2-Chloro-4-methylpyridine

Colorless to light yellow liquid.

a) Firstly, 188 g of 2-amino-4-methylpyridine was fed into a round bottom flask, and then 250 g of sodium nitrite was added into a round bottom flask. Subsequently, 150 g of hydrogen chloride was continuously fed and the reaction temperature was controlled at 20 ° C.The reaction produces primiparous, The crude steamed isolated 229.3 g of 2-chloro-4-methylpyridine (content of 99percent).(1) Weighing 4-methyl-2-picolinic acid (50.4 mg, 0.3 mmol), Sodium carbonate (64.0 mg, 0.6 mmol), NaCl (17.6 mg, 0.3 mmol), tert-butyl hypochlorite (32 μL, 0.3 mmol) into a 25 mL of Schlenk reaction bottle, Then add toluene (5 mL) and place in an 80 °C oil bath for 20 h. After completion of the reaction, the solvent was removed under reduced pressure and eluted with petroleum ether / ethyl acetate.The solvent was separated on a silica gel column, The yield of 4-methyl-2-chloropyridine was 71percent.(a); Into a 2L four-necked flask equipped a stirrer, a thermometer and a gas introduction tube (inlet), 324 g (3.00 mol) of 2-amino-4-methylpyridine and 485 g of methanol were charged and mixed for dissolution, and while keeping the temperature in the system at from 10 to 30°C, 361.4 g (9.90 mol) of hydrogen chloride gas was introduced over a period of one and a half hours. Then, in a 2L four-necked flask equipped with a stirrer, a thermometer, a dropping funnel and an introduction tube (outlet) equipped with a bubble counter having a gas generation apparatus and a diazotization apparatus connected, 414 g (6.00 mol) of sodium nitrite, 211 g (6.60 mol) of methanol and 454 g of water were mixed, and 812.4 g (3.15 mol) of a 38percent sulfuric acid aqueous solution was dropwise added over a period of 5 hours while keeping the temperature in the system at from 20 to 30°C. In the methyl nitrite generation apparatus, simultaneously with dropwise addition of the 38percent sulfuric acid aqueous solution, methyl nitrite gas in an equivalent amount was generated and introduced to the diazotization apparatus through the bubble counter. Further, for diazotization, the reaction apparatus was cooled with water so that the temperature in the system would be kept at from 20 to 30°C. After completion of the introduction of the methyl nitrite gas, stirring was carried out at the same temperature for 13 hours and the reaction was completed. After methanol was distilled off under reduced pressure, 648 g of water was charged, and 518 g of a 40percent sodium hydroxide aqueous solution was dropwise added at 30°C or below to adjust the pH in the system to 12. The formed oil was extracted with 910 g of diethyl ether, the aqueous layer was separated out, and the solvent was distilled off under reduced pressure to obtain 375.3 g of an oil. The oil (crude product) had a composition comprising 70.7percent (yield: 69.5percent) of 2-chloro-4-methylpyridine, 26.6percent (yield: 27.2percent) of 2-methoxy-4-methylpyridine and 2.6percent of 2-amino-4-methylpyridine.

Molecular Weight:127.57
XLogP3:1.9
Hydrogen Bond Acceptor Count:1
Exact Mass:127.0188769
Monoisotopic Mass:127.0188769
Topological Polar Surface Area:12.9
Heavy Atom Count:8
Complexity:74.9
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes