Process for the electrochemically driven cyclization of 2-(1-alkynyl)benzamide derivatives to synthesize iodoisoindolones

Abstract

A method for electrochemically driving 2-(1-alkynyl)benzamide derivative to cyclize and synthesize iodoisoindolone, in which 2-(1-alkynyl)benzamide derivative and tetrabutylammonium iodide are used in an electrolyte and a solvent at room temperature to obtain iodoisoindolone. The electrochemical driving efficiency is higher, the substrate conversion rate is increased to 95%, heavy metal residues are avoided, the requirements of drug intermediates are met, no temperature control energy consumption is needed, the process is simplified, the efficiency is improved, and the functional group tolerance is better.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to an electrochemically driven cyclization method for synthesizing iodoisoindolone from 2-(1-ynyl)benzamide derivatives. Background Technology

[0002] Isoindolones are an important class of nitrogen-containing heterocyclic compounds. This benzo-fused lactam skeleton exists in a variety of naturally occurring pharmacologically active substances, such as alkaloids like fumaridine, chlorhexidine, nifedipine, lenoxamine, and taxane C. Furthermore, numerous molecules containing the isoindol-1-one skeleton exhibit a wide range of biological activities, including vasodilators, anti-HIV drugs, anticancer drugs, antibacterial drugs, anticonvulsants, and sedative-hypnotics. Specific examples of drugs and other compounds with significant medicinal value containing the isoindol-1-one skeleton include chlorothiazide, JM-1232, (S)-PD 172938, pagoclone (Cl-1043), and pazinaclone (DN 2327). Due to their broad medicinal value, the academic community continues to focus on developing novel synthetic methods for isoindol-1-ones to improve the availability of structurally related analogs. Several research teams have developed a variety of innovative synthetic strategies. Of particular note is that alkyne cyclization reactions have been widely applied in the synthesis of isoindolinones, for example, through metal-catalyzed, copper-catalyzed / mediated, ruthenium-catalyzed, and base-catalyzed cyclization pathways. Based on these structural and functional advantages, developing efficient and green synthetic methods for isoindolin-1-one compounds is of great significance for advancing organic synthesis technology and expanding the pathways for preparing functional molecules.

[0003] Currently, the conventional synthesis of isoindole ketones largely relies on cyclization reactions of amide functional groups. However, this method is only suitable for constructing simple indole ketone skeletons and cannot introduce iodine atoms. For the synthesis of iodoisoindole ketones, existing techniques typically involve adding an alkyne starting material (0.25 mmol) to a 25 mL three-necked flask under an inert argon atmosphere in air, followed by the addition of 2 mL of THF. The reaction system is then placed in an ice bath at 0°C. Subsequently, n-butyllithium (1.2 equiv., 1.6 M hexane solution) is added dropwise. After stirring for 10 minutes, iodine (3 equiv.) / iodine monochloride (1.0 mol / THF) dissolved in 1 mL of THF (3 equiv.) is added dropwise to the reaction system, and the reaction is stirred in an ice bath for 20 minutes. After the reaction is complete, the reaction mixture is quenched with a saturated ammonium chloride aqueous solution, diluted with 10 mL of ethyl acetate, washed with 25 mL of a saturated sodium thiosulfate aqueous solution, and dried over anhydrous sodium sulfate. The target product was obtained by silica gel column chromatography (eluent: ethyl acetate / n-hexane = 3:10) after concentration under reduced pressure. The synthetic route is as follows:

[0004] However, the above methods require the use of heavy metal catalysts such as n-butyllithium (up to 1.2 equivalents), which not only leads to high raw material costs, but also makes it difficult to completely remove heavy metal residues, thus limiting the application of subsequent drug intermediates or bioactive molecules. At the same time, the existing methods need to be carried out at a low temperature of 0°C, which requires high equipment cooling capacity, significantly increasing the difficulty and energy consumption of industrial scale-up. In addition, the reaction system requires the addition of iodine reagent, and sodium sulfate solution needs to be added for post-treatment after the reaction, which is cumbersome and further reduces the synthesis efficiency. Summary of the Invention

