A method for preparing PdBr2 and its phosphine derivatives and their applications

Abstract

This invention provides a method for preparing PdBr2 and its phosphine derivatives, and their applications, belonging to the field of chemical engineering technology. The method for preparing PdBr2 provided by this invention includes the following steps: dissolving palladium metal, nitric acid, and a catalyst, followed by baking to obtain an intermediate product; the catalyst contains chloride or sulfide ions; and mixing the intermediate product with a bromide-containing substance to undergo a precipitation reaction to obtain PdBr2. This invention uses a catalyst when dissolving palladium metal with nitric acid. The chloride or sulfide ions in the catalyst coordinate with Pd(II) to form a complex, significantly reducing the redox electrode potential of palladium metal, thereby accelerating the dissolution rate of palladium metal and inhibiting NO3-. ‑ The strong coordination with Pd(II) can be achieved by baking, which can break the Pd-NO coordination bond, and then the introduction of bromide ions can improve the yield of PdBr2.

Description

Technical Field

[0001] This invention belongs to the field of chemical engineering technology, specifically relating to a method for preparing PdBr2 and its phosphine derivatives and their applications. Background Technology

[0002] PdBr2 has a planar square coordination structure with a palladium(II) center in a four-coordinate configuration. Each bromine atom acts as a bridging ligand, thus forming a polymer structure. It is an important precursor for the preparation of various palladium complexes and is often used in the synthesis and loading of palladium catalysts in organic synthesis. Its derived trans and cis isomers have core application value in the field of catalysis. Therefore, PdBr2 is an indispensable universal precursor for obtaining a series of functionalized palladium complexes.

[0003] Currently, the main process for preparing PdBr2 involves reacting metallic palladium with an acid to obtain a divalent palladium salt, followed by a precipitation reaction where the divalent palladium salt is mixed with hydrobromic acid (HBr) or bromate. Although this method can produce PdBr2 of a certain purity, when the acid is nitric acid, the resulting palladium nitrate exhibits two NO atoms coordinated with Pd(II) in its chemical structure, as shown below: , Existing denitrification techniques are insufficient to break the Pd-NO coordination bond. The presence of this coordination bond reduces the electron cloud density at the palladium center, increases steric hindrance, and inhibits Br. - The nucleophilic attack and ligand exchange of PdBr2 hinder its precipitation kinetics, resulting in low yields. Therefore, improving the yield of PdBr2 has become a pressing technical challenge in this field. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing PdBr2 and its phosphine derivatives, and their applications. The preparation method provided by this invention can improve the yield of PdBr2.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a method for preparing PdBr2, comprising the following steps: (1) Mix palladium, nitric acid and catalyst to dissolve, and then bake to obtain an intermediate product; the catalyst contains chloride ions or sulfide ions; (2) The intermediate product obtained in step (1) is mixed with a bromide-containing substance to carry out a precipitation reaction to obtain PdBr2.

[0006] Preferably, the catalyst containing chloride ions in step (1) includes at least one of hydrochloric acid and a chloride salt; the chloride salt includes at least one of NH4Cl and NaCl.

[0007] Preferably, the catalyst containing sulfur ions in step (1) includes at least one of hydrogen sulfide solution and sulfur salt.

[0008] Preferably, the catalyst in step (1) is 0.5 to 2‰ of the mass of metallic palladium.

[0009] Preferably, the baking in step (1) is performed under an infrared lamp.

[0010] This invention also provides a method for preparing a phosphine derivative of PdBr2, comprising the following steps: (1) Mix palladium, nitric acid and catalyst to dissolve, and then bake to obtain an intermediate product; the catalyst contains chloride ions or sulfide ions; (2) The intermediate product obtained in step (1) is mixed with a bromide-containing substance and subjected to a precipitation reaction to obtain PdBr2; (3) The PdBr2 obtained in step (2), organic solvent and phosphine ligand are mixed and then a coordination reaction is carried out to obtain a phosphine derivative of PdBr2.

[0011] Preferably, the phosphine ligand in step (3) includes one of triphenylphosphine, 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl, 4,5-bisdiphenylphosphine-9,9-dimethyloxanthracene, and 1,2-bis(diphenylphosphine)ethane.

[0012] Preferably, the temperature of the coordination reaction in step (3) is -20~0℃.

[0013] The present invention also provides the application of PdBr2 prepared by the preparation method described above and / or the phosphine derivative of PdBr2 prepared by the preparation method described above as a catalyst in catalyzing carbon-carbon coupling reactions or carbon-heteroatom coupling reactions.

[0014] Preferably, the carbon-carbon coupling reaction is a Suzuki coupling reaction or a Heck coupling reaction; the carbon-heteroatom coupling reaction is a Buchwald-Hartwig amination reaction.

[0015] This invention provides a method for preparing PdBr2, comprising the following steps: dissolving palladium metal, nitric acid, and a catalyst in a mixture, followed by baking to obtain an intermediate product; the catalyst contains chloride or sulfide ions; and mixing the intermediate product with a bromide-containing substance to perform a precipitation reaction to obtain PdBr2. This invention utilizes a catalyst when dissolving palladium metal with nitric acid. The chloride or sulfide ions in the catalyst have strong coordination ability and will coordinate with Pd(II) to form a complex, thereby accelerating the dissolution rate of palladium metal and inhibiting NO3-. -The strong coordination with Pd(II) is observed; baking can break the Pd-NO coordination bond, and the subsequent introduction of bromide ions can improve the yield of PdBr2. The results of the examples show that the preparation method of this invention achieves a PdBr2 yield of 99.6%. Attached Figure Description

[0016] Figure 1 The structural formula of the phosphine derivative of PdBr2 prepared in Example 3 is shown below; Figure 2 The structural formula of the phosphine derivative of PdBr2 prepared in Example 5 is shown below; Figure 3 The structural formula of the phosphine derivative of PdBr2 prepared in Example 7 is shown below; Figure 4 The structure of the phosphine derivative of PdBr2 prepared in Example 9 is shown below. Detailed Implementation

[0017] This invention provides a method for preparing PdBr2, comprising the following steps: (1) Mix palladium, nitric acid and catalyst to dissolve, and then bake to obtain an intermediate product; the catalyst contains chloride ions or sulfide ions; (2) The intermediate product obtained in step (1) is mixed with a bromide-containing substance to carry out a precipitation reaction to obtain PdBr2.

