CN115572306A - Synthesis method of novel silane coupling agent trioxy-triethoxy-iminodiacetic acid diethyl ester organosilane - Google Patents

Abstract

The invention relates to the technical field of chemical synthesis, in particular to a method for synthesizing silane coupling agent trioxy-triethoxy-iminodiacetic acid diethyl ester organosilane. The invention firstly uses ethyl iodoacetate and allyloxy triethylene glycol inN,N-1, 8-diazabicyclo [5.4.0 ] in Dimethylformamide (DMF)]Synthesis of diethyl allyloxytrimethyleneglycolacyliminodiacetate in a series of reactions with undec-7-ene (DBU) as catalyst. This derivative was reacted with chloroperoxybenzoic acid (MCPBA) and triphenylphosphine (Ph) ₃ P) are mixed successively in the presence of sodium hydride as a strong base and boron trifluoride etherate (BF) _3• C ₂ H ₆ O) is used as a catalyst, and the epoxypropyl triethylene glycol acyl iminodiacetic acid diethyl ester is synthesized. Finally, the mixture is mixed with (3-chloropropyl) triethoxysilane under the condition of superbase sodium block, and the target product is prepared by reaction under the catalysis of a phase transfer catalyst benzyltriethylammonium chloride (TEBA). The method of the invention fills the defect that the prior art contains the imidoSynthesis of diethyl diacetate headgroup organosilanes is blank.

Description

A new type of silane coupling agent trioxy-triethoxy-iminodiacetate diethyl ester has Synthesis method of organosilane

technical field

The invention relates to the technical field of chemical synthesis, in particular to a method for synthesizing a novel silane coupling agent trioxyl-triethoxyl-iminodiacetate diethyl organosilane.

Background technique

Diethyl iminodiacetate is an important intermediate of medicines, pesticides and materials. For example, it can be used to prepare the brain function drug Joracetam. Industrial metal surface treatment, polymer material industry, pharmaceuticals and other fields.

In nature, many inorganic substances such as glass, quartz, and ceramics contain Si-O-Si bonds, so they generally lack organic groups, so these compounds belong to the category of inorganic polysiloxanes. However, in organosilicon chemistry, it is necessary to connect organic groups to silicon atoms to form siloxane compounds, which can interact with both hydroxyl groups in inorganic substances and long molecular chains in organic polymers. Function, so that two materials with different properties are coupled to improve various properties of biomaterials. Therefore, it is widely used in rubber, plastics, filled composite materials, epoxy encapsulation materials, elastomers, coatings, adhesives and sealants, etc.

Triethylsilyl exists widely in organic compounds and has important applications in organic synthesis. Silicon heterocyclic compounds are widely used in organic synthesis chemistry, materials chemistry and medicinal chemistry because of their unique physical and chemical properties. Therefore, it is of great significance to directly use organic compounds containing triethylsilyl groups in the synthesis of intermediates such as medicines and pesticides. The silylation reaction can protect specific functional groups in the chemical synthesis method to reduce the boiling point and increase the volatility of the compound. This feature has an important application prospect as an intermediate compound in the fields of medicine and pesticides.

Studies have shown that polyethylene glycol (PEG) head group can reduce the interaction between protein and diethyl iminodiacetate in the organism, so the PEG headgroup connected to diethyl iminodiacetate can reduce the entry of biological agents Non-specific adsorption in front of the target improves the targeting of biopharmaceuticals.

At present, there is no relevant synthesis report on organosilicon compounds with diethyl iminodiacetate as the head group, polyethylene glycol as the intermediate chain, and triethylsilyl as the tail.

Contents of the invention

The purpose of the present invention is to solve the synthetic problem of the organosilicon compound that takes diethyl iminodiacetate as the index head group, polyethylene glycol as the chain and triethylsilyl as the tail, and provides a trioxyl- The synthesis method of triethoxy-iminodiacetate diethyl silane solves the problem of building a "molecular bridge" between the interface of inorganic substances and organic substances, and plays a role in realizing the target recognition and controlled release system of biomedicine is of great significance.

Through the organosilicon compound synthesized above, a "molecular bridge" can be built between the interface of inorganic substances and organic substances, and two materials with completely different properties can be connected together. The reactive groups of triethylsilyl group, diethyl iminodiacetate and polyethylene glycol organic functional group can determine the target function of this compound in biomedicine, pesticide targeted recognition and controlled release system.

