Method for preparing functionalized acrylate based on macro-micro reactor

Abstract

The invention discloses a method for preparing functionalized acrylic ester based on a macro-micro reactor, which comprises the following step of: reacting a mixed solution of (methyl) acrylic ester monomers and alcohol in a micro-channel reactor with immobilized enzyme or the macro-micro reactor with immobilized enzyme to obtain the functionalized (methyl) acrylic ester. The method is suitable for (methyl) acrylate and alcohol substrates, the substrate range is wide, and compared with a traditional synthesis method, the microreactor containing the internal component can remarkably shorten the enzymatic transesterification reaction time and improve the conversion rate. The characteristic scale of the macro-micro reactor reaches centimeter level, and high-flux synthesis can be realized. The invention provides a technical scheme for material monomer preparation, and has industrial conversion prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis of material monomers, and in particular relates to a method for preparing functionalized acrylate based on a macro-micro reactor. Background Art

[0002] In the past two decades, as people pay more and more attention to environmental issues, the chemical industry has begun to pay attention to the development of green chemical methods to reduce unnecessary byproducts in the reaction process. Enzymatic processes are seen as an alternative to traditional chemical catalysis because they can minimize unwanted byproducts in the reaction process. In addition, catalysts such as immobilized enzymes can simplify the separation and purification process of products and can be reused.

[0003] Bioenzyme catalysis has attracted wide attention in the field of organic synthesis catalysis due to its mild catalytic conditions, wide range of temperature, pH, pressure, good stereoselectivity, chemical selectivity, easy recycling and reuse, and zero toxicity. Antarctic Candida lipase B (CALB) is a lipase derived from Antarctic Candida, with the commercial name Novozyme 435. Due to its excellent selectivity, thermal stability and catalytic activity, it is widely used in catalyzing transesterification reactions, ring-opening polymerization, esterification reactions and polycondensation reactions.

[0004] Microreactors are usually operated in continuous mode, so for some traditional chemical reactions, flow chemistry can overcome some problems of using enzyme catalysts in traditional reactors, such as using batch reactors at high temperatures and vigorous stirring, which will inactivate the enzyme. In microreactors, biocatalysts are transferred to heterogeneous catalysts through immobilization to be applied to continuous reactions with high activity and high contact with substrates, while providing excellent permeability. In order to break through the limitations of the above-mentioned batch reactor method, it is urgent to apply microflow field technology (such as using microreactors to enhance mass transfer and heat transfer) to improve preparation efficiency, increase the number of enzyme recycling times, simplify separation and purification, and provide technical support for the industrial production and application of enzyme-catalyzed preparation of acrylates.

[0005] (Meth)acrylates are an important class of organic chemical raw materials that can be used to prepare polymer materials with properties such as heat resistance, water resistance, and UV resistance through controlled polymerization. The bulk of commercialized (meth)acrylates is methyl (meth)acrylate. However, the pursuit of better performance requires innovation in the structure of (meth)acrylates, and structural innovation is mainly based on the preparation of functionalized (meth)acrylates with different side chains. New functionalized (meth)acrylates can be used in industry to synthesize high-performance polymers, coatings, adhesives, and other chemicals, and to manufacture materials that are chemically resistant, high-strength, and highly transparent. In pharmaceutical chemistry, they are used to manufacture drug sustained-release systems to control the release rate and duration of drugs, improve drug treatment effects, and reduce adverse reactions. In biology and biomedicine, they can be used to manufacture biosensors, biochips, and biomedical materials.

[0006] The chemical method of (meth)acrylate is mainly synthesized by esterification reaction of (meth)acrylic acid and alcohol, while (meth)acrylate with more complex side chain uses acryloyl chloride as raw material, the reaction steps are more complicated, and there are more by-products. Enzyme catalysis has the advantages of mild reaction conditions, green environmental protection, simplified separation and purification, and repeated use. Previously, a large number of studies reported lipase-catalyzed transesterification reactions, which are widely used in chiral resolution, synthesis of raw materials, food and other fields. However, the enzyme-catalyzed reaction time is long, the catalyst utilization rate is low, and the stirring of the kettle reactor causes the enzyme to inactivate. These factors limit its application in the synthesis of (meth)acrylate.