[0018] The present invention does not have any special limitations on the source of the raw materials, and commercially available products known to those skilled in the art can be used.

[0019] In one embodiment of the present invention, the process for preparing PdBr2 from palladium, nitric acid, and hydrobromic acid is as follows: .

[0020] In this invention, palladium, nitric acid, and a catalyst are mixed and dissolved, and then baked to obtain an intermediate product.

[0021] The present invention does not impose any particular limitation on the shape of the palladium metal; any palladium metal well known to those skilled in the art can be used. As one embodiment, the palladium metal can be sponge palladium.

[0022] In this invention, the mass concentration of the nitric acid is preferably 60-70%; the mole ratio of palladium to nitric acid is preferably 1 mol: (5.0-5.3) L. As one embodiment, the mass concentration of the nitric acid can be 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, or 69%; the mole ratio of palladium to nitric acid can be 1 mol: 5.1 L or 1 mol: 5.2 L.

[0023] In this invention, the catalyst contains chloride or sulfide ions. The chloride or sulfide ions in the catalyst have strong coordination ability and can coordinate with Pd(II) to form complexes, significantly reducing the redox electrode potential of palladium and thus accelerating the dissolution rate of palladium. It can also inhibit NO3-. - Strong coordination with Pd(II).

[0024] In this invention, the catalyst containing chloride ions preferably includes at least one of hydrochloric acid and a chloride salt, more preferably a chloride salt; the chloride salt preferably includes at least one of NH4Cl and NaCl, more preferably NH4Cl.

[0025] In this invention, the catalyst containing sulfur ions preferably includes at least one of hydrogen sulfide solution and sulfur salt; the sulfur salt is preferably sodium sulfide.

[0026] In this invention, the catalyst is preferably 0.5 to 2‰ of the mass of palladium. As one embodiment, the catalyst is preferably 1‰ or 1.5‰ of the mass of palladium. Limiting the mass of the catalyst within the above range further suppresses NO3. - Strong coordination with Pd(II).

[0027] The present invention does not have any special limitations on the operation of dissolving the palladium metal, nitric acid and catalyst mixture, as long as the raw materials are completely dissolved.

[0028] In this invention, the baking is preferably performed under an infrared lamp. The baking process disrupts the Pd-NO coordination bonds, and the subsequent introduction of bromide ions increases the yield of PdBr2.

[0029] The present invention does not have any special limitations on the baking operation; the solvent can be evaporated to obtain a viscous product.

[0030] After obtaining the viscous intermediate product, the present invention mixes the viscous intermediate product with a bromide-containing substance to carry out a precipitation reaction to obtain PdBr2.

[0031] In this invention, the bromide-containing substance preferably includes an aqueous solution of hydrobromic acid or a bromate; the mass concentration of the aqueous solution of hydrobromic acid is preferably 30-40%. As one embodiment, the mass concentration of the aqueous solution of hydrobromic acid can be 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, or 39%. This invention does not impose any specific limitation on the type of bromate; any bromate well-known to those skilled in the art can be used.

[0032] In this invention, the preferred volume ratio of the palladium metal to the bromide-containing substance is 1 mol: (0.5~5) L. As one embodiment, the volume ratio of the palladium metal to the bromide-containing substance can be 1 mol: 0.8 L, 1 mol: 1 L, 1 mol: 2 L, 1 mol: 3 L, or 1 mol: 4 L.

[0033] The present invention does not have any special limitations on the operation of mixing the intermediate product and the bromide-containing substance for precipitation reaction, as long as the two are mixed evenly and no precipitation occurs.

[0034] In one embodiment, the precipitation reaction of the intermediate product and the bromide-containing substance can be carried out by adding a portion of the bromide-containing substance, stirring until completely dissolved, then heating under an infrared lamp until viscous, followed by adding the remaining bromide-containing substance, and heating again under an infrared lamp until dry. This invention does not impose a specific limitation on the ratio of the portion of the bromide-containing substance to the remaining bromide-containing substance; it is sufficient to add the bromide-containing substance in stages.

[0035] After the precipitation reaction is completed, the present invention preferably performs post-processing on the product obtained from the precipitation reaction to obtain PdBr2.

[0036] In this invention, the post-processing preferably includes drying and pulverizing performed sequentially.

[0037] The present invention does not impose any particular limitation on the drying operation; removal of the solvent is sufficient. As one embodiment, the drying can be performed by evaporation.

[0038] The present invention does not impose any special limitations on the pulverization operation; the operation can be carried out according to the actual required particle size.

[0039] This invention employs a catalyst when dissolving palladium with nitric acid. The chloride or sulfide ions in the catalyst have strong coordination ability and will coordinate with Pd(II) to form a complex, significantly reducing the redox electrode potential of palladium and thus accelerating the dissolution rate of palladium. It also inhibits NO3-. - The strong coordination with Pd(II) can be achieved by baking, which can break the Pd-NO coordination bond, and then the introduction of bromide ions can improve the yield of PdBr2.

