CN111519204A - Method for preparing N- (5-chloro-8-quinolyl) benzamide compound by adopting electrochemical microchannel reaction device - Google Patents
Method for preparing N- (5-chloro-8-quinolyl) benzamide compound by adopting electrochemical microchannel reaction device Download PDFInfo
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- 238000006243 chemical reaction Methods 0.000 title claims abstract description 113
- 238000000034 method Methods 0.000 title claims abstract description 24
- -1 N- (5-chloro-8-quinolyl) benzamide compound Chemical class 0.000 title claims abstract description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 86
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 38
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims abstract description 22
- 238000002156 mixing Methods 0.000 claims abstract description 15
- 239000003960 organic solvent Substances 0.000 claims abstract description 12
- YGICLPNGPGZANM-UHFFFAOYSA-N n-quinolin-8-ylbenzamide Chemical class C=1C=CC2=CC=CN=C2C=1NC(=O)C1=CC=CC=C1 YGICLPNGPGZANM-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 3
- 238000005086 pumping Methods 0.000 claims abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 210
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 80
- 239000012046 mixed solvent Substances 0.000 claims description 14
- 150000003936 benzamides Chemical class 0.000 claims 1
- 239000007800 oxidant agent Substances 0.000 abstract description 6
- 230000001590 oxidative effect Effects 0.000 abstract description 4
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- OYLCMWCAQDFBDD-UHFFFAOYSA-N n-(5-chloroquinolin-8-yl)benzamide Chemical class C12=NC=CC=C2C(Cl)=CC=C1NC(=O)C1=CC=CC=C1 OYLCMWCAQDFBDD-UHFFFAOYSA-N 0.000 abstract description 3
- 230000035484 reaction time Effects 0.000 abstract description 3
- 238000005660 chlorination reaction Methods 0.000 abstract description 2
- 238000006555 catalytic reaction Methods 0.000 abstract 1
- 208000012839 conversion disease Diseases 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 239000000047 product Substances 0.000 description 30
- 239000000243 solution Substances 0.000 description 28
- 239000012456 homogeneous solution Substances 0.000 description 25
- 238000002347 injection Methods 0.000 description 25
- 239000007924 injection Substances 0.000 description 25
- 239000011259 mixed solution Substances 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- 238000001228 spectrum Methods 0.000 description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 18
- 229910052799 carbon Inorganic materials 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 15
- 230000014759 maintenance of location Effects 0.000 description 12
- 238000001035 drying Methods 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 11
- 238000005406 washing Methods 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- 238000007865 diluting Methods 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 150000002825 nitriles Chemical class 0.000 description 10
- 238000002386 leaching Methods 0.000 description 9
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 4
- 229910002804 graphite Inorganic materials 0.000 description 4
- 239000010439 graphite Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- SVJQCVOKYJWUBC-OWOJBTEDSA-N (e)-3-(2,3,4,5-tetrabromophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC(Br)=C(Br)C(Br)=C1Br SVJQCVOKYJWUBC-OWOJBTEDSA-N 0.000 description 2
- ZGOLNEGJSWABJV-UHFFFAOYSA-N 4-chloro-n-quinolin-8-ylbenzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NC1=CC=CC2=CC=CN=C12 ZGOLNEGJSWABJV-UHFFFAOYSA-N 0.000 description 2
- WMHRIYVSXYZDGA-UHFFFAOYSA-N 4-methyl-n-quinolin-8-ylbenzamide Chemical compound C1=CC(C)=CC=C1C(=O)NC1=CC=CC2=CC=CN=C12 WMHRIYVSXYZDGA-UHFFFAOYSA-N 0.000 description 2
- LPVJIMCDCKVFHO-UHFFFAOYSA-N 4-nitro-n-quinolin-8-ylbenzamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)NC1=CC=CC2=CC=CN=C12 LPVJIMCDCKVFHO-UHFFFAOYSA-N 0.000 description 2
- 241000801593 Pida Species 0.000 description 2
- ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
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- 150000008282 halocarbons Chemical class 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
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- YBWWRMMAWZGAPQ-UHFFFAOYSA-N n-quinolin-8-ylacetamide Chemical compound C1=CN=C2C(NC(=O)C)=CC=CC2=C1 YBWWRMMAWZGAPQ-UHFFFAOYSA-N 0.000 description 2
- YDYBQLDFERHFHY-UHFFFAOYSA-N n-quinolin-8-ylfuran-2-carboxamide Chemical compound C=1C=CC2=CC=CN=C2C=1NC(=O)C1=CC=CO1 YDYBQLDFERHFHY-UHFFFAOYSA-N 0.000 description 2
- OQTLJZTUGXNZPM-UHFFFAOYSA-N n-quinolin-8-ylnaphthalene-2-carboxamide Chemical compound C1=CC=CC2=CC(C(NC=3C4=NC=CC=C4C=CC=3)=O)=CC=C21 OQTLJZTUGXNZPM-UHFFFAOYSA-N 0.000 description 2
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- PWJLENHIXAKAQE-UHFFFAOYSA-N C(C1=CC=CC=C1)(=O)NC=1C=C(C=C2C(=CC(=NC12)C)C)C Chemical compound C(C1=CC=CC=C1)(=O)NC=1C=C(C=C2C(=CC(=NC12)C)C)C PWJLENHIXAKAQE-UHFFFAOYSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
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- 102100026477 Tubulin-specific chaperone A Human genes 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/20—Processes
- C25B3/27—Halogenation
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- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B15/00—Operating or servicing cells
- C25B15/08—Supplying or removing reactants or electrolytes; Regeneration of electrolytes
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- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B9/00—Cells or assemblies of cells; Constructional parts of cells; Assemblies of constructional parts, e.g. electrode-diaphragm assemblies; Process-related cell features
- C25B9/17—Cells comprising dimensionally-stable non-movable electrodes; Assemblies of constructional parts thereof
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- Materials Engineering (AREA)
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Electrolytic Production Of Non-Metals, Compounds, Apparatuses Therefor (AREA)
Abstract
The invention discloses a method for preparing N- (5-chloro-8-quinolyl) benzamide compounds by adopting an electrochemical microchannel reaction device, which comprises the steps of dissolving 8- (benzoylamino) quinoline compounds in a first organic solvent to prepare a reaction solution A; dissolving dichloromethane and copper acetate in a second organic solvent to prepare a reaction solution B; and respectively pumping the reaction liquid A and the reaction liquid B into a micro mixer of the electrochemical microchannel reaction device at the same time for mixing, and then flowing into a micro reactor for reaction to obtain the catalyst. Compared with the prior art, the invention creatively develops a new method for preparing the chloroquinoline compound by taking methylene dichloride as a chlorination reagent in a micro-flow field electro-catalysis selectivity without the traditional oxidant; meanwhile, the invention utilizes the microchannel reaction device, greatly shortens the reaction time, improves the reaction conversion rate, and obviously improves the yield to 85 percent.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for preparing an N- (5-chloro-8-quinolyl) benzamide compound by adopting an electrochemical microchannel reaction device.
