Alkali-free recyclable decarboxylation reaction method based on water-soluble uranyl salt photocatalysis
By using water-soluble uranyl salt photocatalysts to carry out decarboxylation reactions under alkali-free conditions, the problems of high cost and difficulty in recycling of precious metal catalysts have been solved, achieving efficient and recyclable decarboxylation reactions, broadening the compatibility of functional groups, and conforming to the principles of green chemistry.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- HAINAN UNIV
- Filing Date
- 2026-01-30
- Publication Date
- 2026-05-12
AI Technical Summary
Existing photocatalytic decarboxylation reactions rely on expensive and difficult-to-recycle noble metal catalysts. Traditional methods require alkaline conditions that limit functional group compatibility, while inexpensive metal catalysts are inefficient and difficult to recycle, making it difficult to meet the needs of high-efficiency synthesis.
Water-soluble uranyl salts are used as photocatalysts to carry out decarboxylation reactions under alkaline conditions. Visible light is used to excite uranyl ions for catalysis, generating alkyl radicals that add to electron-deficient olefins. The catalyst can be recovered and recycled through phase separation.
It achieves highly efficient decarboxylation reaction under alkali-free conditions, broadens the functional group tolerance, reduces costs, meets the requirements of green chemistry, is applicable to a variety of carboxylic acids and olefins, and the catalyst can be recycled multiple times.
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Figure CN122010798A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology, and particularly relates to a base-free, cyclic decarboxylation reaction method based on photocatalysis of water-soluble uranyl salts. Background Technology
[0002] Decarboxylation is one of the core strategies for constructing carbon-carbon bonds in organic synthesis and is widely used in the synthesis and preparation of drug molecules, functional materials, and natural products. With the deepening of the concept of green chemistry, photocatalytic decarboxylation has become a research hotspot in recent years due to its advantages such as mild reaction conditions, high atom economy, and environmental friendliness. Traditional photocatalytic decarboxylation systems mostly rely on noble metal complex photocatalysts, such as iridium-based and ruthenium-based complexes. Although these catalysts have excellent catalytic activity, they are expensive and scarce, which is not conducive to large-scale industrial applications. At the same time, some systems use structurally complex organic photocatalysts, which often require multi-step synthesis, significantly increasing the operating and time costs of the reaction. In addition, traditional photocatalytic decarboxylation reactions usually need to be carried out under alkaline conditions. By adding a base to the reaction system, the carboxylic acid raw material is converted into a carboxylate form to achieve activation. This operation not only increases the number of reaction steps but also easily causes side reactions with sensitive functional groups in the reaction system, severely limiting the functional group compatibility of the substrate and further narrowing the applicability of this method.
[0003] To address these issues, researchers have attempted to develop inexpensive metal salts to replace precious metal catalysts. For example, transition metal salts such as iron and copper have been reported to be applicable to photocatalytic decarboxylation reactions. However, these inexpensive metal salt-based catalytic systems generally suffer from low catalytic efficiency, making it difficult to meet the demands of high-efficiency synthesis. Furthermore, iron and copper ions readily react with alkalis in aqueous reaction systems to form hydroxide precipitates, making catalyst recovery difficult and hindering recycling. This results in catalyst waste and increases the complexity of post-reaction processing, which is inconsistent with the requirements of green chemistry development.
