Continuous synthesis method of N, N-diisopropylethylamine

Abstract

The invention discloses a continuous synthesis method of N, N-diisopropylethylamine, which comprises the following steps: taking a mixed solution of ethanol and diisopropylamine as a raw material, taking a fumed silica loaded Zn / Zr oxide as a catalyst, and realizing continuous synthesis of N, N-diisopropylethylamine in a fixed bed reactor under the reaction conditions of normal pressure, nitrogen atmosphere and 250-400 DEG C, compared with the conventional N, N-diisopropylethylamine synthesis technology, the method disclosed by the invention has the advantages that the fumed silica is used for loading the Zn / Zr oxide catalyst for the first time, and hydrogenolysis of the raw material diisopropylamine is avoided, so that the generation of by-products such as triethylamine, diethyl isopropylamine and diethyl butylamine is remarkably reduced, and the effects of high selectivity and high yield are achieved; meanwhile, according to the method, a more stable and efficient production process can be provided, synthesis is carried out without high pressure and hydrogen, the operation safety can be improved, and the requirement on equipment is reduced.

Description

Technical Field

[0001] The invention relates to a continuous synthesis method of N,N-diisopropylethylamine. Background Art

[0002] N,N-diisopropylethylamine (DIEA) is a colorless, transparent liquid that is insoluble in water but easily soluble in organic solvents such as alcohol, ether, and acetone. It is widely used in the fields of medicine, pesticides, catalysis, etc. Its main uses include: (1) manufacturing pharmaceutical anesthetics and pesticide herbicides, and is also an important intermediate for the synthesis of pesticides and pharmaceuticals; (2) used as a condensation agent or organic reaction solvent, such as for the condensation of halogenated hydrocarbons to form urethanes; (3) using DIEA as a basic precatalyst in the presence of methanol or 2,2,2-trifluoroethanol, it can achieve the catalytic enantioselective aldehyde reaction of alkenyl esters with indigo carmine.

[0003] Based on the currently published literature reports, the main routes related to DIEA synthesis are as follows:

[0004] (1) Patent document CN101759571A reported that DIEA is produced by the reaction of diisopropylamine and alkyl halide, with a yield of about 95%. However, the reaction is carried out at a pressure of 0.4 to 2.5 MPa, which means that the reaction equipment must be able to withstand higher pressures, placing higher requirements on the strength and pressure resistance of the equipment. The hydrogen halide generated during the reaction is a corrosive gas that may corrode the equipment and pipelines, thereby shortening the service life of the equipment and increasing the cost of maintenance and replacement.

[0005] (2) Patent document CN102875385A reported that DIEA was synthesized by using triacetaldehyde as raw material, depolymerizing under acidic conditions, and reacting with diisopropylamine using metal hydride as a reducing agent. Although this method has excellent yield, the complexity of its synthesis route and its reliance on highly corrosive reagents place high standards on production equipment. This not only increases production costs, but also poses safety risks.

[0006] (3) Patent document CN117843493A reported: diisopropylamine and ethane halides are used as raw materials, fumed silica loaded metal oxides are used as catalysts, and the solvent is added to a sealed autoclave. The reaction is carried out at a temperature of 90-190°C and a pressure of 0.5-1.2 MPa for 5-10 hours, and the product DIEA is obtained after post-treatment. However, this process requires the use of special high-pressure reaction equipment and strict safety measures to ensure safe operation. The high-pressure reactor needs regular maintenance and overhaul to ensure its good operation and extend its service life.

[0007] (4) Patent document CN114057581A reported that: in the conventional production process of Raney nickel, 3% molybdenum and 8% copper by weight of the prepared Raney nickel are additionally added to obtain a product as a catalyst. Hydrogen is filled into a reaction vessel, and a mixed solution of monoethylamine and acetone is added under a hydrogen environment. The reaction pressure in the reaction vessel is controlled to be 1.6-3.0 MPa by filling hydrogen, and the reaction temperature is controlled to be 120-200°C. The reaction time is 1.5-3.0 h. After the reaction is completed, monoethylamine and acetone are distilled out, and N-ethylisopropylamine is distilled out or N-ethylisopropylamine is further reacted with acetone to distill out isopropanol, and finally DIEA is distilled out. However, Raney nickel itself is a relatively expensive catalyst, and the preparation of the catalyst is complicated. Using high-pressure hydrogen for the reaction may bring safety risks. Although this method improves selectivity, the purity of the final product needs to be ensured by an additional purification step, which increases the complexity of the method.

