A method for preparing 2-arylbenzothiophene sulfone by using oxidative Suzuki coupling reaction

Abstract

The present invention provides a method for preparing 2-arylbenzothiophene sulfone by using an oxidative Suzuki coupling reaction. This preparation method uses benzothiophene sulfone compounds and arylboronic acids as raw materials. In the presence of a palladium catalyst and an oxidant, an organic base is simultaneously added to activate the arylboronic acid. Through an oxidative Suzuki coupling reaction based on C-H bond activation in an organic solvent, 2-arylbenzothiophene sulfone compounds are obtained. These compounds have obvious aggregation-induced emission characteristics. The preparation method of the present invention is simple to operate, has good atom and step economy, excellent regioselectivity, and greatly expands the substrate scope.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing 2-arylbenzothiophene sulfone by using an oxidative Suzuki coupling reaction. Background Art

[0002] Aggregation-induced emission (AIE) materials can effectively inhibit fluorescence quenching caused by aggregation, and show great application value in frontier fields such as optoelectronic devices, chemical sensors, bioimaging and tracing, bacterial discrimination, industrial pollution monitoring, and food quality monitoring. In 2001, the group of Benzhong Tang first proposed the concept of aggregation-induced emission when studying the luminescence behavior of 1-methyl-1,2,3,4,5-pentaphenylsilole, and confirmed the working mechanism of "restriction of intramolecular motion" through a large number of experiments and theoretical calculations, laying the theoretical foundation for AIE research. Due to the poor planarity and large polarity of the thiophene sulfone ring, aryl-substituted benzothiophene sulfone can effectively reduce the intermolecular interaction, show good aggregation-induced emission characteristics, and have important research value.

[0003] Currently, the reported aryl-substituted benzothiophene sulfones are mainly synthesized from benzothiophene as the starting material, successively through bromination, oxidation, and Suzuki coupling reaction.

[0004] The synthesis methods of the reported aryl-substituted benzothiophene sulfone compounds are as follows:

[0005]

[0006] Among them, as the key synthesis step, the Suzuki coupling is based on the cleavage activation of C-Br / C-B bonds, requires a pre-prepared halogenated substrate, and generates halogen-containing waste, having problems such as limited substrate scope and poor environmental friendliness.

[0007] Therefore, it is of great significance to design a more general, concise, and efficient method for synthesizing aryl-substituted benzothiophene sulfone-based aggregation-induced emission material molecules. Summary of the Invention

[0008] To solve the problems existing in the prior art, the present invention provides a method for preparing 2-arylbenzothiophene sulfone by using an oxidative Suzuki coupling reaction. The reaction process of this preparation method is realized through a C-H / C-B bond oxidative coupling reaction based on C-H bond activation, with simple operation and high selectivity of the target product. The prepared 2-arylbenzothiophene sulfone has obvious aggregation-induced emission characteristics and can be used as an aggregation-induced emission material.

[0009] Based on the oxidative Suzuki coupling reaction strategy of C-H bond activation, the present invention designs the following reaction:

[0010] Dissolve the benzothiophene sulfone compound, arylboronic acid, oxidant and organic base in an organic solvent, and carry out a reaction in the presence of a palladium catalyst to obtain 2-arylbenzothiophene sulfone, and its photophysical properties are preliminarily characterized. The results show that the material prepared by the above preparation method exhibits obvious aggregation-induced emission characteristics. Compared with the reported palladium-catalyzed C-Br / C-B bond coupling reaction, the preparation method of the present invention has the advantages of good atomic and step economy, simple operation, environmental friendliness and high selectivity.

