A method for synthesizing 4-methylpyridine by using a Pd / LDH catalyst

Abstract

This invention discloses a method for synthesizing 4-methylpyridine using a Pd / LDH catalyst, belonging to the field of organic chemical synthesis technology. The method includes the following steps: S1, preparing the Pd / LDH catalyst: mixing an aqueous PdCl2 solution with a Mg-Al type LDH support, impregnating at room temperature, drying, and then reducing to obtain the Pd / LDH catalyst; S2, under an inert atmosphere, adding 4-methylpiperidine, the Pd / LDH catalyst, and a low-toxicity solvent to a reaction vessel, stirring the reaction, and then separating and purifying to obtain 4-methylpyridine. This invention, through the combination of a supported Pd / LDH catalyst and a low-toxicity solvent, achieves comprehensive improvements in catalytic efficiency, environmental friendliness, ease of operation, and economy, representing a promising green synthesis route; the reaction conditions are mild, the operation is simple, and the catalyst can be recycled more than 5 times, making it suitable for industrial production.

Description

Technical Field

[0001] This invention relates to the field of organic chemical synthesis, and in particular to a method for synthesizing 4-methylpyridine using a Pd / LDH catalyst. Background Technology

[0002] 4-Methylpyridine is an important organic chemical raw material and fine chemical intermediate, widely used in pharmaceuticals, pesticides, dyes, fragrances, rubber additives, and other fields. For example, in the pharmaceutical field, it can be used as an intermediate in the synthesis of certain antibacterial drugs and central nervous system drugs; in the pesticide field, it can be used to synthesize highly effective insecticides and herbicides.

[0003] Currently, the main industrial methods for producing 4-methylpyridine are the acetaldehyde-ammonia process and the methylglutaronitrile cyclization process. The acetaldehyde-ammonia process requires reaction at 350-400℃ and 2-3MPa, with a yield of only 60-70%, high energy consumption, and demanding equipment requirements. On the other hand, the methylglutaronitrile cyclization process requires the use of highly corrosive reagents, with byproduct content reaching 15-20%, and generates a large amount of acidic wastewater, causing serious environmental pollution.

[0004] In addition, in order to improve catalytic performance, researchers have tried a variety of catalytic synthesis methods, such as the commonly used Pd / C catalyst to achieve the synthesis of 4-methylpyridine. However, this method has the problems of low selectivity and many by-products.

[0005] Based on the above problems, developing a mild, highly selective, and environmentally friendly method for the synthesis of 4-methylpyridine is of great practical significance. Summary of the Invention

[0006] The purpose of this invention is to provide a method for synthesizing 4-methylpyridine using a Pd / LDH catalyst to solve the problems in the prior art. This method has mild reaction conditions, is simple to operate, has high product selectivity, is environmentally friendly, and the catalyst can be recycled, making it suitable for industrial production.

[0007] To achieve the above objectives, the present invention provides a method for synthesizing 4-methylpyridine using a Pd / LDH catalyst, comprising the following steps: S1. Preparation of Pd / LDH catalyst: PdCl2 aqueous solution was mixed with Mg-Al type LDH support by equal volume impregnation method, impregnated at room temperature, dried and reduced to obtain Pd / LDH catalyst. Pd / LDH catalyst is Mg-Al type layered double hydroxide supported palladium catalyst. S2. Under an inert atmosphere, 4-methylpiperidine, Pd / LDH catalyst, and low-toxicity solvent are added to a reaction vessel. After stirring and reacting, 4-methylpyridine is obtained by separation and purification.

[0008] Preferably, in S1, the volume ratio of PdCl2 aqueous solution to Mg-Al type LDH support is 1:1; in the Mg-Al type LDH support, Mg 2+ With Ag 3+ The molar ratio was 3:1; the palladium loading in the obtained Pd / LDH catalyst was 3 mol.

[0009] Preferably, in step S1, the impregnation time is 10-12 hours, the drying temperature is 60-100°C, and the reduction process is carried out in an H2 atmosphere at 300-320°C for 1.5-2 hours.