[0040] This invention also provides a method for preparing a phosphine derivative of PdBr2, comprising the following steps: (1) Mix palladium, nitric acid and catalyst to dissolve, and then bake to obtain an intermediate product; the catalyst contains chloride ions or sulfide ions; (2) The intermediate product obtained in step (1) is mixed with a bromide-containing substance and subjected to a precipitation reaction to obtain PdBr2; (3) The PdBr2 obtained in step (2), organic solvent and phosphine ligand are mixed and then a coordination reaction is carried out to obtain a phosphine derivative of PdBr2.

[0041] The present invention does not have any special limitations on the source of the raw materials, and commercially available products known to those skilled in the art can be used.

[0042] In this invention, the operation for preparing PdBr2 is preferably the same as described above, and will not be repeated here.

[0043] After obtaining PdBr2, the present invention mixes the PdBr2, organic solvent and phosphine ligand and carries out a coordination reaction to obtain a phosphine derivative of PdBr2.

[0044] In this invention, the process flow for the coordination reaction between PdBr2 and the phosphine ligand is as follows: ; Wherein, L is a phosphine ligand, PR3 is triphenylphosphine (PPh3), 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (XPhos) or 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl (SPhos); R2P^PR2 is 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene (XantPhos) or 1,2-bis(diphenylphosphine)ethane (dppe).

[0045] In this invention, the organic solvent is preferably one or more selected from N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), acetonitrile (CH3CN), and tetrahydrofuran (THF). This invention does not impose any particular limitation on the amount of the organic solvent used, as long as all raw materials are completely dissolved.

[0046] In this invention, the phosphine ligand preferably includes one of triphenylphosphine, 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl, 4,5-bisdiphenylphosphine-9,9-dimethyloxanthracene, and 1,2-bis(diphenylphosphine)ethane.

[0047] In this invention, the preferred molar ratio of PdBr2 to the phosphine ligand is 1:(1.0~2.6). As one embodiment, the molar ratio of PdBr2 to the phosphine ligand can be 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.43, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2.0, 1:2.1, 1:2.2, 1:2.3, 1:2.4, or 1:2.5. This invention does not impose any particular limitations on the mixing operation of PdBr2, the organic solvent, and the phosphine ligand; any technique well-known to those skilled in the art for preparing the mixture can be used.

[0048] In this invention, the temperature of the coordination reaction is preferably -20 to 0°C; the time of the coordination reaction is preferably 2 to 4 hours; and the coordination reaction is preferably carried out under stirring conditions. This invention does not impose any particular limitation on the stirring rate; stirring operations well known to those skilled in the art can be used.

[0049] In one embodiment, the temperature of the coordination reaction can be -15°C, -10°C, or -5°C; and the time of the coordination reaction can be 2h, 3h, or 4h.

[0050] After the coordination reaction is completed, the present invention preferably performs post-processing on the product obtained from the coordination reaction to obtain a phosphine derivative of PdBr2.

[0051] In this invention, the post-processing preferably includes sequentially performing filtration, washing, and drying.

[0052] The present invention does not impose any special limitations on the filtration operation; the filter cake can be obtained by using operations well known to those skilled in the art.

[0053] The present invention does not impose any special limitations on the washing operation; the goal is simply to remove impurities.

[0054] The present invention does not impose any special limitations on the drying operation; drying to a constant weight is sufficient.

[0055] The present invention also provides the application of PdBr2 prepared by the preparation method described above and / or the phosphine derivative of PdBr2 prepared by the preparation method described above as a catalyst in catalyzing carbon-carbon coupling reactions or carbon-heteroatom coupling reactions.

[0056] In this invention, the carbon-carbon coupling reaction is preferably the Suzuki coupling reaction or the Heck coupling reaction; the carbon-heteroatom coupling reaction is preferably the Buchwald-Hartwig amination reaction.

[0057] In one embodiment, when the carbon-carbon coupling reaction is a Suzuki coupling reaction, the reaction substrate can be 2-bromo-5-(trifluoromethyl)pyridine and 2,4-difluorophenylboronic acid; the amount of PdBr2 and the phosphine derivative of PdBr2 can independently be 2% of the amount of 2-bromo-5-(trifluoromethyl)pyridine.

[0058] In one embodiment, when the carbon-carbon coupling reaction is a Heck coupling reaction, the reaction substrate can be bromobenzene and 4-methylstyrene; the amount of PdBr2 and the phosphine derivative of PdBr2 can independently be 2% of the amount of bromobenzene.

[0059] In one embodiment, when the carbon-heteroatom coupling reaction is a Buchwald-Hartwig amination reaction, the reaction substrate can be bromobenzene and aniline; the amount of PdBr2 and the phosphine derivative of PdBr2 can independently be 2% of the amount of bromobenzene.

[0060] The present invention does not impose any special limitations on the operation of using PdBr2 and / or phosphine derivatives of PdBr2 as catalysts in catalytic carbon-carbon coupling reactions or carbon-heteroatom coupling reactions; any operation known to those skilled in the art can be used.

[0061] This invention utilizes palladium as a raw material, and efficiently prepares high-purity PdBr2 through nitric acid dissolution and bromide ion conversion in the presence of a chlorine- or sulfur-containing catalyst. This PdBr2 is then reacted with corresponding phosphine ligands to synthesize phosphine derivatives of PdBr2 with well-defined structures. The phosphine derivatives of PdBr2, as catalysts, exhibit high activity, excellent stability, and reproducibility in coupling reactions such as Suzuki, Buchwald-Hartwig, and Heck, significantly outperforming simple mixtures of PdBr2 and its phosphine ligands.

