Preparation method of 4-vinylpyridine

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 4-vinylpyridine, which comprises the following steps: by taking 4-methylpyridine as an initial raw material, carrying out condensation reaction under the action of a catalyst to obtain an intermediate 4-hydroxyethylpyridine, carrying out dehydration reaction on the 4-hydroxyethylpyridine in the presence of a polymerization inhibitor and a solid acid catalyst to obtain the 4-vinylpyridine, the yield is not less than 90% and the purity is not less than 98%; the invention provides the preparation method of the 4-vinylpyridine, the product quality is good, and the preparation method has better technical economy and application prospect.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis technology, and particularly to a preparation method of 4-vinylpyridine. Background Art

[0002] 4-Vinylpyridine (CAS: 100-43-6) is a colorless to light yellow transparent liquid with a pungent odor and is an important intermediate for synthesizing 4-acetylpyridine.

[0003] In the prior art, the reported preparation methods of 4-vinylpyridine mainly include: Patent CN106008325A reports using 4-hydroxyethylpyridine as a raw material, calcium chloride, magnesium chloride or sodium acetate as a catalyst, reacting at 100-190 °C for 5-30 min, and separating the product after the reaction ends. Patent CN106699641A reports using 4-methylpyridine and paraformaldehyde as raw materials, reacting at normal pressure and a temperature of 105-110 °C for 45-70 h to obtain the intermediate 4-hydroxyethylpyridine; then reacting the obtained intermediate at 180 °C in sodium hydroxide and water to obtain the product.

[0004] The above methods for preparing 4-vinylpyridine may have problems such as the limited source of the raw material 4-hydroxyethylpyridine; or the problems of a large amount of catalyst used in the dehydration reaction, difficult separation, and affecting stirring during post-treatment distillation; or the problem of a long condensation reaction time; or the problem that paraformaldehyde is prone to sublimation and block the condenser during the condensation reaction; or the problem that formaldehyde, the raw material for the condensation reaction under normal pressure, easily escapes from the system. Summary of the Invention

[0005] To solve the above problems, the purpose of the present invention is to provide a preparation method of 4-vinylpyridine, which can produce high-quality 4-vinylpyridine.

[0006] To achieve the above purpose, the present invention provides the following technical solutions: The present invention provides a preparation method of 4-vinylpyridine, comprising the following steps: Condensation reaction: Put 4-methylpyridine, paraformaldehyde, a catalyst and pure water into an autoclave. After putting them in, close the autoclave, replace the air with nitrogen, and react at 120-140 °C for 2-6 h. After the reaction ends, release the pressure, transfer the material to a distillation kettle, and distill out water, the catalyst and excessive 4-methylpyridine under negative pressure with a circulating water vacuum pump to obtain the intermediate 4-hydroxyethylpyridine.

[0007]

[0008] (2) Dehydration reaction: Put a solvent, 4-hydroxyethylpyridine, an inhibitor and a solid acid catalyst into a dehydration kettle. After putting them in, heat up and react. After the reaction ends, filter and rectify to obtain the product 4-vinylpyridine.

[0009]

[0010] In step (1), the catalyst is one of diethylamine, triethylamine, diisopropylamine or di-n-propylamine; the distillation temperature is 120 °C; In step (2), the inhibitor is one of hydroquinone, 4-tert-butylcatechol or a combination thereof; the solid acid catalyst is one of HND-582, HND-8 or a combination thereof.

[0011] Furthermore, in step (1), the molar ratio of 4-methylpyridine to the formaldehyde monomer in paraformaldehyde is 2-5:1.

[0012] Furthermore, in step (1), the molar ratio of the catalyst to 4-methylpyridine is 0.01-0.05:1.

[0013] Furthermore, in step (1), the mass ratio of pure water to paraformaldehyde is 1-4:1.

[0014] Furthermore, in step (2), the dosage of the solid acid catalyst is 3-20% of the mass of 4-hydroxyethylpyridine.

[0015] Furthermore, in step (2), the dosage of the inhibitor is 0.1-0.5‰ of the mass of 4-hydroxyethylpyridine.

[0016] Furthermore, in step (2), the volume of the solvent is 2-5 times the mass of 4-hydroxyethylpyridine, and the solvent is one of DMF, ethylene glycol, dimethyl sulfoxide, sulfolane.

[0017] Furthermore, in step (2), the reaction temperature is 150-180 °C, and the reaction time is 6-18 h.