[0008] (5) Patent document CN114149328A reported: N,N-diisopropylethylamine was prepared by reaction of ethanol and diisopropylamine as raw materials in a fixed bed reactor under a hydrogen atmosphere. The reaction pressure was 0.8-1.6 MPa, the reaction temperature was 180-230°C, and Mo-Ni-Cu / Al2O3 catalyst was used. However, this route would bring certain safety risks when reacting in a hydrogen atmosphere, especially under high pressure conditions.

[0009] (6) The document "Study on the Synthesis of N,N-Diisopropylethylamine" reported that: after ethyl chloride is synthesized from ethanol and hydrochloric acid, it is passed into a reactor to react with vaporized diisopropylamine to generate DIEA. At the same time, the byproduct hydrogen chloride reacts with vaporized diisopropylamine to generate salt, which then reacts with sodium hydroxide at the bottom of the tower to generate the raw material diisopropylamine. Although the method of synthesizing ethyl chloride from ethanol and hydrochloric acid has certain industrial applications, it still has problems such as safety, raw material utilization, environmental pollution, equipment requirements, product purity, process complexity and energy consumption, which need to be solved through further process optimization and technological innovation.

[0010] In order to effectively synthesize DIEA (N,N-diisopropylethylamine) in actual production, it is urgent to develop a new synthesis strategy that should have the advantages of simplified synthesis process, easy-to-obtain raw materials and catalysts, abundant raw material conversion, abundant target products, etc. At the same time, this method should also consider key factors such as minimized environmental impact, high operational safety and significant economic benefits to promote the sustainable development of related industries. Summary of the invention

[0011] The present invention aims to develop a method for continuously synthesizing N,N-diisopropylethylamine. The method realizes continuous production in a fixed bed under a hydrogen-free atmosphere at normal pressure, uses a fumed silica-supported Zn / Zr oxide catalyst for the first time, avoids hydrogenolysis of the raw material diisopropylamine, thereby significantly reducing the generation of by-products such as triethylamine, diethylisopropylamine, and diethylbutylamine, and achieves the effects of high selectivity and high yield.

[0012] The present invention has simple synthesis steps, and the raw materials and catalysts are easy to obtain. Continuous synthesis can provide a more stable and efficient production process. At the same time, the present invention does not require high pressure and hydrogen conditions, which can improve the safety of operation and reduce equipment requirements.

[0013] The technical solution of the present invention is as follows:

[0014] A continuous synthesis method of N,N-diisopropylethylamine, comprising:

[0015] Using a mixture of ethanol and diisopropylamine as raw materials and fumed silica-supported Zn / Zr oxide as a catalyst, continuous synthesis of N,N-diisopropylethylamine was achieved in a fixed bed reactor under normal pressure, nitrogen atmosphere, and reaction conditions of 250-400°C.

[0016] Preferably, in the mixed solution of ethanol and diisopropylamine, the molar ratio of ethanol to diisopropylamine is 1 to 5:1;

[0017] The invention prepares N,N-diisopropylethylamine and obtains by-products such as acetaldehyde, butyraldehyde, triethylamine, diethylisopropylamine, diethylbutylamine and the like. The by-products can be sold as by-products after being distilled and purified.

[0018] The catalyst used in the present invention is fumed silica loaded Zn / Zr oxide, with fumed silica as a carrier and ZnO and ZrO2 as loads; based on the total mass of the catalyst, the ZnO loading is 1 to 10 wt.%, and the ZrO2 loading is 1 to 10 wt.% as Zr.

[0019] The catalyst of the present invention is prepared by an impregnation method, wherein a zinc oxide precursor and a zirconium oxide precursor are loaded on a fumed silica carrier by an impregnation method, and then calcined at a high temperature. The specific preparation method is as follows:

[0020] Add zinc oxide precursor and zirconium oxide precursor to the solvent, stir until completely dissolved, add fumed silica carrier, continue stirring for 2 to 8 hours, then evaporate to dryness at 100 to 150° C., dry at 80 to 120° C., grind and place in a muffle furnace, calcine for 2 to 8 hours at 400 to 800° C. in air or oxygen atmosphere, cool to room temperature, and obtain the catalyst, grind and set aside;

[0021] in,

[0022] The zinc oxide precursor is selected from one or more of zinc citrate, zinc acetate, zinc lactate, zinc glycinate, zinc gluconate, zinc acetylacetonate, zinc oxalate, zinc phytate, diethyl zinc, zinc chloride, zinc nitrate, zinc sulfate, and zinc perchlorate;

[0023] The zirconium oxide precursor is selected from one or more of zirconium acetate, zirconium chloride, zirconium oxychloride, zirconium nitrate, zirconium acetylacetonate, zirconium ethanol, zirconium n-propoxide, zirconium isopropoxide, zirconium n-butoxide, zirconium tert-butoxide, and zirconium propionate;

[0024] The solvent is selected from one or more of deionized water, methanol, ethanol, propanol, butanol, n-hexane, benzene, toluene, chloroform, and carbon tetrachloride;

[0025] The preferred high temperature calcination conditions are: air atmosphere, 450° C., 4 h.

