Preparation of 2-chloro-5-iodo-3-pyridinecarbonitrile_Industrial additives

Preparation background and overview of 2-chloro-5-iodo-3-pyridinecarbonitrile

2-Chloro-5-iodo-3-pyridinecarbonitrile can be used as a pharmaceutical synthesis intermediate. If you inhale 2-chloro-5-iodo-3-pyridinecarbonitrile, please move the patient to fresh air; if there is skin contact with ammonium pentaborate, take off contaminated clothing and wash the skin thoroughly with soap and water, such as If you feel unwell, seek medical attention.

Preparation of 2-chloro-5-iodo-3-pyridinecarbonitrile

Step 1: 2-Hydroxy-5-iodonicotinonitrile

Add 9g (0.5 equivalent) N-iodosuccinimide to the solution at room temperature. Add 10g (83 mmol) 2-hydroxynicotinonitrile to 150 ml anhydrous dimethylformamide. The reaction mixture was stirred at 60°C. After stirring for 30 minutes, 9 g (0.5 equivalents) of N-iodosuccinimide was added, and the reaction mixture was stirred at 60 °C for 5 hours. The solvent was evaporated and the precipitate formed was filtered, washed with water and diethyl ether, and dried under vacuum to obtain 2-hydroxy-5-iodonicotinonitrile in powder form. Beige powder, 18.5 g (90%). LCMS (EI, m/z): (M+1) 246.931H NMR: δHppm (MHz, DMSO): 12.79 (1H, s, OH), 8.36 (1H, d, CHarom), 8.04 Pyridinemethylamine (1H, d , CHarom).

Step 2: 2-chloro-5-iodo-3-pyridinecarbonitrile

Add 30.7ml (329mmol) phosphorus oxychloride and 6 drops of sulfuric acid at 0.7°C to 9g (6.6mmol) 2-hydroxy-5-iodonicotinonitrile. The reaction mixture was heated at 110°C for 5 hours and then at room temperature overnight. Pour the reaction mixture into a beaker containing ice and a small amount of water to form a precipitate. The mixture was allowed to gradually return to room temperature, then filtered and rinsed with water. The solid was dried to give 2-chloro-5-iodo-3-pyridinecarbonitrile. Solid, 6.8 g (70%). LCMS (EI, m/z): (M+1) 265.451H NMR: δHppm (MHz, DMSO): 9.61 (1H, d, CHarom), 9.14 (1H, d, CHarom).