Arylsulfonium salt photoinitiator, preparation method and application thereof

Abstract

The present invention provides an arylsulfonium salt photoinitiator, a preparation method, and applications thereof. The present invention discloses an arylsulfonium salt photoinitiator as shown in (I). This initiator has excellent visible light absorption properties and can efficiently initiate the polymerization reaction of N-acryloylglycine in the visible light region (440-450 nm LED light source) to prepare hydrogel materials in situ. Therefore, this photoinitiator can reduce the damage of high-energy light to biological tissues, improving the safety of biomedical applications. It is particularly suitable for the in situ preparation of hydrogel materials in fields such as wound dressings and tissue engineering. #imgabs0#

Description

Technical Field

[0001] The present invention relates to the technical field of photoinitiators, and in particular to an arylsulfonium salt photoinitiator, a preparation method thereof and applications thereof. Background Art

[0002] In recent years, with the continuous development of biomedical technology, hydrogel materials with excellent biocompatibility and biodegradability have shown broad application prospects in drug delivery, wound dressings, tissue engineering, and other fields. In particular, the potential of hydrogel materials in tissue repair and regeneration has attracted the attention of numerous researchers. To meet the needs of these fields, photoinitiators with excellent photopolymerization properties have become an important tool for preparing hydrogels. Traditional photoinitiators mostly rely on ultraviolet or deep ultraviolet (UV) light for excitation, which often causes significant damage to biological tissues. Therefore, the development of photoinitiators with good absorption and initiation efficiency in the visible light region has become a hot topic of current research.

[0003] Arylsulfonium salt photoinitiators, as high-performance photoinitiators, have received increasing attention in recent years. These photoinitiators offer significant advantages due to their high photoinitiation efficiency and ability to effectively control the polymerization reaction. However, most existing arylsulfonium salt photoinitiators suffer from narrow absorption ranges and insufficient absorption in the visible light region, limiting their application in bio-tissue material engineering. For example, domestic invention patent CN107129487A reports a class of LED-excitable sulfonium salts with a thioxanthone conjugated structure. However, their maximum absorption wavelength in the long-wavelength range is 385 nm, which does not reach the visible light region.

[0004] To address these issues, the present invention provides a novel arylsulfonium salt photoinitiator with excellent absorption properties in the visible light region, capable of efficiently initiating the polymerization reaction of N-acryloylglycine (NAG) hydrogels under visible light irradiation. The use of this novel photoinitiator not only enables the efficient preparation of hydrogels under relatively low-energy visible light, avoiding the potential damage to biological tissues caused by ultraviolet light, but also provides a safer and more reliable material preparation solution for the biomedical field. Therefore, the arylsulfonium salt photoinitiator of the present invention has broad application prospects, and is particularly suitable for the in situ preparation of biomedical materials such as wound dressings and tissue engineering, possessing significant scientific value and application potential. Summary of the Invention

[0005] The technical problem addressed by this invention is to overcome the drawback of existing photoinitiators, which are typically excited by ultraviolet light. The invention provides an arylsulfonium salt photoinitiator, its preparation method, and its application. This initiator exhibits excellent visible light absorption properties, enabling efficient polymerization of N-acryloylglycine in the visible light region (440-450 nm LED light source) to form hydrogel materials in situ. Consequently, this photoinitiator can reduce damage to biological tissues caused by high-energy light, improving the safety of biomedical applications. It is particularly suitable for the in situ preparation of hydrogel materials in fields such as wound dressings and tissue engineering.

[0006] The present invention solves the above technical problems through the following technical solutions.

[0007] The present invention provides an arylsulfonium salt photoinitiator as shown in (IV), wherein:

[0008] R1 is optionally replaced by R 1-1 Substituted C 1-6 or optionally replaced by R 1-2 Substituted C 3-10 Substituted cycloalkyl.

[0009] R2 is optionally replaced by R 2-1 Substituted C 1-6 or optionally replaced by R 2-2 Substituted C 3-10 Substituted cycloalkyl.

[0010] R3 is optionally replaced by R 3-1 Substituted C 6-10 The aryl group or optionally replaced by R 3-2 Substituted C 5-10 Heteroaryl, wherein the heteroatom species in the heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3.

[0011] X is an anion, preferably a trifluoromethanesulfonate ion.

[0012] R 1-1 、R 1-2 、R 2-1 、R 2-2 、R 3-1 , and R 3-2 Each independently is C 1-6 of alkyl.

