Palladium complex as well as preparation method and application thereof

Abstract

The invention provides a palladium complex and a preparation method and application thereof, and belongs to the technical field of chemical catalysis. The preparation method of the palladium complex comprises the steps that 2 '-halogen-[1, 1'-biphenyl]-2-ammonium salt, palladium salt, a reducing agent and a solvent are mixed and then subjected to a cyclopalladium reaction, then a phosphine ligand is added for a coordination reaction, aftertreatment is conducted, and the palladium complex is obtained. The post-treatment comprises the steps of removing a solvent and purifying in sequence. According to the invention, the 2 '-halogen-[1, 1'-biphenyl]-2-ammonium salt and the palladium salt are subjected to ring targeting reaction, and then are subjected to coordination reaction with the phosphine ligand, so that the problems of synthesis and treatment of dimers in the traditional route are avoided, and the reaction route is greatly shortened, thereby improving the yield and purity of the product. Experimental results show that the yield of the preparation method provided by the invention reaches 96%, and the purity is greater than 99%.

Description

Technical Field

[0001] This invention belongs to the field of chemical catalysis technology, specifically relating to a palladium complex, its preparation method, and its application. Background Technology

[0002] XPhos Pd G3 is a novel precatalyst for cyclopalladium-encapsulated 2-aminobiphenylmethanesulfonate skeletons, which can generate coordinated Pd(0) active species in situ under alkaline conditions. This precatalyst exhibits high stability and strong catalytic activity, and has been widely used in reactions involving the formation of carbon-carbon and carbon-nitrogen bonds. For example, it demonstrates high catalytic activity in the Suzuki-Miyaura coupling reaction of bromopyridine with phenylboronic acid, and can also be used in the Buchwald-Hartwig amination reaction of halogenated aromatic hydrocarbons with amines (primary and secondary amines).

[0003] Currently, the main method for preparing XPhos Pd G3 involves synthesizing a quaternary ammonium salt containing a biphenyl group using o-aminobiphenyl and methanesulfonic acid, then reacting it with palladium acetate at high temperature to generate a dimer, followed by coordination with an XPhos ligand to synthesize XPhos Pd G3, as reported by Buchwald in Chem Sci. 2013;4:916-920 and patent US 2013 / 0331566 A1. However, this method results in the formation of a dimer, and the post-processing of the dimer is quite complex, leading to a significant decrease in yield (60-70%) and purity (around 95%), which is detrimental to industrial production. Therefore, improving the purity and yield of palladium complex catalysts has become a pressing technical challenge in this field. Summary of the Invention

[0004] The purpose of this invention is to provide a palladium complex, its preparation method, and its applications. The preparation method provided by this invention produces products with high purity and high yield.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a method for preparing palladium complexes, comprising: The 2'-halo-[1,1'-biphenyl]-2-ammonium salt, palladium salt, reducing agent and solvent were mixed and then subjected to a cyclopalladium reaction. Then, a phosphine ligand was added to carry out a coordination reaction, and then post-processing was performed to obtain a palladium complex. The post-processing includes sequential solvent removal and purification.

[0006] Preferably, the structural formula of the 2'-halo-[1,1'-biphenyl]-2-ammonium salt is shown in Formula I: Formula I; In formula I, R 1 It is methanesulfonate, chloride, or p-toluenesulfonate, and Y is chloride or bromide.

[0007] Preferably, the preparation method of the 2'-halo-[1,1'-biphenyl]-2-ammonium salt includes the following steps: (1) After mixing o-haloaniline, acid and first solvent, a salt-forming reaction is carried out to obtain 2-halo-phenyl quaternary ammonium salt; (2) The 2-halo-phenyl quaternary ammonium salt, 2-halophenylboronic acid, palladium (0) catalyst, base and second solvent obtained in step (1) are mixed and coupled to obtain 2'-halo-[1,1'-biphenyl]-2-ammonium salt.

[0008] Preferably, the acid in step (1) is methanesulfonic acid, hydrochloric acid or p-toluenesulfonic acid; the molar ratio of the o-haloaniline to the acid is 1:(1~1.5).

[0009] Preferably, the molar ratio of the 2'-halo-[1,1'-biphenyl]-2-ammonium salt to the palladium salt is 1:(1.0~1.3).

[0010] Preferably, the molar ratio of the palladium salt to the phosphine ligand is 1:(1.0~1.2).

[0011] Preferably, the cyclopalladium reaction is carried out at a temperature of 40-60°C for 30-60 minutes.

[0012] Preferably, the coordination reaction is carried out at room temperature for 30 to 60 minutes.

[0013] The present invention also provides a palladium complex prepared by the preparation method described above, the structural formula of which is shown in Formula II: Formula II; In formula II, R 1 It is an anion, and PR3 is a phosphine ligand.

[0014] The present invention also provides the application of the palladium complex described above as a catalyst in the Heck coupling reaction.

[0015] This invention provides a method for preparing palladium complexes, comprising: mixing 2'-halo-[1,1'-biphenyl]-2-ammonium salt, palladium salt, reducing agent, and solvent, followed by a cyclopalladium reaction; then adding a phosphine ligand for a coordination reaction; and finally performing post-treatment to obtain the palladium complex; the post-treatment includes sequential solvent removal and purification. This invention uses 2'-halo-[1,1'-biphenyl]-2-ammonium salt as a raw material, reacting it with the palladium salt and phosphine ligand in the same reaction system in a one-pot process, avoiding the difficulties of dimer synthesis and processing in traditional routes, significantly shortening the reaction path, and thus improving the yield and purity of the product. Experimental results show that the preparation method provided by this invention achieves a yield of 96% and a purity >99%. Detailed Implementation

[0016] This invention provides a method for preparing palladium complexes, comprising: The 2'-halo-[1,1'-biphenyl]-2-ammonium salt, palladium salt, reducing agent and solvent were mixed and then subjected to a cyclopalladium reaction. Then, a phosphine ligand was added to carry out a coordination reaction, and then post-processing was performed to obtain a palladium complex. The post-processing includes sequential solvent removal and purification.

