CN216678233U - Solid phase organic synthesis equipment - Google Patents

Abstract

The utility model provides solid-phase organic synthesis equipment, which comprises an external framework, wherein an equipment control and data recording component, a reaction reagent preparation component, a reactor component, a waste liquid collection component, a solvent component, a valve component, an electronic device component, a gas and temperature regulation component and a connecting pipeline are arranged in the external framework; the equipment control and data recording component is connected with the electronic device component; the electronic device component is connected with the reaction reagent preparation component, the reactor component, the solvent component, the gas and temperature regulation component; the reaction reagent preparation component, the waste liquid collection component and the solvent component are communicated with the reactor component through connecting pipelines; the valve component is arranged on the connecting pipeline. The utility model has the characteristics of simple and stable operation, wide application range, easy assembly disassembly and replacement and capability of finishing various solid-phase organic synthesis reactions.

Description

Solid phase organic synthesis equipment

Technical Field

The utility model relates to the technical field of solid-phase organic synthesis, in particular to solid-phase organic synthesis equipment.

Background

In 1963, the solid phase peptide synthesis method (SPPS) was first proposed by Bruce Merrifield, a famous biological chemist. The first automatic solid phase polypeptide synthesizer was used in 1966 for mass production of polypeptide, and comprises a reactor unit and a control unit, wherein the reactor unit is used for stirring the reactant by bubbling nitrogen gas, and the first generation of polypeptide synthesizer is realized by controlling computer program. Although it has obvious disadvantages in terms of stirring mode and other functions, it is left after all from the laboratory, facilitating automation of polypeptide synthesis. The synthesis method with milestone significance in polypeptide chemistry is the first choice method for polypeptide synthesis due to convenient and rapid synthesis.

In the eighties of the last century, the reactants were stirred by a nitrogen bubbling reaction method based on the prior art, and a mild and dead-angle-free stirring method by adjusting the air pressure was used for the synthesis reaction. Meanwhile, a stirring mode that the reactor swings left and right around the origin or moves circularly under the vertical condition is also proposed, but the stirring mode has no good effect for technical reasons. In the nineties of the last century, the method is characterized in that the concept of dead-angle-free stirring is further strengthened by combining the concept of the former synthesizer, namely, the upper part of the reactor is relatively fixed, and the lower part of the reactor is rapidly rotated for 360 degrees in a circumference manner, so that solid and liquid in the reactor are driven to make spiral motion from the bottom to the top until the top of the reactor is reached; or a novel stirring mode that the middle point of the reactor is used as the center of a circle, the reactor is stirred in a rotating way at 180 degrees up and down, and the stirring is integrated with nitrogen bubbling. The synthesis purity of the peptide is ensured by a stirring mode without dead angles, so that a solid phase polypeptide synthesis system is further improved.

However, most of these changes are performed around the synthesis of polypeptide products, and the success of solid-phase synthesis of polypeptides has derived a technical revolution, and more other organic small-molecule or large-molecule products are gradually adopting solid-phase synthesis methods, and particularly with the development of gene technology and bioengineering technology in the nineties, the application of solid-phase synthesis of polypeptide nucleic acid synthesis, oligonucleotide synthesis and the like is also emerging, so that an independent subject, namely solid-phase organic synthesis (SPOS), is formed in the last decades.

The difficulty and complexity of solid-phase organic synthesis is far superior to those of solid-phase polypeptide synthesis. Mainly because the reaction type of solid phase organic synthesis is complicated, not only the formation of amido bond is involved, but also more reaction types such as disulfide bond, ester bond, ether bond, phenolic hydroxyl, phosphorous ester bond, oligonucleotide 5' hydroxyl coupling and the like are involved, and several different reaction types or conditions need to be found, so that the temperature control of a reactor, the initial temperature of a reaction reagent and the temperature control of washing liquor are very strict in the operation process, and the requirements of the washing reagent and the washing condition are more diversified.

Therefore, the solid phase synthesis device sold in the market at present is difficult to meet the new requirements of different types of solid phase organic synthesis, and mainly has the following defects: 1) the solid phase synthesis device sold in the market at present mainly synthesizes polypeptide products, the reaction mainly forms amido bonds, and other chemical bonds such as ester bonds, hydroxyl, disulfide bonds, phosphorous ester bonds, oligonucleotide 5' hydroxyl coupling and the like have no corresponding function setting, so that the application of the solid phase synthesis device in other solid phase organic synthesis is limited; 2) the solid phase synthesis device sold in the market at present is either in a small-scale or a pilot-scale mode, and no device can meet the small-scale condition and also can be applied to pilot-scale production equipment; 3) the solid phase synthesis device sold in the market at present has almost corresponding temperature control on reaction temperature, pre-dissolved reaction liquid temperature and washing liquid temperature, so that the application of the solid phase synthesis device in solid phase polypeptide and organic synthesis is limited, and the solid phase synthesis device cannot be used for chemical reaction with harsh conditions.

Patent document CN213295218U discloses a solid phase synthesis device for simultaneously synthesizing multiple polypeptides, and relates to the technical field of polypeptide solid phase synthesis. This solid phase synthesis device of many polypeptides of simultaneous synthesis, including the reaction box, reaction box top both sides all are provided with the funnel, the funnel top is provided with the apron, the apron top is provided with the inlet pipe, the funnel top is provided with the unloading subassembly, the unloading subassembly includes connecting rod, sleeve, first montant, second montant and perpendicular section of thick bamboo, the funnel bottom is provided with vertical section, the sleeve cover is located the connecting rod outside and is connected with the connecting rod rotation. However, this patent document is directed to solid phase polypeptide synthesis and not to solid phase organic synthesis.

SUMMERY OF THE UTILITY MODEL

Aiming at the defects in the prior art, the utility model aims to provide a solid-phase organic synthesis device.

The solid-phase organic synthesis equipment provided by the utility model comprises an external framework, wherein an equipment control and data recording component, a reaction reagent preparation component, a reactor component, a waste liquid collection component, a solvent component, a valve component, an electronic component, a gas and temperature regulation component and a connecting pipeline are arranged in the external framework;

the equipment control and data recording component is connected with the electronic device component;

the electronic device assembly is connected with the reaction reagent preparation assembly, the reactor assembly, the solvent assembly, the gas and temperature regulation assembly;

the reaction reagent preparation assembly, the waste liquid collection assembly and the solvent assembly are communicated with the reactor assembly through the connecting pipeline; the valve assembly is arranged on the connecting pipeline.