[0007] Compared with kettle reactors, the small size of microreactors has a high specific surface area to volume ratio, thereby enhancing the transfer of mass and energy, increasing the reaction rate, reducing the diffusion distance and the reactant retention volume, and thus providing advantages for process intensification. However, at low flow rates, the flow state of the microreactor presents a laminar flow, forming a reverse mixing, a large residence time distribution, and a low flux, and industrialization is difficult to achieve. Therefore, the present invention is based on a macro-microreactor to carry out an enzymatic transesterification reaction, shorten the enzymatic transesterification reaction time, and improve the conversion rate. The characteristic scale of the macro-microreactor reaches the centimeter level, and internal components are added to the macro-microreactor to improve the mixing effect, and high-throughput synthesis can be achieved. At the same time, the macro-microreactor is combined with enzyme catalysis, which increases the number of enzyme recycling times, simplifies the separation and purification steps, and brings technical support to the industrial production and application of enzyme-catalyzed preparation of (methyl) acrylate. Summary of the invention

[0008] Purpose of the invention: The technical problem to be solved by the present invention is to provide a method for preparing functionalized acrylate based on macro-micro reactors in view of the deficiencies in the prior art.

[0009] In order to solve the above technical problems, the present invention discloses the following technical solutions:

[0010] In a first aspect, the present invention discloses a method for preparing functionalized acrylate based on a microreactor.

[0011] The method comprises reacting a mixed solution of (meth) acrylic acid ester monomers and alcohol in a conventional microchannel reactor or macro-microreactor equipped with an immobilized enzyme to obtain functionalized acrylic acid ester.

[0012] In a second aspect, the present invention discloses an application of a macro-microreactor in the preparation of functionalized acrylate.

[0013] The application is to react a mixed solution of (meth)acrylate monomers and alcohol in a macro-microreactor equipped with an immobilized enzyme to obtain functionalized acrylate.

[0014] In the above first and second aspects,

[0015] The reaction is as follows:

[0016]

[0017] Among them, R1 is selected from hydrogen or methyl; R2 is selected from trifluoroethyl, methyl, n-butyl, tert-butyl, benzyl, cyclohexyl; R3 is selected from methyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-hexyl, benzyl, furfuryl, n-undecyl, β-ethyl acrylate, morpholineethyl and propionitrile.

[0018] The (meth)acrylate monomer is any one or a combination of trifluoroethyl acrylate, methyl acrylate, n-butyl acrylate, tert-butyl acrylate, benzyl acrylate, cyclohexyl acrylate, methyl methacrylate and trifluoroethyl methacrylate, preferably trifluoroethyl acrylate, methyl acrylate, trifluoroethyl methacrylate and methyl methacrylate.

[0019]

[0020] The alcohol is any one or a combination of methanol, n-propanol, isopropanol, n-butanol, tert-butanol, n-hexanol, benzyl alcohol, furfuryl alcohol, undecanol, hydroxyethyl acrylate, 2-morpholinoethanol and 3-hydroxypropionitrile.

[0021]

[0022] The molar ratio of the (meth)acrylate monomer to the alcohol is 1:0.5-10, preferably 1:1-10, or 1:0.5-1.5, and more preferably 1:1.

[0023] The preparation method of the microchannel reactor with immobilized enzyme is as follows: placing immobilized lipase in a microchannel tube; or mixing glass beads and immobilized lipase evenly and placing them in a microchannel tube, wherein the glass beads have a particle size of 0.3-0.9 mm, and the immobilized lipase has a particle size of 0.3-0.9 mm. The loading amount of the immobilized enzyme in the microchannel reactor is controlled to be 0.4-0.6 g / mL; the loading amount of the glass beads in the microchannel reactor is controlled to be 0.4-0.6 g / mL. The inner diameter of the microchannel reactor tube is 2-15 mm, such as 3 mm, 4.3 mm, and the retention volume is 1-10 mL.

[0024] Wherein, the macro-microreactor provided with immobilized enzyme is to fill the immobilized lipase in the macro-microreactor, and the macro-microreactor includes a channel shell and an internal component in the channel. The loading amount of the immobilized lipase in the microchannel reactor is controlled to be 0.4-0.6g / mL. The retention volume of the macro-microreactor is 1-10mL; the inner diameter of the channel shell is 3-15mm, such as 4.3-10mm; the internal component is a copper wire with a hollow center, and the diameter of the internal component is 0.5-3mm; the internal component is a spiral internal component, a serpentine internal component, an O-shaped internal component, or a linear internal component; the spiral internal component, the serpentine internal component and the O-shaped internal component have a pitch, and the pitch is 0.5-10mm.