Background
The halogenated aromatic hydrocarbon and the heterocyclic compound are universal construction groups for cross coupling and Grignard reaction, and can be used for constructing various C-C, C-N, C-O and C-S compounds. In addition, aryl halides are often found in drug molecules because the biological properties are often significantly enhanced by the incorporation of halogen atoms. Traditionally, halogenation products are produced by electrophilic substitution of electron-rich aromatic or heterocyclic rings. The electronic nature of the aromatic ring leads to inherent selectivity. Moreover, double halogenated by-products are generally unavoidable. Recently, regioselective halogenation has attracted increasing attention. Also, ortho-metallation-halogen quenching and activation of metallation of the C-metal or C-heteroatom para position are prominent strategies to give overall ortho, meta and para substituted products, respectively. In this case, different halogen sources are used: (1) x2，CuX2，R1R2NX or TBCA; (2) halide (X-) with an exogenous oxidant such as PIDA, O2，O3，NFSI，K2S2O8DDQ; (3) an activated halogenated hydrocarbon, such as DCE. However, X2Is toxic and corrosive. In addition, stoichiometric amounts of oxidizing or halogenating agents, e.g. PIDA, NFSI, K, are used2S2O8，DDQ，CuX2And N-halosuccinimides, are environmentally unfriendly and produce undesirable waste products to the detriment of atom economy. And, found O2Or O3Is the in situ generation of Cl+An effective and green oxidizing agent. However, the scaling-up effect of the gas-liquid reaction limits its further industrial application. In the last few years, activated halogenated hydrocarbons (such as DCE) have been used as green and economical halogenating agents. However, the device is not suitable for use in a kitchenHowever, the use of oxidizing agents limits their intended use. Electrochemistry has become an efficient synthetic method that uses infinite electrons as reagents in the redox process, thereby avoiding the use of hazardous, costly and environmentally unfriendly oxidants and reductants. Therefore, electrosynthesis generally has a high atom economy, avoiding the production of undesirable waste products. In conclusion, the synthesis of the N- (5-chloro-8-quinolyl) benzamide compound by the electrochemical microchannel reaction device has the advantages of high efficiency, environmental friendliness, higher economic benefit and the like. Therefore, it is urgently needed to develop a method for preparing N- (5-chloro-8-quinolyl) benzamide compounds by using an electrochemical microchannel reaction device.
Disclosure of Invention
The purpose of the invention is as follows: the technical problem to be solved by the invention is to provide a method for preparing N- (5-chloro-8-quinolyl) benzamide compounds by adopting an electrochemical microchannel reaction device, aiming at the defects of the prior art, the method can solve the problems of complicated steps, overlong reaction time and the like in the reaction process, can improve the reaction efficiency, and is suitable for industrial production.
In order to solve the technical problem, the invention discloses a method for preparing an N- (5-chloro-8-quinolyl) benzamide compound by adopting an electrochemical microchannel reaction device, which comprises the steps of dissolving an 8- (benzoylamino) quinoline compound in a first organic solvent to prepare a reaction solution A; dissolving dichloromethane and copper acetate in a second organic solvent to prepare a reaction solution B; and respectively pumping the reaction liquid A and the reaction liquid B into a micro mixer of the electrochemical microchannel reaction device at the same time for mixing, and then flowing into a micro reactor for reaction, thus obtaining the catalyst, wherein the reaction principle is shown in figure 1.
Wherein, the first organic solvent and the second organic solvent are respectively and independently selected from acetonitrile, water or a mixed solvent of acetonitrile and water; preferably, the first organic solvent and the second organic solvent are both mixed solvents of acetonitrile and water; further preferably, the volume ratio of acetonitrile to water is 4: 1.
Wherein in the reaction solution A, the 8- (benzoylamino) quinoline compound is N- (quinolin-8-yl) benzamide, 4-methyl-N- (quinolin-8-yl) benzamide, 4-ethyl-N- (quinolin-8-yl) benzoyl, 4-chloro-N- (quinolin-8-yl) benzamide, 4-nitro-N- (quinolin-8-yl) benzamide, 4-phenyl-N- (quinolin-8-yl) benzamide, 2,4, 6-trimethyl- (quinolin-8-yl) benzamide, N- (quinolin-8-yl) -2-naphthamide, Any one of N- (quinolin-8-yl) furan-2-carboxamide and N- (quinolin-8-yl) acetamide.
