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

HRID 1827482Notes

Reaction equation

HRID 1827482 reaction equation
[BrH:1].[CH3:2][C:3]1[CH:8]=[C:7]([CH3:9])[N:6]=[C:5](N)[CH:4]=1.BrBr.N([O-])=O.[Na+].N([O-])=O.[OH-].[Na+]>>[Br:1][C:5]1[CH:4]=[C:3]([CH3:2])[CH:8]=[C:7]([CH3:9])[N:6]=1

Participants

7

Reactant 6

HCID 260Hydrogen BromideHCID 946NitriteHCID 14798Sodium HydroxideHCID 215072-Amino-4,6-dimethylpyridineHCID 24408BromineHCID 23668193Sodium Nitrite

Product 1

HCID 149751952-Bromo-4,6-dimethylpyridineYield 49.3%

Conditions

Temperature
20 °C

Procedure

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)+.

Workup

  1. additionwas added dropwise
  2. extractionextracted with MTBE
  3. washThe organic extracts were washed with water, brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product (29 g of a red oil) was purified by flash chromatography (silica, 350 g)
  8. washeluted with 2–7% ethyl acetate-cyclohexane, which

Sources & evidence

ORD record
ord-9fa78b5d5ad44877ac3b7d524a44b40e
Source dataset
uspto-grants-2006_05
Patent number
US07053107B2

Reaction notes

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