Method for synthesizing p-nitro trifluoromethoxybenzene through microchannel

Abstract

The invention discloses a method for synthesizing p-nitro trifluoromethoxybenzene through a microchannel, and belongs to the field of fine chemical engineering. The method comprises the following steps: heating by adopting a micro-channel reactor, and carrying out continuous flow nitration reaction on trifluoromethoxybenzene and ferric nitrate in the micro-channel reactor to synthesize p-nitro trifluoromethoxybenzene. The method has the advantages of rapid reaction, mild conditions, simple operation, few by-products and easy purification. The process provided by the invention also greatly improves the safety of the reaction process, so that the reaction is safer and more environment-friendly.

Description

Technical Field

[0001] The present invention relates to a method for reacting p-nitro(trifluoromethoxy)benzene in a microchannel reactor, specifically a continuous flow nitration reaction of trifluoromethoxybenzene and iron nitrate in a microchannel reactor, belonging to the field of organic synthesis. Background Art

[0002] P-nitro(trifluoromethoxy)benzene is an important pesticide intermediate and plays an important role in insecticides and herbicides.

[0003] Currently, there are various synthesis methods for p-nitro(trifluoromethoxy)benzene. The domestic disclosed production processes are as follows:

[0004] 1. [Organic Letters, 2020] discloses that 4-(trifluoromethoxy)phenylboronic acid reacts with N-nitrosuccinimide under the photocatalysis of blue LED irradiation in the presence of metal Ru to replace the boronic acid with a nitro group; the raw materials of this route are expensive, which is not conducive to market competition.

[0005]

[0006] 2. WO2016 / 125185, 2016, A2 discloses that phenetole is added to 4-chlorobenzotrifluoride in a chlorine environment, and trichloroanisole is generated through ultraviolet spectrum monitoring, then it is replaced with hydrofluoric acid to generate trifluoromethoxybenzene, and then nitrated with concentrated sulfuric acid + concentrated nitric acid to generate p-nitro(trifluoromethoxy)benzene.

[0007]

[0008] This route is prone to polluting the environment, has a low yield, and is prone to generating impurities such as o-nitro(trifluoromethoxy)benzene.

[0009] 3. [Tetrahedron Letters, 2014, vol. 55, #10, p. 1726 - 1728] discloses that p-tolyltrifluoroborate, bismuth nitrate and anhydrous toluene are added in an argon environment and heated at 120 °C for a reaction to obtain the product. The raw materials of this route are expensive and do not have a market advantage.

[0010]

[0011] In summary, it is crucial to develop a method with a short reaction route, high yield, simple operation and relatively mild conditions for the synthesis of p-nitro(trifluoromethoxy)benzene. The present invention provides a continuous flow chemical reaction route using a microchannel reactor, which has high efficiency, flexibility and safety. Summary of the Invention

[0012] In view of the above deficiencies of the prior art, the present invention provides a more economical and environmentally friendly preparation process mainly aiming at the objectively existing problems in the reaction of the above-mentioned p-nitrotrifluoromethoxybenzene. We utilized the characteristics of the microchannel reactor, such as "continuous", "system closed", "small instantaneous reaction material quantity", and "high degree of automatic control of reaction conditions can be precisely controlled", to carry out the reaction of p-nitrotrifluoromethoxybenzene, and achieved excellent results; the process of the present invention reduces the usage of raw materials and catalysts, reduces the generation of side reactions, and the entire reaction is carried out in a closed system, avoiding contact with toxic and harmful substances, being green and environmentally friendly.

[0013] The present invention discloses a method for synthesizing p-nitrotrifluoromethoxybenzene using a microchannel reactor, that is, heating with a microchannel reactor and continuously flowing nitrating trifluoromethoxybenzene and iron nitrate in the microchannel reactor to synthesize p-nitrotrifluoromethoxybenzene.

[0014] Further, in the above technical solution, the flow chart ( Figure 1 ) and the reaction equation are as follows:

[0015]

[0016] Further, in the above technical solution, it includes the following steps:

[0017] 1) Connect the continuous flow microchannel reactor system;

[0018] 2) Back-pressure the microchannel reactor with a back-pressure valve to reach the pressure inside the microchannel reactor system;

[0019] 3) Heat the micromixer and the preheating device delay pipeline to the reaction temperature by a constant temperature bath;

[0020] 4) System balance and calibration;

[0021] 5) Feed the organic solvent solutions of trifluoromethoxybenzene and iron nitrate through a feed pump, mix them in the micromixer, and complete the reaction at a certain temperature and for a certain time through the preheating device;

[0022] 6) The reacted material enters the receiving tank for storage at room temperature and awaits post-treatment;

[0023] 7) Stop the pump and clean the system.

