Preparation background and overview of 4-methyl-3-bromopyridine
Pyridine and its derivatives are widely distributed in nature. Many plant ingredients such as alkaloids contain pyridine ring compounds in their structures. They are the basis for the production of many important compounds, such as medicines, pesticides, dyes, surfactants, rubber additives, feed additives, food additives, adhesives, etc. Indispensable raw materials in production. 4-Methyl-3-bromopyridine is an important intermediate, mainly used as pharmaceutical intermediates, organic synthesis intermediates, organic solvents, and also used in the production of dyes, spices, and pesticides. At present, the reported synthesis methods of 4-methyl-3-bromopyridine have shortcomings such as low yield and long process route for industrial sodium bicarbonate.
Preparation of 4-methyl-3-bromopyridine
4-Methyl-3-bromopyridine is prepared as follows:
(1) Preparation of 4-methyl-3-aminopyridine: Dissolve 4-methyl-3-nitropyridine (13.8g, 0.1mol) in methanol solution, add 10% Pd/C (0.1 g), the reaction was carried out in an autoclave, hydrogen was introduced until the pressure was 0.5MPa, the temperature was raised to 20°C, and the reaction was carried out for 15 hours. Monitor the reaction with thin layer chromatography until the reaction is complete, cool to room temperature, filter with diatomaceous earth, and wash the filter cake with dichloromethane to prevent Pd/C from catching fire. The filtrate is concentrated under reduced pressure to obtain 2-methyl-4-aminopyridine. The molar yield was 93%.
Preparation of (2) 4-methyl-3-bromopyridine: under cooling in an ice-salt bath, add 2-methyl-4-aminopyridine (10.8g, 0.1mol) to 48% HBr (46ml, 0.4mol), after adding, cool to -5℃, slowly add liquid bromine (15ml, 0.3mol) dropwise, finish adding in 30-35min, then add 42g of 40% sodium nitrite solution dropwise below 0℃, at 1 – Complete the addition within 1.1h. After the addition, continue to stir for 30 minutes below 0°C. Then slowly add 50% sodium hydroxide solution below 20°C to adjust the pH of the solution to 9 methylboric acid. The reaction solution is extracted with ethyl acetate. There is a base layer. Dry with anhydrous sodium sulfate, filter with suction, and concentrate to obtain 4-methyl-3-bromopyridine, with a molar yield of 95%.
