Online photochemical reaction detection system based on liquid chromatography-mass spectrometry

Abstract

The invention relates to the technical field of photochemical reaction devices, and provides an online photochemical reaction detection system based on liquid chromatography-mass spectrometry, which comprises: a photochemical reaction device for photochemical reaction of a compound reaction solution to form a photochemical reaction product; the liquid chromatograph-mass spectrometer is used for carrying out on-line detection on the photochemical reaction product; wherein the photochemical reaction device is directly connected with the liquid chromatograph-mass spectrometer through the automatic sample introduction ring, so that a compound reaction product solution can be directly injected into the liquid chromatograph-mass spectrometer. According to the online photochemical reaction detection system based on liquid chromatography-mass spectrometry provided by the invention, the photochemical reaction device is seamlessly connected with the liquid chromatography-mass spectrometry platform through the automatic sample introduction ring, the compound reaction product is introduced into the liquid chromatography-mass spectrometry instrument, and the liquid chromatography-mass spectrometry instrument performs online detection on the photochemical reaction product, so that high-value compounds and intermediates thereof can be detected, and the detection accuracy is improved. And real-time, online and rapid detection is realized, and the development of the photochemical synthesis industry is assisted.

Description

Technical Field

[0001] The present invention relates to the technical field of photoreaction devices, and particularly to an on-line photoreaction detection system based on liquid chromatography-mass spectrometry. Background Art

[0002] Liquid chromatography-mass spectrometry (LC-MS) instrument is one of the most important scientific test instruments for rapidly identifying the structures of organic compounds at present. It uses liquid chromatography as the separation system and mass spectrometry as the detection system. The sample is ionized after being separated by the mobile phase, and the ion fragments are separated by the mass analyzer according to the mass number, and the mass spectrum is obtained through the detector. Liquid chromatography-mass spectrometry combines the high separation characteristics of liquid chromatography for complex samples with the advantages of high selectivity, high sensitivity of mass spectrometry in detecting relative molecular mass and structural information, realizing the complementary advantages of chromatography and mass spectrometry, and is widely used in many fields such as organic synthesis, drug research and development, food detection and environmental monitoring.

[0003] Photochemical synthesis reaction, as one of the most active fields in current organic synthetic chemistry, directly uses light radiation as the energy source to overcome the reaction barrier and generate the target product through excited-state species. This method is different from traditional thermal chemical reactions. It can directly construct the structure of the target compound, greatly simplifying the synthesis reaction steps, and embodying the modern chemical synthesis concept of high efficiency, atom economy and environmental friendliness. In technical details, the key to photochemical synthesis is to use light waves with specific wavelengths to drive photoreactive intermediates to undergo coupling, elimination, ring opening / ring closing, isomerization and other reactions to quickly construct chemical structures. However, limited by the complexity of photochemical synthesis reactions, the existing photoreaction devices cannot monitor the photochemical synthesis products or intermediates in real time and cannot perform on-line detection of the results of photoreaction. Therefore, the new generation of photoreaction devices should quickly respond to the changes in the conditions of photochemical synthesis reactions. On the basis of accurately regulating parameters such as the incident light wavelength, light intensity, reaction temperature, and reaction time, they should further meet the in-depth requirements such as optimizing reaction kinetics, reducing side reactions, realizing cascade multi-step conversion processes, and quickly screening photoreaction conditions, and achieve real-time, on-line, and rapid detection. As the most important tool for characterizing the structures of organic compounds, liquid chromatography-mass spectrometry is easy to be externally connected to the reaction system and can perform programmed automatic sampling and detection, and naturally becomes an ideal support platform for matching the new generation of photoreaction devices and promoting the development of the photosynthesis industry. Summary of the Invention

[0004] The present invention provides an on-line photoreaction detection system based on liquid chromatography-mass spectrometry to solve the defect in the prior art that the results of photoreaction cannot be detected in real time, on-line and quickly, realize real-time, on-line and rapid detection, and promote the development of the photochemical synthesis industry.

[0005] The present invention provides an on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry, comprising:

[0006] A photochemical reaction device for causing a photochemical reaction of a compound reaction solution to form a photochemical reaction product;

[0007] A liquid chromatography-mass spectrometer for on-line detection of the photochemical reaction product;

[0008] Wherein, the photochemical reaction device is connected to the liquid chromatography-mass spectrometer through an automatic sampling loop on the liquid chromatography-mass spectrometer, so that the compound reaction product solution can be directly injected into the liquid chromatography-mass spectrometer.

