Method and device for photo-catalyzing allyl arylation reaction

Abstract

The invention relates to a method and device for photocatalytic allyl arylation reaction, and the method comprises the following steps: mixing tetrabutylammonium decatungstate, 1, 3-bis (diphenylphosphine) propane nickel chloride, phenanthroline and aryl bromide, and under a protective atmosphere, adding acetonitrile, chlorobenzene, an allyl substrate and triethylamine to form a reaction solution; under the action of external force, the reaction liquid continuously and circularly passes through the illumination area to carry out photocatalytic reaction, and the temperature of the reaction liquid is kept constant in the circulating process. The efficient and stable catalytic system is constructed to cooperate with the continuous flow reaction system, so that the efficient, low-cost and easy-to-industrialize photocatalytic allyl arylation reaction is realized.

Description

Technical Field

[0001] This application relates to the field of organic molecule synthesis technology, and in particular to a method and apparatus for photocatalytic allyl arylization reaction. Background Technology

[0002] Allyl aryl compounds are key structural units constituting drug molecules, natural products, and functional materials. For example, allyl aryl compounds are important precursors for the synthesis of important compounds such as antihistamines, antiviral drugs, and plant growth regulators. Traditional allyl arylation methods mainly rely on pre-functionalized allyl substrates, such as allyl halides and allyl esters. These traditional methods not only require additional steps to synthesize the pre-functionalized substrates, easily generating chemical waste, but also typically use equivalent amounts of Grignard reagents, organolithium reagents, and other organometallic reagents, resulting in harsh reaction conditions and poor functional group compatibility.

[0003] Significant progress has been made in the field of CH bond activation in recent years. Among these advancements, the hydrogen atom transfer strategy has proven effective in directly and selectively activating inert C(sp) bonds. 3 The -H bond, requiring no pre-functionalization, becomes an ideal tool for constructing C / C bonds. Photoredox catalysis, as a mild and green energy input method, makes it possible to initiate hydrogen atom transfer (HAT) processes at room temperature. Combining photocatalysis with the HAT strategy provides a new, atom-economical, and environmentally friendly approach for allyl arylization reactions. For example, in 2023, Professors Long Huang and Magnus Rueping's group reported a photo / nickel co-catalytic system that disclosed a method for selectively controlling the Z / E configuration (geometric isomer) of the reaction product under visible light / nickel co-catalysis by precisely tuning the steric hindrance and electronic properties of the chiral ligand.

[0004] However, such technologies still have several technical problems that need to be solved: (1) Low reaction efficiency and long reaction time: This technology is usually carried out in a traditional batch reactor. Due to the light path attenuation effect in the reaction liquid, the light penetration depth is limited, resulting in low light energy utilization and slow reaction rate. It usually takes several hours or even tens of hours to complete. (2) Difficulty in scale-up production and prominent industrialization bottlenecks: When the batch reaction is scaled up from the milligram level laboratory scale to the gram level or above pilot or production scale, the uneven illumination and heat transfer problems will deteriorate sharply, resulting in a significant decrease in reaction yield and selectivity, making it difficult to achieve stable production. (3) High catalyst cost and complex system: Some technologies still rely on precious metal photocatalysts such as iridium and ruthenium complexes or require equivalent stoichiometric HAT reagents, which increases the cost and post-processing difficulty and does not meet the requirements of green chemistry and cost control. Summary of the Invention

[0005] Therefore, it is necessary to provide a method and apparatus for photocatalytic allyl arylization reaction to address the above problems. This application realizes a high-efficiency, low-cost and easily industrialized photocatalytic allyl arylization reaction by constructing an efficient and stable catalytic system and coordinating it with a continuous flow reaction system.

[0006] A method for photocatalytic allyl arylization reaction includes the following steps:

[0007] Tetrabutylammonium decatungstate, 1,3-bis(diphenylphosphine)propane nickel chloride, phenanthroline and aryl bromide are mixed, and acetonitrile, chlorobenzene, allyl base and triethylamine are added under a protective atmosphere to form a reaction solution;

[0008] Under the action of external force, the reaction liquid continuously circulates through the light-illuminated area to carry out photocatalytic reaction, and the temperature of the reaction liquid remains constant during the circulation process.

[0009] In one embodiment, the reaction solution continuously circulates through the illuminated area at a flow rate of 0.1 mL / min to 10 mL / min.

[0010] In one embodiment, the effective residence time of the reaction solution in the light-illuminated area is 10 min to 30 min.

[0011] In one embodiment, the amount of raw material used satisfies at least one of the following conditions:

[0012] (1) The amount of the tetrabutylammonium decatungstate is 1 mol% to 5 mol% of the molar amount of the aryl bromide.

[0013] (2) The amount of 1,3-bis(diphenylphosphine)propane nickel chloride used is 8 mol% to 20 mol% of the molar amount of the aryl bromide.

[0014] (3) The amount of phenanthroline used is 10 mol% to 25 mol% of the molar amount of the aryl bromide.

[0015] (4) The molar ratio of the allyl substrate to the aryl bromide is (2~10):1;

[0016] (5) The volume ratio of the acetonitrile to the chlorobenzene is (1~5):1;

[0017] (6) The molar ratio of the triethylamine to the aryl bromide is (1~2):1;

[0018] (7) The molar concentration of the aryl bromide in the mixed solvent of acetonitrile and chlorobenzene is 0.05 mol / L to 0.1 mol / L.

[0019] In one embodiment, the aryl bromide includes 2,6-dimethyl-4-bromopyridine, methyl 4-bromobenzoate, 4-bromobenzyl sulfone, p-bromophenyltrimethylsilane, 9-(4-bromophenyl)carbazole, m-bromobenzonitrile, 4-bromo-2-methylbenzonitrile, 5-bromophthalide, 4-bromo-N-methylphthalimide, 4-bromo-2-trifluoromethylpyridine, and 5-bromo-2-trifluoromethylpyrimidine. , , At least one of them.

[0020] In one embodiment, the allyl substrate includes at least one of cyclohexene, cyclooctene, cyclododecene, α-pinene, β-pinene, and 3,6-dihydropyran.

[0021] In one embodiment, the temperature of the reaction solution is 40°C to 60°C.

[0022] In one embodiment, the light source used in the illumination area has a wavelength of 365nm~400nm and a power of 100W~500W.

[0023] An apparatus for realizing the photocatalytic allyl arylation reaction as described above, the apparatus comprising a reaction mixture mixing component, a peristaltic pump, and a photoreaction module;

[0024] The reaction liquid mixing component includes a storage tank, a heater, and a stirrer, wherein the storage tank includes a protective gas inlet, a reaction liquid outlet, and a reaction liquid inlet;

[0025] One end of the peristaltic pump is connected to the reaction liquid outlet of the storage tank via a pipeline, and the other end is connected to the photoreaction module via a pipeline;

[0026] The photoreaction module includes a light source, a photoreaction coil, and a temperature control component. One end of the photoreaction coil is connected to a peristaltic pump via a pipeline, and the other end is connected to the reaction liquid inlet of the storage tank via a pipeline.

[0027] Powered by the peristaltic pump, the reaction liquid flows from the reservoir of the reaction liquid mixing component through the peristaltic pump and the photoreaction coil of the photoreaction module, and then returns to the reservoir of the reaction liquid mixing component for continuous circulation.

[0028] In one embodiment, the photoreactive discs are distributed along a plane and located on one side of the light source;

[0029] Alternatively, the photoreactive coils are distributed around the light source.

[0030] The method described in this application uses tetrabutylammonium decatungstate as a photocatalyst, 1,3-bis(diphenylphosphine)propane nickel chloride as a nickel catalyst, phenanthroline as a specific ligand, and triethylamine as a base to construct a "photo-HAT-nickel" ternary synergistic catalytic system, optimizing the conversion rate and selectivity of the photocatalytic reaction and reducing catalyst costs. Simultaneously, the introduction of a continuous flow circulating reaction system not only achieves excellent mass and heat transfer performance and process controllability but also ensures uniform and efficient utilization of light energy, enabling the method to achieve seamless scale-up from milligram to gram and even hundred-gram scales, and exhibiting excellent process robustness and reliability during scale-up. Furthermore, the method described in this application can directly activate C(sp)-containing... 3 Allyl base compounds with )-H bonds do not require prefunctionalization and have excellent functional group compatibility and broad applicability, providing an efficient and practical synthetic route for constructing libraries of structurally diverse allyl aryl compounds.

