Application of Cu / ETS-10 Catalyst in the Synthesis of 3-Methyleneisoindolin-1-one and Its Derivatives

Abstract

The invention relates to the field of heterogeneous catalytic organic synthesis, and discloses the use of a Cu / ETS-10 catalyst in the catalytic synthesis of 3-methyleneisoindolin-1-one and its derivatives. The invention adopts an isovolumetric impregnation method to prepare the Cu / ETS-10 catalyst, and specifically comprises the following steps: adding 2-iodobenzamide, phenylacetylene, and a zeolite catalyst into a reaction tube in sequence; 2 Add the reaction solvent dimethyl sulfoxide (DMSO) under the atmosphere, put it in a 100-120°C heater to react for 2-12 hours, centrifuge and filter after the reaction, collect the supernatant, concentrate under reduced pressure, separate and purify the crude product by column chromatography to obtain 3-methyleneisoindolin-1-one, with a yield of up to 98%. Compared with the existing technology, this method does not require the addition of other additives such as soluble metal salts and ligands, and the catalyst and product are easy to separate and can be recycled and reused, with simple operation, high efficiency, and green environmental protection.

Description

Technical Field

[0001] The invention relates to the field of heterogeneous catalytic organic synthesis and discloses a preparation method for synthesizing 3-methyleneisoindolin-1-one and derivatives thereof by catalyzing 2-iodobenzamide and terminal alkyne with a heterogeneous catalyst. Technical Background

[0002] 3-Methyleneisoindolin-1-one is widely present in natural biologically active products and drugs, and has excellent local anesthetic activity, sedative activity and vasodilatory activity. It is also an important intermediate for the synthesis of various alkaloids. In addition to its good biological activity, which makes it widely used in the field of biomedicine, it also has important value in the field of materials chemistry.

[0003] At present, a variety of synthesis methods have been reported, such as using benzamide and carboxylic acid compounds as raw materials, using Pd metal salts to catalyze the formation of CN bonds (CN104650033A); using N-substituted o-chlorobenzamide derivatives and terminal alkynes as substrates, adding cyclization under the action of copper salts and nitrogen-containing ligands (CN106699632A); benzamide derivatives and alkynes remove 2-(1-methylhydrazine) pyridine under copper salt catalysis to generate target products (CN113214224A). In these methods, soluble metal salts are used as catalysts, the product yield is low and the chemical selectivity is poor. More importantly, the use of soluble metal salts and ligand additives leads to complex systems, difficult product purification, and difficult catalyst recovery and reuse. These shortcomings not only limit industrial production applications, but also do not meet the chemical community's pursuit of sustainable green synthesis.

[0004] In view of this, the present invention develops a green, clean, environmentally friendly and economical heterogeneous catalytic synthesis method. By using the Cu / ETS-10 heterogeneous catalyst, the coupling-cyclization reaction of halogenated aromatics and terminal alkynes is successfully achieved to generate 3-methyleneisoindolin-1-one and its derivatives. Compared with the traditional homogeneous catalyst, the catalyst used in the present invention avoids the use of soluble metal salts and additives in the Cu / ETS-10 catalytic system, the product purification is simple, and has excellent conversion rate and selectivity. The catalyst of the reaction system is easy to separate, recycle and reuse, which simplifies the reaction system and reduces the discharge of reaction waste. The method has high atomic utilization, is green and environmentally friendly, and is simple to operate, meeting the requirements of green chemistry. Summary of the invention

[0005] The present invention aims to overcome the deficiencies of the prior art and provide a method for preparing 3-methyleneisoindolin-1-one and its derivatives which has high yield, is easy to separate and purify, and is inexpensive.

[0006] The synthesis steps of 3-methyleneisoindolin-1-one and its derivatives involved in the present invention are as follows: 2-iodobenzamide, terminal alkyne and Cu / ETS-10 zeolite catalyst are sequentially added into a reaction tube, a reaction solvent is added under N2 atmosphere, and the reaction is placed in a heater at 100-120°C under magnetic stirring. After the reaction is completed, centrifugation and filtration are performed, and the supernatant is collected, concentrated under reduced pressure, and the crude product is separated and purified by column chromatography to obtain 3-methyleneisoindolin-1-one and its derivatives.

[0007] The reaction temperature in the present invention is 60 to 150°C, preferably 100 to 120°C.

[0008] The reaction time in the present invention is 2 to 12 hours.

