阅读说明：本技术 一种2,5-二（氨基甲基）呋喃选择性氢解制备2-氨基甲基哌啶的方法 (Method for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-bis (aminomethyl) furan ) 是由 王延吉 张树兴 丁晓墅 于 2021-11-10 设计创作，主要内容包括：本发明为一种2,5-二(氨基甲基)呋喃选择性氢解制备2-氨基甲基哌啶的方法。该方法包括以下步骤：将2,5-二(氨基甲基)呋喃、催化剂和有机溶剂加入到反应器中,在1～8MPa的H-(2)压力、120～200℃下反应0.5～8h,得到产物2-氨基甲基哌啶；所述的催化剂为负载型金属催化剂,活性金属为Ru、Rh或Pt；催化剂载体为γ-Al-(2)O-(3)、TiO-(2)、SiO-(2)、ZrO-(2)、CeO-(2)、ZSM-5或活性炭。本发明的反应条件温和,产物选择性可达80％以上,金属催化剂制备过程简单。(The invention relates to a method for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-bis (aminomethyl) furan. The method comprises the following steps: adding 2, 5-bis (aminomethyl) furan, a catalyst and an organic solvent into a reactor, and reacting at 1-8 MPa of H 2 Reacting for 0.5-8 h at 120-200 ℃ under pressure to obtain a product 2-aminomethyl piperidine; the catalyst is a supported metal catalyst, and the active metal is Ru, Rh or Pt; the catalyst carrier is gamma-Al 2 O 3 、TiO 2 、SiO 2 、ZrO 2 、CeO 2 ZSM-5 or activated carbon. The invention has mild reaction condition, the product selectivity can reach more than 80 percent, and goldThe preparation process of the catalyst is simple.)

1. A process for the selective hydrogenolysis of 2, 5-bis (aminomethyl) furan to produce 2-aminomethylpiperidine, characterized in that the process comprises the steps of: adding 2, 5-bis (aminomethyl) furan, a catalyst and an organic solvent into a reactor, and reacting at 1-8 MPa of H₂Reacting for 0.5-8 h at 120-200 ℃ under pressure to obtain a product 2-aminomethyl piperidine;

wherein 2-15 mL of solvent is added into 1mmol of 2, 5-bis (aminomethyl) furan according to the material proportion; adding 0.05-0.5 g of metal catalyst into every 1mmol of 2, 5-bis (aminomethyl) furan;

the catalyst is a supported metal catalyst, and comprises active metal and a carrier; the metal loading is 2 wt% -10 wt%;

the active metal is Ru, Rh or Pt;

the catalyst carrier is gamma-Al₂O₃、TiO₂、SiO₂、ZrO₂、CeO₂ZSM-5 or activated carbon.

2. The process for the selective hydrogenolysis of 2, 5-bis (aminomethyl) furan to 2-aminomethylpiperidine as in claim 1 wherein the organic solvent is tetrahydrofuran, 1, 4-dioxane or n-decane.

3. The process for the selective hydrogenolysis of 2, 5-bis (aminomethyl) furan to 2-aminomethylpiperidine as in claim 1 wherein the reactor is a high pressure reactor.

4. The method for preparing 2-aminomethyl piperidine according to claim 1, wherein the material ratio is preferably 5-10 mL of solvent per 1mmol of 2, 5-bis (aminomethyl) furan; 0.1 to 0.5g of a metal catalyst is added per 1mmol of 2, 5-bis (aminomethyl) furan.

5. The process for the selective hydrogenolysis of 2, 5-bis (aminomethyl) furan to 2-aminomethylpiperidine according to claim 1 wherein the catalyst is prepared by: soaking the aqueous solution of the active metal component precursor and the carrier in the same volume according to the required proportion, standing for 10-15 h, drying at 100-120 ℃ for 10-12 h, calcining at 300-550 ℃ for 2-5 h by using a muffle furnace, and finally reducing for 1-3 h at 200-500 ℃ by using hydrogen.

6. The process for the selective hydrogenolysis of 2, 5-bis (aminomethyl) furan to produce 2-aminomethylpiperidine as in claim 5 wherein the precursor active metal component is a hydrochloride, nitrate or acetate salt.

7. The process for the selective hydrogenolysis of 2, 5-bis (aminomethyl) furan to 2-aminomethylpiperidine according to claim 5 wherein the preferred hydrogen pressure is 3 to 8 MPa; the preferable reaction temperature is 130-180 ℃; the preferable reaction time is 1-4 h.