[0013] The present invention provides an arylsulfonium salt photoinitiator as shown in (I), wherein:

[0014] R3 is optionally replaced by R 3-1Substituted C 6-10 The aryl group or optionally replaced by R 3-2 Substituted C 5-10 Heteroaryl; the heteroatom species in the heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3.

[0015] R2 is optionally replaced by R 2-1 Substituted C 1-6 or optionally replaced by R 2-2 Substituted C 3-10 Substituted cycloalkyl.

[0016] R 3-1 、R 3-2 、R 2-1 and R 2-2 Each independently is C 1-6 of alkyl.

[0017] In the present invention, R3 is C 5-10 Heteroaryl.

[0018] In the present invention, R3 is furyl; preferably .

[0019] In the present invention, R2 is C 1-3 Alkyl, for example methyl, ethyl, n-propyl or isopropyl.

[0020] In the present invention, R2 is methyl.

[0021] In the present invention, R 3-1 、R 3-2 、R 2-1 and R 2-2 Each is independently methyl, ethyl, n-propyl, isopropyl, n-butyl or tert-butyl; preferably methyl.

[0022] In the present invention, preferably, the arylsulfonium salt photoinitiator as shown in (I) is .

[0023] In the present invention, the arylsulfonium salt photoinitiator shown in (I) has the following structure: 、 or .

[0024] The present invention also provides a method for preparing an arylsulfonium salt photoinitiator as shown in (I), which comprises the following steps: reacting the compound as shown in (II) with methyl trifluoromethanesulfonate under alkaline conditions to obtain, , wherein R2 and R3 are as defined above.

[0025] The present invention also provides a use of the arylsulfonium salt photoinitiator shown in (I) as a photocatalyst in a polymerization reaction.

[0026] The present invention also provides a use of the arylsulfonium salt photoinitiator shown in (I) in preparing a hydrogel.

[0027] In the present invention, the hydrogel is poly (N-acryloylglycine) hydrogel.

[0028] The present invention also provides an intermediate compound having the following structure: 、 or .

[0029] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0030] The reagents and raw materials used in the present invention are commercially available.

[0031] The positive progress of the present invention lies in: providing an arylsulfonium salt photoinitiator with visible light absorption characteristics, which has excellent visible light absorption characteristics and can efficiently initiate the polymerization reaction of N-acryloylglycine in the visible light region (440-450 nm LED light source) to prepare hydrogel materials in situ; therefore, the photoinitiator can reduce the damage of high-energy light to biological tissues, improve the safety of applications in the biomedical field, and is particularly suitable for the in situ preparation of hydrogel materials in fields such as wound dressings and tissue engineering. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is the UV-visible absorption spectrum of the sulfonium salt 1 photoinitiator in Example 1.

[0033] Figure 2 This is the UV-visible absorption spectrum of the sulfonium salt 2 photoinitiator of Example 2.

[0034] Figure 3 This is the NMR spectrum of the sulfonium salt 1 photoinitiator in Example 1.

[0035] Figure 4 This is the NMR spectrum of the sulfonium salt 2 photoinitiator in Example 2. DETAILED DESCRIPTION

[0036] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional conditions, methods and conditions, or selected according to the product specifications.

[0037] Example 1: Synthesis of Intermediate 1:

[0038] Under nitrogen, bis(tri(2-methylphenyl)phosphine)palladium (100 mg), 1,1'-bis(diphenylphosphinoferrocene) (200 mg), 4-bromotriphenylamine (5.0 g, 15.42 mmol), and sodium tert-butoxide (3.70 g, 46.26 mmol) were added to a reaction flask. 1,4-dioxane (200 mL) was then added. Hydrazine hydrate solution (80% by mass, 1.85 g, 46.26 mmol) was then added. Reflux the mixture for 4 hours. The solution was cooled, filtered through a short celite column, and the eluate was concentrated to obtain the crude product. The crude product was diluted with ethyl acetate (100 mL), washed with water (60 mL) and saturated brine (60 mL) in that order, and the organic phase was dried over anhydrous sodium sulfate, filtered and concentrated, and separated and purified by column chromatography (ethyl acetate / methanol, volume ratio 99:1) to obtain intermediate 1 (2.89 g, yield: 68.1%); its mass spectrum was [M+H] + (m / z) = 276.1.

