2-amino-5-methylpyridine preparation method

Abstract

The present invention relates to a method for efficiently preparing a compound represented by a formula (I), wherein 2-chloro-5-methylpyridine is adopted as a raw material, copper powder or a copper compound is adopted as a catalyst in the presence of an organic solvent, aminolysis is performed at a temperature of 145-155 DEG C under pressure of 3.5-4.0 MPa, and a post-treatment is performed to obtain the compound represented by the formula (I). The preparation method has characteristics of simple process, high product purity and high yield.

Description

technical field

[0001] The invention relates to a preparation method of 2-amino-5-picoline intermediate of dyestuff, medicine and pesticide. Background technique

[0002] 2-Amino-5-picoline is an important intermediate in the synthesis of dyes, drugs and pesticides. Since the 1990s, it has mainly been used as an intermediate to develop and synthesize new high-efficiency, broad-spectrum, and low-toxicity neonicotinoid insecticides such as pyridoxine, ethimid, Tl-304, and pyridoxone insect growth regulators, pyridoxone and NC-184. Wait;

[0003] The usual preparation method of 2-amino-5-picoline is: under the protection of nitrogen, 3-picoline and sodium amide are reacted with zizibabine, followed by hydrolysis (JP5820803, US4386209 and US4405790). This type of preparation method inevitably produces 13%-22% by-product 2-amino-3-picoline, which is not easy to separate, the yield is not high, and the risk of hydrolysis of sodium amide is high. Contents of the invention [...

Examples

Embodiment 1

[0012] Into a 5-liter autoclave, pump 1.275Kg of 2-chloro-5-picoline, 1.9Kg of methanol, 1.25Kg of liquid ammonia, and add CuSO 4 63.7g. Turn on the stirring, turn on the electric heating of the jacket, set the temperature at 150°C (the equipment is automatically kept warm), when the temperature in the kettle reaches 150°C, the pressure is 4MPa, react for 8 hours, stop heating, cool to 40°C, discharge the pressure, and ventilate Into the air to catch the ammonia for more than 2 hours, until the ammonia is gone. Distill the methanol out of the reaction liquid under normal pressure. When the methanol content is less than 10%, stop the distillation, lower the temperature to 40°C, add an appropriate amount of water to the kettle, stir for 10 minutes, add toluene for extraction 3 times, combine the organic phases, and dry over anhydrous sodium sulfate. , filtered, concentrated, recovered toluene, evaporated the product under reduced pressure from the raffinate, and cooled to obta...

Embodiment 2

[0014] Into a 5-liter autoclave, pump 1.275Kg of 2-chloro-5-picoline, 2.1Kg of absolute ethanol, 1.25Kg of liquid ammonia, and add CuSO 4 51g. Turn on the stirring, turn on the electric heating of the jacket, set the temperature at 150°C (the equipment is automatically kept warm), when the temperature in the kettle reaches 150°C, the pressure is 4MPa, react for 8 hours, stop heating, cool to 40°C, discharge the pressure, and ventilate Into the air to catch the ammonia for more than 2 hours, until the ammonia is gone. Ethanol was evaporated from the reaction liquid under normal pressure. When the ethanol content was less than 10%, the distillation was stopped, the temperature was lowered to 40°C, an appropriate amount of water was added to the kettle, stirred for 10 minutes, and toluene was added to extract 3 times. The organic phases were combined and dried over anhydrous sodium sulfate. , filtered, concentrated, recovered toluene, and evaporated the product under reduced pr...

Embodiment 3

[0016] Into a 5-liter autoclave, 1.275Kg of 2-chloro-5-picoline, 1.9Kg of methanol, 1.25Kg of liquid ammonia, and 63.7g of Cu powder were added. Turn on the stirring, turn on the electric heating of the jacket, set the temperature at 150°C (automatic insulation of the equipment), when the temperature in the kettle reaches 150°C, the pressure is 4MPa, react for 8 hours, stop heating, cool to 40°C, discharge the pressure, and ventilate Into the air to catch the ammonia for more than 2 hours, until the ammonia is gone. Filter and distill methanol out of the filtrate under normal pressure. When the methanol content is less than 10%, stop the distillation, lower the temperature to 40°C, add an appropriate amount of water to the kettle, stir for 10 minutes, add toluene for extraction 3 times, combine the organic phases, anhydrous sodium sulfate Dry, filter, concentrate, recover toluene, evaporate the product under reduced pressure from the residue, and cool to obtain 0.994Kg of whit...