[0009] According to an on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry provided by the present invention, the photochemical reaction device comprises:

[0010] A photochemical reactor for causing a photochemical reaction of a compound reaction solution, which has a flow channel for circulating liquid inside, and controls the temperature of each area of the photochemical reactor by cooling or heating the circulating liquid;

[0011] A liquid chromatography metering pump for injecting the compound reaction solution into the photochemical reactor and controlling the flow rate and pressure of the reaction solution;

[0012] A power supply for controlling the output current and voltage and providing power for the LED array light source in the photochemical reactor;

[0013] A refrigeration thermostat for cooling or heating the circulating liquid to precisely control the temperature of the photochemical synthesis reaction;

[0014] A circulating condenser pump for cooling the circulating condensate for efficient heat dissipation of the LED array light source.

[0015] According to an on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry provided by the present invention, the photochemical reactor comprises:

[0016] A glass chip which has a flow channel inside and can carry the reaction solution of the compound;

[0017] An LED array light source connected to the power supply to provide light for photochemical synthesis;

[0018] A bracket assembly for supporting and fixing the glass chip and the LED array light source, which has a flow channel for circulating liquid inside, and controls the temperature of each area of the photochemical reactor by cooling or heating the circulating liquid;.

[0019] An on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry according to the present invention, wherein the glass chip is made of high borosilicate optical glass and is integrally formed by a melting process, and the glass chip is set as a thin-layer laminar flow reaction model.

[0020] An on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry according to the present invention, wherein the support assembly includes:

[0021] A liquid cooling support, which is closely attached to the glass chip. A first circulating liquid channel is opened inside the liquid cooling support, and the first circulating liquid channel is communicated with the refrigerating thermostat;

[0022] A connection support, which is connected to the glass chip. The connection support is used to connect the glass chip into the continuous flow system of the liquid chromatography-mass spectrometry instrument;

[0023] An LED support, which is connected to the LED array light source. A second circulating liquid channel is arranged inside, and the second circulating liquid channel is communicated with the circulating condenser pump;

[0024] A support bracket, which is arranged at the bottom of the glass chip, and the support bracket is connected to the liquid cooling support and the LED support.

[0025] An on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry according to the present invention, wherein a groove is arranged on one side of the liquid cooling support close to the glass chip, and the shape of the groove is adapted to the glass chip.

[0026] An on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry according to the present invention further includes a perfluoroether rubber sealing gasket, and the perfluoroether rubber sealing gasket is arranged between the connection support and the glass chip.

[0027] An on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry according to the present invention, wherein the auto-injection loop has a loading state and an injection state. In the loading state, the photochemical reactor and the auto-injection loop form a first passage; in the injection state, the auto-injection loop and the liquid chromatography-mass spectrometry instrument form a second passage; the auto-injection loop can switch between the loading state and the injection state.

[0028] An on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry according to the present invention includes a plurality of glass chips, and the plurality of glass chips are connected in series, and each glass chip corresponds to an LED array light source with a different wavelength.

[0029] An on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry according to the present invention, the reaction flow channels on the glass chip are divided into at least two reaction regions, and each of the reaction regions corresponds to the LED array light sources of different wavelengths.

[0030] The on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry provided by the present invention performs a photochemical reaction on a compound reaction solution through a photochemical reaction device to form a photochemical reaction product. The photochemical reaction device and the liquid chromatography-mass spectrometry instrument are connected through an automatic sampling loop, and the photochemical reaction product is introduced into the liquid chromatography-mass spectrometry instrument. The liquid chromatography-mass spectrometry instrument performs on-line detection on the photochemical reaction product. By using flash chemistry and microfluidic continuous photochemical reaction chip technology, a new generation of miniaturized, modularized, and integrated photochemical reactors are developed, which are seamlessly connected to the liquid chromatography-mass spectrometry instrument platform. For high-value compounds and their intermediates, real-time, on-line, and rapid detection is achieved, contributing to the development of the photochemical synthesis industry. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0032] Figure 1 is a structural block diagram of the on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry provided by the present invention;

[0033] Figure 2 is a structural schematic diagram of the photochemical reactor provided by the present invention;

[0034] Figure 3 is an exploded view of the photochemical reactor provided by the present invention;

