Novel water-soluble palladium complex as well as synthesis method and application thereof

Abstract

The invention provides a novel water-soluble palladium complex as well as a synthesis method and application thereof, and belongs to the technical field of metal organic catalysis. The invention provides a novel water-soluble palladium complex, and further provides a synthesis method of the novel water-soluble palladium complex, a catalyst prepared from the novel water-soluble palladium complex, and application of the novel water-soluble palladium complex to an organic synthesis catalytic reaction, especially a Suzuki-Miyaura cross-coupling reaction. The target product can be obtained with high reaction activity, and the method has important significance on synthesis of fine chemicals, biological medicines, new materials and the like.

Description

Technical Field

[0001] This invention belongs to the field of organometallic catalysis technology, and particularly relates to a novel water-soluble palladium complex, its synthesis method, and its application. Background Technology

[0002] The Suzuki-Miyaura cross-coupling reaction is a reliable method for constructing carbon-carbon bonds and is one of the most widely used carbon-carbon bond construction reactions in materials and medicinal chemistry. It offers advantages such as high efficiency, air stability, and the use of non-toxic organoboron reagents, making it widely applicable in the synthesis of pharmaceuticals, agrochemicals, and organic materials. However, traditional Suzuki-Miyaura cross-coupling reactions generally require an exogenous base to promote the transmetallation process. Due to undesirable incompatibility between deboronic acid groups and functional groups, incompatibility of deboronic acid groups or functional groups can sometimes occur. The necessity of the base limits its suitability for highly complex substrates and diverse biomolecules. Furthermore, traditional Suzuki-Miyaura cross-coupling reactions require organic solvents (such as DMF and t-BuOH), posing environmental pollution problems. With increasing environmental protection requirements, developing solvent-free and exogenous base-free reaction conditions has become a research hotspot.

[0003] Currently, phosphine-based ligands, such as TPPTS, are being used, but catalysts derived from them sometimes exhibit performance limitations; Pd(P-Phos)Cl2 complexes, which are widely used in traditional Suzuki-Miyaura cross-coupling reactions, suffer from side reaction problems.

[0004] In summary, the Suzuki-Miyaura cross-coupling reaction currently faces challenges related to substrate suitability, side reactions, and environmental pollution. Therefore, developing a water-soluble complex catalyst with suitable water solvents and high activity is of great significance. Summary of the Invention

[0005] In view of the aforementioned technical problems, this invention provides a novel water-soluble palladium complex, its synthesis method, and its applications. This synthesis method has advantages such as readily available and inexpensive raw materials, short synthesis steps, high yield, simple post-processing, and suitability for industrial production. Furthermore, the novel water-soluble palladium complex exhibits good reactivity and environmental friendliness, making it of great practical value.

[0006] Therefore, the above-mentioned objectives of the present invention are achieved through the following technical solutions.

[0007] In a first aspect, the present invention provides a novel water-soluble palladium complex with the following structural formula: ; in, R1 is independently selected from C1-C6 alkyl and C1-C6 alkoxy groups; R2 is independently selected from Cl, Br, or I.

[0008] Furthermore, R1 is independently selected from C1-C4 alkyl and C1-C4 alkoxy groups; R2 is independently selected from Cl, Br, or I.

[0009] Furthermore, R1 is independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, sec-butyloxy, or tert-butyloxy; R2 is independently selected from Cl, Br, or I.

[0010] Furthermore, the novel water-soluble palladium complex is one of the following compounds: .

[0011] Furthermore, the novel water-soluble palladium complex was prepared by reacting compound II with TPPTS: .

[0012] Further, compound II was stirred with TPPTS in a solution of tetrahydrofuran and water (volume ratio 10:1) for 3-6 hours, then the solvent was removed by rotary evaporation, and the mixture was dried in a vacuum oven at 60°C for 12-18 hours to obtain compound I.

[0013] Furthermore, the volume ratio of compound II to tetrahydrofuran and aqueous solution is 1:15–20.

[0014] Furthermore, the molar ratio of compound II to TPPTS is 1:1.0 to 3.0.

[0015] Furthermore, compound II is one of the following compounds: .

[0016] Furthermore, compound II was prepared by reacting compound III, palladium acetate, and YR2. Wherein, Y is K or Na.

