Aryl sulfonium salt photoinitiator as well as preparation method and application thereof

Abstract

The invention provides an aryl sulfonium salt photoinitiator as well as a preparation method and application thereof. The invention discloses an aryl sulfonium salt photoinitiator as shown in (I). The initiator has an excellent visible light absorption characteristic, and can efficiently initiate a polymerization reaction of N-acryloylglycine in a visible light region (an LED light source of 440-450 nm) to prepare a hydrogel material in situ; therefore, the photoinitiator can reduce the damage of high-energy light to biological tissues, improves the application safety in the field of biomedicine, and is particularly suitable for in-situ preparation of hydrogel materials in the fields of wound dressing, tissue engineering and the like. # imgabs0 #

Description

Technical Field

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

[0002] In recent years, with the continuous development of biomedical technologies, hydrogel materials with excellent biocompatibility and degradability have shown broad application prospects in the fields of drug delivery, wound dressings, tissue engineering, etc. In particular, the potential of hydrogel materials in tissue repair and regeneration has attracted the attention of a large number of researchers. To meet the requirements of these fields, photoinitiators with excellent photopolymerization performance have become important tools for preparing hydrogels. Traditional photoinitiators mostly rely on ultraviolet light or deep ultraviolet light (UV) excitation, and such light sources often cause great damage to biological tissues. Therefore, how to develop photoinitiators with good absorption and initiation efficiency in the visible light region has become one of the current research hotspots.

[0003] As a kind of high-performance photoinitiator, arylsulfonium salt photoinitiators have received increasing attention in recent years. Such photoinitiators have high photoinitiation efficiency and can effectively control the progress of polymerization reactions, showing significant advantages. However, most of the existing arylsulfonium salt photoinitiators have problems such as a narrow absorption range and insufficient absorption in the visible light region, which limit their application in the field of biomedical tissue engineering materials. For example, the domestic invention patent CN107129487A reports a class of LED-excitable sulfonium salts with thioxanthone as the conjugated structure, but the maximum absorption wavelength in the long wavelength band is 385 nm, which does not reach the visible light region.

[0004] In view of the above problems, the present invention provides a new arylsulfonium salt photoinitiator, which has good absorption characteristics in the visible light region and can efficiently initiate the polymerization reaction of N-acryloylglycine (NAG) hydrogel under visible light irradiation. The application of this new type of photoinitiator can not only achieve the efficient preparation of hydrogels under low-energy visible light, avoiding the possible damage to biological tissues caused by ultraviolet light, but also provide a safer and more reliable material preparation scheme 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, and has important scientific value and application potential. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to overcome the defect that existing photoinitiators are usually excited by ultraviolet light, and to provide an arylsulfonium salt photoinitiator, a preparation method thereof and an application thereof. This photoinitiator has excellent visible light absorption characteristics and can efficiently initiate the polymerization of N-acryloylglycine in the visible light region (LED light source of 440 - 450 nm) to in-situ prepare a hydrogel material; therefore, this photoinitiator can reduce the damage of high-energy light to biological tissues and 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.

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

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

[0008] R1 is an optionally R 1-1 substituted C 1-6 alkyl or an optionally R 1-2 substituted C 3-10 substituted cycloalkyl.

[0009] R2 is an optionally R 2-1 substituted C 1-6 alkyl or an optionally R 2-2 substituted C 3-10 substituted cycloalkyl.

[0010] R3 is an optionally R 3-1 substituted C 6-10 aryl or an optionally R 3-2 substituted C 5-10 heteroaryl, wherein the types of heteroatoms in the heteroaryl are 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 are each independently C 1-6 alkyl.

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

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

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

[0016] R 3-1 、R 3-2 、R 2-1 and R 2-2 are each independently C 1-6 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, such as 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 are each 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 as shown in (I) has the following structure: , or .

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

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

[0026] The present invention also provides an application of the above arylsulfonium salt photoinitiator shown in (I) in the preparation of hydrogels.

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

[0028] The present invention also provides an intermediate compound, which has the following structure: 、 or 。

[0029] On the basis of not violating the common knowledge in the art, the above preferred conditions can be combined arbitrarily to obtain the preferred examples of the present invention.

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

[0031] The positive and progressive effects of the present invention are as follows: an arylsulfonium salt photoinitiator with visible light absorption characteristics is provided, which has excellent visible light absorption characteristics and can efficiently initiate the polymerization reaction of N-acryloylglycine in the visible light region (LED light source of 440 - 450 nm) to in-situ prepare a hydrogel material; therefore, this 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 It is the ultraviolet-visible absorption spectrum diagram of the sulfonium salt 1 photoinitiator in Example 1.

