A method for photocatalytic preparation of arylboronic acids based on thianthrenium salts
Patent Information
- Application Number
- CN202610909400.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-06-23
- Publication Date
- 2026-10-16
AI Technical Summary
[0006]基于目前芳基硼酸的合成方法存在需使用贵金属催化剂或强碱、对水/空气敏感、官能团兼容性差、操作复杂且成本高等问题，为解决上述问题，本发明提供了一种基于噻蒽鎓盐光催化制备芳基硼酸的方法，以噻蒽鎓盐与硼源为反应原料，在可见光照射下，无需外加催化剂和强碱，在空气存在下即可高效合成芳基硼酸
本发明首次实现了在无需任何外加光敏剂的条件下，仅依靠可见光照射即可高效驱动芳基噻蒽鎓盐与硼源反应生成芳基硼酸。该方法完全避免了贵金属催化剂的使用，无需添加强碱，也无需严格的惰性气体保护，在空气存在下即可顺利进行，从而彻底克服了传统方法中催化剂成本高昂、对水氧敏感、操作繁琐等技术缺陷。同时，反应条件温和（室温、可见光），操作简便，绿色环保；底物适用范围广泛，可兼容卤素、甲氧基、酯基等多种官能团，展现出优异的官能团耐受性。更为重要的是，本发明摒弃了常规光化学反应所依赖的光敏剂，不仅简化了反应体系、降低了成本，而且意外地获得了比添加光敏剂时更高的转化效率以及更高的纯度（产率可高达99%，纯度可高达99%）。
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Figure CN122917072A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of organic synthesis technology, and specifically to a method for preparing arylboronic acid based on the photocatalysis of thiaanthraium salt. Background Technology
[0002] Arylboronic acids are an important class of intermediates in organic synthesis, widely used in Suzuki-Miyaura coupling reactions, medicinal chemistry, materials science, and chemical biology. Thanks to the unique Lewis acidity, good stability, and diverse reactivity of the borate group, arylboronic acids can participate in the highly selective construction of carbon-carbon and carbon-heteroatom bonds, making them indispensable building blocks in modern organic synthesis. For example, biphenylboronic acid ([1,1'-biphenyl]-4-ylboronic acid) is a key intermediate in the preparation of liquid crystal materials, organic light-emitting diodes (OLEDs), and various biphenyl drugs. Through Suzuki coupling reactions, it can be further used to construct conjugated molecules with specific photoelectric properties. 4-Methoxyphenylboronic acid (p-methoxyphenylboronic acid) is widely used in the synthesis of natural products, pesticides, and antitumor drugs; the synergistic effect of its methoxy and borate groups endows the products with excellent biological activity and physicochemical properties. Furthermore, arylboronic acids are also core structural units of marketed drugs such as bortezomib and criborone, playing an irreplaceable role in precision medicine and smart materials design.
[0003] Given the important applications of arylboronic acids, developing efficient and economical synthetic methods has always been a research hotspot in the field of organic synthesis. Currently, there are two main types of synthetic routes commonly used in industrial production and laboratories. The first type uses aryl halides as raw materials, which undergo cross-coupling reactions with pinacol diboron esters (B2pin2) or alkoxyboranes under the action of noble metal catalysts such as palladium. This method typically achieves yields of 70%-85% and product purity >98%, but it heavily relies on expensive palladium catalysts and phosphine ligands, and requires the addition of strong bases (such as potassium acetate, sodium tert-butoxide, etc.) to promote the reaction process. The second type involves the reaction of aryl lithium or Grignard reagents with trialkyl borate esters, achieving yields of 40%-80% and purity exceeding 95%. However, this process must be carried out under strictly anhydrous and oxygen-free conditions. Aryl lithium and Grignard reagents are extremely sensitive to water and air, making the operation cumbersome and highly dangerous.
[0004] The above-mentioned traditional methods have the following prominent defects in practical applications: (1) They must use precious metal catalysts (such as Pd catalysts) or strong bases, resulting in high raw material costs and environmental unfriendliness; (2) They are sensitive to water or air, requiring inert gas protection and strict dehydration and deoxygenation, which increases equipment investment and operational difficulty; (3) They have poor functional group compatibility, and sensitive groups such as aldehydes, esters, and hydroxyl groups are prone to side reactions under strong base or strong nucleophilic conditions, which seriously limits the substrate range; (4) The overall operation is complex and the production cost is high, which does not conform to the concept of green chemistry and sustainable development, and the drawbacks are more obvious in large-scale synthesis.