[0011] A method for preparing 2-arylbenzothiophene sulfone by using an oxidative Suzuki coupling reaction, comprising:

[0012] In the presence of a palladium catalyst, an oxidative Suzuki coupling reaction occurs between the benzothiophene sulfone compound, arylboronic acid, oxidant and organic base in an organic solvent. After the reaction is completed, post-treatment is carried out to obtain the 2-arylbenzothiophene sulfone;

[0013] Among them, the structural formula of the benzothiophene sulfone compound is shown in formula (I):

[0014]

[0015] The structural formula of the arylboronic acid is shown in formula (II):

[0016]

[0017] The structural formula of 2-arylbenzothiophene sulfone is shown in formula (III):

[0018]

[0019] In formulas (I) to (III), R 1 is one of H, alkyl, methoxy, ester group, phenyl, cyano; m = 1 to 4; when m ≠ 1, multiple R 1 are each independently selected from one of H, alkyl, methoxy, ester group, phenyl, cyano;

[0020] R 2 is one of H, methyl, phenyl;

[0021] R 3 is one of H, alkyl, alkoxy, fluorine atom, trifluoromethyl, cyano, ester group, acyl group, aryl; n = 1 to 5; when n ≠ 1, multiple R 3 are each independently selected from one of H, alkyl, alkoxy, fluorine atom, trifluoromethyl, cyano, ester group, acyl group, aryl.

[0022] Among them, (R 1 ) m , (R 3 )n Each represents one or more substituents on the benzene ring.

[0023] Preferably, R 1 is one of H, C1-C3 alkyl, methoxy, C1-C3 ester group, phenyl, and cyano. More preferably, it is H.

[0024] Preferably, R 3 is one of H, C1-C3 alkyl, C1-C3 alkoxy, fluorine atom, trifluoromethyl, cyano, C1-C3 ester group, C1-C3 acyl group, C6-C8 aryl, and diphenylamino. More preferably, it is one of H and diphenylamino.

[0025] Preferably, R 2 is one of H and phenyl.

[0026] Preferably, the molar ratio of the benzothiophene sulfone compound to the arylboronic acid is 1:(1-5). More preferably, it is 1:(2-4). Even more preferably, it is 1:(2.5-3.5). As a further preferred embodiment, the molar ratio of the benzothiophene sulfone compound to the arylboronic acid is 1:3.

[0027] Preferably, the oxidant is one or more of copper acetate (Cu(OAc)2), copper trifluoromethanesulfonate, copper bromide, and copper acetylacetonate. More preferably, it is copper acetate (Cu(OAc)2).

[0028] Preferably, the molar ratio of the benzothiophene sulfone compound to the oxidant is 1:(1-6). More preferably, it is 1:(3-5). Even more preferably, it is 1:(3.5-4.5). As a further preferred embodiment, the molar ratio of the benzothiophene sulfone compound to the oxidant is 1:4.

[0029] Preferably, the organic base is one or more of pyridine (Py), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and N,N-diisopropylethylamine (DIPEA). More preferably, it is pyridine (Py). The organic base is used to activate the arylboronic acid.

[0030] Preferably, the molar ratio of the benzothiophene sulfone compound to the organic base is 1:(1.5-4). More preferably, it is 1:(2.5-3.5). As a further preferred embodiment, the molar ratio of the benzothiophene sulfone compound to the organic base is 1:3.

[0031] Preferably, the molar ratio of the benzothiophene sulfone compound, the arylboronic acid, the oxidant, and the organic base is 1:3:4:3.

[0032] Preferably, the organic solvent is at least one of toluene, 1,2-dichloroethane, 1,4-dioxane, DMSO (dimethyl sulfoxide), and N,N-dimethylformamide. More preferably, it is DMSO (dimethyl sulfoxide).

[0033] Preferably, the palladium catalyst is Pd(OAc)2 (CAS: 3375 - 31 - 3). This catalyst has the advantages of high activity and strong generality in the reaction process of the present invention.

[0034] Preferably, the dosage of the palladium catalyst is 5 - 15 mol% of the dosage of the benzothiophene sulfone compound. More preferably, it is 8 - 12 mol%. Even more preferably, it is 10 mol%.

[0035] Preferably, the reaction temperature of the oxidative Suzuki coupling reaction is 80 - 120 °C. More preferably, it is 100 °C.

[0036] Preferably, the reaction time of the oxidative Suzuki coupling reaction is 15 - 30 h. More preferably, it is 18 - 23 h.

[0037] Preferably, the oxidative Suzuki coupling reaction is carried out under a nitrogen atmosphere.

[0038] Preferably, after the reaction is completed, the following post-treatment is carried out:

[0039] The reaction mixture is passed through a layer of diatomaceous earth and washed with ethyl acetate. The organic phase is extracted with ethyl acetate and water and concentrated under reduced pressure. Using ethyl acetate / petroleum ether (EtOAc / petroleum ether) as the eluent, the concentrate is purified by silica gel column chromatography to obtain the 2-arylbenzothiophene sulfone.