[0005] To address the problems of "metal contamination, harsh conditions, and low efficiency" in existing methods for synthesizing iodoisoindolones, an electrochemically driven cyclization method for synthesizing iodoisoindolones from 2-(1-ynyl)benzamide derivatives is proposed. This method aims to provide a synthetic route with a broad substrate range, excellent functional group tolerance, simple operation, and high efficiency, meeting the diverse needs of industrial production and academic research for iodoisoindolone compounds. The specific scheme is as follows: In an electrochemical reaction cell, compounds of general formula 1 and general formula 2 are reacted in the presence of an electrolyte and a solvent at room temperature to obtain compounds of general formula 3. Among them, the compound of general formula 1 is a 2-(1-alkynyl)benzamide derivative; the compound of general formula 2 is tetrabutylammonium iodide; in, It is selected from any one of alkyl, aryl, thiophene, and fused-ring groups; It is selected from any one of alkyl, aryl, thiophene, pyrrole, benzofuran, benzothiophene, quinolinyl, and fused ring groups.

[0006] Preferably, the electrolyte is any one of ammonium chloride, triphenylphosphine, triphenylphosphine oxide, tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, and tetrabutylammonium perchlorate.

[0007] Preferably, the solvent is any one or more of methanol, acetonitrile, tetrahydrofuran, dichloromethane, N,N-dimethylamide (DMF), dimethyl sulfoxide (DMSO), and water. The electrolyte is triphenylphosphine or triphenyloxyphosphine.

[0008] Preferably, the solvent is a solution formed by N,N-dimethylamide and water. Preferably, the volume ratio of N,N-dimethylamide to water is 2-6:1.

[0009] Preferably, the molar ratio of the compound of general formula 1, the compound of general formula 2, and the electrolyte is 1:1:0.5 to 1:3:3.

[0010] Preferably, the molar ratio of the compound of general formula 1, the compound of general formula 2, and the electrolyte is 1:1:0.5 to 1:3:3. Preferably, the reaction current is 5 to 15 mA.

[0011] Preferably, after the reaction yields the compound of general formula 3, it is extracted with ethyl acetate and water, separated, dried, concentrated, and recrystallized to obtain iodoisoindolone.

[0012] Preferably, the electrode used in the reaction is any one of C(+) / C(-), C(+) / Pt(-), Pt(+) / Pt(-), or Pt(+) / C(-).

[0013] Compared with existing technologies, the electrochemically driven cyclization synthesis of iodoisoindolone from 2-(1-ynyl)benzamide derivatives provided by this invention precisely guides the reaction towards the target iodocyclized product through precise synergistic control of electrode materials (C(+) / Pt(-)), electrolyte (triphenylphosphine), solvent (DMF / H2O=4:1), and current (10mA). It achieves a self-sustaining cycle of "iodide anodization, electrophilic iodide species activation of alkyne bonds, and iodide anion regeneration after cyclization" solely using electrical energy, completely eliminating heavy metals and chemical oxidants, which presents a non-obvious chemical challenge. It is compatible with various electronic effects, steric hindrances, and complex functional groups sensitive to redox or acid-base reactions, successfully achieving a yield of up to 95% and a wide substrate applicability range, significantly superior to existing technologies.

[0014] This invention offers higher electrochemical driving efficiency, increasing substrate conversion to 95%; avoids heavy metal residues, meeting the requirements for pharmaceutical intermediates; eliminates the need for temperature control and energy consumption, simplifying the process, improving efficiency, and enhancing functional group tolerance. Attached Figure Description

[0015] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0016] Figure 1 The image shows the hydrogen NMR spectrum of the product from Example 1.

[0017] Figure 2 The image shows the carbon NMR spectrum of the product from Example 1.

[0018] Figure 3 The image shows the hydrogen NMR spectrum of the product from Example 2.

[0019] Figure 4The image shows the carbon NMR spectrum of the product from Example 2.

[0020] Figure 5 The image shows the hydrogen NMR spectrum of the product from Example 3.

[0021] Figure 6 The image shows the carbon NMR spectrum of the product from Example 3.

[0022] Figure 7 The image shows the hydrogen NMR spectrum of the product from Example 4.

[0023] Figure 8 The image shows the carbon NMR spectrum of the product from Example 4. Detailed Implementation

[0024] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] This invention provides an electrochemically driven cyclization method for synthesizing iodoisoindolone from 2-(1-alkynyl)benzamide derivatives. In an electrochemical reaction cell, a compound of general formula 1 and a compound of general formula 2 are reacted at room temperature in the presence of an electrolyte and a solvent to obtain a compound of general formula 3. The synthesis route is as follows:

[0026] Among them, the compound of general formula 1 is a 2-(1-alkynyl)benzamide derivative; the compound of general formula 2 is tetrabutylammonium iodide; tetrabutylammonium iodide serves as both an iodine source and a supporting electrolyte, thus realizing the multifunctionality of the reagent; in, It is selected from any one of alkyl, aryl, thiophene, and fused-ring groups; It is selected from any one of alkyl, aryl, thiophene, pyrrole, benzofuran, benzothiophene, quinolinyl, and fused ring groups.