[0025] In the present invention, the immobilized lipase is any one or a combination of Candida antarcticlipase B (CALB), porcine pancreas lipase (Lipase (pocine pancreas)), Candidarugosa lipase (Candidarugosa lipase), Amano Lipase (Amano Lipase from Pseudomonas fluorescens) and lipase PS from Burkholderia cepacia (LPS), preferably Candida antarctic lipase B (CALB), with an enzyme activity of 10000 PLU / g, and the immobilized CALB is purchased from Nanjing Deming Chemical Technology Co., Ltd.

[0026] Wherein, the reaction temperature is 0-100°C, preferably 50-70°C, and more preferably 60°C.

[0027] Wherein, the reaction rate is 0.01-20 mL / min, such as 0.01-5 mL / min; the residence time of the reaction is 0.5-100 min, preferably 1-60 min, preferably 10-30 min.

[0028] The present invention provides a method for preparing functionalized acrylate based on a macro-microreactor, wherein a mixed solution of (meth)acrylate monomers and alcohol is reacted in a macro-microreactor provided with an immobilized enzyme or a microreactor filled with glass beads and an immobilized enzyme. In the method provided by the present invention, after 100 cycles of the immobilized enzyme macro-microreactor, the ester exchange conversion rate is as high as 97%, and the characteristic size of the microreactor reaches the centimeter level, which can achieve gram-level production. In an intermittent reactor, the lipase will be disintegrated due to stirring, which is not conducive to recovery and reuse, while the use of a microreactor can protect the enzyme from being affected, which is a good industrial amplification solution. The present invention constructs an enzyme macro-microreactor platform, regulates the reaction conditions, effectively simplifies the synthesis steps, shortens the preparation time, and eliminates the separation and purification of the product and the enzyme, and a product with higher purity can be obtained by subsequent extraction. The present invention provides a new idea for enzyme-catalyzed synthesis and fluid chemistry, and has important industrial value.

[0029] The present invention provides a method for preparing functionalized acrylate based on a macro-micro reactor, which is simple to operate, has cheap synthetic raw materials, is simple and convenient for post-processing separation and purification, and can realize the scaled-up production of high-value functionalized acrylate. The method effectively improves the specific surface area during the reaction process by introducing a continuous flow micro-reaction as a reaction platform, and glass beads and copper wires as internal components, thereby strengthening the spatiotemporal controllability of the reaction process and effectively shortening the time required for the reaction. At the same time, in the method, the characteristic size of the microreactor reaches the centimeter level, and gram-level production can be achieved. The present invention constructs an enzyme-catalyzed macro-micro reactor platform, regulates the reaction conditions, effectively simplifies the synthesis steps, shortens the preparation time, and eliminates the separation and purification of the product and the enzyme, and a product with higher purity can be obtained by subsequent extraction. The present invention provides a new idea for enzyme-catalyzed synthesis and fluid chemistry, and has important industrial value. The present invention also solves the problems of difficulty in recovering enzyme catalysts and insufficient flux in the prior art.

[0030] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0031] (1) The present invention is based on the macro-microreactor-based enhanced enzymatic transesterification reaction process to rapidly and high-throughput prepare a series of new structural (meth)acrylate material monomers.

[0032] (2) Compared with the traditional tank reactor, the present invention significantly shortens the reaction time and improves the conversion rate based on the macro-micro reactor. For example, the conversion rate of methyl acrylate and benzyl alcohol is increased from 25.34% to 70.52% when the ester exchange reaction time is the same.

[0033] (3) Compared with a typical microreactor (characteristic scale = 1.0 mm), the present invention significantly increases the reaction flux based on the macro-microreactor, for example, the flow rate is increased from 0.01667 ml / min to 0.1 ml / min, and the output per unit time is increased from 0.0103 g / min to 0.0603 g / min.

[0034] (4) Compared with the continuous flow reactor (>2.0 mm without internal components), the present invention significantly improves the conversion rate based on the macro-micro reactor. For example, when trifluoroethyl acrylate and n-hexanol are exchanged for the same reaction time of 10 min, the conversion rate is increased from 73.53% to 97.23%. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments, and the above and other advantages of the present invention will become more clear.

