Water-soluble ruthenium catalyst as well as preparation method and application thereof

Abstract

The invention provides a water-soluble ruthenium catalyst as well as a preparation method and application thereof. The water-soluble ruthenium catalyst disclosed by the invention has the advantages of good water solubility, high catalytic efficiency, high chemical stability and no toxicity; the water-soluble ruthenium catalyst can be used for reduction of carbonyl compounds and catalysis of reduction reaction of carbonyl in bufalin precursor molecules in water to generate bufalin molecules; the polymer ruthenium catalyst is synthesized through a reversible addition-fragmentation transfer polymerization method, and the synthesis method is simple and short in synthesis step.

Description

Technical Field

[0001] The present invention relates to the technical field of catalysts, and in particular to a water-soluble ruthenium catalyst and a preparation method and application thereof. Background Art

[0002] The transition metal ruthenium, located in Group VIII of the fifth period of the periodic table, is a rare and precious metal. Ruthenium exhibits excellent catalytic activity and good electrical and thermal conductivity, making it widely used in electronics, biomedicine, electrochemistry, and optical sensors. In the chemical industry, ruthenium catalysts are used to selectively catalyze the hydrogenation reduction of benzene to synthesize cyclohexene. In the biomedicine field, ruthenium catalysts are used to prepare naproxen, an anti-inflammatory and anti-tumor drug. In the ammonia synthesis industry, ruthenium catalysts have higher catalytic activity than other transition metal catalysts. In the field of optical sensors, the luminescence color, intensity, and lifetime of ruthenium catalysts can vary with the concentration of these ions in the measured system, making them excellent optical sensors for these ions.

[0003] Ruthenium catalysts play an indispensable role in the chemical industry, playing a particularly important role in petrochemicals, chemical materials, and pharmaceutical research and development. However, currently developed ruthenium catalysts have poor water solubility, limiting catalytic reactions to organic solvents, which places significant pressure on the environment.

[0004] The currently developed ruthenium catalysts are insoluble in water and cannot catalyze organic reactions in water. Therefore, it is necessary to improve the existing ruthenium catalysts. Summary of the Invention

[0005] The present invention provides a water-soluble ruthenium catalyst and a preparation method and application thereof, so as to solve or at least partially solve the defects in the prior art.

[0006] In a first aspect, the present invention provides a water-soluble ruthenium catalyst, the chemical structure of which is shown below:

[0007]

[0008] Wherein, m and n are both positive integers, 1≤m≤10, 1≤n≤10.

[0009] In a second aspect, the present invention further provides a method for preparing the water-soluble ruthenium catalyst, comprising the following steps:

[0010] A water-soluble ruthenium catalyst was synthesized in a one-pot method using RAFT reagent, ruthenium-containing olefins and acryloyloxyethyltrimethylammonium chloride as reaction raw materials and AIBN as initiator.

[0011] Wherein, the chemical structural formula of the RAFT agent is:

[0012] The chemical structural formula of the ruthenium-containing olefin is:

[0013] Preferably, the RAFT agent, the ruthenium-containing olefin, acryloyloxyethyltrimethylammonium chloride and AIBN are dissolved in a first solvent, deoxygenated, and reacted at 80-85° C. for 20-27 hours to obtain a water-soluble ruthenium catalyst.

[0014] Preferably, the preparation method of the RAFT agent is:

[0015] Using sodium hydride, 1-butanethiol, and carbon disulfide as raw materials, a first intermediate product is obtained through reaction;

[0016] Using the first intermediate product and elemental iodine as raw materials, a second intermediate product is obtained by reaction;

[0017] The second intermediate product and 4,4'-azobis(4-cyanovaleric acid) are used as raw materials to react and obtain a RAFT agent;

[0018] Wherein, the chemical structural formula of the first intermediate product is:

[0019] The chemical structural formula of the second intermediate product is:

[0020] And / or, the preparation method of the ruthenium-containing olefin is:

[0021] Under alkaline conditions, N-((1R,2R)-2-amino-1,2-diphenylethyl)-4-vinylbenzenesulfonamide and dichlorobis(4-methylisopropylphenyl)ruthenium(II) are used as raw materials to react and obtain ruthenium-containing olefins.