[0062] Under selected conditions, a single PdBr2 catalyst is difficult to effectively form highly catalytically active Pd(0) species, resulting in extremely low product yields. When using a mixed system of PdBr2 and phosphine ligands, species with some catalytic activity can be generated, but due to the formation of "(PR3)" during activation... nThe complex composition and ambiguous structure of the active center of Pd(0) lead to diverse catalytic pathways and unstable reaction efficiency. In contrast, using pre-synthesized, structurally well-defined phosphine derivatives of PdBr2 (Trans-Pd(PPh3)2Br2, Trans-Pd(XPhos)2Br2, and Trans-Pd(SPhos)2Br2) as catalysts exhibits significantly better catalytic activity and reproducibility than mixed systems. In particular, in the Buchwald-Hartwig reaction, the reaction yield catalyzed by Pd(XPhos)Br2 reached 89%, far exceeding the 65% of the corresponding mixed system. This is clearly attributed to the fact that well-defined catalysts can generate structurally uniform Pd(0) through a single, controllable reduction pathway. n -Pd(0)” active species avoid side reactions and activity decay caused by multi-path competition, thereby significantly improving reaction efficiency and operational stability. Therefore, using phosphine derivatives of PdBr2 with well-defined structures as catalysts has outstanding advantages such as high activity, good reproducibility and clear reaction pathways compared to simple mixtures or single PdBr2, and is more suitable for catalytic applications under large-scale and standardized conditions.

[0063] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0064] Example 1 A method for preparing PdBr2 is as follows: Weigh 0.106 g of sponge palladium (1 mmol) and place it in a 50 L beaker. Add 5 mL of 68% concentrated nitric acid in batches, and add 1‰ sodium sulfide of sponge palladium. Stir until completely dissolved. Then transfer the resulting solution to an evaporating dish and bake it under an infrared lamp until it becomes viscous to obtain a viscous intermediate product. Under continuous stirring, 2 mL of a 33% aqueous solution of hydrobromic acid was slowly added in batches and stirred until completely dissolved. Then, the mixture was heated again under an infrared lamp until it became viscous. Subsequently, 2 mL of a 33% aqueous solution of hydrobromic acid was added, and the mixture was heated under an infrared lamp until dry. Finally, the resulting solid was pulverized into powder to obtain PdBr2 with a mass of 2.61 g, a yield of 98.1% (calculated based on the molar amount of Pd), and a purity of 99.5%.

[0065] Example 2 A method for preparing PdBr2 is as follows: Weigh 106g of sponge palladium (1mol) and place it in a 5L beaker. Add 5L of 68% concentrated nitric acid in batches, and add 1‰ of the mass of sponge palladium ammonium chloride. Stir until completely dissolved, then transfer the resulting solution to an evaporating dish and bake it under an infrared lamp until it becomes viscous to obtain the intermediate product. Under continuous stirring, 500 mL of a 33% aqueous solution of hydrobromic acid was slowly added in batches. The mixture was stirred until completely dissolved to allow for precipitation. The solution was then heated again under an infrared lamp until it reached a viscous state. Subsequently, 300 mL of a 33% aqueous solution of hydrobromic acid was added, and the mixture was heated under an infrared lamp until dry. Finally, the resulting solid was pulverized into powder to obtain PdBr2 with a mass of 265 g, a yield of 99.6% (based on the molar amount of Pd), and a purity of 99.2%.

[0066] Example 3 The preparation method of the phosphine derivative Trans-Pd(PPh3)2Br2 of PdBr2 is as follows: Weigh 2.66 g (10 mmol) of PdBr2 from Example 1 into a 100 mL double-necked flask, add 50 mL of acetonitrile, and stir at 60 °C until completely dissolved. After the solution cools to room temperature, transfer it to a low-temperature reaction apparatus and maintain the system temperature at -10 °C. Under stirring, slowly add an acetonitrile solution containing 5.3 g of PPh3 (pre-dissolved in 20 mL of acetonitrile). After the addition is complete, continue stirring at -10 °C for a coordination reaction for 2 h. Gradually, a yellow crystalline solid precipitates. After the reaction is complete, filter through a Buchner funnel, collect the solid product, and wash the filter cake three times with a small amount of cold acetonitrile. Then place the obtained solid in a vacuum drying oven and dry at room temperature for 4 h to obtain a yellow powder product Trans-Pd(PPh3)2Br2 with a mass of 7.5 g and a yield of 95% (calculated based on the molar amount of Pd).

[0067] The phosphine derivatives of PdBr2 prepared in Example 3 were characterized, and the characterization data are as follows: ① Elemental analysis: Measured values: Pd 13.43%, C 54.69%, Br 20.24%, P 7.86%; Theoretical values ​​(°C) 36 H 30 (Br2P2Pd) Pd 13.42%, C 54.68%, Br 20.25%, P 7.85%, the measured values ​​are basically consistent with the theoretical values.

[0068] ② 1 H NMR (500 MHz, Chloroform-d) δ 7.26 – 7.39 (m, 1H), 7.64 (dd, 1H).

[0069] ③13 C NMR (126 MHz, Chloroform-d) δ 128.77, 128.81, 128.84, 128.88,130.19, 130.22, 130.26, 130.29, 130.32, 130.35, 130.38, 134.37, 134.41,134.45, 134.49, 134.53, 134.57, 134.98, 134.99, 135.01, 135.03, 135.05,135.06, 135.08. ④MS(ESI(+)):m / z=710 ℃alcd.790 for [C 36 H 30 [Br2P2Pd], [M-Br] - ).