[0010] Preferably, in S2, the mass ratio of Pd / LDH catalyst to 4-methylpiperidine is 12~18:1.

[0011] Preferably, in step S2, the low-toxicity solvent is one of n-heptane, cyclohexane, or toluene, and the amount used is 8 to 12 times the volume of 4-methylpiperidine, which can balance the reaction efficiency and control of side reactions. When the amount is less than 8 times, the substrate concentration is too high and side reactions are easily caused. When it is more than 12 times, the reaction efficiency decreases.

[0012] Preferably, in step S2, the inert atmosphere is argon or nitrogen, with argon being preferred; the reaction conversion rate under a nitrogen atmosphere is 3-5% lower than that under an argon atmosphere.

[0013] Preferably, in step S2, during the stirring reaction, the temperature is 80~100℃ and the pressure is 90~100kPa, which can promote H2 desorption and increase the reaction rate. When the pressure is below 90kPa, the solvent is prone to volatilization, causing fluctuations in the system concentration. When the pressure is above 100kPa, the desorption of H2 generated by the dehydrogenation reaction is hindered, and the conversion rate decreases. The time is 16-18 hours; A stirring speed of 500~1000 rpm can ensure the uniformity of the reaction system and avoid mass transfer limitations. When the stirring speed is below 500 rpm, the reaction solution is not mixed sufficiently, and the conversion rate drops to below 85%. When the stirring speed is above 1000 rpm, there is no significant gain and energy consumption increases.

[0014] Preferably, in step S2, during the stirring reaction, a refrigerant is used to cool the upper part of the reactor to -5°C to 0°C to condense solvent vapor, avoid solvent loss, and suppress product volatilization; above 0°C, the amount of solvent volatilization increases and the yield decreases; below -5°C, there is no significant gain and the cooling energy consumption increases.

[0015] Preferably, in step S2, the pressure of the stirring reaction is 93~97 kPa.

[0016] Preferably, in step S2, the separation and purification process is as follows: first, the catalyst is separated by centrifugation, then the obtained catalyst is washed with n-heptane, and the supernatant is separated by vacuum distillation or column chromatography to obtain 4-methylpyridine with a purity ≥99.0%; n-Heptane can be recycled after being dried at 80°C; In vacuum distillation, the pressure is 5 kPa, and the fraction at 80-82℃ is collected. In column chromatography separation, a 10:1 volume ratio of petroleum ether to ethyl acetate was used as the eluent.

[0017] Therefore, the method for synthesizing 4-methylpyridine using a Pd / LDH catalyst of the present invention has the following beneficial effects: (1) The Pd / LDH catalyst prepared by the equal volume impregnation method in this invention can achieve high dispersion of palladium (Pd) active component on Mg-Al type layered double hydroxide (LDH) support; the LDH support itself has basic characteristics, which may synergistically promote the dehydrogenation reaction of 4-methylpiperidine, thereby achieving high conversion and selectivity under mild conditions, and the by-products are much lower than those of traditional methods and Pd / C catalytic systems.

[0018] (2) This invention explicitly uses low-toxicity solvents to replace the toxic or highly volatile organic solvents that may be used in the past, thereby reducing the environmental and safety risks in the production process; the catalyst can be recycled more than 5 times, and no large amount of harmful waste is generated during the reaction process. Compared with the methylglutaronitrile cyclization method, it can reduce the discharge of acidic wastewater by 100%.

[0019] (3) The method protected by this invention does not mention harsh conditions such as high temperature and high pressure in the room temperature impregnation, subsequent reduction and reaction steps, which helps to reduce energy consumption and equipment requirements; the energy consumption is low, conventional stirring and cooling equipment is used, the steps are simple, the catalyst recovery method is convenient, and it is easy to scale up industrially.

