CN111217721A

CN111217721A - Preparation method of hydrogel monomer containing azide group

Info

Publication number: CN111217721A
Application number: CN202010063461.9A
Authority: CN
Inventors: 段海峰; 侯兴强; 张甲强; 陈子天
Original assignee: Sina Biotechnology Beijing Co Ltd
Current assignee: Sina Biotechnology Beijing Co Ltd
Priority date: 2020-01-20
Filing date: 2020-01-20
Publication date: 2020-06-02

Abstract

The invention provides a preparation method of a hydrogel monomer containing an azide group, which comprises the steps of firstly utilizing diamine or triamine to react with an azide compound, and then removing an amino protecting group to form an intermediate product with one end being an amino group and the other end being the azide group; then reacting with an acryloyl chloride compound to obtain a compound with a double bond at one end and an azide group at the other end. The preparation method disclosed by the invention can effectively overcome the problems of high toxicity, high explosiveness, personnel safety, environmental hazards and the like caused by adopting sodium azide as a raw material, and can improve the preparation cost and the application range of the polymer monomer.

Description

Preparation method of hydrogel monomer containing azide group

Technical Field

The invention relates to a preparation method for synthesizing an acrylamide hydrogel monomer containing an azide group and application of the acrylamide hydrogel monomer in preparation of a high-molecular hydrogel polymer, and belongs to the field of biomedicine.

Background

The azide group has wide application in the fields of chemical synthesis, biological functional molecule synthesis, biological molecule marking, polymer macromolecule synthesis and the like. Because the azide group is a high-energy-containing group and is also a functional group, the azide group can be conveniently converted into various active groups. Especially, the method plays an important role in the synthesis of high molecular compounds related to biological application, and many important biomolecule labeling reactions achieve the aim by forming heterocyclic molecules with good biocompatibility through click chemistry through the participation of azide groups. Meanwhile, azide groups are very difficult to be conveniently introduced, sodium azide molecules are often adopted to obtain target compounds in the traditional azide group synthesis method, and the sodium azide molecules have high toxicity and explosiveness and are widely limited in use. Therefore, how to synthesize and separate the high-purity polymer monomer with the azide functional group by using a simple and convenient method is a great research hotspot in the synthesis field.

The invention aims at synthesizing an olefin compound with an azide group, in particular an acrylamide compound used as a polymer monomer compound. The acrylamide monomer is a hydrogel substance with wide application in the fields of biology, medicine and the like, belongs to a novel biomedical material with great future prospect, and can be used for biological detection, biological tissue substitution, transplantation, environmental protection, daily chemical application and the like.

Generally, the known literature routes to acrylamide molecules with azide groups all start with the forbidden compound sodium azide, such as: diamine compound is used as initial material, and through reaction with acryloyl chloride compound, the obtained intermediate is substituted with acyl halide compound, and finally sodium azide is used to introduce azide group. This scheme is dangerous, and the target yield obtained is very low, and the discharge of hazardous waste liquid containing highly toxic substances poses very serious environmental pollution problems, so that the use of sodium azide as its raw material has problems that cannot be ignored regardless of the availability of the synthetic route and the availability of raw materials and environmental friendliness. The invention provides a novel preparation method for synthesizing an azide group-containing monomer hydrogel monomer, which can effectively overcome the problems of high toxicity, high explosiveness, personnel safety, environmental hazard and the like caused by adopting sodium azide as a raw material.

Disclosure of Invention

The purpose of the invention is realized by the following technical scheme.

In order to solve the above problems, there is provided a method for preparing a hydrogel monomer having an azide group, comprising,

diamine reacts with azido lipid compounds to obtain a first intermediate product, and the single-end amino of the diamine is modified and protected by a protecting group;

removing an amino protecting group from the first intermediate product to obtain a second intermediate product with one end being an amino group and the other end being an azide group;

reacting the second intermediate product with acryloyl chloride or substituted acryloyl chloride to obtain a hydrogel monomer with a double bond at one end and an azide group at one end;

wherein said substituted acryloyl chloride refers to acryloyl chloride having a methyl or ethyl group or a halogen attached to the carbon;

wherein the azide group of said azidolipid compound is terminal.

According to a preferred embodiment, the diamine contains from 2 to 8 carbon atoms; the diamine refers to a primary amine.

