Continuous reactor for laboratory

Abstract

A continuous reactor for a laboratory comprises a plurality of gas-liquid-solid three-phase reactors which are connected in series to form a whole, each gas-liquid-solid three-phase reactor comprises a reactor body and a plurality of connectors, and the connectors are used for inputting chemical reagents and discharging reaction liquid; and the constant-temperature magnetic stirrer is arranged in the reactor body and is used for controlling the reaction temperature, enhancing the mass transfer efficiency in a gas-liquid-solid three-phase reaction system through magnetic stirring and ensuring uniform mixing of reactants. According to the utility model, a plurality of reactors are connected in series and an efficient temperature control and stirring mechanism is adopted, so that the reactor can avoid the problem of channel blockage while ensuring the mass transfer efficiency and sufficient mixing of reactants, and meets the requirements on efficient, safe and flexible reaction equipment in a laboratory.

Description

Technical Field

[0001] This utility model belongs to the field of laboratory equipment technology, specifically relating to a continuous reactor for laboratory use. Background Technology

[0002] Continuous reaction technology has emerged as a new hot topic in the chemical and pharmaceutical fields in recent years. Due to its excellent mass and heat transfer characteristics and high selectivity, it has attracted widespread attention from academia and industry. Continuous reaction technology is particularly suitable for strongly exothermic and rapid reaction systems, such as nitration, oxidation, and diazotization. Currently, several continuous reaction processes are being used on a large scale in the pharmaceutical and chemical industries.

[0003] Continuous reactors differ significantly from traditional batch reactors. In a continuous reactor, materials react continuously with continuous feeding and discharging. Many chemical reactions are accompanied by the formation of solids during the reaction process. Traditional continuous reactors, such as microchannel reactors or tubular reactors, face problems of clogging and overpressure due to their small channel size.

[0004] Currently, the main types of gas-liquid-solid three-phase reactors on the market include dynamic tubular reactors and multistage continuous stirred tank reactors (CSTRs). Dynamic tubular reactors currently on the market have a minimum liquid holding volume of 100 mL and can only be made of metal, making the reaction phenomena invisible to the naked eye. Multistage continuous stirred tank reactors (CSTRs) are generally made of glass and stainless steel, and currently also have a minimum liquid holding volume of 100 mL, primarily used in later-stage process development and production. However, in the early stages of drug development, the amount of materials is inherently very small, typically in the gram range. Therefore, there is an urgent need for gas-liquid-solid three-phase reactors with smaller reaction volumes to enable early-stage continuous drug manufacturing process development. Utility Model Content

[0005] This invention aims to address the applicability of existing laboratory reaction equipment in gas-liquid-solid three-phase reactions. In the prior art, microchannel reactors and tubular reactors, due to their small channel size, are prone to clogging in reactions involving solid substances, limiting their application in complex three-phase reaction systems. Furthermore, the scale and material design of these devices are often geared towards industrial applications, rather than the needs of small-scale laboratory experimental development, such as the small-scale reagent environments required in the early stages of drug development.

[0006] To address this issue, this invention proposes a gas-liquid-solid three-phase continuous flow reactor particularly suitable for laboratory environments. Through a multi-reactor series design and efficient temperature control and stirring mechanisms, this reactor ensures efficient mass transfer and thorough mixing of reactants while avoiding channel blockage, thus meeting the laboratory's requirements for efficient, safe, and flexible reaction equipment.

[0007] To achieve the above objectives, the technical solution adopted by this utility model is as follows:

[0008] A laboratory continuous reactor, comprising:

[0009] Multiple gas-liquid-solid three-phase reactors are connected in series to form a whole. Each gas-liquid-solid three-phase reactor includes a reactor body and multiple interfaces, which are used for the input of chemical reagents and the discharge of reaction liquid.