Wherein, in the reaction liquid A, the concentration of the 8- (benzoylamino) quinoline compound is 0.15-0.45 mol/L, preferably 0.20 mol/L.
Wherein, in the reaction liquid B, the molar ratio of copper acetate is 75-85: 1, and the concentration of copper acetate is 0.01-0.05 mmol/mL; preferably, the molar ratio of copper acetate is 80:1, and the concentration of copper acetate is 0.03 mmol/mL.
Wherein the flow rate of the reaction liquid A pumped into a micro mixer of the electrochemical microchannel reaction device is 0.10-0.55 mL/min, and preferably 0.15 mL/min.
Wherein the flow rate of the reaction liquid B pumped into a micro mixer of the electrochemical microchannel reaction device is 0.05-0.25 mL/min, and preferably 0.10 mL/min.
Wherein the electrochemical microchannel reaction device (figure 2) comprises a first feeding pump, a second feeding pump, a micromixer, a microreactor, a cathode sheet, an anode sheet and a receiver; wherein the first feeding pump and the second feeding pump are connected to the micro mixer in a parallel mode through connecting pipes, and the micro mixer is connected with the micro reactor and the receiver in a series mode through pipelines; wherein, the two sides of the micro-reactor are respectively provided with a cathode sheet and an anode sheet, as shown in fig. 13.
Wherein, the material of the pipeline and other materials in the microchannel reaction device is polytetrafluoroethylene.
Wherein the anode sheet is a graphite carbon electrode or a platinum sheet electrode, and the graphite carbon electrode is preferred; the cathode sheet is a graphite carbon electrode or a platinum sheet electrode, and the platinum sheet electrode is preferred.
Wherein the pump is an HPLC pump or a syringe pump, preferably an HPLC pump.
The type of the micro mixer is T type, Y type or inverted Y type, and the Y type is preferred.
Wherein, the diameter of the connecting pipe is 0.1-5 mm, and the length is 0.5-60 m.
Wherein the diameter of the connecting pipe between the micro mixer and the micro reactor is 0.5-5 mm, preferably 2-5 mm.
Wherein the volume of the microreactor is 0.5-1.5 mL, and 1.25mL is preferred.
Wherein the current of the reaction is 80-120 mA, preferably 100 mA.
Wherein the reaction temperature is 0-50 ℃, and the reaction residence time is 2-15 min; preferably, the temperature of the reaction is 25 ℃ and the reaction residence time is 5 min.
And after the reaction is finished, collecting the effluent of the microreactor, washing with water, drying, filtering, performing column chromatography separation, and distilling under reduced pressure to obtain the N- (5-chloro-8-quinolyl) benzamide compound.
The column chromatography is to obtain a target product by eluting with a mixed solvent (volume ratio of 1: 10-1: 30) of ethyl acetate/petroleum ether as a mobile phase.
Has the advantages that: compared with the prior art, the invention has the following advantages:
(1) the invention creatively develops a new method for preparing the chloroquinoline compound by taking dichloromethane as a chlorination reagent through the electrocatalysis selectivity of the micro-flow field without the traditional oxidant, and simplifies the operation.
(2) The invention utilizes the microchannel reaction device, greatly shortens the reaction time, improves the yield, has high flux, stable product quality, strong continuity, is beneficial to continuous amplification production, has simple operation, high safety and easy separation, can effectively overcome the defects of the traditional synthesis path, and obviously improves the yield to 85 percent.
Drawings
FIG. 1 is a reaction scheme of the preparation method of the present invention.
FIG. 2 is a schematic diagram of a microchannel reaction apparatus and synthesis route according to the present invention; wherein, 1 is a first feeding pump, 2 is a second feeding pump, 3 is a micro mixer, 4 is an electrochemical micro reactor, and 5 is a receiver.
Fig. 3 shows a hydrogen spectrum and a carbon spectrum of 9 a.
Fig. 4 is a hydrogen spectrum and a carbon spectrum of 9 b.
Fig. 5 is a hydrogen spectrum and a carbon spectrum of 9 c.
Fig. 6 is a hydrogen spectrum and a carbon spectrum of 9 d.
Fig. 7 is a hydrogen spectrum and a carbon spectrum of 9 e.
Fig. 8 is a hydrogen spectrum and a carbon spectrum of 9 f.
FIG. 9 shows a hydrogen spectrum and a carbon spectrum of 9 g.
FIG. 10 is a hydrogen spectrum and a carbon spectrum of 9 h.
Fig. 11 is a hydrogen spectrum and a carbon spectrum of 9 i.
Fig. 12 is a hydrogen spectrum and a carbon spectrum of 9 j.
FIG. 13 is a schematic diagram of a microreactor in which (i) is a graphite carbon electrode, (ii) is a microreactor channel, and (iii) is a platinum-plate electrode.
Detailed Description
The invention will be better understood from the following examples. However, those skilled in the art will readily appreciate that the description of the embodiments is only for illustrating the present invention and should not be taken as limiting the invention as detailed in the claims.
The structures, proportions, and dimensions shown in the drawings and described in the specification are for understanding and reading the present disclosure, and are not intended to limit the scope of the present disclosure, which is defined in the claims, and are not essential to the skilled in the art. In addition, the terms "upper", "lower", "front", "rear" and "middle" used in the present specification are for clarity of description, and are not intended to limit the scope of the present invention, and the relative relationship between the terms and the relative positions may be changed or adjusted without substantial technical changes.
The microchannel reaction apparatus described in the following examples, as shown in fig. 2, includes a first feed pump 1 (a tank for a mixed solution of acetonitrile and water to which methylene chloride and copper acetate are connected), a second feed pump 2 (a tank for a mixed solution of acetonitrile and water to which 8- (benzoylamino) quinoline is connected), a micromixer 3, an electrochemical microreactor 4, and a receiver 5.