[0020] 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

[0021] Figure 1 This is a flowchart of the synthesis process of the present invention; Figure 2 This is a graph showing the change in product purity during the recycling of the Pd / LDH catalyst in Example 1 of this invention. Figure 3 This is a comparison chart of the product purity of Examples 1-8 and Comparative Examples 1-4 of the present invention. Detailed Implementation

[0022] The technical solution of the present invention will be further described below with reference to the accompanying drawings and embodiments.

[0023] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are some embodiments of the present invention, but not all embodiments.

[0024] Example 1 like Figure 1 As shown, this embodiment synthesizes a 4-methylpyridine, and the specific steps are as follows: S1. Preparation of Pd / LDH catalyst: PdCl2 aqueous solution is reacted with Mg-Al type LDH support (Mg 2+ With Ag 3+ The catalyst was mixed in equal volumes at a molar ratio of 3:1, impregnated at room temperature for 12 hours, dried at 80°C, and reduced at 300°C for 2 hours under H2 atmosphere to obtain a Pd / LDH catalyst with a Pd loading of 3 mol%.

[0025] S2. Synthesis of 4-methylpyridine: First, take a 20 mL Schlenk tube, add a Teflon-coated magnetic stir bar, and then add 75 mg of the Pd / LDH catalyst prepared in step S1 and 0.5 mmol of 4-methylpiperidine (Pd / LDH catalyst to 4-methylpiperidine mass ratio 15:1); then connect an argon balloon and use the Schlenk technique to replace the argon balloon three times to ensure the inertness of the system.

[0026] Add 5 mL of n-heptane solvent (10 times the volume of 4-methylpiperidine); place the Schlenk tube in a 100°C oil bath and stir at 800 rpm for 18 hours at 95 kPa pressure, cooling the upper part of the tube wall with a -5°C refrigerant during the reaction. After the reaction, centrifuge to separate the catalyst, wash three times with n-heptane, and dry at 80°C for later use; take the supernatant and separate it by vacuum distillation (5 kPa pressure, collecting the fraction at 80~82°C) to obtain 4-methylpyridine.

[0027] The reaction formula is: The obtained product was characterized as follows: 1 HNMR (400MHz, CDCl3): 8.48 (d,J=5.4Hz,2H), 7.10 (d,J=5.4Hz,2H), 2.55 (s,3H); The product of Example 1 was detected by gas chromatography using an HP-5 capillary column. The initial temperature was 60°C and held for 2 minutes, then the temperature was increased to 150°C at a rate of 10°C / min and held for 5 minutes. The injection port temperature was 200°C, the detector temperature was 250°C, and toluene was used as the internal standard.

[0028] The test results showed that the conversion rate of 4-methylpiperidine was 98%, the selectivity of 4-methylpyridine was 96%, and the purity of the product was 99.5%.

[0029] The recovered and treated Pd / LDH catalyst from Example 1 was used in step S2 of Example 1, and the process was repeated five times. The product was tested each time, and the results are as follows: Figure 2 As shown in Table 1.

[0030] Table 1: Cyclic Performance Results

[0031] Example 2 This embodiment has the same steps and conditions as Embodiment 1, the only difference being that the stirring rate in step S2 is changed to 500 rpm.

[0032] Gas chromatography analysis revealed that the conversion rate of 4-methylpiperidine was 94%, the selectivity of 4-methylpyridine was 95%, and the purity of the product was 99.2%.

[0033] Example 3 This embodiment has the same steps and conditions as Embodiment 1, the only difference being that the pressure in step S2 is changed to 97 kPa.

[0034] Gas chromatography analysis revealed that the conversion rate of 4-methylpiperidine was 97%, the selectivity of 4-methylpyridine was 95%, and the purity of the product was 99.3%.

[0035] Example 4 This embodiment has the same steps and conditions as Embodiment 1, the only difference being that the low-toxicity solvent in step S2 is changed to 5 mL of cyclohexane.

[0036] Gas chromatography analysis revealed that the conversion rate of 4-methylpiperidine was 95%, the selectivity of 4-methylpyridine was 94%, and the purity of the product was 99.2%.

[0037] Example 5 This embodiment is the same as Embodiment 1 in terms of steps and conditions, except that the low-toxicity solvent in step S2 is changed to 5 mL of toluene and the stirring speed is 700 rpm.

