CN101912779B - Catalyst for catalytic synthesis of N-methylpyrrolidine and application thereof - Google Patents

Abstract

The invention relates to the synthesis technology of intermediates in the pharmaceutical and chemical industry, specifically a catalyst for catalytically synthesizing N-methylpyrrolidine and a synthesis method thereof. The catalyst is composed of a carrier and a catalytically active component, wherein the carrier is γ-Al ₂ O ₃ or HZSM series molecular sieves, the catalytic active component is metal M element or its oxide, the catalytic active component content is 0.5% to 20% of the total mass of the catalyst; the catalyst particle size is 4 mesh to 20 mesh. The catalyst is prepared by kneading extrusion method or impregnation method. The catalyst used in the present invention is simple to prepare, and the raw materials are cheap and easy to purchase. Used to catalyze the synthesis of N-methylpyrrolidine, the catalytic reaction conditions are mild, the three wastes are less, and there is no pollution. The conversion rate of tetrahydrofuran is basically maintained above 80%, and the yield of N-methylpyrrolidine is basically maintained above 60%.

Description

Catalyst for catalytically synthesizing N-methylpyrrolidine and its application

technical field

The invention relates to a synthesis technology of an intermediate N-methylpyrrolidine in the pharmaceutical and chemical industry, in particular to a catalyst for catalyzing the synthesis of N-methylpyrrolidine and its application.

Background technique

N-Methylpyrrolidine is an organic base widely used in medicine and chemical industry. It is mainly used in the preparation of broad-spectrum antibiotics cefepime and pamodine, and can also be used as a dye stabilizer and preservative.

The preparation method of existing N-methylpyrrolidine is more, and wherein more representative has following several: the first kind is the N-methylpyrrolidone high-pressure catalytic hydrogenation method that U.S. Patent US4892959 reports, and this method is Under the catalysis of copper-chromium or chromium-aluminum, N-methylpyrrolidone and hydrogen are synthesized at 150°C-300°C and 6.9-34.5MPa under high pressure conditions, and the conversion rate of N-methylpyrrolidone is 85 %, the selectivity is 85%. This method is carried out under high temperature and high pressure, which requires high equipment, is relatively dangerous, and requires a large amount of hydrogen in the reaction process, which makes the industrialization of the method more difficult. The second method is "Chemical Intermediates", 2008, 08: (19-21), which introduces pyrrolidine and methanol on H-13X molecular sieves to catalyze the synthesis of N-methylpyrrolidine. This method is at 300 ° C, pyrrolidine When alkane:methanol=1:3, pyrrolidine is methylated to obtain N-methylpyrrolidine, and this method has many reports, and the yield is about 83% to 91%. This method synthesizes N-methylpyrrolidine The yield is high, but due to the high cost of raw material pyrrolidine, it is almost impossible to achieve industrialized production. The third method is the methylation reaction of pyrrolidine and formaldehyde under the presence of formic acid reported in "Fine and Specialty Chemicals", 2004, 12 (10): 24-25. ℃, under the catalysis of formic acid. After the reaction, acidify with hydrochloric acid, remove impurities by distillation and neutralize with alkali to obtain crude N-methylpyrrolidine with a yield ranging from 54% to 92%. The raw materials of this method are expensive and difficult to obtain, and more formic acid, formaldehyde, hydrochloric acid and sodium hydroxide are consumed in the reaction process, which virtually increases the cost and causes relatively large environmental pollution. The fourth method is disclosed in the Chinese patent CN1810787 by 1,4-dichlorobutane and methylamine under a certain pressure nucleophilic substitution reaction ring closure to obtain N-methylpyrrolidine, the method is at 50 ℃ ~ 200 ℃, 0.4 ~ 4.0Mpa pressure of the liquid phase reaction, the yield of 85.5%. The by-product of this method is hydrochloric acid, which is too large to be recycled, thereby aggravating environmental pollution. At the same time, the post-reaction treatment requires a large amount of sodium hydroxide to neutralize, which increases the cost; and there is a certain pressure in the reaction, which requires high equipment. The fifth method is the catalytic amination of tetrahydrofuran and methylamine to synthesize N-methylpyrrolidine. This method has been reported in the literature, but there are certain deficiencies. U.S. Patent No. 5,136,053 discloses the ammoniation of cyclic esters and NH ₂ R under the catalysis of aluminosilicate to obtain nitrogen-substituted pyrrolidine, but the reaction needs to be carried out under a certain pressure, and the ammonia in the reaction is relatively large, at 5-20 Among them, the increase of the ammonia ratio not only increases the production cost, but also shortens the catalyst life; Now, the Cr-ZSM-5(30) catalyst can catalyze the ammoniation of tetrahydrofuran and methylamine to synthesize N-methylpyrrolidine, but in this process, the catalytic effect of the catalyst is not high, and the yield of the target product is only maintained at around 48%. ; "Journal of Qufu Normal University", 2009,35 (1): 79～81 introduced the reaction of solid superacid catalyzed tetrahydrofuran and methylamine to synthesize N-methylpyrrolidine. Under the optimal process conditions, N-methylpyrrole The yield of alkane is 81.5%, but because the acidity of solid superacid is too strong, the amount of carbon deposition in the reaction process increases, and the catalytic performance of the catalyst (catalyst life is 400h) and life are affected to a certain extent.