The first feed pump 1 and the second feed pump 2 are connected in parallel by a connecting pipe and the micromixer 3, the micromixer 3 and the electrochemical microreactor 4 are connected in series by a connecting pipe, and the electrochemical microreactor 4 and the receiving device 5 are connected in series by a connecting pipe. The reaction raw materials enter a mixer through an HPLC pump or an injection pump and then enter a microreactor for reaction.
The model of the micro mixer is Y type. The model of the electrochemical microchannel reactor is an electrochemical micro-reactor.
Example 1:
24mmol (1.99g) of dichloromethane and 0.3mmol (0.06g) of copper acetate are added to a mixed solution of 10mL of acetonitrile and water (acetonitrile: water ═ 4:1, i.e. 8mL of acetonitrile and 2mL of water) to give a homogeneous solution I, which is added to syringe pump 1; 2.0mmol (0.50g) of N- (quinolin-8-yl) benzamide was dissolved in 10mL of a mixed solution of acetonitrile and water (acetonitrile: water: 4:1, i.e., 8mL of acetonitrile and 2mL of water) to obtain a homogeneous solution ii, which was added to syringe pump 2; injecting the solution I and the solution II into a micro mixer 3 by an injection pump 1 and an injection pump 2 at the flow rates of 0.10mL/min and 0.15mL/min respectively, mixing in the micro mixer 3, and then entering an electrochemical micro-channel reactor 4 for reaction; the reaction volume of the first microchannel reactor is 1.25mL, and the reaction retention time is 5.0 min; the temperature of the electrochemical micro-channel reactor is 25 ℃, and the reaction current is 100 mA; after the reaction in the electrochemical microchannel reactor, the reaction liquid was collected, and the product yield was 85% by HPLC. Diluting the reaction liquid by using dichloromethane for five times, washing, drying and filtering the reaction liquid, and leaching and separating the reaction liquid by using a mixed solvent of ethyl acetate/petroleum ether (1: 30) to obtain a product 9 a;1H NMR(400MHz,CDCl3)10.69(s,1H),8.92–8.87(m,2H),8.60(dd,J＝8.5,1.5Hz,1H),8.07(dd,J＝7.9,1.4Hz,2H),7.66(d,J＝8.4Hz,1H),7.62–7.55(m,4H).13C NMR(101MHz,CDCl3)165.58,148.91,139.47,135.04,134.02,133.64,132.15,129.00,127.48,127.43,126.17,124.64,122.57,116.63.HRMS(ESI)Calcd for C16H12N2OCl[M+H]+:283.0633；found:283.0632.
example 2:
24mmol (1.99g) of dichloromethane and 0.3mmol (0.06g) of copper acetate are added to a mixed solution of 10mL of acetonitrile and water (acetonitrile: water ═ 4:1, i.e. 8mL of acetonitrile and 2mL of water) to give a homogeneous solution I, which is added to syringe pump 1; 2.0mmol (0.50g) of N- (quinolin-8-yl) benzamide was dissolved in 10mL of a mixed solution of acetonitrile and water (acetonitrile: water: 4:1, i.e., 8mL of acetonitrile and 2mL of water) to obtain a homogeneous solution ii, which was added to syringe pump 2; injecting the solution I and the solution II into a micro mixer 3 by an injection pump 1 and an injection pump 2 at the flow rates of 0.10mL/min and 0.15mL/min respectively, mixing in the micro mixer 3, and then entering an electrochemical micro-channel reactor 4 for reaction; the reaction volume of the first microchannel reactor is 1.25mL, and the reaction retention time is 5.0 min; the temperature of the electrochemical micro-channel reactor is 25 ℃, and the reaction current is 80 mA; after the reaction in the electrochemical microchannel reactor, the reaction liquid was collected and the product yield was 65% by HPLC.
Example 3:
24mmol (1.99g) of dichloromethane and 0.3mmol (0.06g) of copper acetate are added to a mixed solution of 10mL of acetonitrile and water (acetonitrile: water ═ 4:1, i.e. 8mL of acetonitrile and 2mL of water) to give a homogeneous solution I, which is added to syringe pump 1; 2.0mmol (0.50g) of N- (quinolin-8-yl) benzamide was dissolved in 10mL of a mixed solution of nitrile and water (acetonitrile: water ═ 4:1, i.e., 8mL of acetonitrile and 2mL of water) to obtain a homogeneous solution ii, which was added to syringe pump 2; injecting the solution I and the solution II into a micro mixer 3 by an injection pump 1 and an injection pump 2 at the flow rates of 0.10mL/min and 0.15mL/min respectively, mixing in the micro mixer 3, and then entering an electrochemical micro-channel reactor 4 for reaction; the reaction volume of the first microchannel reactor is 1.25mL, and the reaction retention time is 5.0 min; the temperature of the electrochemical micro-channel reactor is 25 ℃, and the reaction current is 120 mA; after the reaction in the electrochemical microchannel reactor, the reaction liquid was collected, and the product yield was 70% by HPLC.