[0035] Figure 4 is a structural schematic diagram of the loading state of the automatic sampling loop provided by the present invention;

[0036] Figure 5 is a structural schematic diagram of the injection state of the automatic sampling loop provided by the present invention;

[0037] REFERENCE SIGNS:

[0038] 1, photochemical reaction device; 2, liquid chromatography-mass spectrometry instrument; 3, automatic sampling loop on the liquid chromatography-mass spectrometry instrument;

[0039] 11, photochemical reactor; 12, liquid chromatography metering pump; 13, refrigeration thermostat; 14, circulating condensation pump; 15, power supply;

[0040] 111. Glass chip; 112. LED array light source; 113. Liquid cooling bracket; 114. Connection bracket; 115. LED bracket; 116. Support bracket. Detailed implementation manners

[0041] To make the objectives, technical solutions and advantages of the present invention clearer, the technical solutions in the present invention will be clearly and completely described below with reference to the accompanying drawings in the present invention. Apparently, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present invention without creative efforts shall fall within the protection scope of the present invention.

[0042] In the description of the embodiments of the present invention, it should be noted that the orientation or positional relationship indicated by the terms "center", "longitudinal", "lateral", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc. is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing the embodiments of the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus should not be construed as a limitation to the embodiments of the present invention. In addition, the terms "first", "second", and "third" are only used for descriptive purposes and cannot be construed as indicating or implying relative importance.

[0043] The following combines Figures 1 to 5 to describe the on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry of the present invention.

[0044] As Figure 1 shown, the embodiment of the present invention provides an on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry, including a photochemical reaction device 1, a liquid chromatography-mass spectrometry instrument 2, and an autosampler loop 3 on the liquid chromatography-mass spectrometry instrument. The photochemical reaction device 1 is connected to the liquid chromatography-mass spectrometry instrument 2 through the autosampler loop 3. To solve the shortcoming that the existing photochemical reaction device cannot monitor the photochemical synthesis products or intermediates in real time and cannot perform on-line detection on the results of photochemical reactions, the present invention follows the development trend of cutting-edge technologies, utilizes flash chemistry and microfluidic continuous "photochemical reaction chip" technologies, develops a new generation of photochemical reactors that are miniaturized, modularized, and integrated, seamlessly connects to the liquid chromatography-mass spectrometry instrument platform, and realizes real-time, on-line, and rapid detection for high-value compounds and their intermediates, helping the development of the photochemical synthesis industry.

[0045] Among them, the photochemical reaction device 1 is used for the photochemical reaction of the compound reaction solution to form a photochemical reaction product. When using the photochemical reaction device 1, the compound reaction solution needs to be placed in a container, the light source is turned on, and the parameters of the control system are adjusted to carry out the photochemical reaction. Then, the reaction product can be collected and detected through the collection system and the detection system. The liquid chromatography-mass spectrometry instrument 2 is used for on-line detection of the photochemical reaction product.

[0046] As an important tool for characterizing the structure of organic compounds, the liquid chromatography-mass spectrometry instrument 2 is easy to be externally connected to the reaction system and can be programmed for automatic sampling and detection. It has become an ideal support platform that matches the new generation of photochemical reaction instruments and helps the development of the photosynthesis industry.

[0047] The automatic sampling loop 3 on the liquid chromatography-mass spectrometry instrument is used to connect the photochemical reaction device 1 and the liquid chromatography-mass spectrometry instrument 2, so that the compound reaction product solution can be directly injected into the liquid chromatography-mass spectrometry instrument 2. Its main function is to achieve seamless connection between the photochemical reaction device 1 and the liquid chromatography-mass spectrometry instrument 2, ensuring that the photochemical reaction product can enter the liquid chromatography-mass spectrometry instrument efficiently and accurately for on-line detection.

[0048] The on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry provided by the embodiment of the present invention can seamlessly connect the photochemical reaction device 1 and the liquid chromatography-mass spectrometry instrument 2, and can realize real-time, on-line and rapid detection for high-value compounds and their intermediates, helping the development of the photochemical synthesis industry.

[0049] As Figure 1 shown, in a feasible embodiment of the present invention, the photochemical reaction device 1 includes a photochemical reactor 11, a liquid chromatography metering pump 12, a power supply 15, a refrigeration thermostat 13 and a circulating condensation pump 14. When in use, first inject the compound reaction solution into the photochemical reactor 11 through the liquid chromatography metering pump 12 for photochemical reaction, and then use the liquid chromatography-mass spectrometry instrument 2 to perform real-time on-line detection on the reaction result.

