Preparation method of 3-trifluoromethylpyridine

Abstract

The invention provides a preparation method of 3-trifluoromethylpyridine, and relates to the technical field of preparation of trifluoromethylpyridine intermediates. 3-methylpyridine (3MP) and a polar aprotic solvent are mixed and then introduced into a micro-channel reactor to react with fluorine / nitrogen mixed gas, and the product 3-trifluoromethylpyridine (3-TF) is separated from the solvent through a three-stage vacuum distillation process. Compared with the conventional synthesis technology, the method provided by the invention has the advantages of high reaction yield, easiness in operation, low energy consumption, solvent recycling, high economical efficiency and the like.

Description

Technical Field

[0001] The invention relates to the technical field of preparation of trifluoromethylpyridine intermediates, and in particular to a preparation method of 3-trifluoromethylpyridine. Background Art

[0002] 2-Chloro-5-trifluoromethylpyridine and 2-chloro-3-trifluoromethylpyridine are both very important fluorine-containing pyridine chemical raw materials. 2-Chloro-5-trifluoromethylpyridine (abbreviated as 2,5-CTF) is an important trifluoromethylpyridine intermediate used in the preparation of pharmaceuticals, agricultural chemicals and biological preparations. It can be used to prepare many compounds with special uses, such as: 2-amino-5-trifluoromethylpyridine, 2-hydroxy-5-trifluoromethylpyridine, 2,3-dichloro-5-trifluoromethylpyridine, etc. In terms of pesticides, 2-chloro-5-trifluoromethylpyridine is a key intermediate in the production of insecticides, high-efficiency herbicides fluazifop-butyl (trade name: fluazifop-butyl) and pentothrin, and high-efficiency fungicides. These fluorine-containing pesticides have the advantages of broad-spectrum systemic absorption, high efficiency and low toxicity, good safety, and long lasting effect. They are widely used in foreign countries and have broad market prospects. 2-Chloro-3-trifluoromethylpyridine is a key intermediate in the production of the highly effective herbicide pyridinesulfuron-methyl and has a wide range of uses.

[0003] 3-Trifluoromethylpyridine is an important raw material for preparing 2-chloro-5-trifluoromethylpyridine and 2-chloro-3-trifluoromethylpyridine. Regarding the preparation of 3-trifluoromethylpyridine, the prior art US Pat. No. 4,417,055 provides a method for producing 3-trifluoromethylpyridine, using 3-methylpyridine as a raw material in CuF 2 、BiF 2 、SnF 2 3-Trifluoromethylpyridine is prepared under the action of catalysts such as 2-chloro-3-trifluoromethylpyridine and 2-chloro-5-trifluoromethylpyridine. The method has poor selectivity for 3-trifluoromethylpyridine. While generating 3-trifluoromethylpyridine, a large amount of by-products 2-chloro-5-trifluoromethylpyridine, 2-chloro-3-trifluoromethylpyridine and 2,6-dichloro-3-trifluoromethylpyridine are also generated. Example 9 discloses the highest content of 3-trifluoromethylpyridine in the product, which is only 66.9%, and the highest yield is 75.6%. At the same time, in order to achieve a better implementation effect, this method needs to maintain the temperature range at 400-430°C, and the reaction energy consumption is large.

[0004] Therefore, it is necessary to develop a preparation method of 3-trifluoromethylpyridine with high yield and low energy consumption. Summary of the invention

[0005] The object of the present invention is to provide a method for preparing 3-trifluoromethylpyridine, wherein 3-methylpyridine (3MP) and a polar aprotic solvent are mixed in proportion and introduced into a microchannel reactor to react with a fluorine / nitrogen mixed gas, wherein the reaction is an exothermic reaction, and the temperature, pressure, and material residence time are controlled during the process to generate a product 3-trifluoromethylpyridine (3-TF). The reacted material is subjected to a three-stage vacuum distillation process, and ≥99% of the target product 3-TF is obtained at the top of the first stage tower, and the unreacted 3MP and solvent are respectively recovered at the top of the second stage tower and the top of the third stage tower for recycling.