[0018] Compared with the prior art, the beneficial effects of the present invention are: (1) In the condensation reaction, an organic amine catalyst with a lower boiling point is used. Compared with diethanolamine, triethanolamine with a higher boiling point or inorganic bases such as sodium hydroxide and potassium hydroxide, the post-treatment is simple (after the reaction is completed, only water, the catalyst and excess 4-methylpyridine need to be distilled off to obtain 4-hydroxyethylpyridine).

[0019] (2) Based on the fact that the condensation reaction is an endothermic and reversible reaction, and the property that formaldehyde water is volatile, a high-pressure autoclave is used to react at a higher temperature, with a short reaction time and the problem of low yield caused by the escape of formaldehyde from the reaction system can be avoided.

[0020] (3) The use of an inhibitor in the dehydration reaction solves the problems of easy polymerization and low yield of 4-vinylpyridine.

[0021] (4) In the dehydration reaction, a solid acid that is easy to separate is used as a catalyst, and the operation is simple. After the reaction is completed, the catalyst can be separated by filtration only. Description of the Drawings

[0022] Figure 1 It is the infrared spectrum of 4-vinylpyridine synthesized in Example 1 of the present invention; Figure 2 It is the gas chromatogram of 4-vinylpyridine synthesized in Example 1 of the present invention. Detailed Description of the Invention

[0023] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention. Example 1

[0024] Put 714.94 g of 4-methylpyridine, 60 g of paraformaldehyde (Macklin, 95%), 23.30 g of di-n-propylamine and 180 g of pure water into the autoclave. After charging, close the autoclave. After purging with nitrogen, react at 130 °C for 4 h. After the reaction is completed, release the pressure, transfer the material to the distillation kettle, and distill out water, di-n-propylamine and excessive 4-methylpyridine at -120 °C under negative pressure to obtain 224.12 g of intermediate 4-hydroxyethylpyridine, with a yield of 95.8% and a purity of 97.5% (GC).

[0025] Put 672 mL of DMF, 224.12 g of 4-hydroxyethylpyridine, 0.045 g of hydroquinone and 22.4 g of solid acid catalyst HND-582 into the dehydration kettle. After charging, purge with nitrogen, heat up to 150 °C and react for 16 h. After the reaction is completed, filter and rectify to obtain 182.39 g of 4-vinylpyridine, with a yield of 91.3% (based on paraformaldehyde), a purity of 98.03% (GC), and a water content of 0.02%.

[0026] The product was subjected to infrared detection, and the detection results are as Figure 1 shown. The infrared spectra of the self-made 4-vinylpyridine and the standard sample are in good agreement, and it is determined that the obtained product is the target product. The gas chromatogram of the obtained product is as Figure 2 shown. Example 2

[0027] Charge 714.94 g of 4-methylpyridine, 60 g of paraformaldehyde (Maclean, 95%), 23.3 g of triethylamine and 180 g of pure water into an autoclave. After charging, seal the autoclave. After purging with nitrogen, react at 120 °C for 6 h. After the reaction is completed, relieve the pressure, transfer the material to a distillation kettle, and distill out water, triethylamine and excessive 4-methylpyridine at 120 °C under negative pressure to obtain 224.59 g of intermediate 4-hydroxyethylpyridine, with a yield of 96.0% and a purity of 96.8% (GC).

[0028] Charge 1123 mL of DMF, 224.59 g of 4-hydroxyethylpyridine, 0.045 g of 4-tert-butylcatechol and 33.7 g of solid acid catalyst HND-8 into a dehydration kettle. After charging, purge with nitrogen, heat up to 150 °C and react for 12 h. After the reaction is completed, filter and rectify to obtain 181 g of 4-vinylpyridine, with a yield of 90.6% (based on paraformaldehyde) and a purity of 98.4% (GC), and the water content is 0.04%. Example 3

[0029] Charge 714.94 g of 4-methylpyridine, 60 g of paraformaldehyde (Maclean, 95%), 16.84 g of diethylamine and 120 g of pure water into an autoclave. After charging, seal the autoclave. After purging with nitrogen, react at 140 °C for 5 h. After the reaction is completed, relieve the pressure, transfer the material to a distillation kettle, and distill out water, diethylamine and excessive 4-methylpyridine at 120 °C under negative pressure to obtain 225.29 g of intermediate 4-hydroxyethylpyridine, with a yield of 96.3% and a purity of 97% (GC).