Preferably, the reactor assembly comprises a first reactor assembly and a second reactor assembly;

the electronic device assembly is connected with the first reactor assembly and the second reactor assembly;

the reaction reagent preparation assembly is communicated with the first reactor assembly through the connecting pipeline; the waste liquid collecting assembly is communicated with the first reactor assembly and the second reactor assembly through the connecting pipeline; the solvent assembly is communicated with the first reactor assembly and the second reactor assembly through the connecting pipeline;

the first reactor assembly and the second reactor assembly are switchable.

Preferably, the solvent assembly comprises a first solvent assembly and a second solvent assembly, and the first solvent assembly is communicated with the second solvent assembly through the connecting pipeline;

the electronic device assembly is connected with the first solvent assembly and the second solvent assembly;

the first solvent assembly is communicated with the first reactor assembly and the second reactor assembly through the connecting pipeline; the second solvent assembly is communicated with the second reactor assembly through the connecting pipeline.

Preferably, the valve assembly comprises a solenoid valve, a pneumatic valve and a flow control valve;

the electromagnetic valve, the pneumatic valve and the flow control valve are all arranged on the connecting pipeline; the solenoid valve and the pneumatic valve are used to regulate liquid delivery, and the flow control valve is used to regulate the liquid delivery rate.

Preferably, the connection pipeline between the reaction reagent preparation component and the first reactor component is provided with an electromagnetic valve and a flow control valve, and the connection pipeline between the reaction reagent preparation component and the second reactor component is provided with an electromagnetic valve and a flow control valve;

a pneumatic valve is arranged on the connecting pipeline of the waste liquid collecting assembly and the first reactor assembly, and a pneumatic valve is arranged on the connecting pipeline of the waste liquid collecting assembly and the second reactor assembly;

the connecting pipeline between the first solvent assembly and the first reactor assembly is provided with an electromagnetic valve and a flow control valve, and the connecting pipeline between the first solvent assembly and the second reactor assembly is provided with an electromagnetic valve and a flow control valve;

and the connecting pipeline of the second solvent assembly and the first reactor assembly is provided with an electromagnetic valve and a flow control valve, and the connecting pipeline of the second solvent assembly and the second reactor assembly is provided with an electromagnetic valve and a flow control valve.

Preferably, the first solvent assembly and the second solvent assembly each comprise a plurality of solvent bottles of different volumes;

the jacket heat preservation device or the air-cooled heat preservation device is arranged outside the solvent bottle and used for preserving heat of the solvent bottle.

Preferably, the first reactor assembly comprises a six-channel reactor and the second reactor assembly comprises a twelve-channel reactor;

the six-channel reactor is divided into three independent heat-preservation reaction zones, and the twelve-channel reactor is divided into four independent heat-preservation reaction zones.

Preferably, the heat-preservation reaction zone is provided with a jacket heat-preservation device, and the jacket heat-preservation device is used for adjusting the temperature of the heat-preservation reaction zone.

Preferably, a bubbling and mechanical stirring device is arranged in the six-channel reactor, and a bubbling stirring device is arranged in the twelve-channel reactor;

the electronic device assembly is connected with the bubbling and mechanical stirring device and the bubbling stirring device.

Preferably, the reaction reagent preparing component comprises a reaction reagent preparing area and a plurality of reaction reagent bottles;

the reaction reagent preparation area is provided with an air cooling/heating temperature control device, and the air cooling/heating temperature control device is used for adjusting the temperature of the reaction reagent preparation area.

Compared with the prior art, the utility model has the following beneficial effects:

1. the solid phase synthesizer is optimized, so that the solid phase synthesizer can meet the requirement of polypeptide synthesis and can also perform solid phase synthesis of other chemical molecules;

2. the reactor part components of the solid phase synthesizer are optimized, three/four independent jacket heat preservation components are arranged, three/four different temperatures can be adjusted simultaneously, the stirring mode is carried out in a bubbling and mechanical stirring mode, and the stirring speed is adjustable, so that the synthesis amount of the solid phase carrier from 0.25 millimole to 20 millimoles can be met;

3. according to the utility model, by adjusting the temperature of the reactor, at most 12 small-scale experimental conditions of different reaction types can be developed in the assembly, and no more than 6 pilot-scale experimental conditions can be developed or repeated after the reactor is simply replaced, and the experiment can be completed by bubbling, mechanical stirring or combination of the bubbling and mechanical stirring;

4. the reaction reagent preparation assembly of the solid phase synthesizer is optimized, the temperature control device is arranged in the reaction reagent preparation area, the temperature of the reaction reagent can be adjusted at any time at 0-50 ℃, the chemical reaction with special requirements on the reaction temperature is met, the temperature of the reaction reagent can be adjusted more quickly, and the exploration of reaction experiment conditions needing special temperature control is completed;

5. the solvent assembly of the solid phase synthesizer is optimized, part of solvent bottles are provided with the temperature control devices, the requirements of reaction or washing solvents under the condition of 20-40 ℃ or 0-30 ℃ can be met, and meanwhile, the washing reagent channels are added, so that different reagents can be selected for washing solid phase carriers according to different reaction conditions.

Drawings

Other features, objects and advantages of the utility model will become more apparent upon reading of the detailed description of non-limiting embodiments with reference to the following drawings:

FIG. 1 is a right side view of a solid phase organic synthesis apparatus of the present invention;

FIG. 2 is a front view of the solid phase organic synthesis apparatus of the present invention;

FIG. 3 is a left side view of the solid phase organic synthesis apparatus of the present invention;

FIG. 4 is a schematic perspective view of the solid phase organic synthesis apparatus according to the present invention;

FIG. 5 is a schematic diagram showing the connection relationship of the components of the solid phase organic synthesis apparatus according to the present invention;

FIG. 6 is a schematic diagram showing the connection relationship of the components of the solid phase organic synthesis apparatus according to the present invention.

