Description
4-Nitroindanone (4-Nitro-1-indanone) is an important chemical reagent used as a raw material in organic synthesis for the preparation of other cyclic compounds. In biology, it can inhibit the cysteine protease thioredoxin reductase and also interacts with cardiac potassium channels and is cytotoxic to human erythrocytes. In a rat model of atrial fibrillation, 4-nitro-1-indanone was found to have antiarrhythmic properties.
Uses
4-Nitroindanone is a versatile building block, capable of undergoing microwave-assisted oxidation to form ninhydrins. 4-Nitroindanone also has pharmaceutical relevance, as its thiosemicarbazone derivative has anti-Trypanosoma cruzi properties.
Synthesis
General procedure for the synthesis of 4-nitro-1-indanone and 6-nitro-1-indanone from 1-indanone: To a well-stirred mixture of concentrated sulfuric acid (98%, 13.9 mL) and nitric acid (65%, 2.6 mL) at -10°C, a solution of nitromethane (1.1 mL) with 1-indanone (1.0 g, 7.6 mmol) was slowly added. The rate of addition was controlled so that the temperature increased from -10°C to -5°C in 30 minutes. Stirring of the reaction mixture was continued at this temperature for 15 minutes (tight control of temperature and reaction time is required). Upon completion of the reaction, the mixture was poured into ice water (200 mL) for hydrolysis and the resulting yellow precipitate was collected. The aqueous phase was extracted with dichloromethane (2 x 20 mL) and the organic phase was combined. The organic phase was washed sequentially with potassium bicarbonate solution (2 x 15 mL) and saturated brine (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by fast column chromatography using hexane-ethyl acetate (1:0.2) as eluent. Isolation afforded 4-nitro-1-indanone (compound 25, 0.94 g, 80% yield) with a melting point of 98-100 °C (literature value: 100-101 °C).1H NMR (CDCl3) δ ppm: 2.80 (m, 2H, CH2), 3.53 (m, 2H, CH2), 7.61 (m, 1H, H-Ar), 8.08 (d, J = 8.5 Hz, 1H, H-Ar), 8.47 (d, J = 8.3 Hz, 1H, H-Ar). Simultaneous isolation afforded 6-nitro-1-indanone (compound 26, 0.23 g, 20% yield) with a melting point of 73-74 °C (literature value: 72-73 °C).1H NMR (CDCl3) δ ppm: 2.83 (m, 2H, CH2), 3.28 (m, 2H, CH2), 7.61 (d, J = 8.5 Hz, 1H, H-Ar) 8.44 (dd, J = 2.2 Hz, J = 8.5 Hz, 1H, H-Ar), 8.56 (d, J = 2.2 Hz, 1H, H-Ar).
References
[1] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 22, p. 6818 - 6826
[2] Journal of Medicinal Chemistry, 2003, vol. 46, # 3, p. 399 - 408
[3] Polish Journal of Chemistry, 2008, vol. 82, # 11, p. 2133 - 2140
[4] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 12, p. 3337 - 3339
[5] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 4, p. 884 - 889