[0036] Figure 1 Schematic diagram of the macro-microreactor system used in this experiment.

[0037] Figure 2 It is a macro-micro reactor.

[0038] Figure 3 Example 4 Ethylene glycol diacrylate 1 H NMR spectra.

[0039] Figure 4 Example 4 Ethylene glycol diacrylate 13 C NMR spectrum.

[0040] Figure 5 Example 5 2-n-morpholinoethyl acrylate 1 H NMR spectra.

[0041] Figure 6 Example 5 2-n-morpholinoethyl acrylate 13 C NMR spectrum.

[0042] Figure 7 Example 6 2-ethyl cyanoacrylate 1 H NMR spectra.

[0043] Figure 8 Example 6 2-ethyl cyanoacrylate 13 C NMR spectrum. DETAILED DESCRIPTION

[0044] The experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0045] In the following examples, a 400 MHz Bruker nuclear magnetic resonance instrument was used to 1 H NMR and 13 C NMR was used to characterize the structure of the polymerized product. 1 mL of the reaction solution and the product was placed in a NMR tube, deuterated chloroform was added, and the sample was measured after shaking until it was completely dissolved.

[0046] In the following examples, the Candida antarctic lipase B (CALB) used has a particle size of 0.3-0.9 mm and an enzyme activity of 10,000 PLU / g. The purchaser is Nanjing Deming Chemical Technology Co., Ltd. Porcine pancreatic lipase (Lipase (pocine pancreas)) has an enzyme activity of 30,000 U / g. The purchaser is Shanghai Yuanye Biotechnology Co., Ltd. Candida rugosa has an enzyme activity of 700 U / mg. The purchaser is Shanghai Yuanye Biotechnology Co., Ltd. Amano Lipase from Pseudomonasfluorescens has an enzyme activity of 20,000 U / g. The purchaser is Merck. Burkholderia cepacia (LPS) has an enzyme activity of 23,000 U / mg. The purchaser is Shanghai McLean Biochemical Technology Co., Ltd.

[0047] like Figure 1 As shown, the reaction of the present invention is carried out in a reaction device containing a macro-microreactor or a reaction device containing a glass bead microreactor. The reaction device includes a feed pump, a macro-microreactor filled with lipase or a microreactor filled with lipase and glass beads, a heating device and a receiver; wherein the macro-microreactor filled with lipase and the microreactor filled with lipase and glass beads are provided with a heating device; the feed pump is connected to the macro-microreactor filled with lipase or the microreactor filled with lipase and glass beads, and then connected to the receiver; the connection is a pipeline connection. The pipeline is repeatedly rinsed with toluene or tetrahydrofuran before each use to purify the pipeline.

[0048] Macro-microreactors Figure 2 As shown, there are 4 types, macro-micro reactor SLSI (D-d1), SSI (D-d2-l1), OSI (D-d3-l2), HSI (D-d4-l3). The first macro-micro reactor HSI (D-d4-l3) represents the inner diameter of the reactor D mm, the second represents the diameter of the spiral line d4 mm, and the third represents the pitch l3 mm. SLSI (D-d1) does not have a pitch. The internal components of the macro-micro reactor described in the following embodiments are copper internal components.

[0049] The following examples, Examples 1-8 and Example 10-2, were all carried out in a reaction device containing a macro-microreactor, while Examples 9 and Example 10-1 were carried out in a reaction device containing a glass bead microreactor.

[0050] The enzyme-catalyzed transesterification conversion rate described in the following examples is calculated by the quenched reaction liquid hydrogen spectrum, and the degree of transesterification reaction is calculated by the integral ratio of the corresponding characteristic peaks. Specifically, taking Example 1 as an example, the enzyme-catalyzed transesterification conversion rate = n-hexyl acrylate peak integral / (n-hexyl acrylate integral+trifluoroethyl acrylate integral)*100%.