[0017] This invention does not impose any special restrictions on the source of the raw materials; commercially available products familiar to those skilled in the art can be used.

[0018] In this invention, 2'-halo-[1,1'-biphenyl]-2-ammonium salt, palladium salt, reducing agent and solvent are mixed and then subjected to a cyclopalladium reaction. Then, a phosphine ligand is added to carry out a coordination reaction, and then post-processing is performed to obtain a palladium complex.

[0019] In this invention, the reaction equation for the 2'-halo-[1,1'-biphenyl]-2-ammonium salt and palladium salt is as follows: ; In the formula, Y is a chloride ion or a bromide ion, X is a halogen (bromine ion or iodide ion), and R... 1 It consists of methanesulfonate, chloride, or p-toluenesulfonate.

[0020] In this invention, the preferred structural formula of the 2'-halo-[1,1'-biphenyl]-2-ammonium salt is as shown in Formula I: Formula I; In formula I, R 1 It is methanesulfonate, chloride, or p-toluenesulfonate, and Y is chloride or bromide.

[0021] In this invention, the preparation method of the 2'-halo-[1,1'-biphenyl]-2-ammonium salt preferably includes the following steps: (1) After mixing o-haloaniline, acid and first solvent, a salt-forming reaction is carried out to obtain 2-halo-phenyl quaternary ammonium salt; (2) The 2-halo-phenyl quaternary ammonium salt, 2-halophenylboronic acid, palladium (0) catalyst, base and second solvent obtained in step (1) are mixed and coupled to obtain 2'-halo-[1,1'-biphenyl]-2-ammonium salt.

[0022] This invention uses inexpensive o-haloaniline as a raw material to efficiently construct the 2-aminobiphenyl skeleton when preparing 2'-halo-[1,1'-biphenyl]-2-ammonium salt, avoiding the use of o-aminobiphenyl compounds and reducing costs.

[0023] The present invention preferably involves mixing o-haloaniline, acid, and a first solvent to carry out a salt-forming reaction to obtain a 2-halo-phenyl quaternary ammonium salt.

[0024] In this invention, the reaction equation for the salt formation reaction is as follows: ; In the formula, X is a halogen (bromine ion or iodide ion), and R 1 It consists of methanesulfonate, chloride, or p-toluenesulfonate.

[0025] In this invention, the o-haloaniline is preferably o-bromoaniline or o-iodoaniline; the acid is preferably methanesulfonic acid, hydrochloric acid, or p-toluenesulfonic acid; the first solvent is preferably diethyl ether, tetrahydrofuran, or toluene, more preferably diethyl ether. Addressing the problem of complex anion exchange in existing preparation methods, the anions in the acid of this invention—methanesulfonate, chloride, and p-toluenesulfonate—are all strongly electron-withdrawing, weakly coordinating anions. Throughout the entire synthesis process, from the initial step, the same strongly electron-withdrawing, weakly coordinating anions as the target product are used, thereby avoiding purification difficulties and yield losses caused by subsequent anion substitution, and further improving the yield.

[0026] In this invention, the molar ratio of o-haloaniline to acid is preferably 1:(1~1.5). As one embodiment, the molar ratio of o-haloaniline to acid can be 1:1.1, 1:1.2, 1:1.3, or 1:1.4. Limiting the molar ratio of o-haloaniline to acid within the above range further promotes the salt-forming reaction, thereby ensuring that the raw materials react as completely as possible and increasing the yield.

[0027] The present invention does not have a special limitation on the amount of the first solvent, as long as all raw materials are completely dissolved.

[0028] The present invention does not have any special limitations on the operation of mixing the o-haloaniline, acid and first solvent, and any technical solution for preparing the mixture well known to those skilled in the art can be used.

[0029] In this invention, the preferred temperature for the salt-forming reaction is 15-30°C; the preferred reaction time is 30-60 minutes; and the salt-forming 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.

[0030] In one embodiment, the temperature of the salt formation reaction can be 20°C or 25°C; the time of the salt formation reaction can be 35 min, 40 min, 45 min, 50 min or 55 min.

[0031] After the salt-forming reaction is completed, the present invention preferably performs post-processing on the product obtained from the salt-forming reaction to obtain 2-halo-benzene quaternary ammonium salt.

[0032] In this invention, the post-processing preferably includes sequentially performing vacuum concentration / solid-liquid separation, washing, and drying.

[0033] The present invention does not have any special limitations on the operation of the vacuum concentration; the solvent can be removed by means of operations well known to those skilled in the art.

[0034] The present invention does not impose any particular limitation on the operation of the solid-liquid separation; any operation well known to those skilled in the art can be used to obtain the solid. As one embodiment, the solid-liquid separation can be filtration.

[0035] The present invention does not impose any special limitations on the washing operation; any operation known to those skilled in the art can be used to remove impurities.

[0036] The present invention does not impose any special limitations on the drying operation; drying to a constant weight is sufficient.

[0037] After obtaining the 2-halo-benzene quaternary ammonium salt, the present invention preferably mixes the 2-halo-benzene quaternary ammonium salt, 2-halophenylboronic acid, palladium (0) catalyst, base and second solvent to carry out a coupling reaction to obtain 2'-halo-[1,1'-biphenyl]-2-ammonium salt.

[0038] In this invention, the reaction equation for 2-halo-phenyl quaternary ammonium salt and 2-halophenylboronic acid under the action of palladium (0) catalyst is as follows: ; In the formula, X is a halogen (bromine ion or iodide ion), and R 1 It is methanesulfonate, chloride, or p-toluenesulfonate, and Y is chloride or bromide.