[0022] Preferably, the preparation method of the RAFT agent comprises the following steps:

[0023] mixing sodium hydride and a second solvent to obtain a mixed solution;

[0024] The mixed solution was cooled to 0-2°C, 1-butanethiol was added dropwise, and the mixture was reacted for 10-30 minutes under an inert atmosphere. The temperature was continued to be maintained at 0-2°C, carbon disulfide was added, and the temperature was raised to 20-25°C. The reaction was continued to obtain a first intermediate product;

[0025] Elemental iodine is continuously added to the reaction system and reacted at 20-25°C to obtain a second intermediate product;

[0026] The second intermediate product and 4,4'-azobis(4-cyanovaleric acid) are added to a third solvent, and reacted at 20-25°C under an inert atmosphere to obtain a RAFT agent;

[0027] The method for preparing the ruthenium-containing olefin comprises the following steps:

[0028] N-((1R,2R)-2-amino-1,2-diphenylethyl)-4-vinylbenzenesulfonamide, dichlorobis(4-methylisopropylphenyl)ruthenium(II) and potassium carbonate are added to a fourth solvent, and after deoxygenation, the mixture is reacted at 20-25° C. under the protection of an inert atmosphere to obtain a ruthenium-containing olefin.

[0029] Preferably, the molar volume ratio of the RAFT agent, the ruthenium-containing olefin, the acryloyloxyethyltrimethylammonium chloride, AIBN, and the first solvent is (0.1-0.2) mmol: (1-1.1) mmol: (5-5.1) mmol: (0.03-0.04) mmol: (5-6) mL;

[0030] The first solvent is DMSO;

[0031] And / or, the molar volume ratio of the sodium hydride, 1-butanethiol, carbon disulfide, elemental iodine, 4,4'-azobis(4-cyanovaleric acid), the second solvent, and the third solvent is (36.3-36.5) mmol:(32.04-32.06) mmol:(159.92-159.96) mmol:(20-21) mmol:(47.95-48) mmol:(50-55) mL:(50-55) mL;

[0032] The second solvent is anhydrous ether;

[0033] The third solvent is ethyl acetate;

[0034] and / or, the molar volume ratio of the N-((1R,2R)-2-amino-1,2-diphenylethyl)-4-vinylbenzenesulfonamide, dichlorobis(4-methylisopropylphenyl)ruthenium(II), potassium carbonate, and the fourth solvent is (2-4) mmol:(1-2) mmol:(1.1-1.2) mmol:(150-160) mL;

[0035] The fourth solvent is ethanol;

[0036] And / or, the inert atmosphere includes at least one of nitrogen, helium, neon, and argon.

[0037] In a third aspect, the present invention also provides an application of the water-soluble ruthenium catalyst or the water-soluble ruthenium catalyst prepared by the preparation method in catalyzing the reduction of carbonyl compounds to alcohol compounds or in catalyzing the carbonyl reduction reaction in a toad venom precursor molecule to generate a toad venom molecule.

[0038] Preferably, the chemical structural formula of the carbonyl compound is:

[0039] The chemical structural formula of the alcohol-forming compound is:

[0040] The R group is selected from any one of H, methyl, and Cl;

[0041] The chemical structural formula of the bufalin precursor molecule is:

[0042] Preferably, the application of the water-soluble ruthenium catalyst in catalyzing the reduction of carbonyl compounds to alcohol compounds specifically includes:

[0043] Mixing a carbonyl compound, a water-soluble ruthenium catalyst, sodium formate and water, and reacting at 20-25°C to obtain an alcohol compound;

[0044] The application of the water-soluble ruthenium catalyst in catalyzing the carbonyl reduction reaction in the bufalin precursor molecule to generate the bufalin molecule specifically includes:

[0045] The bufalin precursor molecule, a water-soluble ruthenium catalyst, sodium formate and water are mixed and reacted at 20-25° C. to obtain the bufalin molecule.

[0046] Preferably, in the step of mixing the carbonyl compound, the water-soluble ruthenium catalyst, sodium formate and water, the molar volume ratio of the carbonyl compound, the water-soluble ruthenium catalyst, the sodium formate and the water is (0.4-0.5) mmol: (0.004-0.005) mmol: (2-3) mmol: (1.5-2) mL;

[0047] In the step of mixing the bufalin precursor molecule, the water-soluble ruthenium catalyst, sodium formate and water, the molar volume ratio of the bufalin precursor molecule, the water-soluble ruthenium catalyst, sodium formate and water is (0.1-0.2) mmol: (0.001-0.002) mmol: (0.5-1) mmol: (0.5-1) mL.

[0048] The water-soluble ruthenium catalyst of the present invention, its preparation method and application have the following technical effects compared with the prior art:

[0049] The water-soluble ruthenium catalyst of the present invention has the advantages of good water solubility, high catalytic efficiency, high chemical stability and non-toxicity; and the water-soluble ruthenium catalyst of the present invention can be used for the reduction of carbonyl compounds, and catalyzes the carbonyl reduction reaction in bufalotoxin precursor molecules in water to generate bufalotoxin molecules; the present invention synthesizes a polymer ruthenium catalyst through a reversible addition-fragmentation transfer polymerization method, and the synthesis method is simple and the synthesis steps are short. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] To more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. Those skilled in the art can also derive other drawings based on these drawings without inventive effort.