[0017] Further, compound III was reacted with palladium acetate, YR2, and the catalyst in a solvent at 50°C with stirring for 12–24 h. After cooling to room temperature, the reaction mixture was precipitated in ethyl acetate. The resulting dark brown solid was washed three times with tert-butyl methyl ether to remove unreacted reactants. The crude product was then extracted with cold methanol and precipitated in acetonitrile. This process was repeated several times to obtain compound II. The reaction solvent was one of DMF, DMAC, DMPA, THF, toluene, DMSO, xylene, or n-hexane. The catalyst was one of K2CO3, Na2CO3, NaOH, KOH, KHCO3, NaHCO3, t-BuOK, t-BuONa, or CH3ONa.

[0018] Furthermore, the molar ratio of compound III to YR2 is 1:1.0 to 3.0.

[0019] Furthermore, the molar ratio of compound III to palladium acetate is 1:0.3 to 1.0.

[0020] Furthermore, the molar ratio of compound III to the catalyst potassium tert-butoxide is 1:1.0 to 3.0.

[0021] Furthermore, compound III is one of the following compounds: .

[0022] Furthermore, compound YR2 is one of the following compounds: NaCl, KCl, NaBr, KBr, NaI, KI.

[0023] Furthermore, compound III was prepared by reacting compound IV with 1,3-propanesulfonic acid lactone: .

[0024] Further, compound IV was stirred with 1,3-propanesulfonic acid lactone in a solvent at 25°C for 100–140 h, the reaction mixture was filtered, and the mixture was recrystallized from methanol to obtain compound III; wherein the reaction solvent was one of DMF, DMAC, DMPA, THF, toluene, xylene, n-hexane, or acetone.

[0025] Furthermore, the molar ratio of compound IV to 1,3-propanesulfonic acid lactone is 1:1.0 to 3.0.

[0026] Furthermore, compound IV is one of the following compounds: .

[0027] Furthermore, compound IV was prepared by reacting compound V with glyoxal and ammonium acetate: .

[0028] Further, compound V was slowly added dropwise with a mixture of ammonium acetate and acetic acid to an aqueous solution of acetic acid, formaldehyde, and glyoxal at 70°C. The reaction was carried out at 70°C for 24–36 h. After cooling to room temperature, the mixture was very slowly poured into an aqueous solution of NaHCO3. After filtration, the mixture was washed with deionized water until the water was transparent, then washed three times with tert-butyl methyl ether, and finally dried under vacuum to obtain compound IV.

[0029] Furthermore, in the mixture of compound V with ammonium acetate and acetic acid, the volume ratio of compound V to acetic acid is 1:1.5 to 2.5.

[0030] Furthermore, in an aqueous solution of acetic acid, formaldehyde, and glyoxal at 70°C, the product ratio of compound V to acetic acid is 1:1.5 to 2.5.

[0031] Furthermore, the volume ratio of compound V to glyoxal is 1:0.3 to 2.0.

[0032] Furthermore, the volume ratio of compound V to ammonium acetate is 1:1.0 to 3.0.

[0033] Furthermore, the volume ratio of compound V to formaldehyde is 1:0.5 to 1.0.

[0034] Furthermore, compound V is one of the following compounds: .

[0035] Secondly, the present invention also provides a catalyst prepared from the novel water-soluble palladium complex described above.

[0036] Thirdly, the present invention relates to the application of the novel water-soluble palladium complex described above in catalytic reactions of organic synthesis.

[0037] Furthermore, the organic synthesis catalytic reaction is a Suzuki-Miyaura cross-coupling reaction.

[0038] The Suzuki-Miyaura cross-coupling reaction utilizes the aforementioned novel water-soluble palladium complex to catalyze the Suzuki-Miyaura cross-coupling reaction. Taking the Suzuki-Miyaura cross-coupling between phenylboronic acid and 3-bromo-1,1'-biphenyl as an example, the specific steps include: Step 1: 3-bromo-1,1'-biphenyl and a novel water-soluble palladium complex were placed in a dry, nitrogen-purged double-necked round-bottom flask equipped with a magnetic stir bar and a reflux condenser. The system was evacuated and replaced with N2 for 3 cycles. Degassed water was injected through a syringe and stirred at room temperature for 15 minutes. Step 2: Add phenylboronic acid and base sequentially, heat the reactants and stir under reflux; Step 3: After cooling, dilute the mixture with ethyl acetate, wash with water, dry the organic layer, filter and concentrate.

