Description
2-Chloro-3-methylpyridine is an intermediate for many medicines and pesticides, such as fluazifop, nicosulfuron, and fluazifop. Moreover, with the gradual promotion of these new high-efficiency and low-toxic heterocyclic pesticides, 2-chloro-3-methylpyridine is increasing. The industrial method for preparing 2-chloro-3-methylpyridine is to obtain it by site-specific chlorination of 3-methylpyridine. First, 3-methylpyridine is epoxidized and then chlorinated. The main chlorinated 3-methylpyridine is a mixture of 2-chloro-3-methylpyridine and 2-chloro-5-methylpyridine, of which 2-chloro-3-methylpyridine accounts for 20% (mass).
Chemical Properties
colorless to light yellow liquid
Uses
2-Chloro-3-methylpyridine is an active ingredient and a major constituent of imidaclopide, a systemic insecticide that acts as insect neurotoxin and belongs to a class of chemical called the neonicotinoids.
Application
2-Chloro-3-methylpyridine can be used as an intermediate for Lumacaftor. Lumacaftor is a drug used to treat certain types of cystic fibrosis, particularly by assisting in the transport of CFTR protein to the cell membrane surface, thereby addressing respiratory issues associated with the disease.
Synthesis
General procedure for the synthesis of 2-chloro-3-methylpyridine from 3-methyl-2-pyridinecarboxylic acid: 3-methylpyridine-2-carboxylic acid (56.7 mg, 0.3 mmol), sodium hydroxide (16.0 mg, 0.15 mmol), tetrabutylammonium chloride (TBAC, 26.3 mg, 0.45 mmol) and di-tert-butyl peroxide (DTBP. 165 μL, 0.9 mmol) were placed in a 25 mL Schlenk reaction flask. Subsequently, 1 mL of acetonitrile (CH3CN) was added as a solvent and the reaction mixture was placed in an oil bath at 50 °C for 20 h. The reaction was carried out at a pressure of 1.5 mL. After completion of the reaction, the solvent was removed by distillation under reduced pressure. The crude product was purified by silica gel column chromatography using petroleum ether/ethyl acetate as eluent to give 2-chloro-3-methylpyridine in 70% yield.
References
[1] Patent: CN108586334, 2018, A. Location in patent: Paragraph 0048-0050
