2-amino-3-pyridone as well as preparation method and preparation method thereof

Abstract

The invention provides 2-amino-3-pyridone as well as a preparation method and a preparation method thereof, and relates to the field of chemical reagent analysis. The preparation method of the 2-amino-3-pyridone comprises the following steps of introducing chlorine gas or bromine into a furfural water solution to perform loop opening reaction; reacting obtained mixed liquid with an ammonia sulfamate solution to obtain 2-amino-3-pyridone sulfonate; hydrolyzing the 2-amino-3-pyridone sulfonate under the basic condition to obtain brown 2-amino-3-pyridone with the yield being higher than 75 percent. The yield is effectively improved. The furfural is used as raw materials; the cost is effectively reduced. Through refining by a refining method provided by the invention, the white 2-amino-3-pyridone is obtained; the yield of the white 2-amino-3-pyridone is greater than or equal to 70 percent; the purity is higher than 99 percent.

Description

technical field

[0001] The application relates to the field of chemical reagent synthesis, in particular, to a 2-amino-3-hydroxypyridine and its preparation method and purification method. Background technique

[0002] 2-Amino-3-hydroxypyridine has a wide range of uses, mainly used as pharmaceutical intermediates, such as the preparation of prostate synthase inhibitors, anti-inflammatory drugs, painkillers, antipyretic and pain-relieving tablets, and raw materials for antibacterial drugs; it is also used for the preparation of veterinary drug methyl Pyridinephos; used in the preparation of 2-(BOC-amino)-3-hydroxypyridine; it is also a major ingredient in hair dyes.

[0003] At present, there are two main methods for the preparation of 2-amino-3-hydroxypyridine: 2-nitro-3-hydroxypyridine hydrogenation reduction method, and 3-hydroxypyridine high-pressure ammonia ratio method. The common characteristics of these two methods are The price of the raw material is high, and the y...

Examples

Embodiment 1

[0041] A preparation method of brown 2-amino-3-hydroxypyridine, which comprises:

[0042]Add 350g of water into the first reaction vessel, add 20g of furfural, stir and cool down to 0°C, and start to introduce chlorine gas to carry out the ring-opening reaction. The conditions of the ring-opening reaction include: introducing chlorine gas under continuous stirring, while keeping the reaction temperature at 0-10°C, and the rate of introducing chlorine gas at 2.5-3g / 10min, wherein furfural is added every 20 minutes after the chlorine gas is passed. , add three times altogether, add 10g each time, during, feed chlorine 37g altogether.

[0043] Transfer the mixed liquid agent obtained after the ring-opening reaction to the second reaction container, drop the liquid alkali after cooling to 0°C, adjust the pH of the mixed liquid agent to keep at 1.5-2, and keep the pH of the mixed liquid agent at 1.5-2 The temperature of the mixed solution is 0-10°C, and the time for dropping is ab...

Embodiment 2

[0050] A white 2-amino-3-hydroxypyridine obtained by refining the brown 2-amino-3-hydroxypyridine provided in Example 1 by the following refining method, the refining method comprising:

[0051] Add 45g of brown 2-amino-3-hydroxypyridine obtained in Example 1 into the fourth reaction vessel, add 200ml of dimethylformamide, heat up to 100°C±2°C for 30min, filter while it is hot, and add the filtrate to the fifth In the reaction vessel, the temperature was rapidly cooled to -5°C using an ice-salt bath, and filtered to obtain a white solid.

[0052] Add all the white solid to the sixth reaction vessel, add 200ml of methanol to raise the temperature and reflux for 1 hour, cool down to -5°C, filter, and dry to obtain dry white 2-amino-3-hydroxypyridine.

[0053] Among them, 40g of dry white 2-amino-3-hydroxypyridine has a melting point of 172-174°C. As determined by high performance liquid chromatography, the purity of white 2-amino-3-hydroxypyridine is 99.9%. Calculated, the yiel...

Embodiment 3

[0055] A kind of preparation method of brown 2-amino-3 hydroxypyridine, it comprises:

[0056] Add 370g of water into the first reaction vessel, add 19g of furfural, stir and cool down to 0°C, and start to introduce chlorine gas to carry out the ring-opening reaction. The conditions of the ring-opening reaction include: feeding chlorine gas under continuous stirring, while keeping the reaction temperature at 0-8°C, and the feeding rate of chlorine gas is 2.6-3g / 10min, in which furfural is added every 20 minutes after the chlorine gas feeding , add four times altogether, add 8g each time, during, feed chlorine 39g altogether.