The figures show that:

equipment control and data recording assembly 1 solvent assembly 6

Touch screen 2 first solvent component 601

Reagent dispensing Assembly 3 second solvent Assembly 602

Reactor assembly 4 valve assembly 7

First reactor Assembly 401 electronics Assembly 8

Second reactor assembly 402 gas and temperature regulation assembly 9

Waste liquid collecting assembly 5

Detailed Description

The present invention will be described in detail with reference to specific examples. The following examples will assist those skilled in the art in further understanding the utility model, but are not intended to limit the utility model in any way. It should be noted that it would be obvious to those skilled in the art that various changes and modifications can be made without departing from the spirit of the utility model. All falling within the scope of the present invention.

Example 1:

as shown in fig. 1 to 6, the present embodiment provides a solid-phase organic synthesis apparatus, which includes an external frame, and an apparatus control and data recording assembly 1, a reagent preparing assembly 3, a reactor assembly 4, a waste liquid collecting assembly 5, a solvent assembly 6, a valve assembly 7, an electronic device assembly 8, a gas and temperature regulating assembly 9, and a connecting pipeline are disposed in the external frame. The equipment control and data recording component 1 is connected with an electronic device component 8, the electronic device component 8 is connected with a reaction reagent preparation component 3, a reactor component 4, a solvent component 6 and a gas and temperature regulation component 9, and the reaction reagent preparation component 3, the waste liquid collection component 5 and the solvent component 6 are communicated with the reactor component 4 through connecting pipelines; the valve assembly 7 is arranged on the connecting line.

The reactor assembly includes a first reactor assembly 401 and a second reactor assembly 402. The electronic device assembly 8 is connected with the first reactor assembly 401 and the second reactor assembly 402, the reaction reagent preparing assembly 3 is communicated with the first reactor assembly 401 through a connecting pipeline, the waste liquid collecting assembly 5 is communicated with the first reactor assembly 401 and the second reactor assembly 402 through a connecting pipeline, the solvent assembly 6 is communicated with the first reactor assembly 401 and the second reactor assembly 402 through a connecting pipeline, and the first reactor assembly 401 and the second reactor assembly 402 can be switched to be used.

The solvent assembly 6 comprises a first solvent assembly 601 and a second solvent assembly 602, the first solvent assembly 601 is communicated with the second solvent assembly 602 through a connecting pipeline, the electronic device assembly 8 is connected with the first solvent assembly 601 and the second solvent assembly 602, the first solvent assembly 601 is communicated with the first reactor assembly 401 and the second reactor assembly 402 through a connecting pipeline, and the second solvent assembly 602 is communicated with the second reactor assembly 402 through a connecting pipeline.

The valve assembly 7 comprises an electromagnetic valve, a pneumatic valve and a flow control valve, the electromagnetic valve, the pneumatic valve and the flow control valve are all arranged on a connecting pipeline, the electromagnetic valve and the pneumatic valve are used for adjusting liquid transmission, and the flow control valve is used for adjusting the liquid transmission speed. An electromagnetic valve and a flow control valve are arranged on a connecting pipeline between the reaction reagent preparation component 3 and the first reactor component 401 and used for adjusting the amount of the solvent entering the first reactor component 401, and an electromagnetic valve and a flow control valve are arranged on a connecting pipeline between the reaction reagent preparation component 3 and the second reactor component 402 and used for adjusting the amount of the solvent entering the second reactor component 402; a pneumatic valve is arranged on a connecting pipeline between the waste liquid collecting assembly 5 and the first reactor assembly 401 and used for discharging liquid in the first reactor 401 to enter the waste liquid collecting assembly 5, and a pneumatic valve is arranged on a connecting pipeline between the waste liquid collecting assembly 5 and the second reactor assembly 402 and used for discharging liquid in the second reactor 402 to enter the waste liquid collecting assembly 5; a solenoid valve and a flow control valve are arranged on a connecting pipeline between the first solvent assembly 601 and the first reactor assembly 401 and used for adjusting the amount of the solvent entering the first reactor 401 and entering the first reactor 401, and a solenoid valve and a flow control valve are arranged on a connecting pipeline between the first solvent assembly 601 and the second reactor assembly 402 and used for adjusting the amount of the solvent entering the second reactor 402 and entering the second reactor 402; electromagnetic valves and flow control valves are arranged on the connecting pipelines of the second solvent assembly 602 and the first reactor assembly 401 and used for adjusting the amount of the solvent entering the first reactor 401 and entering the first reactor 401, and electromagnetic valves and flow control valves are arranged on the connecting pipelines of the second solvent assembly 602 and the second reactor assembly 402 and used for adjusting the amount of the solvent entering the second reactor 402 and entering the second reactor 402.

The first reactor assembly 401 comprises a six-channel reactor and the second reactor assembly 402 comprises a twelve-channel reactor, the six-channel reactor being divided into three separate insulated reaction zones and the twelve-channel reactor being divided into four separate insulated reaction zones. The heat preservation reaction zone is provided with a jacket heat preservation device which is used for adjusting the temperature of the heat preservation reaction zone. A bubbling and mechanical stirring device is arranged in the six-channel reactor, a bubbling and stirring device is arranged in the twelve-channel reactor, and the electronic device component 8 is connected with the bubbling and mechanical stirring device and the bubbling and stirring device.

The first solvent assembly 601 and the second solvent assembly 602 both comprise a plurality of solvent bottles with different volumes, and a jacket heat preservation device or an air-cooling heat preservation device is arranged outside the solvent bottles and used for preserving heat of the solvent bottles.

The reaction reagent preparation component 3 comprises a reaction reagent preparation area and a plurality of reaction reagent bottles, wherein the reaction reagent preparation area is provided with an air cooling/heating temperature control device, and the air cooling/heating temperature control device is used for adjusting the temperature of the reaction reagent preparation area.

Adjust reagent through gas and temperature regulation subassembly 9, reactor and solvent subassembly to the settlement temperature, gas to the settlement pressure value, gaseous business turn over and the valve switching are adjusted to rethread equipment control and data recording subassembly 1 to add reagent and solvent into the reactor through the connecting line and react, move electron device 8 and adjust the reaction process, adjust the valve switching after the reaction and discharge the waste liquid collection subassembly 5 with solution in the reactor, record whole process according to time sequencing simultaneously.

