CN113149910B - Method for realizing automatic high-flux synthesis of heterocyclic ionic salt and device used in method - Google Patents
Method for realizing automatic high-flux synthesis of heterocyclic ionic salt and device used in method Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 29
- 150000003839 salts Chemical class 0.000 title abstract description 21
- 125000000623 heterocyclic group Chemical group 0.000 title abstract description 19
- 230000015572 biosynthetic process Effects 0.000 title description 17
- 238000003786 synthesis reaction Methods 0.000 title description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 42
- 238000011068 loading method Methods 0.000 claims abstract description 20
- 239000007788 liquid Substances 0.000 claims abstract description 16
- 238000005481 NMR spectroscopy Methods 0.000 claims abstract description 15
- 238000012988 high-throughput synthesis Methods 0.000 claims abstract description 7
- -1 heterocyclic ion salts Chemical class 0.000 claims description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 150000001450 anions Chemical class 0.000 claims description 9
- 238000004451 qualitative analysis Methods 0.000 claims description 8
- 238000001228 spectrum Methods 0.000 claims description 8
- 150000001768 cations Chemical class 0.000 claims description 7
- 229920001343 polytetrafluoroethylene Polymers 0.000 claims description 6
- 239000004810 polytetrafluoroethylene Substances 0.000 claims description 6
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 239000002699 waste material Substances 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 2
- 238000005086 pumping Methods 0.000 claims description 2
- 238000000967 suction filtration Methods 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims 3
- 235000011114 ammonium hydroxide Nutrition 0.000 claims 3
- 239000007864 aqueous solution Substances 0.000 claims 2
- 239000000243 solution Substances 0.000 claims 2
- DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 claims 1
- 238000005516 engineering process Methods 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 238000001914 filtration Methods 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 abstract description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 51
- 239000000463 material Substances 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 230000002194 synthesizing effect Effects 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 239000012295 chemical reaction liquid Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- 230000004907 flux Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- GGCNIPNYOVWYNK-UHFFFAOYSA-N [O-][N+](NN1N=NC2=NN=NC2=N1)=O Chemical compound [O-][N+](NN1N=NC2=NN=NC2=N1)=O GGCNIPNYOVWYNK-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 229920006324 polyoxymethylene Polymers 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- MCTWTZJPVLRJOU-UHFFFAOYSA-O 1-methylimidazole Chemical group CN1C=C[NH+]=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-O 0.000 description 1
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical group NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 1
- ZKDJXQGCVBEPBK-UHFFFAOYSA-N 3,5-diamino-1,2,4-triazole-3-carboxylic acid Chemical compound NC1=NC(N)(N=N1)C(O)=O ZKDJXQGCVBEPBK-UHFFFAOYSA-N 0.000 description 1
- GTBCBMSWXKGFDX-UHFFFAOYSA-N N([N+](=O)[O-])C=1N=NC=2N(N=1)C=NN=2 Chemical group N([N+](=O)[O-])C=1N=NC=2N(N=1)C=NN=2 GTBCBMSWXKGFDX-UHFFFAOYSA-N 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000011162 core material Substances 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- HUUBMTMJIQHAEN-UHFFFAOYSA-N triazole-1,4-diamine Chemical group NC1=CN(N)N=N1 HUUBMTMJIQHAEN-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/91—Nitro radicals
- C07D233/92—Nitro radicals attached in position 4 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
- C07D213/18—Salts thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/58—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/14—Nitrogen atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
A method for achieving automated high-throughput synthesis of a plurality of heterocyclic ionic salts, comprising: step 1, using a solvent to prepare a solution serving as a reaction compound; step 2, the setting of the sample adding program is carried out on the software equipped with the multi-channel automatic liquid transferring platform, which comprises the following steps: the sample sucking/loading sequence, the sample sucking/loading position, the sample sucking/loading amount, the sample sucking/loading speed, the mechanical arm moving speed and the positions of the gun head taking and gun head unloading; step 3, starting equipment to react; step 4, concentrating the reacted system, filtering and airing; and 5, performing qualitative determination on the target compound by utilizing a nuclear magnetic resonance technology and an infrared technology. The method can efficiently synthesize the heterocyclic ionic salt and effectively reduce the potential risk of operators due to accidents.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly provides a method for high-flux synthesis of heterocyclic ion salts by adopting a multichannel automation technology and a device used by the method.