Example 4:
24mmol (1.99g) of dichloromethane and 0.3mmol (0.06g) of copper acetate are added to a mixed solution of 10mL of acetonitrile and water (acetonitrile: water ═ 4:1, i.e. 8mL of acetonitrile and 2mL of water) to give a homogeneous solution I, which is added to syringe pump 1; 2.0mmol (0.53g) of 4-methyl-N- (quinolin-8-yl) benzamide was dissolved in 10mL of a mixed solution of nitrile and water (acetonitrile: water ═ 4:1, i.e., 8mL of acetonitrile and 2mL of water) to obtain a homogeneous solution ii, which was added to syringe pump 2; injecting the solution I and the solution II into a micro mixer 3 by an injection pump 1 and an injection pump 2 at the flow rates of 0.10mL/min and 0.15mL/min respectively, mixing in the micro mixer 3, and then entering an electrochemical micro-channel reactor 4 for reaction; the reaction volume of the first microchannel reactor is 1.25mL, and the reaction retention time is 5.0 min; the temperature of the electrochemical micro-channel reactor is 25 ℃, and the reaction current is 100 mA; after the reaction in the electrochemical microchannel reactor, the reaction liquid was collected, and the product yield was 83% by HPLC. Diluting the reaction liquid by using dichloromethane for five times, washing, drying and filtering, and leaching and separating by using a mixed solvent of ethyl acetate/petroleum ether (1: 30) to obtain a product 9 b;1H NMR(400MHz,CDCl3)10.64(s,1H),8.89-8.85(m,2H),8.56(dd,J＝8.5,1.5Hz,1H),7.96(dd,J＝7.9,1.4Hz,2H),7.63(d,J＝8.4Hz,1H),7.57(dd,J＝8.5,4.2Hz,1H),7.34(d,J＝8.0Hz,2H),2.45(s,3H).13C NMR(101MHz,CDCl3)165.51,148.81,142.67,139.38,134.07,133.57,132.15,129.62,127.44,127.41,126.10,124.42,122.48,116.54,21.68.HRMS(ESI)Calcd for C17H14N2OCl[M+H]+:297.0789；found:297.0786.
example 5:
24mmol (1.99g) of dichloromethane and 0.3mmol (0.06g) of copper acetate are added to a mixed solution of 10mL of acetonitrile and water (acetonitrile: water ═ 4:1, i.e. 8mL of acetonitrile and 2mL of water) to give a homogeneous solution I, which is added to syringe pump 1; 2.0mmol (0.55g) of 4-ethyl-N- (quinolin-8-yl) benzamide was dissolved in 10mL of a mixed solution of nitrile and water (acetonitrile: water ═ 4:1, i.e., 8mL of acetonitrile and 2mL of water) to obtain a homogeneous solution ii, which was added to syringe pump 2; the injection pump 1 and the injection pump 2 are respectively treated with 0.10mL/min and 0.15mLInjecting the solution I and the solution II into a micro mixer 3 at the flow rate of min, mixing in the micro mixer 3, and then entering an electrochemical micro-channel reactor 4 for reaction; the reaction volume of the first microchannel reactor is 1.25mL, and the reaction retention time is 5.0 min; the temperature of the electrochemical micro-channel reactor is 25 ℃, and the reaction current is 100 mA; after the reaction in the electrochemical microchannel reactor, the reaction liquid was collected, and the product yield was 80% by HPLC. Diluting the reaction liquid by using dichloromethane for five times, washing, drying and filtering, and leaching and separating by using a mixed solvent of ethyl acetate/petroleum ether (1: 30) to obtain a product 9 c;1H NMR(400MHz,CDCl3)10.66(s,1H),8.89–8.86(m,2H),8.58(dd,J＝8.5,1.6Hz,1H),7.99(d,J＝8.2Hz,2H),7.64(d,J＝8.4Hz,1H),7.58(dd,J＝8.5,4.2Hz,1H),7.37(d,J＝8.2Hz,2H),2.75(q,J＝7.6Hz,2H),1.30(t,J＝7.6Hz,3H).13C NMR(101MHz,CDCl3)165.58,148.89,148.84,139.43,134.12,133.56,132.43,128.47,127.52,127.46,126.12,124.42,122.50,116.50,29.00,15.46.HRMS(ESI)Calcd for C18H16N2OCl[M+H]+:311.0946；found:311.0934.
example 6:
24mmol (1.99g) of dichloromethane and 0.3mmol (0.06g) of copper acetate are added to a mixed solution of 10mL of acetonitrile and water (acetonitrile: water ═ 4:1, i.e. 8mL of acetonitrile and 2mL of water) to give a homogeneous solution I, which is added to syringe pump 1; 2.0mmol (0.56g) of 4-chloro-N- (quinolin-8-yl) benzamide was dissolved in 10mL of a mixed solution of nitrile and water (acetonitrile: water ═ 4:1, i.e., 8mL of acetonitrile and 2mL of water) to obtain a homogeneous solution ii, which was added to syringe pump 2; injecting the solution I and the solution II into a micro mixer 3 by an injection pump 1 and an injection pump 2 at the flow rates of 0.10mL/min and 0.15mL/min respectively, mixing in the micro mixer 3, and then entering an electrochemical micro-channel reactor 4 for reaction; the reaction volume of the first microchannel reactor is 1.25mL, and the reaction retention time is 5.0 min; the temperature of the electrochemical micro-channel reactor is 25 ℃, and the reaction current is 100 mA; after the reaction in the electrochemical microchannel reactor, the reaction liquid was collected, and the product yield was 78% by HPLC. Diluting the reaction liquid by using dichloromethane for five times, washing, drying and filteringEluting with mixed solvent of ethyl acetate/petroleum ether (1: 30) to obtain product 9 d;1H NMR(400MHz,CDCl3)10.65(s,1H),8.90(dd,J＝4.2,1.5Hz,1H),8.85(d,J＝8.4Hz,1H),8.61(dd,J＝8.5,1.5Hz,1H),8.01(dt,J＝8.6,1.6Hz,2H),7.66(d,J＝8.4Hz,1H),7.61(dd,J＝8.5,4.2Hz,1H),7.53(dt,J＝8.5,1.6Hz,2H).13C NMR(101MHz,CDCl3)164.32,148.84,139.27,138.35,133.62,133.60,133.27,129.14,128.73,127.33,126.06,124.78,122.50,
116.61.HRMS(ESI)Calcd for C16H11N2OCl2[M+H]+:317.0243；found:317.0287.