[0024] 8) Heat up the reacted liquid, complex it with triphenylborane and o-nitrotrifluoromethoxybenzene, and obtain p-nitrotrifluoromethoxybenzene by distillation.

[0025] Further, in the above technical solution, the flow rate in the reaction is selected from 40 mL / min, 24 mL / min, 12 mL / min, and 6 mL / min.

[0026] Further, in the above technical solution, the molar ratio of trifluoromethoxybenzene to iron nitrate in the reaction is 1.0:1.0 - 1.1.

[0027] Further, in the above technical solution, the reaction temperature is 50 - 60 °C.

[0028] Further, in the above technical solution, the solvent in the reaction is selected from hexafluoroisopropanol and recycled hexafluoroisopropanol.

[0029] Further, in the above technical solution, the ortho-isomer generated in the reaction undergoes complexation by adding triphenylborane, thereby separating and purifying the product and the isomer.

[0030] Advantages of the invention:

[0031] 1) Achieve instantaneously uniform mixing in the reaction; shorten the reaction time (from 120 min in the conventional reaction to 10 min); reduce the three wastes in the traditional route.

[0032] 2) Improve the conversion rate of raw materials, reduce the by-product, i.e., o-nitrotrifluoromethoxybenzene, to 5 - 6% (using the material ratio in Example 1, batch reaction in a kettle, reacting at 40 - 45 °C for 2 hours, the ratio of para / ortho products is 3.2 / 1), increase the yield by more than 12%, and the purification is simpler. Description of the drawings

[0033] Figure 1 It is a reaction flow chart for synthesizing p-nitrotrifluoromethoxybenzene in a microchannel reactor. Detailed implementation manners

[0034] The present invention will be further described below through specific examples. These examples should be understood as only for illustrating the present invention and not for limiting the protection scope of the present invention. After reading the content recorded in the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent changes and modifications also fall within the scope defined by the claims of the present invention.

[0035] Example 1

[0036] For p-nitrotrifluoromethoxybenzene: 16.2 g (0.1 mol) of trifluoromethoxybenzene, 1.1 g of tris(pentafluorophenyl)borane, and 44.4 g (0.11 mol) of iron nitrate nonahydrate are used as raw materials, and 81 mL (5V) of hexafluoroisopropanol is used as the solvent.

[0037]

[0038] 1) Connect the microreactor system;

[0039] 2) The micro-mixer and the preheating device are respectively heated to 55 - 60 °C and 50 - 55 °C by a thermostatic bath, and the system is balanced and calibrated;

[0040] 3) Store the trifluoromethoxybenzene in the storage tank V-1 and enter the first reaction module through the pump P-1 at a volume flow rate of 1.3 mL / min;

[0041] 4) Store the hexafluoroisopropanol solution of iron nitrate and tris(pentafluorophenyl)borane in the storage tank V-2 and enter the second reaction module through the pump P-2 at a volume flow rate of 10.7 mL / min;

[0042] 5) The materials in reaction module 1 and reaction module 2 are mixed in the micro-mixer in the third reaction module through the pump P-3 at a volume flow rate of 40 mL / min, and react in the fourth reaction module at 80 - 85 °C. After passing through the delay pipeline of the tubular reactor, the reaction is completed in 3 minutes;

[0043] 6) The reacted materials enter the receiving tank V-3. It can be known from HPLC detection that p-nitrotrifluoromethoxybenzene accounts for 81.3% and o-nitrotrifluoromethoxybenzene accounts for 9.4%.

[0044] 7) Stop the pump and clean the system.

[0045] Example 2

[0046] For p-nitrotrifluoromethoxybenzene: 16.2 g (0.1 mol) of trifluoromethoxybenzene, 1.1 g of tris(pentafluorophenyl)borane, and 44.4 (0.11 mol) of iron nitrate nonahydrate are used as raw materials, and 81 mL (5V) of hexafluoroisopropanol is used as the solvent.

