A device for purifying and automatically feeding a sample of chromatography at middle-low pressure

Abstract

The utility model discloses a kind of low pressure preparation chromatogram sample purification and automatic feeding device, it is related to the field of pharmaceutical synthesis experiment, and it includes: the upper end of extraction column pipe is set open, lower end is connected and is provided with lower interface, and extraction column pipe is filled with adsorption extraction filler layer above lower interface in;Adsorption extraction filler layer is flexible mechanical compressible material with communicating type porous;Vacuum evaporation heater is sleeved in the outside of extraction column pipe, for the target reaction mixture is removed by vacuum heating evaporation;Liquid channel is connected and is provided with in sample rod along the axial direction, and the outer periphery of one end of sample rod is circumferentially sleeved with sealing assembly;The one end of sample rod setting sealing assembly is pushed into extraction column pipe from upper end opening, for compressing adsorption extraction filler layer;The inner wall of extraction column pipe is tightly attached to the outer wall of sealing assembly, for sealing extraction column pipe. The scheme not only does not need to operate the silica gel micro powder of health threat, also greatly speeds up the purification speed of chemical reaction mixture.

Description

Technical Field

[0001] This utility model relates to the field of experimental equipment for drug synthesis, and in particular to a device for medium- and low-pressure preparation, chromatographic sample purification, and automatic sample injection. Background Technology

[0002] Currently, in the research and development of biomedicine, pesticides, and new materials, it is often necessary to synthesize thousands to tens of thousands of compounds for functional and performance screening. These screening compounds are synthesized on a small scale in the laboratory, and their synthesized products are generally purified using medium- to low-pressure preparative chromatography. These chemical reaction mixtures are typically composed of reaction products, reaction byproducts, unreacted substrates, catalysts and ligands, inorganic and organic acid-base reagents, and polar reaction solvents. Some components can severely affect chromatographic separation efficiency, or even prevent effective chromatographic separation. Therefore, the reaction mixture must be purified to suitable conditions before being injected into the chromatograph.

[0003] Patent document with application number "202311448141.5" discloses "a method for the synthesis and preparation of a spirocyclic diamine". The operation process is as follows: "After the raw materials are basically completely converted, ice water is added dropwise to the reaction system to quench the reaction, then water is added, the mixture is extracted separately, the organic phases are combined, washed with saturated brine, dried with anhydrous sodium sulfate, mixed with silica gel, and subjected to rapid short column chromatography to obtain the intermediate compound, which is a pale yellow oily substance."

[0004] The aforementioned patent literature, in conjunction with existing technology, reveals the following deficiencies in current equipment used for the purification and preparation of chromatographic samples in general chemical reactions: Traditional chemical reaction mixture purification and chromatographic loading processes typically involve a series of cumbersome steps, including liquid-liquid extraction, washing, drying, evaporation to obtain a crude product containing the synthesized product, dissolving it in a suitable solvent, adding a suitable amount of fine silica gel powder for mixing, evaporating to remove the solvent, and finally loading the silica gel containing the product into an empty chromatographic column. The liquid-liquid extraction process, in particular, is tedious, often requiring multiple extractions, and is highly prone to emulsification. It also requires multiple solvent evaporation processes, consuming significant amounts of time, energy, and extraction solvent. Furthermore, the presence of tiny silica gel particles during mixing and evaporation can easily cause explosive reactions, and improper handling can lead to the adhesion or inhalation of toxic silica gel powder, posing a potential health threat to the operator. Utility Model Content

[0005] This invention provides a device for the purification and automatic injection of chromatographic samples prepared under medium and low pressure, which solves the problems of slow purification speed of chemical reaction mixtures and potential health threats posed by silica gel micropowder during operation in the prior art.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: This invention provides a device for medium- and low-pressure preparation, purification, and automatic injection of chromatographic samples. The device includes an extraction column, a vacuum evaporation heater, and an injection rod. The upper end of the extraction column is open, and the lower end is connected to a lower interface. The extraction column is filled with an adsorption extraction packing layer above the lower interface. The adsorption extraction packing layer is a flexible, mechanically compressible material with interconnected porous structure, used to adsorb the target reaction mixture. The vacuum evaporation heater is fitted outside the extraction column and is used to remove the target reaction mixture by vacuum heating and evaporation. The injection rod has a liquid channel connected along the axial direction, and a sealing component is circumferentially fitted on one end of the injection rod. The end of the injection rod with the sealing component is pushed into the extraction column tube from the upper opening to compress the adsorption extraction packing layer. The outer wall of the sealing component is in close contact with the inner wall of the extraction column tube to seal the extraction column tube.