[0051] Figure 1 The water-soluble ruthenium catalyst prepared in Example 1 1 H NMR spectrum;

[0052] Figure 2 is the RAFT agent prepared in Example 1 1 H NMR spectrum;

[0053] Figure 3 The ruthenium-containing olefin prepared in Example 1 1 H NMR spectrum;

[0054] Figure 4 For the alcohol compound prepared in Example 2 1 H NMR spectrum;

[0055] Figure 5 For the alcohol compound prepared in Example 3 1 H NMR spectrum;

[0056] Figure 6 For the alcohol compound prepared in Example 4 1 H NMR spectrum;

[0057] Figure 7 The bufalin prepared in Example 5 1 H NMR spectrum. DETAILED DESCRIPTION

[0058] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0059] The following are detailed descriptions respectively. It should be noted that the order of description of the following embodiments is not intended to limit the preferred order of the embodiments. In addition, in the description of this application, the term "including" means "including but not limited to". Various embodiments of the present invention may be in the form of a range; it should be understood that the description in the form of a range is only for convenience and brevity and should not be understood as a rigid limitation on the scope of the invention; therefore, it should be considered that the range description has specifically disclosed all possible sub-ranges and single numerical values within the range. For example, the range description from 1 to 6 should be considered to have specifically disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as single numbers within the numbered ranges, such as 1, 2, 3, 4, 5 and 6, which apply regardless of the range. In addition, whenever a numerical range is indicated in this article, it is meant to include any cited numbers (fractions or integers) within the indicated range.

[0060] The present invention provides a water-soluble ruthenium catalyst, the chemical structure of which is shown below:

[0061]

[0062] Wherein, m and n are both positive integers, 1≤m≤10, 1≤n≤10.

[0063] The water-soluble ruthenium catalyst of the invention has good water solubility, high catalytic efficiency, high chemical stability and is non-toxic.

[0064] Based on the same inventive concept, the present invention also provides a method for preparing the above-mentioned water-soluble ruthenium catalyst, comprising the following steps:

[0065] S1. A water-soluble ruthenium catalyst was synthesized in a one-pot method using a RAFT agent, a ruthenium-containing olefin, and acryloyloxyethyltrimethylammonium chloride as reaction raw materials and AIBN as an initiator;

[0066] Among them, the chemical structure of the RAFT agent is:

[0067] The chemical formula of ruthenium-containing olefins is:

[0068] In some embodiments, a RAFT agent, a ruthenium-containing olefin, acryloyloxyethyltrimethylammonium chloride, and AIBN (azobisisobutyronitrile) are dissolved in a first solvent, deoxygenated, and reacted at 80-85° C. for 20-27 hours to obtain a water-soluble ruthenium catalyst.

[0069] In some embodiments, the molar volume ratio of the RAFT agent, the ruthenium-containing olefin, the acryloyloxyethyltrimethylammonium chloride, the AIBN, and the first solvent is (0.1-0.2) mmol: (1-1.1) mmol: (5-5.1) mmol: (0.03-0.04) mmol: (5-6) mL;

[0070] The first solvent is DMSO (dimethyl sulfoxide).

[0071] Specifically, in some embodiments, the synthesis route of the water-soluble ruthenium catalyst is as follows:

[0072]

[0073] A water-soluble ruthenium catalyst Ru catalyst was generated using RAFT agent 1a, ruthenium-containing olefin 1b, and acryloyloxyethyltrimethylammonium chloride 1c as raw materials in the presence of chain initiator azobisisobutyronitrile (AIBN).

[0074] In some embodiments, the RAFT agent is prepared by:

[0075] S1, using sodium hydride, 1-butanethiol, and carbon disulfide as raw materials to react to obtain a first intermediate product;

[0076] S2. Using the first intermediate product and elemental iodine as raw materials, reacting to obtain a second intermediate product;

[0077] S3, using the second intermediate product and 4,4'-azobis(4-cyanovaleric acid) as raw materials, reacting to obtain a RAFT agent;

[0078] Among them, the chemical structural formula of the first intermediate product is:

[0079] The chemical structural formula of the second intermediate product is:

[0080] In some embodiments, the method for preparing a RAFT agent comprises the following steps:

[0081] S1, mixing sodium hydride and a second solvent to obtain a mixed solution;

[0082] S2, cooling the mixed solution to 0-2°C, adding 1-butanethiol dropwise, reacting for 10-30 min under inert atmosphere, continuing to maintain the temperature at 0-2°C, adding carbon disulfide, raising the temperature to 20-25°C, and continuing the reaction to obtain a first intermediate product;

[0083] S3, continue to add iodine to the reaction system, react at 20-25 ° C to obtain a second intermediate product;

[0084] S4. Add the second intermediate product and 4,4'-azobis(4-cyanovaleric acid) to the third solvent, and react at 20-25° C. under an inert atmosphere to obtain a RAFT reagent.

