An apparatus for an oxygen-free column chromatography of an oxidizable compound

Abstract

The utility model discloses a kind of oxygen-free column chromatography device for easily oxidizable compound, inert gas is passed through the air pipe of deoxygenated solvent bottle, and solvent is treated by deoxygenation;Chromatography column cylinder is continuously passed through inert gas import, maintains positive pressure in column, effectively isolates air, realizes whole oxygen-free environment, avoids easily oxidizable compound to be oxidized;Each connecting part of device adopts sealing design, deoxygenated solvent bottle and chromatography column cylinder closely cooperate, so that the operation of filling, sample loading, leaching, collection is carried out in relatively sealed environment, reduce the possibility of oxygen entering;The device is provided with pressure balance neck with silica gel drying tube, which facilitates the observation of pressure balance in the column;By controlling the amount of inert gas input, the control of solvent flow rate can be realized, and the whole process is visualized, which facilitates accurate operation of experimental personnel.

Description

Technical Field

[0001] This invention belongs to the field of chemical experimental apparatus technology, specifically relating to an oxygen-free column chromatography apparatus for easily oxidized compounds. Background Technology

[0002] In chemical experiments, column chromatography is a common method for separating and purifying compounds. However, for easily oxidized compounds, they readily react with oxygen in the air during the separation and purification process, leading to compound deterioration and affecting the separation efficiency and product purity. Conventional column chromatography apparatuses struggle to achieve a completely oxygen-free environment throughout the process, and their poor sealing during operation makes it difficult to effectively prevent oxygen interference. Although oxygen-free operation can be performed in a glove box, such apparatuses are expensive, and the use of rubber gloves during experiments restricts operation and space. Therefore, this paper proposes a simple, highly operable, oxidation-resistant column chromatography apparatus that can solve the aforementioned problems in the column chromatography purification of easily oxidized compounds. Utility Model Content

[0003] The purpose of this invention is to overcome the shortcomings of existing technologies and provide an oxygen-free column chromatography device for easily oxidized compounds. This device can achieve fully oxygen-free, relatively sealed operation, and has good pressure balance and flow rate control visualization effects. This invention constructs a three-dimensional inert environment closed-loop system (inert protection, solvent deoxygenation, column bed inert protection), and combines it with low-temperature assisted chromatography (double-layer jacketed chromatography column, cold coal circulation).

[0004] To achieve the above objectives, the present invention adopts the following technical solution:

[0005] This invention provides an oxygen-free column chromatography apparatus for easily oxidized compounds, comprising a chromatography column (1) and a deoxygenated solvent bottle (4); the chromatography column (1) extends upward to form a pressurization tube (3), an eluent inlet neck (3-2), and a chromatography flow control valve (6); the eluent inlet neck (3-2) is nested in the pressurization tube (3) and is not directly connected to the gas pressure balance neck (3-1), which can prevent gas pressure or inert gas from affecting the outflow of eluent; inert gas enters the pressurization tube (3) from the inert gas inlet neck (6-1), and the inert gas valve (6-3) is adjusted to make the inert gas have appropriate pressure to force the deoxygenated solvent flowing out of the deoxygenated solvent bottle (4) into the chromatography column (1), wherein the inert gas outlet neck (6-2) is used to discharge excess inert gas when adjusting the gas pressure;

