Synthesis method of 2-aminopyridine
By using amino-functionalized Zr-MOF catalysts to synthesize 2-aminopyridine under mild conditions, the problems of harsh reaction conditions, serious environmental pollution and high cost in the existing technology have been solved. This method achieves the synthesis of 2-aminopyridine with high selectivity and high yield, which is suitable for industrial production.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-01-04
- Publication Date
- 2026-04-03
AI Technical Summary
Existing methods for synthesizing 2-aminopyridine suffer from harsh reaction conditions, severe environmental pollution, high raw material costs, low product yields, and poor selectivity, making it difficult to meet the needs of industrial production.
2-Aminopyridine is synthesized by catalyzing the reaction of pyridine and hydroxylamine sulfonic acid under mild conditions using amino-functionalized Zr-MOF catalysts. This method uses recyclable ethanol solvent and reusable catalysts, reducing environmental pollution and costs.
This method significantly improves the selectivity and yield of 2-aminopyridine, while maintaining mild reaction conditions, reducing equipment requirements and energy consumption. It aligns with the development concept of green chemistry and lowers production costs.
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Figure CN121779320A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology, and specifically relates to a method for synthesizing 2-aminopyridine. Background Technology
[0002] 2-Aminopyridine, as an important organic chemical intermediate, is widely used in pharmaceuticals, pesticides, dyes, and polymer materials. In the pharmaceutical field, it is a key raw material for the synthesis of various drugs such as antihistamines, antibacterial drugs, and antiviral drugs; in the pesticide field, it can be used to prepare insecticides and herbicides; and in the dye industry, it can serve as an intermediate for azo dyes.
[0003] Currently, the main methods for synthesizing 2-aminopyridine are as follows: 1. Ammonolysis: 2-Chloroprene is reacted with ammonia under high temperature and pressure to produce 2-aminopyridine. This method requires harsh reaction conditions (temperature typically 150-200℃, pressure 5-10MPa), demands sophisticated equipment, and easily generates byproducts such as 2,6-diaminopyridine. Product separation and purification are difficult, resulting in a low yield, generally only 60%-70%.
[0004] 2. Hoffmann degradation method: 2-Aminopyridine is prepared from nicotinamide via a Hoffmann degradation reaction. This method involves multiple reaction steps, requires large amounts of strong alkali (such as sodium hypochlorite and sodium hydroxide), generates a large amount of wastewater, causing significant environmental pollution. Furthermore, over-degradation is prone to occur during the reaction, leading to unstable product yields.
[0005] 3. Catalytic hydrogenation method: Using 2-nitropyridine as a raw material, a hydrogenation reaction is carried out in the presence of a catalyst (such as palladium on carbon or Raney nickel) to produce 2-aminopyridine. Although the reaction conditions are relatively mild, the raw material 2-nitropyridine is expensive, and the catalyst is prone to poisoning and deactivation, resulting in a short lifespan, which increases production costs. At the same time, strict control of hydrogen pressure and reaction temperature is required during the reaction process, making the operation more difficult.
[0006] In summary, existing methods for synthesizing 2-aminopyridine suffer from problems such as harsh reaction conditions, severe environmental pollution, high raw material costs, low product yields, and poor selectivity, making it difficult to meet the demands of industrial production for high efficiency, environmental friendliness, and low cost. Therefore, developing a novel, efficient, environmentally friendly, and low-cost method for synthesizing 2-aminopyridine has significant practical importance and application value. Summary of the Invention
[0007] The purpose of this invention is to provide a method for synthesizing 2-aminopyridine, which has mild reaction conditions, high selectivity and yield, and the advantages of being both environmentally friendly and low-cost.
