Preparation method of 6-bromomethyl-2-pyridinemethanol_Industrial additives

Background and overview^[1][2]

6-Bromomethyl-2-pyridylmethanol is an alcohol derivative that can be used as an organic intermediate and can be obtained by bromination of 2,6-pyridylmethanol.

Preparation method^[1-2]

Method 1: 2-bromomethyl-6-pyridinemethanol. Reflux 2,6-pyridylmethanol (15 g, 108 mmol) in HBr (48% aqueous solution) for 1 h. After cooling to 0 °C, carefully add ice-cold saturated NaOH solution until pH = 14 is reached. The product was immediately extracted with 4 × 100 mL CH₂Cl₂, and the combined organic layers were dried with MgSO₄. All volatiles were removed in vacuo to give a slightly pinkish crude product. Pure 1-bromomethyl-6-pyridinemethanol was obtained by recrystallization from hexane/ethyl acetate (5:1). Yield: 6.26g (28.7%), white microcrystalline solid. 2-Bromomethyl-6-pyridinemethanol. Yield¹H NMR (CDCl₃, 250MHz, 25℃): δ3.93 (s, br, 1H, OH), 4.54 (s, 2H, CH2Br), 4.76 (s, 2H, CH2OH), 7.10 (d 1 H, 3 JHH = 7.7Hz, aryl-H 5), 7.34 (d, 1H, 3HHH = 7.6Hz, aryl phthalocyanine Pigment base-H3), 7.69 (t, 1H, 3HHH = 7.7Hz, aryl-H4). ¹³C {1H} NMR (CDCl₃, 63MHz, 25℃): δ33.44 (CH2Br), 63.98 (CH2OH), 119.89 (Aryl-C3), 122.09 (Aryl-C5), 137.76 (Aryl-C4), 155.72 (Aryl-C2), 159.21 (Aryl-C6).

Method 2: Add PPh₃ (S.24g, 20mmol) and NBS (3.56g, 20mmol) to the 2,6-pyridine dimethanol (4.17g, 30mmol) solution. The resulting solution was stirred at room temperature for 1 hour. The solvent was evaporated and the residue was purified by flash chromatography on a silica gel column. Elution with 2:1 hexane-EtOAc gave the product 6-bromomethyl-2-pyridinemethanol, which was further purified by recrystallization from 1:5 CHCl₃-hexane. Yield 1.61 g (40%).

Main reference materials

[1] Organometallics 2008, 27, 8, 1892-1901

[2] U.S., 6329523, 11 Dec 2001