Method for preparing N-methylisopropylamine through continuous hydrogenation

Abstract

The invention provides a method for preparing N-methylisopropylamine through continuous hydrogenation. Loading the catalyst precursor into a fixed bed reactor, introducing nitrogen, introducing hydrogen, and heating for in-situ reduction to obtain a catalytic hydrogenation solid catalyst; the method comprises the following steps: uniformly stirring and mixing a methylamine aqueous solution with the concentration of 40%, acetone and a solvent, introducing the mixture into a fixed bed reactor at a certain flow rate, and introducing hydrogen; and cooling, rectifying and purifying the reaction liquid flowing out of the tail end of the fixed bed reactor to obtain the target product N-methyl isopropylamine. The method has the advantages of high product yield and stable quality; the method has the characteristics of simple operation process and small environmental pollution, and meets the requirements of industrial clean production.

Description

Technical Field

[0001] The present invention belongs to the field of the development of synthetic processes for pharmaceutical intermediates, and particularly relates to a method for continuously hydrogenating to prepare N-methylisopropylamine. Background Art

[0002] N-methylisopropylamine is a small molecule aliphatic amine, which is used to prepare a variety of pharmaceuticals and pesticide intermediates, especially the advanced intermediate N-methylisopropylaminosulfonamide for preparing the herbicide sulfentrazone.

[0003] The patent document WO2006 / 136571 published by BASF uses an alloy catalyst of zirconium, palladium, and platinum to catalyze the continuous hydrogenation reaction of acetone and methylamine to prepare N-methylisopropylamine. After the reaction at a high temperature above 200 °C and a pressure of 150 MPa, the target product is obtained by rectification. This scheme requires a large investment in equipment, and the working pressure is too high, which is not conducive to safe production.

[0004] The patent document CN102070461 uses isopropylamine and formaldehyde as raw materials to synthesize N-methylisopropylamine through Mannich reaction, ring-opening cleavage, and alkalization; the literature reports that the yield of the Mannich reaction is 85%, and the yield of the decomposition reaction is 50%; this technical scheme will cause the generation of a large amount of formaldehyde-containing wastewater, which does not meet the basic requirements of industrial cleaner production.

[0005] The patent document CN 112851519 uses isopropylamine and dimethyl carbonate as raw materials to prepare N-methylisopropylamine through methylation reaction; however, since the alkalinity and affinity of the generated N-methylisopropylamine are stronger than those of primary amines, further methylation reaction will occur, resulting in the by-product N,N-dimethylisopropylamine; and since the boiling points of the by-product and the main product are close, it is difficult to separate them by rectification.

[0006] The patent document CN 116444378 reports the preparation of N-methylisopropylamine by alkylation reaction of 2-bromopropane and methylamine under alkaline conditions. This scheme will also produce over-alkylation by-products, and an additional acid-binding agent needs to be added to the reaction system, which is not conducive to large-scale industrial production. Summary of the Invention

[0007] As a basic raw material for sulfentrazone, N-methylisopropylamine is used in large amounts. There is an urgent need to develop a new method for continuously and stably preparing N-methylisopropylamine. To solve the problems existing in the prior art, the present invention designs a new synthetic method for N-methylisopropylamine with mild reaction conditions, good chemoselectivity, and convenient for continuous industrial production.

[0008] The present invention provides a method for continuously hydrogenating to prepare N-methylisopropylamine, which mainly includes the following steps:

[0009] A catalyst precursor is loaded into a fixed bed reactor, and nitrogen is introduced and then hydrogen is introduced to heat and in-situ reduce to obtain a catalytic hydrogenation solid catalyst; a 40% methylamine aqueous solution, acetone, and a solvent are stirred and mixed uniformly, and introduced into the fixed bed reactor at a certain flow rate, and hydrogen is introduced; the reaction liquid flowing out of the end of the fixed bed reactor is cooled, rectified, and purified to obtain the target product, nitrogen-methylisopropylamine;

[0010] The chemical reaction equation is as follows:

[0011]

[0012] Preferably, the catalytic hydrogenation solid catalyst is a supported catalyst with γ-Al2O3 as a carrier and at least one of Ni, Cu and Zn as an active component, and the loading amount is 20%. Preferably, the preparation method of the catalytic hydrogenation solid catalyst is as follows: dissolving the metal nitrate, obtaining a catalyst precursor by impregnation, drying and calcination, and then reducing it in situ with hydrogen.