Example 2:

those skilled in the art will understand this embodiment as a more specific description of embodiment 1.

As shown in fig. 1 to 6, the present embodiment provides a solid-phase organic synthesis modular device, which mainly comprises an external frame, a reactor module 4, a reagent preparation module 3, a first solvent module 601, a second solvent module 602, a valve module 7, an electronic device module 8, a device control and data recording module 1, a gas and temperature regulation module 9, a waste liquid collection module 5, and a connecting pipeline, wherein the reactor module 4, the reagent preparation module 3, the first solvent module 601, the second solvent module 602, the valve module 7, the electronic device module 8, the device control and data recording module 1, the gas and temperature regulation module 9, and the waste liquid collection module 5 are arranged in the external frame;

the reactor module is used for carrying out solid-phase organic synthesis reaction under different conditions; the reaction reagent preparation module 3 transfers and adds reaction reagents; the first solvent module 601 and the second solvent module 602 are used for transferring and adding washing reagents; the waste liquid collecting module 5 is used for discharging and collecting reaction reagents and washing reagents; the valve module 7 is mainly responsible for the inlet and outlet of gas, reaction reagent and washing reagent and the discharge of waste liquid.

The equipment control and data recording module 1 regulates the reaction time, temperature control, the inlet and outlet of the reagent and the washing reagent, the running sequence of each step, the recording of the running data and the storage of the information.

The gas and temperature adjusting module 9 adjusts the gas amount entering the reactor module, the first solvent module 601 and the second solvent module 602, and sets and adjusts the temperature of the reactor module, the reagent preparing module 3, the first solvent module 601 and the second solvent module 602.

The single reaction mixed mode of similar reaction unit has been abandoned to the equipment of this embodiment, has adopted two mixed modes, has accelerated reaction rate when making the reactant mix more even, has shortened reaction time. The reactor part has set up the heat preservation module, can carry out the reaction of different temperature of different groups simultaneously to solvent and reaction reagent module also can set up different reagent temperatures according to the reaction demand of difference. In addition, the apparatus of this example allows for two different reaction modes, laboratory bench and pilot scale solid phase synthesis, and allows for the use of other modules in addition to the reactor section.

In the solid phase synthesizer, the technology of the solid phase polypeptide synthesizer and the solid phase nucleic acid synthesizer is the most mature, most of the existing equipment has no control on the temperature of a reactor module, a reaction reagent module and a solvent module, and the temperature is controlled by controlling the temperature of the environment where the equipment is located, so that more electric power or construction cost is consumed, and adverse effects brought to the reaction by sudden change of the environmental temperature are increased, for example, in general polypeptide solid phase synthesis, a synthesis reaction kettle needs to be kept at about 25 ℃ for condensation reaction, and the purity of a synthetic final product is affected by greatly increasing byproducts due to overhigh or overlow temperature, so that higher purification cost is brought; in the process of peptide nucleic acid solid phase synthesis, a reaction kettle needs to be kept at about 40 ℃ for condensation and deprotection reaction, and too high or too low temperature can increase a large amount of reaction impurities, thereby causing purification difficulty.

Considering that the preparation unit of the reaction reagent relates to the formation of chemical bonds such as amido bond, disulfide bond, ester bond, ether bond, phenolic hydroxyl, phosphorous ester bond, oligonucleotide 5 ' hydroxyl and the like, wherein some reagents used in the preparation unit are prone to be decomposed, oxidized, shed of temporary protecting group and the like in the state of normal temperature solution, so that the increase of reaction impurities and the difficulty of precise control of reaction are caused, for example, activators such as diisopropylcarbodiimide for forming amido bond, benzotriazole-N, N, N ', N ' -tetramethylhexafluorophosphate and the like are needed to be carried out at a lower temperature (such as 2-8 ℃) in the process of activating and protecting amino acid, and an excessive temperature can generate activated impurities to influence the subsequent reaction efficiency, and for example, the removal reaction of temporary protecting group is prone to be carried out to form impurities in the state of the nucleic acid monomer and the protected amino acid at normal temperature, for this reason, in the present embodiment, the temperature control is performed on the reaction reagent preparation unit, and the decomposition, oxidation, and falling off of these substances are reduced or suppressed by specifically controlling the temperature.

Meanwhile, the temperature of the solvent module is set, the main solvent module relates to a solvent for removing temporary protecting groups, a capping reagent of unreacted resin, a common washing solvent and the like in the reaction process of forming amide bonds, disulfide bonds, ester bonds, ether bonds, phenolic hydroxyl groups, phosphorous ester bonds, 5' hydroxyl groups of oligonucleotides and the like, and some reagents need to be set to meet the reaction requirements, for example, in the solid-phase synthesis process of peptide nucleic acid, a 2-methylpyrrolidone solution of which the deprotection reagent contains diisopropylethylamine and m-methylphenylthiophenol needs to be stored at about 40 ℃ to achieve the optimal protecting group removal rate; the solid phase organic synthesis is usually performed by using a washing solvent such as dimethylformamide, 2-methylpyrrolidone and the like, and the viscosity of the washing solvent is increased at a lower temperature, so that the washing of the solid phase carrier is not facilitated. The embodiment adds temperature setting and control to the solvent module, and reduces the influence of the solvent on chemical reaction and solid-phase carrier cleaning.

The reactor module is connected with the waste liquid collecting module 5 through a connecting pipeline, and liquid in the pipeline of the reactor module is discharged to the waste liquid collecting module 5 through a vacuum pump (the waste liquid collecting module 5 is arranged at the bottommost part in the external frame or is externally connected).

The reaction reagent preparation module 3 is connected with the reactor module through a connecting pipeline, and an electromagnetic valve and a flow control valve are arranged on the connecting pipeline (a peristaltic pump is also arranged between the reaction reagent preparation module 3 and the reactor module to pump the reaction reagent to the reactor module).

The first solvent module 601 and the second solvent module 602 are connected to the reactor module through a connection pipeline, and the connection pipeline is configured with an electromagnetic valve and a flow control valve.