[0026] The activity of the catalyst was evaluated in a fixed bed reactor. The catalyst dosage was 0.2-1.0 g. The reaction pressure was normal pressure. Nitrogen (10 mL / min) was used to maintain the pressure of the reaction system. The reaction temperature was 250-400°C. 乙醇 :n 二异丙胺 =1:1, 2:1, 3:1, 4:1, 5:1) as raw materials, and pumped into the reaction system pipeline through a high-pressure constant flow pump at a liquid flow rate of 0.01-0.1 mL / min, and then heated and gasified and entered the fixed bed for reaction. The product obtained after the reaction was cooled by a cold trap and liquefied in a collection tank. The product was collected every 2 hours and analyzed on a gas chromatograph (EN-20 capillary column, 30 m long, 0.25 mm inner diameter, 0.25 μm stationary phase liquid film thickness; FID detector). The final ethanol and diisopropylamine conversion rates, product selectivity and yield were calculated using the internal standard method.

[0027] Toluene was used as the internal standard (y represents the peak area ratio, x represents the mass ratio).

[0028] Standard curve of ethanol: y = 2.3927x-0.1837, R 2 =0.9951

[0029] Standard curve of diisopropylamine: y = 1.394x + 0.0273, R 2 =0.9998

[0030] Standard curve of the product: y = 1.3161x-0.279, R 2 =0.998

[0031] The technical principles of the present invention include:

[0032] The catalyst used in the present invention uses fumed silica as a carrier, and ZnO and ZrO2 are loaded by an impregnation method. After high-temperature treatment, the interaction between the oxides and the interaction between the oxides and the carrier can be enhanced, and the dispersibility of the oxides can be improved. At the same time, the loaded Zn / Zr oxide avoids the metal element catalyzing the hydrogenolysis of diisopropylamine, thereby reducing the generation of by-products, so that excellent DIEA selectivity and high yield can be obtained.

[0033] The synthesis method of the present invention has the following advantages:

[0034] Compared with the synthesis route of reacting diisopropylamine and alkyl halide, the method does not generate corrosive gas during the reaction process, and the method is carried out under normal pressure, does not affect the reaction equipment, and does not require the use of special high-pressure reaction equipment.

[0035] Compared with the synthesis route of reacting paraldehyde with metal hydride and diisopropylamine under acidic conditions, the method does not use highly corrosive reagents, is simple to operate, and uses cheap and readily available oxides to prepare the catalyst, thereby reducing costs.

[0036] Compared with the reaction route using a mixed solution of monoethylamine and acetone as raw materials, the method is synthesized under normal pressure and in the absence of hydrogen, has high safety and reduces the requirements on equipment.

[0037] Compared with a synthetic route in which ethyl chloride is synthesized from ethanol and hydrochloric acid as raw materials and then introduced into a reactor to react with diisopropylamine, the method has low requirements on equipment, low process complexity and is more environmentally friendly.

[0038] Compared with the synthesis route using diisopropylamine and ethanol as raw materials, the present method uses an oxide catalyst in a normal pressure hydrogen-free atmosphere for the first time, thereby avoiding hydrogenolysis of the raw material diisopropylamine, reducing the generation of by-products, and achieving the purpose of high selectivity and high yield. DETAILED DESCRIPTION

[0039] The present invention is further described below by means of specific embodiments, but the protection scope of the present invention is not limited thereto.

[0040] In the following embodiments,

[0041] The preparation method of 5Zn8Zr / SiO2 catalyst (wherein 5 and 8 are the mass contents of Zn and Zr, i.e., 5wt.% and 8wt.%) is as follows:

[0042] Weigh 0.6825 g zinc nitrate and 0.3765 g zirconium nitrate and dissolve them in 40 mL deionized water. Stir magnetically (450 r / min). After stirring until completely transparent, add 1.0 g fumed silica carrier (Shanghai Aladdin Biochemical Technology Co., Ltd., hydrophilic, specific surface area: 400 m 2 / g), stir evenly for 2h. After sufficient stirring, transfer to a 110℃ oil bath, stir and evaporate to dryness (110℃, 450r / min). If any white substance remains attached to the inner wall of the beaker during the oil bath evaporation, rinse with deionized water. After evaporation, transfer to an 80℃ forced air oven and dry overnight. After complete drying, grind into fine powder and then send to a muffle furnace for high-temperature calcination (air atmosphere, 450℃, 4h). Cool to room temperature, grind again and bag for storage.