[0013] Taking the catalyst 20% Cu, Ni / γ-Al2O3 as an example, the preparation method is as follows: 24.1g Cu(NO3)2·3H2O and 2.9g Ni(NO3)2·6H2O are stirred evenly in 500mL deionized water. 24.0g Na2CO3 is stirred and dissolved in 500mL deionized water. At room temperature, the above two solutions are slowly added to 300mL deionized water while stirring vigorously. During the addition, the pH value is controlled to be between 7 and 8. After the addition, age for 2 hours; filter, wash with deionized water, and dry the filter cake at 120℃ for 8h. The obtained solid is fully mixed and ground with 36.0g γ-Al2O3 and 50mL deionized water, and then filled into a molding machine (diameter 3mm) for extrusion molding. The molded catalyst is dried at 100℃ for 8h, and then calcined at 500℃ in a muffle furnace for 10h, and then the catalyst is cut into small sections of 3-5mm. Before use, the catalyst was reduced at 300 °C in a hydrogen atmosphere for 3 h.

[0014] Preferably, the molar ratio of the methylamine aqueous solution to acetone is 1:1 to 1:1.6.

[0015] Preferably, the reaction solvent is any one of methanol, isopropanol and ethanol.

[0016] Preferably, the mass ratio of the methylamine aqueous solution to the catalytic hydrogenation solid catalyst is 40:1 to 20:1.

[0017] Preferably, the reaction temperature in the fixed bed reactor is 80-120° C., the reaction pressure is 0.4-2.0 MPa, the reaction feed rate is 1.5-3.0 mL / min, the residence time of the filtrate in the fixed bed reactor is 30-60 min, and the hydrogen pump is set at a flow rate of 3.0 mL / min. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 The gas chromatogram of the fixed bed effluent in the specific embodiment of the present invention is DETAILED DESCRIPTION

[0019] The present invention is described below with reference to specific examples, but the present invention is not limited thereto. In the art, simple replacement or improvement made by technicians in the field to the present invention belongs to the technical solution protected by the present invention.

[0020] Example 1

[0021] A method for preparing nitrogen-methyl isopropylamine by continuous hydrogenation mainly comprises the following steps:

[0022] Stir 24.1g Cu(NO3)2·3H2O and 2.9g Ni(NO3)2·6H2O in 500mL deionized water. Stir and dissolve 24.0g Na2CO3 in 500mL deionized water. At room temperature, slowly drop the two solutions into 300mL deionized water while stirring vigorously. During the addition, control the pH value to be between 7 and 8. After the dropwise addition, age for 2 hours; filter, wash with deionized water, and dry the filter cake at 120℃ for 8h. The obtained solid is fully mixed and ground with 36.0g γ-Al2O3 and 50mL deionized water, and then filled into a molding machine (diameter 3mm) for extrusion molding. The molded catalyst is dried at 100℃ for 8h, and then calcined at 500℃ in a muffle furnace for 10h, and then the catalyst is cut into small sections of 3-5mm. Cu, Ni / γ-Al2O3 catalysts were loaded into a fixed bed reactor with an inner diameter of 10 mm, a length of 650 mm, and a constant temperature zone of 300 mm. N2 was introduced to exhaust the air in the fixed bed reactor, and then H2 was introduced to exhaust the N2. The reactor was heated to 300°C and kept warm for 3 hours to obtain a reduced catalyst. Then the tubular reactor was adjusted to 80°C, the hydrogen pressure of the reactor was adjusted to 1.4 MPa, 45.3 g of acetone and 43.2 g of methylamine aqueous solution were diluted with 300 mL of methanol, and then continuously introduced into the fixed bed reactor using a horizontal flow pump at a feed rate of 1.5 mL / min. The reaction liquid continuously flowed out from the lower end of the fixed bed, and the reaction liquid flowing out after the condensation section was collected. The reaction liquid was distilled at atmospheric pressure to obtain a colorless liquid with a yield of 89%.