Technical Field

The invention relates to a method for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-bis (aminomethyl) furan.

Background

2-aminomethyl piperidine is an important organic compound and an intermediate for synthesizing pesticides and medicines. For the synthesis of pharmaceutically active ingredients, 2-aminomethylpiperidine is an essential building block. One of these pharmaceutically active ingredients is flecainide (flecainide).

2-aminomethyl piperidines are typically prepared by hydrogenation of 2-cyanopyridine. However, the process used is a two-step process and the overall yield is only around 20%. The second step also needs to be carried out in acetic acid or other mineral acids. The use of 2-aminomethylpyridines for the preparation of 2-aminomethylpiperidines also has the above-mentioned problems.

Disclosure of Invention

The invention aims to provide a method for preparing 2-aminomethyl piperidine by selective hydrogenolysis with a biomass derivative 2, 5-di (aminomethyl) furan as a raw material aiming at the defects of the current 2-aminomethyl piperidine synthesis technology. The method uses biomass derived 2, 5-bis (aminomethyl) furan as a raw material, metals Ru, Rh and Pt in the catalyst are metal components, and gamma-Al₂O₃、TiO₂、SiO₂、ZrO₂、CeO₂ZSM-5 or active carbon as carrier. 2, 5-di (aminomethyl) furan is catalyzed under mild conditions to prepare 2-aminomethyl piperidine by selective hydrogenolysis. The invention has mild reaction condition, the product selectivity can reach more than 80 percent, and the preparation process of the metal catalyst is simple.

The technical scheme of the invention is as follows:

a process for the selective hydrogenolysis of 2, 5-bis (aminomethyl) furan to produce 2-aminomethylpiperidine which comprises the steps of: adding 2, 5-bis (aminomethyl) furan, a catalyst and an organic solvent into a reactor, and reacting at 1-8 MPa of H₂Reacting for 0.5-8 h at 120-200 ℃ under pressure to obtain a product 2-aminomethyl piperidine;

wherein 2-15 mL of solvent is added into 1mmol of 2, 5-bis (aminomethyl) furan according to the material proportion; adding 0.05-0.5 g of metal catalyst into every 1mmol of 2, 5-bis (aminomethyl) furan;

the catalyst is a supported metal catalyst, and comprises active metal and a carrier; the metal loading is 2 wt% -10 wt%;

the active metal is Ru, Rh or Pt;

the catalyst carrier is gamma-Al₂O₃、TiO₂、SiO₂、ZrO₂、CeO₂ZSM-5 or activated carbon;

the organic solvent is tetrahydrofuran, 1,4 dioxane or n-decane;

the reactor is a high-pressure reactor;

the material proportion is preferably 5-10 mL of solvent added to 1mmol of 2, 5-bis (aminomethyl) furan; adding 0.1-0.5 g of metal catalyst into every 1mmol of 2, 5-bis (aminomethyl) furan;

the preparation process of the catalyst comprises the following steps: soaking the aqueous solution of the active metal component precursor and the carrier in the same volume according to the required proportion, standing for 10-15 h, drying at 100-120 ℃ for 10-12 h, calcining at 300-550 ℃ for 2-5 h by using a muffle furnace, and finally reducing for 1-3 h at 200-500 ℃ by using hydrogen;

the active metal component precursor is hydrochloride, nitrate or acetate;

the preferred hydrogen pressure is 3-8 MPa; the preferable reaction temperature is 130-180 ℃; the preferable reaction time is 1-4 h.

The invention has the beneficial effects that:

(1) the method realizes the selective hydrogenolysis of 2, 5-di (aminomethyl) furan to prepare the 2-aminomethyl piperidine for the first time. The metal catalyst has good catalytic performance, and the product selectivity can reach more than 80 percent at most.

(2) The reaction condition is mild, and the preparation process of the metal catalyst is simple.

(3) After the reaction is finished, the reaction liquid can be subjected to centrifugal separation, and the metal catalyst is deposited at the bottom and can be recycled, so that the method has a good application prospect.

Detailed Description

The reaction formula for preparing 2-aminomethyl piperidine by selective hydrogenolysis of 2, 5-bis (aminomethyl) furan of the present invention is as follows:

the invention relates to a preparation method of 2, 5-di (aminomethyl) furan by reductive amination of 5-hydroxymethylfurfural which is a biomass platform compound.