[0050] Among them, the photochemical reactor 11 is the main area for carrying out photochemical reactions. When the compound reaction solution is irradiated by the light source here, a photochemical reaction is triggered. The photochemical reactor 11 is used for the photochemical reaction of the compound reaction solution, and the photochemical reactor 11 realizes the purpose of regional temperature control or heat dissipation by cooling or heating the circulating liquid.

[0051] The liquid chromatography metering pump 12 is used to inject the chemical reaction solution into the photoreactor 11 and control the flow rate of the chemical reaction solution to ensure the uniformity of the reaction; the power supply 15 is used to control the output current and voltage, provide power for the photoreactor 11, and stabilize the light intensity. The temperature of the circulating liquid is controlled by the refrigeration thermostat 13, and then the photoreaction temperature is accurately adjusted to ensure the stability of the photoreaction conditions. The circulating condensation pump 14 is used for refrigeration and provides the power for the circulation of the circulating cooling liquid to dissipate heat from the LED light source, ensuring the long-term stable operation of the photoreaction device 1.

[0052] The photoreactor 11 is the core of the photoreaction device 1. It combines the chip-type continuous flow reaction technology and the LED light source, which can greatly improve the yield and efficiency of the photochemical synthesis reaction.

[0053] As Figure 2 and Figure 3 shown, in a feasible embodiment of the present invention, the photoreactor 11 includes a glass chip 111, an LED array light source 112, and a bracket assembly.

[0054] Among them, the glass chip 111 is the core place where the photochemical synthesis reaction occurs, and its design and manufacture demonstrate the combination of engineering technology and materials.

[0055] First, for the material and manufacture of the glass chip 111, high borosilicate optical glass material can be used. This material is selected because of its excellent chemical stability and excellent optical transparency, and is particularly suitable for manufacturing precision chemical and optical equipment; the glass chip is first etched with internal channels by CNC machining or mask method, and then through the melting process and integral molding encapsulation to ensure high-precision processing and quality consistency.

[0056] Secondly, the glass chip 111 has a high load-bearing capacity. The glass chip 111 is manufactured by integral molding, and the glass chip 111 can bear a pressure of up to 2 MPa, with high safety, and can be compatible with high-pressure liquid chromatography systems, enhancing its application potential in various chemical scenarios.

[0057] Thirdly, the glass chip 111 can also be customized with flow channels and pattern designs. The reaction flow channels are arranged on the surface of the glass chip 111, and the internal flow channel width / depth and layout pattern of the reaction flow channels can be customized according to requirements to adapt to the kinetic effects under different photochemical synthesis reaction conditions and flexibly adapt to a variety of photochemical synthesis reactions.

[0058] Finally, the optical glass material used in the processing and manufacture of the glass chip 111 has excellent light permeability. The light absorption characteristics of the system are based on the Beer-Lambert law, and the light transmittance in the visible light and near / mid-ultraviolet regions exceeds 90%, providing ideal light conditions for the photoreaction.

[0059] In addition, the glass chip 111 is based on the thin-layer laminar flow reaction model, has a large specific surface area, high mass and heat transfer efficiency, fast reaction speed, uniform mixing of materials, and no amplification effect, and is particularly suitable for microfluidic continuous reactions; further, the glass chip 111 is directly connected to the liquid chromatography system, facilitating the preparation of materials, easy to control, saving samples, and can effectively enhance the kinetic effect of the reaction, improving the photoreaction efficiency and product purity.

[0060] More specifically, the chip made of glass can withstand the vast majority of acid, alkali, and organic solvent systems, and the sandwich structure has excellent heat exchange performance (1000 - 3500 W·m -2 ·K -1 ), and when combined with the liquid circulation bracket made of metal, it can conveniently and accurately control the photoreaction temperature and adapt to photochemical synthesis reactions under various temperature conditions.

[0061] The LED array light source 112 is connected to the power supply to provide light for photochemical synthesis. As a typical solid light source, the LED array light source 112 has a compact size, is easy to integrate, has strong adaptability, can be flexibly designed and assembled, and is suitable for application scenarios with limited space.

[0062] The LED array light source 112 has good monochromaticity and high light intensity, can be used for photochemical synthesis, can increase the photoreaction speed, and reduce the occurrence of side reactions.