[0039] In this invention, the 2-halophenylboronic acid is preferably 2-chlorophenylboronic acid or 2-bromophenylboronic acid; the palladium (0) catalyst is preferably tetrakis(triphenylphosphine)palladium; the base is preferably potassium carbonate, cesium carbonate or potassium tert-butoxide, more preferably cesium carbonate; the second solvent is preferably at least one of tetrahydrofuran, toluene, 1,4-dioxane and water, more preferably tetrahydrofuran and water.

[0040] In this invention, the preferred molar ratio of the 2-halophenyl quaternary ammonium salt to the 2-halophenylboronic acid is 1:(1.1~2.0); the preferred molar ratio of the palladium (0) catalyst to the 2-halophenyl quaternary ammonium salt is (0.02~0.05):1. As one embodiment, the molar ratio of the 2-halophenyl quaternary ammonium salt to the 2-halophenylboronic acid can be 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, or 1:1.9; the molar ratio of the palladium (0) catalyst to the 2-halophenyl quaternary ammonium salt can be 0.03:1 or 0.04:1. By limiting the molar ratios of the 2-halophenyl quaternary ammonium salt to the 2-halophenylboronic acid and the palladium (0) catalyst to the 2-halophenyl quaternary ammonium salt to the above ranges, this invention can further improve the degree of coupling reaction.

[0041] In this invention, the preferred molar ratio of the base to the 2-halo-phenyl quaternary ammonium salt is (1.5~2.1):1. As one embodiment, the molar ratio of the base to the 2-halo-phenyl quaternary ammonium salt can be 2.0:1. Limiting the molar ratio of the base to the 2-halo-phenyl quaternary ammonium salt to the above range further enhances the degree of coupling reaction.

[0042] The present invention does not have a special limitation on the amount of the second solvent, as long as all raw materials are completely dissolved.

[0043] The present invention does not have any special limitations on the operation of mixing the 2-halo-phenyl quaternary ammonium salt, 2-halophenylboronic acid, palladium (0) catalyst, base and second solvent, and any technical solution for preparing the mixture well known to those skilled in the art can be used.

[0044] In this invention, the coupling reaction temperature is preferably 60-90°C; the coupling reaction is preferably carried out in an inert atmosphere. As one embodiment, the coupling reaction temperature can be 65°C, 70°C, 75°C, 80°C, or 85°C. Limiting the coupling reaction temperature to the above range further promotes the coupling reaction.

[0045] The present invention does not specifically limit the type of inert atmosphere; any inert atmosphere well known to those skilled in the art can be used. As one embodiment, the inert atmosphere is argon.

[0046] The present invention does not impose a specific time limit on the coupling reaction; the endpoint can be determined by monitoring the reaction system.

[0047] In one implementation, the coupling reaction can take 2 to 3 hours.

[0048] In this invention, the coupling reaction is preferably carried out under stirring conditions. This invention does not impose a particular limitation on the stirring rate; any stirring operation well-known to those skilled in the art can be used.

[0049] After the coupling reaction is completed, the product obtained by the coupling reaction is preferably post-processed to obtain 2'-halo-[1,1'-biphenyl]-2-ammonium salt.

[0050] In this invention, the post-processing preferably includes sequentially performing cooling, extraction, drying, and purification.

[0051] The present invention does not impose any special limitations on the cooling operation; any operation known to those skilled in the art can be used to cool to room temperature.

[0052] The present invention does not impose any special limitations on the extraction operation; the target product 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 drying operation; any operation known to those skilled in the art can be used to dry to constant weight.

[0054] In this invention, the purification is preferably carried out using silica gel column chromatography; the eluent used in the silica gel column chromatography purification is preferably petroleum ether and ethyl acetate; and the volume ratio of petroleum ether to ethyl acetate during the silica gel column chromatography purification is preferably gradiented from 80:20 to 60:40. This invention does not impose any particular limitation on the rate of gradient change of the volume ratio of petroleum ether to ethyl acetate, and any operation familiar to those skilled in the art can be used. The silica gel column chromatography purification method of this invention can further purify the target product, thereby improving its purity.

[0055] In this invention, the palladium salt is preferably palladium methanesulfonate, palladium chloride, or palladium p-toluenesulfonate; the reducing agent is preferably carbon monoxide or hydrazine hydrate, more preferably carbon monoxide; and the solvent is preferably tetrahydrofuran, toluene, or 1,4-dioxane, more preferably toluene.

[0056] In this invention, the preferred molar ratio of the 2'-halo-[1,1'-biphenyl]-2-ammonium salt to the palladium salt is 1:(1.0~1.3). As one embodiment, the molar ratio of the 2'-halo-[1,1'-biphenyl]-2-ammonium salt to the palladium salt can be 1:1.1 or 1:1.2. By limiting the molar ratio of the 2'-halo-[1,1'-biphenyl]-2-ammonium salt to the palladium salt to the above range, this invention can further improve the degree of cyclopalladiumization reaction, thereby increasing the yield.

[0057] In this invention, when the reducing agent is carbon monoxide, it is preferred to introduce carbon monoxide; the gas flow rate of the carbon monoxide is preferably 10~100 mL / min; the introduction time is preferably 30~60 min; when the reducing agent is hydrazine hydrate, the molar ratio of the hydrazine hydrate to 2'-halo-[1,1'-biphenyl]-2-ammonium salt is preferably (1.5~2.0):1. As one embodiment, the molar ratio of the hydrazine hydrate to 2'-halo-[1,1'-biphenyl]-2-ammonium salt can be 2.0:1.

[0058] The present invention does not have a special limitation on the amount of solvent used, as long as all raw materials are completely dissolved.