[0033] Figure 2 It is the ultraviolet-visible absorption spectrum diagram of the sulfonium salt 2 photoinitiator in Example 2.

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

[0035] Figure 4 It is the NMR spectrum diagram of the sulfonium salt 2 photoinitiator in Example 2. DETAILED DESCRIPTION OF THE INVENTION

[0036] The present invention will be further illustrated by the following examples, but the present invention is not limited to the scope of the described examples. The experimental methods without specific conditions in the following examples are carried out according to the conventional conditions and methods, or selected according to the product specifications.

[0037] Example 1: Synthesis of Intermediate 1:

[0038] Under nitrogen protection, bis[tris(2-tolyl)phosphine]palladium (100 mg), 1,1'-bis(diphenylphosphino)ferrocene (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, and 1,4-dioxane (200 mL) was added; then a hydrazine hydrate solution (80% by mass, 1.85 g, 46.26 mmol) was added. The reaction was refluxed for 4 hours. The solution was cooled and filtered through a short diatomaceous earth chromatography column, and the eluate was concentrated to obtain the crude product. The crude product was diluted with ethyl acetate (100 mL), washed successively with water (60 mL) and saturated brine (60 mL), the organic phase was dried over anhydrous sodium sulfate, filtered and concentrated, 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] In a three-necked flask, 2-acetylfuran (5.0 g, 45.41 mmol), 4-(methylthio)benzaldehyde (6.91 g, 45.41 mmol) and 200 mL of absolute ethanol were added, stirred until dissolved at room temperature, and then a NaOH solution (5.0 g, 5 mL) was slowly added dropwise to the three-necked flask through a constant pressure dropping funnel, and the reaction was carried out at 60 °C for 10 hours. After the reaction was completed, the reaction solution was filtered and the filtrate was concentrated to 20 mL to precipitate a solid, and the precipitated solid was filtered. The obtained solid was washed once with water (10 mL), then washed with absolute ethanol (10 mL×2), and then dried, and finally recrystallized from absolute ethanol to obtain a pale yellow solid Intermediate 2 (9.89 g, yield: 89.2%); 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 absolute ethanol were mixed and stirred until dissolved. Then, intermediate 1 (2.25 g, 8.19 mmol) was added and refluxed for 15 minutes. Subsequently, intermediate 2 (2.0 g, 8.19 mmol) was added portionwise while refluxing, and the addition was completed within 10 - 15 minutes. The reflux reaction was carried out for 8 hours. After the reaction was completed, it was cooled to room temperature, and a large amount of solid precipitated. The solid was filtered. The obtained solid was washed with 95% ethanol (10 mL × 2), and recrystallized with an absolute 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 1H 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 protection, intermediate 3 (1.0 g, 1.99 mmol) and 40 mL of dichloromethane were added to a 100 mL three-necked flask. After stirring until dissolved, cesium carbonate (5 g) was added. Then, methyl trifluoromethanesulfonate (3.93 g, 23.92 mmol) was slowly added under light protection, and stirred at room temperature in the dark for 12 hours. During the reaction, nitrogen bubbling was used to remove oxygen in the reaction system. After the reaction was completed, the organic solvent was removed by rotary evaporation. The obtained crude product was purified by recrystallization with an acetone / petroleum ether mixed solvent to obtain product sulfonium salt I photoinitiator (1.03 g, yield: 77.7%); the measured value of its HRMS was [M-CF3SO3] + (m / z) =516.2110, and the calculated value was (516.2104). Its 1H NMR spectrum was as follows Figure 3 shown.

[0046] 11H 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 difference is only that 4-(methylthio)benzaldehyde in Intermediate 2 is replaced by 3-(methylthio)benzaldehyde, and the remaining steps remain unchanged; Intermediate 3 is prepared. , and its mass spectrum is [M+H] + (m / z) = 245.1.

[0049]

[0050] The synthesis method of sulfonium salt photoinitiator 2 is similar to that of sulfonium salt photoinitiator 1, the difference is that 4-(methylthio)benzaldehyde in Intermediate 2 is replaced by 3-(methylthio)benzaldehyde, and the remaining steps remain unchanged. The product sulfonium salt photoinitiator 2 is a yellow crystal; the measured value of its HRMS is [M-CF3SO3] + (m / z) = 516.2108, calculated value (516.2104). Its 1H NMR spectrum is as Figure 4 shown.

[0051] 1 1H 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 ultraviolet-visible absorption wavelength.

