5-Chloro-2-nitrobenzoic acid

Chemical Properties

light yellow to yellowish-green crystalline powder.
5-Chloro-2-nitrobenzoic acid is a crystalline solid sparingly soluble in cold water but readily soluble in hot water and also in ethanol and benzene. Its electrolytic dissociation constant is 1.52 × 102 (25 °C), and its melting point is 139 °C.

Uses

5-Chloro-2-nitrobenzoic acid was used as a component of 5,5′-dithiobis-2-nitrobenzoic acid, which found application to the determination of the acid-soluble disulphide content of the blood. Benzene and some of its derivatives (e.g. chloronitrobenzoic acids) have been shown to cause alterations in heme and globin synthesis. Chloronitrobenzoic acids inhibited the activity of δ-aminolevulinic acid (δ-ALA) and enhanced ferrochelatase (FC) activity. 5-Chloro-2-nitrobenzoic acid was also used as component of synthesis of 2-aryl 4(3H)-quinazolinones and 6-pyrrolidinyl-2-(2-substituted phenyl)-4-quinazolinones, which are potential anticancer candidates[1].

Anticancer Research

5-Chloro-2-nitrobenzoic acid has been shown to have potential as a cytotoxic agent against leukemia cells, monocytic cells, and carcinoma cells.

Synthesis

Fe(NO3)3-9H2O (40.6 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), KCl (7.5 mg, 0.1 mmol) and 5-chloro-2-nitrobenzenemethanol (108.5 mg, 1.0 mmol) were added sequentially to the Schlenk tube. Under oxygen atmosphere, DCE (4.0 mL) was added (using a gas bag, commercial size: 2 L, expandable to 5 L). The reaction mixture was stirred at 25 °C and the progress of the reaction was monitored by TLC (unfolding agent: petroleum ether/EtOAc = 5:1) until the reaction was complete (~48 h). After completion of the reaction, the crude reaction mixture was filtered through a short silica gel column (height: 2 cm, diameter: 3 cm) and eluted with Et2O (3 × 25 mL). After evaporation of the solvent, the residue was purified by silica gel column chromatography [eluent: petroleum ether/EtOAc = 15:1 (500 mL) to 2:1 (300 mL)] to afford 5-chloro-2-nitrobenzoic acid (69.9 mg, 57% yield) as a pale yellow solid. The yield of 5-chloro-2-nitrobenzoic acid in the crude product was determined to be 57% by NMR analysis, using CH2Br2 as an internal standard and comparing the spectral data with those reported in the literature, while 5-chloro-2-nitrobenzaldehyde was detected in 38% yield.

References

[1] W. Ferenc, J. Sarzyński, B. Cristóvo. “Thermal and magnetic behaviour of 5-chloro-2-nitrobenzoates of Co(II), Ni(II) and Cu(II).” Journal of Thermal Analysis and Calorimetry 34 1 (2010): 761–767.