[0010] A thermostatic magnetic stirrer, located inside the reactor body, is used to control the reaction temperature and enhance the mass transfer efficiency in the gas-liquid-solid three-phase reaction system through magnetic stirring, ensuring uniform mixing of reactants.

[0011] In some technical solutions, the interface is a standard inverted conical connector, which protrudes from the outer wall of the reactor body.

[0012] In some technical solutions, the interface includes a chemical reagent inlet and a reaction liquid outlet, and the distance between adjacent chemical reagent inlets is smaller than the distance between the chemical reagent inlet and the reaction liquid outlet.

[0013] In some technical solutions, the number of interfaces is 1 to 6; and / or,

[0014] Unused interfaces are sealed with plugs.

[0015] In some technical solutions, the bottom of the reactor body is in direct contact with the heating plate surface of the thermostatic magnetic stirrer, and the temperature of the reaction zone is controlled by the thermostatic magnetic stirrer.

[0016] In some technical solutions, the thermostatic magnetic stirrer is placed in the center of the reaction zone.

[0017] In some technical solutions, the liquid holding volume of the reactor body is between 1 and 50 mL.

[0018] In some technical solutions, the reactor body is made of one or more of the following materials: borosilicate glass, PTFE, PFA, PEEK, 316L stainless steel, and Hastelloy.

[0019] In some technical solutions, each gas-liquid-solid three-phase reactor includes an outer wall and an inner wall, which together constitute the main structure of the gas-liquid-solid three-phase reactor.

[0020] In some technical solutions, multiple gas-liquid-solid three-phase reactors are placed flat on a metal substrate, and the metal substrate is placed on one or more constant-temperature magnetic stirrers.

[0021] The present invention, by adopting the above technical solution, has at least the following beneficial effects:

[0022] 1. This invention utilizes the stirring function of a thermostatic magnetic stirrer to achieve uniform dispersion and full contact of solids, liquids, and gases inside the reactor. By enhancing the mass transfer process in the gas-liquid-solid three-phase reaction, the reaction rate is significantly increased and the reaction time is shortened. Simultaneously, this design avoids incomplete reactions caused by insufficient mixing, ensuring high selectivity and high yield.

[0023] 2. Unlike traditional microchannel reactors and tubular reactors, this invention features a spacious reaction space, avoiding channel blockage caused by solid deposition or accumulation. By rationally arranging the spacing between the chemical reagent inlet and the reaction liquid outlet, the fluid flow path is further optimized, ensuring the stability and continuity of the reaction.

[0024] 3. This reactor features multiple standard inverted conical connectors as interfaces, allowing for multi-channel input of chemical reagents and smooth discharge of reaction liquid. Unused interfaces can be sealed with plugs, flexibly adapting to different experimental needs. This design significantly improves the ease of operation and the applicability of the experiments.

[0025] 4. This invention achieves precise temperature control for each reactor by utilizing the direct contact between the heating plate of the thermostatic magnetic stirrer and the bottom of the reactor, along with the high thermal conductivity of the metal substrate. The uniform temperature distribution ensures the stability of multiple reactors under complex continuous reaction conditions and adapts to the temperature requirements of different reaction stages.

[0026] 5. The main body of this reactor is made of one or more materials selected from borosilicate glass, PTFE, PFA, PEEK, 316L stainless steel, and Hastelloy, and can withstand different corrosive media and high-temperature environments. This design enables the equipment to adapt to various types of chemical reactions and has extremely high laboratory practicality.

[0027] 6. The liquid holding volume of the reactor body of this invention ranges from 1 mL to 50 mL, making it particularly suitable for small-scale laboratory reactions and continuous flow process optimization in drug development. Through its modular design with reactors connected in series, it can be flexibly expanded for research and development of multi-stage reactions. Attached Figure Description

[0028] To more clearly illustrate the technical solutions in the embodiments of this utility model, the drawings and their markings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this utility model. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0029] Figure 1 This is a schematic diagram of the structure of the laboratory continuous reactor described in an embodiment of the present invention.

