Method for preparing 4, 4-dichloro-2-amino-diphenyl ether through continuous hydrogenation

Abstract

The invention discloses a method for preparing 4, 4-dichloro-2-amino-diphenyl ether through continuous hydrogenation, which comprises the following steps: dissolving 4, 4-dichloro-2-nitro-diphenyl ether in a solvent to obtain a solution of 4, 4-dichloro-2-nitro-diphenyl ether; adjusting the flow rate of the 4, 4-dichloro-2-nitro-diphenyl ether solution and hydrogen, mixing the 4, 4-dichloro-2-nitro-diphenyl ether solution and hydrogen in a gas-liquid mixer at the inlet of the micro-packed bed hydrogenation reactor to obtain a gas-liquid mixed fluid, enabling the gas-liquid mixed fluid to flow through a catalyst bed layer and react, and regulating and controlling the reaction temperature; and after the reaction is completed, collecting the effluent reaction liquid, and purifying to obtain the 4, 4-dichloro-2-amino-diphenyl ether. The catalyst is a supported metal catalyst, a carrier of the supported metal catalyst is aluminum oxide, activated carbon or silicon dioxide, and active metal and auxiliary metal are supported on the carrier of the supported metal catalyst. According to the preparation method, the solid catalyst is in full contact with the 4, 4-dichloro-2-nitro-diphenyl ether solution and the hydrogen, and compared with a conventional intermittent hydrogenation preparation mode, the reaction time is shortened, the product purity is high, the safety is high, and industrial large-scale production is facilitated.

Description

Technical Field

[0001] The invention belongs to the field of chemical synthesis, and specifically relates to a method for preparing 4,4-dichloro-2-amino-diphenyl ether by continuous hydrogenation. Background Art

[0002] 4,4-Dichloro-2-amino-diphenyl ether is an azo dye intermediate in the dye field and a key raw material for synthesizing a variety of azo dyes. Through diazotization, coupling and other reactions, azo dyes of different colors and properties can be prepared for dyeing textiles, leather, etc. In the pharmaceutical field, it can be used to synthesize some biologically active drug intermediates and provide important structural fragments for further synthesis of drug molecules. In the pesticide field, it can be used to synthesize some new insecticides and fungicides.

[0003] At present, the synthesis of 4,4-dichloro-2-amino-diphenyl ether at home and abroad mainly adopts hydrazine hydrate to reduce its nitro compound. The synthesis route is as follows:

[0004]

[0005] Patent CN107353185A uses hydrazine hydrate as a reducing agent, ferric chloride as a catalyst, and methanol as a solvent to synthesize 4,4-dichloro-2-amino-diphenyl ether with a yield greater than 98%. However, the hydrazine hydrate used in this method is flammable, explosive, and highly toxic, which brings great safety hazards to the industrial production of this step and is not suitable for industrial scale-up production. Summary of the invention

[0006] Purpose of the invention: The purpose of the present invention is to overcome the deficiencies of the above-mentioned prior art and to provide a method for preparing 4,4-dichloro-2-amino-diphenyl ether by continuous hydrogenation.

[0007] To achieve the above purpose, the technical solution provided by the present invention is as follows:

[0008] The present application provides a method for preparing 4,4-dichloro-2-amino-diphenyl ether by continuous hydrogenation, which comprises:

[0009] Dissolving 4,4-dichloro-2-nitro-diphenyl ether in a solvent to obtain a 4,4-dichloro-2-nitro-diphenyl ether solution;

[0010] The catalyst is loaded into a catalyst bed in a micro-packed bed hydrogenation reactor, the flow rates of 4,4-dichloro-2-nitro-diphenyl ether solution and hydrogen are adjusted, the gas-liquid mixer entering the inlet of the micro-packed bed hydrogenation reactor is mixed to obtain a gas-liquid mixed fluid, the gas-liquid mixed fluid is passed through the catalyst bed and reacted, and the reaction temperature is controlled by a reactor heat exchange chamber of the micro-packed bed hydrogenation reactor;

[0011] After the reaction is completed, the outflowing reaction liquid is collected and purified to obtain 4,4-dichloro-2-amino-diphenyl ether; the purification method is to concentrate the crude solution of 4,4-dichloro-2-amino-diphenyl ether, then salify it with acid, slurry it, and recrystallize it after alkaline release to obtain pure 4,4-dichloro-2-amino-diphenyl ether; the catalyst is a loaded metal catalyst, the carrier of the loaded metal catalyst is alumina, activated carbon or silicon dioxide, and the loaded metal catalyst is loaded with active metal and auxiliary metal on the carrier.