Technical Field
After the energetic material is excited, a large amount of energy can be released. Due to the energy characteristics, the method has wider practical application in the fields of military, industry, civil life and the like. In military applications in particular, energetic materials are used as core materials of weaponry, and the performance of the energetic materials is one of the key factors for determining the advance of weaponry. The energetic material has high energy density and is easy to explode under external stimulation such as impact, friction, electrostatic sparks and the like. Therefore, designing high energy density materials with better performance, lower sensitivity and more environment-friendly is a hot spot in the field of energetic materials in recent years. The heterocyclic ionic salt is rich in N-N, C-N or N = N so that it has a high positive enthalpy of formation and its explosive products are free of contamination (typically nitrogen). The strong electrostatic interaction is helpful for the close packing of unit cells, thereby improving the crystal density. The negative charge of the heterocyclic ionic salt provides favorable conditions for effectively dispersing the negative charge on a chemical bond with low electron cloud density, and finally achieves the purpose of reducing the sensitivity of the energetic material by improving the shearing resistance of the chemical bond, thereby being one of the most advantages of the heterocyclic ionic salt. In terms of structural design, the heterocyclic ionic salt is subjected to acid-base or double decomposition reaction through different anions and cations to form the ionic salt, the synthetic method is simple, and the types of energetic materials are greatly enriched.
In practice, salts of heterocyclic ions are commonly used, including: salts of tetranitrobiimidazole or 6-nitroamino-triazolotetrazine with pyridine, imidazole, triazole or pyrazole.
Although heterocyclic materials have many advantages, the practical efficiency of manual batch synthesis is low due to the wide variety of anions and cations. And the anion and/or cation usually have/has certain energy characteristics, and thus, the synthesis process is potentially dangerous for operators.
Disclosure of Invention
In order to overcome the potential danger to operators in the process of synthesizing heterocyclic materials at present, the invention aims to optimize the defects of potential risk to the safety of the operators, time and labor waste in synthesis and low synthesis efficiency of the manually synthesized heterocyclic ionic salt, and provides a method for automatically synthesizing various heterocyclic ionic salts at high flux by utilizing micro-reaction, multi-channel and automation technologies. Namely, the method takes the heterocyclic ionic salt as a synthesis target, adopts a multichannel automation technology to carry out high-throughput synthesis, can improve the efficiency, reduce the labor cost and greatly improve the synthesis speed, and has important significance for accelerating the synthesis of the novel heterocyclic ionic salt.
Specifically, in a first aspect, the present invention provides a method for realizing automatic high-throughput synthesis of multiple heterocyclic ion salts, the method comprising the following steps:
step 1, using a solvent to prepare a solution of anion and cation compounds with required concentration for reaction;
and 2, setting a sample adding program on software matched with the multi-channel automatic liquid transferring platform, wherein the whole program comprises: taking a gun head, sucking reaction liquid, discharging the reaction liquid, unloading the gun head and resetting an instrument; the specific procedures comprise: the sample sucking/loading sequence, the sample sucking/loading position, the sample sucking/loading amount, the sample sucking/loading speed, the mechanical arm moving speed and the positions of the gun head taking and gun head unloading;
step 3, starting equipment to react;
step 4, concentrating the reacted system, filtering and airing;
and 5, performing qualitative analysis on the target compound by using a nuclear magnetic resonance technology and an infrared technology.
In addition, the number and sequence of the various steps may be varied according to reaction requirements.
Preferably, the heterocyclic ion salt comprises: : tetranitrobiimidazole or 6-nitramino-triazolotetrazine, pyridine, imidazole, triazole, pyrazole, ammonia, hydrazine hydrate and hydroxylamine.
In the present invention, the ratio of the input of the anionic reactant to the input of the cationic reactant is determined by the number of anions (mols) of the anionic reactant.