Contents of the invention

The object of the present invention is to provide a kind of high-efficiency catalyst for catalyzing the synthesis of N-methylpyrrolidine for the deficiencies in various synthesis methods of N-methylpyrrolidine. The catalyst synthesizes N-methylpyrrolidine under normal pressure, has good catalytic performance, mild reaction conditions, and less three wastes, and is more suitable for catalytically synthesizing N-methylpyrrolidine in a fixed bed under industrialization.

Technical scheme of the present invention is:

A catalyst for catalyzing the synthesis _of N-methylpyrrolidine, the catalyst is composed of a carrier and a catalytically active component, wherein the carrier is γ- _Al2O3 or HZSM series molecular sieves, and the catalytically active component is a simple substance of metal M or The content of oxides and catalytically active components is 0.5%-20% of the total mass of the catalyst; the particle size of the catalyst is 4-20 mesh.

The carrier mentioned above is preferably various molecular sieves of HZSM series;

The metal M is one or more of Fe, Ni, Co, Cu, Ni, Cr or Mn;

The catalytically active component is preferably a simple substance or oxide of Fe, Fe/Ni or Co/Ni.

The above-mentioned preparation method of the catalyst used for catalytic synthesis of N-methylpyrrolidine, the catalyst is prepared by kneading extrusion method or impregnation method.

The application of the catalyst for catalytically synthesizing N-methylpyrrolidine described above: using a fixed bed reactor, tetrahydrofuran and methylamine aqueous solution are vaporized and enter the reactor, wherein the methylamine aqueous solution concentration is 40% by mass, and the reaction is normal The pressure and temperature are 320℃～360℃; the molar ratio of tetrahydrofuran and methylamine is 1:1～3; the volume space velocity of the mixed gas of tetrahydrofuran and methylamine passing through the catalyst bed is 3500h ^-1 to 7500h ^-1 , under the action of the catalyst , Aminated to N-methylpyrrolidine.

In the application of the catalyst mentioned above, when the active component of the catalyst is a single substance, H ₂ is passed through at a gas space velocity of 400h ^-1 for 3-4 hours for reduction before the reaction.

The beneficial effects produced by adopting the above-mentioned technical scheme are: the catalyst used in the invention is simple to prepare, and the conventional kneading extrusion method or impregnation method can be used; the catalytic active component adopts common metals such as Fe, Fe/Ni or Co/Ni, The support and catalytically active components are inexpensive and readily available. The prepared catalyst is used to catalyze the synthesis of N-methylpyrrolidine, wherein the conversion rate of tetrahydrofuran is basically kept above 80%, and the yield of N-methylpyrrolidine is basically kept above 60%. Compared with The Journal of Organic Chemistry, 1994 , 59(14): 48% in 3998-4000 has been greatly improved; the activity of the catalyst remains unchanged after 720 hours of continuous operation, compared with the catalyst in "Journal of Qufu Normal University", 2009, 35(1): 79-81 Lifespan has been greatly improved. The catalytic reaction is normal pressure reaction, which does not require high reaction equipment, which improves the safety of the operation process. The by-product in the catalytic process is water, no pollution, less waste. In summary, the catalyst used in the invention is simple to prepare, cheap and easy to obtain; the catalytic activity is stable and has a long life; the reaction raw materials are cheap and easy to obtain; the catalytic reaction conditions are mild, the three wastes are less, and there is no pollution.

