (d, J = 2.32 Hz, 1H), 12.58 (br.s., 1H).