[0030] The meanings of the symbols marked in the figure are as follows:

[0031] 10—Reactor body, 11—Outer wall, 12—Inner wall;

[0032] 21—Chemical reagent inlet, 22—Reaction solution outlet;

[0033] 30—Thermostatic magnetic stirrer. Detailed Implementation

[0034] To more clearly illustrate the technical solutions in the embodiments of this utility model or the prior art, the specific implementation methods of this utility model will be described below with reference to the accompanying drawings. Obviously, the drawings described below are merely some embodiments of this utility model. For those skilled in the art, other drawings and other implementation methods can be obtained based on these drawings without any creative effort.

[0035] To keep the drawings concise, each figure only schematically shows the parts relevant to the utility model, and these do not represent the actual structure of the product. Furthermore, for ease of understanding, in some figures, only one of the components with the same structure or function is schematically depicted, or only one is labeled. In this document, "one" not only means "only one," but can also mean "more than one."

[0036] It should also be further understood that the term “and / or” as used in this application specification and the appended claims means any combination of one or more of the associated listed items and all possible combinations, and includes such combinations.

[0037] In this document, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to fixed connections, detachable connections, or integral connections; they can refer to mechanical connections or electrical connections; they can refer to direct connections or indirect connections through an intermediate medium; and they can refer to the internal connection between two components. Those skilled in the art can understand the specific meaning of the above terms in this utility model based on the specific circumstances.

[0038] like Figure 1According to one embodiment of this application, a laboratory continuous reactor includes multiple gas-liquid-solid three-phase reactors and a thermostatic magnetic stirrer 30. The multiple gas-liquid-solid three-phase reactors are connected in series to form a whole. Each gas-liquid-solid three-phase reactor includes a reactor body 10 and multiple interfaces for inputting chemical reagents and discharging reaction liquid. The thermostatic magnetic stirrer 30 is located inside the reactor body 10 and is used to control the reaction temperature and enhance the mass transfer efficiency in the gas-liquid-solid three-phase reaction system through magnetic stirring to ensure uniform mixing of reactants.

[0039] Through the design of multiple reactors in series and the efficient temperature control and stirring mechanism, this reactor can ensure mass transfer efficiency and thorough mixing of reactants while avoiding channel blockage, thus meeting the laboratory's requirements for efficient, safe, and flexible reaction equipment.

[0040] According to the optimized design of this embodiment, all interfaces are standard inverted conical connectors, each used for the input of chemical reagents and the discharge of reaction liquid. This design allows for more standardized and convenient connection of the reactor's chemical reagent inlet 21 and reaction liquid outlet 22 to external equipment. The shape of the inverted conical connector effectively reduces pressure loss during fluid flow, ensuring smooth input of chemical reagents and rapid discharge of reaction liquid, avoiding fluid blockage or backflow problems caused by unreasonable interfaces. The spacing between adjacent chemical reagent inlets 21 is smaller than the spacing between chemical reagent inlets 21 and reaction liquid outlet 22. This interface layout effectively optimizes the fluid flow path inside the reactor, reducing flow inhomogeneity and dead zones, ensuring good mass transfer and uniform mixing in the gas-liquid-solid three-phase reaction system. Depending on different experimental requirements, the number of interfaces can be from 1 to 6. This flexible design allows the reactor to be configured according to actual applications to meet the needs of reactions of different scales and complexities. In some embodiments, unused interfaces can be sealed with plugs, effectively preventing unnecessary fluid leakage or contamination, maintaining reactor cleanliness and system stability. This interface design not only improves the ease of operation of the reactor but also enhances the versatility of the equipment, enabling it to adapt to various laboratory operating environments. At the same time, it ensures the smooth flow of reactants during the experiment, further improving reaction efficiency and equipment reliability.