[0047]

[0048] 1) Connect the micro-reactor system;

[0049] 2) The micro-mixer and the preheating device are respectively heated to 55 - 60 °C and 50 - 55 °C by a thermostatic bath, and the system is balanced and calibrated;

[0050] 3) Store the trifluoromethoxybenzene in the storage tank V-1 and enter the first reaction module through the pump P-1 at a volume flow rate of 1.3 mL / min;

[0051] 4) Store the hexafluoroisopropanol solution of iron nitrate and tris(pentafluorophenyl)borane in the storage tank V-2 and enter the second reaction module through the pump P-2 at a volume flow rate of 10.7 mL / min;

[0052] 5) The materials in reaction module 1 and reaction module 2 are fed into the micromixer in the third reaction module by pump P-3 at a volume flow rate of 24 mL / min to mix the materials, and react in the fourth reaction module at 55 - 60 °C. After passing through the delay pipeline of the tubular reactor, the reaction is completed in 5 minutes.

[0053] 6) The reacted materials enter the receiving tank V-3. It can be known from HPLC detection that: p-nitrotrifluoromethoxybenzene accounts for 89.2%, and o-nitrotrifluoromethoxybenzene accounts for 6.8%.

[0054] 7) Stop the pump and clean the system.

[0055] Example 3

[0056] For p-nitrotrifluoromethoxybenzene: 16.2 g (0.1 mol) of trifluoromethoxybenzene, 1.1 g of tris(pentafluorophenyl)borane, and 44.4 g (0.11 mol) of ferric nitrate nonahydrate are used as raw materials, and 81 mL (5V) of hexafluoroisopropanol is used as the solvent.

[0057]

[0058] 1) Connect the microreactor system.

[0059] 2) Use a thermostatic bath to cool the micromixer and the preheating device to 55 - 60 °C and 50 - 55 °C respectively, and balance and calibrate the system.

[0060] 3) Store trifluoromethoxybenzene in storage tank V-1 and feed it into the first reaction module by pump P-1 at a volume flow rate of 1.3 mL / min.

[0061] 4) Store the hexafluoroisopropanol solution of ferric nitrate and tris(pentafluorophenyl)borane in storage tank V-2 and feed it into the second reaction module by pump P-2 at a volume flow rate of 10.7 mL / min.

[0062] 5) The materials in reaction module 1 and reaction module 2 are fed into the micromixer in the third reaction module by pump P-3 at a volume flow rate of 12 mL / min to mix the materials, and react in the fourth reaction module at 55 - 60 °C. After passing through the delay pipeline of the tubular reactor, the reaction is completed in 10 minutes.

[0063] 6) The reacted materials enter the receiving tank V-3. It can be known from HPLC detection that: p-nitrotrifluoromethoxybenzene accounts for 95.3%, and o-nitrotrifluoromethoxybenzene accounts for 3.8%.

[0064] 7) Stop the pump and clean the system.

[0065] Example 4

[0066] p-Nitrotrifluoromethoxybenzene: Using 16.2 g (0.1 mol) of trifluoromethoxybenzene, 1.1 g of tris(pentafluorophenyl)borane, and 44.4 g (0.11 mol) of iron(III) nitrate nonahydrate as raw materials, and 81 mL (5V) of hexafluoroisopropanol as the solvent.

[0067]

[0068] 1) Connect the microreactor system.

[0069] 2) Heat the micromixer and preheating device to 55 - 60 °C and 50 - 55 °C respectively by a thermostatic bath, and balance and calibrate the system.

[0070] 3) Store trifluoromethoxybenzene in storage tank V-1 and pump it into the first reaction module at a volumetric flow rate of 1.3 mL / min by pump P-1.

[0071] 4) Store the hexafluoroisopropanol solution of iron(III) nitrate and tris(pentafluorophenyl)borane in storage tank V-2 and pump it into the second reaction module at a volumetric flow rate of 10.7 mL / min by pump P-2.

[0072] 5) Pump the materials in reaction module 1 and reaction module 2 into the micromixer in the third reaction module at a volumetric flow rate of 6 mL / min by pump P-3 to mix the materials, react in the fourth reaction module at 55 - 60 °C, and complete the reaction through the delay pipeline of the tubular reactor in 20 minutes.