[0031] Therefore, the method described in this application solves the core problems of low reaction efficiency, poor selectivity, high cost and difficulty in scale-up production in traditional technologies, and provides an economical, efficient and highly selective synthesis process for the industrial production of photocatalytic allyl arylization reaction. Attached Figure Description

[0032] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0033] Figure 1 This is a schematic diagram of the device structure in one embodiment of this application;

[0034] Figure 2 This is a schematic diagram of the structure of the photoreactive coil in one embodiment of this application;

[0035] Figure 3 This is a schematic diagram of the structure of the photoreacting coil and the light source in another embodiment of this application.

[0036] Reference numerals: 10, reaction liquid mixing component; 20, peristaltic pump; 30, photoreaction module; 301, light source; 302, photoreaction coil. Detailed Implementation

[0037] To facilitate understanding of this application, it will be described in more detail below. However, it should be understood that this application can be implemented in many different forms and is not limited to the embodiments or examples described herein. Rather, these embodiments or examples are provided to provide a more thorough and complete understanding of the disclosure of this application.

[0038] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments or implementations only and is not intended to be limiting of the application. In this application, when numerical ranges are mentioned, unless otherwise specified, such ranges are considered continuous and include the minimum and maximum values ​​of the range, as well as every value between such minimum and maximum values. Further, when a range refers to an integer, it includes every integer between the minimum and maximum values ​​of the range. Furthermore, when multiple ranges are provided to describe a feature or characteristic, the ranges may be combined. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges to which they are included.

[0039] This application provides a method for photocatalytic allyl arylization reaction, comprising the following steps:

[0040] Tetrabutylammonium decatungstate, 1,3-bis(diphenylphosphine)propane nickel chloride, phenanthroline and aryl bromide are mixed, and acetonitrile, chlorobenzene, allyl base and triethylamine are added under a protective atmosphere to form a reaction solution;

[0041] Under the action of external force, the reaction liquid continuously circulates through the light-illuminated area to carry out photocatalytic reaction, and the temperature of the reaction liquid remains constant during the circulation process.

[0042] Through extensive experimentation, the applicant systematically screened various photocatalysts, including noble metal complexes such as tris(2-phenylpyridine)iridium (Ir(ppy)3), Eosin Y organic dyes, and tetrabutylammonium decatungstate (TBADT) and sodium decatungstate (NaDT). The study found that TBADT, as an inexpensive and readily available inorganic metal oxometalate, possesses excellent chemical stability and economic viability, making it a potential candidate for industrial application. Crucially, TBADT exhibits extremely strong oxidizing power under photoexcitation, efficiently abstracting hydrogen atoms from the substrate to generate the critical allyl radical, thereby precisely initiating and driving the entire nickel catalytic cycle. This unique function makes it an ideal bridge connecting the photocatalytic and nickel catalytic cycles.

[0043] In one embodiment of this application, the amount of TBADT photocatalyst is preferably 1 mol% to 5 mol% of the aryl bromide molar. By adjusting the amount of TBADT photocatalyst, its efficient initiation of the reaction can be ensured, while maintaining the cost-effectiveness of the entire catalytic system.

[0044] This application systematically screened various nickel catalysts, including 2,2'-bipyridine nickel bromide (NiBr2·bpy), bis(triphenylphosphine) nickel chloride (NiCl2·(PPh3)2), and 1,3-bis(diphenylphosphine)propane nickel chloride (NiCl2·dppp). It was found that 1,3-bis(diphenylphosphine)propane nickel chloride, as a neutral nickel(II) precursor, possesses a suitable redox potential in the photocatalytic system and readily undergoes single-electron transfer with the photocatalyst to generate active Ni(I) species. Simultaneously, its diphenylphosphine ligand (dppp) is a bidentate ligand, capable of forming a stable chelate with the nickel center, effectively regulating the catalyst's coordination environment and electron cloud density, thus playing a crucial role in subsequent allyl CH activation and enantioselectivity control.

[0045] In one embodiment of this application, the amount of 1,3-bis(diphenylphosphine)propane nickel chloride is preferably 8 mol% to 20 mol% of the molar amount of the aryl bromide. By adjusting the amount of 1,3-bis(diphenylphosphine)propane nickel chloride, not only can sufficient catalytic activity be ensured, but also economic efficiency can be taken into account.

[0046] After determining to use 1,3-bis(diphenylphosphine)propane nickel chloride as the nickel catalyst, the applicant investigated various bidentate nitrogen ligands, including 4,4'-di-tert-butyl-2,2'-bipyridine and 1,10-phenanthroline, and found that the use of sterically hindered phenanthroline ligands played a decisive role in improving the yield. This is because phenanthroline ligands can form a crowded steric environment around the nickel center, creating a unique steric hindrance effect. This steric hindrance effect can precisely control the approach and orientation of the allyl substrate to the nickel catalyst, thereby significantly improving the regioselectivity and correlative selectivity of the reaction.

[0047] In one embodiment of this application, the amount of phenanthroline is preferably 10 mol% to 25 mol% of the molar amount of the aryl bromide. More preferably, the amount of phenanthroline is slightly higher than the amount of 1,3-bis(diphenylphosphine)propane nickel chloride. By adjusting the amount of phenanthroline, it is beneficial to ensure that the nickel catalyst is fully coordinated and forms a highly active catalytic species.

[0048] In one embodiment of this application, the aryl brominated compounds include 2,6-dimethyl-4-bromopyridine, methyl 4-bromobenzoate, 4-bromobenzyl sulfone, p-bromophenyltrimethylsilane, 9-(4-bromophenyl)carbazole, m-bromobenzonitrile, 4-bromo-2-methylbenzonitrile, 5-bromophthalide, 4-bromo-N-methylphthalimide, 4-bromo-2-trifluoromethylpyridine, and 5-bromo-2-trifluoromethylpyrimidine. , , At least one of them.

[0049] The method described in this application has excellent compatibility with functional groups and can tolerate a variety of sensitive groups such as ester groups and ether bonds. It can provide a powerful and practical tool for the later modification and structural transformation of complex drug molecules and has extremely high potential application value.

[0050] It is understood that this application does not restrict the mixing method of tetrabutylammonium decatungstate, 1,3-bis(diphenylphosphine)propane nickel chloride, phenanthroline, and aryl bromides, and conventional mixing processes, such as stirring, can be used. This application does not restrict the order in which tetrabutylammonium decatungstate, 1,3-bis(diphenylphosphine)propane nickel chloride, phenanthroline, and aryl bromides are added, and they can be added sequentially or simultaneously.

[0051] Before adding acetonitrile, chlorobenzene, allyl base material and triethylamine, air and moisture in the system can be removed by using a protective atmosphere. It is understood that the protective atmosphere includes, but is not limited to, nitrogen.

[0052] In one embodiment of this application, the molar ratio of the allyl substrate to the aryl bromide is preferably (2~10):1, including but not limited to any one of 2:1, 4:1, 5:1, 6:1, 8:1, 10:1 or any range between the two. By adjusting the amount of aryl bromide and allyl substrate, it is more beneficial to control the full reaction of the raw materials and reduce costs.

[0053] Triethylamine plays multiple roles in the reaction system of this application. On the one hand, as a base, it can neutralize protons that may be generated during the reaction, maintain the alkaline environment of the reaction system, and promote the catalytic cycle. On the other hand, it can also act as a sacrificial reducing agent to assist the photocatalyst in completing its catalytic cycle.

[0054] In one embodiment of this application, the molar ratio of triethylamine to the aryl bromide is (1~2):1. By adjusting the amount of triethylamine, the catalytic efficiency can be further improved.

[0055] In traditional batch photocatalytic reactions, acetonitrile is the preferred solvent. However, this application considers the poor solubility of sterically hindered phenanthroline ligands in acetonitrile, which could lead to precipitation and blockage of the reaction solution during pumping and flow through microchannels, thus affecting the stable and continuous flow of the reaction solution. Therefore, this application redesigned the solvent system. By screening various benzene-based solvents as co-solvents, chlorobenzene was found to effectively dissolve phenanthroline ligands. More importantly, experiments verified that the addition of chlorobenzene to acetonitrile did not negatively affect the yield and selectivity of the reaction.

