CN115043733A

CN115043733A - Continuous flow nitration synthesis method and micro-channel reactor thereof

Info

Publication number: CN115043733A
Application number: CN202110249392.5A
Authority: CN
Inventors: 李斌栋; 吴亮; 龚文明; 詹乐武; 侯静
Original assignee: Nanjing University of Science and Technology
Current assignee: Nanjing University of Science and Technology
Priority date: 2021-03-08
Filing date: 2021-03-08
Publication date: 2022-09-13

Abstract

The invention discloses a continuous flow nitration synthesis method and a microchannel reactor thereof, wherein the synthesis steps comprise: the mixed acid of concentrated sulfuric acid and fuming nitric acid is used as a nitrating agent, 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene is used as a raw material liquid, two streams of fluid are respectively and synchronously conveyed by an advection pump from an inlet on a sealing plate of a microchannel reactor, enter a flow distribution plate, flow into a reactor plate under gravity and pressure for mixing reaction, the molar ratio of nitric acid to the raw material in the reaction liquid is 1.0-1.5, the reaction residence time in the microchannel reactor is adjusted to be 1-20min, the reaction temperature is 50-100 ℃, and the mixed acid leaves the reactor from an outlet after the reaction is finished. The conversion rate of the reaction raw materials reaches 100 percent. The continuous flow process greatly inhibits the generation of byproducts, the process device is integrated, the safety is high, the processing time is short, the microchannel reactor improves the distribution uniformity of fluid, enhances the mixing efficiency of the fluid, reduces the pressure loss of the reactor, and has the advantages of high reaction efficiency and uniform mixing.

Description

Continuous flow nitration synthesis method and micro-channel reactor thereof

Technical Field

The invention relates to continuous synthesis of an important intermediate of a high-efficiency pesticide lufenuron, in particular to a continuous flow nitration synthesis method and a microchannel reactor thereof, belonging to the field of novel chemical reactions.

Background

The lufenuron is an insect chitin inhibitor published by Nowa company 1997, belongs to benzoyl insecticides, is low in toxicity to human and livestock, has an excellent control effect on fruit trees and other leaf-eating caterpillars by acting on insect larvae and preventing a peeling process, has a unique killing mechanism on thrips, rust mites and trialeurodes vaporariorum, and is suitable for controlling pests generating resistance to synthetic pyrethrin and organophosphorus pesticides. Is safe to crops, can be used for crops such as corn, vegetables, citrus, cotton, potato, grape, soybean and the like, and is suitable for comprehensive pest control. The pesticide can not cause the sucking pests to rampant, and has mild effect on imagoes of beneficial insects and predatory spiders. The pesticide has selectivity and long-lasting property, and has good control effect on late-stage potato stem borers.

The main route for industrial synthesis of lufenuron is as follows:

4-nitro-2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene is a key intermediate for synthesizing lufenuron, and the structural formula of the intermediate is as follows:

the research and report on the synthesis process of 4-nitro-2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene are not abundant at home and abroad, the preparation method mainly adopts a kettle type reaction, and the reaction equation is as follows:

in addition, the lufenuron raw material is not only used as a herbicide, but also used for preventing and treating fleas on pet cats and dogs, preventing and treating termites and the like, and based on the background, foreign companies have extremely high requirements on the quality of lufenuron raw materials, the content of single impurities used in samples is all less than 0.1%, and under the traditional kettle type condition, the raw material product has low quantitative content and more impurities, and the impurities are difficult to remove through later purification, so that the production cost is improved, and the pollution to the environment is increased. Therefore, a new and efficient process synthetic route is needed.