[0030] Charge 901 mL of ethylene glycol, 225.29 g of 4-hydroxyethylpyridine, 0.068 g of hydroquinone and 45.1 g of solid acid catalyst HND-582 into a dehydration kettle. After charging, purge with nitrogen, heat up to 160 °C and react for 10 h. After the reaction is completed, filter and rectify to obtain 181.39 g of 4-vinylpyridine, with a yield of 90.8% (based on paraformaldehyde) and a purity of 98.2% (GC), and the water content is 0.03%. Example 4

[0031] Charge 536.2 g of 4-methylpyridine, 60 g of paraformaldehyde (Maclean, 95%), 14.57 g of diisopropylamine and 120 g of pure water into an autoclave. After charging, seal the autoclave. After purging with nitrogen, react at 130 °C for 4 h. After the reaction is completed, relieve the pressure, transfer the material to a distillation kettle, and distill out water, diisopropylamine and excessive 4-methylpyridine at 120 °C under negative pressure to obtain 225.76 g of intermediate 4-hydroxyethylpyridine, with a yield of 96.5% and a purity of 97.8% (GC).

[0032] Add 452 mL of dimethyl sulfoxide, 225.76 g of 4 - hydroxyethylpyridine, 0.113 g of 4 - tert - butylcatechol, and 11.3 g of solid acid catalyst HND - 8 into the dehydration kettle. After adding, replace the air with nitrogen, heat up to 180 °C and react for 6 h. After the reaction, filter and rectify to obtain 180.59 g of 4 - vinylpyridine, with a yield of 90.4% (based on paraformaldehyde) and a purity of 98.6% (GC), and a water content of 0.06%. Example 5

[0033] Add 536.20 g of 4 - methylpyridine, 129.55 g of aqueous formaldehyde solution (44%), and 20.39 g of di - n - propylamine into the autoclave. After adding, close the autoclave, replace the air with nitrogen, and react at 140 °C for 3 h. After the reaction, release the pressure, transfer the material to the distillation kettle, and distill out water, di - n - propylamine, and excessive 4 - methylpyridine at 120 °C under negative pressure to obtain 223.65 g of intermediate 4 - hydroxyethylpyridine, with a yield of 95.6% and a purity of 98% (GC).

[0034] Add 895 mL of sulfolane, 223.65 g of 4 - hydroxyethylpyridine, 0.089 g of hydroquinone, and 6.7 g of solid acid catalyst HND - 582 into the dehydration kettle. After adding, replace the air with nitrogen, heat up to 180 °C and react for 8 h. After the reaction, filter and rectify to obtain 181.79 g of 4 - vinylpyridine, with a yield of 91.0% (based on formaldehyde) and a purity of 98.4% (GC), and a water content of 0.05%. Example 6

[0035] Add 536.2 g of 4 - methylpyridine, 154.05 g of aqueous formaldehyde solution (37%), and 23.3 g of triethylamine into the autoclave. After adding, close the autoclave, replace the air with nitrogen, and react at 140 °C for 2 h. After the reaction, release the pressure, transfer the material to the distillation kettle, and distill out water, triethylamine, and excessive 4 - methylpyridine at 120 °C under negative pressure to obtain 223.42 g of intermediate 4 - hydroxyethylpyridine, with a yield of 95.5% and a purity of 97.2% (GC).

[0036] Add 782 mL of ethylene glycol, 223.42 g of 4 - hydroxyethylpyridine, 0.022 g of 4 - tert - butylcatechol, and 38 g of solid acid catalyst HND - 8 into the dehydration kettle. After adding, replace the air with nitrogen, heat up to 170 °C and react for 6 h. After the reaction, filter and rectify to obtain 182.79 g of 4 - vinylpyridine, with a yield of 91.5% (based on formaldehyde) and a purity of 98.5% (GC), and a water content of 0.03%. Example 7

[0037] Charge 357.47 g of 4-methylpyridine, 60 g of paraformaldehyde (Macklin, 95%), 19.42 g of di-n-propylamine, and 240 g of pure water into an autoclave. After charging, seal the autoclave. After purging with nitrogen, react at 130 °C for 5 h. After the reaction is completed, release the pressure, transfer the material to a distillation kettle, and distill off water, di-n-propylamine, and excess 4-methylpyridine at 120 °C under negative pressure to obtain 225.52 g of the intermediate 4-hydroxyethylpyridine, with a yield of 96.4% and a purity of 97.6% (GC).