[0005] Therefore, developing a method for synthesizing arylboronic acids that does not require precious metal catalysts and strong bases, is insensitive to water and air, has good functional group compatibility, and is easy to operate is of great scientific significance and application value. Summary of the Invention
[0006] Current methods for synthesizing arylboronic acids suffer from drawbacks such as the need for noble metal catalysts or strong bases, sensitivity to water / air, poor functional group compatibility, complex operation, and high cost. To address these issues, this invention provides a photocatalytic method for preparing arylboronic acids based on thiaanthraium salts. Using thiaanthraium salts and a boron source as reactants, arylboronic acids can be efficiently synthesized in the presence of air under visible light irradiation without the need for external catalysts or strong bases. This method offers mild reaction conditions, a wide range of applicable substrates, and good functional group compatibility. It avoids the use of traditional metal catalysts or strong bases, and boasts advantages such as being environmentally friendly, easy to operate, and having high yields. It is suitable for the rapid construction of arylboronic acid compounds in the fields of medicine and materials.
[0007] Specifically, the following technical solutions are provided: This invention provides a method for preparing arylboronic acid based on thiaanthraium salt photocatalysis, comprising the following steps: The thiaanthraium salt of Formula I was reacted with a boron source under visible light irradiation and in the presence of a solvent to obtain the arylboronic acid compound of Formula II; wherein the boron source was tetrahydroxydiborane and / or bis(pinacol)diborane. The structures of Equations I and II above are as follows: , in, The substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group, or monovalent group of a drug molecule; the substituents in the substituted aryl group and the substituted heteroaryl group are selected from one or more of the following groups: halogen (including F, Cl, Br, I), C1-C10 alkyl, C1-C10 haloalkyl, -COOR1, -OR2, where R1 and R2 are selected from C1-C10 alkyl groups, such as methyl, ethyl, propyl, isopropyl, butyl, etc.
[0008] This invention was discovered unexpectedly during the inventors' exploration of methods for synthesizing arylboronic acids. In the initial stages of exploration, the inventors attempted to utilize known photocatalytic strategies, adding common photosensitizers (such as (ppy)3Ir, [Ir{Dfcf3ppy}2(bpy)]PF6, Eosin Y, etc.) to the reaction system to promote the conversion of arylthianthane salts to tetrahydroxydiborane. However, experimental results showed that, under the conditions of adding commonly used photosensitizers, the yield of the target product, arylboronic acid, did not increase as expected; instead, it was significantly inhibited. Surprisingly, when no external photosensitizer was completely omitted, the reaction system containing thianthane salts and a boron source could proceed smoothly and yield arylboronic acid with excellent conversion rate solely through visible light irradiation.
[0009] Furthermore, the aryl group is a general term for monovalent groups obtained by removing one hydrogen atom from an aromatic hydrocarbon molecule, including but not limited to phenyl, naphthyl, biphenyl, phenanthrene, etc., and the heteroaryl group is a general term for monovalent groups obtained by removing one hydrogen atom from a heteroaryl hydrocarbon molecule, including but not limited to thiophene, pyridinyl, indolyl, carbazolyl, etc.
[0010] Furthermore, the drug molecules include, but are not limited to, indomethacin ethyl ester, oxazolidinone, clofibrate, flurbiprofen, etc.
[0011] Furthermore, the preparation method of the thiaanthraium salt is a known method, as shown in the following reaction equation:
[0012] in, The substituted or unsubstituted aromatic hydrocarbon, substituted or unsubstituted heteroaromatic hydrocarbon, or pharmaceutical molecule; the substituents in the substituted aromatic hydrocarbon and the substituted heteroaromatic hydrocarbon are selected from one or more of the following groups: halogen, C1-C10 alkyl, C1-C10 haloalkyl, -COOR1, -OR2, where R1 and R2 are selected from C1-C10 alkyl groups respectively.
[0013] Furthermore, the thiaanthraium salt may be selected from one of the following structures: .
[0014] Furthermore, the boron source is tetrahydroxydiborane.
[0015] Furthermore, the molar ratio of the thiaanthraium salt shown in Formula I to the boron source is 1:(2-5).
