CN113549939B - Method for continuously electrically synthesizing isoindolinone by using micro-reaction device - Google Patents

Method for continuously electrically synthesizing isoindolinone by using micro-reaction device Download PDF

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CN113549939B
CN113549939B CN202110774274.6A CN202110774274A CN113549939B CN 113549939 B CN113549939 B CN 113549939B CN 202110774274 A CN202110774274 A CN 202110774274A CN 113549939 B CN113549939 B CN 113549939B
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季栋
沈磊
李玉光
花加伟
方正
郭凯
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Nanjing Advanced Biomaterials And Process Equipment Research Institute Co ltd
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Abstract

The invention discloses a new method for continuously electrochemically synthesizing isoindolinone, which takes N-methoxy-2-vinylbenzamide I and sodium trifluoromethanesulfonate II as reaction raw materials, continuously performs electrolytic reaction in a microchannel reaction device in the presence of electrolyte and solvent, and obtains trifluoromethyl functionalized isoindolinone III through intramolecular free radical cascade reaction; the reaction process is shown as a reaction formula. Compared with the prior art, the invention provides a novel preparation method of isoindolinone, and the preparation method has the advantages of green, safe and efficient process operation and mild reaction conditions.

Description

Method for continuously electrically synthesizing isoindolinone by using micro-reaction device
Technical Field
The invention belongs to the field of organic electro-synthesis, and particularly relates to a method for continuously electro-synthesizing isoindolinone by using a micro-reaction device.
Background
Isoindolinones are a class of key structural motifs often found in many natural products, pharmacologically active compounds and materials. It is of great interest because of its outstanding biological activity and a variety of synthetic applications in the preparation of complex molecular frameworks. The most efficient method for preparing functionalized isoindolinone compounds is provided by a series of free radical mediated reactions.
At present, the method for constructing the skeleton of the trifluoromethyl functionalized isoindolinone compound comprises the following steps: (1) Copper-catalyzed intramolecular aminotrifluoromethylation of olefins to prepare trifluoromethyl-functionalized isoindolinones, see references (org. Chem. Front.,2016,3, 222-226); (2) Trifluoromethyl functionalized isoindolinones were prepared using Langlois reagent as the trifluoromethyl source and copper promoted intramolecular aminotrifluoromethylation of the olefin, as described in references (Synlett 2017 (08): 962-965. Although the above methods have been reported, these methods still have some significant drawbacks: the reaction conditions are harsh, and an oxidant and an excessive amount of a metal catalyst are required for the reaction. These drawbacks not only present safety and environmental concerns, but also make industrial scale-up difficult.
Disclosure of Invention
The purpose of the invention is as follows: the technical problem to be solved by the invention is to develop a novel isoindolinone electric synthesis method, and overcome the problems of harsh reaction conditions, and the need of an oxidant and metal of the traditional system.
The technical scheme is as follows: in order to solve the technical problems, the technical scheme adopted by the invention is a method for continuously and electrically synthesizing isoindolinone by using a microchannel reaction device, which comprises the following steps:
(1) Dissolving N-methoxy-2-vinylbenzamide, sodium trifluoromethylsulfinate and electrolyte in a solvent to prepare a homogeneous solution A;
(2) Pumping the homogeneous solution A into a microchannel reaction device provided with an electrode for electrolytic reaction, and collecting effluent liquid, namely the solution containing the isoindolinone shown in the formula III;
Figure BDA0003153900050000011
the reaction equation for continuously and electrically synthesizing isoindolinone by using the microchannel reaction device is as follows:
Figure BDA0003153900050000021
as a preferable scheme:
in the step (1), the electrolyte is one or a combination of more of tetrabutylammonium acetate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium iodide, tetraethylammonium perchlorate and sodium iodide, and tetrabutylammonium acetate is preferred.
In the step (1), the solvent is any one or a combination of more of acetonitrile, water, dichloroethane and methanol, preferably a combination of acetonitrile and water; more preferably, the volume ratio of acetonitrile to water is 4.
In the step (1), the concentration of the N-methoxyl-2-vinylbenzamide is 0.02 to 0.1mmol/mL; the concentration of the sodium trifluoromethanesulfonate is 0.05-0.2 mmol/mL; the concentration of the electrolyte is 0.05-0.3 mmol/mL; preferably, the concentration of the N-methoxy-2-vinylbenzamide is 0.05mmol/mL; the concentration of the sodium trifluoromethanesulfonate is 0.15mmol/mL; the concentration of the electrolyte was 0.1mmol/mL.
In the step (2), the microchannel reaction device provided with the electrode comprises an injection pump, a microchannel reactor, a cathode sheet, an anode sheet and a receiver; wherein, both sides of the microchannel reactor are respectively provided with a cathode sheet and an anode sheet; the injector, the microchannel reactor, and the receiver are connected in series; the connection is a pipeline connection.
Wherein the reaction volume of the microchannel reactor is 200-250 μ L, preferably 225 μ L.
Wherein, the cathode sheet is a platinum sheet; the anode sheet is a graphite plate.
In the step (2), the current intensity of the electrolytic reaction is 5-20 mA, preferably any one of 5mA, 10mA, 15mA and 20mA; more preferably 10mA.
In the step (2), the flow rate of the homogeneous solution A pumped into the microchannel reactor is 22.5-450 muL/min, preferably 225 muL/min; the temperature of the electrolytic reaction is room temperature; the residence time of the reaction is from 0.5 to 10min, preferably 1min.