The micro chemical technology is the advanced technology field of multidisciplinary intersection which is started in the early 90 s of the 20 th century. The whole micro-system is constructed by taking a micro-channel reactor as a core, wherein the micro-channel reactor is a novel miniaturized continuous flow pipeline type reactor manufactured by a micro-processing technology, and the characteristic dimension of the micro-channel reactor is far smaller than that of a conventional tubular reactor and is generally below 1000 mu m. The micro-fluidic chip technology integrates a plurality of or a large number of micro-channel reactors. The characteristics of large specific surface area, small reaction volume, unique laminar flow mass transfer and the like determine that the reactor has excellent heat transfer, mass transfer and mixing performances which are incomparable with the conventional reactor. The good mass transfer performance ensures the rapid mixing of materials, and the improvement of the heat transfer efficiency ensures that the reaction can rapidly react under the isothermal condition. These advantages can be fully exploited in organic synthesis. The microchannel reactor has the advantages of high specific surface area, rapid mixing, high-efficiency mass and heat transfer capacity and intrinsic safety due to the fact that the internal microstructure reaches the size of micron to sub-millimeter, and is particularly suitable for application in rapid exothermic reactions, such as nitration reactions. The application of the microchannel reactor in the nitration process of aromatic hydrocarbon and derivatives thereof has been reported in related patents, US 6861527, US7032607 and the like report the mononitration reaction in the microchannel reactor, CN101544568A and CN101544567A firstly apply the microchannel reactor technology to the nitration synthesis of corresponding dinitrated products by chlorobenzene and toluene mixed acid, the reaction time is greatly shortened, and the conversion rate and the selectivity of the dinitrated products are superior to those of a conventional kettle-type reactor. It can be seen that microchannel reactors have advantages over conventional reactors for such highly exothermic nitration reactions.

Disclosure of Invention

The invention aims to provide a method for preparing high-yield and high-purity 4-nitro-2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene by using a microchannel reactor, and the microchannel reactor related to the method.

The invention adopts a microchannel reactor to carry out nitration process of lufenuron key intermediate

Mixing concentrated sulfuric acid and fuming nitric acid to generate a nitrating agent, wherein the molar ratio of the sulfuric acid to the nitric acid is 1.0-3.0, synchronously pumping the mixed acid and a raw material 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene into a microchannel reactor through a advection pump, contacting and mixing fluid in a channel with a specific microstructure, discharging the fluid to a deposition tank from an outlet of the microchannel reactor after the fluid is subjected to mixing reaction, quenching the fluid, extracting and washing the fluid by dichloroethane in a centrifugal extractor, and carrying out distillation and other treatments to obtain an important lufenuron intermediate, namely 4-nitro-2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene, wherein the dichloroethane is recovered and reused.

In order to achieve the technical effects, the invention adopts the following technical scheme:

a continuous flow nitration synthesis method and a microchannel reactor thereof comprise the following steps: step 1: preparing mixed acid, controlling the molar ratio of sulfuric acid to fuming nitric acid to be 1.0-3.0, and mixing to generate mixed acid; step 2: starting an acid mixing pump and a raw material pump, synchronously conveying the 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene and the mixed acid to a microchannel reactor for mixing reaction, adjusting the flow rate ratio, and controlling the molar ratio of nitric acid to the raw material in the reaction liquid to be 1.0-1.5; and step 3: adjusting the reaction residence time in the microchannel reactor to be 1-20min, and the reaction temperature to be 50-100 ℃; and 4, step 4: after reaction, the fluid at the outlet of the reactor enters a centrifugal extractor, and is added with dichloroethane for extraction, washing and distillation treatment, so as to obtain the 4-nitro-2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene.

Furthermore, the mass fraction of fuming nitric acid is 98%, and the mass fraction of sulfuric acid is 98%.

Furthermore, the rotation speed of the centrifuge extractor is set between 1000rpm and 5000 rpm.

Provided is a microchannel reactor for synthesizing 4-nitro-2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene, which is characterized by comprising the following components in percentage by weight: a sealing plate, a flow distribution plate, a reactor plate and a cylindrical microstructure thereof; the sealing plate is provided with two inlet passages which are respectively called a first inlet passage and a second inlet passage, fluid of the first inlet passage and fluid of the second inlet passage simultaneously enter the flow dividing plate, and the flow dividing plate divides the flow into at least two flows; at the same time, the fluids join in the flow channels of the reactor plate and mix with each other in the columnar microstructure.

Further, the at least one inlet channel of the splitter plate is arranged to flow in a parallel extending arrangement towards the flow direction of the first inlet channel, the at least one inlet channel of the splitter plate is arranged to flow in a parallel extending arrangement towards the flow direction of the second inlet channel, and at least one of the first inlet channel and the at least one second inlet channel are arranged in parallel.