[0004] Uranium is an abundant actinide element, and its common uranium ion (UO2) 2+Uranyl ions possess unique photochemical properties, enabling efficient ligand-to-metal charge transfer (LMCT) under visible light excitation. This process generates excited-state species with strong oxidizing and hydrogen extraction capabilities, theoretically making them suitable as high-performance photocatalysts in organic synthesis reactions. However, the application of uranyl ions in photocatalytic synthesis is still in its early stages of exploration. Their catalytic potential in decarboxylation reactions has not been fully explored, especially the lack of reports on efficient and recyclable photocatalytic decarboxylation for carbon-carbon bond construction under alkaline conditions. Therefore, developing a photocatalytic decarboxylation method based on uranyl ions to achieve efficient decarboxylation under alkaline conditions, while simultaneously addressing the catalyst recycling issue, is of great significance for promoting the industrial application of photocatalytic decarboxylation reactions. Summary of the Invention
[0005] To address the aforementioned problems in the prior art, this invention provides a base-free, recyclable decarboxylation reaction method based on water-soluble uranyl salt photocatalysis. This method utilizes a soluble uranyl salt as a photocatalyst in a base-free, aqueous, or water-organic mixed solvent to achieve the decarboxylation addition reaction of carboxylic acids with electron-deficient olefins, and the catalyst can be easily recovered and recycled.
[0006] To achieve the above objectives, the present invention provides the following technical solution: This invention provides a base-free, cyclic decarboxylation reaction method based on water-soluble uranyl salt photocatalysis, comprising the following steps: Under alkaline conditions, a carboxylic acid compound, an electron-deficient olefin compound, and a water-soluble uranyl salt are mixed and then a reaction medium containing water is added to obtain a mixture. The mixture is then irradiated with visible light to induce a decarboxylation addition reaction in the carboxylic acid compound.
[0007] Furthermore, the carboxylic acid compound is any one of aliphatic carboxylic acids, aryloxyacetic acids, amino acid derivatives, and phenylacetic acids.
[0008] Beneficial effects: This invention selects aliphatic carboxylic acids, aryloxyacetic acids, amino acid derivatives, and phenylacetic acids as carboxylic acid compounds, with aryloxyacetic acids serving as model substrates, demonstrating the universality of the decarboxylation method for the baseless decarboxylation of classical activated acids; the successful conversion of amino acid derivatives highlights their application potential in the later-stage modification of bioactive molecules; the compatibility with phenylacetic acids demonstrates the system's effective handling capability for benzylic radicals; and the good yield of aliphatic carboxylic acids (especially secondary / tertiary carbons) constitutes a key innovation that distinguishes it from other inexpensive metal catalytic systems, clarifying the unique advantages of this uranyl catalytic scheme for challenging unactivated substrates.
[0009] Furthermore, the electron-deficient olefin compound is any one of maleic nitrile compounds, acrylate compounds, benzenesulfonyl vinyl compounds, and vinyl ketone compounds.
[0010] Beneficial Effects: This invention comprehensively and powerfully demonstrates the broad applicability and synthetic value of its catalytic system. Using maleic nitrile as a model, it showcases the system's excellent efficiency with highly active acceptors; the successful conversion of acrylates verifies its universality for the most common alkenes in synthesis; and the smooth conversion of benzenesulfonyl vinyl and vinyl ketone, two strongly electron-withdrawing alkenes, further highlights the unique functional group tolerance of the decarboxylation method of this invention. Together, they construct a diverse and modular C-C bond construction platform, capable of meeting the diverse needs of complex molecular synthesis.
[0011] Furthermore, the water-soluble uranyl salt is uranyl nitrate hexahydrate (UO2(NO3)2·6H2O); The amount of water-soluble uranyl salt added is 1-10 mol% of the molar amount of the carboxylic acid compound, preferably 10 mol%.
[0012] Furthermore, the reaction medium containing water is water or a mixture of water and an organic solvent.
[0013] Furthermore, the volume ratio of water to organic solvent is 1:1; The organic solvent is acetone.
[0014] Furthermore, the ratio of the added carboxylic acid compound to the electron-deficient olefin compound is 1.5:1.
[0015] Furthermore, the visible light is blue light with a wavelength of 440-445 nm.
[0016] Furthermore, the addition reaction is carried out under nitrogen protection at room temperature for 24 hours.
[0017] Furthermore, after the addition reaction is completed, the organic phase is extracted and separated, and the resulting aqueous phase containing the catalyst is directly used in the next round of reaction, thus realizing the recycling of the catalyst.