[0012] In some embodiments, the active metal is palladium, platinum or ruthenium, and the promoter metal is cobalt, iron or zinc.

[0013] In some embodiments, the loading amount of the active metal is 1 wt% to 10 wt%, preferably 1 wt% to 5 wt%, and the loading amount of the auxiliary metal is 0.1 wt% to 2 wt%.

[0014] In some embodiments, the preferred catalyst is 1 wt% loading of platinum, 2 wt% loading of iron, and the carrier is spherical silica.

[0015] In some embodiments, the solvent is methanol, ethanol, isopropanol, or ethyl acetate.

[0016] In some embodiments, the mass ratio of the solvent to 4,4-dichloro-2-nitro-diphenyl ether is 10-20:1.

[0017] In some embodiments, the flow rate of the 4,4-dichloro-2-amino-diphenyl ether solution is 0.01-0.5 mL / (min·mL catalyst bed), for example, the flow rate of the 4,4-dichloro-2-nitro-diphenyl ether solution corresponding to 1 L of catalyst bed is 10-500 mL / min. Preferably, the flow rate is 0.05-0.3 mL / (min·mL catalyst bed).

[0018] In some embodiments, the molar flow rate ratio of the 4,4-dichloro-2-nitro-diphenyl ether solution to hydrogen is 1:4-50, and preferably the molar flow rate ratio of the 4,4-dichloro-2-nitro-diphenyl ether solution to hydrogen is 1:6-15.

[0019] In some embodiments, the reaction temperature is 40-150°C, and the preferred reaction temperature is 50-100°C.

[0020] In some embodiments, the reaction pressure is 0.2-5 MPa, and the preferred reaction pressure is 0.5-3 MPa.

[0021] In some embodiments, the micro-packed bed hydrogenation reactor includes a gas-liquid mixer, a reactor heat exchange chamber, and a catalyst bed.

[0022] In some embodiments, standard conditions are standard conditions, ie, conditions at a temperature of 273.15 K (0° C.) and a pressure of 1 atm (101.325 kPa).

[0023] In some embodiments, the gas-liquid mixer of the present invention is a conventional gas-liquid mixer on the market, the purpose of which is to make the gas and liquid contact the catalyst bed uniformly to avoid wall flow. The catalyst after the reaction is dangerous, mainly because it undergoes oxidation reaction in contact with air, which releases a lot of heat or even burns. Therefore, the catalyst after the reaction is introduced into water under the protection of inert gas to avoid contact with air during the process.

[0024] Beneficial effects: The present invention discloses a method for preparing 4,4-dichloro-2-amino-diphenyl ether by continuous hydrogenation, comprising: dissolving 4,4-dichloro-2-nitro-diphenyl ether in a solvent to obtain a solution thereof; adjusting the flow rate of the 4,4-dichloro-2-nitro-diphenyl ether solution and hydrogen, mixing them in a gas-liquid mixer at the inlet of a micro-packed bed hydrogenation reactor to obtain a gas-liquid mixed fluid, flowing the mixed fluid through a catalyst bed and reacting, and regulating the reaction temperature; after the reaction is completed, collecting the outflowing reaction liquid, purifying it to obtain 4,4-dichloro-2-amino-diphenyl ether; the catalyst is a loaded metal catalyst, the carrier of the loaded metal catalyst is alumina, activated carbon or silicon dioxide, and the loaded metal catalyst is loaded with active metal and auxiliary metal on the carrier. The preparation method of the present invention allows the solid catalyst to fully contact with the 4,4-dichloro-2-nitro-diphenyl ether solution and hydrogen, and does not involve highly toxic compound hydrazine hydrate, which is safer and more environmentally friendly. The solid-supported hydrogenation catalyst is extremely low-risk during loading and unloading, has a lower operating frequency, a small reactor volume, less online material volume, and higher safety, which meets the national requirements for the safe transformation of high-risk processes in the fine chemical industry. Compared with the conventional intermittent hydrogenation preparation method, the reaction time is shortened, the conversion rate is as high as 100%, the dechlorination impurities are low, the product purity is as high as 99.3%, and the operation is highly safe, which is beneficial to industrial scale-up production. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 The present invention is a schematic diagram of the process of preparing crude 4,4-dichloro-2-amino-diphenyl ether in an embodiment of the present invention, wherein: 1: 4,4-dichloro-2-nitro-diphenyl ether solution, 2: hydrogen, 3: pump, 4: micro-packed bed hydrogenation reactor, 4-1: gas-liquid mixer, 4-2: reactor heat exchange chamber, 4-3: catalyst bed, 5: back pressure valve, 6: crude product. DETAILED DESCRIPTION

