A process for the preparation of 3-trifluoromethylpyridines

Abstract

The application provides a preparation method of 3-trifluoromethylpyridine and relates to the technical field of trifluoromethylpyridine intermediate preparation. 3-methylpyridine (3MP) and a polar aprotic solvent are mixed, then are introduced into a microchannel reactor, and are reacted with fluorine / nitrogen mixed gas to obtain product 3-trifluoromethylpyridine (3-TF), and the product and the solvent are separated through a three-stage vacuum rectification process. The method provided by the application has the advantages of high reaction yield, easy operation, low energy consumption, solvent recycling, high economic efficiency and the like, compared with the prior synthesis technology.

Description

Technical Field

[0001] This invention relates to the field of preparation technology of trifluoromethylpyridine intermediates, and more particularly to a method for preparing 3-trifluoromethylpyridine. Background Technology

[0002] 2-Chloro-5-trifluoromethylpyridine and 2-chloro-3-trifluoromethylpyridine are both important fluorinated pyridine chemical raw materials. 2-Chloro-5-trifluoromethylpyridine (abbreviated as 2,5-CTF) is an important trifluoromethylpyridine intermediate used in the preparation of pharmaceuticals, agrochemicals, and biological agents. It can be used to prepare many compounds with special applications, such as 2-amino-5-trifluoromethylpyridine, 2-hydroxy-5-trifluoromethylpyridine, and 2,3-dichloro-5-trifluoromethylpyridine. In pesticides, 2-chloro-5-trifluoromethylpyridine is a key intermediate in the production of insecticides such as chlorfenapyr, herbicides such as quizalofop-P-ethyl (trade name: quizalofop-P-ethyl) and pendimethalin, and fungicides such as fluazinam. These fluorinated pesticides have advantages such as broad-spectrum systemic absorption, high efficiency and low toxicity, good safety, and long-lasting effects, and are widely used abroad, showing broad market prospects. 2-Chloro-3-trifluoromethylpyridine is a key intermediate in the production of the highly effective herbicide pyrsulfuron-methyl and has a wide range of applications.

[0003] 3-Trifluoromethylpyridine is an important raw material for the preparation of 2-chloro-5-trifluoromethylpyridine and 2-chloro-3-trifluoromethylpyridine. Regarding the preparation of 3-trifluoromethylpyridine, US Patent 4417055 provides a method for producing 3-trifluoromethylpyridine using 3-methylpyridine as a raw material in the presence of catalysts such as CuF2, BiF2, and SnF2. This method exhibits poor selectivity for 3-trifluoromethylpyridine, generating large amounts of byproducts such as 2-chloro-5-trifluoromethylpyridine, 2-chloro-3-trifluoromethylpyridine, and 2,6-dichloro-3-trifluoromethylpyridine along with 3-trifluoromethylpyridine. Example 9 discloses the highest content of 3-trifluoromethylpyridine in the product, only 66.9%, with a maximum yield of 75.6%. Furthermore, this method requires maintaining a temperature range of 400–430°C to achieve good implementation results, resulting in high reaction energy consumption.

[0004] Therefore, there is a need to develop a high-yield, low-energy-consumption method for preparing 3-trifluoromethylpyridine. Summary of the Invention

[0005] The purpose of this invention is to provide a method for preparing 3-trifluoromethylpyridine. 3-methylpyridine (3MP) and a polar aprotic solvent are mixed in a specific ratio and then introduced into a microchannel reactor to react with a fluorine / nitrogen mixture. This reaction is exothermic, and the temperature, pressure, and residence time of the materials are controlled throughout the process to produce the product 3-trifluoromethylpyridine (3-TF). After the reaction, the material is subjected to a three-stage vacuum distillation process. ≥99% of the target product 3-TF is obtained at the top of the first stage, while unreacted 3MP and the solvent are recovered at the top of the second and third stages, respectively, for recycling.

[0006] In order to achieve the above-mentioned objectives of the present invention, the following technical solution is adopted:

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

[0008] (1) 3-methylpyridine and a polar aprotic solvent are mixed and then introduced into a microchannel reactor to react with a fluorine / nitrogen mixture.

[0009] (2) The unreacted fluorine / nitrogen mixture after the reaction is absorbed as tail gas, and the liquid phase is distilled under reduced pressure to obtain the product 3-trifluoromethylpyridine, the unreacted 3-methylpyridine and the solvent are recycled.

[0010] Step (1):

[0011] Step (1) includes:

[0012] Fluorine and nitrogen are first introduced into the microchannel reactor in a certain ratio to form a fluorine / nitrogen mixture, and the reactor temperature and pressure are controlled.

