A production method for producing a pyridine carboxylic acid

Abstract

This invention discloses a method for preparing pyridine carboxylic acids. The method involves the oxidation of alkyl pyridines with an oxygen-containing gas under cobalt-manganese solid catalyst catalysis to obtain pyridine carboxylic acids. The reaction is preferably carried out at a temperature of 150-170℃ and a pressure of 2.5-3.5 MPa, using a small-molecule organic acid as the solvent. The preparation method is simple, exhibits excellent production performance, operates under relatively mild conditions, and causes no environmental pollution or equipment corrosion during the process, demonstrating significant industrial application prospects and value.

Description

Technical Field

[0001] This invention relates to a method for preparing pyridine carboxylic acids, specifically a method for obtaining pyridine carboxylic acids by catalytic oxidation of alkylpyridines in a solid-liquid heterogeneous system using oxygen-containing gas. Background Technology

[0002] Pyridine carboxylic acids are those in which a carboxyl group is inserted into the carbonyl group of pyridine, including pyridine-2-carboxylic acid, pyridine-3-carboxylic acid (nicotinic acid), and pyridine-4-carboxylic acid (isonicotinic acid). Pyridine-3-carboxylic acid, also known as nicotinic acid, is a water-soluble vitamin B3 with functions such as improving cardiovascular health, relieving arthritis symptoms, improving digestive function, enhancing immunity, and preventing diabetes. It is also mainly used in industry as a food additive, feed additive, and pharmaceutical raw material. The following mainly introduces the preparation technology of nicotinic acid; the preparation of other pyridine carboxylic acids is similar.

[0003] Nicotinic acid is mainly prepared by oxidizing alkyl pyridines, such as 3-methylpyridine, 2-methyl-5-ethylpyridine, and quinoline. The main methods for nicotinic acid synthesis include chemical synthesis, bio-fermentation, and plant extraction. Bio-fermentation uses nicotinic acid-producing strains to produce nicotinic acid, requiring no chemical reagents, resulting in less environmental pollution, and can generate other useful metabolites during the process. However, this method is costly, produces lower product purity, and requires multiple separations. Plant extraction extracts nicotinic acid from natural plants, offering advantages such as high product purity and no environmental pollution, but it is also costly and unsuitable for large-scale industrial production. Therefore, chemical synthesis is the primary method used in industry.

[0004] Chemical synthesis methods include ammonia oxidation, oxidation, and electrochemical oxidation. Electrochemical oxidation utilizes electrochemical action to electrolyze a 3-methylpyridine solution to obtain nicotinic acid. While relatively environmentally friendly, it consumes a lot of electricity, has low energy utilization, low yield, and complex treatment of byproducts and wastewater. Ammonia oxidation primarily involves the ammonia oxidation of 3-methylpyridine or 2-methyl-5-ethylpyridine under the combined action of ammonia and oxygen-containing gas to obtain 3-cyanopyridine, followed by hydrolysis in alkaline water to obtain nicotinate, and finally acidification to obtain nicotinic acid. This method is relatively mature industrially and can achieve continuous production, but it also presents some problems. This method introduces ammonia and uses a large amount of water during hydrolysis, generating significant amounts of waste gas and wastewater, leading to environmental problems and increased post-treatment costs. Furthermore, this multi-step process is less economical. Oxidation methods are mainly divided into gas-phase oxidation and liquid-phase oxidation.

[0005] The gas-phase oxidation method was proposed by the Russian Academy of Sciences (patent number CN95191372.7), and a similar method is also reported in patent CN99118373.8. This method involves vaporizing 3-methylpyridine and reacting it with oxygen and water vapor at high temperature in the presence of a vanadium-titanium catalyst to produce nicotinic acid. This method achieves a high yield, reaching 82-86%, and the product purity is high. However, this method is energy-intensive and requires high product concentration and precise temperature control; otherwise, tar is easily generated, which adversely affects the catalyst.