[0056] In one embodiment of this application, the volume ratio of acetonitrile to chlorobenzene is preferably (1~5):1, including but not limited to any one of 1:1, 2:1, 3:1, 4:1, 5:1 or any range between the two. By adjusting the amount of acetonitrile and chlorobenzene, it is not only beneficial to retain the good solubility of acetonitrile for each component of the reaction, but also to fully solve the solubility problem of phenanthroline ligands, thereby ensuring the smooth progress of the continuous flow reaction.

[0057] In one embodiment of this application, the molar concentration of the aryl bromide in the mixed solvent of acetonitrile and chlorobenzene is 0.05 mol / L to 0.1 mol / L, including but not limited to any one of 0.05 mol / L, 0.06 mol / L, 0.07 mol / L, 0.08 mol / L, 0.09 mol / L, 0.1 mol / L, or any range between two of these values. By adjusting the molar concentration of the allyl base in the mixed solvent of acetonitrile and chlorobenzene, it is beneficial to further improve the reaction efficiency.

[0058] In one embodiment of this application, the allyl substrate includes, but is not limited to, at least one of cyclohexene, cyclooctene, cyclododecene, α-pinene, β-pinene, and 3,6-dihydropyran.

[0059] The method described in this application uses tetrabutylammonium decatungstate as a photocatalyst, 1,3-bis(diphenylphosphine)propane nickel chloride as a nickel catalyst, phenanthroline as a specific ligand, and triethylamine as a base to construct a "photo-HAT-nickel" ternary synergistic catalytic system. This combines visible light catalysis, hydrogen atom transfer strategies, and inexpensive, abundant nickel metal catalysts for the application of allyl C(sp...) 3 The )-H arylation reaction utilizes the unique redox properties of nickel and the efficient free radical capture ability of low-valence species to achieve precise control of regioselectivity, while significantly reducing catalyst costs.

[0060] Meanwhile, the introduction of a continuous flow circulating reaction system, which deeply integrates the "photo-HAT-nickel" ternary synergistic catalytic system with the continuous flow circulating reaction system, not only achieves excellent mass and heat transfer performance and process controllability, but also ensures uniform and efficient utilization of light energy. This enables the method to be seamlessly scaled up from milligram to gram or even hundred-gram scales, and exhibits excellent process robustness and reliability during the scale-up process.

[0061] Furthermore, the method described in this application can directly activate C(sp)-containing compounds. 3 Allyl base compounds with )-H bonds do not require prefunctionalization and have excellent functional group compatibility and broad applicability, providing an efficient and practical synthetic route for constructing libraries of structurally diverse allyl aryl compounds.

[0062] In one embodiment of this application, the reaction liquid is preheated before passing through the light-irradiated area. The preheating temperature is preferably 40°C to 60°C. It is understood that this application does not limit the preheating method and conventional methods can be used, such as constant temperature water bath heating.

[0063] In one embodiment of this application, the flow rate of the reaction solution continuously circulating through the light-illuminated area is preferably 0.1 mL / min to 10 mL / min, including but not limited to any one of 0.1 mL / min, 0.5 mL / min, 1 mL / min, 5 mL / min, 10 mL / min or any range between two of them.

[0064] Further optimization is achieved when the molar amount of aryl bromide is 1 mmol to 10 mmol, and the flow rate of the reaction solution continuously circulating through the light-illuminated area is 0.1 mL / min to 5 mL / min.

[0065] In one embodiment of this application, the effective residence time of the reaction solution in the light-illuminated area is preferably 10 min to 30 min. More preferably, when the reaction solution is 10 mL to 150 mL, the effective residence time of the reaction solution in the light-illuminated area is 12 min to 18 min.

[0066] By precisely controlling the flow rate and effective residence time, it is beneficial to avoid uneven reaction yields during scale-up reactions, thereby obtaining the target product with stable high yield and high selectivity, providing a reliable method for the industrial production of photocatalytic allyl arylization reaction.

[0067] It should be noted that the effective residence time can be calculated based on the flow rate and reactor volume.

[0068] In one embodiment of this application, the temperature of the reaction solution is preferably maintained at 40°C to 60°C, which helps to avoid problems such as uneven reaction yield caused by temperature difference.

[0069] In one embodiment of this application, the wavelength of the light source used in the illumination area is preferably 365nm~400nm, and the power is 100W~500W.

[0070] Therefore, the method described in this application solves the core problems of low reaction efficiency, poor selectivity, high cost and difficulty in scale-up production in traditional technologies, and provides an economical, efficient and highly selective synthesis process for the industrial production of photocatalytic allyl arylization reaction.

[0071] This application also provides an apparatus for realizing the photocatalytic allyl arylation reaction as described above, combined with... Figure 1 As shown, the device includes a reaction liquid mixing component 10, a peristaltic pump 20, and a photoreaction module 30.

[0072] Specifically, the reaction liquid mixing component 10 includes a storage tank, a heater, and a stirrer. The storage tank includes a protective gas inlet, a reaction liquid outlet, and a reaction liquid inlet. The protective gas inlet allows for vacuuming and protective gas replacement to remove air and moisture from the storage tank. Before the reaction begins, the reaction liquid inlet is used to add raw materials. After the reaction begins, the reaction liquid inlet is used for the circulation of the reaction liquid into the storage tank.

[0073] Preferably, the storage container can be a reaction vessel such as a three-necked flask; the heater can be a constant temperature water bath heater; and the stirrer can be a magnetic stirrer.

[0074] It should be noted that the reaction liquid outlet can be fitted with a pipette, and one end of the pipette must be below the surface of the reaction liquid to ensure that the reaction liquid can be drawn out.

[0075] One end of the peristaltic pump 20 is connected to the reaction liquid outlet of the storage tank through a pipeline, which allows the reaction liquid to be drawn out of the storage tank under the action of external force. The other end is connected to the photoreaction module 30 through a pipeline, that is, the reaction liquid enters the photoreaction module 30 through the peristaltic pump.

[0076] The photoreaction module 30 includes a light source 301, a photoreaction coil 302, and a temperature control component. One end of the photoreaction coil 302 is connected to the peristaltic pump 20 via a pipeline, and the other end is connected to the reaction liquid inlet of the storage container via a pipeline. Powered by the peristaltic pump 20, the reaction liquid flows from the storage container of the reaction liquid mixing component 10, sequentially through the peristaltic pump 20 and the photoreaction coil 302 of the photoreaction module 30, and then returns to the storage container of the reaction liquid mixing component 10 for continuous circulation. Figure 1 As shown.

[0077] In one embodiment of this application, the photoreaction coil 302 is distributed along a plane and located on one side of the light source 301. That is, the light emitted by the light source 301 is received by the planar photoreaction coil 302. This two-dimensional planar photoreaction coil 302 structure is suitable for conventional small-volume photocatalytic reaction systems, especially for photocatalytic reaction systems with less than 2 mmol of aryl bromide (reaction liquid volume less than 20 mL).

[0078] Specifically, such as Figure 2 As shown, the photoreaction coil 302 can be coiled and distributed along the plane. This application does not limit the shape of the coil, including but not limited to square, circular or irregular shapes.

[0079] In one embodiment of this application, combined with Figure 3 As shown, the photoreaction coil 302 is distributed around the light source 301, which significantly improves light energy utilization and achieves uniform illumination, avoiding problems such as uneven reaction yield caused by temperature differences due to uneven illumination. This three-dimensional photoreaction coil 302 structure enables scale-up of the reaction and can operate stably in photocatalytic reaction systems with aryl bromide dosages higher than 5 mmol (reaction liquid volume higher than 50 mL).

[0080] It should be noted that this application does not limit the size of the photoreaction coil 302. When the interface of the photoreaction coil 302 is at the micrometer level, it is beneficial to increase the specific surface area of ​​the reaction, allowing the reaction liquid to receive light in an extremely thin liquid layer, thereby improving the catalytic cycle efficiency. This application does not limit the material of the photoreaction coil 302. Fluorinated ethylene propylene copolymer tubes (FEP tubes) with excellent chemical inertness and light transmittance can be used. In some scenarios with higher requirements for chemical resistance, perfluoroalkoxy resin tubes or quartz tubes can also be selected. The light source 301 includes, but is not limited to, an LED lamp bead array.

[0081] The temperature control component includes a cooling element, which counteracts the heat released by the light source, preventing the temperature of the reaction liquid from continuously rising in the photoreaction module 30.

[0082] In one embodiment of this application, the photoreaction module 30 can also be externally connected to a temperature control component and a light power control component, which can further precisely control the reaction temperature and power.