[0051] Example 1

[0052] 0.6 g CALB with a particle size of 0.3-0.9 mm was filled into the macro-microreactor HSI (4.3-1-3) (retention volume of 1.00 mL). The toluene prepared by Schlenk anhydrous and oxygen-free technology was used to flush the pipeline. 13.91 g (0.0903 mol, 1.0 eq) trifluoroethyl acrylate and 9.23 g (0.0903 mol, 1.0 eq) n-hexanol were added to a 50 mL round-bottom flask to prepare a solution, which was transferred into a syringe. The injection pump flow rate was set to 0.1 mL / min, the residence time was 10 min, the reaction temperature was 60 ° C, the reaction was started, and the reaction solution was collected after 20 min to obtain n-hexyl acrylate. 1 The conversion rate was 97.23% and the yield was 0.0603 g / min by H NMR. After 100 cycles, n-hexyl acrylate was obtained by 1 The conversion rate measured by H NMR can still reach 97%.

[0053] Example 2

[0054] 0.6 g CALB with a particle size of 0.3-0.9 mm was filled into the macro-microreactor SSI (4.3-1-3) (retention volume of 1.00 mL). The toluene prepared by Schlenk anhydrous and oxygen-free technology was used to flush the pipeline. 13.91 g (0.0903 mol, 1.0 eq) trifluoroethyl acrylate and 5.43 g (0.0903 mol, 1.0 eq) n-propanol were added to a 50 mL round-bottom flask to prepare a solution, which was transferred into a syringe. The injection pump flow rate was set to 0.1 mL / min, the residence time was 10 min, the reaction temperature was 60 ° C, the reaction was started, and the reaction solution was collected after 20 min to obtain n-propyl acrylate. 1 The conversion rate was 91.3% and the production rate was 0.0504 g / min by H NMR.

[0055] Example 3

[0056] 2.4 g CALB with a particle size of 0.3-0.9 mm was filled into the macro-microreactor HSI (6-0.5-10) (retention volume of 4.00 mL). The toluene prepared by Schlenk anhydrous and oxygen-free technology was used to flush the pipeline. 15.18 g (0.0903 mol, 1.0 eq) trifluoroethyl methacrylate and 11.84 g (0.0903 mol, 1.0 eq) 2-morpholineethanol were added to a 50 mL round-bottom flask to prepare a solution, which was transferred into a syringe. The injection pump flow rate was set to 0.4 mL / min, the residence time was 10 min, the reaction temperature was 80 ° C, the reaction was started, and the reaction solution was collected after 20 min to obtain ethyl methacrylate morpholine. 1 The conversion rate was 94.60% and the production was 0.0579 g / min by H NMR.

[0057] Example 4

[0058] 0.6 g CALB with a particle size of 0.3-0.9 mm was filled into the macro-microreactor SLSI (4.3-0.5) (retention volume of 1.00 mL). The toluene prepared by Schlenk anhydrous and oxygen-free technology was used to flush the pipeline. 11.57 g (0.0903 mol, 1.0 eq) of n-butyl acrylate and 10.486 g (0.0903 mol, 1.0 eq) of hydroxyethyl acrylate were added to a 50 mL round-bottom flask to prepare a solution, which was transferred into a syringe. The injection pump flow rate was set to 0.1 mL / min, the residence time was 10 min, the reaction temperature was 60 ° C, the reaction was started, and the reaction solution was collected after 20 min to obtain ethylene glycol diacrylate. 1 The conversion rate was 72.6% ( Figure 3 , Figure 4 ), with a production of 0.052g / min.

[0059] Example 5

[0060] 0.6 g CALB with a particle size of 0.3-0.9 mm was filled into the macro-microreactor SSI (4.3-1-6) (retention volume of 1.00 mL). The toluene prepared by Schlenk anhydrous and oxygen-free technology was used to flush the pipeline. 13.91 g (0.0903 mol, 1.0 eq) trifluoroethyl acrylate and 11.84 g (0.0903 mol, 1.0 eq) 2-morpholinoethanol were added to a 50 mL round-bottom flask to prepare a solution, which was transferred into a syringe. The injection pump flow rate was set to 0.1 mL / min, the residence time was 10 min, the reaction temperature was 60 ° C, the reaction was started, and the reaction solution was collected after 20 min to obtain 2-n-morpholinoethyl acrylate. 1 The conversion rate was 90.3% ( Figure 5 , Figure 6 ), with a production of 0.056 g / min.