[0059] The present invention does not have any special limitations on the operation of mixing the 2'-halo-[1,1'-biphenyl]-2-ammonium salt, palladium salt, reducing agent and solvent, and any technical solution for preparing the mixture well known to those skilled in the art can be used.

[0060] In this invention, the preferred temperature for the cyclopalladium oxidation reaction is 40-60°C; the preferred reaction time is 30-60 min. As one embodiment, the temperature for the cyclopalladium oxidation reaction can be 45°C, 50°C, or 55°C; the reaction time can be 35 min, 40 min, 45 min, 50 min, or 55 min. Limiting the temperature and time of the cyclopalladium oxidation reaction to the above ranges further promotes the reaction and ensures that the reactants react as completely as possible.

[0061] After the cyclopalladium reaction is completed, the product obtained by the cyclopalladium reaction is preferably cooled.

[0062] The present invention does not impose any special limitations on the cooling operation; any operation known to those skilled in the art can be used to cool to room temperature.

[0063] This invention involves only cooling after the cyclopalladium reaction is completed, followed by direct addition of phosphine ligands for coordination reaction. This eliminates the need for dimer synthesis and avoids subsequent post-processing of the dimer, significantly shortening the reaction path and thus improving the product yield and purity.

[0064] In this invention, the reaction equation for the palladium intermediate obtained from the cyclotargeting reaction and the phosphine ligand is as follows: ; In formula I, R 1 It is methanesulfonate, chloride, or p-toluenesulfonate. PR3 is 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, 2-dicyclohexylphosphine-2',6'-dimethoxy-1,1'-biphenyl, [2,2'-bis(diphenylphosphine)-1,1'-binaphthyl], or 2-dicyclohexylphosphine-2',6'-diisopropoxy-1,1'-biphenyl.

[0065] In this invention, the phosphine ligand is preferably 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (XPhos), 2-dicyclohexylphosphine-2',6'-dimethoxy-1,1'-biphenyl (SPhos), [2,2'-bis(diphenylphosphine)-1,1'-binaphthyl] (BrettPhos), or 2-dicyclohexylphosphine-2',6'-diisopropoxy-1,1'-biphenyl (RuPhos).

[0066] In this invention, the molar ratio of the palladium salt to the phosphine ligand is preferably 1:(1.0~1.2). As one embodiment, the molar ratio of the palladium salt to the phosphine ligand can be 1:1.1. Limiting the molar ratio of the palladium salt to the phosphine ligand to the above range further promotes the coordination reaction.

[0067] The present invention does not have any special limitations on the operation of adding phosphine ligands, and any technical solution for preparing mixtures well known to those skilled in the art can be used.

[0068] In this invention, the temperature of the coordination reaction is preferably room temperature; the time of the coordination reaction is preferably 30-60 min. As one embodiment, the time of the coordination reaction can be 35 min, 40 min, 45 min, 50 min, or 55 min. Limiting the temperature and time of the coordination reaction to the above ranges further enhances the degree of coordination reaction.

[0069] In this invention, the post-processing includes sequentially removing the solvent and purifying the material.

[0070] This invention does not impose any particular limitation on the solvent removal operation; any operation well-known to those skilled in the art can be used. As one embodiment, the solvent removal can be performed by vacuum evaporation. This invention does not impose any particular limitation on the vacuum evaporation operation; any operation well-known to those skilled in the art can be used to remove the solvent.

[0071] In this invention, the purification is preferably carried out by recrystallization or solvent grinding.

[0072] The present invention does not impose any special limitations on the recrystallization operation; any operation known to those skilled in the art can be used.

[0073] The present invention does not impose any particular limitation on the solvent milling operation; any operation well known to those skilled in the art can be used. As one embodiment, the solvent used for solvent milling can be pentane.

[0074] To address the problem of lengthy routes in existing preparation methods, this invention integrates multiple steps using a one-pot method. Using 2'-halo-[1,1'-biphenyl]-2-ammonium salt as a raw material, it reacts with palladium salt and phosphine ligands, optimizing the one-pot synthesis process. This significantly shortens the synthesis route and effectively improves the overall yield, making it suitable for obtaining the target catalyst with high yield and high purity. It has significant advantages in simplifying the process and reducing costs, laying a solid industrial foundation for its wider research and application.

[0075] The preparation method provided by this invention simplifies the operation, improves the yield, and expands the application of the catalyst in the Heck coupling reaction. It is suitable for the conversion of halogenated aromatics and olefins, and has excellent catalytic activity and industrialization potential.

[0076] The preparation method provided by this invention is efficient and universal. This method is applicable to the synthesis of palladium complexes (XPhos Pd G3 and similar precatalysts). The specific process route is as follows: using a quaternary ammonium salt containing a biphenyl skeleton as raw material, it reacts with palladium salt and phosphine ligand in the same reaction system in a one-pot reaction to obtain the target palladium complex with a defined structure in high yield and high purity.

[0077] Furthermore, in this invention, the 2'-halo-[1,1'-biphenyl]-2-ammonium salt can be prepared using inexpensive and readily available o-haloaniline as a raw material, which reduces costs compared to traditional methods that directly use o-aminobiphenyl compounds.

[0078] Furthermore, this invention achieves synergistic optimization of raw materials and reaction system by employing a unified strong electron-withdrawing weak coordination anion throughout the entire process. By optimizing reaction conditions and using common solvents, this invention significantly reduces operational difficulty and equipment requirements, enabling the reaction to proceed under conventional conditions without the need for a strictly anhydrous and oxygen-free environment, thus improving the robustness and scalability of the process. This invention utilizes the valence state cycle of Pd(II) → Pd(0) → Pd(II) to achieve the capture, assembly, and release of ligands by the palladium center. In the final product synthesis stage, by precisely controlling the molar ratio of palladium salt to 2'-halo-[1,1'-biphenyl]-2-ammonium salt and reacting efficiently with phosphine ligands in the presence of a reducing agent, the yield and purity of the target product are improved, avoiding the cumulative losses caused by multi-step conversions in traditional methods. In summary, this invention achieves lower production costs, higher reaction efficiency, and better scalability through raw material substitution, pathway simplification, condition optimization, and anion consistency design, providing solid support for the industrial application of catalysts such as XPhos Pd G3. It also demonstrates that palladium complexes can catalyze a variety of reaction types and have a wide range of applications.