[0026] The present invention will be further explained below in conjunction with specific examples. This embodiment is implemented under the premise of the technical solution of the present invention. It should be understood that these embodiments are only used to illustrate the present invention and are not used to limit the scope of the present invention. In order to better illustrate the purpose, technical solution and advantages of the present invention, the present invention will be further described below in conjunction with specific examples. In the embodiment, the test method used is a conventional method unless otherwise specified, and the materials, reagents, etc. used, unless otherwise specified, can be obtained from commercial sources. Unless otherwise specified, the units used in the present invention are all international standard units, and the numerical values ​​and numerical ranges appearing in the present invention should be understood to include inevitable systematic errors in industrial production. In addition, in order to better illustrate the present invention, numerous specific details are given in the specific embodiments below. It should be understood by those skilled in the art that the present invention can also be implemented without certain specific details. In other examples, the methods, means, equipment and steps well known to those skilled in the art are not described in detail to highlight the main purpose of the present invention. The following example routes are as follows:

[0027]

[0028] The process for preparing crude 4,4-dichloro-2-amino-diphenyl ether is as follows: Figure 1 As shown, hydrogen and mixed liquid A first pass through 4-1: gas-liquid mixer, and then enter 4-3: catalyst bed for uniform contact to prevent wall flow. The temperature and pressure of 4: micro-packed bed hydrogenation reactor can be regulated. After the reaction is completed, 4,4-dichloro-2-amino-diphenyl ether crude product is obtained through 5: back pressure valve.

[0029] Example 1

[0030] 5 mL of spherical 1% platinum / 2% iron / silicon dioxide catalyst was loaded into a micro-packed bed hydrogenation reactor (5 mL), and the catalyst was gently tapped during the loading process to increase the density of the catalyst loading and prevent catalyst bridging. 5 g of 4,4-dichloro-2-nitro-diphenyl ether was dissolved in 10 times the mass of ethyl acetate (i.e., the mass ratio of ethyl acetate to 4,4-dichloro-2-nitro-diphenyl ether was 10:1), and the mixture was stirred and dissolved until clear to prepare an ethyl acetate solution of compound II. The reaction temperature was controlled to be 80° C., the reaction pressure was 2.0 MPa, the flow rate of the 4,4-dichloro-2-nitro-diphenyl ether solution was 0.4 mL / min (i.e., 0.08 mL / (min·mL catalyst bed)), and the flow rate of hydrogen was 30 mL / min (standard condition, 10 times the molar flow rate of 4,4-dichloro-2-nitro-diphenyl ether). Then, the 4,4-dichloro-2-nitro-diphenyl ether solution and hydrogen were first mixed together through the gas-liquid mixer at the inlet of the micro-packed bed hydrogenation reactor and then entered the catalyst bed in the hydrogenation reactor for hydrogenation reaction. After continuous operation for 1-2 h, the reaction was assumed to reach a steady state, 1 mL of the effluent (compound I crude product solution) was received, 0.1 mL of the reaction solution was taken, diluted to 1 mL with ethyl acetate, and then sent to gas chromatography for analysis. The reaction conversion rate was 100%, and the product purity was 99.3% (gas phase (GC) peak area ratio). A certain amount of crude hydrogenation liquid was taken, concentrated under reduced pressure at 45°C, salified with hydrochloric acid in isopropanol, and then slurried with methyl tert-butyl ether (MTBE), and finally alkali-ionized with sodium hydroxide aqueous solution and crystallized with n-heptane (H-heptane) to obtain pure compound 1 with a gas phase purity of >99.8%. The reaction separation yield was 97%.