[0009] The solvent in the present invention may be one of acetonitrile, dimethyl sulfoxide (DMSO) and 1,2-dichloroethane, preferably DMSO.

[0010] The zeolite catalyst in the present invention is a Cu / ETS-10 zeolite catalyst, and the Cu / ETS-10 zeolite catalyst is synthesized by referring to the existing method, such as;

[0011] Preparation method of Cu / ETS-10:

[0012] After water glass, sodium hydroxide, potassium fluoride aqueous solution and titanium trichloride solution are uniformly mixed, they are loaded into a kettle, crystallized at high temperature, filtered, washed, dried and calcined at high temperature to obtain ETS-10 zeolite, wherein the molar composition of each substance in the gel system is: Na2O:K2O:SiO2:TiO2:H2O=4-20:1-10:6-16:1.5-3:150-200.

[0013] Furthermore, the high temperature crystallization conditions are 190-250° C. for 2-3 days; the high temperature calcination temperature is 400-500° C. to obtain an ETS-10 zeolite catalyst, in which the silicon-titanium ratio in the synthesis system of the zeolite is 1.5-10.

[0014] Furthermore, a certain amount of Cu(NO3)2 was weighed and added to distilled water to obtain a clear and transparent solution, which was then impregnated with ETS-10 zeolite in equal volumes. After standing at room temperature, oven drying and calcining in a muffle furnace, a Cu-loaded ETS-10 catalyst was obtained, namely Cu / ETS-10.

[0015] Furthermore, the supported amount of Cu is 1 to 5 wt.%.

[0016] The reaction involved is:

[0017]

[0018] Ar is selected from or heteroaryl.

[0019] Wherein, R is H, fluorine, chlorine, bromine, methyl, methoxy, tert-butyl, etc.; and is located at the ortho, meta or para position of the aryl alkyne.

[0020] Heteroaryl is thiazolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl or pyrimidinyl.

[0021] Compared with the prior art, the present invention has the following technical advantages:

[0022] The present invention provides a preparation method for synthesizing 3-methyleneisoindolin-1-one and its derivatives by catalyzing 2-iodobenzamide and terminal alkynes using alkaline titanium silicalite Cu / ETS-10. Compared with the existing synthesis technology, the synthesis method has a novel technical route, does not use the traditional homogeneous catalytic system containing soluble metal salts, ligands and various additives, but uses Cu-containing titanium silicalite to synthesize 3-methyleneisoindolin-1-one compounds; the catalyst preparation process is simple, easy to separate and recycle, and can be reused; and the Cu / ETS-10 zeolite has a porous hierarchical structure and a large specific surface area, which can provide metal active sites and alkaline sites for the reaction, and generate the target product with high yield and high selectivity. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is the hydrogen spectrum of the coupling-cyclization product of p-chlorophenylacetylene and 2-iodobenzamide in Example 2;

[0024] 1 H NMR (400MHz, DMSO-d6) δ10.79(s,1H),8.06(dt,J=7.8,1.0Hz,1H),7.77(dt,J=7.5,1.0Hz,1H),7.72( td,J=7.5,1.1Hz,1H),7.68–7.62(m,2H),7.58(td,J=7.4,0.9Hz,1H),7.49–7.42(m,2H),6.77(s,1H).

[0025] Figure 2 This is the hydrogen spectrum of the coupling-cyclization product of p-methylphenylacetylene and 2-iodobenzamide in Example 3; 1 H NMR (400MHz, DMSO-d6) δ10.68(s,1H),8.04(d,J=7.8Hz,1H),7.76(d,J=7.5Hz,1H),7.70(td ,J=7.6,1.2Hz,1H),7.56(d,J=7.7Hz,3H),7.23(d,J=7.9Hz,2H),6.73(s,1H),2.33(s,3H).

[0026] Figure 3 is the hydrogen spectrum of the coupling-cyclization product of Example 43-ethynylpyridine and 2-iodobenzamide; 1 H NMR (400MHz, DMSO-d6) δ10.90(s,1H),8.79(d,J=2.3Hz,1H),8.47(dd,J=4.8,1.6Hz,1H),8.09(dt,J=7.9,1.1Hz, 2H),7.79(dd,J=7.6,1.0Hz,1H),7.76–7.72(m,1H),7.61(dd,J=7.5,1.0Hz,1H),7.46–7.43(m,1H),6.79(s,1H).