[0079] The present invention also provides a palladium complex prepared by the preparation method described above, the structural formula of which is shown in Formula II: Formula II; In formula II, R 1 It is an anion, and PR3 is a phosphine ligand.

[0080] In this invention, the R 1 Preferably, it is composed of methanesulfonate, chloride, or p-toluenesulfonate; the PR3 is preferably 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, 2-dicyclohexylphosphine-2',6'-dimethoxy-1,1'-biphenyl, [2,2'-bis(diphenylphosphine)-1,1'-binaphthyl] or 2-dicyclohexylphosphine-2',6'-diisopropoxy-1,1'-biphenyl.

[0081] The present invention also provides the application of the palladium complex described above as a catalyst in the Heck coupling reaction.

[0082] In this invention, the preferred operation for using the palladium complex as a catalyst in the Heck coupling reaction is as follows: The haloaromatic hydrocarbon, olefin, base, palladium complex, and solvent are mixed and subjected to Heck coupling reaction to obtain arylethylene products.

[0083] In this invention, the equation for the Heck coupling reaction is as follows: ; In the formula, R1 is H, methoxy or methyl, X is halogen, and R2 is phenyl or benzyl.

[0084] In this invention, the halogenated aromatic hydrocarbon is preferably bromobenzene, chlorobenzene, 2-chloro-1,3-xylene, or 2-chloro-m-phenylenediamine; the olefin is preferably styrene or 4-methylstyrene; and the molar ratio of the halogenated aromatic hydrocarbon to the olefin is preferably 1:(1~1.5). As one embodiment, the molar ratio of the halogenated aromatic hydrocarbon to the olefin can be 1:1.1, 1:1.2, 1:1.3, or 1:1.4. By limiting the molar ratio of the halogenated aromatic hydrocarbon to the olefin to the above range, this invention can increase the extent of the Heck coupling reaction, thereby increasing the yield of the target product.

[0085] In this invention, the base is preferably potassium carbonate, cesium carbonate, or potassium tert-butoxide, more preferably potassium carbonate; the molar ratio of the haloaromatic hydrocarbon to the base is preferably 1:(1.0~1.6). As one embodiment, the molar ratio of the haloaromatic hydrocarbon to the base can be 1:1.5. By limiting the molar ratio of the haloaromatic hydrocarbon to the base within the above range, this invention can increase the extent of the Heck coupling reaction, thereby increasing the yield of the target product.

[0086] In this invention, the solvent is preferably N,N-dimethylformamide, toluene, or 1,4-dioxane, more preferably 1,4-dioxane. This invention does not impose any particular limitation on the amount of solvent used, as long as all raw materials are completely dissolved.

[0087] In this invention, the amount of palladium complex is preferably 1-4% of the amount of haloaromatic hydrocarbon. As one embodiment, the amount of palladium complex can be 2% or 3% of the amount of haloaromatic hydrocarbon. Limiting the content of the palladium complex within the above range allows for further catalysis of the Heck coupling reaction.

[0088] The present invention does not have any special limitations on the operation of mixing the haloaromatic hydrocarbons, olefins, bases, palladium complexes and solvents, and any technical solution for preparing the mixture well known to those skilled in the art can be used.

[0089] In this invention, the preferred temperature for the Heck coupling reaction is 80-110°C. As one embodiment, the temperature for the Heck coupling reaction can be 85°C, 90°C, 95°C, 100°C, or 105°C. Limiting the temperature of the Heck coupling reaction to the above range further promotes the reaction and thus increases the yield of the target product.

[0090] The present invention does not impose a specific time limit on the Heck coupling reaction; the endpoint can be determined by monitoring the reaction system.

[0091] In one implementation, the Heck coupling reaction can take 9 to 12 hours.

[0092] After the Heck coupling reaction is completed, the present invention preferably performs post-processing on the product obtained by the Heck coupling reaction to obtain aryl ethylene products.

[0093] In this invention, the post-processing preferably includes sequentially performing cooling, extraction, drying, and purification.

[0094] The present invention does not impose any special limitations on the cooling operation; any operation known to those skilled in the art can be used to cool to room temperature.

[0095] The present invention does not impose any special limitations on the extraction operation; the target product can be obtained by using operations well known to those skilled in the art.

[0096] The present invention does not impose any special limitations on the drying operation; any operation known to those skilled in the art can be used to dry to constant weight.

[0097] In this invention, the purification is preferably carried out by silica gel column chromatography; the eluent used in the silica gel column chromatography purification is preferably petroleum ether and ethyl acetate; the volume ratio of petroleum ether to ethyl acetate during the silica gel column chromatography purification is preferably gradiented from 100:0 to 80:20. This invention does not impose any particular limitation on the rate of gradient change of the volume ratio of petroleum ether to ethyl acetate; any operation familiar to those skilled in the art can be used. The silica gel column chromatography purification method of this invention can further purify the target product, thereby improving its purity.

[0098] This invention expands the application scope of XPhos Pd G3, extending beyond the Suzuki-Miyaura coupling and Buchwald-Hartwig amination reactions to include olefins. Furthermore, the palladium complex can catalyze substrates with higher reaction difficulty in the Heck reaction, further highlighting its advantages as a catalyst precursor.

