WO2022127925A1 - 一种液相合成自动监测系统 - Google Patents

一种液相合成自动监测系统 Download PDF

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WO2022127925A1
WO2022127925A1 PCT/CN2021/139389 CN2021139389W WO2022127925A1 WO 2022127925 A1 WO2022127925 A1 WO 2022127925A1 CN 2021139389 W CN2021139389 W CN 2021139389W WO 2022127925 A1 WO2022127925 A1 WO 2022127925A1
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module
monitoring
sampling
liquid phase
phase synthesis
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PCT/CN2021/139389
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English (en)
French (fr)
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叶新山
姚文龙
熊德彩
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北京大学
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Priority to JP2023534598A priority Critical patent/JP2024500662A/ja
Priority to EP21905847.6A priority patent/EP4239312A4/en
Priority to US18/267,974 priority patent/US20240053304A1/en
Publication of WO2022127925A1 publication Critical patent/WO2022127925A1/zh

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/16—Injection
    • G01N30/22—Injection in high pressure liquid systems
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/16—Injection
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N2030/022—Column chromatography characterised by the kind of separation mechanism
    • G01N2030/027—Liquid chromatography
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • G01N2030/8804—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 automated systems
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P90/00—Enabling technologies with a potential contribution to greenhouse gas [GHG] emissions mitigation
    • Y02P90/02—Total factory control, e.g. smart factories, flexible manufacturing systems [FMS] or integrated manufacturing systems [IMS]

Definitions

  • the invention relates to the technical field of experimental equipment, in particular to an automatic monitoring system for liquid phase synthesis.
  • Liquid phase experimental monitoring is a necessary means to determine experimental results.
  • the mixed reaction solution needs to be placed in the monitor, and the monitoring result can be obtained through the monitor.
  • reaction solution needs to be manually added to the monitor for detection, and the monitoring report generated by the monitor needs to be manually sorted and checked, which makes the entire liquid phase experimental monitoring process time-consuming and labor-intensive.
  • the present invention provides an automatic monitoring system for liquid phase synthesis.
  • the present invention provides the following scheme:
  • An automatic monitoring system for liquid phase synthesis comprising: a novel reactor, a sampling module, a power module, a monitoring and analysis module and an upper computer;
  • the sampling module is connected with the pipeline of the power module; the power module is connected with the pipeline of the monitoring and analysis module; the sampling module, the power module and the monitoring and analysis module are all connected to the upper electromechanical connect;
  • the sampling module is used to absorb the reaction solution contained in the novel reactor; the power module is used to provide suction force for the sampling module according to the suction instruction in the upper computer, and is used to inject the absorbed reaction solution into
  • the monitoring and analysis module is configured to transmit the monitoring report to the upper computer after generating the monitoring report according to the reaction solution; and the upper computer generates the analysis result according to the monitoring report.
  • the novel reactor comprises: a bottle mouth, a bottle body, a sample inlet, an exhaust outlet, a sample outlet, a circulating liquid outlet and a circulating liquid inlet;
  • the bottle body sequentially includes a reaction liner, a temperature circulation layer and a vacuum layer from the inside to the outside; the bottom of the reaction liner is an arc structure;
  • the sampling port is communicated with the reaction liner
  • Both the circulating liquid outlet and the circulating liquid inlet are communicated with the temperature circulating layer, and the circulating liquid outlet and the circulating liquid inlet are arranged diagonally.
  • the sampling module includes: a stainless steel needle, a slide rail and a turntable;
  • the stainless steel needle is connected to the power module through a first pipeline; the first pipeline is arranged on the slide rail, and the slide rail and the horizontal line are at a set angle; the stainless steel needle is fixedly arranged on the One end of the slide rail, and the other end of the slide rail is a free end; the slide rail is used to drive the stainless steel needle to slide, and the stainless steel needle is used to probe into the novel reactor to absorb the reaction solution; the The slide rail is fixedly arranged on the turntable; the turntable and the slide rail are both electromechanically connected with the upper position.
  • the power module includes: a power pump; the power pump is a syringe pump or a plunger pump;
  • the power pump is respectively connected with the pipelines of the sampling module and the monitoring and analysis module.
  • the monitoring and analysis module is a high performance liquid chromatograph.
  • it also includes a cleaning module
  • the cleaning module is respectively connected with the pipelines of the sampling module and the power module.