Further, the splitter plate divides the fluid into at least two streams; the first inlet channel fluid and the second inlet channel fluid are arranged in a staggered way; the divided stream channels are identical in size and the channel-to-channel spacing is also identical.

Furthermore, the left and right arrangement intervals of the columnar microstructures are equal, the upper and lower arrangement intervals are equal, the heights of all the columnar microstructures are equal, the columnar microstructures are arranged in a staggered mode, and the columnar microstructures have a distance of 10-15 cm in the flow channel.

Furthermore, the columnar microstructure microstructures are arranged only in the direct current channel in the channel, and after the mixing reaction is finished, the mixed solution flows out from the first outlet channel; the hydraulic diameter of the flow channel is 300-.

Furthermore, the substrate of the microchannel reactor is made of stainless steel, and the substrates are connected and sealed by stainless steel bolts or vacuum diffusion welding.

Furthermore, the microchannel reactor is externally connected with a centrifugal extractor.

The raw material liquid and the nitrating agent enter the reactor from the inlet of the microchannel reactor, and two streams of fluid pass through the reaction unit containing the columnar microstructure, so that the fluid is forced to have turbulent flow, the mixing effect is enhanced, and the reaction is favorably carried out.

The temperature control mode of the microchannel reactor can adopt an electric heating method and is provided by a constant temperature unit, and a microchannel heat exchange channel can be integrated in the microchannel reactor, and fluid media are led into the heat exchange channel so as to effectively regulate the temperature in the reactor.

Compared with the prior nitrification technology, the method has the following effects:

1. the nitration process of the lufenuron intermediate is a continuous flow reaction, the reaction time is shortened to several seconds to several minutes, and compared with the traditional kettle type process, the selectivity and the yield of reaction products are obviously improved;

2. the mass transfer and heat transfer performance of the adopted microchannel reactor is obviously improved, the temperature runaway phenomenon is avoided, the raw material and the nitrating agent are fully mixed, and the generation of by-products is reduced;

3. the nitration reaction liquid flows out from the outlet of the reactor to a sedimentation tank, the feed liquid is quenched by the reaction liquid, enters a centrifugal extractor for dichloroethane extraction, washing, distillation and other treatments to obtain a nitration product, and the dichloroethane is recycled and reused.

Drawings

FIG. 1(a) is a schematic structural diagram of a microchannel reactor according to an embodiment of the invention; FIG. 1(b) is an exploded view of a microchannel reactor.

FIG. 2 is a schematic view of a flow-splitting configuration of a microchannel reactor of the present invention.

FIG. 3 is a schematic diagram of the structure of a columnar micro-junction arrangement of the microchannel reactor of the present invention.

FIG. 4 is a schematic view of a micro-reaction device of the present invention.

In the figures, the reference numerals denote: 11. a first inlet channel; 12. a second inlet channel; 21. a bypass 1; 22. A branch passage 2; 23. a branch passage 3; 24. a shunt passage 4; 25. a shunt passage 5; 26. a branch passage 6; 27. a branch passage 7; 31. a first inlet channel; 32. a second inlet channel; 41. positioning pins; 51. a reactor plate (3); 61. adjacent microstructure voids; 71. a columnar microstructure; 81. a curved flow channel without microstructures.

Detailed Description

To further explain the technical means and effects of the present invention adopted to achieve the predetermined object, the following detailed description of the embodiments, structural features and effects according to the present invention will be made with reference to the accompanying drawings and preferred embodiments. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

As shown in fig. 1,2 and 3, the microchannel reactor according to an embodiment of the present invention includes a sealing plate 1 and a flow distribution plate 2, the sealing plate 1 of the reactor plate 3 covers the flow distribution plate 2, and the opposite surface of the flow distribution plate 2 is a cylindrical microstructure embedded in the flow channel of the reactor plate 3. The sealing plate 1 is provided with an inlet 4, an inlet 5 and an outlet 6. The reaction liquid flows into the flow channels on the flow distribution plate 2 from the inlet 4 and the inlet 5, and the two flow channels are respectively provided with 3 flow channel holes and 4 flow channel holes. As shown in the schematic diagram of the novel micro-reaction device in fig. 4, the raw material liquid is pumped into the micro-channel reactor module through a pump, the temperature of the constant temperature unit is controlled to be 90 ℃, the reaction is completed, the raw material liquid enters the separation module, the acid liquid and the organic liquid are separated by a centrifugal separator, and the washing operation is carried out. The organic liquid enters an evaporation module along a pipeline for flash evaporation and solvent recovery. And finally collecting the product.

