CN105566209A - Purifying method of beta-trifluoromethylpyridine chloride - Google Patents

Abstract

The invention provides a method for purifying crude beta-trifluoromethylpyridine chloride through a reduced pressure rectification-melt crystallization coupling technology. The method allows a beta-trifluoromethylpyridine chloride product with the purity being greater than 99% to be obtained.

Description

A kind of refining method of β-trifluoromethylpyridine chloride

technical field

The invention belongs to the field of chemical industry, and in particular relates to a method for refining β-trifluoromethylpyridine chloride by adopting a vacuum distillation-melt crystallization coupling process.

Background technique

β-trifluoromethylpyridine chloride is an important chemical raw material for the preparation of pharmaceuticals, agricultural chemicals and biological agents. In terms of pesticides, 2-chloro-5-trifluoromethylpyridine is a key intermediate for the production of high-efficiency herbicide fluazifop-methyl (trade name Jingwenshade), insecticide pyridalyl and other products, 2, 3-dichloro-5-trifluoromethylpyridine is a key intermediate for the synthesis of the pesticide insecticide difenuron, the herbicide haloxyfop (Gaichonen) and the fungicide fluazinam. These fluorine-containing pesticides have Broad-spectrum systemic absorption, long duration, high efficiency and low toxicity, etc., have been widely used at home and abroad.

There are many methods for synthesizing β-trifluoromethylpyridine chloride, among which the one-step method of simultaneous chlorination and fluorination of 3-methylpyridine in the gas phase has the most industrial value. For one-step fluorine chlorination synthesis in a reactor, for example, it is mentioned in "Synthesis of 2-Chloro-5-trifluoromethylpyridine (2,5-CTF)"("Organic Fluorine Industry" 2010 No. 1) , using CrF ₃ /Al ₂ O ₃ as a catalyst, under the condition that the reaction temperature is 430°C and the catalyst residence time is 7s, 2-chloro-5-trifluoromethylpyridine accounts for 51.5% of the crude product; 《2-chloro -5-Trifluoromethylpyridine Synthesis and Application Research ("Fine and Specialty Chemicals" Volume 12 No. 7) mentions that MnF ₃ /C is used as a catalyst, CCl ₄ is used as a diluent, and the reaction product is washed with water, After alkali washing, drying, and distillation to remove CCl ₄ , the analysis results are: 2-chloro-5-trifluoromethylpyridine content is 38.7%, 2-chloro-3-trifluoromethylpyridine content is 14.8%, 2,6- The content of dichloro-3-trifluoromethylpyridine is 22.8%, and the unknown substance is 22.7%.

Due to the difficulty in positioning the chlorination of the pyridine ring, the one-step chlorination and fluorination of 3-picoline has the problems of many by-products, similar boiling points, and difficult purification. US7502279A, CN201210395552.8, US12475780A and other related synthesis patents only mention the separation of products by rectification and other commonly used methods, but the following problems exist when vacuum distillation is used for purification: there are many impurity components and isomers The impurity content is high, it is difficult to obtain high-purity β-trifluoromethylpyridine chloride product (≥99%); a lot of heavy components, tar and solid coke remain in the tower kettle when the rectification ends; the required number of plates Many, high reflux ratio, high energy consumption in the rectification process.

Therefore, it is of great significance to develop a refining method for β-trifluoromethylpyridine chloride.

Contents of the invention

The object of the present invention is to provide a method for refining β-trifluoromethylpyridine chloride with low energy consumption, high yield, high product purity and environmental protection.

The β-trifluoromethylpyridine chloride of the present invention has the following structural formula (I), wherein: X ₁ , X ₂ , X ₃ and X ₄ are independently selected from H or Cl.

For achieving the purpose of the invention, the technical scheme adopted by the present invention is:

A method for refining β-trifluoromethylpyridine chloride, which comprises the steps of refining β-trifluoromethylpyridine chloride by melting crystallization:

(a) The temperature of the crystallizer is raised to 1-5°C above the melting point of β-trifluoromethylpyridine chloride, and the crude product of β-trifluoromethylpyridine chloride is introduced and kept at a constant temperature for 15 minutes to 60 minutes;

(b) cooling down to 4-20°C below the freezing point of β-trifluoromethylpyridine chloride, keeping for 2-5 hours, then discharging the uncrystallized mother liquor, adding β-trifluoromethylpyridine chloride seed crystals while cooling down;

(c) Increase the temperature to make the crystal sweat and discharge sweat;

(d) Raising the temperature of the crystallizer to above the melting point of β-trifluoromethylpyridine chloride to melt the crystal layer to obtain high-purity β-trifluoromethylpyridine chloride.