[0018] The beneficial effects of this invention compared to the prior art are as follows: The decarboxylation reaction method of this invention eliminates the need for pre-activation of carboxylic acids with alkali, directly using carboxylic acids as reactants. This avoids the pre-salting step, simplifies the operation process, broadens the functional group tolerance, and improves atom economy. Furthermore, the use of uranyl nitrate as a photocatalyst in this invention allows for catalyst recycling. Utilizing the water solubility of uranyl salts, catalyst recovery and multiple recycling can be achieved through simple phase separation, significantly reducing costs and environmental burden. In addition, the decarboxylation reaction method of this invention is environmentally friendly and can be carried out in aqueous mixed solvents or even pure water, conforming to green chemistry principles. It has a wide substrate applicability, suitable for various types of carboxylic acids and electron-deficient alkenes, and exhibits excellent functional group compatibility. The conditions are mild, the reaction occurs at room temperature, energy consumption is low, and the operation is safe and simple. Attached Figure Description
[0019] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0020] Figure 1 This is a schematic diagram of the mechanism of the alkali-free cyclic decarboxylation reaction based on the photocatalysis of water-soluble uranyl salts of the present invention; Figure 2 This is a schematic diagram of the general formula for the alkali-free, cyclic decarboxylation reaction based on photocatalysis of water-soluble uranyl salts according to the present invention. Figure 3 This is a comparison diagram of the effects of different photocatalysts on the carboxylic acid reaction in Example 3 of the present invention; Figure 4 The diagram shows the recycling effect of uranyl nitrate photocatalyst in Example 4 and Comparative Example 1 of this invention; Figure 5 The image shows the HRMS spectrum of the free radical capture experiment in Example 6 of this invention. Figure 6 This is a graph showing the product yields of different carboxylic acids and different electron-deficient alkenes after reacting, during the substrate applicability assessment in Example 7 of this invention. Figure 7 This is a yield graph of the products in the reaction process where the reaction medium is pure water in Example 8 of the present invention. Detailed Implementation
[0021] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.
[0022] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.
[0023] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.
[0024] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.
[0025] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.
[0026] In the following embodiments of the present invention, the room temperature refers to 23±2℃.
[0027] All raw materials used in the following embodiments of the present invention can be purchased commercially.
[0028] The mechanism of the alkali-free, cyclic decarboxylation reaction based on the photocatalysis of water-soluble uranyl salt in this invention is as follows: photo-excited uranyl ions (UO2) 2+ The uranium (U) reacts with a carboxylic acid via a single-electron transfer (SET) or hydrogen atom transfer (HAT) to generate carbon dioxide, an alkyl radical, and reduced uranium (V). This alkyl radical then adds to an electron-deficient alkene, forming a new radical intermediate. This intermediate is further reduced and protonated by the reduced uranium (V) via a single-electron transfer to generate the final product, while simultaneously regenerating the ground-state uranyl ion (UO2). 2+ The catalytic cycle is completed, and the mechanism is illustrated in the diagram below. Figure 1 As shown.
[0029] The general formula schematic diagram of the uranyl photocatalytic decarboxylation reaction in the following embodiments of the present invention is shown below. Figure 2 As shown.
[0030] Example 1 Screening of reaction media The reaction formula is:
[0031] The method for screening reaction media is as follows: Under nitrogen protection, 4,4-difluorocyclohexanecarboxylic acid (1a, 0.3 mmol), 1,1-bis(benzenesulfonyl)ethylene (2a, 0.2 mmol), and UO2(NO3)2·6H2O (10 mol%) were placed in a reaction tube, and different reaction media (3.0 mL) were added to each. The resulting mixture was then irradiated with a blue LED (λ=440-445 nm, 40 W) at 25 °C for 24 hours. After the reaction was completed, the mixture was analyzed by... 1 The yield of product 3aa was calculated by ¹H NMR spectroscopy analysis (using 1,3,5-trimethoxybenzene as an internal standard). The reaction medium and the yield of product 3aa are shown in Table 1. As can be seen from Table 1, the best results were achieved when a mixed solvent of acetone and water (volume ratio of acetone to water of 1:1) was used as the reaction medium, with an NMR yield of 99%.