Trioxy-triethoxy-iminodiacetate diethyl organosilane has many advantages such as excellent activity, stable structure at room temperature, good stereoselectivity, and high stability of the formed coupling system. The synthesis method can be used to synthesize a series of silane coupling agents such as silyl chains and variable polyethylene glycol chains, and plays an important role in the field of organosilicon compound synthesis research. Therefore, the study of the synthesis method of trioxy-triethoxy-iminodiacetate diethyl organosilane will fill in the "molecular bridge" between the interface of inorganic substances and organic substances through the connection technology of inorganic silicon compounds. It will open up a new research and application path for precise drug delivery in the field of medicine and pesticides.

The present invention is achieved through the following technical solutions:

Ethyl iodoacetate and allyloxytriethylene glycol in N,N-dimethylformamide (DMF) as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) Synthesis of diethyl allyloxytriglycolyl iminodiacetate in a series of reactions as a catalyst. This derivative is mixed with chloroperoxybenzoic acid (MCPBA) and triphenylphosphine (Ph ₃ P) successively, under the condition of sodium hydride as a strong base, boron trifluoride diethyl ether (BF _{3 ·} C ₂ H ₆ O ) as a catalyst, synthesized to obtain diethyl glycidyl triethylene glycol acyl iminodiacetate. Finally, it is mixed with (3-chloropropyl) triethoxysilane under super alkali sodium block conditions, and the target product trioxy- Triethoxy-diethyliminodiacetate organosilane. The trioxy-triethoxy-iminodiacetate diethyl organosilane structural formula prepared by the present invention is as follows:

The synthetic method of described trioxy-triethoxy-iminodiacetate diethyl organosilane comprises the steps:

1) Synthesis of allyloxytriethylene glycol TG-Ally

Dissolve triethylene glycol in dry tetrahydrofuran (THF), stir at room temperature for 30 minutes, add pure sodium and stir rapidly for 1 hour, add allyl bromide dropwise, and continue the reaction for 6 hours; the residue after vacuum distillation is dissolved in dichloromethane, and Wash with saturated sodium chloride (NaCl) solution, dry over anhydrous magnesium sulfate, filter and concentrate, and purify by column chromatography;

2) Synthesis of allyloxy triglycolic iminodiacetic acid diethyl ester

Mix ethyl iodoacetate and TG-Ally and dissolve in dry DMF, stir at 0°C for 1-2h (preferably 1.5h), quickly add a catalytic amount of DBU, stir continuously at room temperature for 24h, then add 95% ethanol solution to decompose Excess DBU was washed with saturated NaCl solution, dried over anhydrous Na ₂ SO ₄ , filtered and concentrated by column chromatography, and the eluent was ethyl acetate/petroleum ether.

3) Synthesis of Epoxypropyl Triethylene Glycoyl Iminodiacetate Diethyl Ester

Diethyl allyloxytriglycolyl iminodiacetate is mixed with Ph ₃ P and MCPBA and dissolved in dry dichloromethane, then an appropriate amount of sodium hydride powder is added, and slowly heated to 30°C-50°C (preferably 40°C ), stirred rapidly for 30min, quickly added BF _{3 ·} C ₂ H ₆ O dropwise, and stirred continuously at room temperature for 30h after the dropwise addition, and filtered the reaction product after cooling to 0°C in an ice-water mixture; the concentrated filtrate was used Mixed organic solvents were extracted, and the organic phase was distilled under reduced pressure.

4) Synthesis of trioxy-triethoxy-iminodiacetate diethyl silane

Diethyl glycidyl triglycolyl iminodiacetate and (3-chloropropyl) triethoxysilane were dissolved in anhydrous DMF, and stirred at 50°C to 80°C (preferably 60°C) for 2 hours, A catalytic amount of benzyltriethylammonium chloride (TEBA) was added and stirring continued for 12h. The reactant was washed with saturated sodium bicarbonate solution, the organic phase was concentrated under reduced pressure, filtered, concentrated, separated by column chromatography, and placed in a freezer for 3 hours to obtain a white solid.

Further, in the described step 1),

The volume ratio of triethylene glycol to allyl bromide 1 mL: 1.3-2 mL; preferably 1 mL: 1.5 mL.

The mass volume ratio of sodium block to triethylene glycol is 1g: 2-3mL; preferably 1g: 2.8mL;

The volume ratio of THF to triethylene glycol is 3-3.5mL: 1mL; preferably 3mL: 1mL.

In column chromatography, silica gel, EtOAc and EtOAc are used, wherein the volume ratio v/v of EtOAc and EtOAc is 1:1.

