CN102924370A - 2-amino-5-methylpyridine preparation method - Google Patents

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

A kind of preparation method of 2-amino-5-picoline

technical field

The invention relates to a preparation method of 2-amino-5-picoline intermediate of dyestuff, medicine and pesticide. the

Background technique

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;

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

The purpose of the present invention is to provide a new preparation method of 2-amino-5-picoline with high yield and purity. the

The present invention provides a preparation method for the compound shown in formula (I), the structure of formula (I) is shown in Figure 1:

The structure of Fig. 1 formula (I);

The present invention is characterized in that: add a certain amount of one or more organic solvents, 2-chloro-5-picoline, liquid ammonia and catalyst into the autoclave, heat to a certain temperature and a certain pressure to react, and react for a certain period of time , stop responding. Cool, depressurize, and ventilate to drive out excess ammonia. Evaporate a large amount of organic solvent, lower the temperature, add an appropriate amount of water, stir, extract with toluene, dry, concentrate, evaporate the product under reduced pressure, and cool to obtain the compound of formula (I). the

Detailed disclosure of the present invention:

The reaction catalyst is Cu powder, monovalent and divalent copper salt, more preferably Cu powder and CuSO ₄ ; the catalyst dosage is 0.5-20g/100g 2-chloro-5-picoline, more preferably 3-5g/100g 2-chloro -5-picoline; the reaction solvent is one or more mixtures of alcohols, more preferably methanol, ethanol and isopropanol. The mass ratio of 2-chloro-5-picoline to organic solvent is 1:1-20, more preferably 1:10; the reaction temperature range is 50-250°C, more preferably 145-155°C; the reaction pressure range is 1.0- 10.0MPa, more preferably 3.5-4.5MPa; the reaction time range is 1-20 hours, more preferably 7-9 hours.

specific embodiment

The following examples are to illustrate the present invention in detail, but not to limit the present invention. the

Example 1

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 CuSO ₄ were added. 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 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 obtain 0.973Kg of a white solid with a yield of 90%.

Example 2

Into a 5-liter autoclave, 1.275Kg of 2-chloro-5-picoline, 2.1Kg of absolute ethanol, 1.25Kg of liquid ammonia, and 51g of CuSO ₄ were added. 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 for extraction 3 times. The organic phases were combined and dried over anhydrous sodium sulfate. , filtered, concentrated, recovered toluene, and evaporated the product under reduced pressure from the raffinate, and cooled to obtain 0.951Kg of a white solid, with a yield of 88%.

Example 3

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 (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. 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 white solid, with a yield of 92%.

Example 4

1.275Kg of 2-chloro-5-picoline, 1.9Kg of methanol, 1.25Kg of liquid ammonia were pumped into a 5-liter autoclave, and 63.7g of Cu(OAc) ₂ was added. Turn on the stirring, turn on the electric heating of the jacket, set the temperature at 145°C (the equipment is automatically kept warm), when the temperature in the kettle reaches 145°C, the pressure is 3.8MPa, react for 9 hours, stop heating, cool to 40°C, and discharge the pressure. Inject air to catch the ammonia for more than 2 hours until the ammonia gas is gone. Distill 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, and evaporated the product from the raffinate under reduced pressure, and cooled to obtain 0.918Kg of white solid, with a yield of 85%.

Claims (7)

1. a preparation method of 2-amino-5-picoline, is characterized in that comprising the steps: Using copper powder or copper compound as catalyst, in the presence of organic solvent, ammonolysis of 2-chloro-5-methylpyridine and liquid ammonia at 145-155°C and pressure of 3.5-4.5MPa, cooling down, depressurization, air ammonia catchment , remove a large amount of organic solvent by distillation, lower the temperature, add an appropriate amount of water, stir, extract with toluene, dry, concentrate, evaporate the product under reduced pressure, and cool to obtain the compound of formula (I). 2. The preparation method according to claim 1, characterized in that the optional catalysts are Cu powder, monovalent and divalent copper salts, specifically including: Cu powder, CuSO ₄ , CuO, Cu ₂ O, copper acetate, alkali Various organic copper salts or inorganic copper salts such as copper carbonate and copper nitrate, more preferably Cu powder and CuSO ₄ . 3. The preparation method according to claim 1, characterized in that the optional organic solvent is one or more mixtures of alcohols, more preferably methanol, ethanol and isopropanol; 2-chloro-5-picoline The mass ratio to the organic solvent is 1:1-20, more preferably 1:10. 4. according to the preparation method described in claim 1,2, wherein the consumption of Cu powder or CuSO ₄ is 0.5-20g/100g2-chloro-5-picoline, more preferably 3-5g/100g2-chloro-5-methylpyridine base pyridine. 5. The preparation method according to claim 1, the reaction temperature range is 50-250°C, more preferably 145-155°C. 6. The preparation method according to claim 1, the reaction pressure range is 1.0-10.0 MPa, more preferably 3.5-4.5 MPa. 7. The preparation method according to claim 1, the reaction time range is 1-20 hours, more preferably 7-9 hours.

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