Method for synthesizing 4-vinylpyridine by micro-flow field reactor

Abstract

The invention discloses a method for synthesizing 4-vinylpyridine by a micro-flow field reactor. The method comprises the following steps: stirring 4-methylpyridine, a formaldehyde aqueous solution or paraformaldehyde and a catalyst until a homogeneous reaction solution is formed; the reaction liquid enters the micro-flow field reactor of the working section I through an injection pump, the 4-hydroxyethyl pyridine reaction liquid and the alkaline liquid obtained in the working section I enter the micro-flow field reactor of the working section II at the same time, after the reaction is finished, the reaction liquid is collected, a stabilizer is added, rectification is started, and the 4-vinylpyridine is collected. In the method, the intermediate product 4-hydroxyethylpyridine does not need to be separated and directly enters the next step of reaction, and the purity of the product 4-vinylpyridine is up to 99.9% or above. The micro-channel reactor is used, the occupied area is small, the investment cost is reduced, meanwhile, the intrinsic safety of chemical engineering is improved, and the method is suitable for industrial production.

Description

Technical Field

[0001] The present invention belongs to the field of fine chemicals and relates to a method for synthesizing 4-vinylpyridine, specifically to a method for synthesizing 4-vinylpyridine in a microfluidic reactor. Background Art

[0002] 4-Vinylpyridine is a colorless or light yellow liquid with a strong pungent odor and is soluble in water, alcohols, and ether solvents at room temperature. 4-Vinylpyridine is an unstable compound and will gradually degrade under the influence of light and oxygen in the air. 4-Ethylpyridine is commonly used as an intermediate in organic synthesis and can be used to prepare various organic compounds, such as the synthesis of natural products and polymer materials, and can also be used as a raw material for plant growth regulators, dyes, and surfactants.

[0003] Vinylpyridine could initially be extracted from coal tar, but the yield was extremely low and the process was complex. In 1898, scientists first attempted to synthesize vinylpyridine by reacting acetylene with ammonia, but the reaction yield was very low and it had no industrial value (A. Ladenburg, Ann. Vol, 301, 128 (1898)). This method involves the synthesis of 4-hydroxyethylpyridine, without using a catalyst or using an acidic catalyst, and the catalytic effect was not ideal, failing to reach the expected industrial utilization value. At the same time, the acidic catalyst increased the corrosion of the equipment.

[0004] Chinese Patent Application CN106699641A discloses a method for synthesizing 4-vinylpyridine: using 4-methylpyridine and paraformaldehyde as raw materials, putting the raw materials into a traditional reaction kettle, heating to 105 - 110 °C, reacting for 45 - 70 hours, with the raw material conversion of about 40%, generating the intermediate 4-hydroxyethylpyridine. The crude product of 4-hydroxyethylpyridine is purified, transferred to a dehydration kettle, adding an alkali solution, reacting at a temperature of 180 °C, and then obtaining 4-vinylpyridine through rectification. This method has a long reaction time (45 - 70 hours) and a low raw material conversion rate (only about 40%); at the same time, the long reaction time will lead to the successive appearance of di-substituted and tri-substituted pyridine products. These by-products are stable and cannot be converted into the target product 4-vinylpyridine in subsequent reactions, wasting raw materials and increasing the subsequent separation difficulty. The product 4-vinylpyridine itself is unstable and easily polymerizes itself, resulting in a reduced yield.

[0005] Chinese Patent CN86103091A uses 4-methylpyridine and formaldehyde as raw materials to prepare 4-vinylpyridine, and the synthesis route is as follows:

[0006]

[0007] This scheme has certain industrial value, but it also has the same problems as CN106699641A.

[0008] At present, the above-mentioned synthesis method of 4-vinylpyridine is not conducive to large-scale industrial production, and at the same time, the yield is relatively low and the production cost is relatively high. Summary of the Invention

[0009] The object of the present invention is to provide a method for synthesizing 4-vinylpyridine by a microfluidic reactor in view of the above problems.

[0010] The object of the present invention is achieved by the following technical solutions:

[0011] A method for synthesizing 4-vinylpyridine by a microfluidic reactor, comprising: stirring 4-methylpyridine, aqueous formaldehyde solution or paraformaldehyde, and a catalyst to form a homogeneous reaction solution; the reaction solution enters the microfluidic reactor in section I through an injection pump, and the 4-hydroxyethylpyridine reaction solution and the alkaline liquid obtained in section I enter the microfluidic reactor in section II at the same time. After the reaction is completed, the reaction solution is collected, a stabilizer is added, and then distillation is started to collect 4-vinylpyridine.