[0008] To achieve the above objectives, the present invention provides a method for synthesizing 2-aminopyridine, comprising the following steps: Step S1: Prepare amino-functionalized Zr-MOF catalysts; Step S11: Add ZrCl4 and amino-functionalized terephthalic acid ligand to 200-250 mL of N,N-dimethylformamide and stir to react. Step S12: After the reaction is complete, centrifuge at a speed of 3000~5000 r / min to obtain a solid product; Step S13: Wash the solid product 3 to 5 times with 5 times the mass of N,N-dimethylformamide and methanol respectively, and dry it under vacuum at -0.08 to -0.1 MPa to obtain the amino-functionalized Zr-MOF catalyst; Step S2: Synthesis of 2-aminopyridine; Pyridine, hydroxylamine sulfonic acid, amino-functionalized Zr-MOFs catalyst, and ethanol were added to a three-necked flask and stirred to obtain 2-aminopyridine. Step S3: Separate and purify 2-aminopyridine to obtain pure 2-aminopyridine.
[0009] Preferably, in step S11, the molar ratio of ZrCl4 to the amino-functionalized terephthalic acid ligand is 1:(1.2~1.5); the stirring temperature is 40~100℃, and the stirring time is 6~18h; Among them, the amino-functionalized terephthalic acid ligand is 2-aminoterephthalic acid or 5-aminoterephthalic acid.
[0010] Preferably, in step S13, the vacuum drying temperature is 60~80℃ and the vacuum drying time is 8~12h.
[0011] Preferably, in step S2, the molar ratio of pyridine to hydroxylamine sulfonic acid is 1:(1.1~1.3), the mass of the amino-functionalized Zr-MOFs catalyst is 5%~8% of the mass of pyridine, and the volume of ethanol is 5~8 times the volume of pyridine.
[0012] Preferably, the molar ratio of pyridine to hydroxylamine sulfonic acid is 1:1.1, the mass of the amino-functionalized Zr-MOFs catalyst is 6% to 7% of the mass of pyridine, and the volume of ethanol is 5 to 7 times the volume of pyridine.
[0013] Preferably, in step S2, the temperature of the stirring reaction is 40~70℃, and the stirring reaction time is 6~24h.
[0014] Preferably, the temperature of the stirring reaction is 50~60℃, and the stirring reaction time is 8~16h.
[0015] Preferably, step S3 specifically includes: Step S31: 2-Aminopyridine is filtered to remove the amino-functionalized Zr-MOF catalyst, and the filtrate is obtained. Step S32: Distill the filtrate at 80°C to remove ethanol, and obtain the crude product; Step S33: Recrystallize the crude product with ethyl acetate and filter to obtain white crystals, which is pure 2-aminopyridine.
[0016] Preferably, in step S31, the amino-functionalized Zr-MOFs catalyst removed by filtration is dried, recovered, and reused.
[0017] Preferably, in step S33, the mass of ethyl acetate is 3-5 times the mass of the crude product.
[0018] The present invention employs the above-mentioned method for synthesizing 2-aminopyridine, and the beneficial effects are as follows: (1) Catalyst Innovation: This invention is the first to use amino-functionalized Zr-MOFs as a metal-organic framework catalyst for the synthesis of 2-aminopyridine. Zr-MOFs have a large specific surface area and abundant pore structure. After amino functionalization, their surface has more active sites, which can significantly improve the catalytic activity and selectivity for the reaction of pyridine and hydroxylamine sulfonic acid, and effectively suppress the occurrence of side reactions. The examples of this invention show that when using this catalyst, the selectivity of 2-aminopyridine can reach more than 95%, and the yield can reach more than 90%, which is much higher than the yield of existing synthesis methods.
[0019] (2) Mild reaction conditions: The synthesis reaction of the present invention is carried out under mild temperature conditions of 40~70℃, without the need for high temperature and high pressure equipment, which reduces the requirements for equipment and energy consumption, and is simple and easy to operate, making it convenient for industrial production.