[0032] Table 1
[0033] Example 2 Screening of photocatalyst dosage The reaction formula is:
[0034] The method for screening the amount of photocatalyst is as follows: Under nitrogen protection, 4,4-difluorocyclohexanecarboxylic acid (1a, 0.3 mmol), 1,1-bis(benzenesulfonyl)ethylene (2a, 0.2 mmol), and different amounts of UO2(NO3)2·6H2O were placed in a reaction tube. A mixed solvent of acetone and water (1:1, 3.0 mL) was added, and the resulting mixture was then irradiated with a blue LED (λ=440-445 nm, 40 W) at 25 °C for 24 hours. After the reaction was completed, the precipitate was collected by... 1 The yield of product 3aa was determined by ¹H NMR analysis. Table 2 shows the amount of UO₂(NO₃)₂·6H₂O and the yield of product 3aa. Table 2 indicates that a high yield of 99% can be obtained when the photocatalyst dosage is 10 mol%. Considering both cost and efficiency, 10 mol% is the optimal dosage.
[0035] Table 2
[0036] Example 3 Comparison of different decarboxylation photocatalysts The reaction formula is:
[0037] The methods for different decarboxylation photocatalysts are as follows: A base-free, cyclic decarboxylation reaction method based on water-soluble uranyl salt photocatalysis includes the following steps: Under nitrogen protection, 4,4-difluorocyclohexanecarboxylic acid (1a, 0.3 mmol), 1,1-bis(benzenesulfonyl)ethylene (2a, 0.2 mmol), and different photocatalysts (10 mol%) were placed in a reaction tube. A mixed solvent of acetone and water (1:1, 3.0 mL) was added, and the resulting mixture was then irradiated at 25 °C with its respective optimal wavelength light source for 24 hours. 1 The yield of product 3aa was analyzed by HNMR. The yields of product 3aa varied with different photocatalysts, as shown below. Figure 3 As shown in Table 3, through Figure 3 As can be seen from Table 3, only uranyl salts (UO2) 2+ It maintained highly efficient catalytic activity, with an NMR yield of 99%, while Fe... 3+ Cu 2+ The efficiency of other catalysts decreased significantly or failed, demonstrating the unique advantages of uranyl catalysts for challenging substrates.
[0038] Table 3
[0039] Example 4 Experiment on the recycling of uranyl photocatalyst The reaction formula is:
[0040] Under nitrogen protection, 4,4-difluorocyclohexanecarboxylic acid (1a, 0.3 mmol), 1,1-bis(benzenesulfonyl)ethylene (2a, 0.2 mmol), and UO2(NO3)2·6H2O (10 mol%) were placed in a reaction tube, and a mixed solvent of acetone and water (1:1, 3.0 mL) was added. The resulting mixture was then irradiated with blue LED (λ=440-445 nm, 40 W) at 25 °C for 24 hours. After the reaction, the reaction mixture was extracted with dichloromethane (DCM, 3.0 mL × 3), and the extracted organic phases were combined, concentrated, and then... 1The yield of this round of reaction was calculated by ¹H NMR analysis. The aqueous phase containing the catalyst was used directly for the next round of reaction: 4,4-difluorocyclohexanecarboxylic acid (1a, 0.3 mmol), 1,1-bis(benzenesulfonyl)ethylene (2a, 0.2 mmol) and acetone (1.5 mL) were added back to the aqueous phase, and the above reaction and extraction steps were repeated.