[0006] In order to achieve the above-mentioned purpose of the present invention, the following technical solutions are particularly adopted:

[0007] The present invention provides a method for preparing 3-trifluoromethylpyridine, comprising the following steps:

[0008] (1) mixing 3-methylpyridine and a polar aprotic solvent and introducing the mixture into a microchannel reactor to react with a fluorine / nitrogen mixed gas;

[0009] (2) After the reaction, the unreacted fluorine / nitrogen mixed gas is subjected to tail gas absorption, and the liquid phase is subjected to vacuum distillation to obtain the product 3-trifluoromethylpyridine, and the unreacted 3-methylpyridine and the solvent are recycled.

[0010] Step (1):

[0011] Step (1) comprises:

[0012] Fluorine gas and nitrogen gas are first introduced into the microchannel reactor in proportion to form a fluorine / nitrogen mixed gas, and the temperature and pressure of the reactor are controlled;

[0013] The mixed 3-methylpyridine and polar aprotic solvent are introduced into a microchannel reactor under the action of a horizontal flow metering pump to react with a fluorine / nitrogen mixed gas, and the reaction temperature and pressure as well as the material residence time are controlled.

[0014] In some embodiments, the volume content of fluorine gas in the fluorine / nitrogen mixed gas is 60-80%, preferably 70-75%.

[0015] In some embodiments, after the fluorine / nitrogen mixed gas is introduced, the reactor temperature is controlled to be 25-45° C. and the pressure is controlled to be 0.1-1.0 MPa.

[0016] In some embodiments, the molar ratio of the fluorine / nitrogen mixed gas to 3-methylpyridine is 3:1 to 9:1, preferably 4:1 to 6:1.

[0017] In some embodiments, the polar aprotic solvent is one or more selected from acetonitrile, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether and benzonitrile, preferably diethylene glycol dimethyl ether or a combination thereof with other polar aprotic solvents; the water content of the polar aprotic solvent is below 100 ppm.

[0018] In some embodiments, the mass ratio of 3-methylpyridine to the polar aprotic solvent is 1 to 10:100, preferably 5 to 8:100.

[0019] In some embodiments, the reaction temperature is -25 to 25°C, preferably 0 to 5°C (the reaction process uses a -40°C cold medium for temperature control), the pressure is 0.3 to 1.0 MPa, preferably 0.5 to 0.8 MPa, and the material residence time is 5 to 20 s, preferably 10 to 15 s.

[0020] Microchannel reactor:

[0021] The material is highly corrosive, so silicon carbide is used as the material for the microchannel reactor.

[0022] Step (2):

[0023] In some embodiments, the tail gas absorption adopts a water washing and then alkali washing absorption method, and the alkali washing concentration is controlled at 3% to 5%. The gas phase (HF and fluorine gas) after the industrial design reaction can be recovered or made into 40% hydrofluoric acid for sale.

[0024] In some embodiments, the vacuum distillation is a three-stage vacuum distillation, the pressure of the first tower is -90 to -95 KPa, the top temperature of the first tower is 50 to 55°C, and the bottom temperature of the first tower is 100 to 110°C; the pressure of the second tower is -90 to -95 KPa, the top temperature of the second tower is 55 to 60°C, and the bottom temperature of the second tower is 125 to 145°C; the pressure of the third tower is -90 to -95 KPa, the top temperature of the third tower is 65 to 70°C, and the bottom temperature of the third tower is 145 to 165°C.

[0025] After three-stage vacuum distillation (the second and third towers are mainly used for recycling and reuse), the unreacted 3-methylpyridine (2% to 10%) and polar aprotic solvent can be recovered at the top of the tower and recycled according to the ratio of the two (1% to 10%).

[0026] Technical effects:

[0027] (1) The present invention provides a novel method for preparing 3-trifluoromethylpyridine, which does not use a catalyst, directly uses 3-methylpyridine and fluorine gas as raw materials, and uses a microchannel reaction process. Under the action of a polar aprotic solvent, the gas-liquid contact of the materials is more complete, the residence time is short, and the yield of 3-trifluoromethylpyridine is high;

[0028] (2) The process operating conditions are mild, the reaction pressure and temperature are low, the energy consumption is low, and the safety is high;

[0029] (3) The unreacted material 3MP and solvent are recycled, which saves costs and is environmentally friendly.

[0030] The present invention has been described in detail above, but the above embodiments are only illustrative in nature and are not intended to limit the present invention. In addition, this article is not limited by any theory described in the above prior art or invention content or the following examples. DETAILED DESCRIPTION

[0031] The present invention is further described below in conjunction with examples. It should be noted that the following examples are provided for illustrative purposes only and do not constitute a limitation on the scope of protection claimed for the present invention.