[0070] ⑤IR (KBr, ν / cm -1 ): 3058 (w), 3026 (w); 1589 (m), 1573 (m); 1483 (m),1462 (m), 1435 (m); 1096 (m), 1028 (w); 748 (s), 695 (s); 520–505 (w); 350–330(w).

[0071] Example 4 The preparation method of the phosphine derivative Trans-Pd(PPh3)2Br2 of PdBr2 is as follows: Weigh 26.6 g (0.1 mol) of PdBr2 from Example 1 into a 1 L double-necked flask, add 500 mL of acetonitrile, and stir at 60 °C until completely dissolved. After the solution cools to room temperature, transfer it to a low-temperature reaction apparatus and maintain the system temperature at -10 °C. Under stirring, slowly add an acetonitrile solution containing 53 g of PPh3 (pre-dissolved in 200 mL of acetonitrile). After the addition is complete, continue stirring at -10 °C for a coordination reaction for 2 h. Gradually, a yellow crystalline solid precipitates. After the reaction is complete, filter through a Buchner funnel, collect the solid product, and wash the filter cake three times with a small amount of cold acetonitrile. Then place the obtained solid in a vacuum drying oven and dry at room temperature for 4 h to obtain a yellow powder product Trans-Pd(PPh3)2Br2 with a mass of 77.6 g and a yield of 98.2% (calculated based on the molar amount of Pd).

[0072] Example 5 The preparation method of the phosphine derivative Trans-Pd(XPhos)2Br2 of PdBr2 is as follows: Weigh 2.66 g (10 mmol) of PdBr2 from Example 1 into a 100 mL double-necked flask, add 50 mL of DMF, and stir at 60 °C until completely dissolved. After the solution cools to room temperature, transfer it to a low-temperature reaction apparatus and maintain the system temperature at -10 °C. Under stirring, slowly add a DMF solution containing 9.8 g of XPhos. After the addition is complete, continue stirring at -10 °C for a coordination reaction for 2 h. Gradually, a yellow crystalline solid precipitates. After the reaction is complete, filter through a Buchner funnel, collect the solid product, and wash the filter cake three times with a small amount of cold acetonitrile. Then place the obtained solid in a vacuum drying oven and dry at room temperature for 4 h to obtain a yellow powder product Trans-Pd(XPhos)2Br2 with a mass of 11.8 g and a yield of 96.8% (calculated based on the molar amount of Pd).

[0073] The phosphine derivatives of PdBr2 prepared in Example 5 were characterized, and the characterization data are as follows: ① Elemental analysis: Measured values: Pd 8.76%, C 65.57%, Br 13.24%, P 5.12%; Theoretical values ​​(°C) 66 H 98 (Br2P2Pd) Pd 8.77%, C 65.56%, Br 13.25%, P 5.13%, the measured values ​​are basically consistent with the theoretical values.

[0074] ② 1 H NMR (500 MHz, Chloroform-d) δ 1.24 (d, 5H), 1.31 (dd, 9H), 1.35– 1.47 (m, 2H), 1.47 – 1.67 (m, 12H), 1.67 – 1.82 (m, 8H), 2.92 – 3.03 (m,3H), 3.49 (hept, 2H), 7.15 (s, 2H), 7.24 (tdd, 1H), 7.33 (ddd, 1H), 7.41 (td,1H), 7.82 (dt, 1H).

[0075] ③ 13C NMR (126 MHz, Chloroform-d) δ 23.77, 24.45, 24.46, 24.46, 24.47,24.48, 24.49, 24.50, 25.26, 25.28, 25.30, 25.32, 25.33, 26.66, 26.67, 26.68,30.75, 30.79, 30.84, 30.89, 30.93, 31.90, 31.94, 31.97, 32.00, 34.14, 34.18,36.00, 36.09, 36.17, 121.94, 122.00, 122.06, 122.12, 126.96, 126.98, 128.30, 128.32, 129.93, 129.95, 130.44, 130.45, 134.91, 134.96, 139.41, 139.45, 139.46, 139.50, 146.78, 146.85, 147.46, 147.50, 147.54, 147.59.

[0076] ④MS(ESI(+)):m / z=1138 ℃alcd.1218 for [C 66 H 98 ]Br2P2Pd ],[M-Br] - ).

[0077] ⑤IR (KBr, ν / cm -1 ): 3055 (w), 3022 (w); 2958 (m), 2926 (m), 2868 (w); 1601 (m), 1576 (m); 1479 (m), 1462 (m), 1438 (m); 1364 (w); 1102 (m), 1035(w); 823(m); 748(s), 702(s); 525–510(w); 355–335(w).

[0078] Example 6 The preparation method of the phosphine derivative Trans-Pd(XPhos)2Br2 of PdBr2 is as follows: Weigh 26.6 g (0.1 mol) of PdBr2 from Example 1 into a 1 L double-necked flask, add 500 mL of DMF, and stir at 60 °C until completely dissolved. After the solution cools to room temperature, transfer it to a low-temperature reaction apparatus and maintain the system temperature at -10 °C. Under stirring, slowly add a DMF solution containing 98 g of XPhos. After the addition is complete, continue stirring at -10 °C for a coordination reaction for 2 h. Gradually, a yellow crystalline solid precipitates. After the reaction is complete, filter through a Buchner funnel, collect the solid product, and wash the filter cake three times with a small amount of cold acetonitrile. Then place the obtained solid in a vacuum drying oven and dry at room temperature for 4 h to obtain a yellow powder product Trans-Pd(XPhos)2Br2 with a mass of 119.8 g and a yield of 98.2% (calculated based on the molar amount of Pd).