[0083] The method and apparatus for the photocatalytic allyl arylation reaction will be further described below through specific embodiments. However, those skilled in the art will understand that the following embodiments are for illustrative purposes only and should not be considered as limiting the scope of this application. Unless otherwise specified, specific conditions in the embodiments are performed under conventional conditions or conditions recommended by the manufacturer. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0084] Example 1

[0085] In a 25 mL oval flask that has been oven-dried and cooled, the photocatalyst tetrabutylammonium decatungstate (0.02 mmol), 1,3-bis(diphenylphosphine)propane nickel chloride (0.10 mmol), phenanthroline (0.13 mmol), and 2,6-dimethyl-4-bromopyridine (1 mmol) were added sequentially. The flask was sealed with a rubber stopper, and the reaction flask was subjected to three cycles of evacuation and nitrogen purging to completely remove air and moisture from the system. Subsequently, under a nitrogen atmosphere, 10 mL of acetonitrile, 2 mL of chlorobenzene, cyclohexene (5 mmol), and 0.15 mL (1 mmol) of triethylamine were added sequentially using a syringe. The reaction mixture was ultrasonically treated for 15 minutes until a homogeneous and transparent solution (12 mL) was formed.

[0086] Preheat the flask in a 50°C constant-temperature water bath. Start the peristaltic pump to pump the preheated reaction solution at 20 rpm (approximately 0.21 mL / min) into a continuous-flow photochemical reaction module made of FEP tubing with an inner diameter of 0.8 mm (total reaction volume of 3.15 mL). The reaction module is precisely temperature-controlled at 50°C by an externally integrated semiconductor cooler and illuminated by an array of LED beads (center wavelength 365 nm, total power 400 W) surrounding it. Based on the flow rate and reactor volume, the effective residence time of the reaction solution in the reactor is calculated to be 15 minutes. The reaction continues until all the reaction solution has flowed through the photochemical reaction module, at which point all the effluent is collected.

[0087] The collected effluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (v / v 10:1) as eluent, finally yielding the target product 4-(cyclohexyl-2-en-1-yl)-2,6-dimethylpyridine, a colorless liquid weighing 166.4 mg, with a separation yield of 89%. The product was further purified by 1H NMR spectroscopy (NMR spectroscopy). 1 H NMR and carbon spectroscopy (H NMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0088] 1HNMR (600MHz, CDCl3) δ6.78 (s, 2H), 5.91–5.88 (m, 1H), 5.62 (t, J=7.8Hz, 1H), 3.28–3.27 (m, 1H), 2.47 ( s, 6H), 2.08-2.06 (m, 2H), 1.98–1.94 (m, 1H), 1.73–1.68 (m, 1H), 1.62–1.57 (m, 1H), 1.53–1.48 (m, 1H).

[0089] 13 CNMR (150MHz, CDCl3) δ157.6, 156.0, 129.3, 128.7, 119.7, 41.2, 31.8, 25.0, 24.5, 21.1.

[0090] HRMS(ESI): calcd for C 13 H 18 N + (M+H + ):188.1434, found:188.1436.

[0091] Example 2

[0092] The same method as in Example 1 was used, except that the amount of each raw material was increased by 10 times, the volume of the reaction liquid was 120 mL, the flow rate of the peristaltic pump was set to 2.1 mL / min, and the residence time was maintained at 15 minutes.

[0093] After the reaction, post-processing yielded 1.59 g of the target product, with a separation yield of 85% and a regioselectivity of 18:1. This example demonstrates that the proposed method has good linear scale-up capability.

[0094] Example 3

[0095] The same method as in Example 1 was used, except that an equimolar amount of methyl 4-bromobenzoate (215 mg, 1 mmol) was used instead of 2,6-dimethyl-4-bromopyridine.

[0096] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (100:1 v / v) as eluent to finally obtain the target product. It is a colorless liquid, weighing 177 mg, with a separation yield of 82%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 HNMR and carbon spectroscopy (HNMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0097] 1 HNMR (600MHz, CDCl3) δ7.96 (d, J=8.3Hz, 2H), 7.28 (d, J=8.3Hz, 2H), 5.94-5.91 (m, 1H), 5.69 (dd, J=10.1, 2.5Hz, 1H), 3.90 (s, 3H), 3.48-3.44(m, 1H), 2.10-2.09(m, 2H), 2.04–2.00(m, 1H), 1.76–1.71(m, 1H), 1.67–1.62(m, 1H), 1.57-1.52(m, 1H).

[0098] 13 CNMR (150MHz, CDCl3) δ167.3, 152.3, 129.8, 129.4, 129.2, 127.9, 52.1, 42.0, 32.5, 25.1, 21.2.

[0099] HRMS (ESI): calcd for C 14 H 17 O2 + (M+H + ):217.1223, found:217.1220.

[0100] Example 4

[0101] The same method as in Example 1 was used, except that an equimolar amount of 4-bromophenyl sulfone (235 mg, 1 mmol) was used instead of 2,6-dimethyl-4-bromopyridine.

[0102] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (2:1 v / v) as eluent to finally obtain the target product. It is a white solid, weighing 212 mg, with a separation yield of 90%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 HNMR and carbon spectroscopy (HNMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0103] 1HNMR (600MHz, CDCl3) δ7.84 (d, J=8.4Hz, 2H), 7.39 (d, J=8.4Hz, 2H), 5.95–5.93 (m, 1H), 5.65 (dd, J=10.0, 2.5Hz, 1H), 3.50 -3.46(m, 1H), 3.02(s, 3H), 2.10-2.06(m, 2H), 2.03–1.99(m, 1H), 1.72–1.68(m, 1H), 1.64-1.59(m, 1H), 1.54–1.48(m, 1H).

[0104] 13 CNMR (150MHz, CDCl3) δ153.3, 138.2, 129.7, 128.8, 128.6, 127.5, 44.6, 41.8, 32.4, 24.9, 20.9.

[0105] HRMS (ESI): calcd for C 13 H 17 SO2 + (M+H + ):237.0944, found:237.0945.

[0106] Example 5

[0107] The same method as in Example 1 was used, except that an equimolar amount of p-bromophenyltrimethylsilane (229 mg, 1 mmol) was used instead of 2,6-dimethyl-4-bromopyridine.

[0108] The collected effluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether as eluent to finally obtain the target product. It is a colorless liquid, weighing 136 mg, with a separation yield of 59%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 H NMR and carbon spectroscopy (H NMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0109] 1HNMR (600MHz, CDCl3) δ7.49 (d, J=8.0Hz, 2H), 7.24 (d, J=7.9Hz, 2H), 5.93-5.90 (m, 1H), 5.74 (dd, J=10.1, 2.4Hz, 1H), 3.43-3.40(m, 1H), 2.12-2.09(m, 2H), 2.05-2.03(m, 1H), 1.79-1.75(m, 1H), 1.66-1.57(m, 2H), 0.26(s, 9H).

[0110] 13 CNMR (150MHz, CDCl3) δ147.4, 137.7, 133.5, 130.2, 128.5, 127.4, 42.0, 32.6, 25.2, 21.4, 0.9.

[0111] HRMS (ESI): calcd for C 15 H 23 Si + (M+H + ):231.1564, found:231.1564.

[0112] Example 6

[0113] The same method as in Example 1 was used, except that an equimolar amount of 9-(4-bromophenyl)carbazole (322 mg, 1 mmol) was used instead of 2,6-dimethyl-4-bromopyridine.

[0114] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (100:1 v / v) as eluent to finally obtain the target product. It is a white solid, weighing 167 mg, with a separation yield of 52%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 H NMR and carbon spectroscopy (H NMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0115] 1HNMR (600MHz, CDCl3) δ8.15 (d, J=7.7Hz, 2H), 7.50–7.41 (m, 8H), 7.30–7.27 (m, 2H), 5.99–5.96 (m, 1H), 5.82 ( dd, J=10.0, 2.6Hz, 1H), 3.57–3.54 (m, 1H), 2.16–2.11 (m, 3H), 1.85–1.82 (d, J=4.8Hz, 1H), 1.71–1.67 (m, 2H).

[0116] 13 CNMR (150MHz, CDCl3) δ146.1, 141.2, 135.6, 129.9, 129.3, 129.0, 127.1, 126.0, 123.4, 120.4, 119.9, 110.0, 41.7, 32.7, 29.9, 25.2, 21.3.