The valve module 7 includes an electromagnetic valve, a pneumatic valve, and a flow control valve, and adjusts the liquid transmission through the device pipeline by driving the electromagnetic valve and the pneumatic valve to open/close through the device control and data recording module 1, and adjusts the liquid transmission amount through the device pipeline by driving the flow control valve through the device control and data recording module 1.

The electronic device module 8 is connected with the equipment control and data recording module 1 to control the temperature of the reactor module, the reaction reagent preparation module 3, the first solvent module 601 and the second solvent module 602 and normally transmit the information to the equipment control and data recording module 1.

The equipment control and data recording module 1 adjusts the volume and time of reagent inlet and outlet of the reactor module, the reaction reagent preparation module 3, the first solvent module 601 and the second solvent module 602, and records, transmits and stores data in real time.

The gas and temperature adjusting module 9 adjusts the gas pressure in the reaction reagent preparing module 3, the first solvent module 601 and the second solvent module 602, and adjusts the temperature of the reactor module, the reaction reagent preparing module 3, the first solvent module 601 and the second solvent module 602.

The reactor modules comprise a first reactor module 401, a second reactor module 402, which are switchably usable. The first reactor module 401 comprises a 6-channel reactor and the second reactor module 402 comprises a 12-channel reactor, the 6-channel reactor being divided into three separate, insulated reaction zones and the 12-channel reactor being divided into four separate, insulated reaction zones. The heat preservation reaction zone realizes temperature control through a jacket heat preservation device arranged outside the reactor. The 6-channel reactor is internally provided with a bubbling and mechanical stirring device, the 12-channel reactor is internally provided with a bubbling stirring device, and the electronic device module 8 and the equipment control and data recording module 1 are connected with the bubbling and mechanical stirring device or the bubbling stirring device so as to adjust the stirring speed during reaction and the oscillation frequency of the reaction kettle.

The reaction reagent preparation module 3 comprises a plurality of reaction reagent bottles and a reaction reagent preparation area, and the reaction reagents enter the reactor module in a pre-dissolving mode, a nitrogen gas pressing mode or a peristaltic pump needle type suction mode. The reaction reagent preparation area is provided with an air-cooled temperature control system, the temperature is controlled to be 0-50 ℃, and the preferable temperature is controlled to be 2-8 ℃.

The first solvent module 601 and the second solvent module 602 include a plurality of solvent bottles having different volumes. The temperature of the solvent bottle of the first solvent module 601 is controlled in a normal temperature region, and the temperature of the solvent bottle of the second solvent module 602 is controlled in a low temperature region. The low temperature region is 0-15 ℃, and the normal temperature region is 20-40 ℃. The first solvent module 601 comprises 2-4 solvent bottles with the volume of 250-1000 ml, the temperature can be controlled to be 20-40 ℃, and the second solvent module 602 comprises 2-4 solvent bottles with the volume of 250-500 ml, and the temperature can be controlled to be 0-15 ℃. The solvent bottle is externally provided with a jacket heat preservation or air cooling heat preservation device, and the temperature is controlled through the jacket or air cooling.

The pipelines of the solvent module entering the reactor module are all 1/4PP pipe diameters, and the pipeline of the solvent outlet end of the reactor module connected with the waste liquid collecting module 5 is 3/8PP pipe diameters.

The electronic device module 8 is arranged in the external frame and comprises a built-in controller, a temperature detection sensor adapter, a flow sensor and the like, and the electronic device module 8 is connected with the equipment control and data recording module 1 through an integrated USB data line and used for heat preservation of the first reactor module 401, the second reactor module 402, the reaction reagent preparation module 3, the first solvent module 601 and the second solvent module 602 in the equipment.

The equipment control and data recording module 1 is arranged outside the external frame and can be accommodated in the external frame through a sliding rail.

The gas and temperature adjusting module 9 is arranged outside the external frame, the gas and temperature adjusting module 9 adjusts gas pressure in the adjusting module by connecting a manual knob with the reaction reagent preparing module 3, the first solvent module 601 and the second solvent module 602 through a PP pipeline, the temperature is adjusted by setting the temperature through the electronic display, and the temperature of the first reactor module 401, the second reactor module 402, the reaction reagent preparing module 3, the first solvent module 601 and the second solvent module 602 is kept consistent with the set temperature after confirmation.

Example 3:

this embodiment will be understood by those skilled in the art as a more specific description of embodiment 1.

As shown in fig. 1 to 6, the present embodiment relates to a solid-phase organic synthesis modular apparatus; the apparatus is a system capable of synthesizing 20 to 50g (5 to 20mmol) of a pilot scale solid phase carrier.

1. An external framework:

the external frame is used for supporting the reactor module, the reaction reagent preparation module, the solvent module and the like.

Specifically, as shown in fig. 1, the equipment system adopts a vertical structure, the upper layer of the shelf is a touch screen 2, the gas and temperature adjusting module 9, the top is an exhaust port 10, and the middle layer is provided with a first reactor module 401, a second reactor module 402 and a reaction reagent preparation module 3; the lower layer is provided with a waste liquid collecting module 5, a first solvent module 601 and a second solvent module 602, and the equipment control and data recording module 1 is arranged at the rear position of the lower layer. The frame structure can be made of stainless steel or space aluminum and other hard materials.

The first reactor module 401 and the second reactor module 402 are respectively connected with the reaction reagent configuration module 3 through 1/4 corrosion-resistant PP pipelines, electromagnetic valves and flow control valves are configured between the corrosion-resistant PP pipelines, the opening/closing of the electromagnetic valves are adjusted through the touch screen 2, and the volume of liquid flowing through the flow control valves is adjusted; the first reactor module 401/the second reactor module 402 are connected with the first solvent module 601 and the second solvent module 602 through 1/4 corrosion-resistant PP pipelines respectively, electromagnetic valves and flow control valves are arranged between the corrosion-resistant PP pipelines, the corrosion-resistant PP pipelines are connected with the touch screen 2 through lines and USB interfaces, the opening/closing of the electromagnetic valves are adjusted through the touch screen 2, and the volume of the solvent flowing through the corrosion-resistant PP pipelines is adjusted through the flow control valves; the first reactor module 401 and the second reactor module 402 are directly connected with the waste liquid collecting module 5 through 3/8 corrosion-resistant PP pipelines, and the waste liquid collecting module 5 is used for collecting reaction and cleaning waste liquid; a peristaltic pump in the device is connected with the reaction reagent preparation module 3 through an 3/8 corrosion-resistant PP hose, so that liquid in the pipeline enters a reaction kettle in the first reactor module 401 or the second reactor module 402, and the liquid in the pipeline of the first reactor module 401 and the second reactor module 402 is discharged to the waste liquid collection module 5 through a vacuum pump; the electromagnetic valve is opened through the valve module 7 and the electronic device module 8, nitrogen enters the air chamber, the pneumatic valve membrane is pushed, the valve rod is pushed, and the valve rod drives the valve core to open/close and simultaneously controls the starting state of each electrical appliance; the device control and data recording module 1 can record the data of the device operation process.