Further, in the described step 2),

The mass ratio of ethyl iodoacetate to TG-Ally is 1g:2-3g; preferably 1g:2.5g.

The solvent DMF must be anhydrous;

The volume-to-mass ratio of DMF to ethyl iodoacetate is 1 mL: 0.02-0.05 g; preferably 1 mL: 0.05 g;

The volume-to-mass ratio of DBU to TG-Allyl is 1 μL: 0.5g-1.30g; preferably 1 μL: 1.25g;

The volume ratio of 95% ethanol solution to DBU is 1 μL: 1 μL;

In column chromatography, silica gel, EtOAc and Petroleum are used, wherein the volume ratio v/v of EtOAc and Petroleum is 1:2.

Further, in the described step 3),

The mass ratio of allyloxytriglycolyl iminodiacetate to MCPBA is 1g:0.5-1g, preferably 1g:1g.

The mass ratio of allyloxytriglycolyl iminodiacetic acid diethyl ester to Ph ₃ P is 1g:1.5-2g, preferably 1g:2g.

The mixed organic solvent for extracting the filtrate is diethyl ether/ethyl acetate, and the volume ratio v/v is 1:1.

Further, in the described step 4),

The volume ratio of diethyl glycidyl triglycolyl iminodiacetate to (3-chloropropyl)triethoxysilane is 15:1.

The volume ratio of DMF to diethyl glycidyl triglycolyl iminodiacetate is 4-4.5mL: 3mL; preferably 4mL: 3mL

The volume/mass ratio of (3-chloropropyl)triethoxysilane to TEBA is 1 mL: 0.1-0.3 g, preferably 1 mL: 0.2 g.

Compared with the prior art, the present invention has the following beneficial effects:

1) The synthesis of trioxy-triethoxy-iminodiacetate diethyl organosilane of the present invention is an important raw material for the preparation of silicone resin-solidified trypsin carrier, which can make the solidified enzyme insoluble in water and not inactivated solid-phase enzyme It can be used continuously after filtration, which not only improves the utilization rate of biological enzymes, but also reduces environmental pollution and waste of raw materials. This synthesis method fills the coupling agent containing diethyl iminodiacetate in organosilicon in the prior art. Compound synthesis blank.

2) The method of the present invention has few steps, simple operation and high efficiency, relatively conventional raw materials and catalysts, low toxicity or non-toxicity, simple and easy recovery in follow-up treatment, high product yield, and a breakthrough in the synthesis method of biomedical organosilicon compounds. , complex and cumbersome and low yield limitations.

Description of drawings

Fig. 1 is the NMR detection spectrum of the final product prepared in Example 1.

detailed description

In order to make the purpose, technical solutions and advantages of the present invention clearer, the present invention will be described in further detail below in conjunction with the accompanying drawings and embodiments. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. example.

Example 1

(1) Synthesis of allyloxytriethylene glycol TG-Ally

Dissolve 10 mL of triethylene glycol in 30 mL of dry THF, stir at room temperature for 30 min, add 3.5 g of pure sodium and stir rapidly for 1 h, add dropwise 15 mL of allyl bromide, and continue the reaction for 6 h. The residue after vacuum distillation was dissolved in 30 mL of dichloromethane, washed with saturated NaCl solution, dried over anhydrous magnesium sulfate, filtered and concentrated, and purified by column chromatography to obtain 4 g of a colorless oily product with a yield of 80%.

In column chromatography, silica gel, EtOAc and EtOAc are used, wherein the volume ratio v/v of EtOAc and EtOAc is 1:1.

(2) Synthesis of allyloxy triglycolic iminodiacetic acid diethyl ester

Mix 0.5g of ethyl iodoacetate and 1.25g of TG-Ally and dissolve in 10mL of dry anhydrous DMF, stir at 0°C for 1.5h, quickly add 1μL of DBU dropwise, continue stirring for 24h, add 1μL of 95% ethanol to dissolve excess DBU, washed with saturated NaCl solution, dried over anhydrous Na ₂ SO ₄ , filtered and concentrated column chromatography gave 0.4 g of a colorless viscous product with a yield of 75%.

In column chromatography, silica gel, EtOAc and Petroleum are used, wherein the volume ratio v/v of EtOAc and Petroleum is 1:2.