[0079] Example 7 The preparation method of the phosphine derivative Trans-Pd(SPhos)2Br2 of PdBr2 is as follows: Weigh 2.66 g (10 mmol) of PdBr2 from Example 1 into a 100 mL double-necked flask, add 50 mL of DMSO, and stir at 60 °C until completely dissolved. After the solution cools to room temperature, transfer it to a low-temperature reaction apparatus and maintain the system temperature at -10 °C. Under stirring, slowly add a DMSO solution containing 8.5 g of SPhos. After the addition is complete, continue stirring at -10 °C for a coordination reaction for 2 h. Gradually, a yellow crystalline solid precipitates. After the reaction is complete, filter through a Buchner funnel, collect the solid product, and wash the filter cake three times with a small amount of cold acetonitrile. Then place the obtained solid in a vacuum drying oven and dry at room temperature for 4 h to obtain a yellow powder product Trans-Pd(SPhos)2Br2 with a mass of 9.7 g and a yield of 89.2% (calculated based on the molar amount of Pd).

[0080] The phosphine derivatives of PdBr2 prepared in Example 7 were characterized, and the characterization data are as follows: ① Elemental analysis: Measured values: Pd 10.38%, C 61.07%, Br 15.65%, P 6.08%; Theoretical values ​​(°C) 52 H 70 (Br2P2Pd) Pd 10.37%, C 61.06%, Br 15.66%, P 6.07%, the measured values ​​are basically consistent with the theoretical values.

[0081] ②1H NMR (500 MHz, Chloroform-d) δ 1.35 – 1.47 (m, 2H), 1.47 – 1.67(m, 11H), 1.67 – 1.82 (m, 8H), 2.97 (dp, 2H), 3.89 (s, 4H), 6.78 (d, 2H),7.14 (tdd, 1H), 7.30 (t, 1H), 7.36 (ddd, 1H), 7.44 (td, 1H), 7.75 (dt, 1H)。

[0082] ③ 13 C NMR (126 MHz, Common NMR Solvents) δ 25.26, 25.28, 25.30, 25.32,25.33, 26.66, 26.67, 26.68, 30.75, 30.79, 30.84, 30.89, 30.93, 35.98, 36.07,36.16, 56.25, 56.26, 56.27, 56.28, 105.77, 105.79, 105.81, 105.83, 126.51,126.56, 127.66, 127.68, 128.11, 128.12, 129.76, 129.79, 129.92, 129.93,130.74, 130.75, 134.51, 134.55, 136.59, 136.63, 157.40, 157.41, 157.42,157.43。

[0083] ④MS(ESI(+)):m / z=942 ℃alcd.1022 for [C 52 H 70 Br2P2Pd],[M-Br] - )。

[0084] ⑤IR (KBr, ν / cm -1): 3054 (w), 3021 (w); 2957 (m), 2924 (m), 2866 (w); 1602 (m), 1581 (m); 1506 (m), 1478 (m), 1461 (m), 1437 (m); 1262 (m), 1246 (m) [ν℃–O, Ar–OCH3)]; 1178 (w); 1104 (m), 1038 (m); 832 (m); 752 (s), 706 (s); 525–510 (w); 355–335 (w).

[0085] Example 8 The preparation method of the phosphine derivative Trans-Pd(SPhos)2Br2 of PdBr2 is as follows: Weigh 26.6 g (0.1 mol) of PdBr2 from Example 1 into a 1 L double-necked flask, add 500 mL of DMSO, and stir at 60 °C until completely dissolved. After the solution cools to room temperature, transfer it to a low-temperature reaction apparatus and maintain the system temperature at -10 °C. Under stirring, slowly add a DMSO solution containing 85 g of SPhos. After the addition is complete, continue stirring at -10 °C for a coordination reaction for 2 h. Gradually, a yellow crystalline solid precipitates. After the reaction is complete, filter through a Buchner funnel, collect the solid product, and wash the filter cake three times with a small amount of cold acetonitrile. Then place the obtained solid in a vacuum drying oven and dry at room temperature for 4 h to obtain a yellow powder product Trans-Pd(SPhos)2Br2 with a mass of 101.2 g and a yield of 93.1% (calculated based on the molar amount of Pd).

[0086] Example 9 The preparation method of Cis-Pd(XantPhos)Br2, a phosphine derivative of PdBr2, is as follows: Weigh 2.66 g (10 mmol) of PdBr2 from Example 1 into a 100 mL double-necked flask, add 50 mL of THF, heat and stir until completely dissolved. After the solution cools to room temperature, transfer it to a low-temperature reaction apparatus and maintain the system temperature at -10 °C. Under stirring, slowly add a THF solution containing 6.0 g of XantPhos (pre-dissolved in 20 mL of THF). After the addition is complete, continue stirring at -10 °C for a coordination reaction for 2 h. Gradually, a yellow crystalline solid precipitates. After the reaction is complete, filter through a Buchner funnel, collect the solid product, and wash the filter cake three times with a small amount of cold acetonitrile. Then place the obtained solid in a vacuum drying oven and dry at room temperature for 4 h to obtain a yellow powder product Cis-Pd(XantPhos)Br2 with a mass of 8.4 g and a yield of 94.7% (calculated based on the molar amount of Pd).

[0087] The phosphine derivatives of PdBr2 prepared in Example 9 were characterized, and the characterization data are as follows: ① Elemental analysis: Measured values: Pd 13.56%, C 59.84%, Br 20.45%, P 7.94%; Theoretical values ​​(°C) 39 H 48 (Br2P2Pd) Pd 13.55%, C 59.85%, Br 20.46%, P 7.93%, the measured values ​​are basically consistent with the theoretical values.