2. A reactor module:

the first reactor module 401 and the second reactor module 402 are used for carrying solid phase carriers and carrying out chemical reactions (in this embodiment, only the first reactor module 401 is used, the reactors of the first reactor module 401 are 6 channels, and 500ml reactors can be placed in the reactors, the reactors are carried out in a jacket heat preservation mode, and the 6-channel reactors can be divided into three independent heat preservation systems, so that three different temperatures can be simultaneously realized, the stirring mode is carried out in a bubbling and mechanical stirring mode, the stirring speed is adjustable, and meanwhile, the filter sieve plates of the reactors can be independently replaced and used according to design requirements.

3. Solvent module:

the first solvent module 601 and the second solvent module 602 perform addition of washing reagents. The quantity of different solvent bottles in the solvent module is 8, wherein 2 solvent bottle volumes are 8L, 2 solvent bottle volumes are 500ml, through air-cooled control temperature 2 ~ 8 ℃, 4 solvent bottles are 1000ml, the temperature through pressing from both sides the cover mode control about 30 ℃, the bottle adopts the glass material, resistant organic and can be able to bear certain pressure (be less than 1 Mpa). The solvent inlet pipeline is 1/4 pipe diameter, and the liquid discharge end pipeline is 3/8 pipe diameter. The solvent enters the first reactor module 401, a solenoid valve and nitrogen pressure are adopted to provide liquid adding power, and 8 different solutions can be independently added. The solvent discharge system is a corrosion-resistant vacuum pump.

4. A reaction reagent preparation module:

the reagent preparing module 3 adds a reagent. The reaction reagent preparation module 3 is set to 20 reaction reagent bottles, each bottle is set to 100ml, and a reaction reagent preparation area is provided with a wind cooling temperature control system, and the temperature can be controlled between 2 ℃ and 8 ℃. The reaction reagent enters the reactor in a pre-dissolving mode, and a peristaltic pump provides power and a sample injection needle sucks the reaction reagent.

5. Waste liquid collection module:

the waste liquid collection module 5 discharges and collects the reaction reagent and the washing reagent by a vacuum pump. Waste liquid collection module 5 is located the instrument bottommost or external, and two series connection uses of 50L buckets are required to built-in waste liquid bucket, and the material adopts the PP material, and the shape is flat.

6. A valve module:

the valve module 7 adjusts the electric pole operation and the valve, firstly electrify the electromagnetic valve arranged between the reaction reagent module or the solvent module and the reactor module, open the electromagnetic valve, the nitrogen enters the air chamber, push the pneumatic valve membrane, push the valve rod, and the valve rod drives the valve core to open/close, thereby realizing the liquid transfer of the solvent module or the reaction reagent module, and adjusting the amount of the liquid of the solvent module or the reaction reagent module to the reactor module through the entering nitrogen amount and the valve opening/closing time.

7. An electronic device module:

the electronic device module 8 is connected with the equipment control and data recording module 1 through an integrated USB data line; the electronic device module 8 is mainly installed in the whole frame, a controller, an adapter, a flow sensor and the like are arranged in the electronic device module, the controller is used for adjusting the starting state of each electrical appliance, the adapter ensures that equipment hardware is connected with an electronic interface, the flow sensor can measure reagents passing through an equipment pipeline, and the electronic device module system has the functions of abnormity alarming and audit tracking.

8. Gas and temperature regulation module:

the gas regulation is realized by manually regulating the pressure of a gas source, arranging a pressure reducing meter and a distribution valve, distributing the gas to the reactor module and the solvent module through the distribution valve, and monitoring the pressure of the equipment module in real time; the temperature regulation adopts automatic feedback type regulation, after the target temperature is set, the heating or temperature reduction is disconnected when the set temperature is reached, the heating is carried out when the target temperature is lower than the target temperature, the temperature reduction is carried out when the target temperature is higher than the target temperature, and the temperature sensor is connected to monitor the temperature of the reactor module, the temperature of the reaction reagent module and the temperature of the solvent module in real time.

9. The equipment control and data recording module:

the equipment control and data recording module 1 adjusts the reaction time, the reaction temperature, the inlet and outlet of the reaction reagent and the washing reagent, the operation sequence of each step, the recording of the operation data and the storage of the information. The control panel is operated by a display, such as a touch screen 2, and is externally connected to a computer by adopting a USB interface. The 6 reaction systems can be adjusted simultaneously. The synthesis task is completed within more than 24 hours under the permission of the solvent module and the reaction reagent preparation module; the computer records the running process of the task, operates the record, and can print.

The embodiment optimizes the equipment control and data recording module of the solid-phase synthesizer, sets the equipment control and data recording module 1 and the touch screen 2, is a touch screen dual-control system, meets the aims of timely processing through the touch screen when the equipment is abnormal and timely and accurately observing the operation process through the equipment control and data recording module when the equipment is normal, and adjusts the reaction time, the temperature control, the inlet and outlet time of the reagent and the washing reagent and the operation sequence of each step, and records the operation data and stores the information.

Example 4:

those skilled in the art will understand this embodiment as a more specific description of embodiment 1.

As shown in fig. 1 to 6, the present embodiment relates to a solid-phase organic synthesis modular apparatus; the apparatus is capable of performing synthesis of 1g to 5g (0.25mmol to 2.0mmol) of laboratory bench scale solid phase support.