According to a preferred embodiment, the diamine is a substituted diamine with 1-5 PEG chains in the middle.

According to a preferred embodiment, the diamine is 1, 4-butanediamine.

According to a preferred embodiment, the removal of the amino protecting group from the first intermediate product means that the amine protected by the single-end tert-butylcarbonyl group is reacted with gaseous hydrogen chloride to remove the protecting group.

According to a preferred embodiment, the diamine refers to a diamine comprising the structure.

The invention provides a preparation method of a hydrogel monomer containing an azide group, which is characterized by comprising the following steps of,

triamine and an azide lipid compound react to obtain a first intermediate product, wherein one or two of amino groups in the triamine are modified and protected by an amino protecting group;

removing amino protecting groups from the first intermediate product to obtain a second intermediate product with one or two amino ends and at least one end with an azide group;

reacting the second intermediate product with acryloyl chloride or substituted acryloyl chloride to obtain a hydrogel monomer with double bonds and azide groups;

wherein said substituted acryloyl chloride refers to acryloyl chloride having a methyl or ethyl group or a halogen attached to the carbon.

The invention discloses a method for synthesizing a hydrogel monomer containing double bonds and azide groups, which has the following advantages: the introduction of the azide group does not adopt high-toxicity and explosive sodium azide as a raw material, but adopts nontoxic and high-stability azido acetate as an initiator, and the raw material is a commercially available raw material. The synthetic route is greatly simplified from the reported multi-step method, and the method route provided by the invention only needs 2 steps at least, thereby reducing the operation time and improving the safety factor. The method greatly improves the yield of the target product, has few product intermediates, and is easy to purify and synthesize in large quantities. The method does not produce hazardous waste solution containing toxic sodium azide with environmental hazard. The monomer can be used for synthesizing hydrogel polymers with various frameworks, and can further perform various molecular modifications by means of azide groups.

Drawings

Various other advantages and benefits will become apparent to those of ordinary skill in the art upon reading the following detailed description of the preferred embodiments. The drawings are only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the invention. In the drawings:

FIG. 1 is a scheme-HPLC purity profile;

FIG. 2 is a line one LC-MS detection profile;

FIG. 3 is a scheme one LC-MS molecular weight spectrum;

FIG. 4 is a HPLC purity profile of route two;

FIG. 5 is a second LC-MS detection profile of route;

FIG. 6 is a scheme II LC-MS molecular weight spectrum;

FIG. 7 shows a common amino protecting group and removal means.

Detailed Description

Exemplary embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. While only exemplary embodiments of the present disclosure have been shown, it should be understood that the present disclosure may be embodied in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art.

The new preparation route, developed by way of example below, is a hydrogel monomer compound 1 as shown in route one below, the reaction is divided into three steps, the first step starts with a single-ended BOC protected diamine, and the second is not a core key modification step: namely, a key intermediate compound 2 containing an azide group can be obtained through a one-step efficient but unusual amino and ester group exchange reaction by reacting with a non-toxic and excellent-stability commercially available azide acetate compound; secondly, removing a tert-butylcarbonyl protecting group through a simple chemical reaction to obtain a corresponding stable intermediate 3 with one end being an amino group and one end being an azide group; and thirdly, reacting the amino with acryloyl chloride to obtain the target compound. Important bright spots: the method only has three steps of reactions, and each step of reaction has the characteristics of extremely high conversion rate, thorough reaction, mild reaction conditions and stable intermediate, and the final product is obtained in a recrystallization form, the purity can reach 99 percent, and the total yield is not lower than 50 percent.

The synthetic route I of the invention is as follows:

of course, the source of raw materials can be further simplified, and diamine substances without protecting groups are used as raw materials to realize the second synthetic route of the invention, which is as follows:

according to a preferred embodiment, the diamine starting materials of the present invention can be further expanded, for example, into the following categories:

also included are derivatives with substituents in the middle carbon chain, which, while defining the scope, do not require the examples

According to a preferred embodiment, it is also possible to use diamines with a PEG chain in the middle, as follows:

the presence of PEG chains can further increase the hydrophilicity of the polymer, with a number of unique advantages.

According to a preferred embodiment, the diamine refers to a primary amine.