[0038] Charge 677 mL of DMF, 225.52 g of 4-hydroxyethylpyridine, 0.068 g of hydroquinone, and 15.8 g of solid acid catalyst HND-582 into a dehydration kettle. After charging, purge with nitrogen and heat to 150 °C for reaction for 16 h. After the reaction is completed, filter and rectify to obtain 182.39 g of 4-vinylpyridine, with a yield of 91.3% (based on paraformaldehyde) and a purity of 99.2% (GC), and a water content of 0.05%. Example 8

[0039] Charge 893.67 g of 4-methylpyridine, 60 g of paraformaldehyde (Macklin, 95%), 19.42 g of di-n-propylamine, and 60 g of pure water into an autoclave. After charging, seal the autoclave. After purging with nitrogen, react at 140 °C for 3 h. After the reaction is completed, release the pressure, transfer the material to a distillation kettle, and distill off water, di-n-propylamine, and excess 4-methylpyridine at 120 °C under negative pressure to obtain 223.89 g of the intermediate 4-hydroxyethylpyridine, with a yield of 95.7% and a purity of 98.2% (GC).

[0040] Charge 560 mL of DMF, 223.89 g of 4-hydroxyethylpyridine, 0.045 g of 4-tert-butylcatechol, and 22.4 g of solid acid catalyst HND-8 into a dehydration kettle. After charging, purge with nitrogen and heat to 150 °C for reaction for 12 h. After the reaction is completed, filter and rectify to obtain 181 g of 4-vinylpyridine, with a yield of 90.6% (based on paraformaldehyde) and a purity of 98.5% (GC), and a water content of 0.03%. Comparative Example 1

[0041] Charge 893.67 g of 4-methylpyridine, 60 g of paraformaldehyde (Macklin, 95%), 42.5 g of triethanolamine, and 120 g of pure water into an autoclave. After charging, seal the autoclave. After purging with nitrogen, react at 140 °C for 4 h. After the reaction is completed, release the pressure, transfer the material to a distillation kettle, and distill off water, di-n-propylamine, and excess 4-methylpyridine at 120 °C under negative pressure, and then switch the fraction collection flask and continue heating and distilling to obtain 205 g of the intermediate 4-hydroxyethylpyridine, with a yield of 87.63% and a purity of 96.7% (GC). Comparative Example 2

[0042] 893.67 g of 4-methylpyridine, 60 g of paraformaldehyde (Maclean, 95%), 19.42 g of di-n-propylamine, and 60 g of pure water were added to a four-necked flask equipped with a thermometer, a condenser, and a stirrer. After the addition, the temperature was raised to 100 °C and the reaction was carried out for 48 h. After the reaction was completed, water, di-n-propylamine, and excess 4-methylpyridine were distilled off under negative pressure at 120 °C to obtain 108.55 g of the intermediate 4-hydroxyethylpyridine, with a yield of 46.4% and a purity of 90.2% (GC). Comparative Example 3

[0043] 677 mL of DMF, 225.52 g of 4-hydroxyethylpyridine, and 15.8 g of the solid acid catalyst HND-582 were added to a dehydration kettle. After the addition, the system was purged with nitrogen, and the temperature was raised to 150 °C and the reaction was carried out for 16 h. After the reaction was completed, filtration and rectification were carried out to obtain 159 g of 4-vinylpyridine, with a yield of 82.6% and a purity of 98.4% (GC), and the water content was 0.03%. Comparative Example 4

[0044] 677 mL of DMF, 225.52 g of 4-hydroxyethylpyridine, 0.068 g of hydroquinone, and 10 g of sodium acetate were added to a dehydration kettle. After the addition, the system was purged with nitrogen, and the temperature was raised to 150 °C and the reaction was carried out for 16 h. After the reaction was completed, filtration and rectification were carried out to obtain 61.6 g of 4-vinylpyridine, with a yield of 32% and a purity of 97.8% (GC), and the water content was 0.04%. Comparative Example 5

[0045] 677 mL of DMF, 225.52 g of 4-hydroxyethylpyridine, 0.068 g of hydroquinone, and 10 g of sodium hydroxide were added to a dehydration kettle. After the addition, the system was purged with nitrogen, and the temperature was raised to 150 °C and the reaction was carried out for 16 h. After the reaction was completed, filtration and rectification were carried out to obtain 129.6 g of 4-vinylpyridine, with a yield of 67.3% and a purity of 98.5% (GC), and the water content was 0.02%. Comparative Example 6

[0046] 677 mL of xylene, 225.52 g of 4-hydroxyethylpyridine, 0.068 g of hydroquinone, and 15.8 g of the solid acid catalyst HND-582 were added to a dehydration kettle. After the addition, the system was purged with nitrogen, and the temperature was raised to 140 °C and the reaction was carried out for 16 h. After the reaction was completed, filtration and rectification were carried out to obtain 149.3 g of 4-vinylpyridine, with a yield of 77.5% and a purity of 99% (GC), and the water content was 0.03%. Comparative Example 7

