Preparation method for preparing pyridine carboxylic acid

Abstract

The invention discloses a preparation method of pyridine carboxylic acid, which is characterized in that under the catalysis of a cobalt-manganese solid catalyst, oxygen-containing gas oxidizes alkyl pyridine to prepare pyridine carboxylic acid. The reaction is preferably carried out at the temperature of 150-170 DEG C and under the pressure of 2.5-3.5 MPa, and the solvent is micromolecular organic acid. The preparation method is simple, the production performance is excellent, the action condition is mild, no environmental pollution is caused in the preparation process, equipment is not corroded, and the industrial application prospect and value are great.

Description

Technical Field

[0001] The invention relates to a method for preparing pyridine carboxylic acid, which is a method for obtaining pyridine carboxylic acid by catalytic oxidation of alkyl pyridine by oxygen-containing gas in a solid-liquid heterogeneous system. Background Art

[0002] Pyridine carboxylic acids refer to the insertion of a carboxyl group into the C of pyridine, including pyridine-2-carboxylic acid, pyridine-3-carboxylic acid (nicotinic acid), pyridine-4-carboxylic acid (isonicotinic acid), etc. Among them, pyridine-3-carboxylic acid, also known as nicotinic acid, is a water-soluble vitamin B3 that has the functions of improving cardiovascular health, relieving arthritis symptoms, improving digestive system function, enhancing immunity, and preventing diabetes. At the same time, it is mainly used as a food additive, feed additive, and pharmaceutical raw material in industry. The following mainly introduces the preparation technology of nicotinic acid, and the preparation of other pyridine carboxylic acid substances is similar to it.

[0003] Nicotinic acid is mainly prepared by oxidizing alkylpyridines, such as 3-methylpyridine, 2-methyl-5-ethylpyridine and quinoline. The main methods for synthesizing nicotinic acid include chemical synthesis, biological fermentation and plant extraction. Among them, the biological fermentation method is to use nicotinic acid production strains to ferment to produce nicotinic acid. It does not require the addition of chemical reagents, has little pollution to the environment, and can produce other useful metabolites during the production process. However, this method is costly and the product purity is low, requiring multiple separations; the plant extraction method is to extract nicotinic acid from natural plants. The advantage is that the product purity is high and it is pollution-free to the environment, but the cost is high and it is not suitable for large-scale industrial production. Therefore, the industry mainly relies on chemical synthesis.

[0004] Chemical synthesis methods include ammonia oxidation, oxidation, electrochemical oxidation, etc. Among them, the electrochemical oxidation method uses electrochemical action to electrolyze 3-methylpyridine solution to obtain nicotinic acid products. Although it is relatively green, the power consumption is high, the power utilization rate is low, the yield is low, and the treatment of by-products and waste liquids is relatively complicated. The ammonia oxidation method mainly involves ammonia oxidation of 3-methylpyridine or 2-methyl-5-ethylpyridine under the combined action of ammonia and oxygen-containing gas to obtain 3-cyanopyridine, which is then hydrolyzed with alkaline water to obtain nicotinic acid salts, and finally acidified to obtain nicotinic acid products. This method is relatively mature in industry and can achieve continuous production, but it will also cause some problems. This method introduces ammonia and uses a large amount of water during hydrolysis, producing more waste gas and wastewater, which in turn causes more environmental problems and post-processing costs. At the same time, the process is a multi-step method with low economic efficiency. The oxidation method is 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 patent CN99118373.8 also reported a similar method. The method is to gasify 3-methylpyridine and generate nicotinic acid products with oxygen and water vapor under the action of vanadium-titanium catalyst at high temperature. The method has a high yield, which can reach 82-86%, and the product purity is high. However, the method has high energy consumption and requires a high product concentration and precise temperature control, otherwise it is easy to produce tar, which will have an adverse effect on the catalyst.