[0006] The chromatography column (1) extends downwards into a three-port eluent collection tube (2), a first receiving bottle (5-1), a second receiving bottle (5-2), and a third receiving bottle (5-3). The three-port eluent collection tube (2) is equipped with a three-port collection tube stopcock (2-1) and a pressure safety valve (2-2). The three-port collection tube stopcock (2-1) controls the flow of solvent from the chromatography column (1) into the first receiving bottle (5-1), the second receiving bottle (5-2), and the third receiving bottle (5-3). The pressure safety valve (2-2) allows the solvent to flow from the chromatography column (1) into the first receiving bottle (5-1), the second receiving bottle (5-2), and the third receiving bottle (5-3). The first receiving bottle (5-1), the second receiving bottle (5-2), and the third receiving bottle (5-3) are evacuated to provide an oxygen-free environment and allow inert gas to be discharged. The three-way eluent collection tube (2) is connected to the chromatography column (1) via a ball mill interface. When receiving solvent flowing out of the chromatography column (1), the first receiving bottle (5-1), the second receiving bottle (5-2), and the third receiving bottle (5-3) can adjust the angle of the three-way eluent collection tube (2) by adjusting this ball mill interface to ensure that the solvent flows into only one of the receiving bottles.

[0007] The deoxygenating solvent bottle (4) is provided with a first opening (4-1) and a second opening (4-2) at the top. The first opening (4-1) serves as a solvent feeding port. The middle part of the gas blowing pipe (4-3) is connected to the second opening (4-2). A three-way valve is provided at the upper end of the gas blowing pipe (4-3) to regulate the amount of gas flowing in. The lower end of the gas blowing pipe (4-3) extends into the bottom of the deoxygenating solvent bottle (4). The bottom of the deoxygenating solvent bottle (4) is connected to the eluent inlet neck (3-2) and is provided with a deoxygenating solvent bottle valve (4-4) to control the solvent outflow from the bottle. Inert gas enters the deoxygenating solvent bottle (4) containing the solvent to be deoxygenated from the three-way valve of the gas blowing pipe (4-3) for deoxygenation. After the solvent is deoxygenated, the deoxygenating solvent bottle valve (4-4) is opened, and the solvent flows to the eluent inlet neck (3-2) and enters the chromatography column (1).

[0008] In a preferred embodiment of this utility model, the pressurization tube (3) at the upper end of the chromatography column (1) is connected to the chromatography flow control valve (6) and the deoxygenation solvent bottle (4), and the lower end of the chromatography column (1) is connected to the eluent three-port collection tube (2), the first receiving bottle (5-1), the second receiving bottle (5-2) and the third receiving bottle (5-3); a coolant inlet (1-1) is provided on the lower side of the chromatography column (1), and a coolant outlet (1-2) is provided on the upper side of the chromatography column (1).

[0009] In a preferred embodiment of this utility model, the deoxygenating solvent bottle (4) is a Schlenk bottle or a sealed glass bottle, with a first opening (4-1), a second opening (4-2) and a deoxygenating solvent bottle valve (4-4).

[0010] In a preferred embodiment of this utility model, the chromatography column (1) has a double-layer jacket structure, and the double-layer jacket is used to introduce refrigerant for low-temperature treatment.

[0011] In a preferred embodiment of this utility model, the connection between the lower end of the chromatography column (1) and the upper end of the eluent three-port collection tube (2) is a ball mill joint, which can rotate freely; the eluent three-port collection tube (2) is equipped with a three-port collection tube stopcock (2-1) to control the outflow of solvent from the chromatography column (1); a pressure safety valve (2-2) is provided in the middle of the eluent three-port collection tube (2) to allow the first receiving bottle (5-1), the second receiving bottle (5-2) and the third receiving bottle (5-3) to be evacuated to provide an oxygen-free environment and allow inert gas to be discharged.

[0012] In a preferred embodiment of this utility model, the three-port collection tube stopcock (2-1) is a polytetrafluoroethylene stopcock.

[0013] Compared with existing technologies, this utility model provides an oxygen-free column chromatography apparatus for easily oxidized compounds, which has the following advantages:

[0014] (1) Full-process oxygen-free protection: Inert gas is introduced through the venting tube of the deoxygenated solvent bottle to deoxygenate the solvent; inert gas is continuously introduced into the chromatography column through the high-pressure inert gas inlet to maintain positive pressure inside the column, effectively isolate air, realize a full-process oxygen-free environment, and avoid the oxidation of easily oxidized compounds.