[0063] The LED array light source 112 has a wide wavelength range, covering the spectrum from mid-ultraviolet to near-infrared. The wide emission range can match a variety of photochemical synthesis reactions, and the covered wavelengths include: 220 nm, 270 - 280 nm, 305 nm, 310 nm, 325 nm, 335 nm, 365 nm, 375 nm, 385 nm, 395 nm, 405 nm, 415 - 420 nm, 440 - 445 nm, 450 - 455 nm, 465 - 470 nm, 490 nm, 500 nm, 525 nm, 555 nm, 585 - 595 nm, 625 nm, 630 nm, 660 nm, 700 nm, 740 nm, 800 nm, 850 nm, 940 nm, 1064 nm, etc.

[0064] The LED array light source 112 has high energy efficiency, long life, good durability, energy saving and environmental protection, and can output full light at any time without preheating; it emits light directionally, which is convenient for focusing and adjusting the light intensity; it generates low heat, and is particularly suitable for scenarios where strict control of the environmental temperature is required.

[0065] The bracket assembly is used to support and fix the glass chip 111 and the LED array light source 112, ensuring precise alignment between them to achieve efficient photochemical reactions. The bracket assembly is precisely designed and manufactured to accurately fix the glass chip 111 and the LED array light source 112 and ensure the stability of their positional relationship. During the operation of the photoreactor 11, the bracket assembly plays a crucial role. It not only bears the weights of the glass chip 111 and the LED array light source 112 but also withstands the heat and stress generated during the reaction process. Therefore, the bracket assembly needs to have sufficient mechanical strength and stability to ensure the smooth progress of the photochemical reaction.

[0066] As Figure 2 and Figure 3 shown, in a feasible embodiment of the present invention, the bracket assembly includes a liquid-cooled bracket 113, a connection bracket 114, and an LED bracket 115.

[0067] Among them, the liquid-cooled bracket 113 is closely attached to the glass chip 111 to provide stable support for the glass chip 111. A first circulating liquid channel is opened inside the liquid-cooled bracket 113 for sufficient heat exchange with the glass chip 111 and precise temperature control. The first circulating liquid channel is connected to the refrigeration thermostat 13 to form a closed circulation system to ensure the continuous flow of the circulating liquid. The liquid-cooled bracket 113 can be processed and manufactured from aluminum alloy material, closely attached to the glass chip 111, and regulate the temperature of the photochemical synthesis reaction by means of high-efficient heat exchange performance.

[0068] The connection bracket 114 is connected to the glass chip 111. The connection bracket 114 is used to connect the glass chip 111 to the continuous flow system of the liquid chromatography-mass spectrometry instrument 2. The connection bracket 114 is designed with appropriate interfaces to ensure compatibility and tight connection with the liquid chromatography-mass spectrometry instrument 2. The connection bracket 111 is made of corrosion-resistant and heat-resistant materials and is processed and manufactured using materials such as PTFE, FEP, and PEEK.

[0069] The LED bracket 115 is equipped with the LED array light source 112, and a second circulating liquid channel is provided inside. The second circulating liquid channel is connected to the circulating condenser pump 14 to ensure stable heat dissipation of the light source. The LED bracket 115 can also be processed and manufactured from aluminum alloy material, and the second circulating coolant is used to cool the LED array light source 112.

[0070] The support bracket 116 is arranged at the bottom of the glass chip 111, and the support bracket 116 is connected to the liquid-cooled bracket 113 and the LED bracket 115 to form a complete support system. The support bracket 116 can also be processed and manufactured from aluminum alloy material and is used to connect various components to form a support structure.

[0071] As Figure 3As shown, in a feasible embodiment of the present invention, a groove is provided on one side of the liquid-cooling bracket 113 close to the glass chip 111, and the shape of the groove is adapted to the glass chip 111. Since the photochemical reaction temperature has a crucial impact on the synthesis yield, the liquid-cooling bracket 113 is in close contact with the glass chip 111, with better heat dissipation and higher tolerance. Compared with the glass sandwich design in the prior art, the controllable temperature range is wider, and light pollution is avoided. At the same time, the chip-type photochemical reactor has a high surface area factor (1670 - 10000) and a high surface heat transfer coefficient (1000 - 3500W·m -2 ·K -1 ). The excellent heat exchange performance can ensure the precise control of the photochemical reaction temperature. By means of a feedback-type refrigeration thermostat, the reaction temperature of the core chip of the photochemical reactor is regulated to achieve an adjustable photochemical reaction temperature of -20 to 150°C, with a temperature control accuracy of ±0.1°C.