[0006] The liquid phase oxidation method mainly produces nicotinic acid by oxidizing alkylpyridine with an oxidant. The oxidants mainly include potassium permanganate, concentrated nitric acid, concentrated sulfuric acid, NO2, O3, H2O2, oxygen, etc. Although the liquid phase oxidation method is relatively easy to separate the products and the reaction conditions are relatively mild, except for oxygen, other oxidants will cause a lot of corrosion to the reaction device, seriously shortening the service life. In addition, some oxidants will also cause certain pollution to the environment and increase the cost of post-processing. Patent CN200610146981.6 uses ozone and hydrogen peroxide as oxidants, and oxidizes 3-methylpyridine to produce nicotinic acid under the protection of sulfuric acid. Similar methods include patents CN202110512772.3 and patent CN202210801432.7. Although this scheme has a high purity, it introduces substances such as ozone, hydrogen peroxide and sulfuric acid, resulting in extremely high requirements for the corrosion resistance of the reactor. Nippon Chemical Co., Ltd. (patent number CN95100904.4) uses metal salts of cobalt, manganese, cerium and bromide to react at 150°C in a certain pressure of oxygen-containing gas to obtain the product. Since this method uses organic acid as solvent and adds bromide as initiator, it will greatly increase the corrosion resistance of the reaction device. Therefore, titanium is used as the main metal material of the reaction device in this patent, which greatly increases the cost. Japanese patent JP 2001253838 uses N-hydroxyphthalimide (NHPI) instead of bromide in the catalyst system as an initiator. The reaction can be carried out at normal pressure or lower pressure. Although the conversion rate and yield of this method are high, the amount of NHPI used in this method is relatively large, which makes it difficult to remove NHPI and its by-products from the product. Patent CN200510105668.3 uses cobalt, manganese metal salts, bromide and additional initiator to oxidize 3-alkylpyridine to obtain nicotinic acid. Although this method has a high product purity, bromide is introduced into the system, which will aggravate the corrosion of the equipment. Summary of the invention:

[0007] The object of the present invention is to provide a solid catalyst and a method for catalyzing the oxidation of alkyl pyridine with oxygen-containing gas in a solid-liquid heterogeneous system to obtain pyridine carboxylic acid substances. The method uses a cobalt-manganese-based solid catalyst with high activity and good selectivity, so that the oxidation reaction can be carried out at a lower temperature and lower pressure, and a higher yield is obtained, while solving the problem of solvent corrosion of equipment.

[0008] The preparation method of the pyridine carboxylic acid substance of the present invention comprises the following steps: using alkyl pyridine as a raw material, reacting in a solvent containing a small molecule organic acid, under the action of a cobalt-manganese solid catalyst and an initiator NHPI, at a temperature of 130° C. to 180° C. and a pressure of 2.0 to 4.0 MPa, using an oxygen-containing gas as an oxidant for 2 to 18 hours to obtain pyridine carboxylic acid.

[0009] The method for preparing the pyridine carboxylic acid substance is characterized in that the alkyl pyridine can be 2-alkyl pyridine, 3-alkyl pyridine and 4-alkyl pyridine.

[0010] The preparation method of the pyridine carboxylic acid substance 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 when preparing pyridine carboxylic acid, the pressure is 2.0-4.0 MPa, preferably 2.5-3.5 MPa.

[0012] The method for preparing the pyridine carboxylic acid substance is characterized in that the small molecule organic acid comprises formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid or caproic 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 two or more of any metal salts of the corresponding metals;

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

[0015] The method for preparing the pyridine carboxylic acid substance is characterized in that the method for preparing the cobalt-manganese solid catalyst is as follows:

[0016] The 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, and the molar concentration of the total metal salt is ensured to be 1 mol / L. Methanol is added to the metal nitrate mixed solution, and stirred at 600 rpm, triethylamine is added dropwise to the mixed solution, and the pH value is adjusted to 9, wherein the volume ratio of methanol to triethylamine is 1-100:0.1-20, preferably 1-50:0.5-10. The reaction mixture is subjected to condensation reflux reaction in a 40-80°C water bath for 5-24 hours, and then cooled to room temperature. After the mixture is filtered, the solid is washed with methanol and deionized water until the filtrate is neutral, and the solid is dried at 80-150°C for 3-24 hours. Finally, the solid is calcined at 300-800°C for 2-8 hours, and then cooled to room temperature to obtain a catalyst. The mass fractions of cobalt and manganese in the catalyst metal elements 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 pyridinecarboxylic acid substance is characterized in that the mass ratio of the catalyst to the pyridinecarboxylic acid substance 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 pyridine carboxylic acid substances is characterized in that the reaction temperature is 130-180°C, preferably 150-170°C; and the reaction time is 2-18h, preferably 4-10h.