[0057] Transfer the mixed liquid agent obtained after the ring-opening reaction to the second reaction container, drop the liquid alkali after cooling to 0°C, adjust the pH of the mixed liquid agent to keep at 1.5-2, and keep the pH of the mixed liquid agent at 1.5-2 The temperature of the mixed solution is 0-8°C, and the time for dropping is about 2 ho...

technical field

[0001] The application relates to the field of chemical reagent synthesis, in particular, to a 2-amino-3-hydroxypyridine and its preparation method and purification method. Background technique

[0002] 2-Amino-3-hydroxypyridine has a wide range of uses, mainly used as pharmaceutical intermediates, such as the preparation of prostate synthase inhibitors, anti-inflammatory drugs, painkillers, antipyretic and pain-relieving tablets, and raw materials for antibacterial drugs; it is also used for the preparation of veterinary drug methyl Pyridinephos; used in the preparation of 2-(BOC-amino)-3-hydroxypyridine; it is also a major ingredient in hair dyes.

[0003] At present, there are two main methods for the preparation of 2-amino-3-hydroxypyridine: 2-nitro-3-hydroxypyridine hydrogenation reduction method, and 3-hydroxypyridine high-pressure ammonia ratio method. The common characteristics of these two methods are The price of the raw material is high, and the y...

Examples

Embodiment 1

[0041] A preparation method of brown 2-amino-3-hydroxypyridine, which comprises:

[0042]Add 350g of water into the first reaction vessel, add 20g of furfural, stir and cool down to 0°C, and start to introduce chlorine gas to carry out the ring-opening reaction. The conditions of the ring-opening reaction include: introducing chlorine gas under continuous stirring, while keeping the reaction temperature at 0-10°C, and the rate of introducing chlorine gas at 2.5-3g / 10min, wherein furfural is added every 20 minutes after the chlorine gas is passed. , add three times altogether, add 10g each time, during, feed chlorine 37g altogether.

[0043] Transfer the mixed liquid agent obtained after the ring-opening reaction to the second reaction container, drop the liquid alkali after cooling to 0°C, adjust the pH of the mixed liquid agent to keep at 1.5-2, and keep the pH of the mixed liquid agent at 1.5-2 The temperature of the mixed solution is 0-10°C, and the time for dropping is ab...

Embodiment 2

[0050] A white 2-amino-3-hydroxypyridine obtained by refining the brown 2-amino-3-hydroxypyridine provided in Example 1 by the following refining method, the refining method comprising:

[0051] Add 45g of brown 2-amino-3-hydroxypyridine obtained in Example 1 into the fourth reaction vessel, add 200ml of dimethylformamide, heat up to 100°C±2°C for 30min, filter while it is hot, and add the filtrate to the fifth In the reaction vessel, the temperature was rapidly cooled to -5°C using an ice-salt bath, and filtered to obtain a white solid.

[0052] Add all the white solid to the sixth reaction vessel, add 200ml of methanol to raise the temperature and reflux for 1 hour, cool down to -5°C, filter, and dry to obtain dry white 2-amino-3-hydroxypyridine.

[0053] Among them, 40g of dry white 2-amino-3-hydroxypyridine has a melting point of 172-174°C. As determined by high performance liquid chromatography, the purity of white 2-amino-3-hydroxypyridine is 99.9%. Calculated, the yiel...

Embodiment 3

[0055] A kind of preparation method of brown 2-amino-3 hydroxypyridine, it comprises:

[0056] Add 370g of water into the first reaction vessel, add 19g of furfural, stir and cool down to 0°C, and start to introduce chlorine gas to carry out the ring-opening reaction. The conditions of the ring-opening reaction include: feeding chlorine gas under continuous stirring, while keeping the reaction temperature at 0-8°C, and the feeding rate of chlorine gas is 2.6-3g / 10min, in which furfural is added every 20 minutes after the chlorine gas feeding , add four times altogether, add 8g each time, during, feed chlorine 39g altogether.

[0057] Transfer the mixed liquid agent obtained after the ring-opening reaction to the second reaction container, drop the liquid alkali after cooling to 0°C, adjust the pH of the mixed liquid agent to keep at 1.5-2, and keep the pH of the mixed liquid agent at 1.5-2 The temperature of the mixed solution is 0-8°C, and the time for dropping is about 2 ho...

Images