[0007] In one possible implementation, the upper opening of the extraction column tube has a protruding structure extending outward from the periphery.

[0008] In one possible implementation, the extraction column tube is provided with a locking mechanism at the open end to fix the position of the injection rod extending into the extraction column tube.

[0009] In one possible implementation, the locking mechanism is slidably sleeved outside the injection rod, and the locking mechanism is snap-fitted to the protruding structure.

[0010] In one possible implementation, the lower interface is provided with a flow rate control valve.

[0011] In one possible implementation, the upper and lower parts of the adsorption extraction packing layer are respectively provided with an upper sieve plate and a lower sieve plate.

[0012] In one possible implementation, the sealing assembly includes an expansion sealing ring that is fixedly sleeved around the outer periphery of the injection rod.

[0013] In one possible implementation, the end of the injection rod away from the sealing assembly is connected to the liquid channel and has an upper interface.

[0014] In one possible implementation, the upper interface is used to connect to the mobile phase chromatography pump, and the lower interface is used to connect to the inlet of the chromatography column.

[0015] The device for preparing chromatographic samples under medium and low pressure and for automatic sample injection provided in this embodiment completely replaces the traditional, cumbersome, and labor-intensive liquid-liquid extraction process. It eliminates the problem of emulsification and significantly reduces the consumption and waste disposal of toxic and harmful chemical extraction solvents. This method achieves high-efficiency in-situ evaporation through a vacuum evaporation heater, avoiding the boiling problems associated with rotary evaporation. Multiple samples can be processed in parallel, greatly improving working speed and efficiency. The purified sample is eluted in-situ into the chromatographic separation column within the extraction column, automatically completing the sample loading process. This method achieves sample concentration by mechanically compressing and adsorbing the packing material layer with the injection rod. At this point, the elution rate of the target reaction mixture is very fast, resulting in high chromatographic separation efficiency, sharp peaks, high separation between adjacent peaks, high product purity, and better recovery. This device not only greatly improves the purification speed of the reaction mixture but also reduces sample transfer steps, eliminates the use of easily dispersed silica gel powder, and significantly reduces (or eliminates) the amount of volatile extraction solvent used, thereby effectively reducing the health risks to operators. Attached Figure Description

[0016] Figure 1 A schematic diagram of the automatic elution and injection state of a device for preparing chromatographic samples under medium and low pressure and for automatic injection, provided for an embodiment of this utility model; Figure 2 A schematic diagram of the extraction column structure of a device for medium- and low-pressure preparation, purification, and automatic injection of chromatographic samples provided in this embodiment of the present invention; Figure 3 A schematic diagram of the in-situ evaporation state of a device for preparing chromatographic samples and purifying and automatically injecting samples under medium and low pressure, provided for an embodiment of this utility model; Figure 4 This is a schematic diagram of the filtration and washing process of a medium-low pressure preparative chromatographic sample purification and automatic sample injection device provided for an embodiment of this utility model.

[0017] Figure labels and their explanations: 1. Extraction column; 11. Lower interface; 12. Upper interface; 13. Protruding structure; 14. Sealing plug; 2. Adsorption extraction packing layer; 21. Upper sieve plate; 22. Lower sieve plate; 3. Vacuum evaporation heater; 4. Injector rod; 41. Sealing assembly; 411. Expansion sealing ring; 42. Liquid channel; 5. Locking mechanism; 6. Vacuum sealing cap; 61. Vacuum port of sealing cap; 62. Sealing ring of sealing cap; 7. Flow rate control valve; 8. Vacuum filtration flask; 81. Vacuum filtration interface. Detailed Implementation

[0018] To make the objectives, technical solutions, and advantages of the embodiments of this utility model clearer, the technical solutions of the embodiments of this utility model will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this utility model, and not all embodiments. The components of the embodiments of this utility model described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0019] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0020] It should be noted that similar labels and letters in the following figures indicate similar items. Therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures.

[0021] In the description of this utility model, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship commonly used when the product of this utility model is in use. They are only for the convenience of describing this utility model and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this utility model. In addition, the terms "first," "second," and "third," etc., are only used to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0022] Furthermore, terms such as "horizontal" and "vertical" do not imply that components must be absolutely horizontal or suspended, but rather that they can be slightly tilted. For example, "horizontal" simply means that its direction is more horizontal than "vertical," not that the structure must be completely horizontal, but can be slightly tilted.