[0039] Furthermore, in step 1, the molar ratio of 3-bromo-1,1'-biphenyl to the novel water-soluble palladium complex is 200 to 10000:1.

[0040] Furthermore, in step 2, the molar ratio of phenylboronic acid and 3-bromo-1,1'-biphenyl is 1:0.3 to 1.0.

[0041] Furthermore, in step 2, the molar ratio of phenylboronic acid to base is 1:0.5 to 2.0.

[0042] Further, in step 2, the base is one of K2CO3, Na2CO3, NaOH, KOH, KHCO3, NaHCO3, t-BuOK, t-BuONa, or CH3Ona.

[0043] Furthermore, in step 2, the heating reaction temperature is 60–150°C.

[0044] Furthermore, in step 2, the reflux stirring time is 1 to 24 hours.

[0045] Compared with the prior art, the beneficial effects of the present invention are as follows.

[0046] 1. The Suzuki-Miyaura cross-coupling catalyst provided by this invention is a novel water-soluble palladium complex that can use pure water or water as a co-solvent, making it environmentally friendly and convenient for catalyst recycling.

[0047] 2. The novel water-soluble palladium complex catalyst provided by this invention contains an electron-rich NHC electron donor, and has the characteristics of high reactivity, high selectivity of target products, and good stability. It can significantly reduce the amount of catalyst used in the application process and has great practical value.

[0048] 3. The novel water-soluble palladium complex catalyst provided by this invention has the advantages of inexpensive and readily available raw materials, simple preparation, simple post-processing, and suitability for industrial production. Attached Figure Description

[0049] Figure 1 Example 1: 1H NMR spectrum of novel water-soluble palladium complex I-1.

[0050] Figure 2 Example 1: Carbon NMR spectrum of novel water-soluble palladium complex I-1. Detailed Implementation

[0051] Definitions and general terminology: Generally, the term "substituted" means that one or more hydrogen atoms in a given structure or group are replaced by a specific substituent. Unless otherwise indicated, a substituent may be substituted at any of the reasonable substituted positions in the group. When more than one position in a given structural formula can be substituted by one or more specific substituents selected from the group, the substituents may be substituted at the reasonable positions in the structural formula, either in the same or different ways. Substituents described in this invention include, but are not limited to, D, F, Cl, Br, I, N3, -CN, -NO2, -NH2, -OH, -SH, -COOH, -CONH2, -C(=O)NHCH3, -C(=O)N(CH3)2, alkyl, alkoxy, aryl, heteroaryl, etc.

[0052] Additionally, it should be noted that, unless otherwise explicitly stated, the descriptive terms “each…independently is”, “…each independently is”, and “…independently is” used in this invention are interchangeable and should be interpreted broadly. They can mean that the specific options expressed by the same symbols in different groups do not affect each other, or that the specific options expressed by the same symbols in the same group do not affect each other.

[0053] As used in this invention, the term "alkyl" refers to a saturated straight-chain or branched monovalent hydrocarbon group containing 1-20 carbon atoms, wherein the alkyl group may optionally be substituted by one or more substituents described in this invention. In one embodiment, the alkyl group contains 1-6 carbon atoms; in another embodiment, the alkyl group contains 1-4 carbon atoms; and in yet another embodiment, the alkyl group contains 1-3 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl (Me, -CH3), ethyl (Et, -CH2CH3), n-propyl (n-Pr, -CH2CH2CH3), isopropyl (i-Pr, -CH(CH3)2), n-butyl (n-Bu, -CH2CH2CH2CH3), isobutyl (i-Bu, -CH2CH(CH3)2), sec-butyl (s-Bu, -CH(CH3)CH2CH3), tert-butyl (t-Bu, -C(CH3)3), and so on.