[0020] The preparation method of the invention is simple, the production performance is excellent, the action conditions are relatively mild, there is no environmental pollution in the preparation process, and no corrosion to equipment, so the invention has great industrial application prospects and value.

[0021] The advantages of the present invention are as follows:

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

[0023] 2. This process does not require the introduction of ammonia source and water, and both the reaction solution solvent and the post-reaction treatment solvent can be recycled. The overall process generates almost no waste and is environmentally friendly;

[0024] 3. This process uses cheap metal oxides as catalysts, with low preparation costs, and no halogen is introduced during the preparation and use process, which reduces corrosion to the reactor and extends the service life of the reactor;

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

[0026] 5. This process is a one-step process. Compared with the multi-step process, no other reactions are required and it is more economical. DETAILED DESCRIPTION

[0027] The present invention is further described in detail below in conjunction with specific implementation methods. The protection scope of the present invention includes but is not limited to the following embodiments. Any modifications made to the details and forms of the technical solution of the present invention without departing from the meaning and scope of the present application shall fall within the protection scope of the present invention.

[0028] Example 1

[0029] Preparation of catalyst:

[0030] 16.8662g of cobalt sulfate heptahydrate and 6.6918g of manganese sulfate tetrahydrate were dissolved in 90mL of water to ensure that the molar concentration of the total metal salt was 1mol / L. 10ml of methanol was added to the mixed solution of metal nitrates, and stirred at 600rpm. Triethylamine and methanol were added dropwise to the mixed solution, and the pH value was adjusted to 9, and the volume ratio of methanol to triethylamine was ensured to be 1:10. The reaction mixture was reacted in a 60℃ water bath for 16h and then cooled to room temperature. The mixture was filtered and washed three times with methanol, and then the solid was washed with deionized water until the filtrate was neutral. The solid was then dried at a constant temperature of 100℃ for 12h. Finally, the solid was calcined at 400℃ for 5h, and a cobalt-manganese solid catalyst a was obtained after cooling to room temperature. The mass fractions of cobalt and manganese in the catalyst metal elements were 47.63% and 22.20%, respectively.

[0031] Reaction feeding:

[0032] 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 to a reaction kettle equipped with an electromagnetic stirrer, a temperature controller, and a gas introduction tube, and then stirred and oxygen was introduced to control the pressure in the kettle to 3 MPa. The reaction was heated to 160°C and then the timing was started. The reaction temperature was controlled at 160-170°C during the reaction, and the reaction was terminated after 5.5 hours, and then cooled to room temperature.

[0033] Comparative Example 1

[0034] The catalyst preparation steps (process and conditions, the same below) are the same as those in Example 1, except that methanol is removed and triethylamine is replaced with 10wt% ammonia water, that is, "methanol is added to the metal nitrate mixed solution, stirred at 600rpm, triethylamine is added dropwise to the mixed solution, and the pH value is adjusted to 9, wherein the volume ratio of methanol to triethylamine is 1:10." is replaced by "stirring at 600rpm, adding 10wt% ammonia water to the mixed solution, and adjusting the pH value to 9". Finally, a cobalt-manganese solid catalyst a1 is obtained. The mass fractions of cobalt and manganese in the catalyst metal elements are 45.37% and 24.46%, respectively.

[0035] The reaction process and conditions are 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 charging steps (process and conditions) are the same as those in Example 1, except that the cobalt-manganese catalyst is removed, that is, "add 3-methylpyridine 8 mmol, acetic acid 12 ml, cobalt-manganese solid catalyst a 1.92 g, NHPI 65.25 mg" is replaced by "add 3-methylpyridine 8 mmol, acetic acid 12 ml, NHPI 65.25 mg".