[0023] In the description of this utility model, it should also be noted that, unless otherwise explicitly specified and limited, the terms "set," "install," "connect," and "link" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of 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.

[0024] To address the issues of slow purification rates of chemical reaction mixtures in existing technologies and the potential health threats posed by silica gel micropowder during operation, this invention provides a device for the purification and automated injection of chromatographic samples prepared under medium and low pressure.

[0025] like Figures 1-4 As shown in the figure, the device for medium- and low-pressure preparative chromatographic sample purification and automatic injection provided by this utility model includes an extraction column 1, a vacuum evaporation heater 3, and an injection rod 4.

[0026] The upper end of the extraction column 1 is open, and the lower end is connected to a lower interface 11. The extraction column 1 is filled with an adsorption extraction packing layer 2 above the lower interface 11.

[0027] Specifically, the extraction column 1 has an extraction cavity along its length, and the upper end of the extraction column 1 is directly open. The extraction column 1 is used to adsorb and extract the target reaction mixture that is directly added.

[0028] The adsorption-extraction packing layer 2 is a flexible, mechanically compressible material with interconnected porous structures, used to adsorb the target reaction mixture. In other words, the adsorption-extraction packing layer 2 is used to adsorb the target reaction mixture through its internal pore structure.

[0029] The vacuum evaporation heater 3 is installed outside the extraction column 1 and is used to remove the target reaction mixture by vacuum heating and evaporation.

[0030] Specifically, the vacuum evaporation heater 3 is used to achieve vacuum heating and evaporation removal of the reaction solvent (and extraction solvent) in the extraction column 1. After the reaction mixture is added to the extraction column 1, it is adsorbed in the internal pores of the adsorption extraction packing layer 2. On the one hand, the evaporation area is greatly increased, thereby accelerating the evaporation rate and improving working efficiency. On the other hand, the pores support the liquid evaporation, which can effectively prevent evaporation bursts.

[0031] A liquid channel 42 is connected within the injection rod 4 along its axial direction, and a sealing component 41 is circumferentially fitted around one end of the injection rod 4. The end of the injection rod 4 with the sealing component 41 is pushed into the extraction column tube 1 from the top opening to compress the adsorption extraction packing layer 2. The outer wall of the sealing component 41 is in close contact with the inner wall of the extraction column tube 1 to seal the extraction column tube 1.

[0032] The end of the injection rod 4 away from the sealing assembly 41 is connected to the liquid channel 42 and has an upper interface 12.

[0033] The upper interface 12 is used to connect to the mobile phase chromatographic pump of the medium-low pressure chromatograph, and the lower interface 11 is used to connect to the inlet of the chromatographic separation column.

[0034] The sealing assembly 41 includes an expansion sealing ring 411, which is fixedly sleeved on the outer periphery of the injection rod 4.

[0035] Specifically, a liquid channel 42 is provided in the middle of the injection rod 4 along the axial direction. The top of the liquid channel 42 is connected to the upper interface 12. A sealing assembly 41 is provided at the bottom of the injection rod 4. The extraction column 1 is sealed by adjusting the expansion sealing ring 411 in the sealing assembly 41.

[0036] The upper end of the extraction column 1 has a protruding structure 13 extending outward from the outer periphery.

[0037] The extraction column 1 is equipped with a locking mechanism 5 at the open end to fix the position of the injection rod 4 when it extends into the extraction column 1.

[0038] The locking mechanism 5 is slidably sleeved on the outside of the injection rod 4, and the locking mechanism 5 is snapped together with the protruding structure.

[0039] Specifically, the locking mechanism 5 can slide up and down along the injection rod 4, thereby adjusting the position of the injection rod 4 extending into the extraction column tube 1, that is, adjusting the locking position of the extraction column tube 1.

[0040] The protruding structure 13 cooperates with the vacuum sealing cap 6 or the locking mechanism 5 to facilitate the locking of the vacuum sealing cap 6 at the top of the extraction column tube 1, as well as the locking of the top of the extraction column tube 1 with the current position of the injection rod 4.

[0041] The lower interface 11 is equipped with a flow rate control valve 7. The flow rate control valve 7 can be used to adjust and control the flow rate of washing or rinsing.

[0042] The upper part of the adsorption extraction packing layer 2 is provided with an upper sieve plate 21 and a lower sieve plate 22, respectively.