[0031] Embodiment 2-7

[0032] The difference between Example 2-7 and Example 1 is that the catalyst used in the micro-packed bed hydrogenation reactor is the same, but the reaction temperature and pressure are different. The catalyst and condition parameters of the micro-packed bed hydrogenation reactor in Examples 1 and 2-7 are shown in Table 1.

[0033] Table 1 Condition parameters of micro-packed bed hydrogenation reactor in Examples 1, 2-7

[0034]

[0035] It can be seen from Table 1 that when a micro-packed bed hydrogenation reactor is used and 1% platinum / 2% iron / silicon dioxide is used as a catalyst, the most suitable temperature is 70-90°C, with 80°C being the best. If the temperature is too high, dechlorination impurities will be generated; if the pressure is too high, the selectivity of the reaction conversion rate will be slightly affected, and if the pressure is too low, the raw material conversion rate will decrease.

[0036] Embodiment 8-13

[0037] The difference between Examples 8-13 and Example 1 is that the reaction temperature and pressure are the same, but the catalysts used are different. The catalysts and condition parameters of the micro-packed bed hydrogenation reactor in Examples 1, 8-13 and Comparative Examples 1-3 are shown in Tables 2 and 3.

[0038] Table 2 Condition parameters of micro-packed bed hydrogenation reactor in Examples 1, 8-13

[0039]

[0040]

[0041] Table 3 Condition parameters of the micro-packed bed hydrogenation reactor in Comparative Example 1-2

[0042]

[0043] It can be seen from Table 2 Examples 1, 8-9 that compared with the silica carrier, the conversion rate of the carbon carrier and the alumina carrier is lower, and more raw materials remain; it can be seen from Table 3 Comparative Example 1 that when the active metal platinum loading is reduced to 0.1%, the raw material conversion rate drops significantly, and it can be seen from Table 2 Example 10 that when the platinum loading is increased to 5%, the result is not much different from Example 1. From the perspective of economy, a platinum loading of 1% is preferred; it can be seen from Table 2 Example 11 that when the amount of auxiliary metal iron is reduced to 0.1%, the reaction selectivity decreases and the dechlorination impurities increase, but it can be seen from Table 3 Comparative Example 2 that when the amount of auxiliary metal iron is increased to 5%, the reaction conversion rate decreases, so the preferred amount of iron is 2%; it can be seen from Table Examples 12-13 and Comparative Example 3 that when the auxiliary metal type is changed and cobalt and zinc are selected, the reaction selectivity decreases slightly, the dechlorination impurities increase, and the reaction conversion rate decreases significantly when manganese is selected, so the preferred auxiliary metal is iron.

[0044] Examples 14-15

[0045] The difference between Examples 14-15 and Example 1 is that the types of catalyst active metals used in the micro-packed bed hydrogenation reactor are different. The catalysts and condition parameters of the micro-packed bed hydrogenation reactor in Examples 1, 14-15 are shown in Table 4.

[0046] Table 4 Condition parameters of the micro-packed bed hydrogenation reactor in Examples 1, 14-15

[0047]

[0048] It can be seen from Table 4 that when 1% palladium / 2% iron / silicon dioxide and 1% ruthenium / 2% iron / silicon dioxide are used as catalysts, the reaction selectivity decreases, more dechlorination impurities are generated, and platinum is the preferred active metal.

[0049] Examples 16-19

[0050] The difference between Examples 16-19 and Example 1 is that the solvent or solvent multiple used in the micro-packed bed hydrogenation reactor is different. The mass multiple is the mass ratio of the solvent used to 4,4-dichloro-2-nitro-diphenyl ether. The catalyst and condition parameters of the micro-packed bed hydrogenation reactor in Examples 1, 16-19 and Comparative Examples 4-6 are shown in Tables 5 and 6.