[0043] Similarly, the preparation methods of catalysts such as 5Zn2Zr / SiO2, 5Zn3Zr / SiO2, 5Zn4Zr / SiO2, 5Zn5Zr / SiO2 are similar to those described above, wherein the amounts of zirconium nitrate used are 0.0941 g, 0.1412 g, 0.1882 g, and 0.2353 g, respectively.

[0044] Example 1

[0045] The continuous synthesis of N,N-diisopropylethylamine was carried out in a fixed bed reactor, and the amount of catalyst used was 0.2 g (the same below).

[0046] Reaction conditions: 5Zn8Zr / SiO2 catalyst, 4:1 alcohol amine molar ratio, liquid flow rate 0.054mL / min, nitrogen flow rate 10mL / min, normal pressure.

[0047] The experimental data are:

[0048]

[0049]

[0050] Example 2

[0051] Reaction conditions: 5Zn1Zr / SiO2 catalyst, 4:1 alcohol amine molar ratio, liquid flow rate 0.054 mL / min, nitrogen flow rate 10 mL / min, normal pressure.

[0052] The experimental data are:

[0053]

[0054] Example 3

[0055] Reaction conditions: 5Zn2Zr / SiO2 catalyst, 4:1 alcohol amine molar ratio, liquid flow rate 0.054mL / min, nitrogen flow rate 10mL / min, normal pressure.

[0056] The experimental data are:

[0057]

[0058] Example 4

[0059] Reaction conditions: 5Zn3Zr / SiO2 catalyst, 4:1 alcohol amine molar ratio, liquid flow rate 0.054mL / min, nitrogen flow rate 10mL / min, normal pressure.

[0060] The experimental data are:

[0061]

[0062] Example 5

[0063] Reaction conditions: 5Zn4Zr / SiO2 catalyst, 4:1 alcohol amine molar ratio, liquid flow rate 0.054mL / min, nitrogen flow rate 10mL / min, normal pressure.

[0064] The experimental data are:

[0065]

[0066]

[0067] Example 6

[0068] Reaction conditions: 5Zn5Zr / SiO2 catalyst, 4:1 alcohol amine molar ratio, liquid flow rate 0.054mL / min, nitrogen flow rate 10mL / min, normal pressure.

[0069] The experimental data are:

[0070]

[0071] Example 7

[0072] Reaction conditions: 5Zn7Zr / SiO2 catalyst, 4:1 alcohol amine molar ratio, liquid flow rate 0.054mL / min, nitrogen flow rate 10mL / min, normal pressure.

[0073] The experimental data are:

[0074]

[0075] Example 8

[0076] Reaction conditions: 5Zn10Zr / SiO2 catalyst, 4:1 alcohol amine molar ratio, liquid flow rate 0.054mL / min, nitrogen flow rate 10mL / min, normal pressure.

[0077] The experimental data are:

[0078]

[0079] In the following comparative examples, the preparation method of Cu-Co / SiO2 catalysts with different Cu and Co mass contents is as follows:

[0080] The Cu-Co / SiO2 catalysts with different Cu and Co contents were prepared by ammonia evaporation method with a fixed total metal content of Cu and Co at 16 wt.%. Taking 2Cu-14Co / SiO2 catalyst as an example, the 2 and 14 in "2Cu-14Co" stand for 2 wt.% Cu and 14 wt.% Co.

[0081] According to the required mass, accurately weigh copper nitrate trihydrate and cobalt nitrate hexahydrate, dissolve the precursor in 60mL deionized water, stir at room temperature for 3h to form a clear salt solution. Then add hydrophilic gas-phase SiO2 as a carrier and stir overnight. Then add ammonia water drop by drop to adjust the pH value of the solution to 11.0-12.0 to form copper ammonia and cobalt ammonia complex solutions. After stirring at 25°C for 4h, evaporate the ammonia at 90°C. The complex ions will undergo a dehydration reaction with the hydroxyl groups on the surface of SiO2, so that the copper and cobalt ions can be evenly loaded on the surface of gas-phase SiO2. When the pH value of the mixed solution is 6.0-7.0, stop heating. The catalyst is transferred to a blast drying oven, aged at 90°C for 12h, and the solid obtained after evaporation is fully ground using an agate mortar. Then put it in a muffle furnace and calcine it at 450°C for 4h in a static air atmosphere with a heating rate of 1°C / min.