The microchannel reactor technology has gradually become a research hotspot in the technical field of international fine chemical engineering. A microchannel reactor is a three-dimensional structural element that can be used for chemical reactions, fabricated with a fixed matrix by means of special microfabrication techniques. Microchannel reactors typically contain very small channel sizes (equivalent diameters less than 500 μm) and channel diversity in which fluids flow, mix, and react. And therefore have a very large specific surface area (surface area/volume) in such a microfabricated chemical device. The advantages brought by this are the great mass and heat transfer efficiency, i.e. the precise control of the reaction temperature and the instantaneous mixing of the reaction mass in a precise ratio can be realized. These are all key to improve yield, selectivity, safety, and product quality.
The microchannel reactor used in the invention is a microchannel reactor with small channel diameter and high mass transfer efficiency. The isoindolinone is quickly synthesized by using the microchannel reactor, so that the amplification reaction is facilitated, and the reaction process is safe, efficient and green.
Has the beneficial effects that: compared with the prior art, the invention has the following advantages:
(1) The invention reports for the first time the preparation of isoindolinones by electrochemical oxidation;
(2) The microchannel reaction device is combined with the electrochemical device, the distance between a positive electrode and a negative electrode is short, energy conversion is effectively realized, the electric level hot spot effect is avoided, the mass transfer and heat transfer are high-efficient, the reaction is high-efficient and quick, the decomposition of products is avoided, and the reaction efficiency is obviously improved;
(3) The method does not need alkali, oxidant and metal catalyst, is simple and convenient to operate, and is green and efficient;
(4) The invention continuously reacts through the injection pump and the microchannel reaction device, the preparation process is easy to operate and control, the reaction condition is mild, and the invention has better industrial amplification potential.
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FIG. 1 is a schematic view of a microchannel electrosynthesis reaction apparatus of the present invention.
FIG. 2 is a schematic view of a microchannel electrosynthesis reaction apparatus according to the present invention.
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.
Using the apparatus (name: the Asia Flux module, model No.2200554, manufacturer: syrris Ltd.) illustrated in FIGS. 1 and 2, the following procedure was followed: (1) Adding the solution A prepared in proportion into an injection pump a; (2) Injecting the mixture into a microchannel reaction device by an injection pump according to a certain proportion for mixing and reacting; (3) adjusting the required current; (4) Collecting the effluent reaction liquid, and calculating the product yield by an HPLC method; and measuring the product yield by a high performance liquid chromatography, and separating by column chromatography to obtain the target product.
Example 1 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 1mmol (0.302 g) of tetrabutylammonium acetate are dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which is added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 1min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield to be 84% by an HPLC method, and obtaining a product III after column chromatography separation. 1 H NMR(400MHz,Chloroform-d)δ7.74(d,J＝7.5Hz,1H),7.53(d,J＝7.6Hz,1H),7.44–7.37(m,2H),4.86(dd,J＝6.7,4.0Hz,1H),3.88(s,3H),2.97–2.78(m,1H),2.55–2.40(m,1H). 13 C NMR(101MHz,Chloroform-d)δ164.7,140.7,132.6,129.3,129.2,125.2(q,J＝276.0Hz,1C),123.9,122.7(q,J＝2.0Hz,1C),63.8,53.9(q,J＝3.2Hz,1C),35.2(q,J＝28.6Hz,1C).HRMS(TOF)m/z[M+H] + Calcd for C 11 H 11 F 3 NO 2 246.0736found 246.0731.
Example 2 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 1mmol (0.387 g) of tetrabutylammonium hexafluorophosphate were dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which was added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 1min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield to be 77% by an HPLC method, and obtaining a product III after column chromatography separation.
Example 3 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 1mmol (0.329 g) of ammonium tetrabutyltetrafluoroborate are dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which is fed to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 1min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield to be 74% by an HPLC method, and obtaining a product III after column chromatography separation.
Example 4 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 1mmol (0.229 g) of tetraethylammonium perchlorate are dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which is added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 1min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the yield of the product to be 80% by an HPLC method, and obtaining the product III after column chromatography separation.
Example 5 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 0.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 1mmol (0.302 g) of tetrabutylammonium acetate were dissolved in dichloroethane/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which was added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 1min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield to be 69% by an HPLC method, and obtaining a product III after column chromatography separation.
Example 6 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 1mmol (0.302 g) of tetrabutylammonium acetate were dissolved in methanol/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which was added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 1min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield to be 65% by an HPLC method, and obtaining a product III after column chromatography separation.