[0041] Comparative Example 1 Reaction recovery experiment 4,4-Difluorocyclohexanecarboxylic acid (1a, 0.3 mmol), 1,1-bis(benzenesulfonyl)ethylene (2a, 0.2 mmol), and FeCl3·6H2O (5.4 mg, 10 mol%) were placed in a reaction tube, and a mixed solvent of acetone (1.5 mL) and water (1.5 mL) was added. The mixture was stirred vigorously at 25 °C for 2 min, followed by bubbling under a nitrogen atmosphere for 10 min. The resulting solution was irradiated under an LED lamp (λ=390-395 nm, 40 W) for 24 h. After the reaction, the solution was extracted three times with dichloromethane (DCM, 3.0 mL × 3). Since the catalyst is insoluble in dichloromethane, it should remain in the aqueous phase during extraction. After three consecutive extractions, the organic phases were combined and concentrated. The solution was then analyzed by crude... 1 Yield was determined by ¹H NMR, using 1,3,5-trimethoxybenzene as an internal standard. The aqueous phase containing the recovered catalyst was used directly for the next catalytic cycle. Fresh 4,4-difluorocyclohexanecarboxylic acid (1a, 0.3 mmol), 1,1-bis(benzenesulfonyl)ethylene (2a, 0.2 mmol), and acetone (1.5 mL) were added to the remaining aqueous solution. The mixture was irradiated with an LED for 24 hours to complete the second reaction cycle. The same working procedure was then performed to determine the yield and retain the aqueous phase. The same steps were repeated for the third cycle.
[0042] The product yields of Example 4 and Comparative Example 1 were tested after three consecutive cycles, and the results are as follows: Figure 4 As shown, through Figure 4 It can be seen that the uranyl catalyst UO2(NO3)2·6H2O in Example 1 can still maintain a yield of over 95% after being used three times, demonstrating excellent recyclability. In contrast, the reaction efficiency of the iron-containing compound catalyst in Comparative Example 1 decreased significantly.
[0043] Example 5 Gram-scale scale-up experiment The reaction formula is:
[0044] Under nitrogen protection, 2-(4-methoxycarbonylphenoxy)acetic acid (1d, 7.5 mmol), 2-benzylmalonium (2b, 5.0 mmol), and UO2(NO3)2·6H2O (8 mol%) were placed in a reaction vessel, and a mixed solvent of acetone (25.0 mL) and water (5.0 mL) was added. The resulting mixture was then irradiated with blue light at 25 °C for 30 hours. After the reaction, the solvent was removed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / dichloromethane = 1:1-1:3) to give product 3db (1.1053 g), with a separation yield of 73%. This experiment demonstrates that the decarboxylation method of the present invention has good potential for large-scale application.
[0045] Example 6 Free radical capture experiment The reaction formula is:
[0046] Under standard reaction conditions, a mixed solvent of acetone (1.5 mL) and water (1.5 mL) was added to a reaction system containing 4,4-difluorocyclohexanecarboxylic acid (1a, 0.3 mmol), 1,1-bis(benzenesulfonyl)ethylene (2a, 0.2 mmol), and UO2(NO3)2·6H2O (10 mol%). Then, 2,2,6,6-tetramethylpiperidin-1-oxy (TEMPO, 2.0 equivalent) was added. After the reaction was complete, the solution was obtained by... 1 1H NMR analysis showed a significant decrease in the yield of product 3aa to 4%. Simultaneously, high-resolution mass spectrometry (HRMS) detected the signal of the adduct of TEMPO with the decarboxylation radical, such as... Figure 5 As shown in the figure. This experiment confirms that free radical intermediates are generated during the reaction.