(3) Synthesis of Epoxypropyl Triglycolyl Iminodiacetate Diethyl Ester

5g of allyloxy triglycolyl iminodiacetic acid diethyl ester mixed with 5g MCPBA and 10gPh ₃ P successively and dissolved in 30ml of dichloromethane, 0.5g of sodium hydride powder was quickly added to the solution, slowly heated to Stir rapidly at 40°C for 30 min, then add 50 μL of BF _{3 ·} C ₂ H ₆ O dropwise, and continue stirring at room temperature for 30 h after the dropwise addition. After cooling to 0° C. with ice-water mixture, filter, mix the concentrated filtrate with 20 ml of distilled water, and extract with diethyl ether/ethyl acetate mixed solvent (v/v=1:1). The aqueous phase was distilled under reduced pressure to obtain 3 g of a transparent solid product with a yield of 80%.

(4) Synthesis of trioxy-triethoxy-iminodiacetate diethyl organosilane

7.5ml of diethyl epoxypropyl triglycolyl iminodiacetate and 0.5ml of (3-chloropropyl)triethoxysilane were dissolved in 10ml of anhydrous DMF in turn, stirred at 60°C for 2h, then slowly added 0.1 g of TEBA was continuously stirred for 12 hours, the reactant was washed with saturated sodium bicarbonate solution, the organic phase was concentrated under reduced pressure and then filtered. After concentration, it was separated by column chromatography and placed in a freezer for 3 hours to obtain 2 g of white solid. The yield was 70%.

¹ H NMR (500MHz, CDCl ₃ ): δ4.44–4.51 (s, 2H; H-2); 4.08–4.18 (d, J=12.2Hz, 4H; H-1); 3.78–3.88 (m, 2H ; 2CH2, ethoxy); 3.32–3.40 (m, 2H; CH, acetyl), 1.50–1.51 (m, 4H; 2OCH2), 1.48 (m, 4H; OCH2CH2), 1.26–1.31 (brs, 12H; CH3), 1.18 –1.23(t,3J=6.8Hz,9H;CH3); 0.56–0.60(t,3J=6.05and 6.8Hz,2H;CH2).

In column chromatography, silica gel, EtOAc and CH ₃ OH are used, wherein the volume ratio v/v of EtOAc and CH ₃ OH is 1:1, R _f =0.48

From Fig. 1 and the above data results, it can be seen that the final product obtained according to the synthesis method of the present invention meets the characteristics of the target substance.

Application example 1 Synthesis of hexaoxy-triethoxy-iminodiacetate diethyl organosilane

(1) Synthesis of allyloxy polyhexaethylene glycol

Dissolve 10mL of polyhexaethylene glycol in 30mL of dry THF, stir at room temperature for 60min, add 3.5g of pure sodium and stir rapidly for 1h, add dropwise 15mL of allyl bromide, and continue the reaction for 6h. The residue after vacuum distillation was dissolved in 30 mL of dichloromethane, washed with saturated NaCl solution, dried over anhydrous magnesium sulfate, concentrated by filtration and purified by recrystallization to obtain 3 g of a colorless solid product with a yield of 70%.

Recrystallization solvent: petroleum ether (30-60°C)

(2) Synthesis of allyloxy polyhexaethylene glycol acyl iminodiacetate diethyl

DBU，连续搅拌24h后，加入

95％乙醇溶分解多余DBU，用饱和NaCl溶液洗涤，无水Na₂SO₄干燥，过滤浓缩柱层析得到无色针状产物0.5g，产率为80％。Mix 0.5g of ethyl iodoacetate and 1.25g of allyloxy polyhexaethylene glycol, dissolve in 10mL of dry DMF, stir at room temperature for 30min, and add dropwise quickly

DBU, after continuous stirring for 24h, add

The excess DBU was dissolved in 95% ethanol, washed with saturated NaCl solution, dried over anhydrous Na ₂ SO ₄ , filtered and concentrated column chromatography to obtain 0.5 g of a colorless needle product with a yield of 80%.

In column chromatography, silica gel, EtOAc and Petroleum are used, wherein the volume ratio v/v of EtOAc and Petroleum is 1:1.

(3) Synthesis of glycidyl polyhexaethylene glycol acyl iminodiacetate diethyl

5g of allyloxy polyhexaethylene glycol acyl iminodiacetic acid diethyl acetate, 5g of MCPBA and 10g of Ph ₃ P were mixed successively and dissolved in 30ml of dichloromethane, 0.5g of sodium hydride powder was quickly added to the solution, and slowly heated to 40°C, stirred rapidly for 30 min, then added 50 μL of BF _{3 ·} C ₂ H ₆ O dropwise, and stirred continuously at room temperature for 30 h after the dropwise addition. After cooling to 0° C. with ice-water mixture, filter, mix the concentrated filtrate with 20 ml of distilled water, and extract with diethyl ether/ethyl acetate mixed solvent (v/v=1:1). The aqueous phase was distilled under reduced pressure to obtain 2 g of a flaky white solid product with a yield of 60%.