[0099] The high efficiency of the palladium complex XPhos Pd G3 in catalyzing the Suzuki-Miyaura coupling reaction in this invention is mainly due to two factors: First, XPhos Pd G3 can be rapidly and completely reduced in the presence of a base to generate a coordinatingly unsaturated monophosphine-coordinated Pd(0) species (L-Pd). 0The reduction pathway of XPhos Pd G3 directly leads to the target active monomer, which is the most active form in the catalytic cycle. Secondly, the ligands of XPhos Pd G3 are sterically hindered, electron-rich phosphine ligands. These ligands have two key functions: firstly, their steric hindrance is sufficiently large, allowing the electron-rich phosphine atom to form a strong coordination interaction with the empty d orbitals of Pd(0). The sterically hindered substituents effectively prevent the aggregation of newly formed Pd(0) nanoparticles through steric hindrance, thereby inhibiting palladium black deactivation. Secondly, during the reaction, they possess flexible structural characteristics, allowing space to be provided to the substrate during oxidative addition. This also helps stabilize the zero-valent palladium intermediate, making reduction easier.

[0100] The reason why the palladium complex XPhos Pd G3 can catalyze the Heck coupling reaction in this invention is that XPhos Pd G3 possesses a large, electron-rich, monodentate phosphine ligand, which can regulate the electron density and steric hindrance of the palladium center, thereby affecting the oxidative addition rate and making it easier for it to interact with chemical bonds that are normally difficult to react (especially inert C-Cl bonds). Simultaneously, the large-volume alkylphosphine-coordinated palladium complex, as a monocoordinate species, has an advantage in the reductive elimination step in cross-coupling reactions, effectively avoiding side reactions.

[0101] 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.

[0102] Example 1 Pd(OMs)(C 12 H8NH2)(XPhos) The preparation method of palladium complex is as follows: Weigh 1.72 g (10.0 mmol) of o-bromoaniline and dissolve it in 40 mL of diethyl ether. Then add 1.44 g (15.0 mmol) of methanesulfonic acid to obtain a mixture. Stir at 30 °C for 30 min to carry out the salt formation reaction. Then filter the reaction solution, wash it with diethyl ether, and then dry it under vacuum to obtain solid 2-bromo-aminobenzosulfonate. 2-Bromo-aminobenzylsulfonate, 3.13 g (20.0 mmol) of 2-chlorophenylboronic acid, and 462 mg (0.4 mmol) of tetratriphenylphosphine palladium were dissolved in 100 mL of tetrahydrofuran. The mixture was purged with argon three times under stirring. Then, 2.76 g (20.0 mmol) of potassium carbonate solution (20 mL) was slowly added. The mixture was heated to 60 °C for a coupling reaction. After the reaction was completed by TCL monitoring, it was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 80:20 to 60:40) to obtain crystalline 2'-chloro-[1,1'-biphenyl]-2-aminomethanesulfonate. The molar ratio of 2-bromo-aminobenzylsulfonate to 2-chlorophenylboronic acid was 1:2.0; the molar ratio of tetratriphenylphosphine palladium to 2-bromo-aminobenzylsulfonate was 0.04:1. 2'-Chloro-[1,1'-biphenyl]-2-aminomethanesulfonate crystals and 2.6 g (10.0 mmol) of palladium methanesulfonate were dissolved in 40 mL of tetrahydrofuran. CO was introduced at a gas flow rate of 10 mL / min for 30 min, and then the temperature was raised to 40 °C for a cyclopalladium reaction for 30 min, followed by cooling to room temperature. Then, 4.77 g (10.0 mmol) of XPhos was added to the system for coordination reaction at room temperature for 30 min. Then, 90% of the solvent was removed under vacuum. The crude product was ground with pentane to obtain a palladium complex with a yield of 92% and a purity of 99.5%. The molar ratio of 2'-chloro-[1,1'-biphenyl]-2-aminomethanesulfonate to palladium methanesulfonate was 1:1.

[0103] Example 2 Pd(Cl)(C 12 H8NH2)(XPhos) The preparation method of palladium complex is as follows: Weigh 2.19 g (10.0 mmol) of o-iodoaniline and dissolve it in 40 mL of tetrahydrofuran. Then slowly add 0.44 g (12 mmol) of hydrochloric acid in 10 mL of diethyl ether to obtain a mixture. Stir at 25 °C to carry out the salt formation reaction for 45 min. Then filter the reaction solution, wash with diethyl ether, and dry under vacuum to obtain solid 2-bromo-aminophenyl hydrochloride. Dissolve 2-bromo-aminobenzene hydrochloride, 2.35 g (15 mmol) of 2-chlorophenylboronic acid, and 231 mg (0.2 mmol) of tetraphenylphosphine palladium in 75 mL of water. In 1,4-dioxane, argon gas was purged three times under stirring, followed by the slow addition of 6.52 g (20.0 mmol) of cesium carbonate aqueous solution (30 mL). The mixture was heated to 80 °C for coupling reaction. After the reaction was completed by TCL monitoring, it was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether and ethyl acetate as eluent changed from 80:20 to 60:40) to obtain crystalline 2'-chloro-[1,1'-biphenyl]-2-amino hydrochloride; wherein the molar ratio of 2'-chloro-[1,1'-biphenyl]-2-amino hydrochloride to 2-chlorophenylboronic acid was 1:1.5; and the molar ratio of tetrakis(triphenylphosphine)palladium to 2'-chloro-[1,1'-biphenyl]-2-amino hydrochloride was 0.02:1. 1.77 g (10 mmol) of palladium chloride was dissolved in 50 mL of toluene, and 0.97 mL (20 mmol) of hydrazine hydrate was added. The mixture was then heated to 50 °C for a cyclopalladium reaction for 35 min, followed by cooling to room temperature. Then, 5.24 g (11 mmol) of XPhos was added to the system for a coordination reaction at room temperature for 45 min. After removing 90% of the solvent under vacuum, the crude product was ground with pentane to obtain a palladium complex with a yield of 93% and a purity of 99.4%. The molar ratio of 2'-chloro-[1,1'-biphenyl]-2-aminohydrochloride to palladium chloride was 1:1.0, and the molar ratio of hydrazine hydrate to 2'-chloro-[1,1'-biphenyl]-2-aminohydrochloride was 2.0:1.