[0073] 6) The reacted materials enter the receiving tank V-3. It can be detected by HPLC that p-nitrotrifluoromethoxybenzene accounts for 91.7% and o-nitrotrifluoromethoxybenzene accounts for 7.9%.

[0074] 7) Stop the pump and clean the system.

[0075] Example 5

[0076]

[0077] p-Nitrotrifluoromethoxybenzene: Using 16.2 g (0.1 mol) of trifluoromethoxybenzene, 1.1 g of tris(pentafluorophenyl)borane, and 40.4 g (0.1 mol) of iron(III) nitrate nonahydrate as raw materials, and 81 mL (5V) of hexafluoroisopropanol as the solvent.

[0078] 1) Connect the microreactor system.

[0079] 2) Heat the micromixer and preheating device to 55 - 60 °C and 50 - 55 °C respectively by a thermostatic bath, and balance and calibrate the system.

[0080] 3) Store trifluoromethoxybenzene in storage tank V-1 and enter the first reaction module through pump P-1 at a volume flow rate of 1.3 mL / min;

[0081] 4) Store the solution of iron nitrate and tris(pentafluorophenyl)borane in hexafluoroisopropanol in storage tank V-2 and enter the second reaction module through pump P-2 at a volume flow rate of 10.7 mL / min;

[0082] 5) Feed the materials in reaction module 1 and reaction module 2 into the micromixer in the third reaction module through pump P-3 at a volume flow rate of 12 mL / min to mix the materials, react in the fourth reaction module at 55 - 60 °C, and complete the reaction through the delay pipeline of the tubular reactor in 10 minutes;

[0083] 6) The reacted materials enter receiving tank V-3. It can be known from HPLC detection that: p-nitrotrifluoromethoxybenzene accounts for 94.3%, and o-nitrotrifluoromethoxybenzene accounts for 4.4%.

[0084] 7) Stop the pump and clean the system.

[0085] Example 6:

[0086] For p-nitrotrifluoromethoxybenzene: Use 16.2 g (0.1 mol) of trifluoromethoxybenzene, 1.4 g of tris(pentafluorophenyl)borane, and 44.4 g (0.11 mol) of iron nitrate nonahydrate as raw materials, and recycle 81 mL (5V) of hexafluoroisopropanol as the solvent.

[0087]

[0088] 1) Connect the microreactor system;

[0089] 2) Cool the micromixer and preheating device to 55 - 60 °C and 50 - 55 °C respectively by the thermostatic bath, and balance and calibrate the system;

[0090] 3) Store trifluoromethoxybenzene in storage tank V-1 and enter the first reaction module through pump P-1 at a volume flow rate of 1.3 mL / min;

[0091] 4) Store the recycled hexafluoroisopropanol solution of iron nitrate and tris(pentafluorophenyl)borane in storage tank V-2 and enter the second reaction module through pump P-2 at a volume flow rate of 10.7 mL / min;

[0092] 5) Feed the materials in reaction module 1 and reaction module 2 into the micromixer in the third reaction module through pump P-3 at a volume flow rate of 12 mL / min to mix the materials, react in the fourth reaction module at 55 - 60 °C, and complete the reaction through the delay pipeline of the tubular reactor in 10 minutes;

[0093] 6) The materials after the reaction completion enter the receiving tank V-3. As detected by HPLC, p-nitrotrifluoromethoxybenzene accounts for 94.9% and o-nitrotrifluoromethoxybenzene accounts for 4.1%.

[0094] 7) Stop the pump and clean the system.

[0095] Example 7

[0096]

[0097] For p-nitrotrifluoromethoxybenzene: Using 16.2 g (0.1 mol) of trifluoromethoxybenzene, 1.1 g of tris(pentafluorophenyl)borane, and 44.4 g (0.11 mol) of iron(III) nitrate nonahydrate as raw materials, and 81 mL (5V) of hexafluoroisopropanol as the solvent.

[0098] 1) Connect the microreactor system.

[0099] 2) Heat the micromixer and the preheating device to 55 - 60 °C and 50 - 55 °C respectively by a constant temperature bath, and balance and calibrate the system.

[0100] 3) Store trifluoromethoxybenzene in the storage tank V-1 and pump it into the first reaction module at a volumetric flow rate of 1.3 mL / min by pump P-1.