[0061] Example 6

[0062] 1.2 g CALB with a particle size of 0.3-0.9 mm was filled into the macro-microreactor OSI (8-3-1) (retention volume was 2.00 mL). The toluene prepared by Schlenk anhydrous and oxygen-free technology was used to flush the pipeline. 13.93 g (0.0903 mol, 1.0 eq) cyclohexyl acrylate and 6.41 g (0.0903 mol, 1.0 eq) 3-hydroxypropionitrile were added to a 50 mL round-bottom flask to prepare a solution, which was transferred into a syringe. The injection pump flow rate was set to 0.0333 mL / min, the residence time was 60 min, the reaction temperature was 100 ° C, the reaction was started, and the reaction solution was collected after 120 min to obtain 2-ethyl cyanoacrylate. 1 The conversion rate was 84.23% ( Figure 7 , Figure 8 ), with a production of 0.0135 g / min.

[0063] Example 7

[0064] 1.8 g of CALB with a particle size of 0.3-0.9 mm was filled into the macro-microreactor HSI (10-1-3) (retention volume of 3.00 mL), and the pipeline was flushed with toluene prepared by Schlenk anhydrous and oxygen-free technology. 7.77 g (0.0903 mol, 1.0 eq) of methyl acrylate and 9.76 g (0.0903 mol, 1.0 eq) of benzyl alcohol were added to a 50 mL round-bottom flask to prepare a solution, which was transferred into a syringe, and the injection pump flow rate was set to 0.3 mL / min, the residence time was 10 min, the reaction temperature was 60 ° C, the reaction was started, and the reaction solution was collected after 20 min to obtain benzyl acrylate. 1 The conversion rate was 70.52% and the production was 0.0158 g / min by H NMR.

[0065] Example 8

[0066] 3.0 g of CALB with a particle size of 0.3-0.9 mm was filled into the macro-microreactor HSI (5-1-3) (retention volume of 5.00 mL), and the toluene prepared by Schlenk anhydrous and oxygen-free technology was used to flush the pipeline. 11.57 g (0.0903 mol, 1.0 eq) of tert-butyl acrylate and 7.76 g (0.0903 mol, 1.0 eq) of methanol were added to a 50 mL round-bottom flask to prepare a solution, which was transferred into a syringe, and the injection pump flow rate was set to 0.5 mL / min, the residence time was 10 min, the reaction temperature was 80 ° C, the reaction was started, and the reaction solution was collected after 20 min to obtain methyl acrylate. 1 The conversion rate was 92.4% and the production rate was 0.0293 g / min by H NMR.

[0067] Example 9

[0068] 0.6 g CALB with a particle size of 0.3-0.9 mm and 0.6 g glass beads with a particle size of 0.3-0.9 mm were filled into an immobilized enzyme microreactor with an inner diameter of 4.3 mm (retention volume of 1.00 mL), and the pipeline was flushed with toluene prepared by Schlenk anhydrous and oxygen-free technology. 18.0 g (0.1110 mol, 1.0 eq) benzyl acrylate and 8.23 ​​g (0.1110 mol, 1.0 eq) n-butanol were added to a 50 mL round-bottom flask to prepare a solution, which was transferred into a syringe, and the injection pump flow rate was set to 0.0333 mL / min, the residence time was 30 min, the reaction temperature was 60°C, the reaction was started, and the reaction solution was collected after 60 min to obtain n-butyl acrylate. 1 The conversion rate was 83.0% and the production rate was 0.020 g / min by H NMR.

[0069] Example 10

[0070] Example 10-1

[0071] 0.6g CALB with a particle size of 0.3-0.9mm and 0.6g glass beads with a particle size of 0.3-0.9mm were filled into a microreactor with an inner diameter of 4.3mm (retention volume of 1.00mL), and the toluene prepared by Schlenk anhydrous and oxygen-free technology was used to flush the pipeline. 15.18g (0.0903mol, 1.0eq) trifluoroethyl methacrylate and 5.43g (0.0903mol, 1.0eq) n-propanol were added to a 50mL round-bottom flask to prepare a solution, which was transferred into a syringe, and the injection pump flow rate was set to 0.1mL / min, and the residence time was 10min. The reaction temperature was 60°C, and the reaction was started. After 20min, the reaction solution was collected to obtain n-propyl methacrylate. 1The conversion rate was 88.23% as measured by H NMR, and the production per minute was 0.0161 g / min.

