Hydrogen Bromide → 2-Bromo-4,6-dimethylpyridine

Participants

Reaction Conditions

Reaction Steps

A solution of 48% HBr (aq) (Aldrich, 65 mL, 1.2 mol, 10 eq) was cooled to −5° C. and treated with 4,6-dimethyl-pyridin-2-ylamine (Aldrich, 15.0 g, 0.12 mol. 1.0 eq). The thick white salt mixture was stirred with a mechanical stirrer while bromine (Aldrich, 19.7 mL, 0.38 mol, 3.1 eq) was added dropwise. The resultant red mixture was treated with an aqueous solution (32 mL H2O) of NaNO2 (Aldrich, 22.1 g, 0.32 mol, 2.6 eq) over one hour. The temperature was maintained below 5° C. during the nitrite addition, and then gradually warmed to 20° C. over 2 hours. The reaction mixture was adjusted to pH 14 with NaOH (aq), and extracted with MTBE. The organic extracts were washed with water, brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product (29 g of a red oil) was purified by flash chromatography (silica, 350 g) and eluted with 2–7% ethyl acetate-cyclohexane, which gave an orange oil (11.0 g, 48%). 1H NMR (DMSO-d6, 300 MHz) δ 7.30 (1H, s), 7.13 (1H, s), 2.39 (3H, s), 2.26 (3H, s). 13C NMR (DMSO-d6, 75 MHz) δ 159.4, 151.3, 140.9,125.7,124.0, 23.7, 20.3. ESI m/z 186/188 (M +H)+.

Provenance & Evidence