The product of substitution of one or more hydrogen atoms in the ammonia molecule with a hydrocarbon group, called amine, can be classified into primary, secondary, and tertiary amines according to the number of substituted hydrogen atoms in the amine molecule; the amine may be a compound produced by substituting hydrogen in the ammonia molecule with a hydrocarbon group, and the amine may be a derivative in which H in the ammonia molecule is substituted with a hydrocarbon group. The amine referred to in the present invention means a primary amine. Diamine refers to an organic compound containing two NH2 groups. This is a conventional term in the chemical arts.

The azide ester compounds belong to common compounds and can also be called as azido acyl compounds, namely compounds in which an azido group is directly connected with an acyl group.

One end of the product synthesized by the method contains an azide group, and the other end of the product contains a carbon-carbon double bond. The structure has the advantages that the double bond part can continue to carry out addition reaction to form hydrogel substances with long molecular chains, and azide groups form various chemical biomolecules through click chemistry (click chemistry), so that the structure has wide applicability.

Click chemistry, also known as "link chemistry" and "rapid-fit joint combinatorial chemistry", is a synthetic concept introduced in 2001 by the chemist barre charles (K B sharp) and aims to rapidly and reliably complete the chemical synthesis of morphochromic molecules by the splicing of small units. It is particularly emphasized that new combinatorial chemistry methods based on the synthesis of carbon-heteroatom bonds (C-X-C) are developed and that molecular diversity is obtained simply and efficiently by means of these reactions (click reactions). A typical reaction for click chemistry is Copper-Catalyzed Azide-alkynyl Husigen Cycloaddition (Copper-Catalyzed Azide-Alkyne Cycloaddition).

In the present invention, the click chemistry refers to the azide-alkynyl reaction. The catalyst is preferably a complex (Cu-THPTA) of copper sulfate and tris (3-hydroxypropyl triazolemethyl) amine, wherein the molar ratio of the catalyst to the functional acrylamide azide monomer is 1-100. In the actual reaction, reduced monovalent copper ions were used.

In the case of diamines, the conventional technique first protects one of the amino groups, and after the other amino group has reacted, the protecting group can be released, thereby obtaining the effect of reacting only one amino group. When amino group is protected, the present invention relates to a partial protection technique of diamine or triamine. The partially protected diamine or triamine can be obtained only by controlling the conditions and the progress of the reaction.

In the second route, the amino groups are not protected, so that both the amino groups are reacted during the reaction, and the product is difficult to separate.

The diamine according to the present invention may be changed to triamine. The triamine is a primary amine.

The reaction of triamines is analogous to diamines. One or two of the amino groups can be protected first, and after the remaining amino groups have reacted, the protecting groups are removed, i.e., the reaction can continue. It is understood that when an amino group is protected, a compound having a carbon-carbon double bond at one end and an azide group at the other end can be obtained by simply adjusting the ratio of reactants. When two amino groups are protected, a compound having double bonds at both ends and an azide group at one end can be obtained by simply adjusting the ratio of the compound. When there are more azide groups, more modification sites can be provided. When the number of double bonds is large, the crosslinking in the synthesis of the subsequent hydrogel compound is more compact or complicated. The reaction of the triamine may allow more options to be available for the hydrogel or biochemical modification site.

According to a preferred embodiment, said wherein said substituted acryloyl chloride refers to acryloyl chloride with methyl or ethyl groups or halogen attached to the carbon. When the substituents are relatively large, for example, 4 to 10 carbon atoms, the reaction yield decreases through experiments. This reaction can also take place without substituents.

Key materials and suppliers are shown in Table 1 below

Name of raw materials	Suppliers of goods
		BOC-1, 4-butanediamine	Lake south China Huateng pharmaceutical Co., Ltd
Azoic acid methyl ester	Shanghai Shaoshao reagent Limited
		Methacryloyl chloride	Taixi chemical industry (Shanghai) Co Ltd
1, 4-butanediamine	Sigma Aldrich trade company