[0047] Add 677 mL of DMF, 225.52 g of 4 - hydroxyethylpyridine, 0.068 g of hydroquinone and 15.8 g of anhydrous calcium chloride into the dehydration kettle. After adding, replace the air with nitrogen, heat up to 150 °C and react for 16 h. After the reaction is completed, filter and rectify to obtain 164.5 g of 4 - vinylpyridine (the residual calcium chloride in the later stage of rectification affects normal stirring), with a yield of 85.4%, a purity of 99.2% (GC), and a water content of 0.02%. Comparative Example 8

[0048] Add 714.94 g of 4 - methylpyridine, 240 g of paraformaldehyde (Macklin, 95%, 1 equi), 23.30 g of di - n - propylamine and 360 g of pure water into the autoclave. After adding, seal the autoclave, replace the air with nitrogen and react at 140 °C for 4 h (continue to extend the reaction time by 2 h, and the gas - phase content of the reaction solution no longer changes). After the reaction is completed, release the pressure, transfer the material to the distillation kettle, and distill out water, di - n - propylamine and excessive 4 - methylpyridine at 120 °C under negative pressure (there is sublimated paraformaldehyde adhering to the inner wall of the condenser during the distillation process) to obtain the intermediate 4 - hydroxyethylpyridine, with a yield of 52.4% and a purity of 84.5% (GC).

[0049] The analysis conditions for gas chromatography involved above are shown in Table 1.

[0050] Table 1 Gas Chromatography Analysis Conditions

[0051] It should be noted that in this article, relational terms such as first and second are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the term "comprising", "including" or any other variant thereof is intended to cover non - exclusive inclusion, so that a process, method, article or device comprising a series of elements not only includes those elements, but also includes other elements not explicitly listed, or elements inherent to such process, method, article or device.

[0052] It should be noted that the above content only illustrates the technical idea of the present invention and cannot be used to limit the protection scope of the present invention. For those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements all fall within the protection scope of the claims of the present invention.

Claims

1. A preparation method of 4-vinylpyridine, characterized in that, It includes the following steps: (1) Charge 4-methylpyridine, paraformaldehyde, a catalyst, and pure water into an autoclave. After charging, seal the autoclave. After nitrogen replacement, react at 120 - 140 °C for 2 - 6 h. After the reaction ends, relieve the pressure, transfer the material to a distillation kettle, and distill out water, the catalyst, and excessive 4-methylpyridine under negative pressure using a circulating water vacuum pump to obtain the intermediate 4-hydroxyethylpyridine; ； (2) Charge a solvent, 4-hydroxyethylpyridine, an inhibitor, and a solid acid catalyst into a dehydration kettle. After charging, raise the temperature for reaction. After the reaction ends, obtain the product 4-vinylpyridine through filtration and rectification; ； In step (1), the catalyst is one of diethylamine, triethylamine, diisopropylamine, or di-n-propylamine; In step (2), the inhibitor is one or more of hydroquinone and 4-tert-butylcatechol; the solid acid catalyst is one or more of HND-582 and HND-8.

2. The preparation method of 4-vinylpyridine according to claim 1, wherein, In step (1), the molar ratio of 4-methylpyridine to the formaldehyde monomer in paraformaldehyde is 2 - 5:

1.

3. The preparation method of 4-vinylpyridine according to claim 1, characterized in that, In step (1), the molar ratio of the catalyst to 4-methylpyridine is 0.01 - 0.05:

1.

4. The preparation method of 4-vinylpyridine according to claim 1, characterized in that, In step (1), the mass ratio of pure water to paraformaldehyde is 1 - 4:

1.

5. A method for preparing 4-vinylpyridine according to claim 1, characterized in that, In step (1), the distillation temperature is 120 °C.

6. The preparation method of 4-vinylpyridine according to claim 1, characterized in that, In step (2), the mass ratio of the solid acid catalyst to 4-hydroxyethylpyridine is 0.03 - 0.20:

1.

7. A method for preparing 4-vinylpyridine according to claim 1, characterized in that, In step (2), the mass ratio of the inhibitor to 4-hydroxyethylpyridine is 0.0001 - 0.0005:

1.

8. A method for preparing 4-vinylpyridine according to claim 1, characterized in that, In step (2), the mass-volume ratio of 4-hydroxyethylpyridine to the solvent is 1:2 - 5.

9. The preparation method of 4-vinylpyridine according to claim 9, characterized in that, The solvent is one of DMF, ethylene glycol, dimethyl sulfoxide, and sulfolane.

10. The preparation method of 4-vinylpyridine according to claim 1, characterized in that, In step (2), the reaction temperature is 150 - 180 °C, and the reaction time is 6 - 18 h.

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