Synthesis
General procedure for the synthesis of 2-hydroxy-3-methylpyridine from 2-amino-3-methylpyridine:
1. 2.30 g (33.3 mmol) of sodium nitrite was dissolved in 5 mL of water and slowly added dropwise to a solution of 3.60 g (33.3 mmol) of 2-amino-3-methylpyridine at room temperature.
2. The above mixture was added to a mixture consisting of 65 mL of water and 4 mL of concentrated sulfuric acid, and the reaction was stirred for 2 hours at room temperature.
3. At the end of the reaction, the pH of the reaction mixture was adjusted to 7 with sodium carbonate and the water was subsequently removed by distillation under reduced pressure.
4. The mixture was extracted three times with warm ethanol (80 mL each time).
5. The ethanol extracts were combined and the ethanol was removed by distillation under reduced pressure to give the crude product.
6. The crude product was recrystallized from ethyl acetate to give 3.38 g (93% yield) of the target compound 2-hydroxy-3-methylpyridine as colorless crystals with a melting point of 137-139 °C. 7. The product was analyzed by 1H NMR.
7. The product was characterized by 1H NMR (CDCl3), chemical shift δ (ppm): 2.18 (3H, s); 6.22 (1H, dd, J = 7, 7 Hz); 7.3-7.4 (2H, m); 13.14 (1H, s).
References
[1] Patent: US5541317, 1996, A
[2] Chemische Berichte, 1924, vol. 57, p. 1804
[3] Chemische Berichte, 1925, vol. 58, p. 1733
[4] Heterocycles, 1994, vol. 38, # 2, p. 277 - 280