[0054] The term "alkoxy group" indicates that an alkyl group is attached to the remainder of the molecule by an oxygen atom, wherein the alkyl group has the meaning as described in this invention. Unless otherwise specified, the alkoxy group contains 1-12 carbon atoms. In one embodiment, the alkoxy group contains 1-6 carbon atoms; in another embodiment, the alkoxy group contains 1-4 carbon atoms; and in yet another embodiment, the alkoxy group contains 1-3 carbon atoms. The alkoxy group may optionally be substituted by one or more substituents described in this invention. Examples of alkoxy groups include, but are not limited to, methoxy (MeO, -OCH3), ethoxy (EtO, -OCH2CH3), 1-propoxy (n-propyloxy, n-PrO, n-propoxy, -OCH2CH2CH3), 2-propoxy (isopropyloxy, i-PrO, i-propoxy, -OCH(CH3)2), 1-butoxy (n-BuO, n-butoxy, -OCH2CH2CH2CH3), 2-methyl-l-propoxy (i-BuO, i-butoxy, -OCH2CH(CH3)2), 2-butoxy (s-BuO, s-butoxy, -OCH(CH3)CH2CH3), 2-methyl-2-propoxy (t-BuO, t-butoxy, -OC(CH3)3), and so on.

[0055] The term "aryl" refers to a monocyclic, bicyclic, or tricyclic carbocyclic system containing 6-14 ring atoms, 6-12 ring atoms, or 6-10 ring atoms, wherein at least one ring system is aromatic, and each ring system comprises a ring of 3-7 atoms. The aryl group is typically, but not necessarily, linked to the parent molecule via an aromatic ring. The aryl group may optionally be substituted by one or more substituents described in this invention. Examples of aryl groups may include, but are not limited to, phenyl, indenyl, naphthyl, and anthraceneyl.

[0056] The term "heteroaryl" refers to a monocyclic, bicyclic, or tricyclic system containing 5-12, 5-10, or 5-6 ring atoms, wherein at least one ring system is aromatic and at least one ring system contains one or more heteroatoms, wherein each ring system contains a ring consisting of 5-7 atoms. The heteroaryl group is typically, but not necessarily, linked to the parent molecule via the aromatic ring of the heteroaryl group. The heteroaryl group may optionally be substituted by one or more substituents described in this invention. In one embodiment, the 5-10 atom heteroaryl group comprises 1, 2, 3, or 4 heteroatoms independently selected from O, S, and N. Examples of heteroaryl groups include, but are not limited to, 2-furanyl, 3-furanyl, N-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, N-pyrroleyl, 2-pyrroleyl, 3-pyrroleyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-thiophenyl, 3-thiophenyl, pyrazolyl (such as 2-pyrazolyl), etc.

[0057] The term "jk-membered heteroaryl," where j and k are integers greater than 0, and k is greater than j, typically describes the number of ring atoms in a molecule. For example, 5-10-membered heteroaryl groups represent heteroaryl groups composed of 5, 6, 7, 8, 9, or 10 ring atoms. Another example is pyridyl, which is a 6-membered heteroaryl group.

[0058] The term "inert gas" refers to one or more of the following: helium, neon, argon, krypton, xenon, and radon.

[0059] The above technical solutions of the present invention will be specifically described below through embodiments. It should be noted that these embodiments are only used to further illustrate the present invention, but do not constitute any limitation on the present invention. Those skilled in the art can make some non-essential improvements and adjustments based on the content of the present invention.

[0060] This invention provides a novel water-soluble palladium complex with the following structural formula: ; in, R1 is independently selected from C1-C6 alkyl and C1-C6 alkoxy groups; R2 is independently selected from Cl, Br, or I.

[0061] Furthermore, R1 is independently selected from C1-C4 alkyl and C1-C4 alkoxy groups; R2 is independently selected from Cl, Br, or I.

[0062] Furthermore, R1 is independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, sec-butyloxy, or tert-butyloxy; R2 is independently selected from Cl, Br, or I.

[0063] Furthermore, the monophosphine ligand of the monophenol skeleton is one of the following compounds: .

[0064] Furthermore, the novel water-soluble palladium complex was prepared by reacting compound II with TPPTS: .

[0065] Further, compound II was stirred with TPPTS in a tetrahydrofuran and water (10:1) solution for 3-6 hours, then the solvent was removed by rotary evaporation, and the mixture was dried in a vacuum oven at 60°C for 12-18 hours to obtain compound I.