[0013] The mixed 3-methylpyridine and polar aprotic solvent are introduced into a microchannel reactor by a horizontal metering pump to react with a fluorine / nitrogen mixture, while controlling the reaction temperature, pressure, and material residence time.

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

[0015] In some embodiments, after introducing a fluorine / nitrogen mixture, the reactor temperature is controlled at 25–45°C and the pressure at 0.1–1.0 MPa.

[0016] In some embodiments, the molar ratio of the fluorine / nitrogen mixture 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 selected as the material for the microchannel reactor.

[0022] Step (2):

[0023] In some implementations, the exhaust gas absorption employs a method of first washing with water and then washing with alkali, with the alkali concentration controlled at 3% to 5%. For industrial-scale design, the gaseous phase (HF and fluorine) after the reaction can be recovered or processed into 40% hydrofluoric acid for sale.

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

[0025] After three-stage vacuum distillation (the second and third stages are mainly used for recovery and reuse), unreacted 3-methylpyridine (2% to 10%) and polar aprotic solvent can be recovered from the top of the column. According to the ratio of the two (1% to 10%), they can be recycled.

[0026] Technical effects:

[0027] (1) This invention provides a new method for preparing 3-trifluoromethylpyridine without the use of a catalyst. It directly uses 3-methylpyridine and fluorine gas as raw materials and conducts a microchannel reaction process. Under the action of a polar aprotic solvent, the gas-liquid contact of the material 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 small, and the safety is high;

[0029] (3) Unreacted materials 3MP and solvents are recycled, saving costs and being environmentally friendly.

[0030] The present invention has been described in detail above; however, the above embodiments are merely illustrative in nature and are not intended to limit the invention. Furthermore, this document is not limited to the foregoing prior art or the invention itself, or to any theory described in the following embodiments. Detailed Implementation

[0031] The present invention will be further described below with reference to the embodiments. It should be noted that the following embodiments are provided for illustrative purposes only and do not constitute a limitation on the scope of protection of the present invention.

[0032] Unless otherwise specified, the raw materials, reagents, and methods used in the embodiments are all conventional raw materials, reagents, and methods in the art.

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

[0034] Example 1

[0035] Diethylene glycol dimethyl ether (DGE), a polar aprotic organic solvent, was distilled and then dried using molecular sieves to ensure a moisture content ≤10 ppm. 18.6 g / h of 3-methylpyridine (3MP) (moisture content ≤50 ppm) and 400 ml / h of the treated DGE were accurately weighed and continuously stirred for later use. Before the experiment, the microchannel reactor was purged with nitrogen to ensure unobstructed flow. A fluorine / nitrogen mixture with a fluorine content of 75% was introduced into the microchannel reactor (made of silicon carbide) at a rate of 24 L / h, maintaining a pressure of 0.5 MPa and a temperature of 30°C. The 3MP mixture was continuously added using a horizontal flow pump, ensuring a material residence time of 10 s, a reaction temperature of 0°C, and a pressure of 0.5 MPa (temperature controlled by a -40°C cooling medium). Unreacted gas mixture and generated HF were discharged from the reactor outlet into the tail gas absorption system. After 3 hours of reaction, the liquid mixture was collected and subjected to vacuum distillation. The pressure in the first-stage column was controlled at -90 to -95 kPa, the top temperature at 50 to 55 °C, and the bottom temperature at 100 to 110 °C, yielding 69.6 g of 3-trifluoromethylpyridine (purity ≥99%). Qualitative and quantitative analysis of the final product was performed using GC-MS, showing a conversion rate of 95% and a selectivity of 83%. The unreacted 3MP and solvent were collected at the top of the second and third-stage columns (pressure controlled at -90 to -95 kPa, bottom temperature at 125 to 165 °C) and recycled.