[0047] Example 7 Substrate Applicability Scope Investigation The reaction formula is:
[0048] Under nitrogen protection, different carboxylic acids 1 (0.3 mmol), different electron-deficient olefins 2 (0.2 mmol), and UO2(NO3)2·6H2O (8 mol%) were placed in a reaction tube, and a mixed solvent of acetone and water (5:1, 3.0 mL) was added. The resulting mixture was then irradiated with blue light at 25 °C for 24 hours. After the reaction, a series of target products were obtained by conventional post-processing (concentration under reduced pressure, column chromatography separation), the structures of which were all determined by... 1 H NMR, 13 Confirmed by C NMR and HRMS. Yield as follows: Figure 6As shown, through Figure 6 It can be seen that the product yields after the reaction of different carboxylic acids and different electron-deficient alkenes range from 42% to 99%, proving that the decarboxylation reaction method of the present invention has wide applicability to various carboxylic acids (aryloxyacetic acid, amino acid derivatives, phenylacetic acid, cyclic and chain aliphatic carboxylic acids, etc.) and electron-deficient alkenes (maleonitrile, acrylate, vinyl sulfone, vinyl ketone, etc.).
[0049] Example 8 Pure aqueous phase reaction A portion of the substrate was selected, and the reaction was carried out under the same conditions as in Example 8, except that the mixed solvent was replaced with pure water (3.0 mL). The product yield was as follows. Figure 7 As shown, through Figure 7 It can be seen that, except for a few substrates (such as Boc-protected glycine) where the yield decreased, most reactions still achieved acceptable yields (40%-87%), proving that uranyl salt photocatalysis is equally effective in pure water reaction media.
[0050] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A base-free, cyclic decarboxylation reaction method based on water-soluble uranyl salt photocatalysis, characterized in that, Includes the following steps: Under alkaline conditions, a carboxylic acid compound, an electron-deficient olefin compound, and a water-soluble uranyl salt are mixed and then a reaction medium containing water is added to obtain a mixture. The mixture is then irradiated with visible light to induce a decarboxylation addition reaction in the carboxylic acid compound.
2. The alkali-free, cyclic decarboxylation reaction method based on water-soluble uranyl salt photocatalysis according to claim 1, characterized in that, The carboxylic acid compound is any one of aliphatic carboxylic acids, aryloxyacetic acids, amino acid derivatives, and phenylacetic acids.
3. The alkali-free, cyclic decarboxylation reaction method based on water-soluble uranyl salt photocatalysis according to claim 1, characterized in that, The electron-deficient olefin compound is any one of maleic nitrile, acrylate, benzenesulfonyl vinyl, and vinyl ketone compounds.
4. The alkali-free, cyclic decarboxylation reaction method based on water-soluble uranyl salt photocatalysis according to claim 1, characterized in that, The water-soluble uranyl salt is uranyl nitrate hexahydrate; The amount of water-soluble uranyl salt added is 1-10 mol of the molar amount of the carboxylic acid compound.
5. The alkali-free, cyclic decarboxylation reaction method based on water-soluble uranyl salt photocatalysis according to claim 1, characterized in that, The reaction medium containing water is water or a mixture of water and an organic solvent.
6. The alkali-free, cyclic decarboxylation reaction method based on water-soluble uranyl salt photocatalysis according to claim 1, characterized in that, The ratio of the added carboxylic acid compound to the electron-deficient olefin compound is 1.5:
1.
7. The alkali-free, cyclic decarboxylation reaction method based on water-soluble uranyl salt photocatalysis according to claim 1, characterized in that, The visible light is blue light with a wavelength of 440-445 nm.
8. The alkali-free, cyclic decarboxylation reaction method based on water-soluble uranyl salt photocatalysis according to claim 1, characterized in that, The addition reaction was carried out under nitrogen protection for 24 hours.
9. The alkali-free, cyclic decarboxylation reaction method based on water-soluble uranyl salt photocatalysis according to claim 1, characterized in that, After the addition reaction is completed, the organic phase is extracted and separated. The resulting aqueous phase containing the catalyst is directly used in the next round of reaction, thus realizing the recycling of the catalyst.