[0027] This invention utilizes electrochemical anodic oxidation instead of chemical oxidants, using electrons as a cleaning agent to drive the reaction under mild conditions without metals or added oxidants. Tetrabutylammonium iodide is selected as an inexpensive iodine source and supporting electrolyte, which is used to generate electrophilic iodocations in situ at the anode to activate alkyne bonds. Triphenylphosphine is innovatively introduced as a key electrolyte, and its coordination with iodine species is used to precisely control the iodination cyclization pathway. At the same time, an N,N-dimethylformamide / water (4:1) mixed solvent is selected to provide the optimal polarity and proton environment. Finally, through the above precise control, multiple side reaction pathways such as substrate alkyne polymerization, amide decomposition, non-selective iodination, and competitive cyclization are avoided, realizing an electrochemically driven method for the iodination cyclization of alkyne amides to synthesize iodoisoindolones.

[0028] Meanwhile, this invention constructs a closed-loop electrochemical catalytic cycle through the synergistic regulation of electrodes, electrolytes, solvents, and current. It achieves a self-sustaining cycle of "anodic oxidation of iodide anions, activation of alkyne bonds by electrophilic iodine species, and regeneration of iodide anions after cyclization" solely using electrical energy, completely eliminating the need for heavy metals and chemical oxidants. Furthermore, the preparation method of this invention is compatible with various electronic effects, steric hindrances, and complex functional groups sensitive to redox reactions or acids and bases, achieving substrate universality and functional group tolerance, successfully achieving a maximum yield of 95% and a wide range of applicable substrates.

[0029] Furthermore, the electrolyte is any one of ammonium chloride, triphenylphosphine, triphenylphosphine oxide, tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, and tetrabutylammonium perchlorate.

[0030] Furthermore, the solvent is any one or more of methanol, acetonitrile, tetrahydrofuran, dichloromethane, N,N-dimethylamide (DMF), dimethyl sulfoxide (DMSO), and water.

[0031] Furthermore, the electrolyte is triphenylphosphine or triphenylphosphine oxide, which has the dual function of conducting electricity and stabilizing iodide ions, and can precisely control the iodination cyclization reaction, suppressing the generation of elemental iodine and side reactions.

[0032] Furthermore, the solvent is a solution formed by N,N-dimethylamide and water. DMF, as a polar aprotic solvent, can effectively dissolve organic substrates and products. The addition of water increases polarity and dielectric constant, which is beneficial for stabilizing charge-separated intermediates and promoting electron transfer on the electrode surface. At the same time, water, as a proton source, is crucial for the protonation of the cyclization step.

[0033] Furthermore, the volume ratio of the N,N-dimethylamide to water is 2-6:1.

[0034] Furthermore, the molar ratio of the compound of general formula 1, the compound of general formula 2, and the electrolyte is 1:1:0.5 to 1:3:3. If the above molar ratio is too low, it will lead to incomplete iodization, poor conductivity, and a significant decrease in yield. If the ratio is too high, it will cause waste of raw materials, difficulty in separation, and excessive I- is prone to over-oxidation at the anode to generate I3- or I2, which will trigger non-selective iodization or dimerization side reactions, and the yield will actually decrease.

[0035] Furthermore, the molar ratio of the compound of general formula 1, the compound of general formula 2, and the electrolyte is 1:1:0.5 to 1:3:3.

[0036] Furthermore, the reaction current is 5–15 mA.

[0037] Furthermore, the reaction time is 1 to 6 hours. If the time is too short, the substrate conversion will be incomplete and the yield will be low. If the time is too long, the product will undergo excessive electrolysis, resulting in side reactions such as deiodination and dimerization, which will reduce the yield and the purity of the product.

[0038] Furthermore, after the reaction yields the compound of general formula 3, it is extracted with ethyl acetate and water, separated, dried, concentrated, and recrystallized to obtain iodoisoindolone.

