[Synthesis]
General procedure for the synthesis of 5-iodo-6-chloronicotinic acid from 2-chloro-3-iodo-5-methylpyridine: 2-chloro-3-iodo-5-methylpyridine (4.00 g, 15.8 mmol) was dissolved in water (160 mL), and heated at 80 °C until completely dissolved. Potassium permanganate (6.24 g, 39.5 mmol) was added in batches and the reaction mixture was heated to reflux at 100 °C for 3 hours. Upon completion of the reaction, the hot reaction solution was filtered through Celite 545 and the filter cake was washed with hot water (3 x 20 mL). The filtrates were combined, concentrated to half the original volume and subsequently cooled to 0 °C. The pH was adjusted to 1-2 by slow dropwise addition of concentrated aqueous hydrochloric acid (37%, w/w). the precipitate precipitated was collected by filtration, washed with cold water (2 × 5 mL) and dried in a vacuum desiccator to afford 6-chloro-5-iodonicotinic acid (795 mg, 2.8 mmol) as a white solid in 18% yield. The product characterization data were as follows: thin-layer chromatography Rf value (ethyl acetate/cyclohexane, 5/5, v/v) 0.40; melting point 208-210 °C (literature value: 198-200 °C); infrared spectroscopy (KBr) ν 851, 1283, 1365, 1701, 2400-3100 cm-1; 1H NMR (200 MHz, DMSO-d6) δ 8.65 (d, 1H, J = 2.0 Hz, H-4), 8.83 (d, 1H, J = 2.0 Hz, H-2); 13C NMR (50 MHz, DMSO-d6) δ 96.0 (C-5), 126.9 (C-3), 149.4 (C-4 or C-2), 149.6 (C-4 or C-2), 157.1 (C-6) 164.3 (C=O); ESI-MS m/z 281.87 [M-H]-. |