Preparation background and overview of 5-amino-2-methylpyridine
Pyridine compounds are currently one of the most widely developed and applied varieties among heterocyclic compounds. As an important fine chemical raw material, 5-amino-2-methylpyridine, its derivatives mainly include alkylpyridine, halogenated Substituted pyridine, aminopyridine, bromopyridine, picoline, iodopyridine, chloropyridine, lithium nitropyridine carbonate, hydroxypyridine, benzylpyridine, ethylpyridine, cyanopyridine, fluoropyridine, dihydropyridine, etc., among which Pesticides account for about 50% of the total consumption of 5-amino-2-methylpyridine series products, feed additives account for about 30%, and medicine and other fields account for 20%.
5-amino-2-methylpyridine
Preparation and application of 5-amino-2-methylpyridine
5-Amino-2-methylpyridine is an important pharmaceutical and chemical intermediate and an important raw material for the organic synthesis industry, pharmaceutical industry, rubber industry and agricultural chemical industry. It is widely used in the synthesis and research and development of medicines, pesticides and veterinary drugs, and has high application value and market value.
Preparation of 5-amino-2-methylpyridine
Preparation method 1 of 5-amino-2-methylpyridine:
(1) Dissolve 1.54g (0.01mol) of ethyl 5-(2-methylfuran)carboxylate in 15ml of dimethylformamide, add 0.80g of ammonium chloride (0.015mol) and 0.45g of formamide ( 0.01 mol), vented ammonia, refluxed for 24 hours, added dilute hydrochloric acid to adjust the pH to 2, extracted with ethyl acetate to retain the aqueous phase, added sodium hydroxide solution to the aqueous phase to adjust the pH to neutral, extracted with ether to retain the organic phase, and concentrated After drying, 0.89g of 5-amino-3-hydroxy-2-methylpyridine was obtained, with a yield of 71.8%;
(2) Add 0.89g (0.0072mol) of 5-amino-3-hydroxy-2-methylpyridine, 1.92g of phosphorus trichloride (0.014mol) and 0.73g of dimethylformamide (0.01mol) In 12 ml of dichloroethane, reflux the reaction for 6 hours. Add the concentrated mixture to ice water, add a decolorizing agent, adjust the pH of the filtered solution to neutral, extract the organic phase with ethyl acetate, concentrate and dry to obtain 5-amino- 3-Chloro-2-methylpyridine 0.96g, yield 93.9%;
(3) Mix 0.96g (0.0067mol) of 2-amino-3-chloro-4-methylpyridine and 1.83g (0.015mol) of benzoic acid, add copper powder, react at 150°C for 1 hour, and add the reaction solution Add a decolorizing agent to the water, adjust the pH of the filtered solution to 9, filter, and dry the filter cake to obtain 0.65g of crude yellow solid 5-amino-2-methylpyridine, with a yield of 89.3%.
Dissolve 0.65g of crude 5-amino-2-methylpyridine in dilute hydrochloric acid solution until the crude product is completely dissolved to obtain a salt solution. Add ethyl acetate to the salt solution to extract the remaining water phase, and slowly add it to the water phase. Sodium bicarbonate solution until the pH is 9, the solid precipitates completely, filter, wash the filter cake with distilled water, and vacuum dry to obtain 0.53g of light yellow solid 5-amino-2-methylpyridine, with a yield of 81.5% and a purity of 99.2%.
Preparation method two of 5-amino-2-methylpyridine:
1) Add 90% rubidium carbonate, 21g toluene, 538g metallic sodium, 70g ethanolamine, and 1900g 2-methylpyridine into the autoclave. After tightening the kettle lid, open the feeding port of the kettle lid and the feeding port on the dripping tank. , and open the valve between the dripping tank and the kettle body, put the hose into the bottom of the kettle through the feeding port, replace the air with nitrogen for 1 minute, close the feeding port of the kettle lid, raise the temperature to 60°C, add liquid ammonia dropwise, and control the kettle The internal pressure is 3MPa, and the final amount of liquid ammonia added is 600g. Full response.
2) Raise the temperature to 170°C, fill with nitrogen until the pressure is 5MPa, and fully react. When the pressure in the kettle rises to 5.5MPa, release the pressure to 5MPa. Repeat this operation until the pressure in the kettle no longer rises, which is considered the end of the reaction. Return to room temperature.
3) Take out the ammoniated liquid and slowly add it dropwise to water (9kg). Stir thoroughly for hydrolysis extraction and let stand for liquid separation. The water phase is extracted again with 3L toluene and the oil phase is combined. The oil phase is quantified by gas spectrometry. Among them, 1928g of 5-amino-2-methylpyridine.