[0043] The upper sieve plate 21 and the lower sieve plate 22 are both sieve plates with preset apertures, which are used to achieve uniform distribution of liquid during filtration and elution.

[0044] In this embodiment of the invention, the device for medium- and low-pressure preparation of chromatographic samples for purification and automatic injection operates as follows: First, one end of the injection rod 4 with the sealing component 41 is inserted into the extraction column tube 1, and the injection rod 4 is pressed downwards to make the adsorption extraction packing layer 2 reach the set tightness; second, the position of the locking mechanism 5 on the injection rod 4 is adjusted so that the locking mechanism 5 cooperates with the protruding structure 13 to lock the current position of the injection rod 4 inserted into the extraction column tube 1; third, the sealing component 41 at the bottom of the injection rod 4 is adjusted so that the expansion sealing ring 411 completely seals the extraction column tube 1; finally, the upper interface 12 is connected to the mobile phase chromatography pump, and the lower interface 11 is connected to the inlet of the chromatographic separation column.

[0045] The operation of the medium- and low-pressure preparative chromatographic sample purification and automatic injection device provided by this utility model completely replaces the traditional cumbersome and labor-intensive liquid-liquid extraction operation. It eliminates the problem of emulsification and greatly reduces the consumption and waste disposal of toxic and harmful chemical extraction solvents. This solution achieves high-efficiency in-situ evaporation through the vacuum evaporator heater 3, avoiding the problem of boiling over during liquid rotary evaporation. Multiple samples can be processed in parallel, greatly improving working speed and efficiency. The purified sample is eluted in-situ into the chromatographic separation column within the extraction column 1, automatically completing the sample loading process. The sample concentration operation is achieved through the mechanical compression adsorption extraction of the packing layer 2 by the injection rod 4. At this time, the elution rate of the target reaction mixture is very fast, resulting in high chromatographic separation efficiency, sharp chromatographic peaks, high separation between adjacent chromatographic peaks, high product purity, and better recovery rate. This device not only greatly improves the purification speed of the reaction mixture but also reduces the sample transfer steps in the operation process. It does not use easily dispersed silica gel powder, and the amount of volatile extraction solvent is greatly reduced (or eliminated), thereby effectively reducing the health risks to operators.

[0046] In one embodiment of this utility model, the adsorption extraction packing layer 2 has abundant micropores, and the micropores are interconnected, which is conducive to liquid flow and accelerates the transfer of substances.

[0047] In this embodiment, the adsorption extraction packing layer 2 can use organic polymer materials and inorganic materials that are already available in the prior art; such as organic polymer materials such as melamine porous materials, polyurethane porous materials, polyethylene porous materials, polypropylene porous materials, and polytetrafluoroethylene porous materials; or inorganic materials such as porous diatomaceous earth materials.

[0048] In this embodiment, the reaction solvent (and extraction solvent) are removed by in-situ evaporation. After the reaction liquid sample is added to the extraction column 1, the top of the extraction column 1 is sealed with a vacuum sealing cap 6 and a vacuum pump is connected. The bottom of the extraction column 1 is sealed with a sealing plug 14. Then, it is placed in a vacuum heating evaporator, and the appropriate vacuum degree and temperature are adjusted to carry out in-situ vacuum evaporation.

[0049] In this embodiment, the sample to be separated and purified is directly eluted in situ in the extraction column 1 and injected into the separation chromatography column. At this time, the function of the adsorption extraction packing layer 2 is similar to that of silica gel in traditional silica gel mixing, that is, "uniform adsorption of crude product", which automatically completes the solid loading process of the traditional method.

[0050] The specific operating method for using the medium-low pressure preparative chromatographic sample purification and automatic sample injection device of this invention to achieve sample purification and automatic sample loading is as follows: 1) After the chemical synthesis reaction is completed, add a quencher to the reaction flask to terminate the reaction (this step can be ignored if the synthesis reaction does not require quenching).

[0051] 2) Pour all the quenched reaction solution into the extraction column 1 and let it stand until the reaction solution completely wets the adsorption extraction packing layer 2.

[0052] 3) Use the vacuum sealing cap 6 to seal and lock the upper open end of the extraction column 1, and use the sealing plug 14 to seal and block the lower interface 11 of the extraction column 1; then, put the extraction column 1 into the vacuum evaporation heater 3, adjust the appropriate temperature and vacuum, and remove the organic solvent (and extraction solvent) in the reaction solution through the vacuum evaporation heater 3.