technical field

[0001] The invention relates to a preparation method of 2-amino-5-picoline intermediate of dyestuff, medicine and pesticide. Background technique

[0002] 2-Amino-5-picoline is an important intermediate in the synthesis of dyes, drugs and pesticides. Since the 1990s, it has mainly been used as an intermediate to develop and synthesize new high-efficiency, broad-spectrum, and low-toxicity neonicotinoid insecticides such as pyridoxine, ethimid, Tl-304, and pyridoxone insect growth regulators, pyridoxone and NC-184. Wait;

[0003] The usual preparation method of 2-amino-5-picoline is: under the protection of nitrogen, 3-picoline and sodium amide are reacted with zizibabine, followed by hydrolysis (JP5820803, US4386209 and US4405790). This type of preparation method inevitably produces 13%-22% by-product 2-amino-3-picoline, which is not easy to separate, the yield is not high, and the risk of hydrolysis of sodium amide is high. Contents of the invention [...

Examples

Embodiment 1

[0012] Into a 5-liter autoclave, pump 1.275Kg of 2-chloro-5-picoline, 1.9Kg of methanol, 1.25Kg of liquid ammonia, and add CuSO 4 63.7g. Turn on the stirring, turn on the electric heating of the jacket, set the temperature at 150°C (the equipment is automatically kept warm), when the temperature in the kettle reaches 150°C, the pressure is 4MPa, react for 8 hours, stop heating, cool to 40°C, discharge the pressure, and ventilate Into the air to catch the ammonia for more than 2 hours, until the ammonia is gone. Distill the methanol out of the reaction liquid under normal pressure. When the methanol content is less than 10%, stop the distillation, lower the temperature to 40°C, add an appropriate amount of water to the kettle, stir for 10 minutes, add toluene for extraction 3 times, combine the organic phases, and dry over anhydrous sodium sulfate. , filtered, concentrated, recovered toluene, evaporated the product under reduced pressure from the raffinate, and cooled to obta...

Embodiment 2

[0014] Into a 5-liter autoclave, pump 1.275Kg of 2-chloro-5-picoline, 2.1Kg of absolute ethanol, 1.25Kg of liquid ammonia, and add CuSO 4 51g. Turn on the stirring, turn on the electric heating of the jacket, set the temperature at 150°C (the equipment is automatically kept warm), when the temperature in the kettle reaches 150°C, the pressure is 4MPa, react for 8 hours, stop heating, cool to 40°C, discharge the pressure, and ventilate Into the air to catch the ammonia for more than 2 hours, until the ammonia is gone. Ethanol was evaporated from the reaction liquid under normal pressure. When the ethanol content was less than 10%, the distillation was stopped, the temperature was lowered to 40°C, an appropriate amount of water was added to the kettle, stirred for 10 minutes, and toluene was added to extract 3 times. The organic phases were combined and dried over anhydrous sodium sulfate. , filtered, concentrated, recovered toluene, and evaporated the product under reduced pr...

Embodiment 3

[0016] Into a 5-liter autoclave, 1.275Kg of 2-chloro-5-picoline, 1.9Kg of methanol, 1.25Kg of liquid ammonia, and 63.7g of Cu powder were added. Turn on the stirring, turn on the electric heating of the jacket, set the temperature at 150°C (automatic insulation of the equipment), when the temperature in the kettle reaches 150°C, the pressure is 4MPa, react for 8 hours, stop heating, cool to 40°C, discharge the pressure, and ventilate Into the air to catch the ammonia for more than 2 hours, until the ammonia is gone. Filter and distill methanol out of the filtrate under normal pressure. When the methanol content is less than 10%, stop the distillation, lower the temperature to 40°C, add an appropriate amount of water to the kettle, stir for 10 minutes, add toluene for extraction 3 times, combine the organic phases, anhydrous sodium sulfate Dry, filter, concentrate, recover toluene, evaporate the product under reduced pressure from the residue, and cool to obtain 0.994Kg of whit...

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