[0020] (3) Environmentally friendly: The solvent used in this invention is ethanol, which is non-toxic and easy to recycle; at the same time, the catalyst can be recycled and reused. After five cycles, its catalytic activity can still maintain more than 90% of the initial activity, reducing the waste of catalyst and pollution to the environment; no large amount of toxic and harmful wastewater or waste gas is generated during the reaction process, which is in line with the development concept of green chemistry.
[0021] (4) Low cost: The raw materials pyridine and hydroxylamine sulfonic acid used in this invention are relatively inexpensive, and the catalyst is used in small quantities and can be reused, which reduces the cost of raw materials and catalysts, which is conducive to reducing the production cost of 2-aminopyridine and improving the market competitiveness of the product.
[0022] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description
[0023] Figure 1 This is a schematic diagram of the synthesis process in Example 1 of the synthesis method of 2-aminopyridine according to the present invention. Detailed Implementation
[0024] The technical solution of the present invention will be further described below with reference to the accompanying drawings and embodiments.
[0025] Unless otherwise defined, the technical or scientific terms used in this invention shall have the ordinary meaning as understood by one of ordinary skill in the art to which this invention pertains.
[0026] Example 1 like Figure 1 As shown, a method for synthesizing 2-aminopyridine includes the following steps: Step S1: Prepare amino-functionalized Zr-MOF catalysts; Step S11: Add 0.1 mol of ZrCl4 (23.3 g) and 0.12 mol of 2-aminoterephthalic acid (21.74 g) to 200 mL of N,N-dimethylformamide solvent and stir the reaction at 40 °C for 18 h. Step S12: After the reaction is complete, centrifuge at 4000 r / min to obtain a solid product; Step S13: Wash the solid product three times with 5 times the mass of N,N-dimethylformamide and methanol, and then vacuum dry it at -0.09 MPa for 12 hours to obtain the amino-functionalized Zr-MOF catalyst. Step S2: Synthesis of 2-aminopyridine; In a three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add pyridine (0.1 mol, 7.8 g), hydroxylamine sulfonic acid (0.11 mol, 10.68 g), amino-functionalized Zr-MOF catalyst (0.39 g, 5% of the mass of pyridine), and ethanol (40.5 mL, 5 times the volume of pyridine, with a density of 0.98 g / cm³). 3 The volume was calculated to be approximately 8.1 mL. Then, the three-necked flask was placed in a constant temperature water bath and stirred for 24 hours to obtain 2-aminopyridine. Step S3: Separate and purify 2-aminopyridine to obtain pure 2-aminopyridine.
[0027] Step S31: 2-Aminopyridine is filtered to remove the amino-functionalized Zr-MOF catalyst, and the filtrate is obtained. The amino-functionalized Zr-MOF catalyst removed by filtration is dried, recovered, and reused.
[0028] Step S32: Distill the filtrate at 80°C to remove ethanol, and obtain the crude product; Step S33: Recrystallize the crude product with ethyl acetate, the mass of which is 3 times the mass of the crude product. Filter to obtain white crystals, which are pure 2-aminopyridine.
[0029] Example 2 A method for synthesizing 2-aminopyridine includes the following steps: Step S1: Prepare amino-functionalized Zr-MOF catalysts; Step S11: Add 0.1 mol of ZrCl4 (23.30 g) and 0.15 mol of 2-aminoterephthalic acid (27.17 g) to 250 mL of N,N-dimethylformamide solvent and stir the reaction at 100 °C for 6 h. Step S12: After the reaction is complete, centrifuge at 4000 r / min to obtain a solid product; Step S13: Wash the solid product five times each with 5 times the mass of N,N-dimethylformamide and methanol, and then vacuum dry it at -0.09 MPa for 80°C for 8 hours to obtain the amino-functionalized Zr-MOF catalyst. Step S2: Synthesis of 2-aminopyridine; In a three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add (0.1 mol, 7.9 g) pyridine, (0.13 mol, 15.3 g) hydroxylamine sulfonic acid, (0.632 g, 8% of the mass of pyridine) amino-functionalized Zr-MOF catalyst, and (64.8 mL, 8 times the volume of pyridine, with a density of 0.98 g / cm³) 3 The volume was calculated to be approximately 8.1 mL. Then, the three-necked flask was placed in a constant temperature water bath and stirred for 6 hours to obtain 2-aminopyridine. Step S3: Separate and purify 2-aminopyridine to obtain pure 2-aminopyridine.
