2-Bromo-4-methylpyridine

Chemical Properties

2-Bromo-4-methylpyridine is a colorless to orange oily liquid, It decomposes to produce harmful substances such as carbon dioxide, carbon monoxide, nitrogen oxides (NOx), hydrogen bromide.

Uses

An intermediate of pyridinyl pyrrole compounds as proton pump inhibitors with improved gastric acid secretion suppressive activity

Uses

2-Bromo-4-methylpyridine may be used:

• in the total synthesis of ocular age pigment A2-E (2 equiv of retinal (vitamin A) and 1 equiv of ethanolamine)
• in the preparation of methoxy-2-(2-pyridyl)indoles
• in the preparation of 2-(2′,4′-difluorophenyl)-4-methylpyridine, via a Suzuki coupling reaction with 2,4-difluorophenylboronic acid

Application

2-Bromo-4-methylpyridine can be used as an intermediate in organic synthesis and medicinal chemistry, mostly in the structural modification and synthesis of drug molecules. In basic chemistry research, the substance can be used for the synthesis of a series of organic nitrogen ligands containing pyridine units, and has good applications in the basic research of methodology of transition metal catalysis.

Hazard

2-Bromo-4-methylpyridine may cause heritable genetic damage in humans.

Synthesis

695-34-1

4926-28-7

The general procedure for the synthesis of 2-bromo-4-methylpyridine from 2-amino-4-methylpyridine was as follows: 2-amino-4-methylpyridine (120 g, 1.1 mol) was dissolved in 48% hydrobromic acid (1.5 L) and bromine (160 mL, 3.11 mol) was added slowly and dropwise at -20 °C. The reaction mixture was stirred continuously for 3 hours at -15°C to -20°C. Subsequently, aqueous sodium nitrite (NaNO2) (204 g, 2.95 mol) was added to the reaction system in batches. The reaction mixture was gradually warmed up to room temperature over a period of 3 hours. A 20% aqueous sodium hydroxide (NaOH) solution (1.2 Kg NaOH dissolved in 2 L of water) was added and the pH was adjusted to 12 while the temperature was controlled at 0 °C. The reaction mixture was extracted with ether (3 x 250 mL), the organic phase was washed sequentially with water and saturated brine and dried anhydrous. After removing the solvent under reduced pressure, the reaction was purified by fractional distillation to afford 2-bromo-4-methylpyridine (164 g, 86% yield) as a light yellow liquid.

References

[1] Tetrahedron, 2002, vol. 58, # 22, p. 4429 - 4438
[2] Chemische Berichte, 1992, vol. 125, # 5, p. 1131 - 1140
[3] Chemical and Pharmaceutical Bulletin, 1990, vol. 38, # 9, p. 2446 - 2458
[4] Patent: US2008/51397, 2008, A1. Location in patent: Page/Page column 9; 24
[5] Phosphorus, Sulfur and Silicon and the Related Elements, 2002, vol. 177, # 11, p. 2579 - 2587