[0040] Preferably, in the eluent, the volume ratio (v / v) of EtOAc to petroleum ether is 1:(2 - 5).

[0041] Taking Pd(OAc)2 as the palladium catalyst, Cu(OAc)2 as the oxidant, Py (pyridine) as the organic base, and DMSO (dimethyl sulfoxide) as the solvent in the preparation method of the present invention as an example, the reaction formula of the oxidative Suzuki coupling reaction based on C-H activation is specifically as follows:

[0042]

[0043] Taking R 1 、R 2 、R 3 all being H as an example, the reaction mechanism of the above reaction is as follows:

[0044]

[0045] In the reaction, benzo[b]thiophene sulfone and divalent Pd(OAc)2 undergo C-H bond activation to obtain metal intermediate A; then, the complex formed by phenylboronic acid and pyridine is inserted into Pd through transmetalation to generate intermediate B; B undergoes a reductive elimination process to obtain the 2-phenylbenzo[b]thiophene sulfone product, while releasing zero-valent palladium (Pd 0 ) species. The Pd 0 species is oxidized by the Cu(OAc)2 oxidant to an active divalent palladium catalyst, completing the reaction cycle.

[0046] The method for preparing 2-arylbenzo[b]thiophene sulfone by oxidative Suzuki coupling reaction of the present invention uses benzo[b]thiophene sulfone compounds and arylboronic acids as raw materials. In the presence of a palladium catalyst and an oxidant, an organic base is added simultaneously to activate the arylboronic acid, and 2-arylbenzo[b]thiophene sulfone compounds shown in formula (III) are obtained through an oxidative Suzuki coupling reaction based on C-H bond activation in an organic solvent. These compounds have obvious aggregation-induced emission characteristics.

[0047] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0048] The method for preparing 2-arylbenzo[b]thiophene sulfone by oxidative Suzuki coupling reaction of the present invention uses benzo[b]thiophene sulfone compounds as reactants, forms a metal intermediate with palladium acetate of a transition metal through a C-H bond activation strategy, and then sequentially undergoes transmetalation and reductive elimination processes with arylboronic acids to finally obtain 2-arylbenzo[b]thiophene sulfone compounds; this preparation method has good atomic and step economy, excellent regioselectivity, greatly expands the substrate scope, and has mild reaction conditions and simple operation, laying a solid foundation for further screening aggregation-induced emission materials with red emission characteristics. Brief Description of the Drawings

[0049] Figure 1 1H NMR spectrum of product 3a prepared in Example 1; 1

[0050] Figure 2 13C NMR spectrum of product 3a prepared in Example 1; 13

[0051] Figure 3 1H NMR spectrum of product 3b prepared in Example 2; 1

[0052] Figure 4 13C NMR spectrum of product 3b prepared in Example 2; 13

[0053] Figure 5 ​​​​For the product 3c prepared in Example 3 1 1H NMR spectrum;

[0054] Figure 6 For the product 3c prepared in Example 3 13 13C NMR spectrum;

[0055] Figure 7 For the product 3d prepared in Example 4 1 1H NMR spectrum;

[0056] Figure 8 For the product 3d prepared in Example 4 13 13C NMR spectrum;

[0057] Figure 9 Fluorescence intensity test curves of the product 3b prepared in Example 2 and the product 3d prepared in Example 4. Specific embodiments

[0058]

[0059] Accurately add benzothiophene sulfone 1 (0.2 mmol, 1.0 equiv), arylboronic acid 2 (0.6 mmol, 3.0 equiv), Cu(OAc)2 (145 mg, 0.8 mmol, 4.0 equiv), Py (49 μL, 0.6 mmol, 3.0 equiv) and Pd(OAc)2 (4.4 mg, 10 mol%) into a reaction tube, which are dissolved in 1.0 mL of DMSO; the mixture is reacted at 100 °C for 20 hours. The reaction mixture is passed through a layer of diatomaceous earth and washed with ethyl acetate, and the organic phase is extracted with ethyl acetate and water and concentrated under reduced pressure in vacuo. Using ethyl acetate / petroleum ether as the eluent, the concentrate is purified by silica gel column chromatography to obtain the corresponding product 3.