(4) Synthesis of hexaoxy-triethoxy-iminodiacetate diethyl organosilane

Dissolve 7.5ml of glycidyl polyhexaglycolyl iminodiacetic acid diethyl ester and 0.5ml (3-chloropropyl)triethoxysilane in 10ml of anhydrous DMF in turn, stir at 60°C for 2h, slowly Add 0.1 g of TEBA, continue to stir for 12 h, wash the reactant with saturated sodium bicarbonate solution, concentrate the organic phase under reduced pressure, and filter it. After concentration, it is separated by column chromatography and placed in a freezer for 3 h to obtain 0.5 g of a white solid. The yield was 60%.

¹ H NMR (500MHz, CDCl ₃ ): δ4.50(s, 8H; H-2), 4.40(12H; H-1), 4.13(d, J=12.2Hz, 4H; H-1), 3.80– 3.83 (m, 2H; 2CH ₂ , ethoxy), 3.38–3.40 (m, 2H; CH, acetyl), 1 (m, 4H; 2OCH ₂ ), 1.50–1.53 (m, 4H; OCH ₂ CH ₂ ), 1.19 –1.22(brs,12H; CH ₃ ), 0.50(t, ³ J=6.05 and 6.8Hz,2H; CH ₂ ).1.20–1.21(t, ³ J=6.8Hz,9H; CH ₃ )

In column chromatography, silica gel, EtOAc and CH ₃ OH are used, wherein the volume ratio v/v of EtOAc and CH ₃ OH is 1:1, R _f =0.53.

The above are only examples of the present invention, and are not intended to limit the patent scope of the present invention. All equivalent transformations made using the content of the description of the present invention, or directly or indirectly used in other related technical fields, are equally included in the scope of the present invention. within the scope of patent protection.

Claims (10)

1. A synthesis method of trioxy-triethoxy-iminodiacetic acid diethyl ester organosilane is characterized in that,

the structural formula of the triethoxy-diethyl iminodiacetate organosilane is shown as follows:

the synthesis method comprises the following steps:

1) Synthesis of allyloxytrimethylglycol TG-aly

Dissolving triethylene glycol in dry Tetrahydrofuran (THF), stirring at room temperature for 30min, adding pure sodium, quickly stirring for 1h, dropwise adding allyl bromide, and continuously reacting for 6h; dissolving the residue after reduced pressure distillation with dichloromethane, washing with saturated sodium chloride NaCl solution, drying with anhydrous magnesium sulfate, filtering, concentrating, and purifying by column chromatography;

2) Synthesis of allyloxytrimethyleneglycol acyliminodiacetic acid diethyl ester

Mixing ethyl iodoacetate and TG-aly, dissolving in dry DMF, stirring at 0 deg.C for 1-2 hr, quickly adding catalytic amount of DBU, stirring at normal temperature for 24 hr, adding 95% ethanol solution to dissolve excessive DBU, washing with saturated NaCl solution, and adding anhydrous Na ₂ SO ₄ Drying, filtering, concentrating, and performing column chromatography with ethyl acetate/petroleum ether as eluent;

3) Synthesis of epoxypropyl triethylene glycol acyl imino diethyl diacetate

Allyloxytrimethyleneglycol acyliminodiacetic acid diethyl ester with Ph ₃ Mixing P and MCPBA, dissolving in dry dichloromethane, adding appropriate amount of sodium hydride powder, slowly heating to 30-50 deg.C, rapidly stirring for 30min, and rapidly adding BF dropwise ₃ ·C ₂ H ₆ O, continuously stirring for 30 hours at room temperature after the dropwise addition is finished, cooling a reaction product in an ice-water mixture to 0 ℃, and filtering; extracting the concentrated filtrate with mixed organic solvent, and distilling the organic phase under reduced pressure;

4) Synthesis of triethoxy-iminodiacetic acid diethyl ester organosilane

Dissolving epoxypropyl triethylene glycol acyl iminodiacetic acid diethyl ester and (3-chloropropyl) triethoxysilane in anhydrous DMF, stirring at 50-80 deg.C for 2h, adding benzyl triethyl ammonium chloride (TEBA) as catalyst, and continuously stirring for 12h; washing the reactant with saturated sodium bicarbonate solution, concentrating the organic phase under reduced pressure, filtering, concentrating, separating by column chromatography, and standing in a freezing chamber for 3h to obtain white solid.