Detailed ways

Below in conjunction with specific example, the preparation catalyst of the present invention is described in detail:

Implementation Example 1: Preparation of Catalyst Fe/Al ₂ O ₃ by Impregnation Method

Heat and dissolve 45g of ferric nitrate in 1200ml of deionized water, add 1000g of spherical γ-Al ₂ O ₃ , stir evenly, impregnate overnight, dry in a drying oven at 110°C for 20h, and place in a muffle furnace at 550°C in an air atmosphere Calcined for 5 hours to obtain the required catalyst, the size of the catalyst is 4 mesh to 20 mesh; the weight composition of the catalyst is 0.9% of Fe ₂ O ₃ and 99.1% of Al ₂ O ₃ .

Implementation Example 2: Catalyst Ni/Al ₂ O ₃ prepared by kneading and extruding method

Heat and dissolve 600g of nickel nitrate in 1000ml of 1% nitric acid aqueous solution by mass, add 1000g of γ-Al ₂ O ₃ powder, stir evenly, fully grind until completely mixed evenly, extrude into strips, and dry in a drying oven at 110°C for 20h , Calcined in a muffle furnace at 550°C for 5 hours in an air atmosphere to obtain the desired catalyst, the size of the catalyst is 4 mesh to 20 mesh; the weight composition of the catalyst is 17.2% NiO and 82.8% Al ₂ O ₃ .

Implementation example 3: Catalyst Fe-ZSM-5 prepared by impregnation method

Heat and dissolve 225g of ferric nitrate in 800ml of deionized water, add 1000g of HZSM-5 molecular sieve, stir evenly, impregnate overnight, dry in a drying oven at 110°C for 20h, and bake in a muffle furnace at 550°C for 5h in an air atmosphere. The desired catalyst is obtained, and the size of the catalyst is 4 mesh to 20 mesh; the weight composition of the catalyst is Fe ₂ O ₃ 4.1%, ZSM-5 95.9%.

Implementation example 4: preparation of catalyst Co-Ni/ZSM-11 by impregnation method

Heat and dissolve 300g of cobalt nitrate and 75g of nickel nitrate in 800ml of deionized water, add 1000g of HZSM-11, stir evenly, impregnate overnight, dry in a drying oven at 110°C for 20h, and bake in a muffle furnace at 550°C under air atmosphere After 5 hours, the required catalyst was obtained, and the size of the catalyst was 4 mesh to 20 mesh; the weight composition of the catalyst was 8.7% of Co ₂ O ₃ , 1.4% of NiO, and 9.9% of ZSM-118.

Implementation Example 5: Preparation of Catalyst Fe-Ni/ZSM-23 by Impregnation Method

Heat and dissolve 200g of iron nitrate and 70g of nickel nitrate in 800ml of deionized water, add 1000g of HZSM-23, stir evenly, impregnate overnight, dry in a drying oven at 110°C for 20h, and bake in a muffle furnace at 550°C under air atmosphere After 5 hours, the desired catalyst is obtained, and the size of the catalyst is 4 mesh to 20 mesh; the weight composition of the catalyst is 4.4% of Fe ₂ O ₃ , 2.5% of NiO, and 3.1% of ZSM-239.

Below in conjunction with specific examples, the catalyst prepared by the present invention is applied to catalyzing tetrahydrofuran and methylamine to synthesize N-methylpyrrolidine:

Implementation example 6:

Add 1.0L of the catalyst prepared in Example 1 into the fixed-bed reactor, raise the temperature to 310-320°C under the protection of _N2 , and input tetrahydrofuran and 40% methylamine into the fixed-bed reactor at a gas space velocity of 4500h ^-1 Aqueous solution, wherein the molar ratio of tetrahydrofuran and methylamine is 1:1.5, the reaction solution is obtained by catalytic ammoniation, and the product N-methylpyrrolidine is obtained by rectification. Analysis and detection by gas chromatography showed that the conversion rate of tetrahydrofuran was 84%, and the yield of N-methylpyrrolidine was 67%.

Implementation Example 7:

Add 1.0L of the catalyst prepared in Example 1 into the fixed-bed reactor, raise the temperature to 350-500°C under the protection of _N2 , pass _H2 at a gas space velocity of 400h ^-1 for 3-4h reduction, and obtain elemental Fe as the catalyst Catalyst Fe/Al ₂ O ₃ as the active component; under the protection of N ₂ , the temperature is lowered to 310-320°C, and the gas space velocity is 4500h ^-1 , and tetrahydrofuran and 40% methylamine aqueous solution are input into the fixed-bed reactor, wherein tetrahydrofuran and methylamine The amine molar ratio is 1:1.5, and the reaction solution is obtained by catalytic ammoniation, and the product N-methylpyrrolidine is obtained by rectification. Analysis and detection by gas chromatography showed that the conversion rate of tetrahydrofuran was 79%, and the yield of N-methylpyrrolidine was 61%.