[0016] Furthermore, the visible light includes white light, blue light, violet light, etc., preferably violet light with a wavelength of 380-465 nm and an illumination intensity of 10-100 W; more preferably, the visible light is violet light with a wavelength of 380-400 nm, such as violet light with a wavelength of 390 nm.
[0017] Furthermore, the solvent may be selected from one or more of acetonitrile, N,N-dimethylformamide, dimethylacetamide, dimethyl sulfoxide, and tetrahydrofuran.
[0018] Furthermore, the reaction is carried out at a temperature of 0-40 °C (e.g., room temperature) for 2-24 h.
[0019] Furthermore, the reaction can be carried out in air without the need for inert gas protection.
[0020] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention marks the first time that the reaction of arylthiananthium salts with a boron source to produce arylboronic acid can be efficiently driven solely by visible light irradiation without the need for any external photosensitizer. This method completely avoids the use of precious metal catalysts, eliminates the need for strong bases and strict inert gas protection, and can proceed smoothly in the presence of air, thus overcoming the technical shortcomings of traditional methods such as high catalyst costs, sensitivity to water and oxygen, and cumbersome operation. Furthermore, the reaction conditions are mild (room temperature, visible light), the operation is simple, and it is environmentally friendly. The substrates are widely applicable, compatible with various functional groups such as halogens, methoxy groups, and ester groups, exhibiting excellent functional group tolerance. More importantly, this invention eliminates the photosensitizer required for conventional photochemical reactions, simplifying the reaction system, reducing costs, and unexpectedly achieving higher conversion efficiency and higher purity (yield up to 99%, purity up to 99%) compared to methods with photosensitizers.
[0021] This invention provides an economical, efficient, green, and easily scalable new approach to solve many bottleneck problems in the existing synthesis of arylboronic acids, and is applicable to the rapid construction of arylboronic acid compounds in the fields of medicine and materials. Attached Figure Description
[0022] Figure 1 This is a flow chart of the reaction process for preparing arylboronic acid according to the present invention; Figure 2 The 1H NMR spectrum of biphenylboronic acid prepared in Example 1; Figure 3 The 1H NMR spectrum of 4-methoxyphenylboronic acid prepared in Example 4; Figure 4 The 1H NMR spectrum of 4-methylphenylboronic acid prepared in Example 5; Figure 5The image shows the 1H NMR spectrum of the oxadiazon boric acid prepared in Example 6. Detailed Implementation
[0023] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, so that those skilled in the art can better understand and implement the present invention. However, the embodiments described are not intended to limit the present invention.
[0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the specification of this invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The terms “comprising” or “including” used in this invention may also be replaced with the closed form “is” or “consisting of”.
[0025] The raw materials used in the following examples are all commercially available or self-made, and the specific preparation operations and testing methods involved are all conventional methods in the field.
[0026] The thiaanthracite salts used in the following examples were prepared by known methods, as detailed below: Thianthionium salt A1 ( The preparation process of ) is as follows:
[0027] Thianthionium salt A2 ( The preparation process of ) is as follows:
[0028] Thianthionium salt A3 ( The preparation process of ) is as follows:
[0029] Thianthionium salt A4 ( The preparation process of ) is as follows: Example 1
[0030] This embodiment relates to the preparation of biphenylboronic acid, and the specific operations are as follows:
[0031] 0.2 mol of thiaanthraium salt A1 and 0.6 mol of B2(OH)4 were added to 5 mL of DMF and irradiated under a 390 nm ultraviolet LED for 12 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product was purified by column chromatography to obtain biphenylboronic acid with a yield of 99% and a purity of 99%.
[0032] 1H NMR (400 MHz, DMSO-d6): δ 8.11 (s, 2H), 7.88 (d, J = 8.2 Hz, 2H), 7.70-7.67 (m, 2H), 7.63 (d, J = 8.4 Hz, 2H), 7.47 (t, J = 7.7 Hz, 2H), 7.39-7.34 (m, 1H). 13 C NMR (100 MHz, DMSO-d6) δ 142.1, 140.6, 135.3, 129.4, 128.0, 127.2, 126.2. No carbon atoms bonded to boron were detected due to relaxation effects. 11 B NMR (128 MHz, DMSO-d6) δ 26.3. Example 2
[0033] This embodiment involves the screening of photocatalysts and the preparation of biphenylboronic acid under conditions with or without the addition of different photocatalysts. The preparation method is the same as in Example 1, as follows: Group 2-1: 0.2 mol of thiaanthraium salt A1, 0.6 mol of B2(OH)4, and (ppy)3Ir (1 mol%) were added to 5 mL of DMF and irradiated under a 390 nm UV LED for 12 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product was purified by column chromatography to obtain biphenylboronic acid with a yield of 60% and a purity of 99%.