[0027] Figure 4 is the hydrogen spectrum of the coupling-cyclization product of Example 52-ethynylthiophene and 2-iodobenzamide;

[0028] 1 H NMR (400MHz, DMSO-d6) δ10.50(s,1H),8.06(dt,J=7.8,0.9Hz,1H),7.76(dt,J=7.6,1.0Hz,1H),7.69(td,J =7.6,1.2Hz,1H),7.62–7.60(m,2H),7.54(td,J=7.4,0.9Hz,1H),7.17(dd,J=5.1,3.7Hz,1H),6.96(s,1H). DETAILED DESCRIPTION

[0029] The following examples will help to illustrate the present invention but are not intended to limit its scope.

[0030] The preparation method of Cu / ETS-10 is:

[0031] ETS-10 preparation:

[0032] 15.2 mL of water glass was measured and stirred in a 100 mL beaker. After 20 minutes, the prepared NaOH solution (2.9 g of sodium hydroxide dissolved in 10.0 mL of distilled water) was added dropwise thereto. After 20 minutes, the prepared KF solution (2.2 g of potassium fluoride dissolved in 10.0 mL of distilled water) was added dropwise to the above 100 mL beaker for stirring. After the above system was stirred for 20 minutes, 14.1 g of titanium trichloride solution was added dropwise. After stirring the above titanium silica gel for 90 minutes, it was placed in a polytetrafluoroethylene lined kettle for static crystallization at 180 ° C. Subsequently, the solid obtained by washing and filtration was dried in an oven at 100 ° C overnight, and calcined at 450 ° C for 4 hours to obtain ETS-10. The molar ratio of the reaction gel system is Na2O:K2O:SiO2:TiO2:H2O=4.3:1.42:6.3:1:183.1.

[0033] Cu / ETS-10 preparation:

[0034] 0.23 g of copper nitrate trihydrate was weighed and dissolved in 1.0 g of water to obtain a clear and transparent solution, and the prepared solution was mixed evenly with 2.0 g of ETS-10 zeolite, allowed to stand at room temperature, dried at 100° C., and calcined at 450° C. to obtain the target catalyst Cu / ETS-10, wherein the Cu loading was 3 wt.%. The catalyst was applied to the examples. Specific embodiment 1:

[0036] In a 10mL quartz reaction tube, 0.3mmol 2-iodobenzamide, 0.25mmol phenylacetylene, and 20mgCu / ETS-10 were added in sequence, and 1mL DMSO was added under N2 atmosphere. After the operation was completed, the tube was placed in a heater, the reaction temperature was controlled at 100°C, and the reaction was stirred for 6h. After the reaction was completed, the tube was cooled to room temperature, the reaction system was centrifuged and filtered, the supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The reaction liquid phase was analyzed by GC to calculate the conversion rate and selectivity of the reaction.

[0037] The reaction structure is:

[0038] Specific embodiment 2:

[0040] In a 10mL quartz reaction tube, 0.3mmol 2-iodobenzamide, 0.25mmol p-chlorophenylacetylene, and 20mg Cu / ETS-10 were added in sequence, and 1mL DMSO was added under N2 atmosphere. After the operation was completed, the tube was placed in a heater, the reaction temperature was controlled at 100°C, and the reaction was stirred for 6h. After the reaction was completed, the tube was cooled to room temperature, the reaction system was centrifuged and filtered, the supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The reaction liquid phase was analyzed by GC to calculate the conversion rate and selectivity of the reaction.

[0041] The reaction structure is:

[0042] Specific embodiment 3:

[0044] In a 10mL quartz reaction tube, 0.3mmol 2-iodobenzamide, 0.25mmol p-methylphenylacetylene, and 20mg Cu / ETS-10 were added in sequence, and 1mL DMSO was added under N2 atmosphere. After the operation was completed, the tube was placed in a heater, the reaction temperature was controlled at 100°C, and the reaction was stirred for 6h. After the reaction was completed, the tube was cooled to room temperature, the reaction system was centrifuged and filtered, the supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The reaction liquid phase was analyzed by GC to calculate the conversion rate and selectivity of the reaction.