Preferably, the multi-channel automatic liquid transfer platform is provided with more than or equal to 3 channels, and more than 3 reactions can be carried out simultaneously; the more preferable number of the channels is 8-12, 8-12 reactions can be simultaneously carried out, and the reaction speed can be further improved.
Preferably, the amount of reaction substrate is from 100. Mu.l to 1000. Mu.l channels per channel.
Preferably, the reaction is carried out at room temperature under normal pressure, and after completion of the reaction, the reaction mixture is allowed to stand for 10 minutes or longer.
Preferably, the system after the reaction is filtered, dried, filtered, washed by methanol or ethanol, and naturally dried.
In a second aspect of the invention, there is provided apparatus for use in a method of preparing a plurality of heterocyclic ion salts of the first aspect of the invention, the apparatus comprising:
the device for contacting with the reaction solution in the method comprises: anion and cation solution liquid tanks, channels, gun heads, reaction tubes and the like;
(II) automatic liquid platform device that moves of multichannel includes: mechanical arms and the like;
and thirdly, program software for controlling reaction progress is arranged on the multi-channel automatic pipetting platform.
The equipment provided by the invention can be selected according to the known technology, wherein, because the reactant has strong corrosiveness, the equipment is preferably made of corrosion-resistant glass, ceramics, stainless steel, polytetrafluoroethylene materials and the like.
In a third aspect of the invention, there is provided a use of a multichannel automation technique in high throughput synthesis of heterocyclic ion salts, wherein the reaction for synthesizing the heterocyclic ion salts is a microreactor with a reaction substrate amount of 100 μ l to 1000 μ l per channel.
Effects of the invention
The project adopts a multi-channel automatic synthesis instrument, realizes multi-channel automatic synthesis of the energetic material through ion exchange reaction, and obtains physical and chemical performance parameters of the heterocyclic ionic salt. And the method is summarized according to the existing reaction result and the process of optimizing the instrument and the reaction, and has the following advantages:
1. the automatic synthesis platform has the characteristics of high automation degree, simplicity in operation, high flux, rapidness and the like, and successfully synthesizes various energetic ions with high flux (more than or equal to 3 reactions in a single parallel way, preferably more than or equal to 8 reactions in a single parallel way).
2. Due to the fact that the synthesis amount is small, the risk of operators accidentally during the synthesis process of the energetic materials is reduced.
3. The research work integrates multiple disciplines such as automatic processing, material chemistry, combinatorial chemistry, energetic material design and the like, the research method of the multiple disciplines is focused on one point, the discipline cross is strong, and the method has important significance for accelerating the synthesis of novel heterocyclic ionic salt.
Detailed Description
The exemplary embodiments will be described herein in detail, and the embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present invention. Rather, they are merely representative examples of the invention. From these exemplary embodiments, the excellent effects in practical application of the present invention can be more highlighted.
The technical solution of the present invention will be described in detail below with specific examples.
Examples 1-6 automated high throughput Synthesis of multiple heterocyclic Ionic salts
The reaction for synthesizing the heterocyclic ionic salt is as follows:
(I) reaction equipment:
1. the reaction tube processing device is provided with a proper amount of gun heads, more than three rows of reaction tubes (eight rows are used in the embodiment), liquid tanks and various device tanks, wherein the reaction tube processing device comprises gun head tanks, waste gun head tanks and more than three rows of reaction tube tanks (eight rows are used in the embodiment). The liquid tank is made of polytetrafluoroethylene, other devices are made of POM (polyformaldehyde), and the gun head and the reaction tube are made of PP (polypropylene).
2. The setting of the sample adding program is carried out on the software equipped on the multi-channel automatic pipetting platform, and the whole program comprises: taking a gun head, sucking reaction liquid, discharging the reaction liquid, unloading the gun head and resetting the instrument.
3. The setting conditions include: the sample sucking/loading sequence, the sample sucking/loading position, the sample sucking/loading amount, the sample sucking/loading speed, the mechanical arm moving speed and the positions of the gun head taking and gun head unloading.