[0117] HRMS (ESI): calcd for C 24 H 22 N + (M+H + ):324.1727, found:324.1730.

[0118] Example 7

[0119] The same method as in Example 1 was used, except that an equimolar amount of m-bromobenzonitrile (182 mg, 1 mmol) was used instead of 2,6-dimethyl-4-bromopyridine.

[0120] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (20:1 v / v) as eluent to finally obtain the target product. It is a colorless liquid, weighing 149 mg, with a separation yield of 82%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 H NMR and carbon spectroscopy (H NMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0121] 1HNMR (600MHz, CDCl3) δ7.51–7.49 (m, 2H), 7.46–7.45 (m, 1H), 7.40–7.38 (m, 1H), 5.98–5.95 (m, 1H), 5.65 (dd, J=10.1, 2.5H z, 1H), 3.46–3.42 (m, 1H), 2.11–2.09 (m, 2H), 2.05–2.00 (m, 1H), 1.73–1.68 (m, 1H), 1.66–1.60 (m, 1H), 1.54–1.49 (m, 1H).

[0122] 13 CNMR (150MHz, CDCl3) δ148.15, 132.58, 131.59, 129.93, 129.90, 129.19, 128.62, 119.30, 112.38, 41.50, 32.52, 25.00, 20.86.

[0123] HRMS (ESI): calcd for C 13 H 14 N + (M+H + ):184.1121, found:184.1119.

[0124] Example 8

[0125] The same method as in Example 1 was used, except that an equimolar amount of 4-bromo-2-methylbenzonitrile (196 mg, 1 mmol) was used instead of 2,6-dimethyl-4-bromopyridine.

[0126] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (20:1 v / v) as eluent to finally obtain the target product. It is a colorless liquid, weighing 142 mg, with a separation yield of 72%. The sample was analyzed by 1H NMR spectroscopy (NMR spectroscopy). 1 H NMR and carbon spectroscopy (H NMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0127] 1HNMR (600MHz, CDCl3) δ7.51 (d, J=8.0Hz, 1H), 7.15 (s, 1H), 7.11 (d, J=8.2Hz, 1H), 5.95–5.92 (m, 1H), 5.64 (dd, J=10.0, 2.5Hz, 1H) , 3.42–3.39(m, 1H), 2.52(s, 3H), 2.10–2.08(m, 2H), 2.02–1.98(m, 1H), 1.74–1.69(m, 1H), 1.64–1.59(m, 1H), 1.53–1.47(m, 1H).

[0128] 13 CNMR (150MHz, CDCl3) δ152.2, 142.0, 132.6, 129.7, 129.5, 128.7, 125.9, 118.5, 110.3, 42.0, 32.3, 25.0, 21.1, 20.6.

[0129] HRMS (ESI): calcd for C 14 H 16 N + (M+H + ):198.1277, found:198.1278.

[0130] Example 9

[0131] The same method as in Example 1 was used, except that an equimolar amount of 5-bromophthalide (213 mg, 1 mmol) was used instead of 2,6-dimethyl-4-bromopyridine.

[0132] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (20:1 v / v) as eluent to finally obtain the target product. It is a colorless liquid, weighing 143 mg, with a separation yield of 67%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 HNMR and carbon spectroscopy (HNMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0133] 1HNMR (600MHz, CDCl3) δ7.83 (d, J=7.9Hz, 1H), 7.38 (d, J=7.4Hz, 1H), 7.33 (s, 1H), 5.97–5.95 (m, 1H), 5.69 (dd, J=10.1, 2.5Hz, 1H) , 5.28(s, 2H), 3.55–3.53(m, 1H), 2.11–2.10(m, 2H), 2.07–2.04(m, 1H), 1.74–1.72(m, 1H), 1.67–1.63(m, 1H), 1.57–1.52(m, 1H).

[0134] 13 CNMR (150MHz, CDCl3) δ171.2, 154.0, 147.1, 129.6, 129.1, 128.7, 125.6, 123.7, 121.1, 69.6, 42.2, 32.6, 24.9, 20.9.

[0135] HRMS (ESI): calcd for C 14 H 15 O2 + (M+H + ):215.1067, found:215.1065.

[0136] Example 10

[0137] The same method as in Example 1 was used, except that an equimolar amount of 4-bromo-N-methylphthalimide (240 mg, 1 mmol) was used instead of 2,6-dimethyl-4-bromopyridine.

[0138] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (20:1 v / v) as eluent to finally obtain the target product. It is a white solid, weighing 198 mg, with a separation yield of 82%. It was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy. 1 HNMR and carbon spectroscopy (HNMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0139] 1HNMR (600MHz, CDCl3) δ7.71 (d, J=7.7Hz, 1H), 7.67 (s, 1H), 7.51 (d, J=7.6Hz, 1H), 5.97–5.93 (m, 1H), 5.65 (dd, J=10.0, 2.5Hz, 1H) , 3.53–3.50(m, 1H), 3.13(s, 3H), 2.10–2.07(m, 2H), 2.04–2.00(m, 1H), 1.72–1.67(m, 1H), 1.63–1.60(m, 1H), 1.54–1.49(m, 1H).

[0140] 13 CNMR (150MHz, CDCl3) δ168.8, 168.6, 154.1, 133.4, 132.7, 130.2, 130.0, 128.4, 123.2, 122.6, 42.1, 32.5, 24.9, 23.9, 20.9.

[0141] HRMS (ESI): calcd for C 15 H 16 NO2 + (M+H + ):242.1176, found:242.1178.

[0142] Example 11

[0143] The same method as in Example 1 was used, except that an equimolar amount of 4-bromo-2-trifluoromethylpyridine (226 mg, 1 mmol) was used instead of 2,6-dimethyl-4-bromopyridine.

[0144] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (100:1 v / v) as eluent to finally obtain the target product. It is a colorless liquid, weighing 179 mg, with a separation yield of 79%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 H NMR and carbon spectroscopy (H NMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0145] 1HNMR (600MHz, CDCl3) δ8.58 (d, J=2.1Hz, 1H), 7.69 (dd, J=8.1, 2.2Hz, 1H), 7.60 (d, J=8.0Hz, 1H), 6.00–5.97 (m, 1H), 5.65 (dd, J=10 .1, 2.6Hz, 1H), 3.53–3.51(m, 1H), 2.12–2.10(m, 2H), 2.08–2.03(m, 1H), 1.73–1.70(m, 1H), 1.67–1.63(m, 1H), 1.56–1.52(m, 1H).

[0146] 13 CNMR (150MHz, CDCl3) δ150.0, δ146.2 (q, J=34.5Hz), 145.3, 136.4, 130.4, 127.8, 121.9 (d, J=273.7Hz), δ120.2 (q, J=2.7Hz), 39.3, 32.3, 24.9, 20.8.

[0147] HRMS (ESI): calcd for C 12 H 13 F3N + (M+H + ):228.0995, found:228.0994.

[0148] Example 12

[0149] The same method as in Example 1 was used, except that an equimolar amount of 5-bromo-2-trifluoromethylpyrimidine (227 mg, 1 mmol) was used instead of 2,6-dimethyl-4-bromopyridine.

[0150] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (100:1 v / v) as eluent to finally obtain the target product. It is a colorless liquid, weighing 171 mg, with a separation yield of 75%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 HNMR and carbon spectroscopy (HNMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0151] 1HNMR (600MHz, CDCl3) δ8.72 (s, 2H), 6.05–6.01 (m, 1H), 5.63 (dd, J=10.0, 2.6Hz, 1H), 3.54–3.51(m, 1H), 2.13–2.06(m, 3H), 1.71–1.64(m, 2H), 1.56–1.53(m, 1H).

[0152] 13 CNMR (150MHz, CDCl3) δ157.4, δ155.0 (q, J=36.7Hz), 141.6, 131.4, 126.2, 119.8 (q, J=275.1Hz), 37.1, 31.9, 24.7, 20.4.

[0153] HRMS (ESI): calcd for C 11 H 12 F3N2 + (M+H + ):229.0947 found:229.0944.

[0154] Example 13

[0155] The same method as in Example 1 was used, except that an equimolar amount of cyclooctene (382 µL, 2 mmol, 2.0 equiv) was used instead of cyclohexene.

[0156] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (10:1 v / v) as eluent to finally obtain the target product. It is a colorless liquid, weighing 135 mg, with a separation yield of 63%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 H NMR and carbon spectroscopy (H NMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was 9:1.