example 7:
24mmol (1.99g) of dichloromethane and 0.3mmol (0.06g) of copper acetate are added to a mixed solution of 10mL of acetonitrile and water (acetonitrile: water ═ 4:1, i.e. 8mL of acetonitrile and 2mL of water) to give a homogeneous solution I, which is added to syringe pump 1; 2.0mmol (0.59g) of 4-nitro-N- (quinolin-8-yl) benzamide was dissolved in 10mL of a mixed solution of nitrile and water (acetonitrile: water ═ 4:1, i.e., 8mL of acetonitrile and 2mL of water) to obtain a homogeneous solution ii, which was added to syringe pump 2; injecting the solution I and the solution II into a micro mixer 3 by an injection pump 1 and an injection pump 2 at the flow rates of 0.10mL/min and 0.15mL/min respectively, mixing in the micro mixer 3, and then entering an electrochemical micro-channel reactor 4 for reaction; the reaction volume of the first microchannel reactor is 1.25mL, and the reaction retention time is 5.0 min; the temperature of the electrochemical micro-channel reactor is 25 ℃, and the reaction current is 100 mA; after the reaction in the electrochemical microchannel reactor, the reaction liquid was collected, and the product yield was 50% by HPLC. Diluting the reaction liquid by using dichloromethane for five times, washing, drying and filtering, and leaching and separating by using a mixed solvent of ethyl acetate/petroleum ether (1: 10) to obtain a product 9 e;1H NMR(400MHz,CDCl3)10.79(s,1H),8.93(dd,J＝4.3,1.6Hz,1H),8.87(d,J＝8.4Hz,1H),8.66(dd,J＝8.5,1.6Hz,1H),8.44–8.39(m,2H),8.26–8.21(m,2H),7.70(d,J＝8.4Hz,1H),7.66(dd,J＝8.5,4.3Hz,1H).13C NMR(101MHz,CDCl3)163.27,149.92,148.88,140.29,139.00,134.02,133.08,128.54,127.39,126.17,125.54,124.11,122.65,117.21.HRMS(ESI)Calcd for C16H11N3O3Cl[M+H]+:328.0483；found:328.0492.
example 8:
24mmol (1.99g) of dichloromethane and 0.3mmol (0.06g) of copper acetate are added to a mixed solution of 10mL of acetonitrile and water (acetonitrile: water ═ 4:1, i.e. 8mL of acetonitrile and 2mL of water) to give a homogeneous solution I, which is added to syringe pump 1; 2.0mmol (0.65g) of 4-phenyl-N- (quinolin-8-yl) benzamide was dissolved in 10mL of a mixed solution of nitrile and water (acetonitrile: water ═ 4:1, i.e., 8mL of acetonitrile and 2mL of water) to obtain a homogeneous solution ii, which was added to syringe pump 2; injecting the solution I and the solution II into a micro mixer 3 by an injection pump 1 and an injection pump 2 at the flow rates of 0.10mL/min and 0.15mL/min respectively, mixing in the micro mixer 3, and then entering an electrochemical micro-channel reactor 4 for reaction; the reaction volume of the first microchannel reactor is 1.25mL, and the reaction retention time is 5.0 min; the temperature of the electrochemical micro-channel reactor is 25 ℃, and the reaction current is 100 mA; after the reaction in the electrochemical microchannel reactor, the reaction liquid was collected, and the product yield was 72% by HPLC. Diluting the reaction liquid by using dichloromethane for five times, washing, drying and filtering the reaction liquid, and leaching and separating the reaction liquid by using a mixed solvent of ethyl acetate/petroleum ether (1: 30) to obtain a product 9 f;1H NMR(400MHz,CDCl3)10.75(s,1H),8.93–8.90(m,2H),8.61(dd,J＝8.5,1.6Hz,1H),8.15(dt,J＝8.4,1.6Hz,2H),7.78(dt,J＝8.4,1.6Hz,2H),7.69-7.65(m,3H),7.61(dd,J＝8.5,4.2Hz,1H),7.50(tt,J＝7.4,1.6Hz,2H),7.42(tt,J＝7.3,1.2Hz,1H).13CNMR(101MHz,CDCl3)165.29,148.93,144.95,140.11,139.48,134.04,133.66,129.13,128.26,127.98,127.65,127.50,127.40,126.19,124.64,122.59,116.65.HRMS(ESI)Calcdfor C22H16N2OCl[M+H]+:359.0946；found:359.0950.
example 9:
24mmol (1.99g) of dichloromethane and 0.3mmol (0.06g) of copper acetate are added to a mixed solution of 10mL of acetonitrile and water (acetonitrile: water ═ 4:1, i.e. 8mL of acetonitrile and 2mL of water) to give a homogeneous solution I, which is added to syringe pump 1; 2.0mmol (0.58g) of 2,4, 6-trimethyl- (quinoline-8)-yl) benzamide was dissolved in 10mL of a mixed solution of nitrile and water (acetonitrile: water-4: 1, namely 8mL of acetonitrile and 2mL of water) to obtain a homogeneous solution II, and adding the homogeneous solution II into a syringe pump 2; injecting the solution I and the solution II into a micro mixer 3 by an injection pump 1 and an injection pump 2 at the flow rates of 0.10mL/min and 0.15mL/min respectively, mixing in the micro mixer 3, and then entering an electrochemical micro-channel reactor 4 for reaction; the reaction volume of the first microchannel reactor is 1.25mL, and the reaction retention time is 5.0 min; the temperature of the electrochemical micro-channel reactor is 25 ℃, and the reaction current is 100 mA; after the reaction in the electrochemical microchannel reactor, the reaction liquid was collected, and the product yield was 75% by HPLC. Diluting the reaction liquid by using dichloromethane for five times, washing, drying and filtering, and leaching and separating by using a mixed solvent of ethyl acetate/petroleum ether (1: 30) to obtain 9g of a product;1H NMR(400MHz,CDCl3)9.87(s,1H),8.93(d,J＝8.4Hz,1H),8.77(dd,J＝4.2,1.6Hz,1H),8.58(dd,J＝8.5,1.6Hz,1H),7.66(d,J＝8.4Hz,1H),7.56(dd,J＝8.5,4.2Hz,1H),6.93(s,2H),2.39(s,6H),2.34(s,3H).13C NMR(101MHz,CDCl3)169.27,148.86,139.25,139.07,135.27,134.68,133.89,133.54,128.61,127.39,126.15,124.78,122.50,116.76,21.30,19.55.HRMS(ESI)Calcd for C19H18N2OCl[M+H]+:325.1102；found:325.1107.
