Chemical Properties
Solid
Uses
5-Nitrothiophene-2-carboxylic Acid is a reagent used in the preparation of benzothiophene amides which fuctions as nicotinamide ribosyltransferase inhibitors with potential antitumor and anticancer activities. It also functions as an intermediate in varying organic transformations.
Synthesis Reference(s)
Canadian Journal of Chemistry, 44, p. 2881, 1966
DOI: 10.1139/v66-428Journal of Medicinal Chemistry, 34, p. 2112, 1991
Synthesis
General procedure for the synthesis of 5-nitrothiophene-2-carboxylic acid from 5-nitrothiophene-2-carboxaldehyde: 5-nitrothiophene-2-carboxaldehyde (1.685 g, 10.72 mmol) was dissolved in dioxane (30 mL) with sulfamic acid (1.249 g, 12.87 mmol) and cooled down to 0 °C. Subsequently, an aqueous solution of sodium chlorite (1.940 g, 21.44 mmol) was added slowly and dropwise (14 mL). The reaction mixture was gradually warmed to room temperature and stirred continuously for 2 hours. A second batch of 5-nitrothiophene-2-carbaldehyde (1.966 g, 12.51 mmol) was treated at the same molar ratio under the same conditions. The two reaction mixtures were combined and extracted by partitioning with ethyl acetate and water. The organic phase was extracted twice with 5% NaHCO3 solution and discarded. The basic aqueous phase was adjusted to pH=2 with 2N HCl and extracted twice with ethyl acetate. The organic layers were combined, washed with brine and dried over anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure to give 5-nitrothiophene-2-carboxylic acid (Int.53) (3.6 g, 20.79 mmol, MS/ESI+ 173.9 [MH]+).
References
[1] Patent: US4220793, 1980, A
[2] Patent: WO2004/18480, 2004, A1. Location in patent: Page 155
[3] Helvetica Chimica Acta, 2002, vol. 85, # 12, p. 4485 - 4517