[0082] Comparative Example

[0083] Reaction conditions: Cu-Co / SiO2 catalyst, 4:1 alcohol amine molar ratio, liquid flow rate 0.054 mL / min, nitrogen flow rate 10 mL / min, normal pressure, reaction temperature, 300°C.

[0084] The experimental data are:

[0085]

[0086] According to the above experimental results, it can be seen that on the catalysts of Examples 1 to 8, when the reaction temperature is 250°C and 300°C, the raw material diisopropylamine does not undergo hydrogenolysis, and the DIEA selectivity reaches 100%. When the reaction temperature is 350°C, the yield of DIEA on the 5Zn8Zr / SiO2 catalyst is the highest, which is 49.8%. In contrast, when the catalyst contains metals such as Cu and Co, the raw material diisopropylamine is easily hydrogenolyzed, and the DIEA selectivity is generally less than 15%.

[0087] The present invention uses fumed silica loaded Zn / Zr oxide as a catalyst, the selectivity of diisopropylethylamine can reach 100%, and the cost of subsequent product separation will be greatly reduced. From the perspective of industrial production, after the product is separated, the raw materials can be recycled, further improving the conversion rate and yield.

[0088] It should be emphasized that the above are only some embodiments of the present invention. Obviously, the protection scope of the present invention is not limited to these specific examples, but also includes many other possible variations. All variations that can be directly derived or associated with by those skilled in the art based on the content disclosed in the present invention should be regarded as the protection scope of the present invention.

Claims

1. A continuous synthesis method of N,N-diisopropylethylamine, characterized in that: The method comprises: Using a mixture of ethanol and diisopropylamine as raw materials and fumed silica-supported Zn / Zr oxide as a catalyst, continuous synthesis of N,N-diisopropylethylamine was achieved in a fixed bed reactor under normal pressure, nitrogen atmosphere, and reaction conditions of 250-400°C. The fumed silica loads Zn / Zr oxide, with fumed silica as a carrier and ZnO and ZrO2 as loads.

2. The continuous synthesis method of N,N-diisopropylethylamine as claimed in claim 1, characterized in that: In the mixed solution of ethanol and diisopropylamine, the molar ratio of ethanol to diisopropylamine is 1 to 5:

1.

3. The continuous synthesis method of N,N-diisopropylethylamine as claimed in claim 1, characterized in that: Based on the total mass of the catalyst fumed silica loaded Zn / Zr oxide, the loading amount of ZnO as Zn is 1 to 10 wt.%, and the loading amount of ZrO2 as Zr is 1 to 10 wt.%.

4. A fumed silica-supported Zn / Zr oxide, characterized in that: Fumed silica is used as the carrier, and ZnO and ZrO2 are the loads.

5. The method for preparing fumed silica-supported Zn / Zr oxide according to claim 4, characterized in that: The method is as follows: Add zinc oxide precursor and zirconium oxide precursor to the solvent, stir until completely dissolved, add fumed silica carrier, continue stirring for 2 to 8 hours, then evaporate to dryness with stirring at 100 to 150° C., then dry at 80 to 120° C., grind and place in a muffle furnace, calcine for 2 to 8 hours at 400 to 800° C. in air or oxygen atmosphere, and cool to room temperature to obtain.

6. The method for preparing fumed silica-supported Zn / Zr oxide according to claim 5, characterized in that: The zinc oxide precursor is selected from one or more of zinc citrate, zinc acetate, zinc lactate, zinc glycinate, zinc gluconate, zinc acetylacetonate, zinc oxalate, zinc phytate, diethyl zinc, zinc chloride, zinc nitrate, zinc sulfate, and zinc perchlorate.

7. The method for preparing fumed silica-supported Zn / Zr oxide according to claim 5, characterized in that: The zirconium oxide precursor is selected from one or more of zirconium acetate, zirconium chloride, zirconium oxychloride, zirconium nitrate, zirconium acetylacetonate, zirconium ethoxide, zirconium n-propoxide, zirconium isopropoxide, zirconium n-butoxide, zirconium tert-butoxide, and zirconium propionate.

8. The method for preparing fumed silica-supported Zn / Zr oxide according to claim 5, characterized in that: The solvent is selected from one or more of deionized water, methanol, ethanol, propanol, butanol, n-hexane, benzene, toluene, chloroform and carbon tetrachloride.

9. The method for preparing fumed silica-supported Zn / Zr oxide according to claim 5, characterized in that: The calcination conditions are: air atmosphere, 450°C, 4h.

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