[0015] (2) Relatively sealed operation: All connecting parts of the device adopt a sealed design. The deoxygenation solvent bottle and chromatography column are coordinated to ensure that operations such as loading, sample loading, rinsing and collection are carried out in a relatively sealed environment, reducing the possibility of oxygen entering.

[0016] (3) Visual control: A chromatography flow control valve is set up to facilitate observation and adjustment of the pressure balance in the column; the flow rate of the eluent is controlled by controlling the amount of inert gas introduced for pressurization operation, and the whole process is visualized, which facilitates precise operation by the experimenters.

[0017] (4) Complete functions: The chromatography column adopts a double-layer jacket structure to achieve low temperature treatment and meet the separation requirements of different easily oxidized compounds; the fraction collection system adopts Schlenk receiving flasks, which facilitates the collection of different fractions and ensures an oxygen-free environment during the collection process. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the utility model. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 This is a schematic diagram of the structure of an oxygen-free column chromatography apparatus for easily oxidized compounds, provided by an embodiment of the present invention.

[0020] Figure reference numerals: 1. Double-layer chromatography column body; 1-1. Coolant inlet; 1-2. Coolant outlet; 2. Three-port eluent collection tube; 2-1. Three-port collection tube stopcock; 2-2. Pressure safety valve; 3. Pressurization tube; 3-1. Pressure balance neck; 3-2. Eluent inlet neck; 4. Deoxygenating solvent bottle; 4-1. First opening; 4-2. Second opening; 4-3. Gas blowing tube; 4-4. Deoxygenating solvent bottle valve; 5-1. First receiving bottle; 5-2. Second receiving bottle; 5-3. Third receiving bottle; 6. Chromatography flow control valve; 6-1. Inert gas inlet neck; 6-2. Inert gas outlet neck; 6-3. Inert gas regulating valve. Detailed Implementation

[0021] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this application without creative effort are within the scope of protection of this application. The terms "upper," "lower," "front," "rear," "left," and "right," etc., used when describing the installation position or direction of the structure or components in this embodiment are based on the orientation shown in the accompanying drawings. They are merely for convenience of description and are used to distinguish the relative positions of various components or directions, and do not represent the orientation of the device or functional component in this embodiment during use.

[0022] This invention provides an anaerobic column chromatography apparatus for easily oxidized compounds. It is an experimental device specifically designed for separating and purifying compounds that are easily oxidized by air. Based on the traditional column chromatography technique of separating components in a mixture by utilizing the distribution / adsorption differences between the stationary and mobile phases, this apparatus maintains an anaerobic environment throughout the separation process through a special structural design, thus preventing the target compound from oxidizing and deteriorating due to contact with oxygen.

[0023] Specifically, such as Figure 1As shown, an oxygen-free column chromatography apparatus for easily oxidized compounds includes a chromatography column 1 and a deoxygenated solvent bottle 4. The chromatography column 1 extends upwards into a pressurization tube 3, an eluent inlet neck 3-2, and a chromatography flow control valve 6. The eluent inlet neck 3-2 is nested within the pressurization tube 3 and is not directly connected to the pressure balancing neck 3-1, thus preventing pressure or inert gas from affecting the eluent flow. Inert gas enters the pressurization tube 3 from the inert gas inlet neck 6-1. The inert gas valve 6-3 is adjusted to provide appropriate pressure for the inert gas to force the deoxygenated solvent flowing from the deoxygenated solvent bottle 4 into the chromatography column 1. The inert gas outlet neck 6-2 is used to discharge excess inert gas when adjusting the pressure.