[0157] 1 HNMR (600MHz, CDCl3) δ6.87 (s, 2H), 5.77–5.73 (m, 1H), 5.52 (t, J=9.7Hz, 1H), 3.68-3.64 (m, 1H), 2.50 (s, 6H), 2. 34–2.30 (m, 1H), 2.16–2.13 (m, 1H), 1.82–1.80 (m, 1H), 1.76–1.73 (m, 2H), 1.64–1.62 (m, 4H), 0.89–0.86 (m, 1H).

[0158] 13 CNMR (150MHz, CDCl3) δ157.6, 156.3, 132.5, 130.3, 119.6, 41.8, 36.8, 29.8, 29.6, 26.8, 26.7, 26.0, 24.4.

[0159] HRMS (ESI): calcd for C 15 H 22 N + (M+H + ):216.1747 found:216.1748.

[0160] Example 14

[0161] The same method as in Example 1 was used, except that an equimolar amount of cyclododecene (260 µL, 2 mmol, 2.0 equiv) was used instead of cyclohexene.

[0162] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (10:1 v / v) as eluent to finally obtain the target product. It is a colorless liquid, weighing 222 mg, with a separation yield of 82%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 HNMR and carbon spectroscopy (HNMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was 12:1.

[0163] 1 HNMR (600MHz, CDCl3) δ6.79 (s, 2H), 5.55-5.50 (m, 1H), 5.43 (dd, J=15.5, 9.7Hz, 1H), 3.13–3.09 (m, 1H), 2.57 (s, 1H), 2.47 (s, 6H), 2 .22-2.18(m, 1H), 1.96-1.92(m, 1H), 1.75-1.70(m, 1H), 1.60-1.56(m, 3H), 1.52-1.48(m, 3H), 1.44-1.40(m, 2H), 1.36-1.27(m, 6H).

[0164] 13CNMR (150MHz, CDCl3) δ157.7, 155.8, 133.0, 132.3, 119.1, 49.0, 34.1, 32.4, 26.3, 26.1, 25.4, 24.9, 24.8, 24.53, 24.50.

[0165] HRMS (ESI): calcd for C 19 H 30 N + (M+H + ):272.2373. found:272.2377.

[0166] Example 15

[0167] The same method as in Example 1 was used, except that an equimolar amount of α-pinene (317 µL, 2 mmol, 2.0 equiv) was used instead of cyclohexene.

[0168] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (10:1 v / v) as eluent to finally obtain the target product. It is a colorless liquid, weighing 177 mg, with a separation yield of 73%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 HNMR and carbon spectroscopy (HNMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was 6:1.

[0169] 1 HNMR (600MHz, CDCl3) δ6.80and6.78(sands, 0.85and0.15H), 6.76and6.74(sands, 0.15and0.85H), 5.72and5.26(dandd, J=21.1Hz, 0.15and0.85H), 3.2 0–3.11(m, 1H), 2.47–2.46(m, 6H), 2.32–2.26(m, 1H), 2.10–2.02(m, 1H), 1. 77 (s, 1H), 1.31 (s, 1H), 1.24 (s, 3H), 1.19 (s, 3H), 0.97 (s, 1H), 0.74 (s, 2H).

[0170] 13CNMR (150MHz, CDCl3) δ157.4, 157.3, 149.3, 147.1, 145.9, 121.3, 120.7, 120.5, 118.9, 116.9, 47.7, 47.0, 45.6, 44.9, 42.8, 42.0, 40.7, 38.0, 31.9, 31.5, 29.8, 26.5, 26.3, 24.5, 24.4, 23.3, 21.1, 20.7.

[0171] HRMS (ESI): calcd for C 17 H 24 N + (M+H + ):242.1903. found:242.1905.

[0172] Example 16

[0173] The same method as in Example 1 was used, except that equimolar amounts of β-pinene (317 µL, 2 mmol, 2.0 equiv) were used instead of cyclohexene.

[0174] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (10:1 v / v) as eluent to finally obtain the target product. It is a colorless liquid, weighing 157 mg, with a separation yield of 65%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 HNMR and carbon spectroscopy (HNMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was 7:1.

[0175] 1 HNMR (600MHz, CDCl3) δ6.76 (s, 2H), 5.263–5.256 (m, 1H), 3.22–3.13 (m, 2H), 2.48 (s, 6H), 2.34–2.27 (m, 2H), 2.22-2.19 (m, 1H), 2.08-2.06 (m, 1H), 1.91 (t, J=5.4Hz, 1H), 1.20 (s, 3H), 1.13 (d, J=8.5Hz, 1H), 0.75 (s, 3H).

[0176] 13CNMR (150MHz, CDCl3) δ157.4, 149.4, 145.9, 121.4, 119.0, 45.6, 42.8, 40.7, 38.0, 31.9, 31.5, 29.8, 26.3, 24.3, 21.1.

[0177] HRMS (ESI): calcd for C 17 H 24 N + (M+H + ):242.1903. found:242.1903.

[0178] Example 17

[0179] The same method as in Example 1 was used, except that an equimolar amount of 3,6-dihydropyran (178 µL, 2 mmol, 2.0 equiv) was used instead of cyclohexene.

[0180] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (10:1 v / v) as eluent to finally obtain the target product. It is a colorless liquid, weighing 130 mg, with a separation yield of 69%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 H NMR and carbon spectroscopy (H NMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0181] 1 HNMR (600MHz, CDCl3) δ6.87 (s, 2H), 6.58 (dd, J=6.3, 1.8Hz, 1H), 4.70 (dd, J=6.3, 3.3Hz, 1H ), 4.01-3.95(m, 2H), 3.40-3.37(m, 1H), 2.51(s, 6H), 2.19-2.14(m, 1H), 1.84-1.79(m, 1H).

[0182] 13 CNMR (150MHz, CDCl3) δ157.7, 145.6, 119.8, 116.7, 102.2, 63.8, 35.7, 31.4, 24.4.

[0183] HRMS (ESI): calcd for C 12 H 16 NO + (M+H +):190.1226. found:190.1225.

[0184] Example 18

[0185] The same method as in Example 1 was used, except that equimolar amounts were used. (338 mg, 1 mmol) replaces 2,6-dimethyl-4-bromopyridine.

[0186] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (20:1 v / v) as eluent to finally obtain the target product. It is a white solid, weighing 245 mg, with a separation yield of 72%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 H NMR and carbon spectroscopy (H NMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0187] 1 HNMR (600MHz, CDCl3) δ7.98 (d, J=8.1Hz, 2H), 7.28 (d, J=8.2Hz, 2H), 5.94-5.91 (m, 1H), 5.69 (dd, J=10.1, 2.5Hz, 1H), 4.95-4.91 (m, 1H), 3.47-3.45 ( m, 1H), 2.13–2.09 (m, 2H), 2.03–1.95 (m, 2H), 1.74-1.72 (m, 4H), 1.57-1.5 3(m, 4H), 1.15–1.08(m, 3H), 0.92(t, J=6.9Hz, 6H), 0.79(d, J=6.9Hz, 3H).

[0188] 13 CNMR (150MHz, CDCl3) δ166.2, 152.0, 129.8, 129.4, 129.1, 128.4, 127.8, 74.7 , 47.4, 42.0, 41.1, 34.5, 32.5, 31.6, 26.6, 25.1, 23.8, 22.2, 21.2, 20.9, 16.7.

[0189] HRMS (ESI): calcd for C 23 H 33 O2 + (M+H + ):341.2475. found:341.2477.

[0190] Example 19

[0191] The same method as in Example 1 is used, except that... (113.6 mg, 0.2 mmol) replaced 2,6-dimethyl-4-bromopyridine (1 mmol), while the amount of other raw materials was reduced by 5 times.

[0192] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (4:1 v / v) as eluent to finally obtain the target product. It is a white solid, weighing 545 mg, with a separation yield of 48%. It was analyzed by proton nuclear magnetic resonance (NMR) spectroscopy. 1 H NMR and carbon spectroscopy (H NMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0193] 1 HNMR (600MHz, CDCl3) δ7.97 (d, J=7.9Hz, 2H), 7.26 (d, J=7.9Hz, 2H), 5.93–5.90 (m, 1H), 5.68 (d, J=10.2Hz, 1H ), 5.41(d, J=5.1Hz, 1H), 4.86-4.83(m, 1H), 3.45-3.43(m, 1H), 2.46-2.44(m, 2H), 2.09–2.08(m, 2H), 2.03-2 .00(m, 4H), 1.91-1.89(m, 1H), 1.86–1.82(m, 1H), 1.75-1.69(m, 2H), 1.59–1.48(m, 6H), 1.37–1.26(m, 6H), 1 .21–1.02(m, 7H), 1.06(s, 3H), 1.03–0.99(m, 3H), 0.92(d, J=6.5Hz, 3H), 0.87(d, J=4.1Hz, 6H), 0.69(s, 3H).