[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 charging step (process and conditions) is the same as that in Example 1, except that 65.25 mg of NHPI is removed, that is, "add 3-methylpyridine 8 mmol, acetic acid 12 ml, cobalt-manganese solid catalyst a 1.92 g, NHPI 65.25 mg" is replaced by "add 3-methylpyridine 8 mmol, acetic acid 12 ml, NHPI 65.25 mg".

[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 step (process and conditions) is the same as that in Example 1, except that 65.25 mg NHPI is replaced by 46.036 mg N-hydroxysuccinimide, that is, "add 3-picoline 8 mmol, acetic acid 12 ml, cobalt-manganese solid catalyst a 1.92 g, NHPI 65.25 mg" is replaced by "add 3-picoline 8 mmol, acetic acid 12 ml, cobalt-manganese solid catalyst a 1.92 g, N-hydroxysuccinimide 46.036 mg".

[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 those in Example 1, except that 3-picoline is replaced by 4-picoline, that is, “add 3-picoline 8 mmol, acetic acid 12 ml, cobalt-manganese solid catalyst a 1.92 g, NHPI 65.25 mg” is replaced by “add 4-picoline 8 mmol, acetic acid 12 ml, cobalt-manganese solid catalyst a 1.92 g, NHPI 65.25 mg”.

[0048] Example 3

[0049] Preparation of catalyst:

[0050] 21.8273g of cobalt nitrate hexahydrate and 3.7652g of manganese nitrate tetrahydrate were dissolved in 90mL of water to ensure that the molar concentration of the total metal salt was 1mol / L. Methanol was added to the metal nitrate mixed solution, stirred at 600rpm, triethylamine was added dropwise to the mixed solution, and the pH value was adjusted to 9, wherein the volume ratio of methanol to triethylamine was 1:10. The reaction mixture was subjected to condensation reflux reaction in a 65°C water bath for 18h, and then cooled to room temperature. The mixture was filtered and washed three times with methanol, and then the solid was washed with deionized water until the filtrate was neutral. The solid was then dried at a constant temperature of 120°C for 18h. Finally, the solid was calcined at 500°C for 4h, and after cooling to room temperature, a cobalt-manganese solid catalyst b was obtained. The mass fractions of cobalt and manganese in the catalyst metal elements were 60.35% and 11.25%, respectively.

[0051] The reaction process and conditions are 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 those in Example 3;

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

[0055] Example 5

[0056] Preparation of catalyst:

[0057] 7.4724g of cobalt acetate tetrahydrate and 7.2927g of manganese acetate tetrahydrate were dissolved in 60mL of water to ensure that the molar concentration of the total metal salt was 1mol / L. Methanol was added to the metal nitrate mixed solution, stirred at 600rpm, triethylamine was added dropwise to the mixed solution, and the pH value was adjusted to 9, wherein the volume ratio of methanol to triethylamine was 1:10. The reaction mixture was subjected to condensation reflux reaction in a 70°C water bath for 14h, and then cooled to room temperature. The mixture was filtered and washed three times with methanol, and then the solid was washed with deionized water until the filtrate was neutral. The solid was then dried at a constant temperature of 120°C for 16h. Finally, the solid was calcined at 500°C for 5h, and after cooling to room temperature, a cobalt-manganese solid catalyst a was obtained. The mass fractions of cobalt and manganese in the catalyst metal elements were 35.25% and 32.86%, respectively.

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

[0059] Example 6

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

[0061]

[0062] Note: “-” means not monitored.

[0063] By comparing Examples 1-5 and Comparative Examples 1-4 in the table, it can be found that the pH of the mixed solution can be adjusted by triethylamine to ensure that the activity of the catalyst is greatly enhanced, mainly because triethylamine and metal ions undergo a complex reaction. The solid catalyst obtained by calcination can enhance the activity of cobalt and manganese, and improve the conversion rate and yield of the reaction. At the same time, the initiator NHPI is added to better transfer oxygen to the liquid phase, accelerate the oxidation rate of the raw material, and cooperate with the metal active center in the catalyst to enable the reaction to obtain better results.

