Continuous preparation method of N-isopropyl p-fluoroaniline

Abstract

The invention relates to the field of organic synthesis, and discloses a continuous preparation method of N-isopropyl p-fluoroaniline, a fixed bed reactor is adopted, a biological carbon loaded palladium catalyst prepared by using saccharomycetes as a pyrolysis precursor is relatively excellent in stability, and the catalytic activity is not reduced after continuous operation for 3000 hours. The reaction raw materials are p-fluoronitrobenzene and acetone, the yield of the N-isopropyl p-fluoroaniline is as high as 93%, the reaction conditions are mild, and the method is easy for industrial application.

Description

Technical Field

[0001] The invention relates to the field of organic synthesis, and in particular to a continuous preparation method of a chemical intermediate N-isopropyl-p-fluoroaniline. Background Art

[0002] N-isopropyl-p-fluoroaniline is an important chemical intermediate, used as a key intermediate of the important herbicide flufenacet, and determines the quality of flufenacet products. There are many synthetic routes for N-isopropyl-p-fluoroaniline, which are divided according to the raw materials, including the p-fluoroaniline method and the p-fluoronitrobenzene method: (1) Nucleophilic substitution reaction of 4-fluoroaniline and 2-halopropane. This route is mature, but it requires the addition of an acid-binding agent, produces a large amount of wastewater, and the price of 4-fluoroaniline is relatively high. (2) Reductive amination of p-fluoroaniline with acetone. This route has high atom economy and the only byproduct is water. However, p-fluoroaniline is expensive and has poor economic efficiency. In 2010, scholars reported that IrBr3 catalyzed the reductive amination of p-fluoroaniline with acetone to prepare N-isopropyl p-fluoroaniline, with formic acid as the reducing agent (Tetrahedron Letters, 2010, 51, 689-691). In 2015, scholars reported that SiO2@Fe3O4 catalyzed the reductive amination of p-fluoroaniline with acetone to prepare N-isopropyl p-fluoroaniline, with sodium borohydride as the reducing agent (New J. Chem., 2016, 40, 2089-2101). (3) Reductive amination of p-fluoronitrobenzene with acetone. This route has high atom economy, with only water as a byproduct. The price of p-fluoronitrobenzene is low, and the economic efficiency is good. Patents report the preparation of N-isopropyl p-fluoroaniline by reductive amination of p-fluoronitrobenzene with acetone catalyzed by nickel-based catalysts and platinum-carbon (CN107721948A, CN111072498A, CN113461558A).

[0003] The existing technology has the following shortcomings: the existing N-isopropyl-p-fluoroaniline synthesis technology is an intermittent stirred tank process, which has low production efficiency, long auxiliary time, difficulty in automatic control, and difficulty in maintaining the stability of each batch of quality. The catalyst used in the existing synthesis process has problems such as poor selectivity and easy deactivation. Summary of the invention

[0004] In view of the deficiencies in the prior art, the present invention provides a continuous preparation method of N-isopropyl-p-fluoroaniline to achieve the following invention objectives: (1) Realize the continuous preparation of N-isopropyl-p-fluoroaniline; (2) The catalyst has good selectivity and is not easily deactivated. After 3000 hours of continuous use, the activity of the catalyst has not decreased.

[0005] The present invention adopts the following technical solutions: The invention discloses a continuous preparation method of N-isopropyl p-fluoroaniline. A fixed bed reactor is used to carry out a reduction amination reaction of p-fluoronitrobenzene and acetone in a hydrogen atmosphere under the action of a palladium catalyst supported by biocarbon to obtain N-isopropyl p-fluoroaniline.

[0006] The reaction chemical formula of the present invention is:

[0007] In the above technical scheme, in a fixed bed reactor, under the action of a palladium catalyst supported on biochar, p-fluoronitrobenzene and acetone undergo a reductive amination reaction in a hydrogen atmosphere to obtain N-isopropyl p-fluoroaniline; In the above technical solution, a fixed bed reactor is used, and the mass ratio of p-fluoronitrobenzene to acetone is 0.1-1.5, preferably 0.1-0.6; In the above technical scheme, the carrier is biochar prepared by using yeast as a pyrolysis precursor, and palladium is loaded by impregnation to prepare a biochar-loaded palladium catalyst, wherein the palladium is one of palladium nitrate and palladium chloride; the loading amount of palladium is 1-10%, preferably 1-5%; the catalyst is operated continuously for 3000 hours, and the catalytic activity of the catalyst is not lost; In the above technical solution, the volume space velocity of the fluoronitrophenylacetone solution is 0.1-50 h -1 , preferably 0.1-20 h -1 .

[0008] In the above technical solution, the pressure of hydrogen is 0.1-10 MPa, preferably 0.1-5 MPa, and the flow rate of hydrogen is 1-100 mL / min, preferably 5-80 mL / min.