[0088] ② 1 H NMR (500 MHz, Chloroform-d) δ 7.11 (dt, 1H), 7.19 (dd, 1H), 7.26– 7.34 (m, 4H), 7.31 – 7.36 (m, 1H), 7.34 – 7.39 (m, 1H), 7.66 (dt, 4H), 8.04 (dt, 1H).

[0089] ③ 13 C NMR (126 MHz, Chloroform-d) δ 30.85, 35.67, 124.54, 126.39,128.71, 128.78, 130.22, 132.22, 134.37, 134.86, 135.35, 153.68.

[0090] ④MS(ESI(+)):m / z=702 ℃alcd.782 for [C 39 H 48 [Br2P2Pd], [M-Br] - ).

[0091] ⑤IR (KBr, ν / cm -1 ): 3053 (w), 3026 (w); 2962 (m), 2930 (m), 2872 (w); 1601 (m), 1584 (m); 1484 (m), 1472 (m), 1459 (m), 1436 (s); 1252 (s) [ν℃–O–C)]; 1102 (m), 1029 (w); 748 (s), 698 (s); 520–505 (w); 380–350 (w).

[0092] Example 10 The preparation method of Cis-Pd(XantPhos)Br2, a phosphine derivative of PdBr2, is as follows: Weigh 26.6 g (0.1 mol) of PdBr2 from Example 1 into a 1 L double-necked flask, add 500 mL of THF, and stir at 60 °C until completely dissolved. After the solution cools to room temperature, transfer it to a low-temperature reaction apparatus and maintain the system temperature at -10 °C. Under stirring, slowly add a THF solution containing 60 g of XantPhos (pre-dissolved in 200 mL of THF). After the addition is complete, continue stirring at -10 °C for a coordination reaction for 2 h. Gradually, a yellow crystalline solid precipitates. After the reaction is complete, filter through a Buchner funnel, collect the solid product, and wash the filter cake three times with a small amount of cold acetonitrile. Then place the obtained solid in a vacuum drying oven and dry at room temperature for 4 h to obtain a yellow powder product Cis-Pd(XantPhos)Br2 with a mass of 85.1 g and a yield of 95.9% (calculated based on the molar amount of Pd).

[0093] Applications in the Suzuki coupling reaction Application Example 1 2-Bromo-5-(trifluoromethyl)pyridine (5.0 mmol, 1.0 equiv), 2,4-difluorophenylboronic acid (6.5 mmol, 1.3 equiv), and PdBr2 (0.1 mmol, 2 mol%) from Example 1 were sequentially added to a 100 mL round-bottom flask. After three argon exchanges, tetrahydrofuran (20 mL) was added using a syringe. A 10 mL aqueous solution of potassium carbonate (10.0 mmol, 2.0 equiv) was slowly added at room temperature. The mixture was heated to 40 °C, and the reaction mixture turned yellow and was stirred for 19 h. The reaction was monitored by TLC until complete. After cooling to room temperature, the mixture was diluted with water and extracted three times with diethyl ether. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. The residue was purified by silica gel column chromatography (eluent: petroleum ether and ethyl acetate) to obtain the product in 72% yield.

[0094] The equation for the Suzuki coupling reaction in Application Example 1 is as follows: .

[0095] Comparative Application Example 1 Based on Application Example 1, PdBr2 was modified to PPh3 and PdBr2, with a molar ratio of 2:1. The reaction time was 10 h, and other conditions remained unchanged, resulting in a yield of 73%.

[0096] Comparative Application Example 2 Based on Application Example 1, PdBr2 was modified to SPhos and PdBr2, with a molar ratio of 2:1. The reaction time was 10 h, and other conditions remained unchanged, resulting in a yield of 75%.

[0097] Comparative Application Example 3 Based on Application Example 1, PdBr2 was modified to XPhos and PdBr2, with a molar ratio of 2:1. The reaction time was 10 h, and other conditions remained unchanged, resulting in a yield of 74%.

[0098] Application Example 2 Based on Application Example 1, PdBr2 was modified to Pd(PPh3)2Br2 of Example 3, the reaction time was 8h, and other conditions remained unchanged, the yield was 89%.

[0099] Application Example 3 Based on Application Example 1, PdBr2 was modified to Pd(SPhos)2Br2 of Example 7, the reaction time was 8 hours, and other conditions remained unchanged, the yield was 89%.

[0100] Application Example 4 Based on Application Example 1, PdBr2 was modified to Pd(XPhos)2Br2 of Example 5, the reaction time was 8 h, and other conditions remained unchanged, the yield was 91%.

[0101] Application in the Buchwald-Hartwig coupling reaction Application Example 5 PdBr2 (0.1 mmol, 2 mol%) from Example 1 was added to a 100 mL round-bottom flask. After three argon exchanges, 10 mL of 1,4-dioxane was added using a syringe. Triethylamine (5.0 mmol, 1.0 equiv) was slowly added at room temperature, and the mixture was stirred for 15 min. Subsequently, 5.0 mmol of bromobenzene, 7.5 mmol of aniline (1.5 equiv), and 7.5 mmol of potassium tert-butoxide (1.5 equiv) were added, and the temperature was raised to 110 °C. The reaction solution gradually changed from yellow to brownish-black. The reaction was stirred for 20 h, and the reaction was monitored by TLC until complete. The mixture was cooled to room temperature, diluted with water, and extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. The residue was purified by silica gel column chromatography (eluents were petroleum ether and ethyl acetate) to obtain the product in trace yield (a negligible amount).

[0102] The equation for the Buchwald-Hartwig coupling reaction in Application Example 5 is as follows: .

[0103] Comparative Application Example 4 Based on Application Example 5, PdBr2 was modified to be PPh3 and PdBr2 from Example 1, with a molar ratio of 2:1. Other conditions remained unchanged, and the yield was Trace.