[0045] The reaction structure is:

[0046] Specific embodiment 4:

[0048] In a 10mL quartz reaction tube, 0.3mmol 2-iodobenzamide, 0.25mmol 3-ethynylpyridine, and 20mg Cu / ETS-10 were added in sequence, and 1mL DMSO was added under N2 atmosphere. After the operation was completed, it was placed in a heater, the reaction temperature was controlled at 100℃, and the reaction was stirred for 6h. After the reaction was completed, it was cooled to room temperature, the reaction system was centrifuged and filtered, the supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The reaction liquid phase was analyzed by GC to calculate the conversion rate and selectivity of the reaction.

[0049] The reaction structure is:

[0050] Specific embodiment 5:

[0052] In a 10mL quartz reaction tube, 0.3mmol 2-iodobenzamide, 0.25mmol 2-ethynylthiophene, and 20mg Cu / ETS-10 were added in sequence, and 1mL DMSO was added under N2 atmosphere. After the operation was completed, the tube was placed in a heater, the reaction temperature was controlled at 100°C, and the reaction was stirred for 6h. After the reaction was completed, the tube was cooled to room temperature, the reaction system was centrifuged and filtered, the supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The reaction liquid phase was analyzed by GC to calculate the conversion rate and selectivity of the reaction.

[0053] The reaction structure is:

[0054]

[0055] Table 1: Examples 1-5

[0056] Substrate Conversion rate (%) Selectivity (%) Example 1 Phenylacetylene 100 98 Example 2 p-Chlorophenylacetylene 100 98 Example 3 p-Methylphenylacetylene 97 99 Example 4 3-Ethynylpyridine 87 90 Example 5 2-Ethynethiophene 83 92 Specific embodiment 6

[0058] In a 10mL quartz reaction tube, 0.3mmol 2-iodobenzamide, 0.25mmol phenylacetylene, and 20mg Cu / ETS-10 were added in sequence, and 1mL DMSO was added under N2 atmosphere. After the operation was completed, the tube was placed in a heater, the reaction temperature was controlled at 60°C, and the reaction was stirred for 6h. After the reaction was completed, the tube was cooled to room temperature, the reaction system was centrifuged and filtered, the supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The reaction liquid phase was analyzed by GC to calculate the reaction yield. Specific embodiment 7

[0060] In a 10mL quartz reaction tube, 0.3mmol 2-iodobenzamide, 0.25mmol phenylacetylene, and 20mg Cu / ETS-10 were added in sequence, and 1mL DMSO was added under N2 atmosphere. After the operation was completed, the tube was placed in a heater, the reaction temperature was controlled at 120°C, and the reaction was stirred for 6h. After the reaction was completed, the tube was cooled to room temperature, the reaction system was centrifuged and filtered, the supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The reaction liquid phase was analyzed by GC to calculate the reaction yield.

[0061] Table 2: Examples 6-7

[0062] catalyst Reaction temperature Yield (%) Example 6 Cu / ETS-10 60℃ 53 Example 7 Cu / ETS-10 120℃ 98 Specific embodiment 8

[0064] In a 10mL quartz reaction tube, 0.3mmol 2-iodobenzamide, 0.25mmol phenylacetylene, and 20mg Cu / ETS-10 were added in sequence, and 1mL acetonitrile was added under N2 atmosphere. After the operation was completed, the tube was placed in a heater, the reaction temperature was controlled at 100°C, and the reaction was stirred for 6h. After the reaction was completed, the tube was cooled to room temperature, the reaction system was centrifuged and filtered, the supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The reaction liquid phase was analyzed by GC to calculate the reaction yield. Specific embodiment 9

[0066] In a 10mL quartz reaction tube, 0.3mmol 2-iodobenzamide, 0.25mmol phenylacetylene, and 20mgCu / ETS-10 were added in sequence, and 1mL 1,2-dichloroethane was added under N2 atmosphere. After the operation was completed, the tube was placed in a heater, the reaction temperature was controlled at 100℃, and the reaction was stirred for 6h. After the reaction was completed, the tube was cooled to room temperature, the reaction system was centrifuged and filtered, the supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The reaction liquid phase was analyzed by GC to calculate the reaction yield.

[0067] Table 3: Examples 8-9

[0068] catalyst Solvents Yield (%) Example 8 Cu / ETS-10 Acetonitrile 62 Example 9 Cu / ETS-10 1,2-Dichloroethane 75

[0069] Comparative Example 1

[0070] The ETS-10 catalyst was directly applied to the coupling-cyclization reaction of 2-iodobenzamide and phenylacetylene.