[0066] Furthermore, the volume ratio of compound II to tetrahydrofuran and aqueous solution is 1:15–20.

[0067] Furthermore, the molar ratio of compound II to TPPTS is 1:1.0 to 3.0, preferably 1:1.5 to 2.2, and more preferably 1:1.7.

[0068] Furthermore, compound II is one of the following compounds: .

[0069] Furthermore, compound II was prepared by reacting compound III, palladium acetate, and YR2. Wherein, Y is K or Na.

[0070] Further, compound III was reacted with palladium acetate, YR2, and the catalyst in a solvent at 50°C with stirring for 12–24 h. After cooling to room temperature, the reaction mixture was precipitated in ethyl acetate. The resulting dark brown solid was washed three times with tert-butyl methyl ether to remove unreacted reactants. The crude product was then extracted with cold methanol and precipitated in acetonitrile. This process was repeated several times to obtain compound II. The reaction solvent was one of DMF, DMAC, DMPA, THF, toluene, DMSO, xylene, or n-hexane. The catalyst was one of K2CO3, Na2CO3, NaOH, KOH, KHCO3, NaHCO3, t-BuOK, t-BuONa, or CH3ONa.

[0071] Furthermore, the molar ratio of compound III to YR2 is 1:1.0 to 3.0, preferably 1:1.0 to 2.0, and more preferably 1:1.6.

[0072] Furthermore, the molar ratio of compound III to palladium acetate is 1:0.3 to 1.0, preferably 1:0.3 to 0.7, and more preferably 1:0.5.

[0073] Furthermore, the molar ratio of compound III to the catalyst potassium tert-butoxide is 1:1.0 to 3.0, preferably 1:1.0 to 2.0, and more preferably 1:1.5.

[0074] Furthermore, compound III is one of the following compounds: .

[0075] Furthermore, compound YR2 is one of the following compounds: NaCl, KCl, NaBr, KBr, NaI, KI.

[0076] Furthermore, compound III was prepared by reacting compound IV with 1,3-propanesulfonic acid lactone: .

[0077] Further, compound IV was stirred with 1,3-propanesulfonic acid lactone in a solvent at 25°C for 100–140 h, the reaction mixture was filtered, and the mixture was recrystallized from methanol to obtain compound III; wherein the reaction solvent was one of DMF, DMAC, DMPA, THF, toluene, xylene, n-hexane, or acetone.

[0078] Furthermore, the molar ratio of compound IV to 1,3-propanesulfonic acid lactone is 1:1.0 to 3.0, preferably 1:1.5 to 2.5, and more preferably 1:2.0.

[0079] Furthermore, compound IV is one of the following compounds: .

[0080] Furthermore, compound IV was prepared by reacting compound V with glyoxal and ammonium acetate: .

[0081] Further, compound V was slowly added dropwise with a mixture of ammonium acetate and acetic acid to an aqueous solution of acetic acid, formaldehyde, and glyoxal at 70°C. The reaction was carried out at 70°C for 24–36 h. After cooling to room temperature, the mixture was very slowly poured into an aqueous solution of NaHCO3. After filtration, the mixture was washed with deionized water until the water was transparent, then washed three times with tert-butyl methyl ether, and finally dried under vacuum to obtain compound IV.

[0082] Furthermore, in the mixture of compound V with ammonium acetate and acetic acid, the volume ratio of compound V to acetic acid is 1:1.5 to 2.5.

[0083] Furthermore, in an aqueous solution of acetic acid, formaldehyde, and glyoxal at 70°C, the product ratio of compound V to acetic acid is 1:1.5 to 2.5.

[0084] Furthermore, the volume ratio of compound V to glyoxal is 1:0.3 to 2.0, preferably 1:0.5 to 1.0, and more preferably 1:0.8.

[0085] Furthermore, the volume ratio of compound V to ammonium acetate is 1:1.0 to 3.0, preferably 1:1.5 to 2.0, and more preferably 1:1.8.

[0086] Furthermore, compound V is one of the following compounds: .

[0087] The present invention also provides a catalyst prepared from the novel water-soluble palladium complex described above.