[0041] According to the optimized design of this embodiment, the bottom of the reactor body 10 is in direct contact with the heating plate surface of the thermostatic magnetic stirrer 30. This design allows the thermostatic magnetic stirrer 30 to not only control the temperature of the reaction zone but also effectively transfer heat, ensuring a uniform temperature distribution within the reactor. By directly heating the bottom of the reactor through the heating plate of the thermostatic magnetic stirrer 30, the required reaction temperature can be quickly reached and maintained even with a small reaction volume, thereby improving the reaction rate and efficiency and preventing localized overheating or cooling. Furthermore, the thermostatic magnetic stirrer 30 is positioned at the center of the reaction zone, and its stir bar provides uniform hybrid current within the reactor, enhancing the mass transfer efficiency of the gas-liquid-solid three-phase reaction system while ensuring sufficient contact and uniform distribution of reactants throughout the reactor. This optimized design not only improves reaction efficiency but also ensures the stability and controllability of the reaction process through precise temperature control and efficient stirring. In summary, this solution, through the combination of temperature control and stirring functions, effectively improves experimental accuracy and operational reliability in small-volume reactors.

[0042] In one specific embodiment, multiple gas-liquid-solid three-phase reactors are placed horizontally on a metal substrate, which is then placed on one or more thermostatic magnetic stirrers 30. This design allows the metal substrate to act as a heat conduction medium, uniformly distributing the heat provided by the heating plate of the thermostatic magnetic stirrer 30 to each reactor, ensuring temperature consistency within the reactor. Due to the high thermal conductivity of the metal substrate, heat can be quickly and evenly conducted to each reactor, effectively avoiding reduced reaction efficiency or localized overheating caused by uneven heat distribution. The stirring and heating functions of the thermostatic magnetic stirrer 30 also ensure thorough mixing and efficient mass transfer of the gas-liquid-solid three-phase substances within the reactor, further enhancing the reaction rate. The horizontal arrangement of multiple reactors enables parallel operation of multiple stages or groups of reactions within a limited space, improving experimental efficiency and making it particularly suitable for the development and optimization of multi-stage continuous flow reaction processes. In summary, this scheme, through the synergistic effect of the metal substrate and the thermostatic magnetic stirrer 30, not only achieves efficient temperature control but also provides better reactant mixing, ensuring the stability and efficiency of the reaction process.

[0043] According to the specific implementation of this embodiment, the liquid holding volume of the reactor body 10 is between 1 and 50 mL, a design particularly suitable for small-scale laboratory reactions. Small-volume reactors can meet the needs of drug development, chemical synthesis, and other fields requiring small reagent volumes and fast reaction rates. The small liquid holding volume not only reduces the amount of reagents required for the reaction and lowers experimental costs, but also allows for more precise control of reaction conditions, facilitating reaction optimization and process development. This design also makes the reactor volume suitable for small-scale laboratory reactions, offering greater flexibility and efficiently supporting high-throughput experiments.

[0044] According to the specific implementation of this embodiment, the reactor body 10 is made of one or more combinations of borosilicate glass, PTFE, PFA, PEEK, 316L stainless steel, and Hastelloy. These materials possess excellent high-temperature resistance and corrosion resistance, enabling them to withstand various harsh reaction conditions and ensuring the reactor's long lifespan and stability during use. Borosilicate glass provides good light transmittance, suitable for experiments such as photocatalytic reactions, while PTFE, PFA, and PEEK materials have excellent chemical corrosion resistance, suitable for various acid-base and solvent reactions. The use of 316L stainless steel and Hastelloy improves the reactor's mechanical strength under high-temperature and high-pressure conditions, making it particularly suitable for applications involving metal catalysts or high-temperature and high-pressure reactions. The comprehensive use of these high-performance materials not only improves the reactor's durability and applicability but also ensures the accuracy and safety of experimental results.