The supported metal catalyst is a known material, and the composition of the catalyst comprises an active metal and a carrier. The following are Rh/gamma-Al in which the loading is 2 wt%₂O₃But not limited thereto:

first, the gamma-Al of the carrier is measured₂O₃Saturated water absorption amount of (d): accurately weighing 2.0g of the carrier on a watch glass, dropwise adding pure water until the carrier is completely soaked and slightly flows, and recording the volume of the used pure water, namely the saturated water absorption capacity of the carrier.

Step two, preparing a supported metal catalyst by an impregnation method: 2.0g of the carrier was accurately weighed into a crucible. Accurately weigh 0.104g RhCl₃·xH₂O in a beaker, the saturated water absorption of the support measured in the first step was added. The rhodium solution was added dropwise to the support until the support was completely wetted and slightly fluid. After standing for 12 hours, the mixture was dried overnight at 110 ℃ using a drying oven. Finally, the catalyst is roasted by a muffle furnace at 300 ℃ for 3 h.

Step three, catalyst reduction: before use, the catalyst was reduced using a tubular resistance furnace at 300 ℃ with a flow rate H of 100mL/min₂The reduction was carried out for 1h, and the catalyst finally obtained had a theoretical loading of metallic Rh of 2 wt%.

Example 1

1mmol of 2, 5-bis (aminomethyl) furan, 0.1g of Rh/gamma-Al with a loading of 2 wt%₂O₃Adding a catalyst and 5mL of tetrahydrofuran into a 25mL high-pressure reaction kettle, replacing air in the reaction kettle with nitrogen for 4 times, replacing the nitrogen in the reaction kettle with hydrogen for 4 times, and filling hydrogen to 5 MPa. After warming to 150 ℃, stirring was started. The reaction was completed for 8h and cooled to room temperature. Centrifuging to separate supernatant, precipitating catalyst at the bottom, filtering supernatant, and directly analyzing on gas chromatography. By plotting a working curve by an external standard method, the conversion rate of 2, 5-bis (aminomethyl) furan is determined to be 100%, the yield of 2-aminomethyl piperidine is determined to be 80.2%, and the remaining product is 2, 5-bis (aminomethyl) tetrahydrofuran, etc.

Example 2

The other steps are the same as example 1 except thatIn that the added catalyst is Rh/TiO₂As a result of the reaction, the conversion of 2, 5-bis (aminomethyl) furan was 100%, and the yield of 2-aminomethylpiperidine was 64.6%.

Example 3

The other steps were the same as example 1 except that Rh/ZSM-5 was used as the catalyst, and the reaction results in 100% conversion of 2, 5-bis (aminomethyl) furan and 54.0% yield of 2-aminomethylpiperidine.

Example 4

The other procedure was the same as in example 1, except that Pt/ZrO was added as the catalyst₂As a result of the reaction, the conversion of 2, 5-bis (aminomethyl) furan was 86.3%, and the yield of 2-aminomethylpiperidine was 54.0%.

Example 5

The other procedure was the same as in example 1 except that Pt/CeO was used as the catalyst₂As a result of the reaction, the conversion of 2, 5-bis (aminomethyl) furan was 90.2%, and the yield of 2-aminomethylpiperidine was 67.0%.

Example 6

The other steps were the same as in example 1 except that the reaction pressure was 6MPa, the conversion of 2, 5-bis (aminomethyl) furan was 100% and the yield of 2-aminomethylpiperidine was 84.7%.

Example 7

The other steps were the same as in example 1 except that the catalyst loading was 5% by weight, and the reaction results in 100% conversion of 2, 5-bis (aminomethyl) furan and 75.3% yield of 2-aminomethylpiperidine.

Example 8

The other steps were the same as in example 1 except that the catalyst was reused 5 times, and the reaction results in 100% conversion of 2, 5-bis (aminomethyl) furan and 76.5% yield of 2-aminomethylpiperidine.

The object of the present invention was therefore to find a practical, economical and green process which makes it possible to prepare 2-aminomethylpiperidine on an industrial scale in a simple manner. Surprisingly, it has been found that 2-aminomethylpiperidines can be prepared by selective hydrogenolysis starting from biobased-derived 2, 5-bis (aminomethyl) furan.

The above description is only a part of specific examples of the present invention, but the scope of the present invention is not limited thereto, and the present invention is not limited by the order of the examples, and any person skilled in the art of the present invention can easily change or replace the technical scope of the present invention within the technical scope reported by the present invention, and shall be covered by the scope of the present invention. Therefore, the protection scope of the present invention is not limited to the above embodiments, and the protection scope of the claims should be subject to.

The invention is not the best known technology.