[0023] Example 2

[0024] 24.1 g of Cu(NO3)2·3H2O and 4.3 g of Ni(NO3)2·6H2O were stirred evenly in 500 mL of deionized water. 27.0 g of Na2CO3 was stirred and dissolved in 500 mL of deionized water. At room temperature, while stirring vigorously, the above two solutions were slowly added dropwise to 300 mL of deionized water. During the dropping process, the pH value was controlled to be between 7 and 8. After dropping, it was aged for 2 hours; filtered, washed with deionized water, and the filter cake was dried at 120 °C for 8 h. The obtained solid was fully mixed and ground with 36.0 g of γ-Al2O3 and 50 mL of deionized water, and then filled into a former (diameter 3 mm) and extruded into shape. The formed catalyst was dried at 100 °C for 8 h, then calcined in a muffle furnace at 500 °C for 10 h, and then the catalyst was cut into small segments of 3 - 5 mm. The Cu, Ni / γ-Al2O3 catalyst was loaded into a fixed-bed reactor with an inner diameter of 10 mm and a length of 650 mm, and the constant-temperature zone was 300 mm. N2 was introduced to exhaust the air in the fixed-bed reactor, and then H2 was introduced to exhaust N2. The reactor was heated to 300 °C and kept warm for 3 hours to obtain a reduced catalyst. Then the tubular reactor was adjusted to 80 °C, the hydrogen pressure in the reactor was adjusted to 0.6 MPa, 38.8 g of acetone and 43.2 g of aqueous methylamine solution diluted with 300 mL of isopropanol were continuously fed into the fixed-bed reactor at a feeding rate of 1.6 mL / min using a peristaltic pump, and the reaction solution continuously flowed out from the lower end of the fixed-bed. The reaction solution flowing out after the condensation section was collected. The reaction solution was rectified at atmospheric pressure to obtain a colorless liquid with a yield of 93%.

[0025] Example 3

[0026] 24.1 g of Cu(NO3)2·3H2O, 2.9 g of Ni(NO3)2·6H2O, and 1.7 g of Zn(NO3)2·6H2O were stirred evenly in 500 mL of deionized water. 30.0 g of Na2CO3 was stirred and dissolved in 500 mL of deionized water. At room temperature, while stirring vigorously, the above two solutions were slowly added dropwise to 300 mL of deionized water. During the dropping process, the pH value was controlled to be between 7 and 8. After the dropping was completed, it was aged for 2 hours; filtered, washed with deionized water, and the filter cake was dried at 120 °C for 8 h. The obtained solid was fully mixed and ground with 36.0 g of γ-Al2O3 and 50 mL of deionized water, and then filled into a former (diameter 3 mm) and extruded into a shape. The formed catalyst was dried at 100 °C for 8 h, then calcined in a muffle furnace at 500 °C for 10 h, and then the catalyst was cut into small sections of 3 - 5 mm. The Cu, Ni / γ-Al2O3 catalyst was loaded into a fixed-bed reactor with an inner diameter of 10 mm and a length of 650 mm, and the constant temperature zone was 300 mm. N2 was introduced to exhaust the air in the fixed-bed reactor, and then H2 was introduced to exhaust N2. The reactor was heated to 300 °C and kept warm for 3 hours to obtain a reduced catalyst. Then the tubular reactor was adjusted to 80 °C, the hydrogen pressure in the reactor was adjusted to 1.0 MPa, 51.8 g of acetone and 43.2 g of aqueous methylamine solution diluted with 300 mL of isopropanol were continuously fed into the fixed-bed reactor at a feeding rate of 1.6 mL / min using a peristaltic pump, and the reaction liquid continuously flowed out from the lower end of the fixed-bed. The reaction liquid flowing out after the condensation section was collected. The reaction liquid was rectified at atmospheric pressure to obtain a colorless liquid with a yield of 91%.