[0045] According to the specific implementation of this embodiment, each gas-liquid-solid three-phase reactor includes an outer wall 11 and an inner wall 12, which together constitute the main structure of the reactor. This design enhances the mechanical strength and sealing of the reactor, while enabling it to effectively resist the physical and chemical influences of the external environment. The structural design of the inner wall 12 and the outer wall 11 can be optimized according to the required operating conditions of the reactor. For example, a heat insulation layer can be added between the inner wall 12 and the outer wall 11, or the wall thickness can be strengthened to improve the reactor's high-temperature resistance and heat insulation performance. The design of the outer wall 11 can meet the requirements of external pipeline connection and installation, while the inner wall 12 ensures that the reactants can be uniformly mixed in the reactor without interference from the external environment. Specifically, the reactor body can withstand pressures of 0–20 bar and temperatures of 25–200°C. This ensures reactor stability while improving reaction efficiency and reducing the impact of the external environment on the reaction process.

[0046] To better understand and apply the above scheme and to effectively demonstrate its corresponding benefits, the following describes the gas-liquid-solid three-phase reactor provided by this utility model in conjunction with specific embodiments.

[0047] Combining the above embodiments and Figure 1As shown, this embodiment uses the nitro reduction hydrogenation reaction, a common continuous reaction, as an example to illustrate the function of the gas-liquid-solid three-phase reactor. Hydrogenation reactions generally involve three phases: gas, liquid, and solid. The catalysts used are usually heterogeneous catalysts, which cannot be dissolved in the solvent system. Conventional microchannel and tubular reactors would face the problem of catalyst clogging the channels. In addition, hydrogenation is one of the eighteen high-risk processes regulated by the government. Using conventional high-pressure hydrogenation reactors is highly dangerous and the operation is also more complicated. For hydrogenation reactions involving Raney nickel metal catalysts, GSK will not use conventional high-pressure hydrogenation reactors once the temperature exceeds 100 degrees or the pressure exceeds 5 bar. Instead, it will use a continuous hydrogenation reactor.

[0048] Nitro hydrogenation reduction has extremely high requirements for mass transfer. To complete the reaction in a short time, excellent gas-liquid mass transfer is necessary. The gas-liquid-solid three-phase reactor provided by this utility model patent has a small liquid holding volume in the core reaction zone. The solubility of hydrogen in the system is greatly increased under higher pressure, which greatly increases the probability of collision between hydrogen, catalyst and reactants, thereby greatly accelerating the reaction and shortening the reaction time from several hours to within a few minutes. Moreover, it does not face the problem of channel blockage.

[0049] The specific reaction is as follows:

[0050]

[0051] The same stainless steel autoclave, stainless steel microchannel reactor, stainless steel tubular reactor, and stainless steel gas-liquid-solid three-phase reactor with the same liquid holding volume were used for testing. The same substrate EA solution and hydrogen flow rate were used. The material concentration, catalyst, reaction temperature, pipeline material and other parameters were all the same. The only difference was whether the gas-liquid-solid three-phase reactor provided by this utility model was used.

[0052] The experimental procedure is as follows:

[0053] A certain amount of 3-nitrotoluene, 5% Pd / C and ethyl acetate were added to a stainless steel autoclave. The autoclave was purged with nitrogen three times and hydrogen three times. The hydrogen pressure was adjusted to 15 bar. The temperature was raised to 80°C, and stirring was started. Samples were taken for testing after 5 min, 60 min and 180 min of reaction.

[0054] The temperature of the microchannel reactor, tubular reactor, and gas-liquid-solid three-phase reactor was adjusted to 80℃. A diaphragm pump was used to deliver 3-nitrotoluene and ethyl acetate slurry of 5% Pd / C, and a Beijing Qixing Huachuang gas mass flow controller was used to deliver hydrogen. The two materials flowed into the reactor through their respective interfaces to react. The reaction residence time was set to 5 min, and the system pressure was set to 15 bar.