[0071] In a 10mL quartz reaction tube, 0.3mmol 2-iodobenzamide, 0.25mmol phenylacetylene, and 20mg ETS-10 were added in sequence, and 1mL DMSO was added under N2 atmosphere. After the operation was completed, the tube was placed in a heater, the reaction temperature was controlled at 100°C, and the reaction was stirred for 6h. After the reaction was completed, the tube was cooled to room temperature, the reaction system was centrifuged and filtered, the supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The reaction liquid phase was analyzed by GC to calculate the reaction yield.

[0072] Comparative Example 2

[0073] The Cu / Beta catalyst was applied to the coupling-cyclization reaction of 2-iodobenzamide and phenylacetylene. The catalyst was prepared as follows: 0.2281 g of copper nitrate trihydrate was weighed and dissolved in 1.0 g of water to obtain a clear and transparent solution, and the solution was added to 2.0 g of Beta zeolite carrier, allowed to stand at room temperature, dried at 100°C, and calcined at 450°C to obtain the target catalyst Cu / Beta.

[0074] In a 10mL quartz reaction tube, 0.3mmol 2-iodobenzamide, 0.25mmol phenylacetylene, and 20mg Cu / Beta were added in sequence, and 1mL DMSO was added under N2 atmosphere. After the operation was completed, the tube was placed in a heater, the reaction temperature was controlled at 100°C, and the reaction was stirred for 6h. After the reaction was completed, the tube was cooled to room temperature, the reaction system was centrifuged and filtered, the supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The reaction liquid phase was analyzed by GC to calculate the reaction yield.

[0075] Comparative Example 3

[0076] The Cu / TS-1 catalyst was applied to the coupling-cyclization reaction of 2-iodobenzamide and phenylacetylene. The catalyst was prepared as follows: 0.2281 g of copper nitrate trihydrate was weighed and dissolved in 1.0 g of water to obtain a clear and transparent solution, and the solution was poured into 2.0 g of TS-1 zeolite carrier, allowed to stand at room temperature, dried at 100°C, and calcined at 450°C to obtain the target catalyst Cu / TS-1.

[0077] In a 10mL quartz reaction tube, 0.3mmol 2-iodobenzamide, 0.25mmol phenylacetylene, and 20mgCu / TS-1 were added in sequence, and 1mL DMSO was added under N2 atmosphere. After the operation was completed, the tube was placed in a heater, the reaction temperature was controlled at 100°C, and the reaction was stirred for 6h. After the reaction was completed, the tube was cooled to room temperature, the reaction system was centrifuged and filtered, the supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The reaction liquid phase was analyzed by GC to calculate the reaction yield.

[0078] Comparative Example 4

[0079] The Cu / SAPO-11 catalyst was applied to the coupling-cyclization reaction of 2-iodobenzamide and phenylacetylene. The catalyst was prepared as follows: 0.2281 g of copper nitrate trihydrate was weighed and dissolved in 1.0 g of water to obtain a clear and transparent solution, and the solution was poured into 2.0 g of SAPO-11 zeolite carrier, allowed to stand at room temperature, dried at 100°C, and calcined at 450°C to obtain the target catalyst Cu / SAPO-11.

[0080] In a 10mL quartz reaction tube, 0.3mmol 2-iodobenzamide, 0.25mmol phenylacetylene, and 20mg Cu / SAPO-11 were added in sequence, and 1mL DMSO was added under N2 atmosphere. After the operation was completed, the tube was placed in a heater, the reaction temperature was controlled at 100°C, and the reaction was stirred for 6h. After the reaction was completed, the tube was cooled to room temperature, the reaction system was centrifuged and filtered, the supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The reaction liquid phase was analyzed by GC to calculate the reaction yield.

[0081] Comparative Example 5

[0082] The Cu / ZSM-22 catalyst was applied to the coupling-cyclization reaction of 2-iodobenzamide and phenylacetylene. The catalyst was prepared as follows: 0.2281 g of copper nitrate trihydrate was weighed and dissolved in 1.0 g of water to obtain a clear and transparent solution, and the solution was poured into 2.0 g of ZSM-22 zeolite carrier, allowed to stand at room temperature, dried at 100°C, and calcined at 450°C to obtain the target catalyst Cu / ZSM-22.