Example 1

Concentrated sulfuric acid (98%) and fuming nitric acid (98%) are conveyed to a micro mixer to be mixed to generate a nitrating agent, the flow rate is adjusted to enable the molar ratio of the fuming nitric acid to the concentrated sulfuric acid to be 1:3, and the temperature is controlled to be below room temperature. Starting a raw material pump and an acid mixing pump, continuously and synchronously conveying the 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene into the microchannel reactor, controlling the molar ratio of the raw material to nitric acid to be 1:1.3, adjusting the retention time in the channel of the microchannel reactor to be 12min, controlling the reaction temperature to be 90 ℃, allowing a reaction liquid to flow out from an outlet of the reaction channel, extracting, separating, washing, performing rotary evaporation on the feed liquid, and the like to obtain a pesticide intermediate, namely 4-nitro-2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene, wherein the conversion rate of the raw material 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene reaches 100%, and the selectivity of a nitration product reaches 99.6%.

Example 2

The procedure is as in example 1, the molar ratio of sulfuric acid to nitric acid is fixed at 3:1, and the molar ratio of the starting material, 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene, to nitric acid is varied only, with the feed being fed in a stoichiometric ratio of 1: 1.5. The conversion rate of the raw material 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene reaches 100 percent, and the selectivity of the nitration product reaches 99.5 percent.

Example 3

The procedure is as in example 1, fixing the molar ratio of sulfuric acid to nitric acid at 3:1, varying only the molar ratio of the starting materials 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene to nitric acid, which are fed in a stoichiometric ratio of 1:1. The conversion rate of the raw material 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene reaches 95.4 percent, and the selectivity of the nitration product reaches 99.4 percent.

Example 4

The procedure is as in example 1, the molar ratio of starting material 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene to nitric acid is fixed at 1.3:1, and the molar ratio of sulfuric acid to nitric acid is varied only, with the feed being fed at a stoichiometric ratio of 1: 2. The conversion rate of the raw material 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene reaches 98.6 percent, and the selectivity of the nitration product reaches 99.2 percent.

Example 5

The procedure is as in example 1, starting from 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene at a 1.3:1 molar ratio to nitric acid and fed at a stoichiometric ratio of 1:1, varying only the molar ratio of sulfuric acid to nitric acid. The conversion rate of the raw material 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene is 96.5 percent, and the selectivity of the nitration product is 99.1 percent.

Example 6

The procedure is as in example 1, except that the starting materials 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene and nitric acid are fixed at a molar ratio of 1.3:1 and the feed is fixed at a molar ratio of sulfuric acid to nitric acid of 3: 1. Only the residence time was changed to 20 min. The conversion rate of the raw material 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene reaches 100 percent, and the selectivity of the nitration product reaches 99.5 percent.

Example 7

The procedure is as in example 1, except that the starting materials 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene and nitric acid are fixed at a molar ratio of 1.3:1 and the feed is fixed at a molar ratio of sulfuric acid to nitric acid of 3: 1. Only the residence time was changed to 1 min. The conversion rate of the raw material 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene reaches 85.4 percent, and the selectivity of the nitration product reaches 99.1 percent.

Example 8

The procedure is as in example 1, except that the starting materials 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene and nitric acid are fixed at a molar ratio of 1.3:1 and the feed is fixed at a molar ratio of sulfuric acid to nitric acid of 3: 1. Only the reaction temperature was changed to 80 ℃. The conversion rate of the raw material 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene reaches 95.1 percent, and the selectivity of the nitration product reaches 99.6 percent.

Example 9

The procedure is as in example 1, except that the starting materials 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene and nitric acid are fixed at a molar ratio of 1.3:1 and the feed is fixed at a molar ratio of sulfuric acid to nitric acid of 3: 1. Only the reaction temperature was changed to 100 ℃. The conversion rate of the raw material 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene reaches 100 percent, and the selectivity of the nitration product reaches 99.3 percent.