[0051] Table 5 Condition parameters of micro-packed bed hydrogenation reactor in Examples 1, 16-19

[0052]

[0053]

[0054] Table 6 Condition parameters of the micro-packed bed hydrogenation reactor in Comparative Examples 4-6

[0055]

[0056] From Tables 5 and 6, it can be seen that the effect of using ethyl acetate solvent is better. Considering the energy consumption during desolventization, the preferred solvent addition amount is 10 times the mass. The reaction selectivity of alcohol solvent is reduced and the dechlorinated impurities are increased. In the comparative example, tetrahydrofuran and dioxane have poor hydrogen solubility, resulting in poor effect, low conversion rate and selectivity.

[0057] Examples 20-21

[0058] The difference between Examples 20-21 and Example 1 is that the liquid feed flow rate of the micro-packed bed continuous flow reaction is different. The catalyst and condition parameters of the micro-packed bed hydrogenation reactor in Examples 1, 20-21 are shown in Table 7 (the liquid flow rate in Table 7 is the flow rate through 5 mL of the catalyst bed).

[0059] Table 7 Condition parameters of micro-packed bed hydrogenation reactor in Examples 20-21

[0060]

[0061] From Table 7, it can be seen that when using a 5mL micro-packed bed reactor for hydrogenation, a liquid rate of 0.4mL / min is more appropriate. When the flow rate is reduced to 0.2mL / min, the production capacity will be too low, the reaction selectivity will decrease, and the dechlorination impurities will increase. When it is increased to 0.6mL / min, the raw material conversion is incomplete.

[0062] Embodiment 22

[0063] Refer to Example 1 to verify the enlarged production of 4,4-dichloro-2-amino-diphenyl ether:

[0064] 500 mL of spherical 1% platinum / 2% iron / silicon dioxide catalyst was loaded into a micro-packed bed hydrogenation reactor (500 mL), and the catalyst was gently tapped during the loading process to increase the density of the catalyst loading and prevent catalyst bridging. 4,4-dichloro-2-nitro-diphenyl ether (Compound II, 30.0 kg, 105.9 mol, 1.0 eq) was dissolved in ethyl acetate (300 kg), and stirred and dissolved until clear to prepare an ethyl acetate solution of Compound II. The reaction temperature was controlled to be 80°C, the reaction pressure was 2.0Mpa, the flow rate of the compound II solution was 40.0mL / min (i.e., 0.08mL / (min·mL catalyst bed)), and the hydrogen flow rate was 3.0L / min (standard condition, 10 times the molar flow rate of the compound II). Then, the compound II solution and hydrogen were mixed together through the gas-liquid mixer at the inlet of the micro-packed bed hydrogenation reactor and then entered the catalyst bed in the hydrogenation reactor for hydrogenation reaction. After continuous operation for 1-2h, the reaction reached a steady state by default, 1mL of the effluent (compound I crude solution) was received, 0.1mL of the reaction solution was diluted to 1mL with ethyl acetate and sent to gas chromatography for analysis, the reaction conversion rate was 100%, and the product purity was 99.1% (gas phase (GC) peak area ratio). The reactor was operated continuously for 5 days, and the catalyst activity was stable.

[0065] Comparative Example 7

[0066] Conventional intermittent hydrogenation production method for preparing compound I:

[0067] Under nitrogen protection, ethyl acetate (45.0kg, 19w / w), 4,4-dichloro-2-nitro-diphenyl ether (Compound II, 5.0kg, 17.7mol) and 10% palladium carbon catalyst (1.0kg, 0.2w / w) were added to a 100L high-pressure hydrogenation reactor. Nitrogen / vacuum replacement 3 times, hydrogen / vacuum replacement 1 time, hydrogen was introduced, and the pressure rose to 2.5MPa. The temperature was controlled at 40-50°C, the pressure was controlled at 2.5Mpa, the reaction was carried out for 24h, and the sampling was controlled to determine that Compound II disappeared completely and the reaction was stopped. The temperature was lowered to 20-25°C, nitrogen / vacuum replacement was carried out 3 times, the reaction liquid was filtered, and the filtrate was transferred to a 100L reactor. The crude reaction liquid filtered out entered the subsequent separation and purification system. The crude reaction liquid had a conversion rate of 98.7% and a purity of 83.6%.