In the above step (b), as a preferred mode, the cooling rate is 0.02 to 0.1 °C/min, and the temperature is lowered to 4 to 20 °C below the freezing point of β-trifluoromethylpyridine chloride; as a further preferred mode, the cooling rate 0.05-0.08°C/min, and β-trifluoromethylpyridine chloride seed crystals are added at ±1-3°C of the freezing point of β-trifluoromethylpyridine chloride.

In the above step (c), as a preferred mode, the sweating temperature rise rate is 0.03-0.1 °C/min, and the sweating temperature is raised to ±0-5 °C of the melting point of β-trifluoromethylpyridine chloride; as a further preferred mode, sweating The heating rate is 0.06-0.08°C/min.

As a preferred mode, the mother liquor and sweat obtained in the above steps (b) and (c) are recycled to the vacuum distillation step as feed.

The β-trifluoromethylpyridine chloride crude product in the above-mentioned step (a) can be obtained by vacuum distillation, comprising the following steps:

Put the mixture containing β-trifluoromethylpyridine chloride into the rectification tower for vacuum rectification, the rectification pressure is 5-20kPa, the rectification reflux ratio is 3-30, and β-trifluoromethylpyridine is collected from the top of the tower Crude picoline chloride.

As a preferred mode, the rectification pressure is 10-15kPa, the rectification reflux ratio is first controlled to 3-15, and then 10-30; as a further preferred mode, the rectification reflux ratio is first controlled to 6-10 , and then controlled to 15-20. .

As a preferred mode, in the refining method of β-trifluoromethylpyridine chloride described in the present invention, it is preferred to adopt a vacuum distillation-melt crystallization coupling process to purify the β-trifluoromethylpyridine chloride product, that is The crude product of β-trifluoromethylpyridine chloride is preliminarily separated by rectification under reduced pressure, and then further refined by melting crystallization.

The refining method provided by the invention has the following advantages:

(1) The purity of the obtained target product β-trifluoromethylpyridine chloride is higher than 99%, and the maximum impurity content is less than 0.2%, which can meet the requirements for the preparation of pharmaceuticals, agricultural chemicals and biological agents;

(2) Through the coupling of rectification and crystallization, the mother liquor and sweat discharged from the crystallization process are recycled, which greatly improves the yield compared with a single crystallization process.

detailed description

The present invention will be further described below in conjunction with specific examples, but the present invention is not limited to these specific implementations. Those skilled in the art will realize that the present invention covers all alternatives, modifications and equivalents as may be included within the scope of the claims.

The yield per pass of the product in the following examples=(product quality×product purity)/(crystallization raw material quality×crystallization raw material purity).

Embodiment 1: vacuum distillation

The product of 2-chloro-5-trifluoromethylpyridine obtained by gas-phase fluorination and chlorination of 3-picoline was used as a raw material for batch distillation experiments. The mass content of the main substance in the product is: 3-trifluoromethyl Pyridine 4.3%, 2-chloro-5-trifluoromethylpyridine 28.1%, 2-chloro-3-trifluoromethylpyridine 10.6%, 2,3-dichloro-5-trifluoromethylpyridine 4.0%, others 53.0%.

Take 567g of the above-mentioned product in a three-neck flask, connect a rectification column with a length of 1.4m and a diameter of 5cm to the flask, add zeolite into the flask and start heating, the liquid starts to reflux after boiling, and the top of the tower begins to be extracted after 1 hour of reflux Fractions, the fractions with a boiling point of 98-103°C were collected. The pressure of the rectification process is about 15kPa, the reflux ratio is controlled to be 6-10 in the early stage, and 10-20 in the later stage. Through gas chromatographic analysis, the content of the main substances in the cuts collected is: the mass fraction of 2-chloro-5-trifluoromethylpyridine is 86.8% (its recovery rate at the top of the tower is 79.6%), 3-chloro-5- The mass fraction of trifluoromethylpyridine is 2.8%, and the mass fraction of 2-chloro-3-trifluoromethylpyridine is 1.7%.

Embodiment 2: vacuum distillation

The product of 2-chloro-5-trifluoromethylpyridine obtained by gas-phase fluorination and chlorination of 3-picoline was used as a raw material for batch distillation experiments. The mass content of the main substance in the product is: 3-trifluoromethyl Pyridine 4.3%, 2-chloro-5-trifluoromethylpyridine 28.1%, 2-chloro-3-trifluoromethylpyridine 10.6%, 2,3-dichloro-5-trifluoromethylpyridine 4.0%, others 53.0%.