[0006] Liquid-phase oxidation primarily produces nicotinic acid by oxidizing alkylpyridines with oxidants. Oxidants mainly include potassium permanganate, concentrated nitric acid, concentrated sulfuric acid, NO2, O3, H2O2, and oxygen. Although liquid-phase oxidation facilitates product separation and operates under relatively mild reaction conditions, all oxidants except oxygen cause significant corrosion to the reaction apparatus, severely shortening its lifespan. Furthermore, some oxidants can pollute the environment and increase post-treatment costs. Patent CN200610146981.6 uses ozone and hydrogen peroxide as oxidants and oxidizes 3-methylpyridine to nicotinic acid under the protection of sulfuric acid. Similar methods include patents CN202110512772.3 and CN202210801432.7. While this method achieves higher purity, the introduction of ozone, hydrogen peroxide, and sulfuric acid places extremely high demands on the corrosion resistance of the reaction vessel. Nippon Chemical Co., Ltd. (Patent No. CN95100904.4) uses metal salts of cobalt, manganese, and cerium, along with bromides, to react at 150°C under a certain pressure of oxygen-containing gas to obtain the product. Because this method uses organic acid as a solvent and adds bromides as an initiator, the corrosion resistance of the reaction apparatus is greatly increased. Therefore, this patent uses titanium as the main metal material of the reaction apparatus, significantly increasing the cost. Japanese Patent JP 2001253838 uses N-hydroxyphthalimide (NHPI) instead of bromides in the catalyst system as an initiator. The reaction can be carried out at atmospheric pressure or lower pressure. Although this method has a higher conversion rate and yield, the amount of NHPI used is relatively large, making it difficult to remove NHPI and its byproducts from the product. Patent CN200510105668.3 uses metal salts of cobalt and manganese, along with bromides and an additional initiator, to oxidize 3-alkylpyridine to obtain nicotinic acid. Although this method produces products with high purity, it introduces bromides into the system, which can exacerbate equipment corrosion. Summary of the Invention:

[0007] The purpose of this invention is to provide a solid catalyst and a method for catalyzing the oxidation of alkylpyridines to pyridine carboxylic acids in a solid-liquid heterogeneous system using oxygen-containing gas. This method utilizes a highly active and selective cobalt-manganese-based solid catalyst, enabling the oxidation reaction to proceed at lower temperatures and pressures, achieving higher yields, while simultaneously addressing the problem of solvent corrosion of equipment.

[0008] The method for preparing pyridine carboxylic acids of the present invention includes using alkylpyridine as a raw material, reacting in a solvent of a small molecule organic acid, under the action of a cobalt-manganese solid catalyst and an initiator NHPI, at a temperature of 130℃-180℃ and a pressure of 2.0-4.0 MPa, with oxygen-containing gas as an oxidant for 2-18 hours to obtain pyridine carboxylic acids.

[0009] The method for preparing the pyridine carboxylic acid substances described therein is characterized in that the alkylpyridine can be 2-alkylpyridine, 3-alkylpyridine, or 4-alkylpyridine.

[0010] The method for preparing the pyridine carboxylic acid substances is characterized in that the alkyl group of the alkyl pyridine is not limited to methyl (-CH3), ethyl (-CH2CH3), propyl (-CH2CH2CH3), isopropyl (-CH(CH3)2), butyl (-CH2CH2CH2CH3), isobutyl (-CH2CH(CH3)2), etc.

[0011] The method for preparing pyridine carboxylic acid substances is characterized in that the oxygen-containing gas can be air, oxygen-enriched air, or oxygen, the oxygen content in the gas is 30-100%, and the pressure during the preparation of pyridine carboxylic acid is 2.0-4.0 MPa, preferably 2.5-3.5 MPa.

[0012] The method for preparing the pyridine carboxylic acid substances is characterized in that the small molecule organic acid includes formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, or hexanoic acid.