[0085] In some embodiments, the molar volume ratio of sodium hydride, 1-butanethiol, carbon disulfide, iodine, 4,4'-azobis(4-cyanovaleric acid), the second solvent, and the third solvent is (36.3-36.5) mmol: (32.04-32.06) mmol: (159.92-159.96) mmol: (20-21) mmol: (47.95-48) mmol: (50-55) mL: (50-55) mL;

[0086] The second solvent was anhydrous ether.

[0087] The third solvent is ethyl acetate.

[0088] Specifically, the synthesis route of the RAFT agent is as follows:

[0089]

[0090] In some embodiments, the method for preparing ruthenium-containing olefins comprises the following steps:

[0091] Under alkaline conditions, N-((1R,2R)-2-amino-1,2-diphenylethyl)-4-vinylbenzenesulfonamide and dichlorobis(4-methylisopropylphenyl)ruthenium(II) are used as raw materials to react and obtain ruthenium-containing olefins.

[0092] In some embodiments, the method for preparing ruthenium-containing olefins comprises the following steps:

[0093] N-((1R,2R)-2-amino-1,2-diphenylethyl)-4-vinylbenzenesulfonamide, dichlorobis(4-methylisopropylphenyl)ruthenium(II) and potassium carbonate are added to a fourth solvent, and after deoxygenation, the mixture is reacted at 20-25° C. under the protection of an inert atmosphere to obtain a ruthenium-containing olefin.

[0094] In some embodiments, the molar volume ratio of N-((1R,2R)-2-amino-1,2-diphenylethyl)-4-vinylbenzenesulfonamide, dichlorobis(4-methylisopropylphenyl)ruthenium(II), potassium carbonate, and the fourth solvent is (2-4) mmol:(1-2) mmol:(1.1-1.2) mmol:(150-160) mL;

[0095] The fourth solvent is ethanol.

[0096] In some embodiments, the synthesis route of ruthenium-containing olefins is as follows:

[0097]

[0098] Due to the poor water solubility of current ruthenium catalysts, currently developed catalytic reactions are limited to reaction systems using organic solvents, which places significant pressure on the environment. The present invention synthesizes a polymer ruthenium catalyst through reversible addition-fragmentation transfer polymerization. This catalyst exhibits excellent water solubility, high catalytic efficiency, and non-toxicity. The catalytic effect of this new catalyst in aqueous phase was demonstrated using the reduction of carbonyl compounds to alcohols as an example. The synthesis method of the water-soluble ruthenium catalyst of the present invention is simple and involves a short synthesis process.

[0099] In some embodiments, the inert atmosphere includes at least one of nitrogen, helium, neon, and argon.

[0100] Based on the same inventive concept, the present invention also provides an application of the above-mentioned water-soluble ruthenium catalyst or the water-soluble ruthenium catalyst prepared by the above-mentioned preparation method in catalyzing the reduction of carbonyl compounds to alcohol compounds or in catalyzing the carbonyl reduction reaction in a bufatoxin precursor molecule to generate a bufatoxin molecule.

[0101] Specifically, the water-soluble ruthenium catalyst of the present invention can be used to reduce carbonyl compounds of various types to alcohol compounds. For example, under the catalysis of the water-soluble ruthenium catalyst, sodium formate as a hydrogen source, water as a solvent, and under room temperature reaction conditions, acetophenones with electron-donating or electron-withdrawing groups attached to the benzene ring can adapt to this reaction system. Furthermore, the water-soluble ruthenium catalyst of the present invention can also be used in the synthesis of anti-tumor drugs. For example, the water-soluble ruthenium catalyst catalyzes the reduction of the carbonyl group in a bufalin precursor molecule in water to produce the bufalin molecule.

[0102] In some embodiments, the carbonyl compound has the chemical formula:

[0103] The chemical structure of the alcohol compound is:

[0104] The R group is selected from any one of H, methyl (Me), and Cl.

[0105] In some embodiments, the chemical formula of the bufalin precursor molecule is:

[0106] In some embodiments, the use of a water-soluble ruthenium catalyst in catalyzing the reduction of a carbonyl compound to an alcohol compound specifically includes:

[0107] The carbonyl compound, a water-soluble ruthenium catalyst, sodium formate and water are mixed and reacted at 20-25° C. to obtain an alcohol compound.

[0108] In some embodiments, in the step of mixing the carbonyl compound, the water-soluble ruthenium catalyst, sodium formate and water, the molar volume ratio of the carbonyl compound, the water-soluble ruthenium catalyst, sodium formate and water is (0.4-0.5) mmol: (0.004-0.005) mmol: (2-3) mmol: (1.5-2) mL.