[0024] The chromatography column 1 extends downwards to form a three-port eluent collection tube 2, a first receiving bottle 5-1, a second receiving bottle 5-2, and a third receiving bottle 5-3. The three-port eluent collection tube 2 is equipped with a three-port collection tube stopcock 2-1 and a pressure safety valve 2-2. The three-port collection tube stopcock 2-1 controls the flow of solvent from the chromatography column 1 into the first receiving bottle 5-1, the second receiving bottle 5-2, and the third receiving bottle 5-3. The pressure safety valve 2-2 can evacuate the first receiving bottle 5-1, the second receiving bottle 5-2, and the third receiving bottle 5-3 to provide an oxygen-free environment and allow inert gas to be discharged. The three-port eluent collection tube 2 is connected to the chromatography column 1 via a ball mill interface. When receiving solvent from the chromatography column 1, the first receiving bottle 5-1, the second receiving bottle 5-2, and the third receiving bottle 5-3 can adjust this ball mill interface to change the angle of the three-port eluent collection tube 2, ensuring that the solvent flows into only one of the receiving bottles.

[0025] The deoxygenating solvent bottle 4 has a first opening 4-1 and a second opening 4-2 at its top. The first opening 4-1 serves as the solvent feeding port. The middle part of the venting pipe 4-3 is connected to the second opening 4-2. A three-way valve is provided at the upper end of the venting pipe 4-3 to regulate the amount of gas flowing in. The lower end of the venting pipe 4-3 extends into the bottom of the deoxygenating solvent bottle 4. The bottom of the deoxygenating solvent bottle 4 is connected to the eluent inlet neck 3-2 and is equipped with a deoxygenating solvent bottle valve 4-4 to control the outflow of solvent from the bottle. Inert gas enters the deoxygenating solvent bottle 4 containing the solvent to be deoxygenated through the three-way valve of the venting pipe 4-3 for deoxygenation. After the solvent is deoxygenated, the deoxygenating solvent bottle valve 4-4 is opened, and the solvent flows to the eluent inlet neck 3-2 and enters the chromatography column 1.

[0026] In this embodiment, the pressurization tube 3 at the upper end of the chromatography column 1 is connected to the chromatography flow control valve 6 and the deoxygenation solvent bottle 4. The lower end of the chromatography column 1 is connected to the eluent three-port collection tube 2, the first receiving bottle 5-1, the second receiving bottle 5-2 and the third receiving bottle 5-3. A coolant inlet 1-1 is provided on the lower side of the chromatography column 1, and a coolant outlet 1-2 is provided on the upper side of the chromatography column 1.

[0027] The deoxygenation solvent bottle 4 is a Schlenk bottle or a sealed glass bottle, equipped with a first opening 4-1, a second opening 4-2, and a deoxygenation solvent bottle valve 4-4. The chromatography column 1 has a double-jacketed structure, which is used to introduce a refrigerant for low-temperature treatment, meeting the separation requirements of temperature-sensitive and easily oxidized compounds. The inert gas is Ar or N2.

[0028] In this embodiment, the venting tube 4-3 connected to the top of the deoxygenated solvent bottle 4 extends into the bottom of the bottle and is used to introduce inert gas to deoxygenate the solvent in the bottle; the deoxygenated solvent bottle valve 4-4 connected to the bottom of the deoxygenated solvent bottle 4 is connected to the inlet neck 3-2 of the chromatography column 1 and is used to transport the deoxygenated solvent to the chromatography column 1.

[0029] The eluent inlet neck 3-2 of the chromatography column 1 receives solvent from the deoxygenated solvent bottle; the inert gas inlet neck 6-1 of the chromatography column 1, together with the high-pressure inert gas cylinder, can be used for pressurized operation and can also be used to introduce inert gas to maintain positive pressure inside the column; the inert gas outlet neck 6-2 is used to balance the gas pressure inside the column and can be connected to a silica gel drying tube to prevent external moisture from entering.

[0030] The operation procedure of an oxygen-free column chromatography apparatus for easily oxidized compounds is as follows:

[0031] Solvent deoxygenation: Add solvent to deoxygenated solvent bottle 4, and introduce inert gas through the venting tube to deoxygenate the solvent. Solvent deoxygenation can largely prevent the compound from being oxidized by air.