[0013] The method for preparing pyridine carboxylic acid substances is characterized in that the precursors of the active components cobalt and manganese in the cobalt-manganese solid catalyst are one or more of any metal salts of the corresponding metals.

[0014] For example, the precursor of cobalt can be one or more of cobalt nitrate, cobalt chloride, cobalt sulfate, and cobalt acetate; the precursor of manganese can be one or more of manganese nitrate and manganese acetate.

[0015] The method for preparing the pyridine carboxylic acid derivative is characterized by the following method for preparing the cobalt-manganese solid catalyst:

[0016] Cobalt and manganese precursors are dissolved in water at a molar ratio of 0.1-10:0.1-10, preferably 0.5-5:0.5-5, ensuring a total metal salt molar concentration of 1 mol / L. Methanol is added to the metal nitrate mixture while stirring at 600 rpm. Triethylamine is added dropwise to the mixture to adjust the pH to 9, with a methanol to triethylamine volume ratio of 1-100:0.1-20, preferably 1-50:0.5-10. The reaction mixture is refluxed in a water bath at 40-80°C for 5-24 h, followed by cooling to room temperature. The mixture is filtered, and the solid is washed with methanol and deionized water until the filtrate is neutral. The solid is then dried at 80-150°C for 3-24 h. Finally, the solid is calcined at 300-800°C for 2-8 h, followed by cooling to room temperature to obtain the catalyst. The mass fractions of cobalt and manganese in the catalyst are 0.67%-72.64% and 0.68%-62.62%, respectively, preferably 6.21%-66.25% and 6.18%-57.85%.

[0017] The method for preparing the pyridine carboxylic acid is characterized in that the mass ratio of the catalyst to the pyridine carboxylic acid is 1:0.1-10, preferably 1:1-5.

[0018] The method for preparing the pyridine carboxylic acid substance is characterized in that the mass ratio of the initiator NHPI (N-hydroxyphthalimide) to the pyridine carboxylic acid substance is 1:0.01-0.5, preferably 1:0.05-0.3.

[0019] The method for preparing the pyridine carboxylic acid substances is characterized in that the reaction temperature is 130-180℃, preferably 150-170℃; and the reaction time is 2-18h, preferably 4-10h.

[0020] The preparation method of this invention is simple, has excellent production performance, operates under relatively mild conditions, and causes no environmental pollution or equipment corrosion during the preparation process. It has great industrial application prospects and value.

[0021] The advantages of this invention are as follows:

[0022] 1. Compared with gas-phase oxidation, the reaction temperature is lower and energy consumption is less;

[0023] 2. This process introduces no ammonia source or water, and both the solvent in the reaction solution and the solvent in the post-reaction treatment can be recovered. The entire process generates almost no waste, making it green and environmentally friendly.

[0024] 3. This process uses inexpensive metal oxides as catalysts, resulting in lower preparation costs. Furthermore, no halogens are introduced during preparation and use, reducing corrosion of the reactor and extending its service life.

[0025] 4. This process uses oxygen as an oxidant, which greatly reduces corrosion to the reactor compared to other oxidants;

[0026] 5. This process is a one-step process, which, compared to multi-step processes, does not require additional reactions and is more economical. Detailed Implementation

[0027] The present invention will be further described in detail below with reference to specific embodiments. The scope of protection of the present invention includes, but is not limited to, the following embodiments. Any modifications to the details and form of the technical solution of the present invention without departing from the meaning and scope of this application shall fall within the scope of protection of the present invention.

