A method for synthesizing 2-piperidinemethanol

Abstract

The application discloses a synthesis method of 2-piperidinemethanol and belongs to the technical field of organic synthesis. The method takes biomass derivative 2,5-dihydroxymethylfuran as raw material, adds a supported bimetallic catalyst, a solvent and an ammonia source, and reacts under the condition of 0.1-8 MPa H2 pressure and 80-230 DEG C for 0.3-10 h, so as to obtain the target product 2-piperidinemethanol through one-pot selective hydrogenolysis-amination two-step coupling reaction. The active metal of the catalyst is any two of Ni, Co, Cu, Ru, Pd, Pt and Rh, and the total metal loading is 2wt%-30wt%. The raw material is renewable, the reaction condition is mild, the product selectivity is high (up to 85%), the catalyst is stable and easy to recover, the repeated use performance is good, the process route is simple and easy to enlarge, the method solves many drawbacks of the traditional synthesis method, realizes the green and efficient synthesis of 2-piperidinemethanol, and has wide application prospect in the fields of drug synthesis, environmental protection and catalysis.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to a method for synthesizing 2-piperidine methanol by hydrogenolysis-amination of bio-based 2,5-dihydroxymethylfuran. Background Technology

[0002] 2-Piperidinemethanol is an important chemical intermediate with wide applications in drug synthesis, carbon dioxide capture, volatile aldehyde absorption, and as a catalyst ligand. Currently, the traditional synthetic route for 2-piperidinemethanol uses petroleum-based 2-methylpyridine as a raw material, first generating 2-pyridinecarboxaldehyde through oxidation, and then further hydrogenating 2-pyridinecarboxaldehyde to obtain 2-piperidinemethanol.

[0003] However, the aforementioned traditional synthetic methods have significant drawbacks: the oxidation step requires a high temperature of approximately 300°C, and the yield of 2-pyridinecarboxaldehyde is low (approximately 60%); in the subsequent hydrogenation step, the catalyst is prone to deactivation due to the easy coordination of the reactants or products with the metal catalyst. From the perspective of green chemistry and sustainable development, developing new synthetic routes with renewable reactants, mild reaction conditions, high efficiency, and stable catalysts is of great significance. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a method for synthesizing 2-piperidinemethanol from the biomass derivative 2,5-dihydroxymethylfuran via a one-pot selective hydrogenolysis-amination reaction. This method features mild reaction conditions, a short process route, high product selectivity, and a stable and easily recyclable catalyst.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: A method for synthesizing 2-piperidinemethanol includes the following steps: adding 2,5-dihydroxymethylfuran, a catalyst, a solvent, and an ammonia source into a reactor, and reacting the reactor under a hydrogen atmosphere at a temperature of 80-230°C and a hydrogen pressure of 0.1-8 MPa for 0.3-10 h to obtain 2-piperidinemethanol.

[0006] The catalyst is a supported bimetallic catalyst, and its active metal component is any two of Ni, Co, Cu, Ru, Pd, Pt and Rh, with a total metal loading of 2 wt% to 30 wt%. The catalyst support is γ-Al2O3, TiO2, SiO2, ZrO2, CeO2, ZSM-5 or activated carbon.

[0007] The active components of the supported bimetallic catalyst are preferably Co and Pt, and the support is preferably CeO2.

[0008] The solvent is selected from any one of water, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, and isopropanol. The ammonia source is selected from any one of ammonia gas, ammonia water, and hydrazine hydrate.

[0009] The material ratio is as follows: 1-20 mL of solvent is added for every 1 mmol of 2,5-dihydroxymethylfuran; 0.01-1 g of catalyst is added for every 1 mmol of 2,5-dihydroxymethylfuran. The preferred ratio is 5-10 mL of solvent and 0.1-0.5 g of catalyst for every 1 mmol of raw material.

[0010] The preferred reaction conditions are: hydrogen pressure 0.1~1 MPa, reaction temperature 140~180℃, and reaction time 1~3 hours.

[0011] The supported bimetallic catalyst of this invention can be prepared by a conventional equal-volume impregnation method. Typical preparation steps include: impregnating the support with an aqueous solution of the active metal component precursor (such as hydrochloride, nitrate, or acetate) in equal volume; allowing it to stand for 10-15 hours; drying at 100-120°C for 10-12 hours; calcining at 300-550°C for 2-5 hours; and finally reducing with hydrogen at 200-500°C for 1-3 hours.