[0032] Initial deoxygenation: After evacuating the chromatography column through the three-port collection tube 2 of the eluent at the bottom of the column, an inert gas is introduced. This process is repeated several times to ensure that there is no oxygen in the column.

[0033] Silica gel column packing: Wet packing is the optimal method for silica gel column packing. The silica gel sol is first deoxygenated by ultrasonication with inert gas before being poured into the chromatography column. The deoxygenated solvent (4) flows into the chromatography column, and inert gas is introduced by adjusting the chromatography flow control valve (6). The silica gel column is then compacted, and this process is repeated several times to ensure that the column is oxygen-free.

[0034] Sample loading: The sample dissolved in the deoxygenated solvent is dropped directly into the chromatography column from the top of the column.

[0035] Elution separation: Use the same elution procedure as for "silicone column packing" to elute the chromatography column with deoxygenating solvents of different polarities to purify the sample.

[0036] Fraction collection: By adjusting the ball mill interface between the chromatography column 1 and the three-necked eluent collection tube 2, the angle of the three-necked eluent collection tube 2 is changed, and different fractions are collected into the corresponding Schlenk receiving flasks.

[0037] Example 1: Anaerobic column chromatography purification of Fam-phosphoramide monomer

[0038] Fam-phosphorous amide is easily oxidized; therefore, column chromatography separation is optimally performed under low-temperature, anaerobic conditions. First, follow... Figure 1 The apparatus was set up. An appropriate amount of silica gel was added to petroleum ether and stirred until homogeneous. The mixture was then sonicated and deoxygenated using inert gas. This deoxygenated silica gel was then packed into column 1 of the chromatography column. An appropriate amount of petroleum ether was first added to the deoxygenation flask for later use. Argon gas was then introduced through the inert gas inlet neck 6-1 to compact the silica gel column. The column was cooled by a refrigerant to ensure low-temperature separation; the refrigerant flowed in from the coolant inlet 1-1 and out from the coolant outlet 1-2. 5g of Fam-phosphoramide compound was added for sample separation. A gradient eluent of petroleum ether and ethyl acetate was added to the deoxygenation flask, and after deoxygenation, it was added dropwise to the column for separation and purification. This apparatus significantly reduced the oxidation rate of the compound, increasing the product recovery rate from less than 40% to approximately 85%.

[0039] Those skilled in the art should understand that this utility model is not limited to the above embodiments. The embodiments and descriptions in the specification are merely preferred examples of this utility model and are not intended to limit it. Various changes and modifications can be made to this utility model without departing from its spirit and scope, and all such changes and modifications fall within the scope of this utility model as claimed. The scope of protection of this utility model is defined by the appended claims and their equivalents.