[0028] Example 1

[0029] Catalyst preparation:

[0030] 16.8662 g of cobalt sulfate heptahydrate and 6.6918 g of manganese sulfate tetrahydrate were dissolved in 90 mL of water to ensure a total metal salt molar concentration of 1 mol / L. 10 mL of methanol was added to the metal nitrate mixture while stirring at 600 rpm. Triethylamine and methanol were added dropwise to the mixture to adjust the pH to 9, ensuring a methanol to triethylamine volume ratio of 1:10. The reaction mixture was reacted in a 60 °C water bath for 16 h, then cooled to room temperature. The mixture was filtered and washed three times with methanol, followed by washing the solid with deionized water until the filtrate was neutral. The solid was then dried at 100 °C for 12 h. Finally, the solid was calcined at 400 °C for 5 h and cooled to room temperature to obtain cobalt-manganese solid catalyst a. The mass fractions of cobalt and manganese in this catalyst were 47.63% and 22.20%, respectively.

[0031] Reaction feeding:

[0032] In a reactor equipped with an electromagnetic stirrer, temperature controller, and gas inlet tube, 8 mmol of 3-methylpyridine, 12 ml of acetic acid, 1.92 g of cobalt-manganese solid catalyst a, and 65.25 mg of NHPI were added. The mixture was then stirred, oxygen was introduced, and the pressure inside the reactor was maintained at 3 MPa. The reactor was heated to 160 °C, and timing was started. The reaction temperature was maintained at 160-170 °C during the reaction, which was completed after 5.5 hours. The reactor was then cooled to room temperature.

[0033] Comparative Example 1

[0034] The catalyst preparation steps (process and conditions, the same below) are the same as in Example 1, except that methanol is removed and triethylamine is replaced with 10 wt% ammonia water. Specifically, the steps are: "Add methanol to a mixed solution of metal nitrates while stirring at 600 rpm, add triethylamine dropwise to the mixed solution, and adjust the pH to 9, wherein the volume ratio of methanol to triethylamine is 1:10." This is replaced with "Stir at 600 rpm, add 10 wt% ammonia water dropwise to the mixed solution, and adjust the pH to 9." The resulting cobalt-manganese solid catalyst a1 is obtained. The mass fractions of cobalt and manganese in this catalyst are 45.37% and 24.46%, respectively.

[0035] The reaction feeding process (process and conditions) is the same as in Example 1.

[0036] Comparative Example 2

[0037] The catalyst preparation steps (process and conditions, the same below) are the same as in Example 1;

[0038] The reaction feeding steps (process and conditions) are the same as in Example 1, except that the cobalt-manganese catalyst is removed, that is, "add 8 mmol of 3-methylpyridine, 12 ml of acetic acid, 1.92 g of cobalt-manganese solid catalyst a, and 65.25 mg of NHPI" is replaced with "add 8 mmol of 3-methylpyridine, 12 ml of acetic acid, and 65.25 mg of NHPI".

[0039] Comparative Example 3

[0040] The catalyst preparation steps (process and conditions, the same below) are the same as in Example 1;

[0041] The reaction feeding steps (process and conditions) are the same as in Example 1, except that 65.25 mg of NHPI is removed. That is, "add 8 mmol of 3-methylpyridine, 12 ml of acetic acid, 1.92 g of cobalt-manganese solid catalyst a, and 65.25 mg of NHPI" is replaced with "add 8 mmol of 3-methylpyridine, 12 ml of acetic acid, and 65.25 mg of NHPI".

[0042] Comparative Example 4

[0043] The catalyst preparation steps (process and conditions, the same below) are the same as in Example 1;

[0044] The reaction feeding steps (process and conditions) are the same as in Example 1, except that 65.25 mg NHPI is replaced with 46.036 mg N-hydroxysuccinimide, that is, "add 8 mmol of 3-methylpyridine, 12 ml of acetic acid, 1.92 g of cobalt-manganese solid catalyst a, and 65.25 mg of NHPI" is replaced with "add 8 mmol of 3-methylpyridine, 12 ml of acetic acid, 1.92 g of cobalt-manganese solid catalyst a, and 46.036 mg of N-hydroxysuccinimide".