[0088] This invention relates to the application of the novel water-soluble palladium complex described above in catalytic reactions of organic synthesis.

[0089] Furthermore, the organic synthesis catalytic reaction is a Suzuki-Miyaura cross-coupling reaction.

[0090] The Suzuki-Miyaura cross-coupling reaction utilizes the aforementioned novel water-soluble palladium complex to catalyze the Suzuki-Miyaura cross-coupling reaction. Taking the Suzuki-Miyaura cross-coupling between phenylboronic acid and 3-bromo-1,1'-biphenyl as an example, the specific steps include: Step 1: 3-bromo-1,1'-biphenyl and a novel water-soluble palladium complex were placed in a dry, nitrogen-purged double-necked round-bottom flask equipped with a magnetic stir bar and a reflux condenser. The system was evacuated and replaced with N2 for 3 cycles. Degassed water was injected through a syringe and stirred at room temperature for 15 minutes. Step 2: Add phenylboronic acid and base sequentially, heat the reactants and stir under reflux; Step 3: After cooling, dilute the mixture with ethyl acetate, wash with water, dry the organic layer, filter and concentrate.

[0091] Further, in step 1, the molar ratio of 3-bromo-1,1'-biphenyl to the novel water-soluble palladium complex is 200 to 10000:1, preferably 200 to 2000:1, more preferably 800 to 1200:1, and particularly preferably 800:1, 1000:1 or 1200:1.

[0092] Further, in step 2, the molar ratio of phenylboronic acid to 3-bromo-1,1'-biphenyl is 1:0.3 to 1.0, preferably 1:0.3 to 0.7, more preferably 1:0.5 to 0.7, and particularly preferably 1:0.6 to 0.7; Further, in step 2, the molar ratio of phenylboronic acid to base is 1:0.5 to 2.0, preferably 1:1.0 to 2.0, more preferably 1:1.0 to 1.5, and particularly preferably 1:1.3 to 1.4; Further, in step 2, the alkali is one of K2CO3, Na2CO3, NaOH, KOH, KHCO3, NaHCO3, t-BuOK, t-BuONa or CH3Ona; preferably K2CO3 or Na2CO3.

[0093] Furthermore, in step 2, the heating reaction temperature is 60-150°C, preferably 80-120°C, and more preferably 90°C, 100°C, or 110°C; Furthermore, in step 2, the reflux stirring time is 1 to 24 hours, preferably 12 to 24 hours, more preferably 16 to 24 hours, and particularly preferably 18 hours, 20 hours, or 22 hours.

[0094] Specifically, the synthesis method of the novel water-soluble palladium complex involved in this invention is described in detail below.

[0095] Example 1.

[0096] Step 1) Preparation of 1-methyl-1H-imidazole (compound IV-1): Add 60 mL of acetic acid, 18 mL of formaldehyde, and 27.6 mL of glyoxal aqueous solution to a 500 mL round-bottom flask equipped with a reflux tube. Heat the flask in an oil bath at 70 °C and stir for a period of time. In another round-bottom flask, add 33.6 mL (0.239 mol) of 2,4,6-trimethylaniline, 18.48 g (0.240 mol) of ammonium acetate, and 60 mL of acetic acid, and stir until a homogeneous solution is formed. Add this solution dropwise to the first round-bottom flask at 70 °C. After reacting for 30 h, cool it to room temperature and pour it very slowly into an aqueous solution of NaHCO3. Filter and wash with deionized water until the water is almost transparent. Wash three times with tert-butyl methyl ether to remove all unreacted contents. Dry under vacuum to give 1-methyl-1H-imidazole (yield 75%) (compound IV-1).

[0097] Step 2) Preparation of 1-methyl-3-(3-sulfonylpropyl)imidazolium (zwitterion) (compound III-1): In a 500 mL round-bottom flask, 10 g (0.08186 mol) of 1,3-propanesulfonic acid lactone was dissolved in 160 mL of acetone; in another round-bottom flask, 8.006 g (0.04299 mol) of 1-methyl-1H imidazole was dissolved in 160 mL of acetone. The 1,3-propanesulfonic acid lactone solution was slowly added to the second solution at 0 °C and stirred at 25 °C for 120 hours. The reaction mixture was filtered to give a brown solid, which was recrystallized from methanol to give 1-methyl-3-(3-sulfonylpropyl)imidazolium (zwitterion) (yield 72%) (compound III-1).