[0009] In the above technical solution, the reaction temperature is 90-220°C, preferably 100-200°C.

[0010] Preparation process of yeast pyrolysis carbon: In an inert atmosphere, the yeast dry powder is pyrolyzed at 600-1000°C for 1-4h, preferably 700-800°C, preferably 1-2h; ground into powder to obtain yeast biochar. The inert atmosphere is one or more of nitrogen or argon; The yeast biochar prepared as above is used as a carrier, active metals are loaded by an impregnation method, and sodium borohydride is used for reduction to obtain a biochar-loaded palladium catalyst.

[0011] Compared with the prior art, the present invention has the following beneficial effects: The present invention uses a fixed bed reactor for the first time, and p-fluoronitrobenzene and acetone undergo a reductive amination reaction to implement a continuous production process of N-isopropyl p-fluoroaniline; after continuous operation for 3000 hours, the catalytic activity of the catalyst is not lost (or decreased). The catalyst has excellent stability. The reaction raw materials are p-fluoronitrobenzene and acetone, the yield of N-isopropyl p-fluoroaniline is as high as 93%, the reaction conditions are mild, and it is easy to apply industrially. DETAILED DESCRIPTION

[0012] The technical scheme of the present invention is described in detail below in conjunction with the embodiments, but the scope of the present invention is not limited to the following embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0013] Example 1

[0014] Take 10g of yeast powder in a quartz boat, place the quartz boat in a tube furnace, and pass nitrogen for 30min at room temperature (gas flow rate of 10mL / min). Then keep the nitrogen gas flow rate unchanged and raise the temperature to 800℃ (heating rate of 5℃ / min). Still keep the nitrogen gas flow rate unchanged, keep pyrolysis at 800℃ for 1h, and then slowly cool down to 30℃ (cooling rate of 5℃ / min). Grind the black solid in the quartz boat into powder in an agate mortar to obtain a biochar carrier with a mass of 3.6g.

[0015] Preparation of catalyst: 2 g of the above biochar carrier was added to 200 mL of water. After 5 minutes of ultrasonication, 33 mL of PdCl2 stock solution (1000 mg / L) was added dropwise to the dispersion under stirring. After 1 hour of ultrasonication, 20 mL of sodium borohydride (2 g / L) was added dropwise to the dispersion while stirring, and further stirred for 1 hour. The obtained mixed solution was filtered and washed with deionized water several times. The obtained solid was vacuum dried at 60 ° C for 4 hours to obtain a biochar-supported palladium catalyst with a palladium content of 1 wt%.

[0016] 2g of the above biochar carrier was added to 200mL of water. After 5 minutes of ultrasonication, 165mL of PdCl2 stock solution (1000mg / L) was added dropwise to the dispersion under stirring. After 1 hour of ultrasonication, 100mL of sodium borohydride (2g / L) was added dropwise to the dispersion while stirring, and further stirred for 1h. The obtained mixed solution was filtered and washed with deionized water several times. The obtained solid was vacuum dried at 60°C for 4h to obtain a palladium catalyst supported by biochar with a palladium content of 5wt%.

[0017] 2g of the above biochar carrier was added to 200mL of water. After 5 minutes of ultrasonication, 330mL of PdCl2 stock solution (1000mg / L) was added dropwise to the dispersion under stirring. After 1 hour of ultrasonication, 200mL of sodium borohydride (2g / L) was added dropwise to the dispersion while stirring, and further stirred for 1h. The obtained mixed solution was filtered and washed with deionized water several times. The obtained solid was vacuum dried at 60℃ for 4h to obtain a biochar-supported palladium catalyst with a palladium content of 10wt%.

[0018] Example 2

[0019] Fill the fixed bed reactor with 20 mL of the biochar-loaded palladium catalyst with a palladium mass content of 1% prepared in Example 1, pass nitrogen for 30 minutes to exhaust the air in the reaction system (in the fixed bed reactor), then deliver ethanol to the reaction system through a metering pump for 30 minutes to keep the reactor full, and heat it to 100°C at the same time. After the reactor temperature stabilizes, pass nitrogen to exhaust all ethanol. Set the hydrogen to 5 mL / min, and adjust the system pressure to 0.1 MPa through the back pressure valve at the tail gas end of the fixed bed reactor. Pass a solution of p-fluoronitrobenzene in acetone through a metering pump, the mass ratio of p-fluoronitrobenzene to acetone is 0.1, and the volumetric space velocity is 0.1 h -1 After 30 minutes of reaction, samples were taken every 1 hour and analyzed by liquid phase analysis. The average yield of N-isopropyl-p-fluoroaniline (12 hours) was 93%.