(II) reaction procedure of example 1:
step 1, preparing 0.1mol/L1,1'2,2' -tetranitrobiimidazole and pyridine methanol solution, and putting the methanol solution in a liquid tank of an anion solution and a cation solution;
and 2, setting a specific sample adding program on software matched with the multi-channel automatic liquid transfer platform, wherein the setting comprises the following steps: the sample sucking/loading sequence, the sample sucking/loading position, the sample sucking/loading amount, the sample sucking/loading speed, the mechanical arm moving speed and the positions of the gun head taking and gun head unloading;
step 3, starting the equipment to react: taking a gun head from a gun head groove, moving the gun head to a polytetrafluoroethylene liquid groove to suck 1,1'2,2' -tetranitrobiimidazole 200 mu l 8, injecting the gun head into a reaction tube of the reaction tube groove, then pumping the used gun head into the waste gun head groove, taking a new gun head at a new row of positions of the gun head groove again, sucking 400 mu l of pyridine solution in the polytetrafluoroethylene liquid groove, and spitting the solution into the reaction tube added with 1,1'2,2' -tetranitrobiimidazole solution;
step 4, standing for more than half an hour at normal pressure and room temperature to complete the reaction;
step 5, carrying out suction filtration, washing a product with methanol, and naturally drying;
and 6, performing qualitative analysis on the product by a nuclear magnetic resonance hydrogen spectrum and a nuclear magnetic resonance carbon spectrum, wherein the qualitative analysis comprises the following steps:
1: tetranitrobiimidazole bipyridine salt
1H NMR(500MHz,DMSO)δ8.98(d,J＝5.6Hz,1H),8.50(t,J＝7.8Hz,1H),8.12–7.79(m,1H).13C NMR(126MHz,DMSO)δ144.96(s),144.18(s),141.85(s),139.80(s),127.03(s)。
(III) example 2-6 reaction procedure:
referring to reaction steps 1 to 5 of example 1 above, except that pyridine was replaced with 3-aminopyrazole, imidazole, 1-methylimidazole, 3, 5-diaminotriazole, pyrazole, respectively, to complete the reaction; and 6, performing qualitative analysis on the obtained product through a nuclear magnetic resonance hydrogen spectrum and a nuclear magnetic resonance carbon spectrum, wherein the qualitative analysis comprises the following steps:
2: tetranitrobiimidazole bis 3-aminopyrazolium salts
1H NMR(500MHz,DMSO)δ7.93(d,J＝2.6Hz,1H),5.93(d,J＝2.5Hz,1H).13C NMR(126MHz,DMSO)δ147.80(s),143.55(s),140.44(s),134.23(s),94.21(s).
3: tetranitrobiimidazole-bisimidazole salt
1H NMR(500MHz,DMSO)δ9.23(s,1H),7.77(d,J＝0.7Hz,1H).13C NMR(126MHz,DMSO)δ144.18(s),140.75(s),135.24(s),119.93(s).
4: tetranitrobiimidazole bis 1-methylimidazolium salts
1H NMR(500MHz,DMSO)δ9.13(s,1H),7.84–7.46(m,1H),3.88(s,1H).13C NMR(126MHz,DMSO)δ144.24(s),140.74(s),136.59(s),123.51(s),120.53(s),35.84(s).
5: tetranitrobiimidazole-bis 3, 5-diamino-1, 2, 4-triazolate
13C NMR(126MHz,DMSO)δ152.37(s),144.28(s),140.75(s).