The invention applies the continuous flow technology to the nitration reaction of the lufenuron intermediate 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene, the product quality yield is nearly quantitative, the qualitative content is more than 99.5 percent, and the reaction time is greatly shortened compared with a kettle type reaction. Provides a continuous micro-reaction technology for the safe nitration synthesis of the synthetic pesticide. In addition, the micro-channel reactor can realize the industrialized production of the subsequent process due to the characteristic of parallel amplification.

Comparative example 1

The reaction conditions and results are shown in Table 1 for the same molar ratio of the respective substances as in example 1

TABLE 1 comparison of experimental results for microchannel reactor and conventional reactor

As can be seen from the above table, the reaction efficiency of the continuous flow reaction is significantly improved compared to the conventional reactor.

According to the mixed acid nitration method of the lufenuron intermediate by adopting the microchannel reactor, the micro mixer is adopted for acid matching, so that the intrinsic safety of the reaction is guaranteed, and the operation convenience is improved. The method has the characteristics of uniform reaction system, high reaction selectivity and efficiency, simple, safe and efficient process, provides a new nitration process for safe nitration production, and has important significance.

Claims

1. A method for continuous flow nitration synthesis, comprising the steps of: step 1: preparing mixed acid, controlling the molar ratio of sulfuric acid to fuming nitric acid to be 1.0-3.0, and mixing to generate mixed acid; and 2, step: starting an acid mixing pump and a raw material pump, synchronously conveying the 2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene and the mixed acid to a microchannel reactor for mixing reaction, adjusting the flow rate ratio, and controlling the molar ratio of nitric acid to the raw material in the reaction liquid to be 1.0-1.5; and step 3: adjusting the reaction residence time in the microchannel reactor to be 1-20min, and the reaction temperature is 50-100 ℃; and 4, step 4: after reaction, the fluid at the outlet of the reactor enters a centrifugal extractor, and is added with dichloroethane for extraction, washing and distillation treatment, so as to obtain the 4-nitro-2, 5-dichloro-1- (1,1,2,3,3, 3-hexafluoropropoxy) benzene.

2. The synthesis method according to claim 1, wherein the mass fraction of fuming nitric acid is 98% and the mass fraction of sulfuric acid is 98%.

3. The method of claim 1, wherein the centrifuge extractor speed is set between 1000rpm and 5000 rpm.

4. The microchannel reactor for synthesis according to any one of claims 1-3, comprising: a sealing plate (1), a flow distribution plate (2), a reactor plate (3) and a columnar microstructure thereof; the sealing plate (1) is provided with two inlet passages which are respectively called a first inlet passage and a second inlet passage, fluid of the first inlet passage and fluid of the second inlet passage simultaneously enter the flow dividing plate (2), and the flow dividing plate (2) divides the flow into at least two flows; at the same time, the fluids are merged in the flow channels of the reactor plate (3) and mixed with each other in the columnar microstructure.

5. The microchannel reactor of claim 4 wherein the flow distribution plate (2) has at least one inlet channel fluid running parallel to the flow direction of the first inlet channel, the flow distribution plate (2) has at least one inlet channel fluid running parallel to the flow direction of the second inlet channel, and at least one of the first inlet channel is aligned parallel to at least one of the second inlet channel.

6. The microchannel reactor of claim 4, wherein the splitter plate (2) divides the fluid into at least two streams; the first inlet channel fluid and the second inlet channel fluid are arranged in a staggered way; the divided stream passages have the same size and the same distance between the passages.

7. The microchannel reactor of claim 4, wherein the columnar microstructures have equal left and right arrangement spacing, equal top and bottom arrangement spacing, equal height of all columnar microstructures, staggered arrangement of the columnar microstructures, and a distance of 10cm to 15cm between the columnar microstructures in the flow channel.

8. The microchannel reactor of claim 4, wherein the columnar microstructure is arranged only in the through-channels of the channel, and after the mixing reaction is completed, the mixed liquid flows out of the first outlet channel; the hydraulic diameter of the flow channel is 300-500 μm.

9. The microchannel reactor of claim 4, wherein the microchannel reactor base plates are made of stainless steel, and the base plates are sealed by stainless steel bolting or vacuum diffusion welding.

10. The microchannel reactor of claim 4, wherein the microchannel reactor is externally connected to a centrifugal extractor.