[0060] The present invention will be further described below in conjunction with specific embodiments.

[0061] Example 1

[0062]

[0063] In a reaction tube, 1a (33.2 mg, 0.2 mmol, 1.0 equiv) of benzo[b]thiophene sulfone, 2a (73.2 mg, 0.6 mmol, 3.0 equiv) of phenylboronic acid, Cu(OAc)₂ (145 mg, 0.8 mmol, 4.0 equiv), Py (49 μL, 0.6 mmol, 3.0 equiv) and Pd(OAc)₂ (4.4 mg, 10 mol%) were accurately added and dissolved in 1.0 mL of DMSO; the mixture was reacted at 100 °C for 20 hours.

[0064] After the reaction was completed, the reaction mixture was passed through a layer of diatomaceous earth and washed with ethyl acetate. The organic phase was extracted with ethyl acetate and water and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography using EtOAc / petroleum ether (v / v, 1:3) as the eluent to obtain the corresponding product 3a with a yield of 75%.

[0065] NMR data of product 3a: 1 H NMR (600 MHz, CDCl₃): δ = 7.85 - 7.83 (m, 2H), 7.78 - 7.60 (m, 1H), 7.57 (td, J = 7.8, 1.2 Hz, 1H), 7.51 - 7.44 (m, 4H), 7.41 (d, J = 7.2 Hz, 1H), 7.30 (d, J = 1.2 Hz, 1H) ppm.

[0066] 13 C NMR (151 MHz, CDCl₃): δ = 142.8, 137.2, 133.9, 131.3, 130.5, 130.1, 129.4, 127.3, 126.7, 125.2, 123.8, 121.7 ppm.

[0067] Figure 1 For the product 3a prepared in Example 1 1 H NMR spectrum;

[0068] Figure 2 For the product 3a prepared in Example 1 13 C NMR spectrum.

[0069] Example 2

[0070]

[0071] In a reaction tube, 1a of benzo[b]thiophene sulfone (33.2 mg, 0.2 mmol, 1.0 equiv), 2b of 4-diphenylaminophenylboronic acid (173 mg, 0.6 mmol, 3.0 equiv), Cu(OAc)₂ (145 mg, 0.8 mmol, 4.0 equiv), Py (49 μL, 0.6 mmol, 3.0 equiv) and Pd(OAc)₂ (4.4 mg, 10 mol%) were accurately added and dissolved in 1.0 mL of DMSO; the mixture was reacted at 100 °C for 20 hours.

[0072] After the reaction was completed, the reaction mixture was passed through a layer of diatomaceous earth and washed with ethyl acetate. The organic phase was extracted with ethyl acetate and water and concentrated under reduced pressure. Using EtOAc / petroleum ether (v / v, 1:2) as the eluent, the concentrate was purified by silica gel column chromatography to obtain the corresponding product 3b with a yield of 61%.

[0073] Nuclear magnetic resonance data of product 3b: 1 H NMR (400 MHz, CDCl₃): δ = 7.74 (d, J = 7.6 Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.55 (t, J = 7.6 Hz, 1H), 7.45 (t, J = 7.6 Hz, 1H), 7.36 (d, J = 7.6 Hz, 1H), 7.31 (t, J = 7.6 Hz, 4H), 7.16 - 7.08 (m, 9H) ppm.

[0074] 13 C NMR (101 MHz, CDCl₃): δ = 149.9, 146.9, 142.6, 137.0, 133.8, 131.9, 129.7, 129.4, 127.6, 125.6, 124.7, 124.3, 122.1, 121.6, 120.7, 119.8 ppm.

[0075] Figure 3 For the product 3b prepared in Example 2 1 H NMR spectrum;

[0076] Figure 4 For the product 3b prepared in Example 2 13 C NMR spectrum.