[0109] In some embodiments, the synthesis route of a water-soluble ruthenium catalyst in catalyzing the reduction of a carbonyl compound to an alcohol compound is as follows:

[0110]

[0111] In some embodiments, the alcohol compound is

[0112] In some embodiments, the use of a water-soluble ruthenium catalyst in catalyzing the reduction reaction of the carbonyl group in a bufalin precursor molecule to generate a bufalin molecule specifically includes:

[0113] The bufalin precursor molecule, a water-soluble ruthenium catalyst, sodium formate and water are mixed and reacted at 20-25° C. to obtain the bufalin molecule.

[0114] In some embodiments, in the step of mixing the bufatoxin precursor molecule, the water-soluble ruthenium catalyst, sodium formate and water, the molar volume ratio of the bufatoxin precursor molecule, the water-soluble ruthenium catalyst, sodium formate and water is (0.1-0.2) mmol: (0.001-0.002) mmol: (0.5-1) mmol: (0.5-1) mL.

[0115] Specifically, bufotolin, also known as bufotoxin, has a molecular formula of C 24 H 34 O4.

[0116] In some embodiments, the synthesis route for the water-soluble ruthenium catalyst to catalyze the carbonyl reduction reaction of a bufalin precursor molecule to generate a bufalin molecule is as follows:

[0117]

[0118] The following further illustrates the water-soluble ruthenium catalyst of the present application, its preparation method, and application using specific examples. This section further illustrates the present invention in conjunction with specific examples, but should not be construed as limiting the present invention. Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in the art.

[0119] Example 1

[0120] The present invention provides a water-soluble ruthenium catalyst, the chemical structure of which is as follows:

[0121]

[0122] Wherein, m and n are both positive integers, 1≤m≤10, 1≤n≤10.

[0123] The preparation method of the water-soluble ruthenium catalyst comprises the following steps:

[0124] In a 50 mL round-bottom flask, a RAFT agent (29 mg, 0.1 mmol), a ruthenium-containing olefin (674 mg, 1.0 mmol), acryloyloxyethyltrimethylammonium chloride (1210 mg, 5.0 mmol), and a chain initiator, azobisisobutyronitrile (AIBN) (5 mg, 0.03 mmol), were dissolved in DMSO (5 mL). After deoxygenation with argon for 45 minutes, the mixture was placed in an 80°C bath and reacted for 20 to 27 hours. Air was then introduced to terminate the reaction. After cooling to room temperature, the mixture was precipitated with ether by centrifugation and washed three times with ether in an ice bath. The resulting polymer mixture was dialyzed against deionized water (DIW) using a dialysis bag with a molecular weight cutoff of 1500 and finally lyophilized to obtain a pale yellow solid product (99% conversion), i.e., a water-soluble ruthenium catalyst. Figure 1 The water-soluble ruthenium catalyst prepared in Example 1 1 H NMR spectra;

[0125] The preparation method of the RAFT agent comprises the following steps:

[0126] S1. Sodium hydride (NaH) (1.45 g, 36.3 mmol) and anhydrous ether (50 mL) were added to a 100 mL round-bottom flask to obtain a mixed solution, which was cooled to 0°C, and 1-butanethiol (2.89 g, 32.04 mmol) was then added dropwise to the round-bottom flask; the mixture was reacted for 30 minutes under argon protection, and the temperature was maintained at 0°C. Carbon disulfide (12.18 g, 159.92 mmol) was added dropwise to the mixture, and the reaction temperature was raised to room temperature (25°C). The reaction was continued for 4 hours to obtain the first intermediate product; iodine (5.08 g, 20 mmol) was then added to the reaction system, and the reaction was continued at room temperature for 4 hours; after the reaction was completed, the sodium iodide solid was removed by filtration, and the mixture was heated to 40°C with 1 mol / L The filtrate was washed several times with a Na2S2O3 aqueous solution to remove unreacted iodine; 50 mL of ethyl acetate and 50 mL of ice water were added to the reaction mixture, stirred thoroughly, and separated using a separatory funnel. The aqueous layer was extracted three times with 50 mL of ethyl acetate, and the organic layers were combined, dried over anhydrous sodium sulfate, and rotary distilled to remove ethyl acetate to obtain a second intermediate product;

[0127] S2. The second intermediate product obtained in the previous step, 4,4'-azobis(4-cyanovaleric acid) (13.44 g, 47.95 mmol) and 50 ml of ethyl acetate were added to a 100 ml round-bottom flask; the solution was refluxed and stirred overnight under an argon atmosphere. After the reaction stopped, 50 ml of ethyl acetate and 50 ml of ice water were added to the reaction mixture, and the mixture was stirred thoroughly and separated using a separatory funnel. The aqueous layer was extracted three times with 50 ml of ethyl acetate, and the organic layers were combined. The organic layers were dried over anhydrous sodium sulfate and rotary distilled to remove ethyl acetate to obtain the initial product; ethyl acetate: petroleum ether = 1:2 (volume ratio) was used as the eluent, and a pure light yellow liquid product (28% yield) was obtained by column chromatography, which was the RAFT agent;