[0101] 4) Store the hexafluoroisopropanol solution of iron(III) nitrate and tris(pentafluorophenyl)borane in the storage tank V-2 and pump it into the second reaction module at a volumetric flow rate of 10.7 mL / min by pump P-2.

[0102] 5) Pump the materials in reaction module 1 and reaction module 2 into the micromixer in the third reaction module at a volumetric flow rate of 12 mL / min by pump P-3 to mix the materials, and react in the fourth reaction module at 55 - 60 °C. Complete the reaction through the delay pipeline of the tubular reactor in 10 min.

[0103] 6) The materials after the reaction completion enter the receiving tank V-3. As detected by HPLC, p-nitrotrifluoromethoxybenzene accounts for 95.3% and o-nitrotrifluoromethoxybenzene accounts for 3.8%.

[0104] 7) Distill under reduced pressure at 20 - 25 °C to remove hexafluoroisopropanol.

[0105] 8) Add water to the viscous oil to wash away iron(III) nitrate and residual hexafluoroisopropanol.

[0106] 9) Add dichloromethane to dissolve the product, then add 2.42 g (0.01 mol) of triphenylborane, stir for 30 min at 20 - 25 °C, and then distill under reduced pressure to remove dichloromethane.

[0107] 10) The obtained product was heated to 90 - 95 °C through a distillation device and distilled to obtain 18.4 g of p-nitrotrifluoromethoxybenzene with a yield of 88.9%. HPLC: 99.5%;

[0108] 1 1H-NMR (CDCl3): δ 6.95 (q, 1H), 6.47 (dd, 1H), 5.84 (m, 1H), 4.04 (dd, 1H), 2.39 - 2.05 (d, 2H)

[0109] 11) Stop the pump and clean the system.

[0110] The above embodiments describe the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments. What is described in the above embodiments and the specification only illustrates the principles of the present invention. Without departing from the scope of the principles of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of protection of the present invention.

Claims

1. A method for synthesizing p-nitrotrifluoromethoxybenzene in a microchannel, characterized in that: The method comprises the following steps: heating with a microchannel reactor, and nitrating trifluoromethoxybenzene with ferric nitrate in the microchannel reactor to synthesize p-nitrotrifluoromethoxybenzene.

2. The method for synthesizing p-nitrotrifluoromethoxybenzene by microchannel according to claim 1, characterized in that: The specific steps include: 1) Connecting a continuous flow microchannel reactor system; 2) back pressure is applied to the microchannel reactor by a back pressure valve, and the pressure in the microchannel reactor system reaches a certain level; 3) heating the micro mixer and preheating device to the reaction temperature by a constant temperature bath; 4) System balance and calibration; 5) trifluoromethoxybenzene and an organic solvent solution of ferric nitrate are fed through a feed pump, mixed in a micro mixer, and reacted at a certain temperature and within a certain time by a preheating device; 6) The materials after the reaction are put into the receiving tank for storage at room temperature and then processed; 7) Stop the pump and clean the system; 8) After the reaction, the feed solution is heated, triphenylborane is used to complex with o-nitrotrifluoromethoxybenzene, and p-nitrotrifluoromethoxybenzene is obtained by distillation.

3. The method for synthesizing p-nitrotrifluoromethoxybenzene by microchannel according to claim 2, characterized in that: The flow rate in the reaction is selected from 40 mL / min, 24 mL / min, 12 mL / min and 6 mL / min.

4. The method for synthesizing p-nitrotrifluoromethoxybenzene by microchannel according to claim 2, characterized in that: The molar ratio of trifluoromethoxybenzene to ferric nitrate is 1.0:1.0-1.

1.

5. The method for synthesizing p-nitrotrifluoromethoxybenzene by microchannel reactor according to claim 2, characterized in that: The organic solvent is selected from hexafluoroisopropanol or recycled hexafluoroisopropanol.

6. The method for synthesizing p-nitrotrifluoromethoxybenzene by microchannel reactor according to claim 2, characterized in that: The reaction temperature is 50-60°C.

7. The method for synthesizing p-nitrotrifluoromethoxybenzene by microchannel reactor according to claim 2, characterized in that: The ortho isomer generated in the reaction is complexed by adding triphenylborane, so that the product and the isomer are separated and purified.

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