[0098] Step 3) Preparation of bis(1-methyl-3-(3-sulfonylpropyl sodium salt)imidazolium-2-ylidene)palladium diiodide (compound II-1): Under an inert atmosphere, 6.93 g (0.02247 mol) zwitterionic acid, 5.505 g (0.03672 mol) NaI, 3.78 g (0.03369 mol) potassium tert-butoxide, and 2.52 g (0.01122 mol) palladium acetate were mixed in a 250 mL round-bottom flask. 112 mL of DMSO was added, and the mixture was stirred at 50 °C for 20 h. After cooling to room temperature, the reaction mixture was precipitated in ethyl acetate and filtered to obtain a dark brown solid. The product was washed three times with tert-butyl methyl ether to remove unreacted reactants. The crude product was then extracted with cold methanol and precipitated in acetonitrile. This process was repeated several times to obtain a purified product of a grayish-white solid, yielding bis(1-methyl-3-(3-sulfonylpropyl sodium salt)imidazolium-2-ylidene)palladium diiodide (yield 61%) (compound II-1).

[0099] Step 4) Preparation of the novel water-soluble palladium complex I-1: Under inert conditions, 153.45 mg (0.1571 mmol) of bis(1-methyl-3-(3-sulfonylpropyl sodium salt)imidazolium-2-yl)palladium diiodide and 187.578 mg (0.2954 mmol) of TPPTS (90% purity) were mixed in a 50 mL round-bottom flask and stirred at 30 °C in 3 mL of THF / water (10:1) for 3 hours. The solvent was then removed by rotary evaporation, and the mixture was dried in a vacuum oven at 60 °C for 12 hours to obtain a novel water-soluble palladium complex I-1 (yield 80%).

[0100] The 1H and 1C NMR spectra of the novel water-soluble palladium complex I-1 are shown below. Figure 1 , Figure 2 The detailed analysis is as follows: 1 H NMR (400 MHz, DMSO- D 6) δ 7.61 – 7.57(m, 3H), 7.46 (dd, J = 19.1, 2.5Hz, 1H), 7.37 – 7.32 (m, 2H), 7.09 (tt, J = 7.4, 1.4 Hz, 2H), 6.76 (s, 1H), 3.61 – 3.52 (m, 2H), 2.46 (t, J = 1.9 Hz, 2H), 2.37 (d, J = 3.9 Hz, 2H), 2.28 (d, J = 2.3 Hz, 1H), 2.12 (d, J= 22.6 Hz, 1H), 1.83 (s, 3H), 1.74 – 1.69 (m, 3H). 13 C NMR (101 MHz, DMSO- D 6) δ 148.88, 148.80, 137.40, 136.45, 136.32,135.39, 133.73, 133.58, 131.14, 130.89, 129.27, 128.94, 128.88, 126.93,122.42, 67.55, 50.86, 48.78, 26.34, 25.66, 21.74, 21.30, 21.18. Example 2-12.

[0101] Referring to the preparation method in Example 1, the reaction substrates in steps 1-4 were expanded and replaced, while other aspects remained unchanged, to obtain a series of novel water-soluble palladium complexes. The yields of the final products in Examples 2-12 were 78%, 79%, 77%, 82%, 80%, 78%, 82%, 81%, 78%, 82%, and 80%, respectively. The reaction substrates and final products of each example are shown in Tables 1-2.

[0102] Table 1. Reaction substrates and final products of Examples 2-7.

[0103] Table 2. Reaction substrates and final products of Examples 8-12.

[0104] Example 1 Verification: The key process parameters in steps 1-3 of the preparation method of the protected ligand were examined, proving that the preparation method is optimized.

[0105] Table 3 Results of the investigation of key process parameters in Example 1.