[0128] RAFT agents 1 H NMR Figure 2 As shown, 1 H NMR (400MHz, CDCl3) δ3.36 (t, J = 7.4Hz, 2H), 2.76-2.63 (m, 2H), 2.61-2.46 (m, 1H), 2.47 -2.33(m,1H),1.90(s,3H),1.80-1.59(m,2H),1.52-1.33(m,2H),0.96(t,J=7.2Hz,3H);

[0129] The method for preparing ruthenium-containing olefins comprises the following steps:

[0130] To a 250 mL round-bottom flask, N-((1R,2R)-2-amino-1,2-diphenylethyl)-4-vinylbenzenesulfonamide (760 mg, 2 mmol), dichlorobis(4-methylisopropylphenyl)ruthenium(II) (612 mg, 1 mmol), potassium carbonate (160 mg, 1.1 mmol), and anhydrous ethanol (150 mL) were added. After deoxygenation with argon for 20 minutes, the mixture was reacted under argon protection at room temperature for 4 hours. After the reaction, the potassium carbonate was removed by filtration, and the ethanol was removed by rotary distillation. A pure yellow solid product (90% yield) was obtained by column chromatography using ethyl acetate:petroleum ether = 1:4 (volume ratio) as the eluent, which was the ruthenium-containing olefin.

[0131] Ruthenium-containing olefins 1 H NMR Figure 3 As shown, 1H NMR (400MHz, DMSO) δ7.20-6.99(m,7H),6.87-6.46(m,8H),5.90-5.50(m,5H),5.28(d,J=11.0Hz,1H), 3.74(d,J=11.2Hz,1H),3.57(d,J=11.2Hz,1H),3.08-2.88(m,1H),2.29(s,3H),1.33(d,J=6.8Hz,6H).

[0132] Example 2

[0133] This example provides the use of the water-soluble ruthenium catalyst in Example 1 in catalyzing the reduction of carbonyl compounds to alcohol compounds. Specifically, the reaction synthesis route is:

[0134]

[0135] The specific application includes the following steps:

[0136] Acetophenone (48 mg, 0.4 mmol), the water-soluble ruthenium catalyst prepared in Example 1 (60 mg, 0.004 mmol), sodium formate (136 mg, 2 mmol) and water (1.5 mL) were added to a 10 mL round-bottom flask and reacted at room temperature for 13 hours. After the reaction, 5 mL of ethyl acetate and 5 mL of ice water were added to the reaction mixture, stirred thoroughly, and separated using a separatory funnel. The aqueous layer was extracted three times with 5 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate, and rotary distilled to remove ethyl acetate to obtain a primary product. A pure colorless liquid product (60% yield) was obtained by column chromatography using ethyl acetate:petroleum ether = 1:10 (volume ratio) as the eluent, i.e., an alcohol compound.

[0137] Alcohol compounds 1 H NMR Figure 4 As shown, 1 H NMR (400MHz, CDCl3) δ7.43-7.34 (m, 4H), 7.34-7.25 (m, 1H), 4.91 (q, J = 6.4Hz, 1H), 2.08 (s, 1H), 1.52 (d, J = 6.4Hz, 3H).

[0138] Example 3

[0139] This example provides the use of the water-soluble ruthenium catalyst in Example 1 in catalyzing the reduction of carbonyl compounds to alcohol compounds. Specifically, the reaction synthesis route is:

[0140]

[0141] The specific application includes the following steps:

[0142] To a 10 mL round-bottom flask, add p-methylacetophenone (54 mg, 0.4 mmol), the water-soluble ruthenium catalyst prepared in Example 1 (60 mg, 0.004 mmol), sodium formate (136 mg, 2 mmol), and water (1.5 mL). The mixture was reacted at room temperature for 95 hours. After the reaction, 5 mL of ethyl acetate and 5 mL of ice water were added to the reaction mixture, stirred thoroughly, and separated using a separatory funnel. The aqueous layer was extracted three times with 5 mL of ethyl acetate, and the organic layers were combined. The organic layer was dried over anhydrous sodium sulfate and the ethyl acetate was removed by rotary distillation to obtain the initial product. Using ethyl acetate: petroleum ether = 1:10 (volume ratio) as the eluent, the pure colorless liquid product (61% yield) was separated by column chromatography to obtain the alcohol compound.

[0143] Alcohol compounds 1 H NMR Figure 5 As shown, 1 H NMR (400MHz, CDCl3) δ7.29 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 4.88 (q, J = 6.4 Hz, 1H), 2.38 (s, 3H), 2.07 (s, 1H), 1.51 (d, J = 6.4 Hz, 3H).