[0012] The molar ratio of the 4-methylpyridine to the aqueous formaldehyde solution (calculated as formaldehyde) or paraformaldehyde (the relative molecular weight of paraformaldehyde is calculated as 30) is 1:1 to 10:1, preferably 1:1 to 3:1, and more preferably 2.95:1 to 3:1.

[0013] As a preferred technical solution of the method for synthesizing 4-vinylpyridine by the microfluidic reactor of the present invention, solid paraformaldehyde is preferably used.

[0014] The catalyst is a basic catalyst; the basic catalyst is one or a mixture of triethylamine, DABCO (1,4-diazabicyclo[2.2.2]octane), dimethylamine, monomethylamine, DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), preferably triethylamine or DABCO. The molar ratio of the catalyst to 4-methylpyridine is 3:100 to 10:100, preferably 0.3:100 to 5:100.

[0015] Specifically, in a pressure vessel, 4-methylpyridine, aqueous formaldehyde solution or paraformaldehyde, and a catalyst are stirred until fully dissolved to form a homogeneous reaction solution; the temperature of the pressure vessel is 50 to 120 °C, preferably 100 to 110 °C; the pressure of the pressure vessel is 0 to 1 MPa, preferably 0.1 MPa; the stirring reaction time is generally 1 hour.

[0016] The reaction temperature in Section I is 150 - 300 °C, preferably 200 - 240 °C, more preferably 220 - 240 °C; the reaction pressure in Section I is 0.5 - 10 MPa, preferably 1 - 2 MPa; the reaction residence time is 20 seconds - 10 minutes, preferably 15 seconds - 1 minute, more preferably 15 seconds - 30 seconds.

[0017] The basic liquid is an aqueous solution of one or a mixture of several of hydroxides or carbonates of alkali metals with a mass fraction of 20% - 32%; the hydroxides of alkali metals are one or a mixture of sodium hydroxide and potassium hydroxide, and the carbonates of alkali metals are one or a mixture of sodium carbonate and potassium carbonate.

[0018] The molar ratio of the total amount of one or several of the hydroxides or carbonates of alkali metals in the basic liquid to 4 - methylpyridine is 1:1.

[0019] Preferably, the basic liquid is an aqueous solution of sodium hydroxide or potassium hydroxide with a mass fraction of 20% - 32%.

[0020] The reaction temperature in Section II is 150 - 300 °C, preferably 190 - 240 °C; the reaction pressure in Section II is 0.1 - 3 MPa, preferably 2 - 3 MPa; the reaction residence time is 5 seconds - 100 seconds, preferably 10 seconds - 20 seconds.

[0021] The micro - flow field reactor in Section I is a micro - channel reactor with a heart - shaped channel; the micro - flow field reactor in Section II is a micro - channel reactor with a heart - shaped channel.

[0022] Specifically, the micro - flow field reactors in both Section I and Section II are Corning reactors (heart - shaped channel, made of silicon carbide).

[0023] The stabilizer is one or a mixture of methylene blue and p - tert - butylcatechol (TBC), preferably methylene blue.

[0024] The addition amount of the stabilizer is 0.095 - 0.1% wt of the theoretical yield of 4 - vinylpyridine. The theoretical yield of 4 - vinylpyridine is calculated based on the feeding amount of formaldehyde or paraformaldehyde.

[0025] The stabilizer is added in the form of an aqueous solution; the mass fraction of the aqueous solution of the stabilizer is 0.9 - 1%, preferably about 1%.

[0026] The rectification is atmospheric rectification.

[0027] Advantages of the present invention:

[0028] 1. The present invention uses a microchannel reactor, which increases the reaction temperature in the synthesis process of 4 - hydroxyethylpyridine, reduces the residence time of the product in the reactor, avoids and reduces the generation of by - products. In the first - step synthesis process of 4 - hydroxyethylpyridine, only about 0.05% of disubstituted pyridine is generated, and no trisubstituted pyridine product is formed.

[0029] 2. With the increase of the reaction temperature and the use of a catalyst in the synthesis process of 4 - hydroxyethylpyridine, the conversion rate and yield of the reaction in the synthesis process of 4 - hydroxyethylpyridine are greatly improved. The yield of 4 - hydroxyethylpyridine can reach 95%, thereby further increasing the yield of 4 - vinylpyridine in section II. The yield of 4 - vinylpyridine is above 60%, even above 85%, and can reach up to above 91% at most.