[0034] Group 2-2: 0.2 mol of thiaanthracite salt A1, 0.6 mol of B2(OH)4, and [Ir{Dfcf3ppy}2(bpy)]PF6 (1 mol%) were added to 5 mL of DMF and irradiated under a 390 nm UV LED for 12 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product was purified by column chromatography to obtain biphenylboronic acid with a yield of 56% and a purity of 99%.
[0035] Groups 2-3: 0.2 mol of thiaanthracite salt A1, 0.6 mol of B2(OH)4, and Eosin Y (1 mol%) were added to 5 mL of DMF and irradiated under a 390 nm UV LED for 12 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product was purified by column chromatography to obtain biphenylboronic acid with a yield of 43% and a purity of 99%.
[0036] Groups 2-4: 0.2 mol of thiaanthraium salt A1 and 0.6 mol of B2(OH)4 were added to 5 mL of DMF and irradiated under a 390 nm ultraviolet LED for 12 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product was purified by column chromatography to obtain biphenylboronic acid with a yield of 99% and a purity of 99%.
[0037] The effects of photocatalyst type on the yield and purity of the target product are summarized in the table below:
[0038] As shown in the table above, the yield of the target product can be significantly improved without the addition of an additional photocatalyst. Example 3
[0039] This embodiment involves the selection of light wavelengths to prepare biphenylboronic acid under conditions with or without the addition of different photocatalysts. The preparation method is the same as in Example 1, as detailed below: Group 3-1: 0.2 mol of thiaanthraium salt A1 and 0.6 mol of B2(OH)4 were added to 5 mL of acetonitrile and irradiated under a blue LED with a wavelength of 465 nm for 12 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product was purified by column chromatography to obtain biphenylboronic acid with a yield of 50% and a purity of 99%.
[0040] Group 3-2: 0.2 mol of thiaanthraium salt A1 and 0.6 mol of B2(OH)4 were added to 5 mL of acetonitrile and irradiated under a 430 nm ultraviolet LED for 12 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product was purified by column chromatography to obtain biphenylboronic acid with a yield of 41% and a purity of 99%.
[0041] Group 3-3: 0.2 mol of thiaanthracite salt A1 and 0.6 mol of B2(OH)4 were added to 5 mL of acetonitrile and irradiated under a 390 nm ultraviolet LED for 12 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product was purified by column chromatography to obtain biphenylboronic acid with a yield of 81% and a purity of 99%.
[0042] Groups 3-4: 0.2 mol of thiaanthracite salt A1 and 0.6 mol of B2(OH)4 were added to 5 mL of acetonitrile and irradiated under sunlight for 12 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the mixture was purified by column chromatography. Biphenylboronic acid was not obtained.
[0043] The effects of light wavelength on the yield and purity of the target product are summarized in the table below:
[0044] As shown in the table above, irradiation with 390 nm ultraviolet light can significantly improve the yield of the target product. Example 4
[0045] This embodiment relates to the preparation of 4-methoxyphenylboronic acid, and the specific operations are as follows:
[0046] 0.2 mol of thiaanthraium salt A2 and 0.6 mol of B2(OH)4 were added to 5 mL of DMF and irradiated under a 390 nm ultraviolet LED for 12 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product was purified by column chromatography to obtain biphenylboronic acid with a yield of 90% and a purity of 95%.
[0047] 1 H NMR (400 MHz, CDCl3): δ 8.15 (d, J = 8.7 Hz, 2H), 7.01 (s, J = 8.6Hz, 2H), 3.88 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 142.1, 140.6, 135.3, 129.4, 128.0, 127.2, 126.2. Due to relaxation effects, no carbon atoms bonded to boron were detected. 11 B NMR (128 MHz, DMSO-d6) δ 30.73. Example 5
[0048] This embodiment relates to the preparation of 4-methylphenylboronic acid, and the specific operations are as follows:
[0049] 0.2 mol of thiaanthraium salt A3 and 0.6 mol of B2(OH)4 were added to 5 mL of DMF and irradiated under a 390 nm ultraviolet LED for 12 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product was purified by column chromatography to obtain biphenylboronic acid with a yield of 99% and a purity of 95%.