[0036] Example 2

[0037] Diethylene glycol dimethyl ether (DGE), a polar aprotic organic solvent, was distilled and then dried using molecular sieves to ensure a moisture content ≤10 ppm. 18.6 g / h of 3-methylpyridine (3MP) (moisture content ≤50 ppm) and 400 ml / h of the treated DGE were accurately weighed and continuously stirred for later use. Before the experiment, the microchannel reactor was purged with nitrogen to ensure unobstructed flow. A fluorine / nitrogen mixture with a fluorine content of 70% was introduced into the reactor at a rate of 36 L / h, maintaining a pressure of 0.5 MPa and a temperature of 30°C. The 3MP mixture was continuously added using a horizontal pump, ensuring a residence time of 8 seconds, a reaction temperature of 0°C, and a pressure of 0.5 MPa (temperature controlled by a -40°C cooling medium). Unreacted gas mixture and generated HF were discharged from the reactor outlet into the tail gas absorption system. After 3 hours of reaction, the liquid mixture was collected and subjected to vacuum distillation. The first-stage column was controlled at -90 to -95 kPa, with a top temperature of 50 to 55 °C and a bottom temperature of 100 to 110 °C, yielding 65 g of 3-trifluoromethylpyridine (purity ≥99%). Qualitative and quantitative analysis of the final product was performed using GC-MS, showing a conversion rate of 92% and a selectivity of 81%. The second and third-stage columns (pressure controlled at -90 to -95 kPa, bottom temperature 125 to 165 °C) yielded unreacted 3MP and solvent at the top, which were recycled.

[0038] Example 3

[0039] Diethylene glycol dimethyl ether (DGE), a polar aprotic organic solvent, was distilled and then dried using molecular sieves to ensure a moisture content ≤10 ppm. 18.6 g / h of 3-methylpyridine (3MP) (moisture content ≤50 ppm) and 250 ml / h of the treated DGE were accurately weighed and continuously stirred for later use. Before the experiment, the microchannel reactor was purged with nitrogen to ensure unobstructed flow. A fluorine / nitrogen mixture with a fluorine content of 75% was introduced into the reactor at a rate of 36 L / h, maintaining a pressure of 0.5 MPa and a temperature of 30°C. The 3MP mixture was continuously added using a horizontal flow pump, ensuring a material residence time of 12 s, a reaction temperature of 5°C, and a pressure of 0.8 MPa (temperature controlled by a -40°C cooling medium). Unreacted gas mixture and generated HF were discharged from the reactor outlet into the tail gas absorption system. After 5 hours of reaction, the liquid mixture was collected and subjected to vacuum distillation. The pressure in the first-stage column was controlled at -90 to -95 kPa, the top temperature at 50 to 55 °C, and the bottom temperature at 100 to 110 °C, yielding 118 g of 3-trifluoromethylpyridine (purity ≥99%). Qualitative and quantitative analysis of the final product was performed using GC-MS, showing a conversion rate of 98% and a selectivity of 85%. The unreacted 3MP and solvent were collected at the top of the second and third-stage columns (pressure controlled at -90 to -95 kPa, temperature 125 to 165 °C) and recycled.

[0040] Example 4

[0041] Diethylene glycol dimethyl ether (DGE), a polar aprotic organic solvent, was distilled and then dried using molecular sieves to ensure a moisture content ≤10 ppm. 18.6 g / h of 3-methylpyridine (3MP) (moisture content ≤50 ppm) and 250 ml / h of the treated DGE were accurately weighed and continuously stirred for later use. Before the experiment, the microchannel reactor was purged with nitrogen to ensure unobstructed flow. A fluorine / nitrogen mixture with a fluorine content of 75% was introduced into the reactor at a rate of 24 L / h, maintaining a pressure of 0.5 MPa and a temperature of 30°C. The 3MP mixture was continuously added using a horizontal flow pump, ensuring a residence time of 18 s, a reaction temperature of 5°C, and a pressure of 1.0 MPa (temperature controlled by a -40°C cooling medium). Unreacted gas mixture and generated HF were discharged from the reactor outlet into the tail gas absorption system. After 8 hours of reaction, the liquid mixture was collected and subjected to vacuum distillation. The pressure in the first-stage column was controlled at -90 to -95 kPa, the top temperature at 50 to 55 °C, and the bottom temperature at 100 to 110 °C, yielding 180 g of 3-trifluoromethylpyridine (purity ≥99%). Qualitative and quantitative analysis of the final product was performed using GC-MS, showing a conversion rate of 93% and a selectivity of 84%. The unreacted 3MP and solvent were collected at the top of the second and third-stage columns (pressure controlled at -90 to -95 kPa, temperature 125 to 165 °C) and recycled.

