5-Amino-2-chloro-3-picoline

Chemical Properties

Light yellow solid

Uses

5-Amino-2-chloro-3-picoline serves as a precursor for the synthesis of dihalopicolines. Diazotization of the compound yields 2-chloro-5-iodo-3-picoline, while subsequent treatment of the diazonium intermediate with copper powder affords 2,5-dichloro-3-picoline[6].

Synthesis

The general procedure for the synthesis of 2-chloro-3-methyl-5-nitropyridine from 2-chloro-3-methyl-5-nitropyridine was as follows: over a period of 2 h, iron powder (9.75 g, 0.174 mol, Sigma-Aldrich) was added in batches to a stirred 2-chloro-3-methyl-5-nitropyridine (10 g, 0.058 mol, Combi) acetic acid/ water (29 mL:88 mL) solution. After 3 hours of reaction, the mixture was filtered through diatomaceous earth and the filter cake was washed with ethyl acetate. After separation of the organic layer, the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed sequentially with aqueous sodium bicarbonate and brine and dried over anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure to give 6-chloro-5-methylpyridin-3-amine as a brown solid (8.0 g, 97% yield). Mass spectrum (MS) m/z = 142.03 [M + H]+. 1H-NMR (300 MHz, DMSO-d6) δ: 7.54 (d, J = 30 Hz, 1H), 6.91-6.90 (dd, J = 0.6 Hz and 2.7 Hz, 1H), 5.39 (s, 2H), 2.17 (s, 3H).

References

[1] Patent: WO2014/138484,  2014,  A1. Location in patent: Page/Page column 156
[2] Patent: WO2016/22724,  2016,  A1. Location in patent: Page/Page column 296
[3] Journal of Organic Chemistry,  2011,  vol. 76,  # 23,  p. 9841 - 9844
[4] Synthetic Communications,  2006,  vol. 36,  # 9,  p. 1235 - 1245
[5] Organic Letters,  2016,  vol. 18,  # 11,  p. 2774 - 2776
[6] Setliff, F. L., & Lane, J. E. (1976). Some 2,5- and 5,6-dihalonicotinic acids and their precursors. IV. Journal of Chemical & Engineering Data, 21(2), 246–247. https://doi.org/10.1021/je60069a037