[0104] Example 3 Pd(OTs)(C 12 H8NH2)(XPhos) The preparation method of palladium complex is as follows: 1.72 g (10.0 mmol) of o-bromoaniline was dissolved in 55 mL of toluene, and then 2.24 g (13 mmol) of p-toluenesulfonic acid was added to obtain a mixture. The mixture was stirred at 30 °C for 1 h to form a salt. The reaction solution was then filtered, washed with diethyl ether, and dried under vacuum to obtain solid 2-bromo-aminobenzene-p-methylbenzenesulfonate. 2-Bromo-aminobenzene-p-methylbenzenesulfonate, 4.01 g (20 mmol) of 2-bromophenylboronic acid, and 347 mg (0.3 mmol) of tetrakis(triphenylphosphine)palladium were dissolved in 90 mL of toluene. The mixture was purged with argon three times under stirring. Then, 2.24 g (20.0 mmol) of potassium tert-butoxide in 10 mL of toluene was slowly added. The mixture was heated to 90 °C for a coupling reaction. After the reaction was completed by TCL monitoring, it was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 80:20 to 60:40) to obtain crystalline 2'-chloro-[1,1'-biphenyl]-2-amino-p-methylbenzenesulfonate. The molar ratio of 2-bromo-aminobenzene-p-methylbenzenesulfonate to 2-bromophenylboronic acid was 1:2.0; the molar ratio of tetrakis(triphenylphosphine)palladium to 2-bromo-aminobenzene-p-methylbenzenesulfonate was 0.03:1. Crystalline 2'-chloro-[1,1'-biphenyl]-2-amino-p-toluenesulfonate and 5.82 g (13 mmol) of palladium p-toluenesulfonate were dissolved in 50 mL of 1,4-dioxane. CO was introduced at a gas flow rate of 10 mL / min for 60 min, and the mixture was heated to 60 °C for 1 h for cyclopalladiumization. The mixture was then cooled to room temperature, and 6.20 g (13 mmol) of XPos was added to the system for coordination reaction at room temperature for 1 h. 90% of the solvent was then removed under vacuum. The crude product was ground with pentane to obtain a palladium complex with a yield of 96% and a purity of 99.6%. The molar ratio of 2'-chloro-[1,1'-biphenyl]-2-amino-p-toluenesulfonate to palladium p-toluenesulfonate was 1:1.3.

[0105] Example 4 Pd(OMs)(C 12 H8NH2)(SPhos) The preparation method of palladium complex is as follows: Weigh 1.72 g (10.0 mmol) of o-bromoaniline and dissolve it in 50 mL of diethyl ether. Then add 2.24 g (13 mmol) of p-toluenesulfonic acid to obtain a mixture. Stir at 30 °C for 45 min to form a salt. Then filter the reaction solution, wash with diethyl ether, and dry under vacuum to obtain solid 2-bromo-aminobenzoic acid salt. 2-Bromo-aminobenzylsulfonate, 1.72 g (11 mmol) of 2-chlorophenylboronic acid, and 231 mg (0.2 mmol) of tetratriphenylphosphine palladium were dissolved in 100 mL of tetrahydrofuran. The mixture was purged with argon three times under stirring. Then, 2.76 g (20.0 mmol) of potassium carbonate solution (25 mL) was slowly added. The mixture was heated to 70 °C for a coupling reaction. After the reaction was completed by TCL monitoring, it was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 80:20 to 60:40) to obtain crystalline 2'-chloro-[1,1'-biphenyl]-2-aminomethanesulfonate. The molar ratio of 2-bromo-aminobenzylsulfonate to 2-chlorophenylboronic acid was 1:1.1, and the molar ratio of tetratriphenylphosphine palladium to 2-bromo-aminobenzylsulfonate was 0.02:1. 3.12 g (12 mmol) of palladium methanesulfonate and crystalline 2'-chloro-[1,1'-biphenyl]-2-aminomethanesulfonate were dissolved in 50 mL of tetrahydrofuran. CO was introduced at a gas flow rate of 10 mL / min for 30 min, and then the mixture was heated to 40 °C for a cyclopalladium reaction for 30 min, followed by cooling to room temperature. Then, 5.74 g (14 mmol) of SPhos was added to the system for a coordination reaction at room temperature for 30 min. 90% of the solvent was then removed under vacuum. The crude product was ground with pentane to obtain a palladium complex with a yield of 95% and a purity of 99.3%. The molar ratio of 2'-chloro-[1,1'-biphenyl]-2-aminomethanesulfonate to palladium methanesulfonate was 1:1.2.