Take 267g of the above-mentioned product in a three-necked flask, connect a rectification column with a length of 1.4m and a diameter of 5cm to the flask, add zeolite to the flask and start heating, the liquid starts to reflux after boiling, and the top of the tower begins to be extracted after 1 hour of reflux Fractions, the fractions with a boiling point of 104-107°C were collected. The pressure of the rectification process is about 15kPa, the reflux ratio is controlled to be 6-15 in the early stage, and 10-20 in the later stage. Through gas chromatography analysis, the content of main substances in the collected fractions is: the mass fraction of 2-chloro-3-trifluoromethylpyridine is 90.2%, the mass fraction of 2-chloro-5-trifluoromethylpyridine is 2.3% , The mass fraction of 2,3-dichloro-5-trifluoromethylpyridine is 1.4%.

Embodiment 3: vacuum distillation

The product of 2-chloro-5-trifluoromethylpyridine obtained by gas-phase fluorination and chlorination of 3-picoline was used as a raw material for batch distillation experiments. The mass content of the main substance in the product is: 3-trifluoromethyl Pyridine 4.3%, 2-chloro-5-trifluoromethylpyridine 28.1%, 2-chloro-3-trifluoromethylpyridine 10.6%, 2,3-dichloro-5-trifluoromethylpyridine 4.0%, others 53.0%.

Take 267g of the above-mentioned product in a three-necked flask, connect a rectification column with a length of 1.4m and a diameter of 5cm to the flask, add zeolite to the flask and start heating, the liquid starts to reflux after boiling, and the top of the tower begins to be extracted after 1 hour of reflux Fractions, the fractions with a boiling point of 105-107°C were collected. The pressure of the rectification process is about 10kPa, the reflux ratio is controlled to be 6-15 in the early stage, and 15-30 in the later stage. According to gas chromatography analysis, the content of the main substances in the collected fractions was: 2,3-dichloro-5-trifluoromethylpyridine with a mass fraction of 92.4%.

Example 4: Melt crystallization

Take 30 g of the crude 2-chloro-5-trifluoromethylpyridine prepared in Example 1 and place it in a glass sleeve-type crystallizer. The inner tube of the crystallizer has a diameter of 25 mm and a length of 200 mm, and an outer tube of diameter 35 mm and a length of 160 mm. Raise the temperature of the crystallizer to 30°C for 0.5h, then cool down to 24°C at a cooling rate of 0.07°C/min, add a small amount of 2-chloro-5-trifluoromethylpyridine seed crystals from the top of the crystallizer, and continue to cool at 0.07°C /min cooling rate down to 18 ℃, constant temperature 4h. Open the valve at the bottom of the crystallizer to discharge the uncrystallized mother liquor, and the quality of the mother liquor is 30% of the crude crystal. After the mother liquor is drained, the crystallizer is heated up to sweat at a rate of 0.08°C/min, and the sweating temperature is 35°C. Sweat is released and collected together with the mother liquor as a raw material for vacuum distillation. After the sweating process is over, the temperature of the crystallizer is raised to 40° C. to melt the crystals to obtain 15.3 g of the product. After analysis by gas chromatography, the concentration of 2-chloro-5-trifluoromethylpyridine in the product was 98.8%, and the single-pass crystallization yield was 58.2%.

Example 5: Melt crystallization

Crystallizer is with embodiment 4. Take 15g of the crude 2-chloro-5-trifluoromethylpyridine prepared in Example 1 in a crystallizer, raise the temperature of the crystallizer to 30°C for 0.5h, and then cool down to 24°C at a cooling rate of 0.07°C/min. Add a small amount of 2-chloro-5-trifluoromethylpyridine seed crystals from the top of the crystallizer, continue cooling down to 16°C at a cooling rate of 0.07°C/min, and keep the temperature constant for 4h. Open the valve at the bottom of the crystallizer to discharge the uncrystallized mother liquor, and the quality of the mother liquor is 22% of the crude crystal. After the mother liquor is drained, the crystallizer is heated up to sweat at a rate of 0.06°C/min, and the sweating temperature is 28°C. Sweat is released and collected together with the mother liquor as a raw material for vacuum distillation. After the sweating process is over, the temperature of the crystallizer is raised to 40° C. to melt the crystals to obtain 6.4 g of the product. After analysis by gas chromatography, the concentration of 2-chloro-5-trifluoromethylpyridine in the product was 99.1%, and the single-pass crystallization yield was 48.5%.