  • the cleaning module includes: a first liquid container, a second liquid container and a solenoid valve;
  • the stainless steel needle sucks the cleaning liquid in the first liquid container; the second liquid container, the power module and the monitoring and analysis module are all connected with the pipeline of the solenoid valve.
  • the cleaning solution is an organic solvent.
  • the present invention discloses the following technical effects:
  • the liquid phase synthesis automatic monitoring system provided by the present invention can realize automatic sampling, monitoring and reporting analysis of the reaction solution by setting a sampling module, a power module, a monitoring and analysis module and a host computer, thereby improving the experimental monitoring efficiency and reducing the experimental operation input. Labor costs.
  • Fig. 1 is the structural representation of liquid phase synthesis automatic monitoring system provided by the invention
  • Fig. 2 is the structural representation of the novel reactor provided by the embodiment of the present invention.
  • FIG. 3 is a schematic structural diagram of a sampling module provided by an embodiment of the present invention.
  • 1 New type reactor 1-1 bottle mouth, 1-2 injection port, 1-3 exhaust port, 1-4 sampling port, 1-5 bottle body, 1-51 reaction liner, 1-52 temperature circulation layer , 1-53 vacuum layer, 1-6 circulating liquid outlet, 2 sampling module, 2-1 slide rail, 2-11 slide plate, 2-12 support frame, 2-2 turntable, 2-3 stainless steel needle, 2- 4 first pipeline, 3 power module, 4 monitoring and analysis module, 5 upper computer, 6 cleaning module, 6-1 first liquid container, 6-2 second liquid container, 6-3 solenoid valve.
  • the purpose of the present invention is to provide a liquid phase synthesis automatic monitoring system to realize automatic sampling, automatic monitoring and automatic analysis in the whole experimental monitoring process, thereby improving the experimental monitoring efficiency and reducing the labor cost of experimental operation input.
  • Fig. 1 is the structural schematic diagram of the liquid phase synthesis automatic monitoring system provided by the present invention, as shown in Fig. 1, a kind of liquid phase synthesis automatic monitoring system, including: novel reactor 1, sampling module 2, power module 3, monitoring and analysis module 4 and the host computer 5.
  • the sampling module 2 is connected with the pipeline of the power module 3; the power module 3 is connected with the pipeline of the monitoring and analysis module 4; the sampling module 2, the power module 3 and the monitoring and analysis module are connected 4 are all electrically connected to the upper computer 5 .
  • the sampling module 2 is used to absorb the reaction solution contained in the novel reactor 1; the power module 3 is used to provide suction force for the sampling module 2 according to the suction instruction in the upper computer 5, and is used to The absorbed reaction solution is injected into the monitoring and analysis module 4; the monitoring and analysis module 4 is used to generate a monitoring report according to the reaction solution, and then transmit the monitoring report to the host computer 5; the host computer 5 according to the Monitoring reports generate analysis results.
  • the novel reactor 1 provided by the present invention preferably includes: bottle mouth 1-1, bottle body 1-5, sample inlet 1-2, exhaust port 1-3, sampling port 1-4, circulation Liquid outlet 1-6 and circulating liquid inlet (not shown in the figure).
  • the injection port 1-2 and the bottle mouth 1-1 form a set angle (preferably 60°); the exhaust port 1-3 and the injection port 1-2 are connected to the bottle mouth.
  • the center line of 1-1 is centrally symmetrical.
  • the bottle body 1-5 sequentially includes a reaction inner tank 1-51, a temperature circulation layer 1-52 and a vacuum layer 1-53 from the inside to the outside; the tank bottom of the reaction inner tank 1-51 is an arc structure.
  • the sampling ports 1-4 communicate with the reaction inner tank 1-51.
  • the circulation liquid outlet 1-6 and the circulation liquid inlet are both communicated with the temperature circulation layer 1-52, and the circulation liquid outlet 1-6 and the circulation liquid inlet are arranged diagonally.
  • the above sampling module includes: a stainless steel needle 2-3, a slide rail 2-1 and a turntable 2-2;
  • the stainless steel needle 2-3 is connected to the power module 2 through a first pipe 2-4; the first pipe 2-4 is arranged on the slide rail 2-1, and the slide rail 2-1 is connected to the power module 2.