[0053] 4) After the solvent has evaporated and been completely removed, take out the extraction column 1 and remove the vacuum sealing cap 6 at the top and the sealing plug 14 at the bottom; then install the flow control valve 7 at the lower interface 11 and install the entire device on top of the filtration flask 8 or other filtration equipment; finally, add washing solvent from the top of the extraction column 1 and filter and wash to remove water-soluble inorganic salts, catalysts or high-boiling-point solvents.

[0054] The vacuum sealing cap 6 has a vacuum port 61 at the top, and a sealing ring 62 is provided between the vacuum sealing cap 6 and the extraction column tube 1; the filtration flask 8 is connected to a filtration vacuum port 81; the washing solvent is such as distilled water or other washing solvents.

[0055] 5) Vacuum drying of extraction column 1 is performed again using vacuum evaporation heater 3.

[0056] 6) Push one end of the injection rod 4 with the sealing component 41 into the extraction column tube 1 from the top opening, compress the adsorption extraction packing layer 2 to a suitable tightness and lock the current position of the injection rod 4; adjust the sealing component 41 at the bottom of the injection rod 4 until the expansion sealing ring 411 completely seals the extraction column tube 1.

[0057] 7) After the extraction column 1 is assembled, connect the upper interface 12 to the mobile phase chromatography pump and the lower interface 11 to the inlet of the chromatography separation column. Adjust the appropriate operating parameters so that the analytes in the adsorption extraction packing layer 2 are directly eluted into the chromatography separation column by the mobile phase, and the separation and purification of the reaction products are automatically completed.

[0058] The above description is merely a preferred embodiment of this utility model and is not intended to limit the utility model. Various modifications and variations can be made to this utility model by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this utility model should be included within the protection scope of this utility model.

Claims

1. A device for low to medium pressure preparation of chromatographic sample purification and automated injection, characterized in that, This includes the extraction column, vacuum evaporation heater, and injection rod; The upper end of the extraction column is open, and the lower end is connected to a lower interface. The extraction column is filled with an adsorption extraction packing layer above the lower interface. The adsorption extraction packing layer is a flexible, mechanically compressible material with interconnected porous structure, used to adsorb the target reaction mixture. The vacuum evaporation heater is fitted outside the extraction column and is used to remove the target reaction mixture by vacuum heating and evaporation. The injection rod has a liquid channel connected along the axial direction, and a sealing component is circumferentially fitted on one end of the injection rod. The end of the injection rod with the sealing component is pushed into the extraction column tube from the upper opening to compress the adsorption extraction packing layer. The outer wall of the sealing component is in close contact with the inner wall of the extraction column tube to seal the extraction column tube.

2. The apparatus for medium-low pressure preparative chromatographic sample purification and automatic sample introduction of claim 1, wherein, The upper end of the extraction column tube has a protruding structure extending outward from the outer periphery.

3. The apparatus for medium-low pressure preparative chromatographic sample purification and automatic sample introduction of claim 2, wherein, The extraction column is equipped with a locking mechanism at the open end to fix the position of the injection rod extending into the extraction column.

4. The apparatus for medium-low pressure preparative chromatographic sample purification and automatic sample introduction of claim 3, wherein, The locking mechanism is slidably sleeved on the outside of the injection rod, and the locking mechanism is snapped together with the protruding structure.

5. The apparatus for medium-low pressure preparative chromatographic sample purification and automatic sample introduction of claim 1, wherein, The lower interface is equipped with a flow rate control valve.

6. The apparatus for medium-low pressure preparative chromatographic sample purification and automatic sample introduction of claim 1, wherein, The upper and lower parts of the adsorption extraction packing layer are respectively provided with an upper sieve plate and a lower sieve plate.

7. The apparatus for medium-low pressure preparative chromatographic sample purification and automatic sample introduction of claim 1, wherein, The sealing assembly includes an expansion sealing ring, which is fixedly sleeved on the outer periphery of the injection rod.

8. The apparatus for medium-low pressure preparative chromatographic sample purification and automatic sample introduction of claim 1, wherein, The end of the injection rod away from the sealing assembly is connected to the liquid channel and has an upper interface.

9. The apparatus for medium-low pressure preparative chromatographic sample purification and automatic sample introduction of claim 8, wherein, The upper interface is used to connect to the mobile phase chromatography pump, and the lower interface is used to connect to the inlet of the chromatography column.

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