[0106] Application: Suzuki-Miyaura cross-coupling reaction In a dry, nitrogen-purged 25 mL double-necked round-bottom flask equipped with a magnetic stir bar and a reflux condenser, 3-bromo-1,1'-biphenyl (125 mg, 0.536 mmol) and a catalyst (0.536 μmol) were charged. The system was evacuated and backfilled with N2 for three cycles. 5 mL of degassed water was injected via syringe. The resulting mixture was stirred at room temperature for 15 minutes, followed by the sequential addition of phenylboronic acid (98.1 mg, 0.804 mmol) and a base (1.07 mmol). The reaction mixture was heated to 100 °C and stirred under reflux for 20 hours. After cooling, the mixture was diluted with ethyl acetate (20 mL), washed with water, and the organic layer was dried, filtered, and concentrated. Quantitative analysis was performed using 1,3,5-trimethoxybenzene (TMB) as an internal standard. 1 Yield was determined by 1H NMR (qNMR), and the results are shown in Table 4.

[0107] Table 4 shows the application effects of each embodiment in the Suzuki-Miyaura cross-coupling reaction.

[0108] As shown in Tables 1-13 above, under the same reaction conditions and with the addition of the same amount of K2CO3, the novel water-soluble palladium complex exhibits good yield and TON, both of which are higher than those of the standard ligand Pd(P-Phos)Cl2.

[0109] The results from Table 2#, 14#, and 15# show that under the same reaction conditions, for the same novel water-soluble palladium complex I-1, the reaction yield and TON were higher when K2CO3 was added than when NaOH or KOH were used.

[0110] The above specific embodiments are used to explain and illustrate the present invention, and are only preferred embodiments of the present invention, not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made to the present invention within the spirit and scope of the claims shall fall within the protection scope of the present invention.

Claims

1. A novel water-soluble palladium complex, characterized in that, The structure of the water-soluble palladium complex is shown in the following formula: ； wherein, R1 is independently selected from C1-C6 alkyl, C1-C6 alkoxy; R2 is independently selected from Cl, Br or I.

2. The novel water soluble palladium complex of claim 1, wherein, The novel water-soluble palladium complex is prepared by reacting compound II with TPPTS: 。 3. The novel water soluble palladium complex of claim 2, wherein, The compound II and TPPTS are stirred in a solution of tetrahydrofuran and water for 3-6 hours, and then the solvent is removed by rotary evaporation and dried in a vacuum oven at 60°C for 12-18 hours to obtain compound I; wherein the molar ratio of compound II and TPPTS is 1:1.0-3.

0.

4. The novel water soluble palladium complex of claim 2, wherein, The compound II is prepared by reacting compound III with compound palladium acetate, YR2: ； wherein Y is K or Na.

5. The novel water soluble palladium complex of claim 4, wherein, The compound III is prepared by reacting compound IV with 1,3-propanesultone: 。 6. The novel water soluble palladium complex of claim 5, wherein, The compound IV is prepared by reacting compound V with glyoxal and ammonium acetate: 。 7. The novel water-soluble palladium complex according to any one of claims 1-6 for use in catalyzing organic synthesis reaction.

8. Use according to claim 7, wherein the compound is ###0002### The organic synthesis reaction is Suzuki-Miyaura cross-coupling reaction.

9. Use according to claim 8, wherein the compound is ###0002### The novel water-soluble palladium complex is used to catalyze Suzuki-Miyaura cross-coupling reaction, and the Suzuki-Miyaura cross-coupling between phenylboronic acid and 3-bromo-1,1'-biphenyl is taken as an example, which comprises the following steps: Step 1: A dry, nitrogen-flushed, double-necked round-bottom flask equipped with a magnetic stirring rod and a reflux condenser is charged with 3-bromo-1,1'-biphenyl and the novel water-soluble palladium complex, the system is evacuated and filled with N2 for 3 cycles, degassed water is injected through a syringe, and stirred at room temperature for 15 minutes; Step 2: Phenylboronic acid and base are added in turn, the reaction is heated and stirred under reflux; Step 3: After cooling, the mixture is diluted with ethyl acetate, washed with water, dried, filtered and concentrated.

10. Use according to claim 9, characterized in that, The molar ratio of 3-bromo-1,1'-biphenyl and the novel water-soluble palladium complex is 200-10000:1; the molar ratio of phenylboronic acid and 3-bromo-1,1'-biphenyl is 1:0.3-1.0; the molar ratio of phenylboronic acid and base is 1:0.5-2.0.

Images