TABLE 1

Example 1

The first step is as follows: measuring BOC-1.4 butanediamine (95.50mmol, 18.27mL, 1.1eq) by using a measuring cylinder, adding into a cleaned and dried 250mL single-mouth reaction bottle, and stirring; measuring methyl azide acetate (86.90mmol, 8.46mL and 1.0eq) by using an injector, adding the methyl azide acetate into a 250mL single-mouth reaction bottle at one time, and stirring; reacting at room temperature for 30min-1h until all liquid generates white solid, determining the reaction process by TLC, and completely treating the reaction; 250mL of DCM were added with the remainder of the material and the mixture was heated to reflux at 52 ℃ in an oil bath. TLC tracking, complete reaction, adding silica gel into the system, mixing samples, separating by a chromatographic column layer, eluting residual methyl azide acetate and other small polar impurities by 100% PE, eluting the product by 100% EA, and collecting. Solvent EA was removed using a rotary evaporator at 40 ℃ and oil pumped to dryness to afford intermediate 2 as a white solid (24.1g, 88.8mmol, 93.1% yield).

The second step is that: the white solid intermediate 2 obtained in the first step (24.1g, 88.8mmol, 1.0eq) was taken and added to a 1000mL single-neck flask washed and dried, and 500mL of 1, 4-dioxane was added to dissolve and stirred. Weighing 500g of solid sodium chloride in another cleaned and dried 1000mL single-neck bottle, weighing 100mL of concentrated sulfuric acid in a dropping funnel, and dropping into the 1000mL single-neck bottle with the dropping speed controlled at 60 d/min. HCl (g) generated by sodium chloride and concentrated sulfuric acid is introduced into a 500mL 1, 4-dioxane reaction system through an acid corrosion resistant guide pipe, is vigorously stirred and is tracked by TLC, and the HCl (g) is treated when the reaction is complete (8-15 h). The precipitated white solid was collected by suction filtration, washed with 200mL of 1, 4-dioxane, and pumped to dryness with an oil pump to obtain intermediate 3(12.2g, 71.2mmol, yield 80.1%) as a white solid.

The third step: taking the white solid intermediate 3(12.2g, 71.2mmol, 1.0eq) obtained in the second step into 1000mL of a washed and dried single-neck bottle, adding 500mL of anhydrous methanol for dissolving, adding Et3N (24.7mL, 178.0mmol, 2.5eq), stirring, cooling a liquid nitrogen ethanol system to-20 ℃, and keeping the temperature. Methacryloyl chloride (85.44mmol, 8.2mL, 1.2eq) is measured by a 10mL syringe and dissolved in 25mL of ultra-dry THF, the mixture is transferred to a dropping funnel and slowly dropped into a methanol system, the dropping speed is controlled to be 120d/min, the temperature is kept at minus 20 ℃, the temperature is freely raised to Rt after dropping, and the reaction is carried out for 15 to 18 hours. TLC, determining that the reaction is complete, removing the solvent in the reaction system at 45 ℃ by using a rotary evaporator to obtain a slightly off-white sticky solid crude product, adding 500mL of THF into the crude product, stirring for 30min, performing suction filtration, washing the white solid by using 200mL of THF, collecting mother liquor, and removing the solvent at 45 ℃ to obtain a colorless oily liquid (or slightly yellow). Adding appropriate amount of silica gel into colorless oily liquid, stirring with DCM, separating with chromatographic column, eluting with 100% PE to remove small polar impurities, eluting with 100% EA to obtain product, and collecting. Removing solvent EA at 40 ℃ by using a rotary evaporator to obtain a white solid crude product; if colorless oily liquid is obtained, 50mL of mixed solvent with the volume ratio of PE/EA being 1/1 is used for 1-3 times to obtain crude white solid. The crude product is dissolved to the maximum saturation by using a mixed solvent with the volume ratio of PE/EA being 1/1 at 60 ℃, and is freely cooled and recrystallized for 15-20 h. Needle crystals were recrystallized and filtered off, and the white solid was washed with 100% PE and dried by oil pump to give pure 4 (11.9g, 49.8mmol, yield 70%, purity 99%; LC/MS:240.1,241.1; melting point: 84 ℃,1H NMR (400MHz, Deuterium Oxide) δ 5.62(t, J ═ 1.0Hz,1H), 5.42-5.22 (m,1H),3.96(s,2H),3.22(q, J ═ 2.7Hz,4H),1.88(dd, J ═ 1.6,1.0Hz,3H),1.52(dq, J ═ 6.6,3.2Hz,4H) as the desired product as a white solid.