[0039] Furthermore, the electrode used in the reaction is any one of C(+) / C(-), C(+) / Pt(-), Pt(+) / Pt(-), and Pt(+) / C(-). The present invention is further illustrated by the following examples and comparative examples. Example 1

[0040] The reaction equation is as follows: In a 25 mL electrochemical reaction cell, 1a (0.5 mmol), triphenylphosphine (0.65 mmol), N,N-dimethylamide (DMF) (8 mL), water (2 mL), a magnetic electrode, and 2a (0.65 mmol) were added sequentially. The electrochemical reaction cell was equipped with a graphite rod anode (30 mm × 15 mm × 3 mm) as the anode and a Pt sheet (35 mm × 15 mm × 0.5 mm) as the cathode. The above mixed solution was electrolyzed at a constant current (10 mA) for 3 h at room temperature. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. 60 mL of ethyl acetate and 20 mL of water were added for extraction and separation (ethyl acetate was chosen as the extractant because it has good solubility for moderately polar products, is immiscible with water, has a low boiling point and is easy to remove, making it the preferred choice to ensure high recovery rate and purity). The organic layers were combined and dried with anhydrous Na2SO4 (anhydrous sodium sulfate was chosen as the desiccant because it has moderate drying efficiency, large water absorption capacity, does not adsorb products, and is mild and neutral, making it suitable for various products of this invention). The compound was concentrated and recrystallized to obtain iodoisoindolinone 3a in 95% yield. The obtained iodoisoindolinone 3a was subjected to proton NMR and carbon NMR analysis, and the results are shown in the following spectra. Figure 1 , 2 As shown. (E)-3-(Iodo(phenyl)methylene)isoindolin-1-one (3b). Yellow solid; 1H NMR (400MHz, CDCl3) δ 8.95 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 7.6 Hz, 1H), 7.76−7.74(m, 1H), 7.63−7.61 (m, 1H), 7.59 (s, 1H), 7.44−7.40 (m, 4H), 7.37− 7.33 (m,1H); 13C NMR (100 MHz, CDCl3) δ 166.0, 141.9, 136.1, 135.4, 132.0, 131.0,130.1, 129.2, 129.1, 128.9, 123.8, 123.7, 72.9. Example 2

[0041] The reaction equation is as follows:

[0042] In a 25 mL electrochemical reaction cell, 1b (0.5 mmol), triphenylphosphine (0.65 mmol), N,N-dimethylamide (DMF) (8 mL), water (2 mL), a magnetic flux, and 2a (0.65 mmol) were added sequentially. The electrolytic cell was equipped with a graphite rod anode (30 mm × 15 mm × 3 mm) as the anode and a Pt sheet (35 mm × 15 mm × 0.5 mm) as the cathode. The above mixture was electrolyzed at a constant current (10 mA) for 3 h at room temperature. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. 60 mL of ethyl acetate and 20 mL of water were added for extraction and separation. The organic layers were combined, dried over anhydrous Na₂SO₄, concentrated, and recrystallized to obtain compound iodoisoindolone 3b, with a yield of 97%. The obtained compound iodoisoindolone 3b was analyzed by proton NMR and carbon NMR. The results are shown in the following spectral diagram. Figure 3 , 4 As shown.

[0043] (E)-3-(Iodo(phenyl)methylene)-5,6-dimethoxyisoindolin-1-one(5q).yellow solid; 1H NMR (400 MHz, CDCl3) δ 7.61 (s, 1H), 7.46−7.45 (m, 4H),7.41−7.39 (m, 1H), 7.17 (s, 1H), 5.86 (s, 1H), 3.88 (s, 3H), 3.38 (s, 3H);13C NMR (100 MHz, CDCl3) δ 167.5, 152.3, 150.5, 141.1, 137.8, 129.7, 129.1,129.0, 128.5, 124.6, 105.2, 104.7, 76.0, 56.1, 55.4. Example 3

[0044] The reaction equation is as follows: In a 25 mL electrochemical reaction cell, 1c (0.5 mmol), triphenylphosphine (0.65 mmol), N,N-dimethylamide (DMF) (8 mL), water (2 mL), a magnetic flux, and 2a (0.65 mmol) were added sequentially. The electrolytic cell was equipped with a graphite rod anode (30 mm × 15 mm × 3 mm) as the anode and a Pt sheet (35 mm × 15 mm × 0.5 mm) as the cathode. The above mixed solution was electrolyzed at a constant current (10 mA) for 3 h at room temperature. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. 60 mL of ethyl acetate and 20 mL of water were added for extraction and separation. The organic layers were combined, dried over anhydrous Na₂SO₄, concentrated, and recrystallized to obtain compound iodoisoindolone 3c, with a yield of 91%. The obtained compound iodoisoindolone 3c was analyzed by proton NMR and carbon NMR. The results are shown in the following spectral diagram. Figure 5 , 6 As shown.