[0194] 13CNMR (150MHz, CDCl3) δ166.1, 152.0, 139.8, 129.8, 129.4, 129.1, 128.8, 127.8, 122.8, 74.5, 56.8, 56.3, 50.2, 42.4, 42.0, 39. 9, 39.7, 38.4, 37.2, 36.8, 36.3, 35.9, 32.5, 32.1, 32.0, 28.4, 28.1, 28.0, 25.1, 24.4, 24.0, 23.0, 22.7, 21.2, 19.5, 18.9, 12.0.

[0195] HRMS (ESI): calcd for C 40 H 59 O2 + (M+H + ):571.4510. found:571.4505.

[0196] Example 20

[0197] The same method as in Example 1 was used, except that equimolar amounts were used. (442 mg, 1 mmol) replaces 2,6-dimethyl-4-bromopyridine.

[0198] The collected eluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (100:1 v / v) as eluent to finally obtain the target product. It is a white solid, weighing 297 mg, with a separation yield of 67%. It was analyzed by proton nuclear magnetic resonance spectroscopy (NMR). 1 H NMR and carbon spectroscopy (H NMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0199] 1HNMR (600MHz, CDCl3) δ7.94(d, J=8.0Hz, 2H), 7.28(d, J=8.1Hz, 2H), 5.93-5.91(m, 2H), 5.6(d d, J=10.1, 2.6Hz, 1H), 5.48 (d, J=2.8Hz, 1H), 4.60 (d, J=3.7Hz, 1H), 4.36-4.32 (m, 2H), 4.09 (t , J=4.7Hz, 2H), 3.46-3.44(m, 1H), 2.09-2.07(m, 2H), 2.03–2.02-1.99(m, 1H), 1.73–1.70(m, 1 H), 1.65-1.60 (m, 1H), 1.54 (s, 3H), 1.51-1.49 (m, 1H), 1.40 (s, 3H), 1.30 (s, 3H), 1.26 (s, 3H).

[0200] 13 CNMR (150MHz, CDCl3) δ165.2, 152.9, 129.9, 129.2, 129.0, 128.0, 127.4, 112.3, 109.4, 105.2 , 83.5, 80.0, 76.5, 72.7, 67.2, 41.9, 32.4, 32.4, 26.9, 26.8, 26.2, 25.3, 25.0, 21.04, 21.02.

[0201] HRMS (ESI): calcd for C 25 H 33 O7 + (M+H + ):445.2221. found:445.2223.

[0202] Example 21

[0203] In a 25 mL oval flask that has been oven-dried and cooled, the photocatalyst tetrabutylammonium decatungstate (0.02 mmol), 1,3-bis(diphenylphosphine)propane nickel chloride (0.1 mmol), phenanthroline (0.13 mmol), and 2,6-dimethyl-4-bromopyridine (1 mmol) were added sequentially. The flask was sealed with a rubber stopper, and the reaction flask was subjected to three cycles of evacuation and nitrogen purging to completely remove air and moisture from the system. Subsequently, under a nitrogen atmosphere, 10 mL of acetonitrile, 2 mL of chlorobenzene, cyclohexene (5 mmol), and 0.15 mL of triethylamine were added sequentially to the flask using a syringe. The reaction mixture was ultrasonically treated for 15 minutes until a homogeneous and transparent solution (12 mL) was formed.

[0204] Preheat the flask in a 40°C constant-temperature water bath. Start the peristaltic pump to pump the preheated reaction solution at 20 rpm (approximately 0.21 mL / min) into a continuous-flow photochemical reaction module made of FEP tubing with an inner diameter of 0.8 mm (total reaction volume of 3.15 mL). The reaction module is precisely temperature-controlled at 40°C by an externally integrated semiconductor cooler and illuminated by an array of LED beads (center wavelength 365 nm, total power 400 W) surrounding it. Based on the flow rate and reactor volume, the effective residence time of the reaction solution in the reactor is calculated to be 10 minutes. The reaction continues until all the reaction solution has flowed through the photochemical reaction module, at which point all the effluent is collected.

[0205] The collected effluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (v / v) as eluent, finally yielding the target product 4-(cyclohexyl-2-en-1-yl)-2,6-dimethylpyridine, a colorless liquid weighing 120 mg, with a separation yield of 64%. The sample was further purified by 1H NMR spectroscopy (NMR spectroscopy). 1 H NMR and carbon spectroscopy (H NMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0206] Example 22

[0207] In a 25 mL oval flask that has been oven-dried and cooled, the photocatalyst tetrabutylammonium decatungstate (0.02 mmol), 1,3-bis(diphenylphosphine)propane nickel chloride (0.1 mmol), phenanthroline (0.13 mmol), and 2,6-dimethyl-4-bromopyridine (1 mmol) were added sequentially. The flask was sealed with a rubber stopper, and the reaction flask was subjected to three cycles of evacuation and nitrogen purging to completely remove air and moisture from the system. Subsequently, under a nitrogen atmosphere, 10 mL of acetonitrile, 2 mL of chlorobenzene, cyclohexene (5 mmol), and 0.15 mL of triethylamine were added sequentially to the flask using a syringe. The reaction mixture was ultrasonically treated for 15 minutes until a homogeneous and transparent solution (12 mL) was formed.

[0208] Preheat the flask in a 60°C constant-temperature water bath. Start the peristaltic pump to pump the preheated reaction solution at 20 rpm (approximately 0.21 mL / min) into a continuous-flow photochemical reaction module made of FEP tubing with an inner diameter of 0.8 mm (total reaction volume of 3.15 mL). The reaction module is precisely temperature-controlled at 60°C by an externally integrated semiconductor cooler and illuminated by an array of LED beads (center wavelength 365 nm, total power 400 W) surrounding it. Based on the flow rate and reactor volume, the effective residence time of the reaction solution in the reactor is calculated to be 30 minutes. The reaction continues until all the reaction solution has flowed through the photochemical reaction module, at which point all the effluent is collected.

[0209] The collected effluent was quenched with saturated NH4Cl solution, extracted with EtOAc, and the organic layers were combined, dried, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (v / v) as eluent, finally yielding the target product 4-(cyclohexyl-2-en-1-yl)-2,6-dimethylpyridine, a colorless liquid weighing 155 mg, with a separation yield of 83%. The sample was further purified by 1H NMR spectroscopy. 1 H NMR and carbon spectroscopy (H NMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0210] Comparative Example 1

[0211] Add the photocatalyst tetrabutylammonium decatungstate (0.004 mmol), nickel chloride-1,3-bis(diphenylphosphine)propane (0.02 mmol), phenanthroline (0.026 mmol), and 2,6-dimethyl-4-bromopyridine (0.2 mmol) to a dry 8 mL reaction vial, and cap the vial. After evacuating and backfilling with nitrogen three times, add 4 mL of acetonitrile, cyclohexene (1 mmol), and 0.03 mL of triethylamine using a syringe. Irradiate with a 370 nm blue light at 50 °C for 18 hours.

[0212] After the reaction was completed, saturated NH4Cl solution was added for quenching, and the mixture was extracted with EtOAc. The combined organic layers were dried over Mg2SO4, filtered, and concentrated under vacuum. The crude material was purified by silica gel column chromatography to obtain the compound. The final product, 4-(cyclohexyl-2-en-1-yl)-2,6-dimethylpyridine, was obtained as a colorless liquid with a weight of 31.8 mg, and the separation yield was 85%. The compound was further purified by 1H NMR spectroscopy (NMR spectroscopy). 1 H NMR and carbon spectroscopy (H NMR) 13 The structure was confirmed by C NMR, and gas chromatography-mass spectrometry (GC-MS) analysis showed that the regioselectivity of the product was >20:1.