[0030] 3. The intermediate product 4 - hydroxyethylpyridine does not need to be separated and directly enters the next reaction, which simplifies the reaction process, reduces losses. After simple rectification purification, the obtained product 4 - vinylpyridine has a purity of up to more than 99.9%.

[0031] 4. The present invention uses a microchannel reactor, which occupies less land area, reduces the investment cost, and at the same time improves the inherent safety of the chemical industry, and is suitable for industrial production. Specific Embodiments

[0032] The following specific examples are used to further illustrate the technical solutions of the present invention, but the protection scope of the present invention is not limited thereto.

[0033] In the examples, the micro - flow field reactor in section I and the micro - flow field reactor in section II are both Corning reactors (heart - shaped channels, made of silicon carbide).

[0034] Example 1

[0035] 279 kg (3 kmol) of 4 - methylpyridine, 30 kg (1 koml) of solid paraformaldehyde, and 10.1 kg (100 mol) of triethylamine are added to an autoclave, heated to 110 °C, the pressure is maintained at 0.1 MPa, and stirred for 1 hour. At this time, the system is fully dissolved to form a homogeneous reaction solution.

[0036] Pump the reaction solution in the autoclave into the microchannel reactor in section I through an injection pump, control the reaction temperature at 200 - 210 °C, the reaction pressure at 1 MPa, and the reaction residence time at 30 seconds to generate the intermediate 4 - hydroxyethylpyridine; take sodium hydroxide with the same amount of substance as 4 - methylpyridine and prepare an aqueous sodium hydroxide solution with a mass fraction of 32%. The 4 - hydroxyethylpyridine reaction solution obtained in section I and the aqueous sodium hydroxide solution with a mass fraction of 32% enter the microchannel reactor in section II simultaneously, control the reaction temperature at 190 - 200 °C, the reaction pressure at 2 - 3 MPa, and the reaction residence time at 20 seconds; after the reaction is completed, collect the 4 - vinylpyridine reaction solution in a 4 - vinylpyridine collection kettle (the 4 - vinylpyridine collection kettle is added with an aqueous methylene blue solution prepared from 0.1 kg of methylene blue and 10 kg of purified water).

[0037] Then pump the 4 - vinylpyridine reaction solution in the 4 - vinylpyridine collection kettle into a distillation device, perform atmospheric distillation, collect fractions according to the boiling point, and collect 191.8 kg of 4 - methylpyridine, which can be reused; 1.3 kg of 4 - hydroxyethylpyridine, 90.3 kg of 4 - vinylpyridine (calculated based on the feed amount of paraformaldehyde, with a molar yield of 86% and a purity of 99.93%).

[0038] Example 2

[0039] Add 93 kg (1 kmol) of 4 - methylpyridine, 30 kg (1 koml) of solid paraformaldehyde, and 10.1 kg (100 mol) of triethylamine to the autoclave, heat up to 110 °C, maintain the pressure at 0.1 MPa, and stir for 1 hour. At this time, the system is fully dissolved to form a homogeneous reaction solution.

[0040] Pump the reaction solution in the autoclave into the microchannel reactor in section I through an injection pump, control the reaction temperature at 200 - 210 °C, the reaction pressure at 1 MPa, and the reaction residence time at 30 seconds; take potassium hydroxide with the same amount of substance as 4 - methylpyridine and prepare an aqueous potassium hydroxide solution with a mass fraction of 20%. The 4 - hydroxyethylpyridine reaction solution obtained in section I and the 20% aqueous potassium hydroxide solution enter the microchannel reactor in section II simultaneously, control the reaction temperature at 190 - 200 °C, the reaction pressure at 2 - 3 MPa, and the reaction residence time at 20 seconds; after the reaction is completed, collect the 4 - vinylpyridine reaction solution in a 4 - vinylpyridine collection kettle (the 4 - vinylpyridine collection kettle is added with an aqueous methylene blue solution prepared from 0.1 kg of methylene blue and 10 kg of purified water).

[0041] Then, pump the 4-vinylpyridine reaction solution in the 4-vinylpyridine collection kettle into the distillation device, perform atmospheric distillation, collect fractions according to the boiling point, and 13 kg of 4-methylpyridine can be collected and reused; 0.5 kg of 4-(2-hydroxyethyl)pyridine, 77.7 kg of 4-vinylpyridine (calculated based on the feed of paraformaldehyde, molar yield 74%, purity 99.91%).