[0068] In summary, the process description of Example 22 and Comparative Example 7, in a micro-packed bed continuous hydrogenation reactor, after preparing the ethyl acetate solution of compound II, 1% platinum / 2% iron / silicon dioxide catalyst is used, the raw material liquid is mixed with hydrogen at a gas-liquid mixer through a feed pump at a specific temperature and pressure and then enters the reaction bed to react, 4,4-dichloro-2-amino-diphenyl ether can be easily and stably obtained, and the continuous process is easy to amplify, and the consumption of 6.0kg compound II can be achieved every day using a 500mL reactor, and the reaction conversion rate is 100%, and the product purity is 99.1% (gas phase (GC) peak area accounts for), and the palladium carbon catalyst metal loading used in the intermittent process is high, and the catalyst dosage is large, and the catalyst cost is relatively high. And the reaction rate is relatively low, and the reaction time needs 24h, and the production efficiency is relatively low. Reaction selectivity is relatively poor, and dechlorination impurities are relatively high, and product purity is only 83.6%.

[0069] The above specific implementation methods further illustrate the purpose, technical solutions and beneficial effects of the present application in detail. It should be understood that the above are only specific implementation methods of the present application and are not used to limit the protection scope of the present application. Any modifications, equivalent substitutions, improvements, etc. made on the basis of the technical solutions of the present application should be included in the protection scope of the present application.

Claims

1. A method for preparing 4,4-dichloro-2-amino-diphenyl ether by continuous hydrogenation, characterized in that: include: Dissolving 4,4-dichloro-2-nitro-diphenyl ether in a solvent to obtain a 4,4-dichloro-2-nitro-diphenyl ether solution; The catalyst is loaded into a catalyst bed in a micro-packed bed hydrogenation reactor, the flow rates of 4,4-dichloro-2-nitro-diphenyl ether solution and hydrogen are adjusted, the gas-liquid mixer entering the inlet of the micro-packed bed hydrogenation reactor is mixed to obtain a gas-liquid mixed fluid, the gas-liquid mixed fluid is passed through the catalyst bed and reacted, and the reaction temperature is controlled by a reactor heat exchange chamber of the micro-packed bed hydrogenation reactor; After the reaction is completed, the outflowing reaction liquid is collected and purified to obtain 4,4-dichloro-2-amino-diphenyl ether; the catalyst is a loaded metal catalyst, the carrier of the loaded metal catalyst is alumina, activated carbon or silicon dioxide, and the loaded metal catalyst has active metal and auxiliary metal loaded on the carrier.

2. The method according to claim 1, characterized in that The active metal is palladium, platinum or ruthenium, and the auxiliary metal is cobalt, iron or zinc.

3. The method according to claim 1 or 2, characterized in that: The loading amount of the active metal is 1 wt% to 10 wt%, and the loading amount of the auxiliary metal is 0.1 wt% to 2 wt%.

4. The method according to claim 1, characterized in that The solvent is methanol, ethanol, isopropanol or ethyl acetate.

5. The method according to claim 1 or 4, characterized in that: The mass ratio of the solvent to 4,4-dichloro-2-nitro-diphenyl ether is 10-20:

1.

6. The method according to claim 1, characterized in that The flow rate of the 4,4-dichloro-2-amino-diphenyl ether solution is 0.01-0.5 mL / (min·mL catalyst bed).

7. The method according to claim 1 or 6, characterized in that: The molar flow rate ratio of the 4,4-dichloro-2-nitro-diphenyl ether solution to the hydrogen is 1:4-50.

8. The method according to claim 1, characterized in that: The reaction temperature is 40-150°C.

9. The method according to claim 1 or 8, characterized in that: The reaction pressure is 0.2-5 MPa.

10. The method according to claim 1, characterized in that The micro-packed bed hydrogenation reactor comprises a gas-liquid mixer, a reactor heat exchange chamber, and a catalyst bed.

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