[0077] Example 3

[0078]

[0079] In a reaction tube, accurately add 3-phenylbenzo[b]thiophene 1,1-dioxide 1b (48.4 mg, 0.2 mmol, 1.0 equiv), phenylboronic acid 2a (73.2 mg, 0.6 mmol, 3.0 equiv), Cu(OAc)₂ (145 mg, 0.8 mmol, 4.0 equiv), Py (49 μL, 0.6 mmol, 3.0 equiv) and Pd(OAc)₂ (4.4 mg, 10 mol%) dissolved in 1.0 mL of DMSO; the mixture is reacted at 100 °C for 20 hours.

[0080] After the reaction is completed, the reaction mixture is passed through a layer of diatomaceous earth and washed with ethyl acetate. The organic phase is extracted with ethyl acetate and water and concentrated under reduced pressure in vacuo. Using EtOAc / petroleum ether (v / v, 1:3) as the eluent, the concentrate is purified by silica gel column chromatography to obtain the corresponding product 3c in a yield of 60%.

[0081] The synthesis of benzo[b]thiophene 1,1-dioxide 1b used in this example was referenced from: Liu, G.; Tian, K.; Li, C.; You, C.; Tan, X.; Zhang, H.; Zhang, X.; Dong, X.-Q. Nickel-Catalyzed Asymmetric Hydrogenation of Cyclic Alkenyl Sulfones, Benzo[b]thiophene 1,1-Dioxides, with Mechanistic Studies. Org. Lett. 2021, 23, 668 - 675.

[0082] The nuclear magnetic resonance data of product 3c: 1 ¹H NMR (400 MHz, CDCl₃): δ = 7.88 - 7.84 (m, 1H), 7.57 - 7.52 (m, 2H), 7.50 - 7.43 (m, 5H), 7.36 - 7.27 (m, 6H) ppm.

[0083] 13 ¹³C NMR (101 MHz, CDCl₃): δ = 138.2, 137.6, 136.5, 133.6, 133.4, 131.1, 130.2, 129.8, 129.6, 129.5, 129.3, 129.2, 128.9, 127.2, 124.3, 121.7 ppm.

[0084] Figure 5 For the product 3c prepared in Example 3 1 ¹H NMR spectrum;

[0085] Figure 6For the product 3c prepared in Example 3 13 13C NMR spectrum.

[0086] Example 4

[0087]

[0088] In a reaction tube, accurately add 3-phenylbenzo[b]thiophene sulfone 1b (48.4 mg, 0.2 mmol, 1.0 equiv), 4-(diphenylamino)phenylboronic acid 2b (173 mg, 0.6 mmol, 3.0 equiv), Cu(OAc)2 (145 mg, 0.8 mmol, 4.0 equiv), Py (49 μL, 0.6 mmol, 3.0 equiv) and Pd(OAc)2 (4.4 mg, 10 mol%) dissolved in 1.0 mL of DMSO; the mixture is reacted at 100 °C for 20 h.

[0089] After the reaction is completed, the reaction mixture is passed through a layer of diatomaceous earth and washed with ethyl acetate. The organic phase is extracted with ethyl acetate and water and concentrated under reduced pressure. Using EtOAc / petroleum ether (v / v, 1:3) as the eluent, the concentrate is purified by silica gel column chromatography to obtain the corresponding product 3d with a yield of 65%.

[0090] Nuclear magnetic resonance data of product 3d: 1 1H NMR (400 MHz, CDCl3): δ = 7.84 - 7.82 (m, 1H), 7.51 - 7.44 (m, 5H), 7.38 - 7.31 (m, 4H), 7.29 - 7.25 (m, 4H), 7.21 - 7.19 (m, 1H), 7.11 - 7.05 (m, 6H), 6.88 (d, J = 8.4 Hz, 2H) ppm.

[0091] 13 13C NMR (151 MHz, CDCl3): δ = 149.1, 146.9, 137.4, 136.2, 135.5, 134.0, 133.6, 131.8, 130.0, 129.60, 129.57, 129.4, 129.2, 125.7, 124.2, 123.9, 121.5, 121.2, 119.5 ppm.

[0092] Figure 7 For the product 3d prepared in Example 4 1 1H NMR spectrum;

[0093] Figure 8 For the product 3d prepared in Example 4 13 13C NMR spectrum.