2. The method according to claim 1, wherein in step 1),

volume ratio of triethylene glycol to allyl bromide 1mL:1.3-2mL;

the mass-to-volume ratio of the sodium lumps to the triethylene glycol is 1g:2-3mL;

the volume ratio of THF to triethylene glycol was 3-3.5mL:1mL;

in column chromatography, silica gel and Et are used ₂ O and EtOAc, wherein Et ₂ The volume ratio v/v of O and EtOAc is 1.

3. The method according to claim 1, wherein in step 2),

the mass ratio of ethyl iodoacetate to TG-aly is 1g:2-3g;

the solvent DMF must be anhydrous;

the volume-mass ratio of DMF to iodoethyl acetate is 1mL:0.02-0.05g;

the volume mass ratio of DBU to TG-aly is 1 mu L:0.5g to 1.30g;

the volume ratio of the 95% ethanol solution to the DBU is 1 mu L:1 mu L of the solution;

in column chromatography, silica gel, etOAc and Petroleum are used, wherein the volume ratio v/v of EtOAc and Petroleum is 1.

4. The method according to claim 1, wherein, in the step 3),

the mass ratio of allyloxytrimethyleneglycol acyl iminodiacetic acid diethyl ester to MCPBA is 1g:0.5-1g;

allyloxy groupTriethylene glycol acyl iminodiacetic acid diethyl ester and Ph ₃ The mass ratio of P is 1g:1.5-2g;

the mixed organic solvent of the extraction filtrate is diethyl ether/ethyl acetate, and the volume ratio v/v is 1.

5. The method according to claim 1, wherein, in the step 4),

the volume ratio of the glycidyl triethylene glycol acyl iminodiacetic acid diethyl ester to the (3-chloropropyl) triethoxysilane is 15:1;

the volume ratio of DMF to diethyl epoxypropyltriglycol acyliminodiacetate is 4-4.5mL:3mL;

the volume-to-mass ratio of (3-chloropropyl) triethoxysilane to TEBA is 1mL:0.1-0.3g.

6. The method of claim 1,

in the step 2) of synthesizing allyloxytrimethyleneglycol acyl diethyl iminodiacetate, iodoethyl acetate and allyloxytrimethylene glycol are mixed and then dissolved in dry DMF, and the mixture is stirred for 1.5 hours at the temperature of 0 ℃;

in the step 3), during the synthesis of the glycidyl triethylene glycol acyl diethyl iminodiacetate, adding a proper amount of sodium hydride powder, and slowly heating to 40 ℃;

in the step 4) of synthesizing the triethoxy-iminodiacetic acid diethyl ester organosilane, dissolving epoxypropyl triethylene glycol acyl iminodiacetic acid diethyl ester and (3-chloropropyl) triethoxysilane in anhydrous DMF, and stirring for 2h at 60 ℃.

7. The method according to claim 1, wherein, in the step 1),

the volume ratio of triethylene glycol to allyl bromide is preferably 1mL:1.5mL;

the mass-to-volume ratio of the sodium lumps to the triethylene glycol is preferably 1g:2.8mL;

the volume ratio of THF to triethylene glycol is preferably 3mL:1mL.

8. The method according to claim 1, wherein in step/2),

the mass ratio of ethyl iodoacetate to TG-aly is preferably 1g:2.5g;

the volume-to-mass ratio of DMF to iodoethyl acetate is preferably 1mL:0.05g;

the volume mass ratio of DBU to allyloxytrimethylene glycol is preferably 1 μ L:1.25g.

9. The method according to claim 1, wherein, in the step 3),

the mass ratio of allyloxytrimethyleneglycol acyliminodiacetic acid diethyl ester to MCPBA is preferably 1g:1g of a compound;

allyloxytrimethyleneglycol acyliminodiacetic acid diethyl ester with Ph ₃ The mass ratio of P is preferably 1g:2g of the total weight of the composition.

10. The method according to claim 1, wherein, in the step 4),

the volume ratio of DMF to diethyl epoxypropyltriglycol acyliminodiacetate is preferably 4mL:3mL;

the volume-to-mass ratio of (3-chloropropyl) triethoxysilane to TEBA is preferably 1mL:0.2g.

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