[0039] Synthesis of intermediate 2:

[0040] 2-Acetylfuran (5.0 g, 45.41 mmol), 4-(methylmercapto)benzaldehyde (6.91 g, 45.41 mmol), and 200 mL of anhydrous ethanol were added to a three-necked flask and stirred at room temperature until dissolved. Then, a NaOH solution (5.0 g, 5 mL) was slowly added dropwise to the three-necked flask via a constant pressure addition funnel. The reaction was allowed to react at 60°C for 10 hours. After completion of the reaction, the reaction solution was filtered and the filtrate was concentrated to 20 mL to precipitate a solid, which was then filtered. The resulting solid was washed once with water (10 mL) and then with anhydrous ethanol (10 mL x 2), then dried and recrystallized from anhydrous ethanol to obtain intermediate 2 (9.89 g, 89.2% yield) as a pale yellow solid. Its mass spectrum was [M+H] + (m / z) = 245.0.

[0041] Synthesis of intermediate 3:

[0042] In a 250 mL three-necked flask, sodium hydroxide (2 g) and 150 mL of anhydrous ethanol were mixed and stirred to dissolve. Then, intermediate 1 (2.25 g, 8.19 mmol) was added and refluxed for 15 minutes. Intermediate 2 (2.0 g, 8.19 mmol) was then added in batches while refluxed and added over 10-15 minutes. The reaction was refluxed for 8 hours. After the reaction was completed, it was cooled to room temperature and a large amount of solid precipitated and filtered. The obtained solid was washed with 95% ethanol (10 mL × 2) and recrystallized with anhydrous ethanol / ethyl acetate mixed solvent to obtain yellow solid intermediate 3 (3.6 g, yield: 87.7%); its mass spectrum was [M+H] + (m / z) = 502.2.

[0043] 1 H NMR (400 MHz, CDCl3) δ 7.75 (t, 1H), 7.33–7.17 (m, 6H), 7.19-7.17(m, 2H), 7.17–7.07 (m, 8H), 7.16–7.01 (m, 1H), 7.06–7.00 (m, 1H), 7.03–6.94(m, 1H), 6.60 (dd, 1H), 5.38 (t, 1H), 3.65 (dd, 1H), 3.38 (dd, 1H), 2.44 (s,3H).

[0044] Synthesis of sulfonium salt photoinitiator 1:

[0045] Under nitrogen, intermediate 3 (1.0 g, 1.99 mmol) and 40 mL of dichloromethane were added to a 100 mL three-necked flask. After stirring to dissolve, cesium carbonate (5 g) was added. Methyl trifluoromethanesulfonate (3.93 g, 23.92 mmol) was then slowly added in the dark. The reaction was stirred at room temperature for 12 hours in the dark, with nitrogen bubbling to remove oxygen from the reaction system. After the reaction, the organic solvent was removed by rotary evaporation. The crude product was purified by recrystallization from an acetone / petroleum ether mixture to obtain the sulfonium salt I photoinitiator (1.03 g, 77.7% yield); its HRMS value was [M-CF3SO3]. + (m / z) =516.2110, calculated value (516.2104). Its H NMR spectrum is as follows Figure 3 shown.

[0046] 1H NMR (400 MHz, CDCl3) δ 7.97–7.90 (m, 2H), 7.79 (t, 1H), 7.37 (d,2H), 7.33–7.24 (m, 6H), 7.17–7.11 (m, 2H), 7.11–7.06 (m, 6H), 7.00–6.94 (m,1H), 6.60 (dd, 1H), 5.41 (t, 1H), 3.62 (dd, 1H), 3.36 (dd, 1H), 3.33 (s, 6H).

[0047] Example 2: Synthesis of sulfonium salt photoinitiator 2.

[0048] Referring to the synthesis method of intermediate 2, the only difference is that 4-(methylmercapto)benzaldehyde in intermediate 2 is replaced by 3-(methylmercapto)benzaldehyde, and the other steps remain unchanged; intermediate 3 is prepared , its mass spectrum is [M+H] + (m / z) = 245.1.

[0049]

[0050] The synthesis of sulfonium photoinitiator 2 is similar to that of sulfonium photoinitiator 1, except that 4-(methylmercapto)benzaldehyde in intermediate 2 is replaced by 3-(methylmercapto)benzaldehyde. The remaining steps remain unchanged. The product, sulfonium photoinitiator 2, is yellow crystals; its HRMS value is [M-CF3SO3] + (m / z) = 516.2108, calculated value (516.2104). Its H NMR spectrum is as follows Figure 4 shown.