  • the horizontal lines are at a set angle (preferably 60°); the stainless steel needle 2-3 is fixedly arranged at one end of the slide rail 2-1, and the other end of the slide rail 2-1 is a free end; the slide rail 2-1 is a free end;
  • the rail 2-1 is used to drive the stainless steel needle 2-3 to slide, and the stainless steel needle 2-3 is used to probe into the novel reactor 1 to absorb the reaction solution; the slide rail 2-1 is fixedly arranged in the on the turntable 2-2; both the turntable 2-2 and the slide rail 2-3 are electrically connected to the upper computer 5.
  • the slide rail 2-1 includes a slide plate 2-11 and a support frame 2-12.
  • the sliding plate 2-11 moves down along the support frame, so that the stainless steel needle 2-3 penetrates into the novel reactor 1 to draw the reaction solution.
  • the support frame 2-12 is fixed on the turntable 2-2, and the turntable 2-2 can drive the entire slide rail 2-1 to rotate, so that the stainless steel needle can absorb the liquids in different containers.
  • the slide rail 2-1 is fixed with the position of the novel reactor 1 and can be adjusted up and down.
  • the slide rail 2-1 may be provided with a slideway so as to fix the first conduit 2-4.
  • the turntable 2-2 (machining module) drives the supporting slide rail 2-1 to rotate to different positions at a certain angle in different directions and stay there.
  • Stainless steel needles 2-3 are preferably 9# needles in the present invention.
  • a pierceable sealing rubber pad and an organic filter head are also arranged.
  • the selection specifications of organic filter heads include 0.22um, 0.45um and 0.8um.
  • the above-mentioned power module 3 includes: a power pump; the power pump is a syringe pump or a plunger pump; the power pump selected in the present invention has a strong suction force and also has a suction function.
  • the back suction function is set to facilitate the cleaning of the pipelines of the entire liquid phase synthesis automatic monitoring system.
  • the power pump is respectively connected with the pipelines of the sampling module 2 and the monitoring and analysis module 4 .
  • the above-mentioned monitoring and analysis module 4 is preferably a high performance liquid chromatograph (HPLC).
  • HPLC high performance liquid chromatograph
  • the liquid chromatograph is improved as follows: disassemble and adjust the sample injection part, connect with the online sample injection six-way valve through loop, and accept the short-circuit signal of the upper computer to control and trigger the operation, and the operation method Fixed selection, automatic flushing after the end of the running method.
  • the high performance liquid chromatograph gives a report in TXT format based on the extracted reaction solution sample for the host computer to extract data and generate an analysis report.
  • the liquid phase synthesis automatic monitoring system provided by the present invention further includes a cleaning module 6 .
  • the cleaning module 6 is connected to the sampling module 1 and the power module 3 via pipelines respectively.
  • the cleaning module includes: a first liquid container 6-1, a second liquid container 6-2 and a solenoid valve 6-3.
  • the stainless steel needle 2-3 can absorb the cleaning liquid in the first liquid container; the second liquid container 6-2, the power module 3 and the monitoring and analysis module 4 are connected to the pipeline of the solenoid valve. After the power module sucks the cleaning liquid in the second liquid container 6-2 into the power pump through the suction function, it can be injected into the monitoring and analysis module 4 to clean it.
  • the cleaning solution used in the present invention is preferably an organic solvent.
  • the solenoid valve 6-3 is preferably a three-way solenoid valve. Connect the loop and waste of the HPLC. The difference between it and the six-way valve in HPLC is that it is online alone and is controlled by the host computer.
  • liquid phase synthesis automatic monitoring system provided by the present invention to automatically sample, monitor and report and analyze the reaction solution, it is necessary to rely on software programs.
  • the specific advantages of the liquid phase synthesis automatic monitoring system provided by the present invention will be described in detail below in conjunction with the software program implanted in the host computer. Since the key point of the present invention is to protect the hardware structure, only the spiritual level is explained for the software control part.
  • the invention utilizes Shimadzu's DB version (database version) to analyze the liquid phase, reserves short-circuit joints for control and triggering, controls the liquid phase to run automatically according to the short-circuit signal from the upper computer to the PLC, and automatically generates a PDF version report after the operation is completed. And the TXT report of the ASCII code of the original data, the upper computer extracts the TXT report.