[0072] Example 10-2

[0073] 1.8g CALB with a particle size of 0.3-0.9mm was filled into the macro-microreactor OSI (4.3-1-3) (retention volume of 3.00mL), and the toluene prepared by Schlenk anhydrous and oxygen-free technology was used to flush the pipeline. 9.03g (0.0903mol, 1.0eq) methyl methacrylate and 10.48g (0.0903mol, 1.0eq) hydroxyethyl acrylate were added to a 50mL round-bottom flask to make a solution, which was transferred into a syringe, and the injection pump flow rate was set to 0.05mL / min, and the residence time was 60min. The reaction temperature was 60℃, and the reaction was started. After 120min, the reaction solution was collected to obtain ethylene glycol dimethacrylate. 1 The conversion rate was 75.43% and the production was 0.027 g / min by H NMR.

[0074] Comparative Example 1

[0075] Prepare a 50mL Schlenk round-bottom flask, add 0.6g CALB with a particle size of 0.3-0.9mm, 13.91g (0.0903mol, 1.0eq) trifluoroethyl acrylate and 9.23g (0.0903mol, 1.0eq) n-hexanol. React at 60°C, take a point at 10min to monitor the reaction conversion rate. Obtain n-hexyl acrylate by 1 The conversion rate was 35.48% as measured by H NMR.

[0076] Comparative Example 2

[0077] Prepare a 50mL Schlenk round-bottom flask, add 0.6g CALB with a particle size of 0.3-0.9mm, 0.6g glass beads with a particle size of 0.3-0.9mm, 18.0g (0.1110mol, 1.0eq) benzyl acrylate and 8.23g (0.1110mol, 1.0eq) n-butanol. React at 60°C, take a point at 10min to monitor the reaction conversion rate. Obtain n-butyl acrylate by 1 The conversion rate was 37.04% as measured by H NMR.

[0078] Comparative Example 3

[0079] Prepare a 50mL Schlenk round-bottom flask, add 0.6g CALB with a particle size of 0.3-0.9mm, 9.04g (0.0903mol, 1.0eq) methyl methacrylate and 6.69g (0.0903mol, 1.0eq) tert-butyl alcohol. React at 60°C, take a point at 10min to monitor the reaction conversion rate. Obtain tert-butyl methacrylate by 1 The conversion rate was 10.57% as measured by H NMR.

[0080] Comparative Example 4

[0081] Prepare a 50mL Schlenk round-bottom flask, add 0.6g CALB with a particle size of 0.3-0.9mm, 7.77g (0.0903mol, 1.0eq) methyl acrylate, and 9.76g (0.0903mol, 1.0eq) benzyl alcohol. React at 60°C, take a point at 10min, and monitor the reaction conversion rate. Obtain benzyl acrylate by 1 The conversion rate was 25.34% as determined by H NMR.

[0082] Comparative Example 5

[0083] 0.6 g of CALB with a particle size of 0.3-0.9 mm was filled into a copper tube continuous flow microreactor with an inner diameter of 4.3 mm (retention volume of 1.00 mL), and the pipeline was flushed with toluene prepared by Schlenk anhydrous and oxygen-free technology. 13.91 g (0.0903 mol, 1.0 eq) of trifluoroethyl acrylate and 9.23 g (0.0903 mol, 1.0 eq) of n-hexanol were added to a 50 mL round-bottom flask to prepare a solution, which was transferred into a syringe, and the injection pump flow rate was set to 0.1 mL / min, the residence time was 10 min, the reaction temperature was 60°C, the reaction was started, and the reaction solution was collected after 20 min to obtain n-hexyl acrylate. 1 The conversion rate was 73.53% and the yield was 0.0481 g / min by H NMR. After 100 cycles, n-hexyl acrylate was obtained by 1 The conversion rate measured by H NMR was still 69.4%.

[0084] Comparative Example 6

[0085] 0.6 g CALB with a particle size of 0.3-0.9 mm was filled into a microreactor with an inner diameter of 1 mm (retention volume of 1.00 mL), and the toluene prepared by Schlenk anhydrous and oxygen-free technology was used to flush the pipeline. 13.91 g (0.0903 mol, 1.0 eq) trifluoroethyl acrylate and 9.23 g (0.0903 mol, 1.0 eq) n-hexanol were added to a 50 mL round-bottom flask to prepare a solution, which was transferred into a syringe, and the injection pump flow rate was set to 0.1 mL / min and the reaction temperature was set to 60°C. The reaction was started. The injection pump alarmed due to the high flow rate, so the flow rate was changed to 0.01667 mL / min, the residence time was 60 min, and the reaction solution was collected after 120 min to obtain n-hexyl acrylate. 1 The conversion rate was 77.53% and the production was 0.0103 g / min by H NMR.