Example 6: Melt crystallization

Crystallizer is with embodiment 4. Take 20 g of the crude 2-chloro-5-trifluoromethylpyridine prepared in Example 1 in a crystallizer, raise the temperature of the crystallizer to 30° C. for 0.5 h, and then cool down to 24° C. at a cooling rate of 0.07° C./min. Add a small amount of 2-chloro-5-trifluoromethylpyridine seed crystals from the top of the crystallizer, continue cooling down to 18°C at a cooling rate of 0.07°C/min, and keep the temperature constant for 4h. Open the valve at the bottom of the crystallizer to discharge the uncrystallized mother liquor, and the quality of the mother liquor is 30% of the crude crystal. After the mother liquor is drained, the crystallizer is heated up to sweat at a rate of 0.06°C/min, and the sweating temperature is 30°C. Sweat is released and collected together with the mother liquor as a raw material for vacuum distillation. After the sweating process was over, the temperature of the crystallizer was raised to 40° C. to melt the crystals to obtain 7.4 g of the product. After analysis by gas chromatography, the concentration of 2-chloro-5-trifluoromethylpyridine in the product was 99.4%, and the single-pass crystallization yield was 42.3%.

Example 7: Melt crystallization

Crystallizer is with embodiment 4. Get 567g rectification raw material (the mass content of main substance is: 3-trifluoromethylpyridine 4.3%, 2-chloro-5-trifluoromethylpyridine 28.1%, 2-chloro-3-trifluoromethylpyridine 10.6% , 2,3-dichloro-5-trifluoromethylpyridine 4.0%, other 53.0%.), carry out rectification under reduced pressure according to the method of Example 1, the 2-chloro-5-trifluoromethylpyridine of gained Put all the crude product into the crystallizer, raise the temperature of the crystallizer to 30°C for 0.5h, then cool down to 24°C at a cooling rate of 0.07°C/min, add a small amount of 2-chloro-5-trifluoromethylpyridine from the top of the crystallizer For the seed crystal, continue to cool down to 18°C at a cooling rate of 0.07°C/min, and keep the temperature constant for 4h. Open the valve at the bottom of the crystallizer to discharge the uncrystallized mother liquor, and the quality of the mother liquor is 30% of the crude crystal. After the mother liquor is drained, the crystallizer is heated up to sweat at a rate of 0.06°C/min, and the sweating temperature is 30°C. Sweat is released and collected together with the mother liquor as a raw material for vacuum distillation.

The obtained sweat and mother liquor are passed into the rectification tower together with the raw material of 567g rectification under vacuum obtained in addition, the rectification under vacuum step described in Example 1 is repeated, and the cut obtained at the top of the tower repeats the aforementioned melt crystallization operation again, 104.2 g of product were obtained. Define the cycle yield of the product = (the quality of the product obtained by crystallization after recycling × the product purity) / (the quality of the rectification raw material × the purity of the rectification raw material). After analysis by gas chromatography, the concentration of 2-chloro-5-trifluoromethylpyridine in the crystallized product was 99.4%, and the cycle yield of 2-chloro-5-trifluoromethylpyridine was 65.0%.

Example 8: Melt crystallization

Crystallizer is with embodiment 4. Take 18g of the crude 2-chloro-3-trifluoromethylpyridine prepared in Example 2 in a crystallizer, raise the temperature of the crystallizer to 39°C for 0.5h, then cool down to 30°C at a cooling rate of 0.05°C/min, Add a small amount of 2-chloro-3-trifluoromethylpyridine seed crystals from the top of the crystallizer, continue cooling down to 26°C at a cooling rate of 0.05°C/min, and keep the temperature constant for 4h. Open the valve at the bottom of the crystallizer to discharge the uncrystallized mother liquor, and the quality of the mother liquor is 29% of the crude crystal. After the mother liquor is drained, the crystallizer is heated up to sweat at a rate of 0.07°C/min, and the sweating temperature is 38°C. Sweat is released and collected together with the mother liquor as a raw material for vacuum distillation. After the sweating process was over, the temperature of the crystallizer was raised to 45° C. to melt the crystals to obtain 7.9 g of the product. After analysis by gas chromatography, the concentration of 2-chloro-3-trifluoromethylpyridine in the product was 99.2%, and the single-pass crystallization yield was 48.2%.