[0213] Comparative Example 2

[0214] The same method as Comparative Example 1 was used, except that the amount of each raw material was increased by 5 times (i.e., 5 mmol scale, reaction volume of 20 mL). After the reaction, post-processing yielded 89 mg of the target product, with a separation yield of only 48% and a regioselectivity of approximately 10:1.

[0215] Comparative Example 3

[0216] The same method as in Example 1 was used, except that the mixed reaction solvent was replaced with pure acetonitrile (12 mL). The reaction solution was introduced into the continuous flow apparatus in the form of an emulsion to start the reaction. After about 15 minutes, the reaction solution was observed to become turbid, and a large amount of solid precipitated on the inner wall of the FEP tube, which caused the pump pressure to rise and the reaction to be interrupted.

[0217] Comparative Example 4

[0218] The same method as in Example 1 was used, except that the peristaltic pump was replaced with a syringe pump for feeding. In a 1 mmol scale reaction, the effluent was collected at different time points for analysis, and it was found that the product yield fluctuated between 55% and 83%, indicating that the reaction results were uneven and unstable.

[0219] As demonstrated in Examples 1-12, this invention exhibits excellent compatibility with aryl bromides. Whether the (hetero)aromatic ring contains strong electron-withdrawing groups (such as ester groups, sulfone groups, Examples 3-4, 6-10) or electron-donating groups (such as trimethylsilyl groups, Example 5), the target product can be obtained in moderate to high yields (59-99%) and with high regioselectivity (>20:1). More notably, this method is also applicable to biologically active heterocyclic aromatic hydrocarbons, such as pyridine (Examples 1, 2, 11) and pyrimidine (Example 12), with yields all exceeding 75%. This fully demonstrates that this catalytic system is insensitive to the electronic properties and ring structure of (hetero)aromatic bromides, exhibiting excellent substrate universality.

[0220] As demonstrated in Examples 13-17, this invention exhibits a wide range of applicability to allyl-based compounds. Besides standard cyclohexene, larger-sized cyclododecene (Example 14), structurally complex natural product molecules such as α-pinene and β-pinene (Examples 15-16), and oxacyclohexene containing heteroatoms (Example 17) all readily undergo allyl arylation, yielding the target product in good to excellent yields (63%-82%). This proves the good applicability of this method to cyclic alkenes of different sizes, electronic properties, and heteroatom substitutions.

[0221] To verify the application potential of this application in the synthesis of complex molecules, Examples 18-20 selected drug molecules or natural product derivatives containing multiple sensitive functional groups as substrates for testing. As shown in Examples 18-20, complex aryl bromides derived from menthol (Example 18), cholesterol (Example 19), and diacetone-D-glucose (Example 20) were all successfully transformed in the reaction system of this application. Although the yield and selectivity decreased slightly due to the increased molecular complexity, the corresponding coupling products were still obtained in considerable yields (48%-72%). This result is significant, demonstrating that the reaction conditions of this invention are mild, have excellent functional group compatibility, and can tolerate multiple sensitive groups such as ester groups and ether bonds. It provides a powerful and practical tool for the later modification and structural transformation of complex drug molecules, possessing extremely high potential application value.

[0222] The batch reaction in Comparative Example 2, conducted on the same scale (1 mmol) for 18 hours, yielded only 48% yield. In contrast, the embodiments of this application shorten the reaction time to 15 minutes, achieving a yield as high as 89%. This data comparison clearly demonstrates the overwhelming efficiency advantage of this technology, with a reaction efficiency improvement of over 100 times, representing an order-of-magnitude increase. Furthermore, by using the inexpensive organic photocatalyst TBADT, replacing the expensive precious metal catalysts in existing technologies, the cost of raw materials is significantly reduced.

[0223] As can be seen from Examples 1 and 2, when the reaction scale is increased by 10 times, the yield and selectivity remain almost unchanged. This application has successfully achieved stable linear scale-up from laboratory scale (1 mmol) to pilot scale (10 mmol), which fully demonstrates that the continuous flow process of this invention has excellent linear scale-up effect and robustness, completely overcomes the fatal defect of "scale-up failure" in traditional batch photochemical reactions, and solves the industrialization problem.

[0224] In summary, this application, through systematic collaborative innovation, fundamentally solves the core pain points of photocatalytic allyl arylization reaction in terms of efficiency, scale-up, and universality, and provides a truly industrial-value-added green, efficient, and reliable synthetic route.

[0225] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0226] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. A method for photocatalytic allyl arylization reaction, characterized in that, Includes the following steps: Tetrabutylammonium decatungstate, 1,3-bis(diphenylphosphine)propane nickel chloride, phenanthroline and aryl bromide are mixed, and acetonitrile, chlorobenzene, allyl base and triethylamine are added under a protective atmosphere to form a reaction solution; Under the action of external force, the reaction liquid continuously circulates through the light-illuminated area to carry out photocatalytic reaction, and the temperature of the reaction liquid remains constant during the circulation process.

2. The method for photocatalytic allyl arylization reaction according to claim 1, characterized in that, The reaction solution continuously circulates through the illuminated area at a flow rate of 0.1 mL / min to 10 mL / min.

3. The method for photocatalytic allyl arylization reaction according to claim 1, characterized in that, The effective residence time of the reaction solution in the illuminated area is 10 min to 30 min.

4. The method for photocatalytic allyl arylization reaction according to claim 1, characterized in that, The amount of raw materials used must meet at least one of the following conditions: (1) The amount of the tetrabutylammonium decatungstate is 1 mol% to 5 mol% of the molar amount of the aryl bromide. (2) The amount of 1,3-bis(diphenylphosphine)propane nickel chloride used is 8 mol% to 20 mol% of the molar amount of the aryl bromide. (3) The amount of phenanthroline used is 10 mol% to 25 mol% of the molar amount of the aryl bromide. (4) The molar ratio of the allyl substrate to the aryl bromide is (2~10):1; (5) The volume ratio of the acetonitrile to the chlorobenzene is (1~5):1; (6) The molar ratio of the triethylamine to the aryl bromide is (1~2):1; (7) The molar concentration of the aryl bromide in the mixed solvent of acetonitrile and chlorobenzene is 0.05 mol / L to 0.1 mol / L.

5. The method for photocatalytic allyl arylization reaction according to claim 1, characterized in that, The aryl brominated compounds include 2,6-dimethyl-4-bromopyridine, methyl 4-bromobenzoate, 4-bromobenzyl sulfone, p-bromophenyltrimethylsilane, 9-(4-bromophenyl)carbazole, m-bromobenzonitrile, 4-bromo-2-methylbenzonitrile, 5-bromophthalide, 4-bromo-N-methylphthalimide, 4-bromo-2-trifluoromethylpyridine, and 5-bromo-2-trifluoromethylpyrimidine. , , At least one of them.

6. The method for photocatalytic allyl arylization reaction according to claim 1, characterized in that, The allyl substrate includes at least one of cyclohexene, cyclooctene, cyclododecene, α-pinene, β-pinene, and 3,6-dihydropyran.

7. The method for photocatalytic allyl arylization reaction according to claim 1, characterized in that, The temperature of the reaction solution is 40℃~60℃.

8. The method for photocatalytic allyl arylization reaction according to claim 1, characterized in that, The light source used in the illumination area has a wavelength of 365nm~400nm and a power of 100W~500W.

9. An apparatus for carrying out a method for photocatalytic allyl arylation reaction as described in any one of claims 1 to 8, characterized in that, The device includes a reaction solution mixing component, a peristaltic pump, and a photoreaction module; The reaction liquid mixing component includes a storage tank, a heater, and a stirrer, wherein the storage tank includes a protective gas inlet, a reaction liquid outlet, and a reaction liquid inlet; One end of the peristaltic pump is connected to the reaction liquid outlet of the storage tank via a pipeline, and the other end is connected to the photoreaction module via a pipeline; The photoreaction module includes a light source, a photoreaction coil, and a temperature control component. One end of the photoreaction coil is connected to a peristaltic pump via a pipeline, and the other end is connected to the reaction liquid inlet of the storage tank via a pipeline. Powered by the peristaltic pump, the reaction liquid flows from the reservoir of the reaction liquid mixing component through the peristaltic pump and the photoreaction coil of the photoreaction module, and then returns to the reservoir of the reaction liquid mixing component for continuous circulation.

10. The apparatus according to claim 9, characterized in that, The photoreactive discs are distributed along a plane and located on one side of the light source; Alternatively, the photoreactive coils are distributed around the light source.

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