  • Shimadzu's DB version database version
  • reaction principle of "pre-activation” as an example, whether it is a common activation method or a light-mediated activation method, after the donor is activated, "sampling monitoring” needs to monitor whether the donor is fully activated, that is, activation monitoring, and then give Feedback of activation results, if not fully activated, continue to activate or repeatedly activate or continue to activate with light; if it is fully activated, add receptors, enter the "reaction time", and “sample to monitor” whether the receptors completely disappear after a certain time and temperature. Whether a new compound is formed, that is, reaction monitoring, and then give feedback on the reaction result. Whether the receptor remains is the key to judging whether to continue the next cycle reaction.
  • the receptor still remains, continue to prolong the reaction time or increase the reaction temperature to continue the reaction. If the receptor has disappeared or is below a certain limit, it can continue by default. In the next cycle, the activation reaction can be continued and monitored; if the receptor is always present above a certain limit, consider terminating the automated synthesis.
  • the present invention designs the above-mentioned online monitoring system capable of automatic sampling, sample injection, triggering, cleaning of pipelines, extraction of reports, and report comparison and judgment.
  • the software control program implanted in the upper computer mainly includes “sampling monitoring” and “monitoring”. result” two instructions.

Abstract

一种液相合成自动监测系统，包括：反应器（1）、取样模块（2）、动力模块（3）、监测分析模块（4）和上位机（5 ）；取样模块（2）与动力模块（3）的管路连接；动力模块（3）监测分析模块(4)的管路连接；取样模块(2)、动力模块(3)和监测分析模块(4)均与上位机(5)电连接；取样模块(2)用于吸取新型反应器(1)中盛装的反应溶液；动力模块(3)用于根据上位机(5)中的吸取指令为取样模块(2)提供吸取力，并用于将吸取的反应溶液注入监测分析模块(4)中；监测分析模块(4)用于根据反应溶液生成监测报告后，将监测报告传输给上位机(5)；上位机(5)根据监测报告生成分析结果。以上结构设置，能够实现对反应溶液的自动取样、进样、监测和报告分析，进而提高实验监测效率、降低实验操作投入的人力成本。

Description

一种液相合成自动监测系统