1. An external framework:

the external frame is used for supporting the reactor module, the reaction reagent preparation module, the solvent module and the like.

Specifically, as shown in fig. 1, the equipment system adopts a vertical structure, the upper layer of the shelf is a touch screen 2, the gas and temperature adjusting module 9, the top is an exhaust port 10, and the middle layer is provided with a first reactor module 401, a second reactor module 402 and a reaction reagent preparation module 3; the lower layer is provided with a waste liquid collecting module 5, a first solvent module 601 and a second solvent module 602, and the equipment control and data recording module 1 is arranged at the rear position of the lower layer. The frame structure can be made of stainless steel or space aluminum and other hard materials. The first reactor module 401, the second reactor module 402 and the reaction reagent configuration module 3 are connected through 1/4 corrosion-resistant PP pipelines, electromagnetic valves and flow control valves are arranged between the corrosion-resistant PP pipelines, the opening/closing of the electromagnetic valves is adjusted through the touch screen 2, and the volume of the flowing liquid is adjusted through the flow control valves; the first reactor module 401 is connected with the first solvent module 601 and the second solvent module 602 (and the second reactor module 402 is connected with the first solvent module 601 and the second solvent module 602) respectively through 1/4 corrosion-resistant PP pipelines, electromagnetic valves and flow control valves are adjusted through a valve module 7 and an electronic device module 8, the electromagnetic valves and the flow control valves are connected with the touch screen 2 through lines and USB interfaces, the opening/closing of the electromagnetic valves are adjusted through the touch screen 2, and the volume of the solvent flowing through the flow control valves is adjusted; the first reactor module 401 and the second reactor module 402 are directly connected with the waste liquid collecting module 5 through 3/8 corrosion-resistant PP pipelines, and the waste liquid collecting module 5 is used for collecting reaction and cleaning waste liquid; a peristaltic pump in the device is connected with the reaction reagent preparation module 3 through an 3/8 corrosion-resistant PP hose, so that liquid in the pipeline enters the reaction kettle in the first reactor module 401/the second reactor module 402, and the liquid in the pipeline of the first reactor module 401 and the second reactor module 402 is discharged to the waste liquid collection module 5 through a vacuum pump; the valve module 7 and the electronic device module 8 regulate the operation of the electric pole and the opening/closing of the valve through electromagnetic signals, and simultaneously regulate the starting state of each electric appliance; the equipment control and data recording module 1 records the data of the equipment operation process.

2. A reactor module:

the first reactor module 401 and the second reactor module 402 are used for carrying solid phase carriers and carrying out chemical reactions (only the second reactor module 402 is used in the embodiment), the reactors of the second reactor module 402 are 12 channels, 12 100ml reactors are placed, the reactors are carried out in a jacket heat preservation mode, the 12 reactors are divided into four independent heat preservation systems, four different reaction temperatures can be controlled simultaneously, the stirring mode is carried out in a nitrogen bubbling mode, and the filter sieve plates of the reactors can be replaced and used independently according to design requirements.

3. Solvent module:

the first solvent module 601 and the second solvent module 602 perform addition of washing reagents. The number of different solvent bottles in the solvent module is 8, the volume of 2 solvent bottles is required to be 4L, the volume of 2 solvent bottles is 250ml, the temperature is controlled to be 0-15 ℃ through air cooling, the volume of 4 solvent bottles is 250ml, the temperature is controlled to be 30-40 ℃ through jacket heat preservation, and the bottle body is made of PP materials, is organic and can resist the pressure less than 1 Mpa. The solvent inlet pipeline is 1/4 pipe diameter, and the liquid discharge end pipeline is 3/8 pipe diameter. The solvent entering system adopts an electromagnetic valve and nitrogen pressure to provide liquid adding power, and 8 different solutions can be independently added. The solvent discharge system adopts a vacuum pump system, and the vacuum pump adopts a corrosion-resistant pump body.

4. A reaction reagent preparation module:

the reaction reagent preparing module 3 adds a reaction reagent. The reaction reagent preparation module needs to set 20 reaction reagent bottles, each bottle is set to be 15ml, the reaction reagent preparation area is provided with a temperature control system, and the temperature can be controlled between 2 ℃ and 8 ℃. The reaction reagent enters the reactor in a pre-dissolving mode, a peristaltic pump and a sample injection needle suction mode.

5. A waste liquid collection unit:

the waste liquid collection module 5 discharges and collects the reaction reagent and the washing reagent by a vacuum pump. The waste liquid collecting unit is located the instrument bottommost or external, and two of 50L buckets are required to be connected in series for use to built-in waste liquid bucket, and the material adopts the PP material, and the shape is flat.

6. A valve module:

the valve module 7 adjusts the valve rod operation and the valve core opening/closing, and adjusts the amount of the liquid of the solvent module or the reaction reagent module to the reactor module through the entering nitrogen amount and the valve opening/closing time.

7. An electronic device module:

the electronic device module 8 is installed in the whole frame, a controller, an adapter, a flow sensor and the like are arranged in the electronic device module, the controller is adopted to adjust the starting state of each electrical appliance, the adapter ensures that equipment hardware is connected with an electronic interface, the flow sensor can measure reagents passing through an equipment pipeline, and the electronic device module system has the functions of abnormity alarming and audit tracking.

8. Gas and temperature regulation module:

the gas regulation is realized by manually regulating the pressure of a gas source, arranging a pressure reducing meter and a distribution valve, distributing the gas to the reactor module and the solvent module through the distribution valve, and monitoring the pressure of the equipment module in real time; the temperature regulation adopts automatic feedback regulation, after the target temperature is set, the heating or temperature reduction is disconnected when the set temperature is reached, the heating is carried out when the target temperature is lower than the target temperature, the temperature reduction is carried out when the target temperature is higher than the target temperature, and the temperature sensor is arranged to monitor the temperature of the reactor module, the temperature of the reaction reagent module and the temperature of the solvent module in real time.