[0042] Example 5 (mainly to verify the effect of the 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 at a volume ratio of 1:1:1, distilled, and then added to a molecular sieve for drying to ensure a moisture content ≤10 ppm. 18.6 g / h of 3-methylpyridine (3MP) (moisture content ≤50 ppm) and 250 ml / h of the treated mixed solvent were accurately weighed and continuously stirred for later use. Before the experiment, the microchannel reactor was purged with nitrogen to ensure unobstructed flow. A fluorine / nitrogen mixture with a fluorine content of 75% was introduced into the reactor at a rate of 36 L / h, maintaining a pressure of 0.5 MPa. The 3MP mixed solution was continuously added using a horizontal flow pump, ensuring a material residence time of 12 s, a reaction temperature of 5°C, and a pressure of 0.8 MPa (temperature controlled by a -40°C cold medium). Unreacted mixed gas and generated HF from the reactor outlet were introduced into the tail gas absorption system. After 5 hours of reaction, the liquid mixture was collected and distilled under reduced pressure. The pressure of the first-stage column was controlled at -90 to -95 kPa, the top temperature at 50 to 55 °C, and the bottom temperature at 100 to 110 °C, yielding 125 g of 3-trifluoromethylpyridine (purity ≥99%). The final product was qualitatively and quantitatively analyzed by GC-MS, showing a conversion rate of 98% and a selectivity of 87%. Compared to Example 3, although the yield of 3-TF was improved in this experiment, the mixed solvent made reduced pressure distillation inconvenient, increasing the difficulty of solvent recovery and reuse.

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

[0045] 18.6 g / h of 3-methylpyridine (3MP) (with moisture content ≤50 ppm) was accurately weighed in a nonpolar aprotic organic solvent. Before the experiment, the microchannel reactor was purged with nitrogen to ensure unobstructed flow. A fluorine / nitrogen mixture with a fluorine content of 75% was introduced into the reactor at a rate of 36 L / h, maintaining a reactor pressure of 0.5 MPa. 3MPa was continuously added using a horizontal flow pump, ensuring a material residence time of 12 s, a reaction temperature of 5°C, and a pressure of 0.8 MPa (temperature controlled by a -40°C cooling medium). Unreacted gas mixture and generated HF were discharged from the reactor outlet into the tail gas absorption system. After 5 hours of reaction, the liquid mixture was collected and subjected to vacuum distillation. The pressure of the first-stage column was controlled at -90 to -95 kPa, the top temperature at 50 to 55 °C, and the bottom temperature at 100 to 110 °C, yielding 72 g of 3-trifluoromethylpyridine (purity ≥99%). The final target product was qualitatively and quantitatively analyzed by GC-MS, and the conversion rate was 78% and the selectivity was 65%.

[0046] The above embodiments are merely illustrative of the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein, without departing from the spirit and substance defined by the claims of the present invention; and such modifications or substitutions are still within the scope defined by the claims of the present invention.

Claims

1. A method for preparing 3-trifluoromethylpyridine, characterized in that, Includes the following steps: (1) Fluorine and nitrogen are first introduced into the microchannel reactor to form a fluorine / nitrogen mixture, in which the fluorine content is 60-80%; 3-methylpyridine and a polar aprotic solvent are mixed and then introduced into the microchannel reactor to react with the fluorine / nitrogen mixture; the reaction temperature is -25 to 25°C, the pressure is 0.3 to 1.0 MPa, and the material residence time is 5 to 20 s; the molar ratio of the fluorine / nitrogen mixture to 3-methylpyridine is 3:1 to 9:1; the polar aprotic solvent is one or more selected from diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, and tetraethylene glycol dimethyl ether; (2) The unreacted fluorine / nitrogen mixture after the reaction is absorbed as tail gas, and the liquid phase is distilled under reduced pressure to obtain the product 3-trifluoromethylpyridine. The unreacted 3-methylpyridine and the solvent are recycled.

2. The preparation method according to claim 1, characterized in that, Step (1) The fluorine content in the fluorine / nitrogen mixture is 70-75%.

3. The preparation method according to claim 1, characterized in that, Step (1) After introducing the fluorine / nitrogen mixed gas, control the reactor temperature to 25-45℃ and the pressure to 0.1-1.0MPa.

4. The preparation method according to claim 1, characterized in that, In step (1), the molar ratio of the fluorine / nitrogen mixture and 3-methylpyridine is 4:1 to 6:

1.

5. The preparation method according to claim 1, characterized in that, In step (1), the mass ratio of 3-methylpyridine to the polar aprotic solvent is 1 to 10:

100.

6. The preparation method according to claim 5, characterized in that, In step (1), the mass ratio of 3-methylpyridine to the polar aprotic solvent is 5 to 8:

100.

7. The preparation method according to claim 1, characterized in that, Step (1) The reaction temperature is 0-5℃, the pressure is 0.5-0.8MPa, and the material residence time is 10-15s.

8. The preparation method according to claim 1, characterized in that, The exhaust gas absorption in step (2) adopts a water washing plus alkali washing absorption method, with the alkali washing concentration controlled at 3% to 5%.

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