[0086] Comparative Example 7

[0087] 0.6 g CALB with a particle size of 0.3-0.9 mm was filled into a microreactor with an inner diameter of 1 mm (retention volume of 1.00 mL), and the toluene prepared by Schlenk anhydrous and oxygen-free technology was used to flush the pipeline. 15.18 g (0.0903 mol, 1.0 eq) trifluoroethyl methacrylate and 11.84 g (0.0903 mol, 1.0 eq) 2-morpholineethanol were added to a 50 mL round-bottom flask to prepare a solution, which was transferred into a syringe, and the injection pump flow rate was set to 0.01667 mL / min, the residence time was 60 min, the reaction temperature was 80°C, the reaction was started, and the reaction solution was collected after 120 min to obtain ethyl methacrylate morpholine. 1 The conversion rate was 81.36% and the production was 0.0123 g / min by H NMR.

[0088] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A method for preparing functionalized acrylate based on a microreactor, characterized in that: The mixed solution of acrylic acid ester monomer and alcohol is reacted in a microchannel reactor equipped with an immobilized enzyme or a macro-microreactor equipped with an immobilized enzyme to obtain functionalized acrylic acid ester.

2. Use of a macro-microreactor in the preparation of functionalized acrylate; preferably, a mixed solution of acrylate monomers and alcohol is reacted in a macro-microreactor equipped with an immobilized enzyme to obtain functionalized acrylate.

3. The method according to claim 1 or the use according to claim 2, characterized in that: The acrylic acid ester monomer is any one or a combination of trifluoroethyl acrylate, methyl acrylate, n-butyl acrylate, tert-butyl acrylate, benzyl acrylate, cyclohexyl acrylate, methyl methacrylate and trifluoroethyl methacrylate; preferably, the alcohol is any one or a combination of n-propanol, isopropanol, n-butanol, tert-butanol, n-hexanol, benzyl alcohol, furfuryl alcohol, undecanol, hydroxyethyl acrylate, 2-morpholinoethanol and 3-hydroxypropionitrile; the molar ratio of the acrylic acid ester monomer to the alcohol is 1:0.5-10, preferably 1:1-10.

4. The method according to claim 1 or the use according to claim 2, characterized in that: The alcohol is methanol; The molar ratio of the acrylic acid ester monomer to the alcohol is 1:0.5-10, preferably 1:1-10.

5. The method according to claim 1, characterized in that: The preparation method of the microchannel reactor with immobilized enzyme is as follows: glass beads with a diameter of 0.3-0.9 mm and immobilized lipase are placed in a microchannel with an inner diameter of 2-15 mm, and the retention volume is 1-5 mL.

6. The method or use according to claim 5, characterized in that: The loading amounts of the immobilized enzyme and the glass beads in the microchannel reactor are controlled to be independently selected from 0.4-0.6 g / mL.

7. The method according to claim 1 or the use according to claim 2, characterized in that: The macro-micro reactor provided with immobilized enzyme is to fill the immobilized lipase in the macro-micro reactor, and the macro-micro reactor comprises a channel shell and internal components in the channel.

8. The method or use according to claim 7, characterized in that: The loading amount of the immobilized lipase in the microchannel reactor is controlled to be 0.4-0.6 g / mL; preferably, the retention volume of the macro-microreactor is 1-10 mL; the inner diameter of the channel shell is 3-15 mm; the diameter of the internal component is 0.5-3 mm; the internal component is a spiral internal component, a serpentine internal component, an O-shaped internal component, or a linear internal component; the spiral internal component, the serpentine internal component and the O-shaped internal component have a pitch of 0.5-10 mm.

9. The method or use according to claim 5 or 7, characterized in that: The immobilized lipase is any one or a combination of Candida antarctic lipase B, Lipasepocine pancrea, Candida rugosa lipase, Amano Lipase from Pseudomonasfluorescens and Lipase PS from Burkholderia cepacia.

10. The method according to claim 1 or the use according to claim 2, characterized in that: The reaction temperature is 0-100°C; the reaction rate is 0.01-5 mL / min; and the reaction residence time is 1-60 min.

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