[0051] 1 H NMR (400 MHz, CDCl3) δ 8.09 (dt, 1H), 7.84 (t, 1H), 7.71 (t, 1H), 7.61 (t, 1H), 7.39 (dt, 1H), 7.30–7.22 (m, 6H), 7.15–7.06 (m, 6H), 7.06–7.02(m, 2H), , 7.02–6.96 (m, 1H), 6.60 (dd, 1H), 5.29 (t, 1H), 3.60 (dd, 1H), 3.39 (dd, 1H), 3.31 (s, 6H).

[0052] Effect Example 1: Determination of UV-visible absorption wavelength.

[0053] The sulfonium salt photoinitiator 1 of Example 1 and the sulfonium salt photoinitiator 2 of Example 2 were prepared in acetonitrile at 5×10 -5 mol / L dilute solution, and tested its UV-visible absorption spectrum data, respectively as follows Figure 1 and Figure 2 shown.

[0054] It can be seen that the maximum absorption wavelengths of sulfonium salt photoinitiator 1 and sulfonium salt photoinitiator 2 in the low energy region are 445 nm and 442 nm, respectively. Therefore, a blue light band LED light source can be used to realize the photoinitiation reaction.

[0055] Effect Example 2: Preparation of poly (N-acryloylglycine) hydrogel by photopolymerization.

[0056] Preparation of hydrogel samples I, II, and III: 10 g of N-acryloylglycine monomer and 1 g of sulfonium salt photoinitiator 1 were dissolved in 90 mL of deionized water to obtain a mixed solution of N-acryloylglycine monomer and photoinitiator. Under nitrogen protection, the solution was stirred using a mechanical stirrer for 10-15 minutes until the solution was clear and transparent. Subsequently, the solution was placed in an ultrasonic cleaner and sonicated at room temperature for 3 minutes to ensure that the photoinitiator and monomer were fully and evenly dissolved. The prepared solution was then injected into a 50 mm × 50 mm × 1 mm square mold. The mold was then placed under a 450 nm wavelength LED light source for photocuring. The light intensity was set to 50 mW / cm² and the exposure time was 20 minutes. After the light irradiation was completed, the mold was removed and cooled at room temperature for 5-10 minutes to obtain the cured hydrogel sample I.

[0057] The same method was used to prepare hydrogel sample II by using sulfonium salt photoinitiator 2 instead of sulfonium salt photoinitiator 1.

[0058] Using the same method, the commercially available initiator 1173 (2-hydroxy-2-methyl-1-phenyl-1-propanone, with a maximum absorption wavelength of 331 nm) was used instead of the sulfonium salt photoinitiator 1, but hydrogel could not be successfully prepared. Furthermore, the light source was replaced with UV-LED (275 nm) to prepare hydrogel sample III.

[0059] Performance testing of hydrogel samples I, II and III

[0060] The mechanical properties of hydrogel samples I, II, and III were tested according to the test methods of national standards GB / T 1040 and GB / T 528. Tensile specimens were prepared using a dumbbell cutter and subjected to tensile testing using an electronic universal testing machine at a rate of 50 mm / min. The tests determined the tensile strength, tensile strength at break, and elongation at break of the hydrogels.

[0061] Table 1 Mechanical test data of hydrogel samples I-III:

[0062]

[0063] As shown in Table 1. The tensile strength and tensile strength at break of hydrogel samples I and II were both between 2.35 and 2.53 MPa, demonstrating excellent tensile strength. The elongation at break exceeded 1200%, demonstrating excellent ductility. However, the mechanical properties of hydrogel sample III were far lower than those of the first two samples. This was attributed to the fact that the sample was prepared using the commonly used commercial photoinitiator 1173, which has insufficient absorption of visible light, resulting in poor polymerization and insufficient mechanical properties of the resulting hydrogel. The above tests demonstrate that the sulfonium salt photoinitiator prepared by the present invention was successfully used to prepare a hydrogel material by photoinitiated polymerization under the excitation of an LED light source (wavelength of 450 nm) in the visible light band.

[0064] The sulfonium salt photoinitiator prepared in this invention absorbs light in the visible range and can therefore be excited by light sources within the visible range, acting as a visible light initiator. The photoinitiated polymerization reaction under a 450 nm LED light source allows the preparation of hydrogel materials, which has potential applications in the in-situ preparation of biomedical materials.

Claims

1. An arylsulfonium salt photoinitiator, characterized in that The arylsulfonium salt photoinitiator is selected from: or .

2. Use of the arylsulfonium salt photoinitiator according to claim 1 in preparing a hydrogel.

3. An intermediate compound of an arylsulfonium salt photoinitiator having the following structure: or .

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