[0053] The sulfonium salt photoinitiator 1 of Example 1 and the sulfonium salt photoinitiator 2 of Example 2 were respectively prepared into 5×10 -5 mol / L dilute solutions in acetonitrile, and their ultraviolet-visible absorption spectral data were tested, as shown in Figure 1 and Figure 2 respectively.

[0054] It can be seen that the maximum absorption wavelengths of the sulfonium salt photoinitiator 1 and the sulfonium salt photoinitiator 2 in the low-energy region are 445 nm and 442 nm respectively. Therefore, an LED light source in the blue light band can be used to initiate the photopolymerization 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 with a mechanical stirrer for 10 - 15 minutes until the solution was clear and transparent. Subsequently, the solution was placed in an ultrasonic cleaner and ultrasonically treated at room temperature for 3 minutes to ensure that the photoinitiator and monomer were fully and uniformly dissolved. Then, the prepared solution was injected into a 50 mm×50 mm×1 mm square mold. Then, the mold was placed under an LED light source with a wavelength of 450 nm for photocuring, the light intensity was set at 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] Using the same method, hydrogel sample II was prepared by replacing the sulfonium salt photoinitiator 1 with the sulfonium salt photoinitiator 2.

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

[0059] Performance testing of hydrogel samples I, II and III Combined with the test methods of national standards GB / T 1040 and GB / T 528, the mechanical properties of hydrogel samples I, II and III were respectively tested. A dumbbell-shaped cutter was used to prepare the tensile samples, and an electronic universal testing machine was used for tensile testing, with a tensile rate of 50 mm / min. The tensile strength, breaking tensile strength and elongation at break of the hydrogel were tested.

[0060] Table 1 Mechanical test data of hydrogel samples I - III:

[0061] As shown in Table 1. The tensile strength and the tensile strength at break of hydrogel samples I and II are both between 2.35 - 2.53 Mpa, showing excellent tensile resistance. The elongation at break exceeds 1200%, showing excellent ductility. However, the mechanical properties of hydrogel sample III are much lower than those of the first two samples. The reason is that this sample is prepared from the commercially available common photoinitiator 1173, and the photoinitiator 1173 has insufficient absorption in the visible light band, resulting in poor polymerization effect and insufficient mechanical properties of the obtained hydrogel. The above tests prove that the sulfonium salt photoinitiator prepared by the present invention successfully realizes photoinitiated polymerization reaction to prepare hydrogel materials under the excitation of a LED light source (wavelength 450 nm) in the visible light band.

[0062] The sulfonium salt photoinitiator prepared by the present invention has absorption in the visible light band, so it can be excited under a light source in the visible light band and used as a visible light photoinitiator. The realization of photoinitiated polymerization reaction to prepare hydrogel materials under a LED light source with a wavelength of 450 nm has application potential in the in-situ preparation of biomedical materials.

Claims

1. An arylsulfonium salt photoinitiator as shown in (I), wherein: , R3 is an optionally R 3-1 -substituted C 6-10 aryl or an optionally 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; R2 is an optionally R 2-1 -substituted C 1-6 alkyl or an optionally R 2-2 -substituted C 3-10 substituted cycloalkyl; R 3-1 , R 3-2 , R 2-1 and R 2-2 are each independently C 1-6 alkyl.

2. The arylsulfonium salt photoinitiator as shown in (I) according to claim 1, characterized in that, R3 is C 5-10 heteroaryl.

3. The arylsulfonium salt photoinitiator as shown in (I) according to claim 1, characterized in that, R3 is .

4. The arylsulfonium salt photoinitiator as shown in (I) according to claim 1, characterized in that, R2 is methyl, ethyl, n-propyl or isopropyl.

5. The arylsulfonium salt photoinitiator as shown in (I) according to claim 1, characterized in that, R 3-1 、R 3-2 、R 2-1 and R 2 -2 are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl or tert-butyl.

6. The arylsulfonium salt photoinitiator as shown in (I) according to any one of claims 1-5, characterized in that, The arylsulfonium salt photoinitiator as shown in (I) is .

7. The arylsulfonium salt photoinitiator as shown in (I) according to claim 1, characterized in that, The arylsulfonium salt photoinitiator as shown in (I) is selected from: , or .

8. A preparation method of an arylsulfonium salt photoinitiator as shown in (I), characterized in that, It comprises the following steps: under alkaline conditions, reacting the compound shown in (II) with methyl trifluoromethanesulfonate to obtain, , wherein R2 and R3 are as defined in claim 1.

9. Use of an arylsulfonium salt photoinitiator as shown in (I) according to any one of claims 1-7 as a photocatalyst in a polymerization reaction.

10. An intermediate compound having the following structure: , or .

Images