[0038] Gas chromatography analysis revealed that the conversion rate of 4-methylpiperidine was 96%, the selectivity of 4-methylpyridine was 93%, and the purity of the product was 99.1%.

[0039] Example 6 This embodiment is the same as the steps and conditions in Embodiment 1, except that the amount of Pd / LDH catalyst in step S2 is changed to 60 mg (with a mass ratio of 12:1 to 4-methylpiperidine), and the pressure is 93 kPa.

[0040] Gas chromatography analysis revealed that the conversion rate of 4-methylpiperidine was 92%, the selectivity of 4-methylpyridine was 94%, and the purity of the product was 99.2%.

[0041] Example 7 This embodiment is the same as the steps and conditions in Embodiment 1, except that the amount of Pd / LDH catalyst in step S2 is changed to 90 mg (with a mass ratio of 18:1 to 4-methylpiperidine).

[0042] Gas chromatography analysis revealed that the conversion rate of 4-methylpiperidine was 99%, the selectivity of 4-methylpyridine was 95%, and the purity of the product was 99.4%.

[0043] Example 8 This embodiment has the same steps and conditions as Embodiment 1, the only difference being that the inert atmosphere in step S2 is replaced with nitrogen.

[0044] Gas chromatography analysis revealed that the conversion rate of 4-methylpiperidine was 93%, the selectivity of 4-methylpyridine was 94%, and the purity of the product was 99.2%.

[0045] Comparative Example 1 This comparative example uses a Pd / C catalyst to prepare 4-methylpyridine. The specific preparation steps are as follows: First, take a 20 mL Schlenk tube, add a Teflon-coated magnetic stir bar, and then add 75 mg of Pd / C catalyst and 0.5 mmol of 4-methylpiperidine. Then, connect an argon balloon and use the Schlenk technique to replace the catalyst three times to ensure the system is inert.

[0046] Add 5 mL of n-heptane solvent; place the Schlenk tube in a 100°C oil bath and stir at 800 rpm for 18 hours under 95 kPa pressure, cooling the upper part of the tube wall with a -5°C refrigerant during the reaction. After the reaction, centrifuge to separate the catalyst, wash it three times with n-heptane, and dry it at 80°C for later use; take the supernatant and separate it by vacuum distillation (pressure 5 kPa, collect the fraction at 80~82°C) to obtain 4-methylpyridine.

[0047] Gas chromatography analysis revealed that the conversion rate of 4-methylpiperidine was 85%, the selectivity of 4-methylpyridine was 78%, the content of by-products reached 22%, and the purity of the product was 97.5%.

[0048] Comparative Example 2 This comparative example follows the same steps as Example 1, except that the oil temperature in step S2 is changed to 150°C.

[0049] Gas chromatography analysis revealed a 4-methylpiperidine conversion rate of 99%, but the 4-methylpyridine selectivity decreased to 82%, the byproduct content increased to 18%, and the product purity was 98.0%.

[0050] Comparative Example 3 This comparative example uses the commonly used industrial acetaldehyde-ammonia process to synthesize 4-methylpyridine. The specific preparation steps are as follows: S1. Take a 50mL high-pressure reactor, check the sealing of the reactor body, add a Teflon-coated magnetic stir bar, and add 15mmol acetaldehyde (0.81g) and 5mmol ammonia (0.085g) in sequence, ensuring that the molar ratio of acetaldehyde to ammonia is 3:1, and stir evenly to ensure that the raw materials are fully mixed.

[0051] S2. Seal the high-pressure reactor and replace the air inside the reactor with nitrogen three times to eliminate the interference of air on the reaction. Then start the heating device to slowly raise the temperature inside the reactor to 380°C, while adjusting the pressure to 2.5MPa. Maintain this temperature and pressure conditions and stir the reaction continuously at a stirring rate of 800rpm for 6 hours (the conventional reaction time in industry).

