[Synthesis]
General procedure for the synthesis of 2-iodo-6-methylpyridine from 2-bromo-6-methylpyridine and acetyl chloride: to an anhydrous acetonitrile (13 mL) solution of 2-bromo-6-methylpyridine (2.0 g, 11.6 mmol) and sodium iodide (2.78 g, 18.6 mmol) was slowly added acetyl chloride (1.9 g, 24.4 mmol) dropwise, and the reaction mixture formed a light-yellow The reaction mixture formed a pale yellow suspension. The suspension was heated to reflux. After 16 hours of reaction, the conversion was shown to be 50% by gas chromatography (GC) analysis. Subsequently, acetyl chloride (1 eq.) and sodium iodide (0.8 eq.) were added additionally and refluxing was continued for 16 h. GC analysis showed 90% conversion with the presence of bromine and chlorine by-products detected. Upon completion of the reaction, the mixture was cooled to room temperature, diluted with 10% aqueous potassium carbonate and 5% aqueous sodium bisulfite (75 mL each), and extracted with ether (2 x 75 mL). The organic phases were combined, washed with potassium carbonate/sodium bisulfite solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford 2.39 g (94%) of the crude product 2-iodo-6-methylpyridine as a dark oil, which was directly used in the subsequent reaction without further purification. The structure of the product was confirmed by 1H NMR (CDCl3): δ 2.52 (s, 3H), 7.10 (d, 1H, J = 7.51 Hz), 7.20 (t, 1H, J = 7.69 Hz), 7.58 (d, 1H, J = 7.69 Hz). Ref: Tetrahedron Lett. 1990, 31, 6757. |