9. The equipment control and data recording module:

the equipment control and data recording module 1 adjusts the reaction time, the reaction temperature, the inlet and outlet of the reaction reagent and the washing reagent, the operation sequence of each step, the recording of the operation data and the storage of the information. The control panel is operated by a display, such as the touch screen 2 in fig. 2, and is externally connected to a computer by adopting a USB interface, so that 6 reaction systems can be adjusted and operated simultaneously. The synthesis task is completed within more than 24 hours under the permission of the solvent module and the reaction reagent preparation module; the computer records the running process of the task, operates the record, and can print.

The utility model has the characteristics of simple and stable operation, wide application range, easy module disassembly and replacement and capability of finishing various solid-phase organic synthesis reactions.

In the description of the present application, it is to be understood that the terms "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", and the like indicate orientations or positional relationships based on those shown in the drawings, and are only for convenience in describing the present application and simplifying the description, but do not indicate or imply that the referred device or element must have a specific orientation, be constructed in a specific orientation, and be operated, and thus, should not be construed as limiting the present application.

The foregoing description of specific embodiments of the present invention has been presented. It is to be understood that the present invention is not limited to the specific embodiments described above, and that various changes or modifications may be made by one skilled in the art within the scope of the appended claims without departing from the spirit of the utility model. The embodiments and features of the embodiments of the present application may be combined with each other arbitrarily without conflict.

Claims (10)

1. The solid-phase organic synthesis equipment is characterized by comprising an external framework, wherein an equipment control and data recording component (1), a reaction reagent preparation component (3), a reactor component (4), a waste liquid collection component (5), a solvent component (6), a valve component (7), an electronic device component (8), a gas and temperature regulation component (9) and a connecting pipeline are arranged in the external framework;

the equipment control and data recording component (1) is connected with the electronic device component (8);

the electronic device assembly (8) is connected with the reaction reagent preparation assembly (3), the reactor assembly (4), the solvent assembly (6) and the gas and temperature regulation assembly (9);

the reaction reagent preparation component (3), the waste liquid collection component (5) and the solvent component (6) are communicated with the reactor component (4) through the connecting pipeline; the valve component (7) is arranged on the connecting pipeline.

2. The solid phase organic synthesis apparatus of claim 1, wherein the reactor assembly comprises a first reactor assembly (401) and a second reactor assembly (402);

the electronics assembly (8) is connected to the first reactor assembly (401), the second reactor assembly (402);

the reaction reagent preparation assembly (3) is communicated with the first reactor assembly (401) through the connecting pipeline; the waste liquid collecting assembly (5) is communicated with the first reactor assembly (401) and the second reactor assembly (402) through the connecting pipeline; the solvent assembly (6) is communicated with the first reactor assembly (401) and the second reactor assembly (402) through the connecting pipeline;

the first reactor assembly (401) and the second reactor assembly (402) are switchable.

3. The solid-phase organic synthesis apparatus according to claim 2, wherein the solvent assembly (6) comprises a first solvent assembly (601) and a second solvent assembly (602), the first solvent assembly (601) and the second solvent assembly (602) are communicated through the connecting pipeline;

the electronic device assembly (8) is connected with the first solvent assembly (601) and the second solvent assembly (602);

the first solvent assembly (601) is communicated with the first reactor assembly (401) and the second reactor assembly (402) through the connecting pipeline; the second solvent assembly (602) is disposed in communication with the second reactor assembly (402) via the connecting line.

4. The solid phase organic synthesis apparatus according to claim 3, wherein the valve assembly (7) comprises a solenoid valve, a pneumatic valve and a flow control valve;

the electromagnetic valve, the pneumatic valve and the flow control valve are all arranged on the connecting pipeline; the solenoid valve and the pneumatic valve are used to regulate liquid delivery, and the flow control valve is used to regulate the liquid delivery rate.

5. The solid-phase organic synthesis apparatus according to claim 4, wherein the connection pipeline between the reaction reagent preparation assembly (3) and the first reactor assembly (401) is provided with an electromagnetic valve and a flow control valve, and the connection pipeline between the reaction reagent preparation assembly (3) and the second reactor assembly (402) is provided with an electromagnetic valve and a flow control valve;

a pneumatic valve is arranged on the connecting pipeline of the waste liquid collecting assembly (5) and the first reactor assembly (401), and a pneumatic valve is arranged on the connecting pipeline of the waste liquid collecting assembly (5) and the second reactor assembly (402);

the connecting pipeline of the first solvent assembly (601) and the first reactor assembly (401) is provided with an electromagnetic valve and a flow control valve, and the connecting pipeline of the first solvent assembly (601) and the second reactor assembly (402) is provided with an electromagnetic valve and a flow control valve;

and the connecting pipeline between the second solvent assembly (602) and the first reactor assembly (401) is provided with an electromagnetic valve and a flow control valve, and the connecting pipeline between the second solvent assembly (602) and the second reactor assembly (402) is provided with an electromagnetic valve and a flow control valve.

6. The solid phase organic synthesis apparatus of claim 3, wherein the first solvent assembly (601) and the second solvent assembly (602) each comprise a plurality of solvent bottles of different volumes;

the jacket heat preservation device or the air-cooled heat preservation device is arranged outside the solvent bottle and used for preserving heat of the solvent bottle.

7. The solid phase organic synthesis apparatus of claim 2, wherein the first reactor assembly (401) comprises a six-channel reactor and the second reactor assembly (402) comprises a twelve-channel reactor;

the six-channel reactor is divided into three independent heat-preservation reaction zones, and the twelve-channel reactor is divided into four independent heat-preservation reaction zones.

8. The solid-phase organic synthesis apparatus according to claim 7, wherein the incubation reaction zone is provided with a jacket incubation device for adjusting the temperature of the incubation reaction zone.

9. The solid-phase organic synthesis apparatus according to claim 7, wherein a bubbling and mechanical stirring device is arranged in the six-channel reactor, and a bubbling stirring device is arranged in the twelve-channel reactor;

the electronic device assembly (8) is connected with the bubbling and mechanical stirring device and the bubbling stirring device.

10. The solid-phase organic synthesis apparatus according to claim 1, wherein the reaction reagent preparation assembly (3) comprises a reaction reagent preparation area and a plurality of reaction reagent bottles;

the reaction reagent preparation area is provided with an air cooling/heating temperature control device, and the air cooling/heating temperature control device is used for adjusting the temperature of the reaction reagent preparation area.

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