[0144] Example 4

[0145] This example provides the use of the water-soluble ruthenium catalyst in Example 1 in catalyzing the reduction of carbonyl compounds to alcohol compounds. Specifically, the reaction synthesis route is:

[0146]

[0147] The specific application includes the following steps:

[0148] In a 10 ml round-bottom flask, p-chloroacetophenone (62 mg, 0.4 mmol), the water-soluble ruthenium catalyst prepared in Example 1 (60 mg, 0.004 mmol), sodium formate (136 mg, 2 mmol) and water (1.5 mL) were added to the mixture and reacted at room temperature for 18 hours. After the reaction, 5 mL of ethyl acetate and 5 mL of ice water were added to the reaction mixture, and the mixture was stirred thoroughly and separated using a separatory funnel. The aqueous layer was extracted three times with 5 mL of ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate. The ethyl acetate was removed by rotary distillation to obtain a preliminary product. The product was separated by column chromatography using ethyl acetate: petroleum ether = 1:10 (volume ratio) as the eluent to obtain a pure colorless liquid product (90% yield), i.e., an alcohol compound.

[0149] Alcohol compounds 1 H NMR Figure 6As shown, 1 H NMR (400MHz, CDCl3) δ7.36-7.26 (m, 4H), 4.87 (q, J = 6.4Hz, 1H), 2.21 (s, 1H), 1.48 (d, J = 6.4Hz, 3H).

[0150] Example 5

[0151] This example provides the use of the water-soluble ruthenium catalyst in Example 1 in catalyzing the carbonyl reduction reaction of a bufalin precursor molecule to produce a bufalin molecule. Specifically, the reaction synthesis route is:

[0152]

[0153] The specific application includes the following steps:

[0154] To a 10 mL round-bottom flask, add the bufalin precursor molecule (0.1 mmol), the water-soluble ruthenium catalyst prepared in Example 1 (15 mg, 0.001 mmol), sodium formate (34 mg, 0.5 mmol), and water (0.5 mL). The mixture was reacted at room temperature for 24 hours. After the reaction, 5 mL of ethyl acetate and 5 mL of ice water were added to the reaction mixture, stirred thoroughly, and separated using a separatory funnel. The aqueous layer was extracted three times with 5 mL of ethyl acetate, and the organic layers were combined. The organic layer was dried over anhydrous sodium sulfate and the ethyl acetate was removed by rotary distillation to obtain the initial product. Using ethyl acetate: petroleum ether = 1:1 (volume ratio) as the eluent, the product was separated by column chromatography to obtain a pure white solid product (50% yield), namely, bufalin.

[0155] Toad venom 1 H NMR Figure 7 As shown, 1 H NMR (400MHz, DMSO) δ7.94(d,J=9.6Hz,1H),7.52(s,1H),6.29(d,J=9.6Hz,1H),4.17(d,J=21.6Hz,2H),3.90(s,1H), 2.45(s,1H),2.15-1.88(m,2H),1.87-1.54(m,7H),1.54-1.25(m,8H),1.25-0.95(m,4H),0.86(s,3H),0.60(s,3H).

[0156] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A water-soluble ruthenium catalyst, characterized in that The chemical structural formula of the water-soluble ruthenium catalyst is shown below: Wherein, m and n are both positive integers, 1≤m≤10, 1≤n≤10.

2. A method for preparing a water-soluble ruthenium catalyst according to claim 1, characterized in that: The following steps are involved: A water-soluble ruthenium catalyst was synthesized in a one-pot method using RAFT reagent, ruthenium-containing olefins and acryloyloxyethyltrimethylammonium chloride as reaction raw materials and AIBN as initiator. Wherein, the chemical structural formula of the RAFT agent is: The chemical structural formula of the ruthenium-containing olefin is:

3. The method for preparing a water-soluble ruthenium catalyst according to claim 2, wherein: A RAFT agent, a ruthenium-containing olefin, acryloyloxyethyltrimethylammonium chloride and AIBN are dissolved in a first solvent, and after deoxygenation, the mixture is reacted at 80-85° C. for 20-27 hours to obtain a water-soluble ruthenium catalyst.

4. The method for preparing a water-soluble ruthenium catalyst according to claim 3, wherein: The preparation method of the RAFT agent is: Using sodium hydride, 1-butanethiol, and carbon disulfide as raw materials, a first intermediate product is obtained through reaction; Using the first intermediate product and elemental iodine as raw materials, a second intermediate product is obtained by reaction; The second intermediate product and 4,4'-azobis(4-cyanovaleric acid) are used as raw materials to react and obtain a RAFT agent; Wherein, the chemical structural formula of the first intermediate product is: The chemical structural formula of the second intermediate product is: And / or, the preparation method of the ruthenium-containing olefin is: Under alkaline conditions, N-((1R,2R)-2-amino-1,2-diphenylethyl)-4-vinylbenzenesulfonamide and dichlorobis(4-methylisopropylphenyl)ruthenium(II) are used as raw materials to react and obtain ruthenium-containing olefins.