Implementation Example 8:

Add 1.2L of the catalyst prepared in Example 2 into the fixed bed reactor, raise the temperature to 330-340°C under the protection of _N2 , and input tetrahydrofuran and 40% methylamine into the fixed bed reactor at a gas space velocity of 4800h ^-1 Aqueous solution, wherein the molar ratio of tetrahydrofuran and methylamine is 1:1.5, the reaction solution is obtained by catalytic ammoniation, and the product N-methylpyrrolidine is obtained by rectification. Analysis and detection by gas chromatography showed that the conversion rate of tetrahydrofuran was 87%, and the yield of N-methylpyrrolidine was 69%.

Implementation Example 9:

Add 1.2L of the catalyst prepared in Example 1 into the fixed-bed reactor, raise the temperature to 350-500°C under the protection of _N2 , pass _H2 into the reactor at a gas space velocity of 400h ^-1 for 3-4h reduction, and obtain elemental Ni as the catalyst The catalyst of the active component is Ni/Al ₂ O ₃ ; under the protection of N ₂ , the temperature is lowered to 330-340°C, and the gas space velocity is 4800h ^-1 , and tetrahydrofuran and 40% methylamine aqueous solution are input into the fixed-bed reactor, wherein tetrahydrofuran and methylamine The amine molar ratio is 1:1.5, and the reaction solution is obtained by catalytic ammoniation, and the product N-methylpyrrolidine is obtained by rectification. Analysis and detection by gas chromatography showed that the conversion rate of tetrahydrofuran was 81%, and the yield of N-methylpyrrolidine was 62%.

Implementation Example 10:

Add 1.5L of the catalyst prepared in Example 3 into the fixed bed reactor, raise the temperature to 310-320°C under the protection of _N2 , and input tetrahydrofuran and 40% methylamine into the fixed bed reactor at a gas space velocity of 5000h ^-1 Aqueous solution, wherein the molar ratio of tetrahydrofuran and methylamine is 1:1.5, the reaction solution is obtained by catalytic ammoniation, and the product N-methylpyrrolidine is obtained by rectification. Analysis and detection by gas chromatography showed that the conversion rate of tetrahydrofuran was 85%, and the yield of N-methylpyrrolidine was 72%.

Implementation Example 11:

Add 1.5L of the catalyst prepared in Example 3 into the fixed-bed reactor, raise the temperature to 350-500°C under the protection of _N2 , pass _H2 at a gas space velocity of 400h ^-1 for 3-4h reduction, and obtain elemental Fe as the catalyst Catalyst Fe-ZSM-5 as the active component; under the protection of _N2 , the temperature is lowered to 310-320°C, and the gas space velocity is 5000h ^-1 , and tetrahydrofuran and 40% methylamine aqueous solution are input into the fixed-bed reactor, wherein tetrahydrofuran and methylamine The amine molar ratio is 1:1.5, and the reaction solution is obtained by catalytic ammoniation, and the product N-methylpyrrolidine is obtained by rectification. Analysis and detection by gas chromatography showed that the conversion rate of tetrahydrofuran was 82%, and the yield of N-methylpyrrolidine was 70%.

Implementation Example 12:

Add 1.2L of the catalyst prepared in Example 4 into the fixed bed reactor, raise the temperature to 310-320°C under the protection of _N2 , and input tetrahydrofuran and 40% methylamine into the fixed bed reactor at a gas space velocity of 4500h ^-1 Aqueous solution, wherein the molar ratio of tetrahydrofuran and methylamine is 1:2, the reaction liquid is obtained by catalytic amination, and the product N-methylpyrrolidine is obtained by rectification. Analysis and detection by gas chromatography showed that the conversion rate of tetraoxyfuran was 91%, and the yield of N-methylpyrrolidine was 87%.

Implementation Example 13:

Add 1.5L of the catalyst prepared in Example 4 into the fixed-bed reactor, raise the temperature to 330-340°C under the protection of _N2 , and input tetrahydrofuran and 40% methylamine into the fixed-bed reactor at a gas space velocity of 5500h ^-1 Aqueous solution, in which the molar ratio of tetrahydrofuran and methylamine is 1:2, the reaction liquid is obtained by catalytic ammoniation, and the product N-methylpyrrolidine is obtained after rectification. Analysis and detection by gas chromatography showed that the conversion rate of tetrahydrofuran was 90%, and the yield of N-methylpyrrolidine was 88%.