[0094] Fluorescence intensity tests were carried out on the above products 3b and 3d:

[0095] Dissolve product 3b in dichloromethane to prepare solutions with concentrations of 1.2×10 -2 mol / L, 1.2×10 -3 mol / L, 1.2×10 -4 mol / L, 1.2×10 -5 mol / L respectively. Dissolve product 3d in dichloromethane to prepare solutions with concentrations of 1.3×10 - 2 mol / L, 1.3×10 -3 mol / L, 1.3×10 -4 mol / L, 1.3×10 -5 mol / L respectively. Test the fluorescence intensities of products 3b and 3d at different concentrations, and the test results are as follows Figure 9 shown. It can be seen from Figure 9 that in dilute solutions, the fluorescence intensities of 3b and 3d are very weak. As the solution concentration increases, the luminescence intensity increases significantly, which conforms to the typical characteristics of aggregation-induced emission.

Claims

1. A method for preparing 2-arylbenzothiophene sulfone by using an oxidative Suzuki coupling reaction, characterized in that, Comprising: In the presence of a palladium catalyst, a benzothiophene sulfone compound, an arylboronic acid, an oxidant and an organic base undergo an oxidative Suzuki coupling reaction in an organic solvent. After the reaction is completed, post-treatment is carried out to obtain the 2-arylbenzothiophene sulfone; Among them, the structural formula of the benzothiophene sulfone compound is shown as formula (I): The structural formula of the arylboronic acid is shown as formula (II): The structural formula of the 2-arylbenzothiophene sulfone is shown as formula (III): In formulas (I) to (III), R 1 is one of H, C1-C3 alkyl, methoxy, phenyl, and cyano; m = 1-4; when m≠1, multiple Rs 1 are each independently selected from one of H, C1-C3 alkyl, methoxy, phenyl, and cyano; R 2 is one of H, methyl, and phenyl; R 3 is one of H, C1-C3 alkyl, C1-C3 alkoxy, fluorine atom, trifluoromethyl, cyano, C6-C8 aryl, diphenylamino; n = 1-5; when n≠1, multiple Rs 3 are each independently selected from one of H, C1-C3 alkyl, C1-C3 alkoxy, fluorine atom, trifluoromethyl, cyano, C6-C8 aryl, diphenylamino; The oxidant is copper acetate; The organic base is pyridine.

2. The method for preparing 2-arylbenzothiophene sulfone by using an oxidative Suzuki coupling reaction according to claim 1, characterized in that, The molar ratio of the benzothiophene sulfone compound to the arylboronic acid is 1:(1 - 5).

3. The method for preparing 2-arylbenzothiophene sulfone by using oxidative Suzuki coupling reaction according to claim 1, wherein The molar ratio of the benzothiophene sulfone compound to the oxidant is 1:(1 - 6).

4. The method for preparing 2-arylbenzothiophene sulfone by using oxidative Suzuki coupling reaction according to claim 1, wherein The molar ratio of the benzothiophene sulfone compound to the organic base is 1:(1.5 - 4).

5. The method for preparing 2-arylbenzothiophene sulfone by using oxidative Suzuki coupling reaction according to claim 1, wherein The organic solvent is at least one of toluene, 1,2-dichloroethane, 1,4-dioxane, dimethyl sulfoxide, N,N-dimethylformamide.

6. The method for preparing 2-arylbenzothiophene sulfone by using oxidative Suzuki coupling reaction according to claim 1, characterized in that, The palladium catalyst is Pd(OAc)2; The dosage of the palladium catalyst is 5 - 15 mol% of the dosage of the benzothiophene sulfone compound.

7. The method for preparing 2-arylbenzothiophene sulfone by using oxidative Suzuki coupling reaction according to claim 1, characterized in that, The reaction temperature of the oxidative Suzuki coupling reaction is 80 - 120 °C.

8. The method for preparing 2-arylbenzothiophene sulfone by using an oxidative Suzuki coupling reaction according to claim 1, wherein After the reaction is completed, the following post-treatment is carried out: The reaction mixture is passed through a layer of diatomaceous earth and washed with ethyl acetate. The organic phase is extracted with ethyl acetate and water and concentrated under reduced pressure in vacuo. Using ethyl acetate / petroleum ether as the eluent, the concentrate is purified by silica gel column chromatography to obtain the 2-arylbenzothiophene sulfone.

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