The HPLC purity detection profile is shown in FIG. 1. The LC-MS detection spectrum is shown in FIG. 2. The LC-MS molecular weight spectrum is shown in FIG. 3.

Example 2

The first step is as follows: accurately measuring 1, 4-butanediamine (114.0mmol, 11.4mL and 1.0eq) by using a syringe into a 250mL reaction bottle which is cleaned and dried, opening a magnetic stirrer for stirring, accurately measuring methyl azide acetate (114.0mmol, 11.04mL and 1.0eq) by using the syringe, adding the methyl azide acetate into the 250mL reaction bottle containing the 1, 4-butanediamine at one time, reacting at room temperature for 30min-1h, tracking and monitoring the reaction by TLC, adding a proper amount of silica gel and dissolving the DCM after the reaction is completed, removing the solvent DCM at 40 ℃ by using a rotary evaporator for uniform sample mixing, separating and purifying by using a chromatographic column, eluting by using a DCM/MeOH mixed solvent (elution gradient DCM/MeOH:50/1 → 30/1 → 25/1 → 20/1 → 10/1), collecting an organic phase of a target reaction compound by TLC, removing the solvent by using the rotary evaporator at 40 ℃ to obtain a colorless oil, transferring the oil to a 100mL single-mouth, the residual solvent was pumped off by an oil pump to give intermediate 6(5.82g, 34.0mmol, yield 15.4%) as a white solid.

The second step is that: putting the white solid intermediate 6(34.1mmol, 5.82g and 1.0eq) in a 250mL reaction bottle, accurately weighing 15mL methanol in a measuring cylinder to dissolve, opening a magnetic stirrer to stir, then weighing Et3N (44.2mmol, 4.41mL and 1.3eq) to add into a methanol system, cooling to-20 ℃ by using a liquid nitrogen/ethanol system and keeping the temperature, accurately weighing 5mL of ultra-dry THF by using an injector to put into a clean and dry 50mL single-neck round-bottom flask, weighing methacryloyl chloride (3.2mL, 34.1mmol and 1.0eq) in a measuring cylinder to dissolve into the ultra-dry 5mL THF, fully dissolving, transferring into a 25mL dropping funnel by using the injector, slowly adding into the methanol reaction system, keeping the temperature to-20 ℃ in the process, finishing dropping of the methacryloyl chloride/THF solution, removing the liquid nitrogen/ethanol cooling system, freely heating to room temperature, reacting for 15h, determining the reaction process by TLC, and completely reacting, removing solvent by using a rotary evaporator at 40 ℃ to obtain a colorless oily liquid crude product, adding a proper amount of silica gel, dissolving DCM, removing the solvent DCM by using the rotary evaporator at 40 ℃, uniformly stirring samples, separating and purifying by using a chromatographic column, eluting by using a PE/EA mixed solvent (elution gradient PE/EA:100/1 → 50/1 → 25/1 → 10/1 → 1/1), collecting a target compound PE/EA ═ 1/1 organic phase, removing the solvent by using the rotary evaporator at 40 ℃ to obtain a colorless oily substance, transferring the oily substance to a 500mL single-neck round-bottom flask, adding a small amount of mixed solvent with the volume ratio PE/EA ═ 1/1 repeatedly, heating to 60 ℃ for reflux to completely dissolve the mixed solvent to the maximum saturation, freely cooling for recrystallization for 15-20h, recrystallizing to separate needle-shaped crystals, and performing suction filtration to obtain a white solid, washing with 100% PE (the recrystallization step was repeated 3 times), transferring the white solid to a 100mL single-neck round-bottom flask, and pumping off the remaining solvent with an oil pump to obtain pure 4 (1.2 g; 5.15 mmol; yield 15.1%; purity 98%; LC/MS:239.9, 241.0; melting point: 84 ℃; 1H NMR (400MHz, Deuterium Oxide) δ 5.62(t, J ═ 1.0Hz,1H), 5.42-5.22 (m,1H),3.96(s,2H),3.22(q, J ═ 2.7Hz,4H),1.88(dd, J ═ 1.6,1.0Hz,3H),1.52(dq, J ═ 6.6,3.2Hz, 4H)) as a white solid.

HPLC purity detection spectrum is shown in FIG. 4.LC/MS detection spectrum is shown in FIG. 5.LC/MS molecular weight spectrum is shown in FIG. 6.