Example 7 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 0.5mmol (0.078 g) of sodium trifluoromethanesulfonate II and 1mmol (0.302 g) of tetrabutylammonium acetate were dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which was added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 1min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield by an HPLC method to be 60%, and obtaining a product III after column chromatography separation.
Example 8 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.0mmol (0.156 g) of sodium trifluoromethanesulfonate II and 1mmol (0.302 g) of tetrabutylammonium acetate are dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which is added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 1min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield to be 71% by an HPLC method, and obtaining a product III after column chromatography separation.
Example 9 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 2mmol (0.312 g) of sodium trifluoromethanesulfonate II and 1mmol (0.302 g) of tetrabutylammonium acetate are dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies below) to give a homogeneous solution A, which is added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 1min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield to be 81% by an HPLC method, and obtaining a product III after column chromatography separation.
Example 10 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 0.5mmol (0.151 g) of tetrabutylammonium acetate were dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which was added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 1min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield by an HPLC method to be 70%, and obtaining a product III after column chromatography separation.
Example 11 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 2mmol (0.604 g) of tetrabutylammonium acetate are dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which is added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 1min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield to be 77% by an HPLC method, and obtaining a product III after column chromatography separation.
Example 12 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 3mmol (0.906 g) of tetrabutylammonium acetate are dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which is added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 1min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield to be 76% by an HPLC method, and obtaining a product III after column chromatography separation.
Example 13 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 1mmol (0.302 g) of tetrabutylammonium acetate are dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which is added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =200 mu L, and the reaction time is 0.89min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the yield of the product to be 80% by an HPLC method, and obtaining the product III after column chromatography separation.
Example 14 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 1mmol (0.302 g) of tetrabutylammonium acetate are dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which is added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =250 μ L, and the reaction time is 1.11min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield to 82% by an HPLC method, and obtaining a product III after column chromatography separation.
Example 15 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 1mmol (0.302 g) of tetrabutylammonium acetate are dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which is added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 5mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 1min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield to be 67% by using an HPLC method, and obtaining a product III after column chromatography separation.
Example 16 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 1mmol (0.302 g) of tetrabutylammonium acetate are dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which is added to syringe pump a; the injection flow rate of the injection pump a is 225 mu L/min; the applied current was 20mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 1min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield by an HPLC method to be 70%, and obtaining a product III after column chromatography separation.
Example 17 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 1mmol (0.302 g) of tetrabutylammonium acetate are dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which is added to syringe pump a; the injection flow rate of the injection pump a is 450 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 0.5min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield to be 72% by an HPLC method, and obtaining a product III after column chromatography separation.
Example 18 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 1mmol (0.302 g) of tetrabutylammonium acetate are dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which is added to syringe pump a; the injection flow rate of the injection pump a is 45 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 5min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield to 65% by an HPLC method, and obtaining a product III after column chromatography separation.
Example 19 synthesis of compound iii:
0.5mmol (0.0886 g) of compound I, 1.5mmol (0.234 g) of sodium trifluoromethanesulfonate II and 1mmol (0.302 g) of tetrabutylammonium acetate are dissolved in acetonitrile/water (10 mL, volume ratio 4/1, the same applies hereinafter) to give a homogeneous solution A, which is added to syringe pump a; the injection flow rate of the injection pump a is 22.5 mu L/min; the applied current was 10mA; the reaction volume of the microchannel reactor is V =225 μ L, and the reaction time is 10min; after one period of reaction in the microchannel reactor, collecting reaction liquid, calculating the product yield to be 62% by an HPLC method, and obtaining a product III after column chromatography separation.
While the invention has been described with respect to a number of specific embodiments and methods, it will be appreciated by those skilled in the art that various modifications, additions and substitutions can be made without departing from the scope and spirit of the invention. All the components not specified in the present embodiment can be realized by the prior art.