[0020] Example 3

[0021] Fill the fixed bed reactor with 20 mL of the biochar-loaded palladium catalyst with a palladium mass content of 10% prepared in Example 1, pass nitrogen for 30 minutes to exhaust the air in the reaction system (in the fixed bed reactor), then deliver ethanol to the reaction system through a metering pump for 30 minutes to keep the reactor full, and heat it to 200°C at the same time. After the reactor temperature stabilizes, pass nitrogen to exhaust all ethanol. Set the hydrogen to 80 mL / min, and adjust the system pressure to 5 MPa through the back pressure valve at the tail gas end of the fixed bed reactor. Pass a solution of p-fluoronitrobenzene in acetone through a metering pump, the mass ratio of p-fluoronitrobenzene to acetone is 0.6, and the volumetric space velocity is 20 h -1 After 30 minutes of reaction, samples were taken every 1 hour and analyzed by liquid phase analysis. The average yield of N-isopropyl-p-fluoroaniline (12 hours) was 97%.

[0022] Example 4

[0023] Fill the fixed bed reactor with 20 mL of the palladium catalyst with a palladium mass content of 5% biochar-loaded prepared in Example 1, pass nitrogen for 30 minutes to exhaust the air in the reaction system (inside the fixed bed reactor), then deliver ethanol to the reaction system through a metering pump for 30 minutes to keep the reactor full, and heat it to 150°C at the same time. After the reactor temperature stabilizes, pass nitrogen to exhaust all ethanol. Set the hydrogen to 60 mL / min, and adjust the system pressure to 2 MPa through the back pressure valve at the tail gas end of the fixed bed reactor. Pass a solution of p-fluoronitrobenzene in acetone through a metering pump, the mass ratio of p-fluoronitrobenzene to acetone is 0.4, and the volumetric space velocity is 10 h -1 After 30 minutes of reaction, samples were taken every 1 hour and analyzed by liquid phase analysis. The average yield of N-isopropyl-p-fluoroaniline (12 hours) was 95%.

[0024] Example 5

[0025] Fill the fixed bed reactor with 20 mL of the palladium catalyst with a biochar load of 5% palladium mass content prepared in Example 1, pass nitrogen for 30 minutes to exhaust the air in the reaction system, and then use a metering pump to deliver ethanol to the reaction system (inside the fixed bed reactor) for 30 minutes to keep the reactor full, and at the same time raise the temperature to 180°C. After the reactor temperature stabilizes, pass nitrogen to exhaust all ethanol. Set the hydrogen to 40 mL / min, and adjust the system pressure to 1 MPa through the back pressure valve at the tail gas end of the fixed bed reactor. Pass a solution of p-fluoronitrobenzene in acetone through a metering pump, the mass ratio of p-fluoronitrobenzene to acetone is 0.5, and the volumetric space velocity is 5 h -1 After 30 minutes of reaction, samples were taken every 1 hour and analyzed by liquid phase analysis. The average yield of N-isopropyl-p-fluoroaniline (12 hours) was 96%.

[0026] Example 6

[0027] Fill the fixed bed reactor with 20 mL of the palladium catalyst with a biochar load of 1% palladium mass content prepared in Example 1, pass nitrogen for 30 minutes to exhaust the air in the reaction system, and then deliver ethanol to the reaction system (inside the fixed bed reactor) through a metering pump for 30 minutes to keep the reactor full, and at the same time heat it to 120°C. After the reactor temperature stabilizes, pass nitrogen to exhaust all ethanol. Set the hydrogen to 5 mL / min, and adjust the system pressure to 4 MPa through the back pressure valve at the tail gas end of the fixed bed reactor. Pass a solution of p-fluoronitrobenzene in acetone through a metering pump, the mass ratio of p-fluoronitrobenzene to acetone is 0.2, and the volumetric space velocity is 0.5 h -1 After 30 minutes of reaction, samples were taken every 1 hour and analyzed by liquid phase analysis. The average yield of N-isopropyl-p-fluoroaniline (12 hours) was 98%.

[0028] Example 7

[0029] Fill the fixed bed reactor with 20 mL of the palladium catalyst with a biochar load of 5% palladium mass content prepared in Example 1, pass nitrogen for 30 minutes to exhaust the air in the reaction system (inside the fixed bed reactor), then deliver ethanol to the reaction system through a metering pump for 30 minutes to keep the reactor full, and heat it to 160°C at the same time. After the reactor temperature stabilizes, pass nitrogen to exhaust all ethanol. Set the hydrogen to 8 mL / min, and adjust the system pressure to 3 MPa through the back pressure valve at the tail gas end of the fixed bed reactor. Pass a solution of p-fluoronitrobenzene in acetone through a metering pump, the mass ratio of p-fluoronitrobenzene to acetone is 0.3, and the volumetric space velocity is 1.2 h -1 After 30 minutes of reaction, samples were taken every 1 hour and analyzed by liquid phase analysis. The average yield of N-isopropyl-p-fluoroaniline (12 hours) was 97%.