[0055] The molar ratios of all the experimental materials mentioned above are as follows:

[0056] Hydrogen: 3-nitrotoluene = 5:1, catalyst 5% Pd / C: 3-nitrotoluene = 0.05:1.

[0057] All reaction solutions and effluents from experiments were analyzed using Agilent liquid chromatography.

[0058] The experimental results are shown in the table below:

[0059]

[0060]

[0061] During the experiment using a microchannel reactor, the system experienced overpressure. The diaphragm pump pressure rapidly increased from 15 bar to 25 bar before stopping. Subsequently, no continuous flow of gas-liquid mixture was observed at the reactor outlet, indicating that the microchannel reactor was clogged. No clogging was observed when using a tubular reactor or a gas-liquid-solid three-phase reactor.

[0062] As shown in the table above, the gas-liquid-solid three-phase reactor represents a significant leap in reaction rate compared to the high-pressure hydrogenation reactor. Compared to tubular reactors, the gas-liquid-solid three-phase reactor offers a ~5% improvement in conversion rate and a ~12% improvement in selectivity, demonstrating clear advantages. Furthermore, the gas-liquid-solid three-phase reactor avoids the channel clogging problem compared to microchannel reactors.

[0063] In summary, the gas-liquid-solid three-phase reactor of this invention has demonstrated its application potential in this template reaction, providing more options and references for the design of such reactions, especially continuous reactions.

[0064] The preferred embodiment of this utility model is provided as an inspiration. Based on the above description, those skilled in the art can make various changes and modifications without departing from the technical concept of this utility model.

[0065] The technical scope of this utility model is not limited to the contents of the specification, but must be determined according to the scope of the claims.

Claims

1. A laboratory continuous reactor, characterized in that, include: Multiple gas-liquid-solid three-phase reactors are connected in series to form a whole. Each gas-liquid-solid three-phase reactor includes a reactor body and multiple interfaces, which are used for the input of chemical reagents and the discharge of reaction liquid. A thermostatic magnetic stirrer, located inside the reactor body, is used to control the reaction temperature and enhance the mass transfer efficiency in the gas-liquid-solid three-phase reaction system through magnetic stirring, ensuring uniform mixing of reactants.

2. The laboratory continuous reactor according to claim 1, characterized in that, The interface is a standard inverted conical connector, which extends from the outer wall of the reactor body.

3. The laboratory continuous reactor according to claim 1 or 2, characterized in that, The interface includes a chemical reagent inlet and a reaction liquid outlet, and the distance between adjacent chemical reagent inlets is smaller than the distance between the chemical reagent inlet and the reaction liquid outlet.

4. The laboratory continuous reactor according to claim 1, characterized in that, The number of interfaces is 1 to 6; and / or, Unused interfaces are sealed with plugs.

5. The laboratory continuous reactor according to claim 1, characterized in that, The bottom of the reactor body is in direct contact with the heating plate of the thermostatic magnetic stirrer, and the temperature of the reaction zone is controlled by the thermostatic magnetic stirrer.

6. The laboratory continuous reactor according to claim 5, characterized in that, The thermostatic magnetic stirrer is placed in the center of the reaction zone.

7. The laboratory continuous reactor according to claim 1, characterized in that, The liquid holding volume of the reactor body is between 1 and 50 mL.

8. The laboratory continuous reactor according to claim 1, characterized in that, The reactor body is made of one of the following materials: borosilicate glass, PTFE, PFA, PEEK, 316L stainless steel, and Hastelloy.

9. The laboratory continuous reactor according to claim 1 or 8, characterized in that, Each gas-liquid-solid three-phase reactor includes an outer wall and an inner wall, which together constitute the main structure of the gas-liquid-solid three-phase reactor.

10. The laboratory continuous reactor according to claim 1, characterized in that, Multiple gas-liquid-solid three-phase reactors are placed flat on a metal substrate, which is then placed on one or more constant-temperature magnetic stirrers.

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