[0052] S3. After the reaction is complete, turn off the heating and stirring devices. After the reaction vessel has cooled naturally to room temperature and the pressure has dropped to atmospheric pressure, slowly open the vessel lid and collect the reaction mixture. Detect the product using the same gas chromatography detection method as in Example 1, and simultaneously separate 4-methylpyridine by vacuum distillation (pressure 5 kPa, collect the fraction at 80-82°C).

[0053] The yield of 4-methylpyridine was 65%, the content of by-products was 18% (mainly heterocyclic compounds such as pyridine and 2-methylpyridine), and the purity of the product was 96.8%. The energy consumption of the entire reaction was recorded by an energy consumption monitoring instrument, and it was calculated that the energy consumption of this process was 3.2 times that of Example 1. In addition, a small amount of carbon was deposited on the reactor wall after the reaction, which required additional treatment.

[0054] Comparative Example 4 This comparative example uses the existing methylglutaronitrile cyclization process to synthesize 4-methylpyridine. The specific preparation steps are as follows: S2. Take a 50mL three-necked flask, install a stirring device, thermometer and condenser, add a Teflon-coated magnetic stir bar, and add 10mmol methylglutaronitrile (1.14g) and 20mmol concentrated hydrochloric acid (37% by mass, 1.82mL) in sequence. The concentrated hydrochloric acid is used as a catalyst. Stir evenly to make the methylglutaronitrile completely dispersed in the concentrated hydrochloric acid.

[0055] S2. Start the stirring device and stir at a stirring rate of 800 rpm. At the same time, heat the three-necked flask with an oil bath to stabilize the temperature of the reaction system at 120°C. Maintain this temperature and continue to reflux the reaction for 8 hours. During the reaction, condense the volatilized material through a condenser and reflux it back into the reaction system.

[0056] S3. After the reaction is complete, turn off the heating and stirring devices and allow the reaction system to cool to room temperature. Slowly add sodium hydroxide solution (20% by mass) to the system to adjust the pH to neutral. At this point, the system will separate into layers, with a large amount of acidic wastewater in the lower layer and an organic phase in the upper layer. Collect the organic phase by separation, dry it with anhydrous magnesium sulfate, filter it, and detect the product using the same gas chromatography detection method as in Example 1. Then, separate 4-methylpyridine by vacuum distillation.

[0057] Testing revealed that the yield of 4-methylpyridine was 68%, the content of byproducts was 16% (mainly glutaramide and cyanopyridine derivatives), and the purity of the product was 97.2%. The reaction process generates a large amount of acidic wastewater (approximately 25 mL of acidic wastewater with pH ≤ 2 is generated for every 10 mmol of methylglutaronitrile), which must be neutralized before discharge. This results in high environmental treatment costs, and the concentrated hydrochloric acid is highly corrosive, placing stringent requirements on the materials used in the reaction equipment.

[0058] The purity of the products from Examples 1-8 and Comparative Examples 1-4 was compared, such as... Figure 3 As shown, the results indicate that the method of the present invention can achieve the synthesis of 4-methylpyridine with high selectivity and high purity under mild conditions. Compared with traditional methods and existing catalytic systems, it does not require high temperature and high pressure, has high selectivity and fewer by-products, and achieves comprehensive improvement in catalytic efficiency, environmental friendliness, ease of operation and economy. It is a promising green synthesis route.