[0027] Example 4

[0028] 24.1 g of Cu(NO3)2·3H2O, 2.9 g of Ni(NO3)2·6H2O, and 0.6 g of Zn(NO3)2·6H2O were stirred evenly in 500 mL of deionized water. 30.0 g of Na2CO3 was stirred and dissolved in 500 mL of deionized water. At room temperature, while stirring vigorously, the above two solutions were slowly added dropwise to 300 mL of deionized water. During the dropping process, the pH value was controlled to be between 7 and 8. After dropping, it was aged for 2 hours; filtered, washed with deionized water, and the filter cake was dried at 120 °C for 8 h. The obtained solid was fully mixed and ground with 36.0 g of γ-Al2O3 and 50 mL of deionized water, and then filled into a former (diameter 3 mm) to extrude into a shape. The formed catalyst was dried at 100 °C for 8 h, then calcined in a muffle furnace at 500 °C for 10 h, and then the catalyst was cut into small sections of 3 - 5 mm. The Cu, Ni / γ-Al2O3 catalyst was loaded into a fixed-bed reactor with an inner diameter of 10 mm and a length of 650 mm, and the constant temperature zone was 300 mm. N2 was introduced to exhaust the air in the fixed-bed reactor, and then H2 was introduced to exhaust N2. The reactor was heated to 300 °C and kept warm for 3 hours to obtain a reduced catalyst. Then the tubular reactor was adjusted to 80 °C, the hydrogen pressure in the reactor was adjusted to 1.0 MPa, 38.8 g of acetone and 43.2 g of aqueous methylamine solution diluted with 300 mL of methanol were continuously introduced into the fixed-bed reactor at a feeding rate of 1.8 mL / min using a peristaltic pump, and the reaction solution continuously flowed out from the lower end of the fixed-bed. The reaction solution flowing out after the condensation section was collected. The reaction solution was rectified at atmospheric pressure to obtain a colorless liquid with a yield of 97%.

Claims

1. A method for continuously hydrogenating to prepare N-methylisopropylamine, characterized in that, It includes the following steps: Before loading the catalyst precursor into the fixed-bed reactor, nitrogen is introduced, and then hydrogen is introduced for in-situ reduction by heating to obtain a solid catalytic hydrogenation catalyst; an aqueous methylamine solution with a concentration of 40%, acetone, and a solvent are stirred and mixed evenly, and are fed into the fixed-bed reactor at a certain flow rate, and hydrogen is introduced; the reaction solution flowing out from the end of the fixed-bed reactor is cooled and purified by distillation to obtain the target product N-methylisopropylamine; The chemical reaction equation is as follows:

2. The synthesis method according to claim 1, wherein The solid catalytic hydrogenation catalyst is a supported catalyst with γ-Al2O3 as the carrier and at least one of Ni, Cu, and Zn as the active component, and the loading amount is 20%; the preparation method of the solid catalytic hydrogenation catalyst is as follows: dissolve the metal nitrate, and obtain the catalyst precursor through impregnation, drying, and calcination, and then perform in-situ reduction with hydrogen.

3. The synthesis method according to claim 1, wherein The molar ratio of the aqueous methylamine solution to acetone is 1:1 to 1:1.

6.

4. The synthesis method according to claim 1, characterized in that, The reaction solvent is any one of methanol, isopropanol, and ethanol.

5. The synthesis method according to claim 1, characterized in that The mass ratio of the aqueous methylamine solution to the solid catalytic hydrogenation catalyst is 40:1 to 20:

1.

6. The synthesis method according to claim 1, wherein, The reaction temperature in the fixed-bed reactor is 80-120°C, the reaction pressure is 0.4-2.0 MPa, the feeding rate of the reaction is 1.5-3.0 mL / min, the residence time of the filtrate in the fixed-bed reactor is 30-60 min, and the flow rate set by the hydrogen pump is 3.0 mL / min.

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