[0045] 2-(Cyclohexylethynyl)benzamide (3c). white solid; TLC;1H NMR (400MHz, CDCl3) δ 8.14−8.11 (m, 1H), 7.75 (s, 1H), 7.50−7.48 (m, 1H), 7.41−7.38(m, 2H), 6.44 (s, 1H), 2.70−2.63 (m, 1H), 1.92−1.89 (m, 2H), 1.77−1.71 (m,2H), 1.56−1.53 (m, 2H), 1.39−1.35 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 168.2,133.8, 133.6, 130.8, 130.2, 128.0, 120.9, 101.7, 79.6, 32.2, 29.8, 25.6, 24.8. Example 4

[0046] The reaction equation is as follows:

[0047] In a 25 mL electrochemical reaction cell, 1d (0.5 mmol), triphenylphosphine (0.65 mmol), N,N-dimethylamide (DMF) (8 mL), water (2 mL), a magnetic flux, and 2a (0.65 mmol) were added sequentially. The electrolytic cell was equipped with a graphite rod anode (30 mm × 15 mm × 3 mm) as the anode and a Pt sheet (35 mm × 15 mm × 0.5 mm) as the cathode. The above mixture was electrolyzed at a constant current (10 mA) for 3 h at room temperature. The reaction progress was monitored by thin-layer chromatography until the reaction was complete. 60 mL of ethyl acetate and 20 mL of water were added for extraction and separation. The organic layers were combined, dried over anhydrous Na₂SO₄, concentrated, and recrystallized to obtain compound iodoisoindolone 3d, with a yield of 87%. The obtained compound iodoisoindolone 3d was analyzed by proton NMR and carbon NMR. The results are shown in the following spectra. Figure 7 , 8 shown. (Z)-3-(Iodomethylene)isoindolin-1-one (3d). Yield: (56mg, 82%); white solid; 1H NMR (400 MHz, CDCl3) δ 8.80 (d, J = 8.0 Hz, 1H),7.90 (s, 1H), 7.84−7.79 (m, 1H), 7.68−7.64 (m, 1H), 7.61−7.56 (m, 1H), 6.22(s, 1H); 13C NMR (100 MHz, CDCl3) δ 165.8, 140.7, 135.3, 132.5, 132.3, 130.2,124.3, 123.8, 54.5. Example 5

[0048] The electrolyte triphenylphosphine in Example 1 was replaced with ammonium chloride, and everything else was the same as in Example 1. Thin-layer chromatography was used to monitor the reaction, and a reaction product was generated, with a reaction yield of 15%. Example 6

[0049] The electrolyte triphenylphosphine in Example 1 was replaced with tetra-n-butylhexafluorophosphate ammonium, and everything else was the same as in Example 1. Thin-layer chromatography was used to monitor the reaction, and reaction products were generated. The reaction yield was 18%. Example 7

[0050] The solvent in Example 1 was replaced with methanol, and everything else was the same as in Example 1. Thin-layer chromatography was used to monitor the reaction, and the reaction product was generated. The reaction yield was 26%. Example 8

[0051] Replacing the solvent in Example 1 with methanol, while maintaining the same procedure as in Example 1, thin-layer chromatography monitoring revealed the formation of reaction products, with a reaction yield of 23%. Examples 1 through 8 demonstrate that the electro-driven method of this invention can prepare the target product. Examples 1, 5, and 6 show that triphenylphosphine and tetrabutylammonium iodide (raw material) work synergistically as an electrolyte. Their combined conductivity and stabilizing effect on iodide ions allows for precise control of the iodination cyclization reaction, suppressing the formation of elemental iodine and side reactions. Other electrolytes (such as tetrabutylammonium salts and ammonium chloride) lack this synergistic effect, resulting in low yields and numerous byproducts. Therefore, triphenylphosphine is the preferred electrolyte. Examples 1, 7, and 8 show that DMF, as a polar aprotic solvent, effectively dissolves organic substrates and products. The addition of water increases polarity and dielectric constant, facilitating the stabilization of charge-separated intermediates and promoting electron transfer on the electrode surface. Simultaneously, water, as a proton source, is crucial for the protonation of the cyclization step; an appropriate amount of water can inhibit excessive oxidation of the substrate and product. Comparative Example 1

[0052] The solvent in Example 1 was replaced with DMF (without water), and everything else was the same as in Example 1. Thin-layer chromatography was used to monitor the reaction, and no reaction products were generated.