[0104] Comparative Application Example 5 Based on Application Example 5, PdBr2 was modified to be SPhos and PdBr2 from Example 1, with a molar ratio of 2:1. Other conditions remained unchanged, and the yield was 71%.

[0105] Comparative Application Example 6 Based on Application Example 5, PdBr2 was modified to be XPhos and PdBr2 from Example 1, with a molar ratio of 2:1. Other conditions remained unchanged, and the yield was 65%.

[0106] Application Example 6 Based on Application Example 5, PdBr2 was modified to Pd(PPh3)2Br2 of Example 3, with other conditions remaining unchanged, and the yield was 64%.

[0107] Application Example 7 Based on Application Example 5, PdBr2 was modified to Pd(SPhos)2Br2 of Example 7, with other conditions remaining unchanged, and the yield was 83%.

[0108] Application Example 8 Based on Application Example 5, PdBr2 was modified to Pd(XPhos)2Br2 of Example 5, with other conditions remaining unchanged, and the yield was 89%.

[0109] Applications in Heck coupling reactions Application Example 9 PdBr2 (0.1 mmol, 2 mol%) from Example 1 was added to a 100 mL round-bottom flask. After three argon exchanges, 10 mL of 1,4-dioxane was added using a syringe. The mixture was then slowly added at room temperature with 5.0 mmol triethylamine (1.0 equiv) and stirred for 15 min. Subsequently, 5 mmol bromobenzene, 10.0 mmol 4-methylstyrene (2.0 equiv), and 5.5 mmol potassium carbonate (1.1 equiv) were added, and the mixture was heated to 120 °C and stirred for 24 h. The reaction was monitored by TLC until complete. After cooling to room temperature, the mixture was diluted with water and extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. The residue was purified by silica gel column chromatography (eluent: petroleum ether and ethyl acetate) to obtain the product, yield Trace.

[0110] The equation for the Heck coupling reaction in Example 9 is as follows: .

[0111] Comparative Application Example 7 Based on Application Example 9, PdBr2 was modified to be PPh3 and PdBr2 from Example 1, with a molar ratio of 2:1. Other conditions remained unchanged, and the yield was 32%.

[0112] Comparative Application Example 8 Based on Application Example 9, PdBr2 was modified to be SPhos and PdBr2 from Example 1, with a molar ratio of 2:1. Other conditions remained unchanged, and the yield was 22%.

[0113] Comparative Application Example 9 Based on Application Example 9, PdBr2 was modified to be XPhos and PdBr2 from Example 1, with a molar ratio of 2:1. Other conditions remained unchanged, and the yield was 35%.

[0114] Application Example 10 Based on Application Example 9, PdBr2 was modified to Pd(PPh3)2Br2 of Example 3, with other conditions remaining unchanged, and the yield was 41%.

[0115] Application Example 11 Based on Application Example 9, PdBr2 was modified to Pd(SPhos)2Br2 of Example 7, with other conditions remaining unchanged, and the yield was 12%.

[0116] Application Example 12 Based on Application Example 9, PdBr2 was modified to Pd(XPhos)2Br2 of Example 5, with other conditions remaining unchanged, and the yield was 31%.

[0117] As can be seen from the above examples and comparative examples, the preparation method provided by the present invention can improve the yield of PdBr2.

[0118] 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 method for preparing PdBr2, comprising the following steps: (1) Mix palladium, nitric acid and catalyst to dissolve, and then bake to obtain an intermediate product; the catalyst contains chloride ions or sulfide ions; (2) The intermediate product obtained in step (1) is mixed with a bromide-containing substance to carry out a precipitation reaction to obtain PdBr2.

2. The preparation method according to claim 1, characterized in that, The catalyst containing chloride ions in step (1) includes at least one of hydrochloric acid and chloride salts; the chloride salts include at least one of NH4Cl and NaCl.

3. The preparation method according to claim 1, characterized in that, The catalyst containing sulfur ions in step (1) includes at least one of hydrogen sulfide solution and sulfur salt.

4. The preparation method according to claim 1, characterized in that, In step (1), the catalyst is 0.5 to 2‰ of the mass of metallic palladium.

5. The preparation method according to claim 1, characterized in that, The baking in step (1) is performed under an infrared lamp.

6. A method for preparing a phosphine derivative of PdBr2, comprising the following steps: (1) Mix palladium, nitric acid and catalyst to dissolve, and then bake to obtain an intermediate product; the catalyst contains chloride ions or sulfide ions; (2) The intermediate product obtained in step (1) is mixed with a bromide-containing substance and subjected to a precipitation reaction to obtain PdBr2; (3) The PdBr2 obtained in step (2), organic solvent and phosphine ligand are mixed and then a coordination reaction is carried out to obtain a phosphine derivative of PdBr2.

7. The preparation method according to claim 6, characterized in that, The phosphine ligand in step (3) includes one of triphenylphosphine, 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl, 4,5-bisdiphenylphosphine-9,9-dimethyloxanthracene, and 1,2-bis(diphenylphosphine)ethane.

8. The preparation method according to claim 6, characterized in that, The temperature of the coordination reaction in step (3) is -20~0℃.

9. The use of PdBr2 prepared by the preparation method according to any one of claims 1 to 5 and / or the phosphine derivative of PdBr2 prepared by the preparation method according to any one of claims 6 to 8 as a catalyst in catalyzing carbon-carbon coupling reactions or carbon-heteroatom coupling reactions.

10. The application according to claim 9, characterized in that, The carbon-carbon coupling reaction is a Suzuki coupling reaction or a Heck coupling reaction; the carbon-heteroatom coupling reaction is a Buchwald-Hartwig amination reaction.

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