[0030] Step S31: 2-Aminopyridine is filtered to remove the amino-functionalized Zr-MOF catalyst, and the filtrate is obtained. The amino-functionalized Zr-MOF catalyst removed by filtration is dried, recovered, and reused.
[0031] Step S32: Distill the filtrate at 80°C to remove ethanol, and obtain the crude product; Step S33: Recrystallize the crude product with ethyl acetate, the mass of which is 3 times the mass of the crude product. Filter to obtain white crystals, which are pure 2-aminopyridine.
[0032] Example 3 A method for synthesizing 2-aminopyridine includes the following steps: Step S1: Prepare amino-functionalized Zr-MOF catalysts; Step S11: Add 0.1 mol of ZrCl4 (23.30 g) and 0.13 mol of 2-aminoterephthalic acid (23.55 g) to 220 mL of N,N-dimethylformamide solvent and stir the reaction at 90 °C for 18 h. Step S12: After the reaction is complete, centrifuge at 4000 r / min to obtain a solid product; Step S13: Wash the solid product four times each with 5 times the mass of N,N-dimethylformamide and methanol, and then vacuum dry it at -0.09 MPa for 70°C for 10 hours to obtain the amino-functionalized Zr-MOF catalyst. Step S2: Synthesis of 2-aminopyridine; In a three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add (0.1 mol, 7.9 g) pyridine, (0.12 mol, 14.1 g) hydroxylamine sulfonic acid, (0.395 g, 5% of the mass of pyridine) amino-functionalized Zr-MOF catalyst, and (40.5 mL, 5 times the volume of pyridine, with a density of 0.98 g / cm³) 3 The volume was calculated to be approximately 8.1 mL. Then, the three-necked flask was placed in a constant temperature water bath and stirred for 10 h to obtain 2-aminopyridine. Step S3: Separate and purify 2-aminopyridine to obtain pure 2-aminopyridine.
[0033] Step S31: 2-Aminopyridine is filtered to remove the amino-functionalized Zr-MOF catalyst, and the filtrate is obtained. The amino-functionalized Zr-MOF catalyst removed by filtration is dried, recovered, and reused.
[0034] Step S32: Distill the filtrate at 80°C to remove ethanol, and obtain the crude product; Step S33: Recrystallize the crude product with ethyl acetate, the mass of which is 3 times the mass of the crude product. Filter to obtain white crystals, which are pure 2-aminopyridine.
[0035] Comparative Example 2-Aminopyridine was synthesized using the traditional ammonolysis method: 2-chloropyridine (0.1 mol) and ammonia (25%, 0.5 mol) were added to a high-pressure reactor and reacted at 180 °C and 8 MPa for 10 h. After the reaction was completed, the mixture was cooled to room temperature, the pressure was released, the reaction solution was distilled, the fraction was collected, and 2-aminopyridine was obtained by recrystallization with ethyl acetate.
[0036] Experimental Example 1 The pure 2-aminopyridine prepared in Examples 1-3 and the 2-aminopyridine prepared in the comparative examples were tested, and the results are shown in Table 1.
[0037] Table 1 Test Results
[0038] As shown in Table 1, the synthesis method of the present invention is significantly superior to the traditional ammonolysis method in terms of yield and selectivity, and the reaction conditions are milder, more environmentally friendly, and lower in cost.
[0039] Experimental Example 2 The amino-functionalized Zr-MOFs catalysts removed by filtration in Examples 1-3 were dried, recovered, and reused 5 times, and their initial activity was tested.