[0083] In a 10mL quartz reaction tube, 0.3mmol 2-iodobenzamide, 0.25mmol phenylacetylene, and 20mg Cu / ZSM-22 were added in sequence, and 1mL DMSO was added under N2 atmosphere. After the operation was completed, the tube was placed in a heater, the reaction temperature was controlled at 100°C, and the reaction was stirred for 6h. After the reaction was completed, the tube was cooled to room temperature, the reaction system was centrifuged and filtered, the supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The reaction liquid phase was analyzed by GC to calculate the reaction yield.

[0084] Table 4: Reactivity results of Comparative Examples 1-5

[0085] catalyst Time(h) Yield (%) Example 1 Cu / ETS-10 6 98 Comparative Example 1 ETS-10 6 - Comparative Example 2 Cu / Beta-1 6 27 Comparative Example 3 Cu / TS-1 6 52 Comparative Example 4 Cu / SAPO-11 6 39 Comparative Example 5 Cu / ZSM-22 6 44

[0086] As shown in Table 4, no target product was generated when only ETS-10 catalyst was used. The target product could be generated when Cu / SAPO-11, Cu / ZSM-22, Cu / Beta and Cu / TS-1 catalysts were used, but the catalytic yield was still lower than that of Cu / ETS-10, so Cu / ETS-10 catalyst was the best choice.

[0087] The above describes the optional embodiments of the present invention to teach those skilled in the art how to implement and reproduce the present invention. The raw materials and equipment used in the present invention, unless otherwise specified, are all commonly used raw materials and equipment in the art; the methods used in the present invention, unless otherwise specified, are all conventional methods in the art. In order to teach the scheme of the present invention, some conventional technical aspects have been simplified and omitted. Those skilled in the art should understand that variations arising from this aspect are all within the scope of protection of the present invention.

Claims

1. A method for synthesizing 3-methyleneisoindolin-1-one and its derivatives by catalyzing 2-iodobenzamide and terminal alkynes using a heterogeneous catalyst Cu / ETS-10, characterized in that: Add compound (1) and compound (2) in the reaction formula, and Cu / ETS-10 catalyst into a reaction tube, add a reaction solvent under a N2 atmosphere, and react at a heating condition of 60-150°C. After the reaction is completed, centrifuge and filter, collect the supernatant, and concentrate under reduced pressure. The crude product is separated and purified by column chromatography to obtain the target compound (3); The reaction formula is: ； Ar is selected from any one of aryl, heteroaryl, and substituted aryl; the aryl is phenyl; the heteroaryl is thiazolyl, pyrazolyl, imidazolyl, pyridyl, pyridazinyl, or pyrimidinyl; the substituent on the substituted aryl is one or more of fluorine, chlorine, bromine, methyl, methoxy, and tert-butyl; the substituent is located at the ortho, meta, or para position of the aryl acetylenic group; The reaction solvent is one or a mixture of acetonitrile, dimethyl sulfoxide and 1,2-dichloroethane; The Cu / ETS-10 catalyst is prepared by using ETS-10 zeolite as a carrier and loading copper by an equal volume impregnation method. The loading amount of Cu in the Cu / ETS-10 catalyst is 1-5wt.%; The preparation method of ETS-10 zeolite is as follows: After water glass, sodium hydroxide, potassium fluoride aqueous solution and titanium trichloride solution are evenly mixed to form a titanium silical gel system, the system is loaded into a kettle, crystallized at a high temperature of 190-250°C, filtered, washed, dried, and calcined at a high temperature of 400-500°C to obtain ETS-10 zeolite, wherein the molar composition of each substance in the titanium silical gel system is: Na2O:K2O:SiO2:TiO2:H2O=4-20:1-10:6-16:1.5-3:150-200.

2. The method for synthesizing 3-methyleneisoindolin-1-one and its derivatives by catalyzing 2-iodobenzamide and terminal alkynes using a heterogeneous catalyst Cu / ETS-10 according to claim 1, characterized in that: The reaction temperature is 100-120°C.

3. The method for synthesizing 3-methyleneisoindolin-1-one and its derivatives by catalyzing 2-iodobenzamide and terminal alkynes using a heterogeneous catalyst Cu / ETS-10 according to claim 1, characterized in that: The reaction time is 2 to 12 hours.

4. The method for synthesizing 3-methyleneisoindolin-1-one and its derivatives by catalyzing 2-iodobenzamide and terminal alkynes using a heterogeneous catalyst Cu / ETS-10 according to claim 1, characterized in that: The reaction solvent is DMSO.

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