本申请要求于2020年12月19日提交中国专利局、申请号为202011509012.9、发明名称为“一种液相合成自动监测系统”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本发明涉及实验设备技术领域，特别是涉及一种液相合成自动监测系统。
背景技术
液相实验监测是确定实验结果的必要手段。现有液相实验监测需要将混合好的反应溶液放置到监测仪，通过监测仪得到监测结果。
但是现有技术在进行监测过程中，需要人工将反应液添加到监测仪中进行检测，并且，监测仪生成的监测报告需要人工整理核对，这就导致整个液相实验监测过程费时费力。
因此，提供一种新型液相合成自动监测装置，以实现液相合成实验的自动监测、分析，进而提高实验监测效率、降低实验操作的人力消耗是本领域亟待解决的一个技术难题。
发明内容
为解决现有技术中存在的上述问题，本发明提供了一种液相合成自动监测系统。
为实现上述目的，本发明提供了如下方案：
一种液相合成自动监测系统，包括：新型反应器、取样模块、动力模块、监测分析模块和上位机；
所述取样模块与所述动力模块的管路连接；所述动力模块和所述监测分析模块的管路连接；所述取样模块、所述动力模块和所述监测分析模块均与所述上位机电连接；
所述取样模块用于吸取所述新型反应器中盛装的反应溶液；所述动力模块用于根据所述上位机中的吸取指令为所述取样模块提供吸取力，并用于将吸取的反应溶液注入所述监测分析模块中；所述监测分析模块用于根据反应溶液生成监测报告后，将所述监测报告传输给所述上位机；所述上位机根据所述监测 报告生成分析结果。
优选地，所述新型反应器包括：瓶口、瓶身、进样口、排气口、取样口、循环出液口和循环进液口；
所述进样口与所述瓶身间呈设定角度；所述排气口和所述进样口以所述瓶口的中心线为中心对称设置；
所述瓶身由内及外依次包括反应内胆、温度循环层和真空层；所述反应内胆的胆底为弧形结构；
所述取样口与所述反应内胆连通；
所述循环出液口和所述循环进液口均与所述温度循环层连通，且所述循环出液口和所述循环进液口对角设置。
优选地，所述取样模块包括：不锈钢针头、滑轨和转盘；
所述不锈钢针头通过第一管道与所述动力模块连接；所述第一管道设置在所述滑轨上，且所述滑轨与水平线间呈设定角度；所述不锈钢针头固定设置在所述滑轨的一端，所述滑轨的另一端为自由端；所述滑轨用于带动所述不锈钢针头进行滑动，所述不锈钢针头用于探入所述新型反应器中吸取反应溶液；所述滑轨固定设置在所述转盘上；所述转盘和所述滑轨均与所述上位机电连接。
优选地，所述动力模块包括：动力泵；所述动力泵为注射泵或柱塞泵；
所述动力泵分别与所述取样模块和所述监测分析模块的管路连接。
优选地，所述监测分析模块为高效液相色谱仪。
优选地，还包括清洗模块；
所述清洗模块分别与所述取样模块和所述动力模块的管路连接。
优选地，所述清洗模块包括：第一盛液器、第二盛液器和电磁阀；
所述不锈钢针头吸取所述第一盛液器中的清洗液；所述第二盛液器、所述动力模块和所述监测分析模块均与所述电磁阀的管路连接。
优选地，所述清洗液为有机溶剂。
根据本发明提供的具体实施例，本发明公开了以下技术效果：
本发明提供的液相合成自动监测系统，通过设置取样模块、动力模块、监 测分析模块和上位机能够实现对反应溶液的自动取样、监测和报告分析，进而提高实验监测效率、降低实验操作投入的人力成本。
说明书附图
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动性的前提下，还可以根据这些附图获得其他的附图。
图1为本发明提供的液相合成自动监测系统的结构示意图；
图2为本发明实施例提供的新型反应器的结构示意图；
图3为本发明实施例提供的取样模块的结构示意图。
符号说明：
1新型反应器，1-1瓶口，1-2进样口，1-3排气口，1-4取样口，1-5瓶身，1-51反应内胆，1-52温度循环层，1-53真空层，1-6循环出液口，2取样模块，2-1滑轨，2-11滑动板，2-12支撑架，2-2转盘，2-3不锈钢针头，2-4第一管道，3动力模块，4监测分析模块，5上位机，6清洗模块，6-1第一盛液器，6-2第二盛液器，6-3电磁阀。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
本发明的目的是提供一种液相合成自动监测系统，以实现整个实验监测过程中的自动取样、自动监测和自动分析，进而提高实验监测效率、降低实验操作投入的人力成本。
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合附图和具体实施方式对本发明作进一步详细的说明。
图1为本发明提供的液相合成自动监测系统的结构示意图，如图1所示，一种液相合成自动监测系统，包括：新型反应器1、取样模块2、动力模块3、监测分析模块4和上位机5。