[0072] In a feasible embodiment of the present invention, it further includes a perfluoroether rubber sealing gasket, which is arranged between the connection bracket 114 and the glass chip 111. The material of the perfluoroether rubber sealing gasket has good tolerance to organic solvents, acids, alkalis, etc. The core glass chip is manufactured by a melting process, and the integrally formed internal flow channel can bear a pressure of up to 2MPa, which can be compatible with a liquid chromatography system with a relatively high pressure.

[0073] It should be noted that a plurality of interfaces can be sequentially arranged along the circumferential direction on the automatic sampling loop 3, such as Figure 4 and Figure 5 shown. The automatic sampling loop 3 is set to six-way, that is, a first interface, a second interface, a third interface, a fourth interface, a fifth interface, and a sixth interface are sequentially arranged along the circumferential direction. The connection or cut-off between multiple interfaces can be controlled by a six-way valve. Among them, the first interface is connected to the photochemical reactor 11, the second interface is connected to the product collection bottle, the fourth interface is connected to the liquid chromatography - mass spectrometry instrument 2, and the fifth interface is connected to the liquid chromatography metering pump 12. The third interface and the sixth interface are connected.

[0074] Such as Figure 4 and Figure 5As shown, in a feasible embodiment of the present invention, the autosampler loop 3 has a loading state and an injection state. In the loading state, the photoreactor 11 and the autosampler loop 3 form a first passage; in the injection state, the autosampler loop 3 and the liquid chromatography-mass spectrometry instrument 2 form a second passage; the autosampler loop 3 can switch between the loading state and the injection state. The autosampler loop controls the six-port valve with the hardware configuration and software instructions of the instrument itself; in the "Loading" state, the photoreactor and the autosampler loop 3 form a first passage, and the photoreaction products pass through the autosampler loop 3 and are collected by the product collection bottle; in the "Injection" state, the liquid chromatography-mass spectrometry instrument 2 and the autosampler loop 3 form a passage, and the reaction solution passes through the autosampler loop and is detected by the liquid chromatography-mass spectrometry instrument; the autosampler loop can be programmed to switch between the "Injection" and "Loading" states to realize real-time on-line automatic sampling and detection of the photoreaction.

[0075] With the continuous development of photochemical synthesis technology, many high-value compounds need to undergo multi-step conversion processes during photochemical synthesis, which necessarily requires the photoreactor to be able to perform continuous multi-step discrete photoreactions and use independent photoreaction conditions for each step.

[0076] In a feasible embodiment of the present invention, there are multiple glass chips 111, and the multiple glass chips 111 are connected in series, and each glass chip 111 corresponds to an LED array light source 112 with a different wavelength.

[0077] In a feasible embodiment of the present invention, the reaction flow channels on the glass chip 111 are divided into at least two reaction regions, and each reaction region corresponds to an LED array light source 112 with a different wavelength.

[0078] An on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry according to the present invention can be used for real-time, on-line, and rapid screening of the photochemical reaction synthesis conditions of the dydrogesterone system. By connecting two photoreaction chips in series, namely a photoreactor with a wavelength of 280 nm and a photoreactor with a wavelength of 325 nm, a tandem photochemical synthesis reaction is realized. Under the conditions of a reaction temperature of 0-30 °C, a flow rate of 0.15-3 mL / min, and a photoreaction optical path of 0.25-2 mm, the reaction parameters are screened and optimized to synthesize the precursor of the active pharmaceutical ingredient. For the core two-step photoreaction, the one-way reaction yield can reach 51%, and the comprehensive cyclic recovery yield can reach 85%.

[0079] In the description of the embodiments of the present invention, it should be noted that unless otherwise clearly defined and limited, the terms "connected" and "connected to" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium. For those of ordinary skill in the art, the specific meanings of the above terms in the embodiments of the present invention can be understood according to specific circumstances.