[0059] Therefore, this invention provides a method for synthesizing 4-methylpyridine using a Pd / LDH catalyst. By utilizing a structurally tunable LDH support to efficiently load Pd, a high-performance and easily recyclable heterogeneous catalytic system is constructed. Combined with a low-toxicity solvent, this method achieves the green, efficient, and selective synthesis of 4-methylpyridine, while also possessing good process feasibility and economic efficiency. Specifically, the reaction conditions of this invention are mild, carried out at 80-100℃ and 90-100kPa, requiring no high temperature or high pressure, with low equipment requirements and energy consumption less than 31% of the acetaldehyde-ammonia method; the operation is simple, using conventional stirring and cooling equipment, the steps are simple, the catalyst recovery method is easy, and it is easy to scale up industrially; the product selectivity is high, using a Mg-Al type Pd / LDH catalyst, the selectivity of 4-methylpyridine can reach more than 95% under optimized conditions, and the total content of by-products is ≤5% (mainly ≤3% of 3-methylpyridine and a small amount of 4-methylpyridine). The partial dehydrogenation product of methylpiperidine is ≤2%, which is much lower than that of traditional methods and Pd / C catalytic systems. It is environmentally friendly, using low-toxicity solvents such as n-heptane and cyclohexane. The catalyst can be recycled more than 5 times (after 5 cycles, the conversion rate is still ≥92% and the selectivity is ≥93%). No large amount of harmful waste is generated during the reaction. Compared with the methylglutaronitrile cyclization method, it can reduce acidic wastewater discharge by 100%. It is highly flexible, supports the selection of a variety of low-toxicity solvents, and has a certain tolerance range for the catalyst-to-substrate mass ratio. The process parameters can be flexibly adjusted according to the needs of industrial production.

[0060] 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 4-methylpyridine using a Pd / LDH catalyst, characterized in that, Includes the following steps: S1. Preparation of Pd / LDH catalyst: PdCl2 aqueous solution is mixed with Mg-Al type LDH support, impregnated at room temperature, dried and then reduced to obtain Pd / LDH catalyst; S2. Under an inert atmosphere, 4-methylpiperidine, Pd / LDH catalyst, and low-toxicity solvent are added to a reaction vessel. After stirring and reacting, 4-methylpyridine is obtained by separation and purification.

2. The method for synthesizing 4-methylpyridine using a Pd / LDH catalyst according to claim 1, characterized in that: In S1, the volume ratio of PdCl2 aqueous solution to Mg-Al type LDH support is 1:1; in the Mg-Al type LDH support, Mg 2+ With Ag 3+ The molar ratio was 3:1; the palladium loading in the obtained Pd / LDH catalyst was 3 mol.

3. The method for synthesizing 4-methylpyridine using a Pd / LDH catalyst according to claim 1, characterized in that: In S1, the impregnation time is 10~12h, the drying temperature is 60~100℃, and the reduction process is carried out in H2 atmosphere at 300~320℃ for 1.5~2h.

4. The method for synthesizing 4-methylpyridine using a Pd / LDH catalyst according to claim 1, characterized in that: In S2, the mass ratio of Pd / LDH catalyst to 4-methylpiperidine is 12~18:

1.

5. The method for synthesizing 4-methylpyridine using a Pd / LDH catalyst according to claim 1, characterized in that: In S2, the low-toxicity solvent is one of n-heptane, cyclohexane, or toluene, and the amount used is 8 to 12 times the volume of 4-methylpiperidine.

6. The method for synthesizing 4-methylpyridine using a Pd / LDH catalyst according to claim 1, characterized in that: In S2, the inert atmosphere is argon or nitrogen.

7. The method for synthesizing 4-methylpyridine using a Pd / LDH catalyst according to claim 1, characterized in that: In step S2, during the stirring reaction, the temperature is 80~100℃, the pressure is 90~100kPa, the time is 16~18h, and the stirring rate is 500~1000rpm.

8. The method for synthesizing 4-methylpyridine using a Pd / LDH catalyst according to claim 1, characterized in that: In step S2, during the stirring reaction, a refrigerant is used to cool the upper part of the reactor to -5℃ to 0℃.

9. The method for synthesizing 4-methylpyridine using a Pd / LDH catalyst according to claim 1, characterized in that: In step S2, the pressure of the stirring reaction is 93~97 kPa.

10. The method for synthesizing 4-methylpyridine using a Pd / LDH catalyst according to claim 1, characterized in that: In S2, the separation and purification process is as follows: first, the catalyst is separated by centrifugation, then the obtained catalyst is washed with n-heptane, and the supernatant is separated by vacuum distillation or column chromatography to obtain 4-methylpyridine with a purity ≥99.0%.

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