[0032] Unless otherwise specified, the raw materials, reagents, methods, etc. used in the examples are conventional raw materials, reagents, methods in the art.

[0033] The microchannel reactor comes from Shandong Haomai, and the equipment model is C1-.

[0034] Example 1

[0035] After distilling the polar aprotic organic solvent diethylene glycol dimethyl ether, add molecular sieves for drying to make its moisture ≤10ppm. Accurately weigh 3-methylpyridine (3MP) 18.6g / h (moisture ≤50ppm) and treated diethylene glycol dimethyl ether 400ml / h, stir and mix continuously for use. Before the experiment, use nitrogen to purge the microchannel reactor to keep it unobstructed. According to the control of 75% fluorine gas content in the fluorine / nitrogen mixed gas, 24L / h of the mixed gas is passed into the microchannel reactor (silicon carbide material), and the pressure of the microchannel reactor is maintained at 0.5Mpa and the temperature is 30℃. Use a horizontal flow pump to continuously add 3MP mixed solution to ensure that the material residence time is 10s, the reaction temperature is 0℃, and the pressure is 0.5MPa (-40℃ cold medium temperature control). The unreacted mixed gas and the generated HF at the reactor outlet enter the tail gas absorption system. After 3 hours of reaction, the liquid phase mixture is collected and subjected to vacuum distillation. The pressure of the first tower is controlled at -90 to -95 KPa, the tower top temperature is 50 to 55°C, and the tower bottom temperature is 100 to 110°C to obtain 69.6 g of 3-trifluoromethylpyridine (purity ≥ 99%); the final target product is qualitatively and quantitatively analyzed by GC-MS, and the conversion rate is 95% and the selectivity is 83%. The second tower and the third tower (pressure is controlled at -90 to -95 KPa, and the tower bottom temperature is 125 to 165°C) are used to obtain the unreacted 3MP and solvent at the top of the tower, which are recycled.

[0036] Example 2

[0037] After distilling the polar aprotic organic solvent diethylene glycol dimethyl ether, add molecular sieves for drying to make its moisture ≤10ppm. Accurately weigh 3-methylpyridine (3MP) 18.6g / h (moisture ≤50ppm) and treated diethylene glycol dimethyl ether 400ml / h, stir and mix continuously for use. Before the experiment, use nitrogen to purge the microchannel reactor to keep it unobstructed. According to the control of 70% fluorine gas content in the fluorine / nitrogen mixed gas, 36L / h of mixed gas is passed into the reactor to maintain the pressure of the microchannel reactor at 0.5MPa and the temperature at 30℃. Use a horizontal flow pump to continuously add 3MP mixed solution to ensure that the material residence time is 8s, the reaction temperature is 0℃, and the pressure is 0.5MPa (-40℃ cold medium temperature control). The unreacted mixed gas and the generated HF at the reactor outlet enter the tail gas absorption system. After 3 hours of reaction, the liquid phase mixture is collected and subjected to vacuum distillation. The pressure of the first tower is controlled at -90 to -95 KPa, the tower top temperature is 50 to 55°C, and the tower bottom temperature is 100 to 110°C to obtain 65 g of 3-trifluoromethylpyridine (purity ≥ 99%). The final target product is qualitatively and quantitatively analyzed by GC-MS. After analysis, the conversion rate is 92% and the selectivity is 81%. The second tower and the third tower (pressure is controlled at -90 to -95 KPa, and the tower bottom temperature is 125 to 165°C) are used. The unreacted 3MP and solvent are obtained at the top of the tower and recycled.