[0053] In this invention, the volume ratio of N,N-dimethylamide to water is 4:1. DMF, as a polar aprotic solvent, can effectively dissolve organic substrates and products. The addition of water increases polarity and dielectric constant, which is beneficial for stabilizing charge separation intermediates and promoting electron transfer on the electrode surface.

[0054] Meanwhile, water, as a proton source, is crucial for the protonation of the cyclization step, and the reaction hardly occurs in pure DMF. A suitable amount of water can also inhibit excessive oxidation of the substrate or product; other solvents cannot simultaneously achieve both solubility and reaction efficiency.

[0055] The above-disclosed embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of the invention. Those skilled in the art will understand that implementing all or part of the above-described embodiments and making equivalent changes in accordance with the claims of the present invention are still within the scope of the invention.

Claims

1. A method for the electrochemically driven cyclization synthesis of iodoisoindolone from a 2-(1-ynyl)benzamide derivative, characterized in that: In an electrochemical reaction cell, compounds of general formula 1 and general formula 2 were reacted at room temperature in the presence of an electrolyte and a solvent to yield compound of general formula 3; the synthetic route is as follows: Among them, the compound of general formula 1 is a 2-(1-ynyl)benzamide derivative; the compound of general formula 2 is tetrabutylammonium iodide; among them, It is selected from any one of alkyl, aryl, thiophene, and fused-ring groups; It is selected from any one of alkyl, aryl, thiophene, pyrrole, benzofuran, benzothiophene, quinolinyl, and fused ring groups.

2. The method for the electrochemically driven cyclization synthesis of iodoisoindolone from 2-(1-ynyl)benzamide derivatives according to claim 1, characterized in that: The electrolyte is any one of ammonium chloride, triphenylphosphine, triphenylphosphine oxide, tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, and tetrabutylammonium perchlorate.

3. The method for the electrochemically driven cyclization synthesis of iodoisoindolone from 2-(1-ynyl)benzamide derivatives according to claim 2, characterized in that: The solvent is a solution prepared by mixing one or more of methanol, acetonitrile, tetrahydrofuran, dichloromethane, N,N-dimethylamide, and dimethyl sulfoxide with water.

4. The method for synthesizing iodoisoindolone by electrochemically driven cyclization of 2-(1-ynyl)benzamide derivatives according to claim 2, characterized in that: The electrolyte is triphenylphosphine or triphenyloxyphosphine.

5. The method for the electrochemically driven cyclization synthesis of iodoisoindolone from 2-(1-ynyl)benzamide derivatives according to claim 3, characterized in that: The solvent is a solution prepared by mixing N,N-dimethylamide and water.

6. The method for the electrochemically driven cyclization synthesis of iodoisoindolone from 2-(1-ynyl)benzamide derivatives according to claim 5, characterized in that: The volume ratio of N,N-dimethylamide to water is 2-6:

1.

7. The method for the electrochemically driven cyclization synthesis of iodoisoindolone from a 2-(1-ynyl)benzamide derivative according to claim 3 or 4, characterized in that: The molar ratio of the compound of general formula 1, the compound of general formula 2, and the electrolyte is 1:1:0.5 to 1:3:

3.

8. The method for the electrochemically driven cyclization synthesis of iodoisoindolone from a 2-(1-ynyl)benzamide derivative according to claim 7, characterized in that: The reaction current is 5–15 mA.

9. The method for the electrochemically driven cyclization synthesis of iodoisoindolone from a 2-(1-ynyl)benzamide derivative according to claim 8, characterized in that: After the reaction yields the compound of general formula 3, it is extracted with ethyl acetate and water, separated, dried, concentrated, and recrystallized to obtain iodoisoindolone.

10. The method for the electrochemically driven cyclization synthesis of iodoisoindolone from 2-(1-ynyl)benzamide derivatives according to claim 9, characterized in that: The electrodes used during the reaction are any one of C(+) / C(-), C(+) / Pt(-), Pt(+) / Pt(-), and Pt(+) / C(-).

Images