所述取样模块2与所述动力模块3的管路连接；所述动力模块3和所述监测分析模块4的管路连接；所述取样模块2、所述动力模块3和所述监测分析模块4均与所述上位机5电连接。
所述取样模块2用于吸取所述新型反应器1中盛装的反应溶液；所述动力模块3用于根据所述上位机5中的吸取指令为所述取样模块2提供吸取力，并用于将吸取的反应溶液注入所述监测分析模块4中；所述监测分析模块4用于根据反应溶液生成监测报告后，将所述监测报告传输给所述上位机5；所述上位机5根据所述监测报告生成分析结果。
下面对本发明提供的上述各模块的具体结构进行说明。
如图2所示，本发明提供的新型反应器1优选包括：瓶口1-1、瓶身1-5、进样口1-2、排气口1-3、取样口1-4、循环出液口1-6和循环进液口(图中未示出)。
所述进样口1-2与所述瓶口1-1间呈设定角度(优选为60°)；所述排气口1-3和所述进样口1-2以所述瓶口1-1的中心线为中心对称设置。
所述瓶身1-5由内及外依次包括反应内胆1-51、温度循环层1-52和真空层1-53；所述反应内胆1-51的胆底为弧形结构。
所述取样口1-4与所述反应内胆1-51连通。
所述循环出液口1-6和所述循环进液口均与所述温度循环层1-52连通，且所述循环出液口1-6和所述循环进液口对角设置。
如图3所示，上述取样模块包括：不锈钢针头2-3、滑轨2-1和转盘2-2；
所述不锈钢针头2-3通过第一管道2-4与所述动力模块2连接；所述第一管道2-4设置在所述滑轨2-1上，且所述滑轨2-1与水平线间呈设定角度(优选为60°)；所述不锈钢针头2-3固定设置在所述滑轨2-1的一端，所述滑轨2-1的另一端为自由端；所述滑轨2-1用于带动所述不锈钢针头2-3进行滑动，所述不锈钢针头2-3用于探入所述新型反应器1中吸取反应溶液；所述滑轨2-1固定设置在所述转盘2-2上；所述转盘2-2和所述滑轨2-3均与所述上位机5电连接。
其中，滑轨2-1包括滑动板2-11和支撑架2-12。滑动板2-11沿支撑架向 下运动，使得不锈钢针头2-3探入新型反应器1中以吸取反应溶液。支撑架2-12固定在转盘2-2上，转盘2-2可带动整个滑轨2-1进行旋转，以便不锈钢针头吸取不同容器中的液体。滑轨2-1是和新型反应器1的位置配合固定的，可升降调节。为了使第一管道2-4的固定更加牢固，滑轨2-1上可以设置有滑道以便固定第一导管2-4。转盘2-2(机加工模组)带动支撑滑轨2-1朝不同方向的一定角度转动不同位置并停留。
不锈钢针头2-3在本发明优选9#针头。在不锈钢针2-3和第一导管2-4连接位置处，还设置有可穿刺密闭橡胶垫和有机滤头。其中，有机滤头的选择规格包括0.22um、0.45um和0.8um。使用时，在有机滤头前端用脱脂棉轻微堵塞，相当于初步过滤反应溶液中的分子筛，再通过有机滤头的滤膜过滤满足进液相要求，实现双重过滤，这样能够有效避免堵塞有机滤头。
上述动力模块3包括：动力泵；所述动力泵为注射泵或柱塞泵；本发明中所选用的动力泵在具有较强吸取力的同时，还具有倒吸功能。设置倒吸功能，是为了便于对整个液相合成自动监测系统的管路进行清洗。
所述动力泵分别与所述取样模块2和所述监测分析模块4的管路连接。
上述监测分析模块4优选为高效液相色谱仪(HPLC)。本发明为便于实现自动监测的功能，对该液相色谱仪进行以下改进：拆卸调整进样部分，和在线进样六通阀通过loop连接，接受上位机的短接信号控制触发运行，运行方法固定选择好，运行方法结束后自动冲洗。高效液相色谱仪依据提取的反应溶液样本给出TXT格式的报告，供上位机提取数据并生成分析报告。
基于上述内容，为了便于对整个系统进行清洗，本发明提供的液相合成自动监测系统还包括清洗模块6。
所述清洗模块6分别与所述取样模块1和所述动力模块3管路连接。
该清洗模块包括：第一盛液器6-1、第二盛液器6-2和电磁阀6-3。
在转盘2-2带动下，所述不锈钢针头2-3能够吸取到第一盛液器中的清洗液；所述第二盛液器6-2、所述动力模块3和所述监测分析模块4均与所述电磁阀的管路连接。动力模块通过倒吸功能将第二盛液器6-2中的清洗液吸入到动力泵中后，可注入监测分析模块4中，以便对其进行清洗。本发明采用的清 洗液优选为有机溶剂。
其中，电磁阀6-3优选为三通电磁阀。连接HPLC的loop和废液。其与HPLC中的六通阀的区别在于它是单独在线，受上位机的控制。
在本发明中实现的滑轨2-1和转盘2-2的滑动旋转，均是采用现有的伺服电机进行，因其为现有常规技术，在此不再进行赘述。
在采用本发明提供的液相合成自动监测系统对反应溶液进行自动取样、监测和报告分析的过程中，需要依赖于软件程序。下面结合上位机中植入的软件程序对本发明提供的液相合成自动监测系统的具体优点进行详细说明。因本发明的重点在于保护硬件结构，因此针对软件控制部分只做精神层面的说明。