[0050] 1 H NMR (400 MHz, DMSO-d6: δ 7.91 (s, 2H), 7.68 (d, J = 7.8 Hz, 2H), 7.14 (d, J = 7.5 Hz, 2H), 2.30 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 139.4, 134.2, 128.1, 21.2. Due to relaxation effects, no carbon atoms bonded to boron were detected. 11 B NMR (128 MHz, DMSO-d6) δ 28.0. Example 6
[0051] This embodiment relates to the preparation of oxadiazon boric acid, and the specific operation is as follows:
[0052] 0.2 mol of thiaanthraium salt A4 and 0.6 mol of B2(OH)4 were added to 5 mL of DMF and irradiated under a 390 nm ultraviolet LED for 12 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product was purified by column chromatography to obtain biphenylboronic acid with a yield of 99% and a purity of 95%.
[0053] 1 H NMR (400 MHz, DMSO-d6): δ 8.81 (s, 1H), 7.82 (s, 2H), 7.66 (d, J =8.4 Hz, 2H), 7.58 (d, J = 8.7 Hz, 2H), 7.46-7.39 (m, 2H), 7.19 (t, J = 7.4Hz, 1H), 7.12 (d, J = 9 Hz, 2H) 7.08 (d, J = 7.5 Hz, 2H), 6.65 (d, J = 8.0Hz, 2H), 2.04 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 172.3, 157.8, 155.9, 152.9, 147.1, 135.6, 130.8, 130.3, 126.9, 124.2, 119.3, 118.6, 111.3, 84.6, 23.6. No boron-bonded carbon atoms were detected due to relaxation effects. 11 B NMR (128 MHz, DMSO-d6) δ 34.52. The embodiments described above are merely preferred examples to fully illustrate the present invention, and the scope of protection of the present invention is not limited thereto. Equivalent substitutions or modifications made by those skilled in the art based on the present invention are all within the scope of protection of the present invention. The scope of protection of the present invention is defined by the claims.
Claims
1. A method for preparing arylboronic acid based on thiaanthraium salt photocatalysis, characterized in that, Includes the following steps: The thiaanthraium salt of Formula I was reacted with a boron source under visible light irradiation and in the presence of a solvent to obtain the arylboronic acid compound of Formula II; wherein the boron source was tetrahydroxydiborane and / or bis(pinacol)diborane. The structures of Equations I and II above are as follows: ， in, It is a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, or a monovalent group of a drug molecule; the substituents in the substituted aryl group and the substituted heteroaryl group are selected from one or more of the following groups: halogen, C1-C10 alkyl, C1-C10 haloalkyl, -COOR1, -OR2, where R1 and R2 are selected from C1-C10 alkyl groups respectively.
2. The method according to claim 1, characterized in that, The aryl group is phenyl, naphthyl, biphenyl, or phenanthrene; The heteroaryl group is thienyl, pyridyl, indolyl, or carbazoyl; The drug molecule is indomethacin ethyl ester, oxazolidinone, clofibrate, or flurbiprofen.
3. The method according to claim 1, characterized in that, The thiaanthraium salt is selected from one of the following structures: ； The boron source is tetrahydroxydiborane.
4. The method according to claim 1, characterized in that, The molar ratio of the thiaanthraium salt shown in Formula I to the boron source is 1:(2-5).
5. The method according to claim 1, characterized in that, The visible light is violet light with a wavelength of 380-465 nm and an illumination intensity of 10-100 W.
6. The method according to claim 5, characterized in that, The visible light is violet light with a wavelength of 380-400 nm.
7. The method according to claim 1, characterized in that, The solvent is selected from one or more of acetonitrile, N,N-dimethylformamide, dimethylacetamide, dimethyl sulfoxide, and tetrahydrofuran.
8. The method according to claim 1, characterized in that, The reaction is carried out at a temperature of 0-40 °C for 2-24 hours.
9. The method according to claim 1, characterized in that, The reaction takes place in air.