[0012] The synthesis reaction of this invention is a two-step coupled reaction, eliminating the need to separate intermediate products and achieving efficient one-pot synthesis: First, 2,5-dihydroxymethylfuran undergoes a hydrogenolysis-amination reaction in the presence of a supported bimetallic catalyst and H2 and an ammonia source to generate 2-amino-1,6-hexanediol; second, 2-amino-1,6-hexanediol undergoes an intramolecular amination reaction, closing the ring to generate the target product 2-piperidinemethanol, as shown in the following reaction formula: Compared with the prior art, the present invention has the following significant advantages: 1. Sustainable raw materials: For the first time, 2,5-dihydroxymethylfuran, a biomass derivative, is used as a raw material to replace traditional petroleum-based raw materials, which is in line with the green chemical development strategy. The raw materials are widely available and renewable.

[0013] 2. Mild reaction conditions: The reaction is carried out at relatively low hydrogen pressure and temperature, avoiding the high-temperature oxidation step in the traditional route, resulting in low energy consumption and high operational safety.

[0014] 3. High product selectivity: The use of a supported bimetallic catalyst results in significant synergistic catalysis, effectively suppressing side reactions. The selectivity of the product 2-piperidinemethanol can reach 85%, and the yield is better than that of traditional methods.

[0015] 4. Stable catalyst performance: The catalyst has a simple preparation process, high catalytic activity, and good stability. It can be recycled at least 10 times without significant deactivation, is easy to separate and recover, and has good prospects for industrial application.

[0016] 5. Short process route: The two-step coupled reaction is achieved in a one-pot process, eliminating the need to separate intermediate products, which simplifies the production process, improves production efficiency, and is suitable for large-scale industrial production. Detailed Implementation

[0017] The present invention will be further illustrated by the following examples, but the scope of protection of the present invention is not limited thereto.

[0018] Catalyst preparation example: Weigh 2.0 g of TiO2 support into a crucible, and weigh the corresponding mass of RuCl3·3H2O and CuCl2·2H2O according to the loading to prepare an aqueous solution. Add the solution dropwise to the support until the support is completely wetted and slightly flowing. After standing for 12 h, dry at 100 °C overnight, calcine at 450 °C for 3 h, and reduce at 500 °C and 100 mL / min hydrogen atmosphere for 4 h before use to obtain a 20Cu-2Ru / TiO2 catalyst with a total metal loading of 22 wt% (Cu 20 wt%, Ru 2 wt%).

[0019] Using the same method described above, other supported bimetallic catalysts such as 20Co-2Ru / TiO2 and 20Co-2Pt / CeO2 can be prepared by simply adjusting the type and amount of the active metal component precursor and the type of support.

[0020] Example 1 1 mmol of 2,5-dihydroxymethylfuran, 0.1 g of 20Cu-2Ru / TiO2 catalyst, and 5 mL of ammonia water were added to a 25 mL high-pressure reactor. The reactor was purged with nitrogen four times to purge air, and then with hydrogen four times to purge nitrogen. The pressure was increased to 1 MPa, and the reactor was heated to 135 °C with stirring for 5 h. After cooling to room temperature, the catalyst was separated by centrifugation. The supernatant was filtered and analyzed directly by gas chromatography. Using the external standard method, a working curve was established, confirming a 100% conversion of 2,5-dihydroxymethylfuran, a 53% yield of 2-piperidine methanol, and the remaining products including byproducts such as 2,5-hydroxymethyltetrahydrofuran and intermediates such as 2-amino-1,6-hexanediol.

[0021] Example 2: The remaining steps are the same as in Example 1, except that the catalyst is replaced with 20Co-2Ru / TiO2. The reaction results are: 100% conversion of 2,5-dihydroxymethylfuran and 46% yield of 2-piperidinemethanol.

[0022] Example 3: The remaining steps are the same as in Example 1, except that the catalyst is replaced with 20Co-2Pt / CeO2. The reaction results are: 100% conversion of 2,5-dihydroxymethylfuran and 81% yield of 2-piperidinemethanol.