本发明利用岛津的DB版(数据库版)分析液相，预留控制触发的短接接头，结合上位机给PLC的短接信号控制液相根据需要自动运行，运行结束后自动生成PDF版报告和原始数据的ASCII码的TXT报告，上位机提取TXT报告。
在上位机中设置“在线监测”界面，一直提取最新产生的TXT报告。根据液相的命名方式，使得新产生的TXT报告的命名始终处于上一个TXT报告的下面，以方便于上位机的提取，上位机提取到新的TXT报告后可以根据内部植入的逻辑关系进行对比、判断和分析。
以“预活化”一釜的反应原理为例，不管是普通活化方式还是光介导活化方式，在给体活化后“取样监测”需要监测给体是否被完全活化，即活化监测，然后给出活化结果反馈，如未活化完全则继续活化或者反复活化或者继续光照活化，如果已完全活化则加入受体，进入“反应时间”，一定时间和温度后“取样监测”受体是否完全消失，同时是否有新化合物生成，即反应监测，然后给出反应结果反馈。受体是否剩余是判断是否继续进行下一步循环反应的关键，如果受体仍有剩余则继续延长反应时间或者升高反应温度以继续反应，如果受体已消失或者低于一定限度可默认继续进行下一个循环，可继续活化反应并监测；如果受体一直存在高于一定限度则考虑终止自动化合成。
综上本发明设计了以上能够自动取样、进样、触发、清洗管路、提取报告和报告对比判断的在线监测系统，其上位机中植入的软件控制程序主要包含 “取样监测”和“监测结果”两个指令。
本说明书中各个实施例采用递进的方式描述，每个实施例重点说明的都是与其他实施例的不同之处，各个实施例之间相同相似部分互相参见即可。
本文中应用了具体个例对本发明的原理及实施方式进行了阐述，以上实施例的说明只是用于帮助理解本发明的方法及其核心思想；同时，对于本领域的一般技术人员，依据本发明的思想，在具体实施方式及应用范围上均会有改变之处。综上所述，本说明书内容不应理解为对本发明的限制。

Claims (8)

  1. 一种液相合成自动监测系统，其特征在于，包括：新型反应器、取样模块、动力模块、监测分析模块和上位机；
    所述取样模块与所述动力模块的管路连接；所述动力模块和所述监测分析模块的管路连接；所述取样模块、所述动力模块和所述监测分析模块均与所述上位机电连接；
    所述取样模块用于吸取所述新型反应器中盛装的反应溶液；所述动力模块用于根据所述上位机中的吸取指令为所述取样模块提供吸取力，并用于将吸取的反应溶液注入所述监测分析模块中；所述监测分析模块用于根据反应溶液生成监测报告后，将所述监测报告传输给所述上位机；所述上位机根据所述监测报告生成分析结果。
  2. 根据权利要求1所述的液相合成自动监测系统，其特征在于，所述新型反应器包括：瓶口、瓶身、进样口、排气口、取样口、循环出液口和循环进液口；
    所述进样口与所述瓶口间呈设定角度；所述排气口和所述进样口以所述瓶口的中心线为中心对称设置；
    所述瓶身由内及外依次包括反应内胆、温度循环层和真空层；所述反应内胆的胆底为弧形结构；
    所述取样口与所述反应内胆连通；
    所述循环出液口和所述循环进液口均与所述温度循环层连通，且所述循环出液口和所述循环进液口对角设置。
  3. 根据权利要求1所述的液相合成自动监测系统，其特征在于，所述取样模块包括：不锈钢针头、滑轨和转盘；
    所述不锈钢针头通过第一管道与所述动力模块连接；所述第一管道设置在所述滑轨上，且所述滑轨与水平线间呈设定角度；所述不锈钢针头固定设置在所述滑轨的一端，所述滑轨的另一端为自由端；所述滑轨用于带动所述不锈钢针头进行滑动，所述不锈钢针头用于探入所述新型反应器中吸取反应溶液；所述滑轨固定设置在所述转盘上；所述转盘和所述滑轨均与所述上位机电连接。
  4. 根据权利要求1所述的液相合成自动监测系统，其特征在于，所述动 力模块包括：动力泵；所述动力泵为注射泵或柱塞泵；
    所述动力泵分别与所述取样模块和所述监测分析模块的管路连接。
  5. 根据权利要求1所述的液相合成自动监测系统，其特征在于，所述监测分析模块为高效液相色谱仪。
  6. 根据权利要求3所述的液相合成自动监测系统，其特征在于，还包括清洗模块；
    所述清洗模块分别与所述取样模块和所述动力模块的管路连接。
  7. 根据权利要求6所述的液相合成自动监测系统，其特征在于，所述清洗模块包括：第一盛液器、第二盛液器和电磁阀；
    所述不锈钢针头吸取所述第一盛液器中的清洗液；所述第二盛液器、所述动力模块和所述监测分析模块均与所述电磁阀的管路连接。
  8. 根据权利要求7所述的液相合成自动监测系统，其特征在于，所述清洗液为有机溶剂。
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