[0045] Example 2

[0046] The catalyst preparation steps (process and conditions, the same below) are the same as in Example 1;

[0047] The reaction feeding steps (process and conditions) are the same as in Example 1, except that 3-methylpyridine is replaced with 4-methylpyridine, that is, "add 8 mmol of 3-methylpyridine, 12 ml of acetic acid, 1.92 g of cobalt-manganese solid catalyst a, and 65.25 mg of NHPI" is replaced with "add 8 mmol of 4-methylpyridine, 12 ml of acetic acid, 1.92 g of cobalt-manganese solid catalyst a, and 65.25 mg of NHPI".

[0048] Example 3

[0049] Catalyst preparation:

[0050] 21.8273 g of cobalt nitrate hexahydrate and 3.7652 g of manganese nitrate tetrahydrate were dissolved in 90 mL of water to ensure a total molar concentration of 1 mol / L for the metal salts. Methanol was added to the metal nitrate mixture while stirring at 600 rpm. Triethylamine was added dropwise to the mixture to adjust the pH to 9, with a methanol to triethylamine volume ratio of 1:10. The reaction mixture was refluxed at 65 °C for 18 h, then cooled to room temperature. The mixture was filtered and washed three times with methanol, followed by washing the solid with deionized water until the filtrate was neutral. The solid was then dried at 120 °C for 18 h. Finally, the solid was calcined at 500 °C for 4 h and cooled to room temperature to obtain cobalt-manganese solid catalyst b. The mass fractions of cobalt and manganese in this catalyst were 60.35% and 11.25%, respectively.

[0051] The reaction feeding process (process and conditions) is the same as in Example 1.

[0052] Example 4

[0053] The preparation steps (process and conditions, the same below) of the catalyst are the same as in Example 3;

[0054] The reaction feeding steps (process and conditions) are the same as in Example 1, except that 3-methylpyridine is replaced with 2-methylpyridine, that is, "add 8 mmol of 3-methylpyridine, 12 ml of acetic acid, 1.92 g of cobalt-manganese solid catalyst a, and 65.25 mg of NHPI" is replaced with "add 8 mmol of 2-methylpyridine, 12 ml of acetic acid, 1.92 g of cobalt-manganese solid catalyst a, and 65.25 mg of NHPI".

[0055] Example 5

[0056] Catalyst preparation:

[0057] 7.4724 g of cobalt acetate tetrahydrate and 7.2927 g of manganese acetate tetrahydrate were dissolved in 60 mL of water to ensure a total metal salt molar concentration of 1 mol / L. Methanol was added to the metal nitrate mixture while stirring at 600 rpm. Triethylamine was added dropwise to the mixture to adjust the pH to 9, with a methanol to triethylamine volume ratio of 1:10. The reaction mixture was refluxed in a 70°C water bath for 14 h, then cooled to room temperature. The mixture was filtered and washed three times with methanol, followed by washing the solid with deionized water until the filtrate was neutral. The solid was then dried at 120°C for 16 h. Finally, the solid was calcined at 500°C for 5 h and cooled to room temperature to obtain cobalt-manganese solid catalyst a. The mass fractions of cobalt and manganese in this catalyst were 35.25% and 32.86%, respectively.

[0058] The reaction feed (process and conditions) are the same as in Example 2.

[0059] Example 6

[0060] After each reaction, 18 ml of methanol and 96 mg of nitrobenzene were added as a diluent to the reaction solutions of Examples 1-5 and Comparative Examples 1-4, respectively. After thorough mixing, a portion was taken out, centrifuged, and 375 μl of the supernatant was collected and diluted with 80 ml of methanol. Finally, the reaction results were analyzed by high-performance liquid chromatography (HPLC). The conversion rate of the starting material and the selectivity of the target product were calculated at 500 h and 1000 h, respectively.

[0061]

[0062] Note: "-" indicates that it was not monitored.