[0042] Example 3

[0043] Add 279 kg (3 kmol) of 4-methylpyridine, 81 kg (1 kmol) of 37% aqueous formaldehyde solution, and 15.2 kg (100 mol) of DBU to the autoclave, heat up to 90 °C, maintain the pressure at 0.1 MPa, and stir for 1 hour. At this time, the system is fully dissolved to form a homogeneous reaction solution.

[0044] Pump the reaction solution in the autoclave into the microchannel reactor in section I through an injection pump, control the reaction temperature at 200 - 210 °C and the reaction pressure at 1 MPa, and the reaction residence time at 30 seconds; take sodium hydroxide with the same amount of substance as 4-methylpyridine and prepare a 32% aqueous sodium hydroxide solution. The 4-(2-hydroxyethyl)pyridine reaction solution obtained in section I and the 32% aqueous sodium hydroxide solution enter the microchannel reactor in section II simultaneously, control the reaction temperature at 190 - 200 °C, the reaction pressure at 2 - 3 MPa, and the reaction residence time at 20 seconds; after the reaction, collect the 4-vinylpyridine reaction solution in the 4-vinylpyridine collection kettle (the 4-vinylpyridine collection kettle is added with an aqueous methylene blue solution prepared from 0.1 kg of methylene blue and 10 kg of purified water).

[0045] Then, pump the 4-vinylpyridine reaction solution in the 4-vinylpyridine collection kettle into the distillation device, perform atmospheric distillation, collect fractions according to the boiling point, and 219 kg of 4-methylpyridine can be collected and reused; 1.8 kg of 4-(2-hydroxyethyl)pyridine, 65.1 kg of 4-vinylpyridine (calculated based on the feed of formaldehyde, molar yield 62%, purity 99.93%).

[0046] Example 4

[0047] Add 279 kg (3 kmol) of 4-methylpyridine, 30 kg (1 kmol) of solid paraformaldehyde, and 11.2 kg (100 mol) of DABCO to the autoclave, heat up to 110 °C, maintain the pressure at 0.1 MPa, and stir for 1 hour. At this time, the system is fully dissolved to form a homogeneous reaction solution.

[0048] The reaction solution in the autoclave is pumped into the microfluidic reactor in Section I by an injection pump, controlling the reaction temperature at 230 °C, the reaction pressure at 2 MPa, and the reaction residence time at 15 seconds; sodium hydroxide with the same amount of substance as 4-methylpyridine is taken and formulated into an aqueous sodium hydroxide solution with a mass fraction of 32%. The 4-hydroxyethylpyridine reaction solution obtained in Section I and the 32% aqueous sodium hydroxide solution enter the microfluidic reactor in Section II simultaneously, controlling the reaction temperature at 190 - 200 °C, the reaction pressure at 2 - 3 MPa, and the reaction residence time at 20 seconds; after the reaction, the 4-vinylpyridine reaction solution is collected in a 4-vinylpyridine collection kettle (the 4-vinylpyridine collection kettle is added with an aqueous methylene blue solution prepared from 0.1 kg of methylene blue and 10 kg of purified water).

[0049] Then, the 4-vinylpyridine reaction solution in the 4-vinylpyridine collection kettle is pumped into a distillation device, and distilled under normal pressure. The fractions are collected according to the boiling point. 190 kg of 4-methylpyridine can be recycled; 0.7 kg of 4-hydroxyethylpyridine, 98 kg of 4-vinylpyridine (calculated based on the feed of paraformaldehyde, with a molar yield of 93.5% and a purity of 99.9%).

[0050] Example 5

[0051] 102 kg (1.1 kmol) of 4-methylpyridine, 81 kg (1 kmol) of 37% aqueous formaldehyde solution, and 10.1 kg (100 mol) of triethylamine are added to the autoclave, heated to 110 °C, and maintained at a pressure of 0.1 MPa and stirred for 1 hour. At this time, the system is fully dissolved to form a homogeneous reaction solution.