Implementation Example 14:

Add 1.5L of the catalyst prepared in Example 4 into the fixed-bed reactor, raise the temperature to 330-340°C under the protection of _N2 , and input tetrahydrofuran and 40% methylamine into the fixed-bed reactor at a gas space velocity of 5000h ^-1 Aqueous solution, in which the molar ratio of tetrahydrofuran and methylamine is 1:3, the reaction solution is obtained by catalytic ammoniation, and the product N-methylpyrrolidine is obtained after rectification. Analysis and detection by gas chromatography showed that the conversion rate of tetrahydrofuran was 94.5%, and the yield of N-methylpyrrolidine was 89%.

Implementation Example 15:

Add 1.5L of the catalyst prepared in Example 4 into the fixed bed reactor, raise the temperature to 350-500°C under the protection of _N2 , pass _H2 into the reactor at a gas space velocity of 400h ^-1 for 3-4h reduction, and obtain elemental Co and Ni Catalyst Co-Ni/ZSM-11, which is the catalytic active component; N ₂ protects and lowers the temperature to 330-340°C, and feeds tetrahydrofuran and 40% methylamine aqueous solution into the fixed-bed reactor at a gas space velocity of 5000h ^-1 , wherein The molar ratio of tetrahydrofuran to methylamine is 1:3, and the reaction solution is obtained through catalytic ammoniation, and the product N-methylpyrrolidine is obtained after rectification. Analysis and detection by gas chromatography showed that the conversion rate of tetrahydrofuran was 91%, and the yield of N-methylpyrrolidine was 86%.

Implementation Example 16:

Add 1.5L of the catalyst prepared in Example 5 into the fixed bed reactor, raise the temperature to 330-340°C under the protection of _N2 , and input tetrahydrofuran and 40% methylamine into the fixed bed reactor at a gas space velocity of 5000h ^-1 The mixed solution of aqueous solution, wherein the molar ratio of tetrahydrofuran and methylamine is 1:3, the reaction solution is obtained by catalytic ammoniation, and the product N-methylpyrrolidine is obtained after rectification. Analysis and detection by gas chromatography showed that the conversion rate of tetrahydrofuran was 93%, and the yield of N-methylpyrrolidine was 86%.

Implementation Example 17:

According to the selected catalyst and reaction conditions of the above-mentioned implementation example 14, sampling at intervals of 100 hours, analysis and detection by gas chromatography, the conversion rate of tetrahydrofuran and the selectivity of N-methylpyrrolidine, the stability and life of the catalyst are investigated. The results are shown in Table 1.

Table 1: Catalyst stability and life test results

It can be seen from Table 1 that the conversion rate of tetrahydrofuran and the yield of N-methylpyrrolidine did not decrease significantly when the catalyst continued to react for 720 hours. Therefore, the activity of the catalyst was stable and the catalyst life was long. The activity of the catalyst remained basically unchanged after 720 hours of continuous reaction.

The spherical and powdery γ-Al ₂ O ₃ and HZSM series molecular sieves used in the present invention are all purchased from Nankai University Catalyst Factory.

Claims (4)

1. the method for a catalytic synthesis of N-methylpyrrolidine; It is characterized by step comprises: adopt fixed bed reactors; Oxolane and methylamine water solution get into reactor after vaporizing, wherein methylamine water solution concentration is mass percent 40%, react to be 320 ℃～360 ℃ of normal pressure, temperature; Oxolane and methylamine mol ratio are 1: 1～3; Oxolane and methylamine water solution mist are 3500h through the volume space velocity of beds ^-1To 7500h ^-1, under catalyst action, ammonification obtains the N-crassitude;

Wherein said catalyst is made up of carrier and catalytic active component, and wherein carrier is γ-Al ₂O ₃Or HZSM series molecular sieve, catalytic active component is simple substance or its oxide of metal M, catalytic active component content is 0.5%～20% of catalyst gross mass; Catalyst particle size is 4 orders～20 orders;

Described metal M is one or more among Fe, Ni, Co, Cu, Cr or the Mn.

2. the method for catalytic synthesis of N-methylpyrrolidine according to claim 1, it is characterized by said carrier is each molecular sieve analog of HZSM series.

3. the method for catalytic synthesis of N-methylpyrrolidine according to claim 1 is characterized by simple substance or oxide that said catalytic active component is Fe, Fe/Ni or Co/Ni.

4. the method for catalytic synthesis of N-methylpyrrolidine according to claim 1 is characterized by when the catalyst activity component is simple substance, before reaction with the catalyst oxidation thing of preparation with gas space velocity 400h ^-1Logical H ₂Reduction 3～4h.