5. The method for preparing a water-soluble ruthenium catalyst according to claim 4, wherein: The preparation method of the RAFT agent comprises the following steps: mixing sodium hydride and a second solvent to obtain a mixed solution; The mixed solution was cooled to 0-2°C, 1-butanethiol was added dropwise, and the mixture was reacted for 10-30 minutes under an inert atmosphere. The temperature was continued to be maintained at 0-2°C, carbon disulfide was added, and the temperature was raised to 20-25°C. The reaction was continued to obtain a first intermediate product; Elemental iodine is continuously added to the reaction system and reacted at 20-25°C to obtain a second intermediate product; The second intermediate product and 4,4'-azobis(4-cyanovaleric acid) are added to a third solvent, and reacted at 20-25°C under an inert atmosphere to obtain a RAFT agent; The method for preparing the ruthenium-containing olefin comprises the following steps: N-((1R,2R)-2-amino-1,2-diphenylethyl)-4-vinylbenzenesulfonamide, dichlorobis(4-methylisopropylphenyl)ruthenium(II) and potassium carbonate are added to a fourth solvent, and after deoxygenation, the mixture is reacted at 20-25° C. under the protection of an inert atmosphere to obtain a ruthenium-containing olefin.

6. The method for preparing a water-soluble ruthenium catalyst according to claim 5, wherein: The molar volume ratio of the RAFT agent, the ruthenium-containing olefin, acryloyloxyethyltrimethylammonium chloride, AIBN, and the first solvent is (0.1-0.2) mmol: (1-1.1) mmol: (5-5.1) mmol: (0.03-0.04) mmol: (5-6) mL; The first solvent is DMSO; And / or, the molar volume ratio of the sodium hydride, 1-butanethiol, carbon disulfide, elemental iodine, 4,4'-azobis(4-cyanovaleric acid), the second solvent, and the third solvent is (36.3-36.5) mmol:(32.04-32.06) mmol:(159.92-159.96) mmol:(20-21) mmol:(47.95-48) mmol:(50-55) mL:(50-55) mL; The second solvent is anhydrous ether; The third solvent is ethyl acetate; and / or, the molar volume ratio of the N-((1R,2R)-2-amino-1,2-diphenylethyl)-4-vinylbenzenesulfonamide, dichlorobis(4-methylisopropylphenyl)ruthenium(II), potassium carbonate, and the fourth solvent is (2-4) mmol:(1-2) mmol:(1.1-1.2) mmol:(150-160) mL; The fourth solvent is ethanol; And / or, the inert atmosphere includes at least one of nitrogen, helium, neon, and argon.

7. Use of the water-soluble ruthenium catalyst as claimed in claim 1 or the water-soluble ruthenium catalyst prepared by the preparation method according to any one of claims 2 to 6 in catalyzing the reduction of carbonyl compounds to alcohol compounds or in catalyzing the reduction reaction of carbonyl groups in a bufatoxin precursor molecule to produce a bufatoxin molecule.

8. The use according to claim 7, characterized in that The chemical structural formula of the carbonyl compound is: The chemical structural formula of the alcohol-forming compound is: The R group is selected from any one of H, methyl, and Cl; The chemical structural formula of the bufalin precursor molecule is:

9. The use according to claim 8, characterized in that The application of the water-soluble ruthenium catalyst in catalyzing the reduction of carbonyl compounds to alcohol compounds specifically includes: Mixing a carbonyl compound, a water-soluble ruthenium catalyst, sodium formate and water, and reacting at 20-25°C to obtain an alcohol compound; The application of the water-soluble ruthenium catalyst in catalyzing the carbonyl reduction reaction in the bufalin precursor molecule to generate the bufalin molecule specifically includes: The bufalin precursor molecule, a water-soluble ruthenium catalyst, sodium formate and water are mixed and reacted at 20-25° C. to obtain the bufalin molecule.

10. The use according to claim 9, characterized in that In the step of mixing the carbonyl compound, the water-soluble ruthenium catalyst, sodium formate and water, the molar volume ratio of the carbonyl compound, the water-soluble ruthenium catalyst, the sodium formate and the water is (0.4-0.5) mmol: (0.004-0.005) mmol: (2-3) mmol: (1.5-2) mL; In the step of mixing the bufalin precursor molecule, the water-soluble ruthenium catalyst, sodium formate and water, the molar volume ratio of the bufalin precursor molecule, the water-soluble ruthenium catalyst, sodium formate and water is (0.1-0.2) mmol: (0.001-0.002) mmol: (0.5-1) mmol: (0.5-1) mL.

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