[0063] Comparing Examples 1-5 with Comparative Examples 1-4 in the table, it can be seen that adjusting the pH of the mixture with triethylamine significantly enhances the catalyst activity, mainly because triethylamine undergoes a complexation reaction with metal ions. Further calcination of the resulting solid catalyst enhances the activity of cobalt and manganese, improving the conversion rate and yield of the reaction. Simultaneously, the addition of the initiator NHPI facilitates the transfer of oxygen to the liquid phase, accelerating the oxidation rate of the raw materials. Combined with the active metal centers in the catalyst, this results in a better reaction outcome.

Claims

1. A method for preparing pyridine carboxylic acids, characterized in that: Using alkylpyridine as a raw material, pyridine carboxylic acid is obtained by reacting in a solvent of small molecule organic acid under the action of a cobalt-manganese solid catalyst and initiator NHPI at a temperature of 130 ℃-180 ℃ and a pressure of 2.0-4.0 MPa with oxygen-containing gas as an oxidant for 2-18 h. The cobalt-manganese solid catalyst is prepared as follows: Cobalt and manganese precursors were dissolved in water at a cobalt to manganese molar ratio of 0.1-10:0.1-10, ensuring a total metal salt molar concentration of 0.1-10 mol / L (calculated as cobalt and manganese), resulting in a mixed metal salt solution. Methanol was added to the metal salt solution while stirring at 300-1000 rpm. Triethylamine and methanol were added dropwise to the solution, adjusting the pH to 8-10, with a methanol to triethylamine volume ratio of 1-100:0.1-20. The reaction mixture was reacted in a water bath at 40-80 °C for 5-24 h, followed by cooling to room temperature. The mixture was filtered, and the solid was washed sequentially with methanol and deionized water until the filtrate was neutral. The solid was then dried at 80-150 °C for 3-24 h. Finally, the solid was calcined at 300-800 °C for 2-8 h, followed by cooling to room temperature to obtain the catalyst. The alkylpyridine is one or more of 2-alkylpyridine, 3-alkylpyridine, and 4-alkylpyridine; wherein the alkyl group in the alkylpyridine is methyl (-CH3), and the small molecule organic acid is formic acid or acetic acid.

2. The preparation method according to claim 1, characterized in that: Cobalt and manganese precursors were dissolved in water at a cobalt to manganese molar ratio of 0.5-5:0.5-5, ensuring that the total molar concentration of the metal salts (calculated as cobalt and manganese) was 0.5-5 mol / L, to obtain a mixed metal salt solution. Methanol was added to the mixed metal salt solution while stirring at 500-800 rpm. Triethylamine and methanol were added dropwise to the mixed solution, and the pH was adjusted to 8.5-9.5, wherein the volume ratio of methanol to triethylamine was 1-50:0.5-10.

3. The preparation method according to claim 1, characterized in that: The oxygen-containing gas can be one or more of air, oxygen-enriched air, or oxygen. The oxygen volume content in the oxygen-containing gas is 30-100%. When preparing pyridine carboxylic acid, the pressure of the oxygen-containing gas is 2.0-4.0 MPa.

4. The method for preparing pyridine carboxylic acids as described in claim 1, characterized in that: The precursors of cobalt are one or more of cobalt nitrate, cobalt chloride, cobalt sulfate, and cobalt acetate; the precursors of manganese are one or more of manganese nitrate, manganese chloride, manganese sulfate, and manganese acetate.

5. The preparation method according to claim 1, characterized in that: The mass fraction ratio of cobalt to manganese in this catalyst is 0.01-106.

82.

6. The preparation method according to claim 1, characterized in that: The mass ratio of the catalyst to alkylpyridine is 1:0.1-10.

7. The preparation method according to claim 1, characterized in that: The mass ratio of the initiator NHPI (N-hydroxyphthalimide) to the alkylpyridine substance is 0.01-0.5:1; the molar concentration of the small molecule organic acid solution of alkylpyridine is 0.4-1 mol / L.

8. The preparation method according to claim 1, characterized in that: The reaction temperature is 150-170 ℃; the reaction time is 4-10 h.

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