[0038] Example 3

[0039] After distillation of the polar aprotic organic solvent diethylene glycol dimethyl ether, add molecular sieves for drying to make its moisture ≤10ppm. Accurately weigh 3-methylpyridine (3MP) 18.6g / h (moisture ≤50ppm) and treated diethylene glycol dimethyl ether 250ml / h, stir and mix continuously for use. Before the experiment, use nitrogen to purge the microchannel reactor to keep it unobstructed. According to the control of 75% fluorine gas content in the fluorine / nitrogen mixed gas, 36L / h of mixed gas is passed into the reactor to maintain the pressure of the microchannel reactor at 0.5MPa and the temperature at 30℃. Use a horizontal flow pump to continuously add 3MP mixed solution to ensure that the material residence time is 12s, the reaction temperature is 5℃, and the pressure is 0.8MPa (-40℃ cold medium temperature control). The unreacted mixed gas and the generated HF at the reactor outlet enter the tail gas absorption system. After 5 hours of reaction, the liquid phase mixture is collected and subjected to vacuum distillation. The pressure of the first tower is controlled at -90 to -95 KPa, the tower top temperature is 50 to 55°C, and the tower bottom temperature is 100 to 110°C to obtain 118 g of 3-trifluoromethylpyridine (purity ≥ 99%); the final target product is qualitatively and quantitatively analyzed by GC-MS, and the conversion rate is 98% and the selectivity is 85%. The second tower and the third tower (pressure is controlled at -90 to -95 KPa, temperature is 125 to 165°C), and the unreacted 3MP and solvent are obtained at the top of the tower for recycling.

[0040] Example 4

[0041] After distillation of the polar aprotic organic solvent diethylene glycol dimethyl ether, add molecular sieves for drying to make its moisture ≤10ppm. Accurately weigh 3-methylpyridine (3MP) 18.6g / h (moisture ≤50ppm) and treated diethylene glycol dimethyl ether 250ml / h, stir and mix continuously for use. Before the experiment, use nitrogen to purge the microchannel reactor to keep it unobstructed. According to the control of 75% fluorine gas content in the fluorine / nitrogen mixed gas, 24L / h of mixed gas is passed into the reactor to maintain the pressure of the microchannel reactor at 0.5MPa and the temperature at 30℃. Use a horizontal flow pump to continuously add 3MP mixed solution to ensure that the material residence time is 18s, the reaction temperature is 5℃, and the pressure is 1.0MPa (-40℃ cold medium temperature control). The unreacted mixed gas and the generated HF at the reactor outlet enter the tail gas absorption system. After 8 hours of reaction, the liquid phase mixture is collected and subjected to vacuum distillation. The pressure of the first tower is controlled at -90 to -95 KPa, the tower top temperature is 50 to 55°C, and the tower bottom temperature is 100 to 110°C to obtain 180 g of 3-trifluoromethylpyridine (purity ≥ 99%). The final target product is qualitatively and quantitatively analyzed by GC-MS. After analysis, the conversion rate is 93% and the selectivity is 84%. The second tower and the third tower (pressure is controlled at -90 to -95 KPa, temperature is 125 to 165°C), and the unreacted 3MP and solvent are obtained at the top of the tower for recycling.

[0042] Example 5 (mainly verifying the effect of mixed solvent, compared with the best example 3)

[0043] Polar aprotic organic solvents diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, and tetraethylene glycol dimethyl ether were mixed in a volume ratio of 1:1:1, distilled, and then added to molecular sieves for drying to make the moisture content ≤10ppm. Accurately weigh 3-methylpyridine (3MP) 18.6g / h (moisture content ≤50ppm) and 250ml / h of the treated mixed solvent, and stir and mix continuously for use. Before the experiment, nitrogen was used to purge the microchannel reactor to keep it unobstructed. According to the control of 75% fluorine gas content in the fluorine / nitrogen mixed gas, 36L / h of the mixed gas was passed into the reactor to maintain the pressure of the microchannel reactor at 0.5MPa. The 3MP mixed solution was continuously added using a horizontal flow pump to ensure that the material residence time was 12s, the reaction temperature was 5℃, and the pressure was 0.8MPa (-40℃ cold medium temperature control). The unreacted mixed gas and the generated HF at the reactor outlet entered the tail gas absorption system. After 5 hours of reaction, the liquid phase mixture was collected and subjected to vacuum distillation. The pressure of the first tower was controlled at -90 to -95 KPa, the tower top temperature was 50 to 55°C, and the tower bottom temperature was 100 to 110°C to obtain 125 g of 3-trifluoromethylpyridine (purity ≥ 99%). The final target product was qualitatively and quantitatively analyzed by GC-MS. After analysis, the conversion rate was 98% and the selectivity was 87%. Compared with Example 3, although the yield of 3-TF was improved in this experiment, the mixed solvent was not convenient for vacuum distillation, which made it more difficult to recover and reuse the solvent.