[0030] Example 8

[0031] Fill the fixed bed reactor with 20 mL of the palladium catalyst with a biochar load of 5% palladium mass content prepared in Example 1, pass nitrogen for 30 minutes to exhaust the air in the reaction system (inside the fixed bed reactor), then deliver ethanol to the reaction system through a metering pump for 30 minutes to keep the reactor full, and heat it to 160°C at the same time. After the reactor temperature stabilizes, pass nitrogen to exhaust all ethanol. Set the hydrogen to 8 mL / min, and adjust the system pressure to 3 MPa through the back pressure valve at the tail gas end of the fixed bed reactor. Pass a solution of p-fluoronitrobenzene in acetone through a metering pump, the mass ratio of p-fluoronitrobenzene to acetone is 0.3, and the volumetric space velocity is 1.2 h -1 After 30 minutes of reaction, samples were taken every 2 hours for liquid phase analysis; after 100 hours of continuous operation, samples were taken every 12 hours for liquid phase analysis. The average yield of N-isopropyl-p-fluoroaniline (3000 hours) was 94%.

[0032] Comparative Example

[0033] Compared with the reaction results without using a catalyst, the biochar-supported palladium catalyst used in the present invention has obvious advantages, and the specific data are shown in Table 1 (except that the biochar-supported palladium catalyst is not added, the other processes and conditions are the same as Example 2).

[0034] Compared with catalysts prepared using other carriers or other active metals, the catalyst of the present invention has obvious advantages. The catalyst preparation scheme (process and conditions) is the same as the preparation method of the catalyst in Example 1 of the present invention, except that the type and content of the carrier or active metal used are different. The catalytic reaction process and conditions are the same as Example 2, except that a different catalyst is used.

[0035] Table 1 shows the separation yield of N-isopropyl-p-fluoroaniline under different catalysts

Claims

1. A continuous preparation method of N-isopropyl-p-fluoroaniline, Features: In a fixed bed reactor, p-fluoronitrobenzene and acetone undergo a reductive amination reaction in a hydrogen atmosphere over a biochar-supported palladium catalyst to obtain N-isopropyl p-fluoroaniline. A fixed bed reactor is used, the mass ratio of p-fluoronitrobenzene to acetone is 0.1-1.5; the reaction temperature is 90-220°C; the hydrogen pressure is 0.1-10 MPa; The carrier is biochar prepared by using yeast as a pyrolysis precursor, and palladium is loaded on the biochar through an impregnation method to prepare a biochar-loaded palladium catalyst; the mass loading amount of palladium in the catalyst is 1-10%; Specific preparation process of the catalyst: 1) In an inert atmosphere, the yeast dry powder is pyrolyzed at 600-1000°C for 1-4 hours; ground into powder to obtain yeast biochar; 2) Active metals are loaded on the carrier by an impregnation method, and then reduced by sodium borohydride to obtain a biocarbon-loaded palladium catalyst.

2. The continuous preparation method of N-isopropyl-p-fluoroaniline according to claim 1, Features: A fixed bed reactor is used, and the mass ratio of p-fluoronitrobenzene to acetone is 0.1-0.

6.

3. The continuous preparation method of N-isopropyl-p-fluoroaniline according to claim 1, Features: The mass loading of palladium in the catalyst is 1-5%; The specific preparation process of the catalyst is as follows: in an inert atmosphere, the yeast dry powder is pyrolyzed at 700-800°C for 1-2 hours; ground into powder to obtain yeast biochar; The inert atmosphere is one or more of nitrogen and argon.

4. The continuous preparation method of N-isopropyl-p-fluoroaniline according to claim 1, It is characterized in that The volume space velocity of the mixed solution of p-fluoronitrobenzene and acetone is 0.1-50 h -1 .

5. The continuous preparation method of N-isopropyl-p-fluoroaniline according to claim 1, Features: The pressure of hydrogen is 0.1-5MPa; when the catalyst is 20 mL, the flow rate of hydrogen is 1-100mL / min.

6. The continuous preparation method of N-isopropyl-p-fluoroaniline according to claim 5, Features: The pressure of hydrogen is 0.2-8MPa; when the catalyst is 20 mL, the hydrogen flow rate is 20-80 mL / min.

7. The continuous preparation method of N-isopropyl-p-fluoroaniline according to any one of claims 1 to 6, Features: The reaction temperature is 100-200°C.

8. The continuous preparation method of N-isopropyl-p-fluoroaniline according to claim 1, Features: Step 2) in the specific preparation process of the catalyst is to disperse 2 g of biochar carrier and the required 500-1500 mg / L palladium source solution into 100-300 mL of water, add 15-40 mL of 1-5 g / L sodium borohydride while stirring, and stir the reaction for 0.1-6 hours; the palladium source is one or both of palladium nitrate and palladium chloride.

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