[0023] Example 4: The remaining steps are the same as in Example 3, except that the solvent is replaced with 5 mL of water and 0.7 MPa of ammonia gas is introduced as the ammonia source. The reaction results are: 93% conversion of 2,5-dihydroxymethylfuran and 76% yield of 2-piperidine methanol.

[0024] Example 5: The remaining steps are the same as in Example 3, except that the reaction temperature is adjusted to 155℃. The reaction results are: 100% conversion of 2,5-dihydroxymethylfuran and 85% yield of 2-piperidinemethanol.

[0025] Example 6: The remaining steps are the same as in Example 3, except that the initial hydrogen pressure is adjusted to 0.5 MPa. The reaction results are: 96% conversion of 2,5-dihydroxymethylfuran and 83% yield of 2-piperidinemethanol.

[0026] Example 7: The remaining steps are the same as in Example 3, except that the initial hydrogen pressure is adjusted to 8 MPa. The reaction results are: 100% conversion of 2,5-dihydroxymethylfuran and 38% yield of 2-piperidinemethanol.

[0027] Example 8: The remaining steps are the same as in Example 3. The catalyst recovered after the reaction is recycled 10 times. The reaction results are: 100% conversion of 2,5-dihydroxymethylfuran, 79% yield of 2-piperidine methanol, and no obvious deactivation.

[0028] The synthesis method of this invention uses renewable raw materials, has mild reaction conditions, high product yield, and recyclable catalyst. The process route is simple and easy to scale up, solving many drawbacks of traditional 2-piperidine methanol synthesis methods. It can realize the green and efficient industrial production of 2-piperidine methanol and has broad application prospects in drug synthesis, environmental protection, catalysis and other related fields.

Claims

1. A method for synthesizing 2-piperidinemethanol, characterized in that, Using bio-based 2,5-dihydroxymethylfuran as a raw material, a hydrogenolysis-amination reaction was carried out in the presence of a supported bimetallic catalyst, solvent, and ammonia source at a temperature of 80-230℃ and a hydrogen pressure of 0.1-8 MPa for 0.3-10 h to obtain 2-piperidinemethanol; The supported bimetallic catalyst comprises an active component and a support, with the total loading of the active component being 2wt% to 30wt%. The active component is any two of Ni, Co, Cu, Ru, Pd, Pt, and Rh. The support is γ-Al2O3, TiO2, SiO2, ZrO2, CeO2, ZSM-5, or activated carbon.

2. The synthesis method according to claim 1, characterized in that, The hydrogen pressure of the reaction is 0.1~1 MPa, the reaction temperature is 140~180℃, and the reaction time is 1~3 h.

3. The synthesis method according to claim 1, characterized in that, The material ratio is as follows: for every 1 mmol of 2,5-dihydroxymethylfuran, add 1~20 mL of solvent and 0.01~1 g of the supported bimetallic catalyst.

4. The synthesis method according to claim 3, characterized in that, Add 5-10 mL of solvent to every 1 mmol of 2,5-hydroxymethylfuran, and then add 0.1-0.5 g of the supported bimetallic catalyst.

5. The synthesis method according to claim 1, characterized in that, The solvent is selected from any one of water, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, and isopropanol.

6. The synthesis method according to claim 1, characterized in that, The ammonia source is selected from any one of ammonia gas, ammonia water, or hydrazine hydrate.

7. The synthesis method according to claim 1, characterized in that, The active components of the supported bimetallic catalyst are Co and Pt, and the support is CeO2.

8. The synthesis method according to any one of claims 1 to 7, characterized in that, The supported bimetallic catalyst is prepared by the following steps: an aqueous solution of the active metal component precursor is impregnated with the support in equal volumes, allowed to stand for 10-15 hours, dried at 100-120°C for 10-12 hours, calcined at 300-550°C for 2-5 hours, and finally reduced with hydrogen at 200-500°C for 1-3 hours; the active metal component precursor is a hydrochloride, nitrate, or acetate of the corresponding metal.

9. The synthesis method according to claim 1, characterized in that, After the reaction is completed, the supported bimetallic catalyst is recovered by centrifugation and recycled at least 10 times.

Images