Claims

1. A method for preparing a pyridine carboxylic acid, characterized in that: Alkyl pyridine is used as a raw material, in a solvent containing a small molecule organic acid (with a carbon number in the range of 1-6), under the action of a cobalt-manganese solid catalyst and an initiator NHPI, at a temperature of 130° C.-180° C. and a pressure of 2.0-4.0 MPa, and with an oxygen-containing gas as an oxidant, the reaction is carried out for 2-18 hours to obtain pyridine carboxylic acid.

2. The preparation method according to claim 1, characterized in that: The alkylpyridine can be one or more of 2-alkylpyridine, 3-alkylpyridine and 4-alkylpyridine; wherein the alkyl group in the alkylpyridine is one or more of methyl (-CH3), ethyl (-CH2CH3), propyl (-CH2CH2CH3), isopropyl (-CH(CH3)2), butyl (-CH2CH2CH2CH3), isobutyl (-CH2CH(CH3)2).

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 volume content of oxygen in the oxygen-containing gas is 30-100%. When preparing pyridinecarboxylic acid, the pressure of the oxygen-containing gas is 2.0-4.0 MPa, preferably 2.5-3.5 MPa.

4. The preparation method according to claim 1, characterized in that: The small molecule organic acid includes one or more of formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid or caproic acid.

5. The method for preparing a pyridine carboxylic acid according to claim 1, wherein: The precursors of the active components cobalt and manganese in the cobalt-manganese solid catalyst are one or two or more of any metal salts of the corresponding metal (cobalt or manganese); For example, the precursor of cobalt can be one or two or more of cobalt nitrate, cobalt chloride, cobalt sulfate, and cobalt acetate; the precursor of manganese can be one or two or more of manganese nitrate, manganese chloride, manganese sulfate, and manganese acetate; The cobalt-manganese solid catalyst preparation method is as follows: The cobalt and manganese precursors are dissolved in water at a molar ratio of cobalt to manganese of 0.1-10:0.1-10 (preferably 0.5-5:0.5-5), and the molar concentration of the total metal salt (in terms of cobalt and manganese) is ensured to be 0.1-10 mol / L (preferably 0.5-5 mol / L) to obtain a metal salt mixed solution; methanol is added to the metal salt mixed solution, while stirring at a speed of 300-1000 rpm (preferably 500-800 rpm), triethylamine and methanol are added dropwise to the mixed solution, and the pH value is adjusted. to 8-10 (preferably 8.5-9.5), wherein the volume ratio of methanol to triethylamine is 1-100:0.1-20 (preferably 1-50:0.5-10); the reaction mixture is reacted in a 40-80°C water bath for 5-24 hours, and then cooled to room temperature; the mixture is filtered, and the solid is washed with methanol and deionized water in sequence until the filtrate is neutral, and the solid is dried at 80-150°C for 3-24 hours; finally, the solid is calcined at 300-800°C for 2-8 hours, and then cooled to room temperature to obtain a catalyst.

6. The preparation method according to claim 6, characterized in that: The mass fraction ratio of cobalt to manganese in the catalyst metal elements is 0.01-106.82, preferably 0.11-10.

72.

7. The preparation method according to claim 1, characterized in that: The mass ratio of the catalyst to the alkyl pyridine is 1:0.1-10, preferably 1:1-5.

8. The preparation method according to claim 1, characterized in that: The mass ratio of the initiator NHPI (N-hydroxyphthalimide) to the alkyl pyridine substance is 0.01-0.5:1, preferably 0.05-0.3:1; the molar concentration of the small molecule organic acid (carbon number in the range of 1-6) of alkyl pyridine is 0.4-1 mol / L, preferably 0.6-0.8 mol / L.

9. The preparation method according to claim 1, characterized in that: The reaction temperature is 130-180° C., preferably 150-170° C.; the reaction time is 2-18 h, preferably 4-10 h.

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