Claims

1. An oxygen-free column chromatography apparatus for easily oxidized compounds, characterized in that, The system includes a chromatography column (1) and a deoxygenated solvent bottle (4). The chromatography column (1) extends upward to form a pressurization tube (3), an eluent inlet neck (3-2), and a chromatography flow control valve (6). The eluent inlet neck (3-2) is nested in the pressurization tube (3) and is not directly connected to the gas pressure balance neck (3-1), which can prevent gas pressure or inert gas from affecting the eluent outflow. Inert gas enters the pressurization tube (3) from the inert gas inlet neck (6-1). The inert gas valve (6-3) is adjusted to give the inert gas appropriate pressure to force the deoxygenated solvent flowing out of the deoxygenated solvent bottle (4) into the chromatography column (1). The inert gas outlet neck (6-2) is used to discharge excess inert gas when adjusting the gas pressure. The chromatography column (1) extends downwards into a three-port eluent collection tube (2), a first receiving bottle (5-1), a second receiving bottle (5-2), and a third receiving bottle (5-3). The three-port eluent collection tube (2) is equipped with a three-port collection tube stopcock (2-1) and a pressure safety valve (2-2). The three-port collection tube stopcock (2-1) controls the flow of solvent from the chromatography column (1) into the first receiving bottle (5-1), the second receiving bottle (5-2), and the third receiving bottle (5-3). The pressure safety valve (2-2) allows the solvent to flow from the chromatography column (1) into the first receiving bottle (5-1), the second receiving bottle (5-2), and the third receiving bottle (5-3). The first receiving bottle (5-1), the second receiving bottle (5-2), and the third receiving bottle (5-3) are evacuated to provide an oxygen-free environment and allow inert gas to be discharged. The three-way eluent collection tube (2) is connected to the chromatography column (1) via a ball mill interface. When receiving solvent flowing out of the chromatography column (1), the first receiving bottle (5-1), the second receiving bottle (5-2), and the third receiving bottle (5-3) can adjust the angle of the three-way eluent collection tube (2) by adjusting this ball mill interface to ensure that the solvent flows into only one of the receiving bottles. The deoxygenating solvent bottle (4) is provided with a first opening (4-1) and a second opening (4-2) at the top. The first opening (4-1) serves as a solvent feeding port. The middle part of the gas blowing pipe (4-3) is connected to the second opening (4-2). A three-way valve is provided at the upper end of the gas blowing pipe (4-3) to regulate the amount of gas flowing in. The lower end of the gas blowing pipe (4-3) extends into the bottom of the deoxygenating solvent bottle (4). The bottom of the deoxygenating solvent bottle (4) is connected to the eluent inlet neck (3-2) and is provided with a deoxygenating solvent bottle valve (4-4) to control the solvent outflow from the bottle. Inert gas enters the deoxygenating solvent bottle (4) containing the solvent to be deoxygenated from the three-way valve of the gas blowing pipe (4-3) for deoxygenation. After the solvent is deoxygenated, the deoxygenating solvent bottle valve (4-4) is opened, and the solvent flows to the eluent inlet neck (3-2) and enters the chromatography column (1).

2. The oxygen-free column chromatography apparatus for easily oxidized compounds according to claim 1, characterized in that, The pressurization tube (3) at the upper end of the chromatography column (1) is connected to the chromatography flow control valve (6) and the deoxygenation solvent bottle (4). The lower end of the chromatography column (1) is connected to the eluent three-port collection tube (2), the first receiving bottle (5-1), the second receiving bottle (5-2), and the third receiving bottle (5-3). A coolant inlet (1-1) is provided on the lower side of the chromatography column (1), and a coolant outlet (1-2) is provided on the upper side of the chromatography column (1).

3. The oxygen-free column chromatography apparatus for easily oxidized compounds according to claim 1, characterized in that, The deoxygenated solvent bottle (4) is a Schlenk bottle or a sealed glass bottle with a first opening (4-1), a second opening (4-2) and a deoxygenated solvent bottle valve (4-4).

4. The oxygen-free column chromatography apparatus for easily oxidized compounds according to claim 1, characterized in that, The chromatography column (1) has a double-layer jacket structure, and the double-layer jacket is used to introduce refrigerant for low-temperature treatment.

5. The oxygen-free column chromatography apparatus for easily oxidized compounds according to claim 1, characterized in that, The connection between the lower end of the chromatography column (1) and the upper end of the eluent three-port collection tube (2) is a ball mill joint, which can rotate freely; the eluent three-port collection tube (2) is equipped with a three-port collection tube stopcock (2-1) to control the outflow of solvent from the chromatography column (1); a pressure safety valve (2-2) is provided in the middle of the eluent three-port collection tube (2) to allow the first receiving bottle (5-1), the second receiving bottle (5-2) and the third receiving bottle (5-3) to be evacuated to provide an oxygen-free environment and allow inert gas to be discharged.

6. The oxygen-free column chromatography apparatus for easily oxidized compounds according to claim 5, characterized in that, The three-port collection tube stopcock (2-1) is a polytetrafluoroethylene stopcock.

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