example 10:
24mmol (1.99g) of dichloromethane and 0.3mmol (0.06g) of copper acetate are added to a mixed solution of 10mL of acetonitrile and water (acetonitrile: water ═ 4:1, i.e. 8mL of acetonitrile and 2mL of water) to give a homogeneous solution I, which is added to syringe pump 1; 2.0mmol (0.60g) of N- (quinolin-8-yl) -2-naphthamide was dissolved in 10mL of a mixed solution of nitrile and water (acetonitrile: water: 4:1, i.e., 8mL of acetonitrile and 2mL of water) to obtain a homogeneous solution II, which was added to syringe pump 2; injecting the solution I and the solution II into a micro mixer 3 by an injection pump 1 and an injection pump 2 at the flow rates of 0.10mL/min and 0.15mL/min respectively, mixing in the micro mixer 3, and then entering an electrochemical micro-channel reactor 4 for reaction; the reaction volume of the first microchannel reactor is 1.25mL, and the reaction retention time is 5.0 min; the temperature of the electrochemical micro-channel reactor is 25 ℃, and the reaction current is 100 mA;after the reaction in the electrochemical microchannel reactor, the reaction liquid was collected, and the product yield was 75% by HPLC. Diluting the reaction liquid by using dichloromethane for five times, washing, drying and filtering, and leaching and separating by using a mixed solvent of ethyl acetate/petroleum ether (1: 30) to obtain a product for 9 hours;1H NMR(400MHz,CDCl3)10.83(s,1H),8.96–8.92(m,2H),8.61(dd,J＝8.5,1.4Hz,1H),8.59(s,1H),8.12(dd,J＝8.6,1.6Hz,1H),8.06–8.03(m,1H),8.00(d,J＝8.6Hz,1H),7.94–7.91(m,1H),7.68(d,J＝8.4Hz,1H),7.64–7.57(m,3H).13C NMR(101MHz,CDCl3)165.63,148.92,139.43,135.14,134.04,133.73,132.87,132.20,129.37,128.90,128.18,128.11,127.95,127.53,127.02,126.19,124.70,123.78,122.57,116.81.HR-MS(ESI)Calcd for C20H14N2OCl[M+H]+:333.0789；found:333.0789.
example 11:
24mmol (1.99g) of dichloromethane and 0.3mmol (0.06g) of copper acetate are added to a mixed solution of 10mL of acetonitrile and water (acetonitrile: water ═ 4:1, i.e. 8mL of acetonitrile and 2mL of water) to give a homogeneous solution I, which is added to syringe pump 1; 2.0mmol (0.48g) of N- (quinolin-8-yl) furan-2-carboxamide was dissolved in 10mL of a mixed nitrile and water solution (acetonitrile: water ═ 4:1, i.e., 8mL of acetonitrile and 2mL of water) to obtain a homogeneous solution II, which was added to syringe pump 2; injecting the solution I and the solution II into a micro mixer 3 by an injection pump 1 and an injection pump 2 at the flow rates of 0.10mL/min and 0.15mL/min respectively, mixing in the micro mixer 3, and then entering an electrochemical micro-channel reactor 4 for reaction; the reaction volume of the first microchannel reactor is 1.25mL, and the reaction retention time is 5.0 min; the temperature of the electrochemical micro-channel reactor is 25 ℃, and the reaction current is 100 mA; after the reaction in the electrochemical microchannel reactor, the reaction liquid was collected, and the product yield was 60% by HPLC. Diluting the reaction liquid by using dichloromethane for five times, washing, drying and filtering, and leaching and separating by using a mixed solvent of ethyl acetate/petroleum ether (1: 30) to obtain a product 9 i;1H NMR(400MHz,CDCl3)10.72(s,1H),8.93(dd,J＝4.2,1.6Hz,1H),8.82(d,J＝8.4Hz,1H),8.59(dd,J＝8.5,1.6Hz,1H),7.65–7.58(m,3H),7.31(d,J＝3.6,0.8Hz,1H),6.60(dd,J＝3.5,1.7Hz,1H).13C NMR(101MHz,CDCl3)156.49,149.03 148.29,144.79,139.34,133.62,133.56,127.40,126.18,124.79,122.59,116.71115.53,112.68.HRMS(ESI)Calcd for C14H10N2O2Cl[M+H]+:273.0425；found:273.0406.