[0040] Testing revealed that the catalytic activity of the amino-functionalized Zr-MOFs catalysts removed by filtration in Examples 1-3 remained above 90% of their initial activity, thereby reducing catalyst waste and environmental pollution.
[0041] Therefore, the present invention adopts the above-mentioned method for synthesizing 2-aminopyridine, which has mild reaction conditions, high selectivity and yield, and the advantages of being both environmentally friendly and low-cost.
[0042] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.
Claims
1. A method for synthesizing 2-aminopyridine, characterized in that, Includes the following steps: Step S1: Prepare amino-functionalized Zr-MOF catalysts; Step S11: Add ZrCl4 and amino-functionalized terephthalic acid ligand to 200-250 mL of N,N-dimethylformamide and stir to react. Step S12: After the reaction is complete, centrifuge at a speed of 3000~5000 r / min to obtain a solid product; Step S13: Wash the solid product 3 to 5 times with 5 times the mass of N,N-dimethylformamide and methanol respectively, and dry it under vacuum at -0.08 to -0.1 MPa to obtain the amino-functionalized Zr-MOF catalyst; Step S2: Synthesis of 2-aminopyridine; Pyridine, hydroxylamine sulfonic acid, amino-functionalized Zr-MOFs catalyst, and ethanol were added to a three-necked flask and stirred to obtain 2-aminopyridine. Step S3: Separate and purify 2-aminopyridine to obtain pure 2-aminopyridine.
2. The method for synthesizing 2-aminopyridine according to claim 1, characterized in that: In step S11, the molar ratio of ZrCl4 to the amino-functionalized terephthalic acid ligand is 1:(1.2~1.5); the stirring temperature is 40~100℃, and the stirring time is 6~18h. Among them, the amino-functionalized terephthalic acid ligand is 2-aminoterephthalic acid or 5-aminoterephthalic acid.
3. The method for synthesizing 2-aminopyridine according to claim 1, characterized in that: In step S13, the vacuum drying temperature is 60~80℃ and the vacuum drying time is 8~12h.
4. The method for synthesizing 2-aminopyridine according to claim 1, characterized in that: In step S2, the molar ratio of pyridine to hydroxylamine sulfonic acid is 1:(1.1~1.3), the mass of the amino-functionalized Zr-MOFs catalyst is 5%~8% of the mass of pyridine, and the volume of ethanol is 5~8 times the volume of pyridine.
5. The method for synthesizing 2-aminopyridine according to claim 4, characterized in that: The molar ratio of pyridine to hydroxylamine sulfonic acid is 1:1.1, the mass of the amino-functionalized Zr-MOF catalyst is 6% to 7% of the mass of pyridine, and the volume of ethanol is 5 to 7 times the volume of pyridine.
6. The method for synthesizing 2-aminopyridine according to claim 1, characterized in that: In step S2, the temperature of the stirring reaction is 40~70℃, and the stirring reaction time is 6~24h.
7. The method for synthesizing 2-aminopyridine according to claim 6, characterized in that: The temperature for the stirring reaction is 50~60℃, and the stirring reaction time is 8~16h.
8. The method for synthesizing 2-aminopyridine according to claim 1, characterized in that, Step S3 is as follows: Step S31: 2-Aminopyridine is filtered to remove the amino-functionalized Zr-MOF catalyst, and the filtrate is obtained. Step S32: Distill the filtrate at 80°C to remove ethanol, and obtain the crude product; Step S33: Recrystallize the crude product with ethyl acetate and filter to obtain white crystals, which is pure 2-aminopyridine.
9. The method for synthesizing 2-aminopyridine according to claim 8, characterized in that: In step S31, the amino-functionalized Zr-MOF catalyst removed by filtration is dried, recovered, and reused.
10. The method for synthesizing 2-aminopyridine according to claim 8, characterized in that: In step S33, the mass of ethyl acetate is 3 to 5 times the mass of the crude product.