Claims (8)

1. A method for continuously and electrically synthesizing isoindolinone by using a microchannel reaction device is characterized by comprising the following steps:
(1) Dissolving N-methoxy-2-vinylbenzamide, sodium trifluoromethanesulfonate and electrolyte in a solvent to prepare a homogeneous solution A;
(2) Pumping the homogeneous solution A into a microchannel reaction device provided with an electrode for electrolytic reaction, and collecting effluent liquid, namely the solution containing the isoindolinone shown in the formula III; the current intensity of the electrolytic reaction is 5-20 mA, the temperature is room temperature, and the residence time of the reaction is 0.5-10 min;
Figure FDA0003849088050000011
2. the method for continuously electrically synthesizing isoindolinone according to claim 1, wherein in the step (1), the electrolyte is selected from the group consisting of tetrabutylammonium acetate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium iodide, tetraethylammonium perchlorate and sodium iodide.
3. The method for continuously electrosynthesis of isoindolinone according to claim 1, wherein in step (1), the solvent is any one or a combination of acetonitrile, water, dichloroethane and methanol.
4. The method for continuously electrosynthesis of isoindolinone using microchannel reaction device as set forth in claim 1, wherein in step (1), the concentration of N-methoxy-2-vinylbenzamide in said homogeneous solution a is 0.02-0.1 mmol/mL; the concentration of the sodium trifluoromethanesulfonate is 0.05-0.2 mmol/mL; the concentration of the electrolyte is 0.05-0.3 mmol/mL; the mol ratio of the N-methoxy-2-vinylbenzamide to the sodium trifluoromethanesulfonate to the electrolyte is 1: (1-4): (1-6).
5. The method for continuously electrosynthesis of isoindolinone with the microchannel reaction device according to claim 1, wherein in step (2), the microchannel reaction device provided with the electrode comprises a syringe pump, a microchannel reactor, a cathode sheet, an anode sheet and a receiver; wherein, both sides of the microchannel reactor are respectively provided with a cathode sheet and an anode sheet; the injection pump, the microchannel reactor and the receiver are connected in series; the connection is a pipeline connection.
6. The method for continuously electrosynthesis of isoindolinone using microchannel reaction device as recited in claim 5, wherein said cathode sheet is a platinum sheet; the anode sheet is a graphite plate.
7. The method for continuously electrosynthesis of isoindolinone using a microchannel reactor as set forth in claim 1, wherein the microchannel reactor has a reaction volume of 200 to 250 μ L.
8. The method for continuously electrosynthesis of isoindolinone using a microchannel reactor device as set forth in claim 1, wherein in step (2), the flow rate of the homogeneous solution A pumped into the microchannel reactor is 22.5-450 μ L/min.
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CN111235598B (en) * 2020-01-16 2022-03-25 中国药科大学 Method for continuously electrosynthesis of spiro [4.5] trienone by using micro-reaction device
CN111364057B (en) * 2020-03-11 2022-04-29 中国药科大学 Method for continuously preparing C-3-position polyfluoromethyl substituted coumarin by using electrochemical microchannel reaction device
CN111690947B (en) * 2020-06-17 2021-10-15 浙江工业大学 Electrochemical synthesis method of trifluoromethylated aryl amide derivative

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