example 12:
24mmol (1.99g) of dichloromethane and 0.3mmol (0.06g) of copper acetate are added to a mixed solution of 10mL of acetonitrile and water (acetonitrile: water ═ 4:1, i.e. 8mL of acetonitrile and 2mL of water) to give a homogeneous solution I, which is added to syringe pump 1; 2.0mmol (0.37g) of N- (quinolin-8-yl) acetamide was dissolved in 10mL of a mixed solution of nitrile and water (acetonitrile: water ═ 4:1, i.e., 8mL of acetonitrile and 2mL of water) to obtain a homogeneous solution ii, which was added to syringe pump 2; injecting the solution I and the solution II into a micro mixer 3 by an injection pump 1 and an injection pump 2 at the flow rates of 0.10mL/min and 0.15mL/min respectively, mixing in the micro mixer 3, and then entering an electrochemical micro-channel reactor 4 for reaction; the reaction volume of the first microchannel reactor is 1.25mL, and the reaction retention time is 5.0 min; the temperature of the electrochemical micro-channel reactor is 25 ℃, and the reaction current is 100 mA; after the reaction in the electrochemical microchannel reactor, the reaction liquid was collected, and the product yield was 75% by HPLC. Diluting the reaction liquid by using dichloromethane for five times, washing, drying and filtering the reaction liquid, and leaching and separating the reaction liquid by using a mixed solvent of ethyl acetate/petroleum ether (1: 30) to obtain a product 9 j;1H NMR(400MHz,CDCl3)9.74(s,1H),8.84(dd,J＝4.2,1.6Hz,1H),8.70(d,J＝8.4Hz,1H),8.56(dd,J＝8.5,1.6Hz,1H),7.60–7.55(m,2H),2.35(s,3H).13CNMR(101MHz,CDCl3)168.90,148.79,138.89,133.91,133.59,127.39,126.03,124.34,122.45,116.48,25.26.HRMS(ESI)Calcd for C11H10N2OCl[M+H]+:221.0476；found:221.0478.
table 1 shows the structural formula of the N- (5-chloro-8-quinolyl) benzamide compound products prepared in examples 1-12, which is determined by nuclear magnetic characterization, and nuclear magnetic maps of the products are shown in FIGS. 3-12.
The present invention provides a method and a method for preparing N- (5-chloro-8-quinolyl) benzamide compound by using an electrochemical microchannel reaction device, and a method and a way for implementing the technical scheme are many, and the above description is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be regarded as the protection scope of the present invention. All the components not specified in the present embodiment can be realized by the prior art.
Claims (10)
1. A method for preparing N- (5-chlorine-8-quinolyl) benzamide compounds by adopting an electrochemical microchannel reaction device is characterized in that 8- (benzoylamino) quinoline compounds are dissolved in a first organic solvent to prepare a reaction solution A; dissolving dichloromethane and copper acetate in a second organic solvent to prepare a reaction solution B; and respectively pumping the reaction liquid A and the reaction liquid B into a micro mixer of the electrochemical microchannel reaction device at the same time for mixing, and then flowing into a micro reactor for reaction to obtain the catalyst.
2. The method according to claim 1, wherein the first organic solvent and the second organic solvent are each independently selected from acetonitrile, water, or a mixed solvent of acetonitrile and water.
3. The method according to claim 1, wherein the concentration of the 8- (benzoylamino) quinoline compound in the reaction solution A is 0.15-0.45 mol/L.
4. The method according to claim 1, wherein the molar ratio of dichloromethane to copper acetate in the reaction solution B is 75-85: 1, and the concentration of copper acetate is 0.01-0.05 mmol/mL.
5. The method according to claim 1, wherein the flow rate of the reaction solution A pumped into the micromixer of the electrochemical microchannel reaction device is 0.10-0.55 mL/min.
6. The method according to claim 1, wherein the flow rate of the reaction solution B pumped into the micromixer of the electrochemical microchannel reaction device is 0.05-0.25 mL/min.
7. The method of claim 1, wherein the electrochemical microchannel reactor device comprises a first feed pump, a second feed pump, a micromixer, a microreactor, a cathode sheet, an anode sheet, and a receiver; wherein the first feeding pump and the second feeding pump are connected to the micro mixer in a parallel mode through connecting pipes, and the micro mixer is connected with the micro reactor and the receiver in a series mode through pipelines; wherein, the two sides of the micro-reactor are respectively provided with a cathode sheet and an anode sheet.
8. The method of claim 7, wherein the microreactor has a volume of 0.5 to 1.5 mL.
9. The method of claim 1, wherein the current of the reaction is 80 to 120 mA.
10. The method according to claim 1, wherein the reaction temperature is 0 to 50 ℃ and the reaction residence time is 2 to 15 min.
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| CN112239871A (en) * | 2020-10-21 | 2021-01-19 | 南京先进生物材料与过程装备研究院有限公司 | Method for continuously preparing C-2 chloro-substituted quinoline by using electrochemical microchannel reaction device |
| CN112410809A (en) * | 2020-11-12 | 2021-02-26 | 南京工业大学 | Method for synthesizing fluorine-containing quinolinone compounds by electrocatalysis of indole by using electrochemical microchannel reaction device |
| CN112695337A (en) * | 2020-12-17 | 2021-04-23 | 中国药科大学 | Method for continuously preparing 1- (methylsulfonyl) -2- (phenylethynyl) benzene by adopting electrochemical microchannel |
| CN112695337B (en) * | 2020-12-17 | 2022-03-11 | 中国药科大学 | Method for continuously preparing 1- (methylsulfonyl) -2- (phenylethynyl) benzene by adopting electrochemical microchannel |
| CN114737209B (en) * | 2022-05-13 | 2023-11-14 | 南京先进生物材料与过程装备研究院有限公司 | Method for preparing 2-formamidobenzamide derivative through continuous electrochemical reaction |
| CN115011977A (en) * | 2022-07-25 | 2022-09-06 | 南京工业大学 | Method for continuously and electrically synthesizing indoline compound by using micro-reaction device |
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