The experimental results show that: the method for synthesizing the target compound 4 by using the route one has the advantages of short steps, only three steps, easily-bought raw materials on the market, easily-met reaction conditions, no dangerous operation and high-toxicity waste generation, simple experiment post-treatment and purification, high-purity target compound, high purity of over 99 percent, high yield and total yield of 52.1 percent. Compared with the first route, the second route has the advantages of short steps, easily purchased raw materials, easily met reaction conditions, no dangerous operation and high-toxicity waste generation, and finally obtained target compounds with high purity of 98%, but seems to be a short two-step reaction, a large amount of byproducts are generated in the process, the properties are extremely similar, the byproducts are difficult to remove in the post-treatment, so that a large amount of target compounds are lost in the impurity removal of final products, and the total yield is only 2.3%. However, referring to the synthesis method of related similar compounds, a diamine compound is mostly used as a starting material, and reacts with an acryloyl chloride compound, so that an obtained intermediate undergoes a substitution reaction with an acyl halide compound, and finally sodium azide is used to introduce an azide group. The scheme has the disadvantages of danger, raw material control, difficult release synthesis in experiments, difficult purification, very low obtained target yield compared with the synthesis method of the second route, serious environmental pollution caused by discharged hazardous waste liquid containing high-toxicity substances, and obvious complementary advantages of the first route and the second route.

Example 3

The protection of diamines or triamines is a common technique. Referring to fig. 7, various amino protection techniques are shown. This protection technique and the corresponding deprotection technique can replace the amino protection means in examples 1 and 2. The material proportion and the conditions of the reaction need to be adjusted correspondingly.

The invention provides a simple preparation method of a functional monomer of an azide-containing polymer, and meanwhile, the route is also suitable for the synthesis of other monomers containing azide groups, such as: the C4-C10 chain, C4-C10 contain double-end-group amino groups such as a modified group chain, a PEG chain and the like as compounds of an intermediate skeleton, and a group containing unsaturated double bonds at one end can be acryloyl and analogues thereof.

The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the appended claims.

Claims

1. A preparation method of hydrogel monomer containing azide groups is characterized by comprising the steps of reacting diamine with azide compounds to obtain a first intermediate product, wherein single-end amino groups of the diamine are modified and protected by protecting groups; removing an amino protecting group from the first intermediate product to obtain a second intermediate product with one end being an amino group and the other end being an azide group; reacting the second intermediate product with acryloyl chloride or substituted acryloyl chloride to obtain a hydrogel monomer with a double bond at one end and an azide group at one end; wherein said substituted acryloyl chloride refers to acryloyl chloride having a methyl or ethyl group or a halogen attached to the carbon; wherein the azide group of said azidolipid compound is terminal.

2. The method of claim 1, wherein the diamine contains 2 to 8 carbon atoms; the diamine refers to a primary amine.

3. The method of claim 1 or 2, wherein the diamine is a substituted diamine with 1-5 PEG chains in the middle.

4. A process according to any preceding claim, wherein the diamine is 1, 4-butanediamine.

5. The process of any preceding claim, wherein the first intermediate deamination step is carried out by reacting a mono-terminal tert-butylcarbonyl-protected diamine with gaseous hydrogen chloride to remove the protecting group.

6. The method of any of the preceding claims, wherein the diamine refers to a diamine comprising the structure:

7. the method of any one of the preceding claims, wherein an azide-containing hydrogel monomer is prepared by reacting a triamine with an azide compound to obtain a first intermediate product, wherein one or both of the amine groups of the triamine are modified and protected with an amino protecting group; removing amino protecting groups from the first intermediate product to obtain a second intermediate product with one or two amino ends and at least one end with an azide group; reacting the second intermediate product with acryloyl chloride or substituted acryloyl chloride to obtain a hydrogel monomer with double bonds and azide groups; wherein said substituted acryloyl chloride refers to acryloyl chloride having a methyl or ethyl group or a halogen attached to the carbon.

8. The method according to any of the preceding claims, characterized in that the triamine is a primary amine.

9. A hydrogel prepared using the hydrogel monomer of any one of claims 1 to 8.

10. A method for synthesizing a hydrogel, which comprises using the hydrogel monomer according to any one of claims 1 to 8.