Example 9: Melt crystallization

Crystallizer is with embodiment 4. Get 15g of the 2,3-dichloro-5-trifluoromethylpyridine crude product obtained in Example 3 in a glass sleeve type crystallizer, the inner tube diameter of the crystallizer is 25mm, and the length is 200mm, and the outer tube diameter is 35mm, and the length is 160mm . Raise the temperature of the crystallizer to 12°C for 0.5h, then cool down to 4°C at a cooling rate of 0.07°C/min, add a small amount of 2,3-dichloro-5-trifluoromethylpyridine seed crystals from the top of the crystallizer, and continue Cool down to -2°C at a cooling rate of 0.07°C/min, and keep the temperature constant for 4 hours. Open the valve at the bottom of the crystallizer to discharge the uncrystallized mother liquor, and the quality of the mother liquor is 25% of the crude crystal. After the mother liquor is drained, the crystallizer is heated up to sweat at a rate of 0.07°C/min, and the sweating temperature is 9°C. Sweat is released and collected together with the mother liquor as a raw material for vacuum distillation. After the sweating process is over, the temperature of the crystallizer is raised to 12° C. to melt the crystals to obtain 7.0 g of the product. After analysis by gas chromatography, the concentration of 2,3-dichloro-5-trifluoromethylpyridine in the product was 99.0%, and the single-pass crystallization yield was 50.2%.

Claims (9)

1. a process for purification for β-5-flumethiazine chloro thing, is characterized in that adopting fusion-crystallization method refining beta-5-flumethiazine chloro thing, comprises the following steps:

A crystallizer is warming up to more than β-5-flumethiazine chloro thing fusing point 1 ~ 5 DEG C by (), pass into β-5-flumethiazine chloro thing crude product and constant temperature 15min ~ 60min;

B () is cooled to 4 ~ 20 DEG C, below β-5-flumethiazine chloro thing zero pour, discharge uncrystallized mother liquor, add β-5-flumethiazine chloro thing crystal seed while wherein lowering the temperature after keeping 2 ~ 5h;

C () raised temperature makes crystal sweating, discharge sweat;

D crystallizer is warming up to more than β-5-flumethiazine chloro thing fusing point by (), crystal layer is melted, and obtains highly purified β-5-flumethiazine chloro thing.

2. according to the process for purification of β according to claim 1-5-flumethiazine chloro thing, it is characterized in that, in described step (b), rate of temperature fall is 0.02 ~ 0.1 DEG C/min, be cooled to 4 ~ 20 DEG C, below β-5-flumethiazine chloro thing zero pour.

3. according to the process for purification of β according to claim 2-5-flumethiazine chloro thing, it is characterized in that described rate of temperature fall is 0.05 ~ 0.08 DEG C/min, β-5-flumethiazine chloro thing zero pour ± 1 ~ 3 DEG C add β-5-flumethiazine chloro thing crystal seed.

4. according to the process for purification of β according to claim 1-5-flumethiazine chloro thing, it is characterized in that in described step (c), sweating temperature rise rate is 0.03 ~ 0.1 DEG C/min, sweating be warming up to β-5-flumethiazine chloro thing fusing point ± 0 ~ 5 DEG C.

5., according to the process for purification of β according to claim 4-5-flumethiazine chloro thing, it is characterized in that described sweating temperature rise rate is 0.06 ~ 0.08 DEG C/min.

6., according to the process for purification of β according to claim 1-5-flumethiazine chloro thing, it is characterized in that the β-5-flumethiazine chloro thing crude product in described step (a) is obtained by rectification under vacuum, comprise the following steps:

Mixture containing β-5-flumethiazine chloro thing is added rectifying tower and carries out rectification under vacuum, rectifying pressure is 5 ~ 20kPa, and rectifying reflux ratio is 3 ~ 30, collects obtain β-5-flumethiazine chloro thing crude product from tower top.

7. according to the process for purification of β according to claim 6-5-flumethiazine chloro thing, it is characterized in that described rectifying pressure is 10 ~ 15kPa, it is 3 ~ 15 that rectifying reflux ratio first controls, control again to be 10 ~ 30.

8., according to the process for purification of β according to claim 7-5-flumethiazine chloro thing, it is characterized in that described rectifying reflux ratio first to control be 6 ~ 10, control again to be 15 ~ 20.

9., according to the process for purification of β according to claim 6-5-flumethiazine chloro thing, it is characterized in that the mother liquor that obtains in described step (b) and (c) and sweat are circulated to rectification under vacuum step as charging.