[0044] Comparative Example 1 (mainly to verify the effect of solvent-free, compared with the best embodiment 3)

[0045] Under the action of non-polar aprotic organic solvent, accurately weigh 3-methylpyridine (3MP) 18.6g / h (water content ≤50ppm). Before the experiment, use nitrogen to purge the microchannel reactor to keep it unobstructed. According to the control of 75% fluorine content in the fluorine / nitrogen mixed gas, 36L / h of the mixed gas is passed into the reactor to maintain the pressure of the microchannel reactor at 0.5MPa. 3MP is continuously added using a horizontal flow pump to ensure that the material residence time is 12s, the reaction temperature is 5°C, and the pressure is 0.8MPa (-40°C cold medium temperature control). The unreacted mixed gas at the reactor outlet and the generated HF enter the tail gas absorption system. After reacting for 5 hours, the liquid mixture was collected and distilled under reduced pressure. The pressure of the first tower was controlled at -90 to -95 KPa, the top temperature was 50 to 55° C., and the bottom temperature was 100 to 110° C. to obtain 72 g of 3-trifluoromethylpyridine (purity ≥ 99%). The final target product was qualitatively and quantitatively analyzed by GC-MS. The analysis showed that the conversion rate was 78% and the selectivity was 65%.

[0046] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that the technical solutions described in the above embodiments may be modified, or some or all of the technical features thereof may be replaced by equivalents, without departing from the spirit and essence of the claims of the present invention; and these modifications or replacements are still within the scope defined by the claims of the present invention.

Claims

1. A method for preparing 3-trifluoromethylpyridine, characterized in that: The following steps are involved: (1) mixing 3-methylpyridine and a polar aprotic solvent and introducing the mixture into a microchannel reactor to react with a fluorine / nitrogen mixed gas; (2) After the reaction, the unreacted fluorine / nitrogen mixed gas is subjected to tail gas absorption, and the liquid phase is subjected to vacuum distillation to obtain the product 3-trifluoromethylpyridine, and the unreacted 3-methylpyridine and the solvent are recycled.

2. The preparation method according to claim 1, characterized in that: Step (1) comprises: Fluorine gas and nitrogen gas are first introduced into the microchannel reactor in proportion to form a fluorine / nitrogen mixed gas, and the temperature and pressure of the reactor are controlled; The mixed 3-methylpyridine and polar aprotic solvent are introduced into a microchannel reactor under the action of a horizontal flow metering pump to react with a fluorine / nitrogen mixed gas, and the reaction temperature and pressure as well as the material residence time are controlled.

3. The preparation method according to claim 2, characterized in that: The fluorine content in the fluorine / nitrogen mixed gas is 60-80%, preferably 70-75%.

4. The preparation method according to claim 2, characterized in that: After the fluorine / nitrogen mixed gas is introduced, the reactor temperature is controlled to be 25-45°C and the pressure is controlled to be 0.1-1.0 MPa.

5. The preparation method according to claim 2, characterized in that: The molar ratio of the fluorine / nitrogen mixed gas to 3-methylpyridine is 3:1 to 9:1, preferably 4:1 to 6:

1.

6. The preparation method according to claim 2, characterized in that: The polar aprotic solvent is one or more selected from acetonitrile, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether and benzonitrile.

7. The preparation method according to claim 2, characterized in that: The mass ratio of 3-methylpyridine to the polar aprotic solvent is 1 to 10:100, preferably 5 to 8:

100.

8. The preparation method according to claim 2, characterized in that: The reaction temperature is -25 to 25°C, preferably 0 to 5°C, the pressure is 0.3 to 1.0 MPa, preferably 0.5 to 0.8 MPa, and the material residence time is 5 to 20 s, preferably 10 to 15 s.

9. The preparation method according to claim 1, characterized in that: The tail gas absorption in step (2) adopts water washing plus alkali washing absorption method, and the alkali washing concentration is controlled at 3% to 5%.

10. The preparation method according to claim 1, characterized in that: The vacuum distillation in step (2) is a three-stage vacuum distillation, wherein the pressure of the first-stage tower is -90 to -95 KPa, the tower top temperature of the first-stage tower is 50 to 55°C, and the tower bottom temperature of the first-stage tower is 100 to 110°C; the pressure of the second-stage tower is -90 to -95 KPa, the tower top temperature of the second-stage tower is 55 to 60°C, and the tower bottom temperature of the second-stage tower is 125 to 145°C; the pressure of the third-stage tower is -90 to -95 KPa, the tower top temperature of the third-stage tower is 65 to 70°C, and the tower bottom temperature of the third-stage tower is 145 to 165°C.