[0080] In the description of this specification, the descriptions referring to the terms "one embodiment", "some embodiments", "mode", "specific mode", or "some modes", etc. mean that the specific features, structures, materials, or characteristics described in connection with the embodiment or mode are included in at least one embodiment or mode of the embodiments of the present invention. In this specification, the schematic descriptions of the above terms do not necessarily refer to the same embodiment or mode. Moreover, the specific features, structures, materials, or characteristics described can be combined in a suitable manner in any one or more embodiments or modes. In addition, without contradiction, those skilled in the art can combine and combine the different embodiments or modes described in this specification and the features of different embodiments or modes.

[0081] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments or equivalently replace some of the technical features. However, such modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. An on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry, characterized in that, Comprising: A photochemical reaction device (1) for carrying out a photochemical reaction on a compound reaction solution to form a photochemical reaction product; A liquid chromatography - mass spectrometry instrument (2) for on - line detection of the photochemical reaction product; An auto - sampling loop (3) for connecting the photochemical reaction device (1) and the liquid chromatography - mass spectrometry instrument (2) and introducing the photochemical reaction product into the liquid chromatography - mass spectrometry instrument (2).

2. The online photochemical reaction detection system based on liquid chromatography-mass spectrometry according to claim 1, wherein The photochemical reaction device (1) includes: A photochemical reactor (11) for carrying out a photochemical reaction on a compound reaction solution, and the photochemical reactor (11) is cooled and temperature - controlled by circulating liquid; A liquid chromatography metering pump (12) for injecting a chemical reaction solution into the photochemical reactor (11) and controlling the flow rate of the chemical reaction solution; A power supply (15) for controlling the output current and voltage and providing power for the photochemical reactor (11); A refrigerating thermostat (13) for cooling or heating the circulating liquid to precisely control the temperature of the circulating liquid; A circulating condensation pump (14) for cooling the circulating liquid for efficient heat dissipation of the photochemical reactor.

3. The on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry according to claim 2, wherein The photochemical reactor (11) includes: A glass chip (111) having a reaction flow channel inside; An LED array light source (112) electrically connected to the power supply (15) to provide light for photochemical synthesis; A bracket assembly for supporting and fixing the glass chip (111) and the LED array light source (112).

4. The on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry according to claim 3, characterized in that, The glass chip (111) is made of high - borosilicate optical glass and is integrally formed by a melting process.

5. The online photochemical reaction detection system based on liquid chromatography-mass spectrometry according to claim 3, wherein The bracket assembly includes: A liquid - cooled bracket (113) closely attached to the glass chip (111), with a first circulating liquid channel opened inside the liquid - cooled bracket (113), and the first circulating liquid channel is connected to the refrigerating thermostat (13); A connecting bracket (114) connected to the glass chip (111), and the connecting bracket (114) is used to connect the glass chip (111) to the continuous flow system of the liquid chromatography - mass spectrometry instrument (2); An LED bracket (115) connected to the LED array light source (112), with a second circulating liquid channel provided inside, and the second circulating liquid channel is connected to the circulating condensation pump (14); A support bracket (116) arranged at the bottom of the glass chip (111), and the support bracket (116) is connected to the liquid - cooled bracket (113) and the LED bracket (115).

6. The online photochemical reaction detection system based on liquid chromatography-mass spectrometry according to claim 5, wherein One side of the liquid - cooled bracket (113) close to the glass chip (111) is provided with a groove, and the shape of the groove is adapted to the glass chip (111).

7. The online photochemical reaction detection system based on liquid chromatography-mass spectrometry according to claim 5, characterized in that, It further includes a perfluoroether rubber sealing gasket, and the perfluoroether rubber sealing gasket is arranged between the connecting bracket (114) and the glass chip (111).

8. The on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry according to claim 2, characterized in that, The automatic sampling loop (3) has a loading state and an injection state. In the loading state, the photoreactor (11) and the automatic sampling loop (3) form a first passage; in the injection state, the automatic sampling loop (3) and the liquid chromatography-mass spectrometry instrument (2) form a second passage; the automatic sampling loop (3) can switch between the loading state and the injection state.

9. The online photochemical reaction detection system based on liquid chromatography-mass spectrometry according to claim 3, characterized in that A plurality of the glass chips (111) are included, and the plurality of glass chips (111) are connected in series, and each of the glass chips (111) corresponds to the LED array light source (112) of a different wavelength.

10. The on-line photochemical reaction detection system based on liquid chromatography-mass spectrometry according to claim 3, characterized in that, The reaction flow channels on the glass chip (111) are divided into at least two reaction regions, and each of the reaction regions corresponds to the LED array light source (112) of a different wavelength.

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