6: tetranitrobiimidazole-bispyrazole salts
1H NMR(500MHz,DMSO)δ7.94(d,J＝1.3Hz,2H),6.49(d,J＝1.9Hz,1H).13C NMR(126MHz,DMSO)δ139.32(s),138.78(s),134.01(s),105.88(s)。
Examples 7-9 automated high throughput Synthesis of multiple heterocyclic ion salts
Referring to reaction steps 1 to 5 of the above example 1, except that 1,1'2,2' -tetranitrobiimidazole was replaced with 6-nitroamino-1, 2,4-triazolo [4,3-b ] [1,2,4,5] tetrazine and pyridine was replaced with ammonia, hydrazine hydrate, and 50% aqueous hydroxylamine solution, respectively, to complete the reaction; and 6, performing qualitative analysis on the obtained product through a nuclear magnetic resonance hydrogen spectrum and a nuclear magnetic resonance carbon spectrum, wherein the qualitative analysis comprises the following steps:
7: 6-nitroamino-1, 2, 4-triazolo [4,3-b ]][1,2,4,5]Tetrazine ammonium salt: 1 H NMR([D6]DMSO):δ7.17(s,4H),9.45(s,1H)； 13 C NMR([D6]DMSO):137.03,148.63,158.91ppm；
8: 6-nitroamino-1, 2, 4-triazolo [4,3-b ]][1,2,4,5]Tetrazine hydrazine salt: 1 H NMR([D6]DMSO):δ7.03(s,5H),9.45(s,1H)； 13 C NMR([D6]DMSO):136.93,148.54,158.97ppm；
9: 6-nitroamino-1, 2, 4-triazolo [4,3-b ]][1,2,4,5]Tetrazine hydroxylamine salts: 1 H NMR([D6]DMSO):δ9.45(s,1H),9.90(s,1H),10.10(s,3H)； 13 C NMR([D6]DMSO):136.57,149.29,152.77ppm；
by applying the method, the ion exchange reactions which are simultaneously carried out each time are more than or equal to 8, and the selected anions and cations are common structures in the field of energetic materials, so that the feasibility and the high efficiency of synthesizing the heterocyclic ionic salt by the method are proved, and the potential risk of operators due to accidents can be effectively reduced.
Other embodiments of the disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the disclosure disclosed herein. This application is intended to cover any variations, uses, or adaptations of the disclosure following, in general, the principles of the disclosure and including such departures from the present disclosure as come within known or customary practice within the art to which the disclosure pertains. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the disclosure being indicated by the following claims.
Claims (1)
1. A method for automated high-throughput synthesis of multiple heterocyclic ion salts, comprising the steps of:
step 1, preparing 0.1 mol/L6-nitro-amino-1, 2, 4-triazolo [4,3-b ] [1,2,4,5] tetrazine, ammonia water, hydrazine hydrate and 50% hydroxylamine aqueous solution in a liquid tank of anion and cation solution;
step 2, setting a specific sample adding program on software provided with the multi-channel automatic liquid transferring platform, comprising the following steps of: the sample sucking/loading sequence, the sample sucking/loading position, the sample sucking/loading amount, the sample sucking/loading speed, the mechanical arm moving speed and the positions of the gun head taking and gun head unloading;
step 3, starting the equipment to react: taking a gun head from a gun head groove, moving the gun head to a polytetrafluoroethylene liquid groove to absorb 200 mu L multiplied by 8 of 6-nitro-amino-1, 2, 4-triazolo [4,3-b ] [1,2,4,5] tetrazine, injecting the absorbed gun head into a reaction tube of a reaction tube groove, then pumping the used gun head into a waste gun head groove, taking a new gun head at a new row position of the gun head groove again, respectively absorbing 400 mu L multiplied by 8 of ammonia water in the polytetrafluoroethylene liquid groove, and spitting the liquid into a reaction tube added with 6-nitro-amino-1, 2,4,5] tetrazine solution; replacing the ammonia water with hydrazine hydrate and 50% hydroxylamine aqueous solution, and repeating the operations in the step 2 and the step 3;
step 4, standing for more than half an hour at normal pressure and room temperature to complete the reaction;
step 5, suction filtration, washing the product with methanol, and naturally drying;
and 6, performing qualitative analysis on the product by a hydrogen spectrum and a carbon spectrum of nuclear magnetic resonance as follows: 6-nitroamino-1, 2, 4-triazolo [4,3-b ] [1,2,4,5] tetrazine ammonium salt, 6-nitroamino-1, 2, 4-triazolo [4,3-b ] [1,2,4,5] tetrazine hydrazine salt and 6-nitroamino-1, 2, 4-triazolo [4,3-b ] [1,2,4,5] tetrazine hydroxylamine salt.
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