[0052] The reaction solution in the autoclave is pumped into the microfluidic reactor in Section I by an injection pump, controlling the reaction temperature at 230 °C, the reaction pressure at 2 MPa, and the reaction residence time at 15 seconds; sodium hydroxide with the same amount of substance as 4-methylpyridine is taken and formulated into an aqueous sodium hydroxide solution with a mass fraction of 32%. The 4-hydroxyethylpyridine reaction solution obtained in Section I and the 32% aqueous sodium hydroxide solution enter the microfluidic reactor in Section II simultaneously, controlling the reaction temperature at 240 °C, the reaction pressure at 2 - 3 MPa, and the reaction residence time at 10 seconds; after the reaction, the 4-vinylpyridine reaction solution is collected in a 4-vinylpyridine collection kettle (the 4-vinylpyridine collection kettle is added with an aqueous methylene blue solution prepared from 0.1 kg of p-tert-butylcatechol and 10 kg of purified water).

[0053] Then, the 4-vinylpyridine reaction solution in the 4-vinylpyridine collection kettle is pumped into a distillation device, and distilled under normal pressure. The fractions are collected according to the boiling point. 18.6 kg of 4-methylpyridine can be recycled; 0.2 kg of 4-hydroxyethylpyridine, 89 kg of 4-vinylpyridine (calculated based on the feed of formaldehyde, with a molar yield of 84.8% and a purity of 99.9%).

Claims

1. A method for synthesizing 4-vinylpyridine using a microfluidic field reactor, characterized in that: include: Stir 4-methylpyridine, formaldehyde solution or paraformaldehyde, and a catalyst until a homogeneous reaction solution is formed; The reaction liquid enters the microfluidic field reactor of section I through a syringe pump, and the 4-hydroxyethylpyridine reaction liquid and alkaline liquid obtained in section I simultaneously enter the microfluidic field reactor of section II. After the reaction is completed, the reaction liquid is collected, a stabilizer is added to start distillation, and 4-vinylpyridine is collected.

2. The method for synthesizing 4-vinylpyridine using a microfluidic field reactor according to claim 1, characterized in that: The molar ratio of 4-methylpyridine to formaldehyde solution or paraformaldehyde is 1:1 to 10:1, preferably 1:1 to 3:1, and more preferably 2.95:1 to 3:

1.

3. The method for synthesizing 4-vinylpyridine using a microfluidic field reactor according to claim 1, characterized in that: The catalyst is an alkaline catalyst; the alkaline catalyst is one of triethylamine, DABCO, dimethylamine, monomethylamine, DBU or a mixture of several thereof; the molar ratio of the catalyst to 4-methylpyridine is 3:100 to 10:

100.

4. The method for synthesizing 4-vinylpyridine using a microfluidic field reactor according to claim 3, characterized in that: The alkaline catalyst is triethylamine or DABCO.

5. The method for synthesizing 4-vinylpyridine using a microfluidic field reactor according to claim 1 or 3, characterized in that: The molar ratio of the catalyst to 4-methylpyridine is 3:100 to 5:

100.

6. The method for synthesizing 4-vinylpyridine using a microfluidic field reactor according to claim 1, characterized in that: The microfluidic field reactor of the I section is a microchannel reactor with a heart-shaped channel; the reaction temperature of the I section is 150-300°C, preferably 200-240°C, and more preferably 220-240°C; the reaction pressure of the I section is 0.5-10MPa, preferably 1-2MPa; the reaction residence time is 20 seconds to 10 minutes, preferably 15 seconds to 1 minute, and more preferably 15 seconds to 30 seconds.

7. The method for synthesizing 4-vinylpyridine using a microfluidic field reactor according to claim 1, characterized in that: The alkaline liquid is a mixed aqueous solution of one or more of alkali metal hydroxides or carbonates with a mass fraction of 20% to 32%; the alkali metal hydroxide is one or more of sodium hydroxide and potassium hydroxide, and the alkali metal carbonate is one or more of sodium carbonate and potassium carbonate.

8. The method for synthesizing 4-vinylpyridine using a microfluidic field reactor according to claim 1, characterized in that: The molar ratio of the total amount of one or more of the hydroxides or carbonates of alkali metals in the alkaline liquid to 4-methylpyridine is 1:

1.

9. The method for synthesizing 4-vinylpyridine using a microfluidic field reactor according to claim 1, characterized in that: The microfluidic field reactor of the II section is a microchannel reactor with a heart-shaped channel; the reaction temperature of the II section is 150-300°C, preferably 190-240°C; the reaction pressure of the II section is 0.1-3MPa, preferably 2-3MPa; the reaction residence time is 5 seconds to 100 seconds, preferably 10 seconds to 20 seconds.

10. The method for synthesizing 4-vinylpyridine using a microfluidic field reactor according to claim 1, characterized in that: The stabilizer is one of methylene blue and p-tert-butylcatechol or a mixture thereof.

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