[0106] Example 5 Pd(Cl)(C 12 H8NH2)(SPhos) The preparation method of palladium complex is as follows: Weigh 2.19 g (10.0 mmol) of o-iodoaniline and dissolve it in 40 mL of tetrahydrofuran. Then slowly add 0.44 g (12 mmol) of hydrochloric acid in 10 mL of diethyl ether to obtain a mixture. Stir at 25 °C to carry out the salt formation reaction for 45 min. Then filter the reaction solution, wash with diethyl ether, and dry under vacuum to obtain solid 2-bromo-aminophenyl hydrochloride. 2-Bromo-aminophenyl hydrochloride, 2.35 g (15 mmol) of 2-chlorophenylboronic acid, and 231 mg (0.2 mmol) of tetratetraphenylphosphine palladium were dissolved in 75 mL of 1,4-dioxane. The mixture was purged with argon three times under stirring. Then, 6.52 g (20.0 mmol) of cesium carbonate aqueous solution (30 mL) was slowly added. The mixture was heated to 80 °C for a coupling reaction. After the reaction was completed by TCL monitoring, it was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 80:20 to 60:40) to obtain crystalline 2'-chloro-[1,1'-biphenyl]-2-aminohydrochloride. The molar ratio of 2-bromo-aminophenyl hydrochloride to 2-chlorophenylboronic acid was 1:1.5, and the molar ratio of tetratetraphenylphosphine palladium to 2-bromo-aminophenyl hydrochloride was 0.02:1. 1.77 g (10 mmol) of palladium chloride was dissolved in 50 mL of toluene, and 0.97 mL (20 mmol) of hydrazine hydrate was added. The mixture was then heated to 50 °C for a cyclopalladium reaction for 35 min, followed by cooling to room temperature. Then, 4.51 g (11 mmol) of SPhos was added to the system for a coordination reaction at room temperature for 45 min. After that, 90% of the solvent was removed under vacuum. The crude product was ground with pentane to obtain a palladium complex with a yield of 94% and a purity greater than 99.7%. The molar ratio of 2'-chloro-[1,1'-biphenyl]-2-aminohydrochloride to palladium chloride was 1:1.0.

[0107] Example 6 Pd(OTs)(C 12 H8NH2)(SPhos) The preparation method of palladium complex is as follows: 1.72 g (10.0 mmol) of o-bromoaniline was dissolved in 55 mL of toluene, and then 2.24 g (13 mmol) of p-toluenesulfonic acid was added to obtain a mixture. The mixture was stirred at 30 °C for 1 h to form a salt. The reaction solution was then filtered, washed with diethyl ether, and dried under vacuum to obtain solid 2-bromo-aminobenzene-p-methylbenzenesulfonate. 2-Bromo-aminobenzene-p-methylbenzenesulfonate, 4.01 g (20 mmol) of 2-bromophenylboronic acid, and 347 mg (0.3 mmol) of tetrakis(triphenylphosphine)palladium were dissolved in 90 mL of toluene. The mixture was purged with argon three times under stirring. Then, 2.24 g (20.0 mmol) of potassium tert-butoxide in 10 mL of toluene was slowly added. The mixture was heated to 90 °C for a coupling reaction. After the reaction was completed by TCL monitoring, it was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 80:20 to 60:40) to obtain crystalline 2'-chloro-[1,1'-biphenyl]-2-amino-p-methylbenzenesulfonate. The molar ratio of 2-bromo-aminobenzene-p-methylbenzenesulfonate to 2-bromophenylboronic acid was 1:2.0; the molar ratio of tetrakis(triphenylphosphine)palladium to 2-bromo-aminobenzene-p-methylbenzenesulfonate was 0.03:1. Crystalline 2'-chloro-[1,1'-biphenyl]-2-amino-p-toluenesulfonate and 5.82 g (13 mmol) of palladium p-toluenesulfonate were dissolved in 50 mL of 1,4-dioxane. CO was introduced at a gas flow rate of 10 mL / min for 60 min, and the mixture was heated to 60 °C for 1 h for cyclopalladiumization. The mixture was then cooled to room temperature, and 5.75 g (14 mmol) of SPhos was added to the system for coordination reaction at room temperature for 1 h. 90% of the solvent was then removed under vacuum. The crude product was ground with pentane to obtain a palladium complex with a yield of 96% and a purity of 99.5%. The molar ratio of 2'-chloro-[1,1'-biphenyl]-2-amino-p-toluenesulfonate to palladium p-toluenesulfonate was 1:1.3.

[0108] Example 7 Pd(OMs) (C 12 H8NH2)(BerttPhos) The preparation method of palladium complex is as follows: Weigh 1.72 g (10.0 mmol) of o-bromoaniline and dissolve it in 50 mL of diethyl ether. Then add 2.24 g (13 mmol) of p-toluenesulfonic acid to obtain a mixture. Stir at 30 °C for 45 min to form a salt. Then filter the reaction solution, wash with diethyl ether, and dry under vacuum to obtain solid 2-bromo-aminobenzoic acid salt. 2-Bromo-aminobenzylsulfonate, 1.72 g (11 mmol) of 2-chlorophenylboronic acid, and 231 mg (0.2 mmol) of tetratriphenylphosphine palladium were dissolved in 100 mL of tetrahydrofuran. The mixture was purged with argon three times under stirring. Then, 2.76 g (20.0 mmol) of potassium carbonate solution (25 mL) was slowly added. The mixture was heated to 80 °C for a coupling reaction. After the reaction was completed by TCL monitoring, it was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 80:20 to 60:40) to obtain crystalline 2'-chloro-[1,1'-biphenyl]-2-aminomethanesulfonate. The molar ratio of 2-bromo-aminobenzylsulfonate to 2-chlorophenylboronic acid was 1:1.1, and the molar ratio of tetratriphenylphosphine palladium to 2-bromo-aminobenzylsulfonate was 0.02:1. 3.12 g (12 mmol) of palladium methanesulfonate and crystalline 2'-chloro-[1,1'-biphenyl]-2-aminomethanesulfonate were dissolved in 50 mL of tetrahydrofuran, CO was introduced, and the mixture was heated to 40 °C for a cyclopalladium reaction for 30 min, followed by cooling to room temperature. Then, 6.44 g (12 mmol) of Bertt Phos was added to the system for a coordination reaction at room temperature for 30 min, and then 90% of the solvent was removed under vacuum. The crude product was ground with pentane to obtain a palladium complex with a yield of 95% and a purity of 99.7%. The molar ratio of 2'-chloro-[1,1'-biphenyl]-2-aminomethanesulfonate to palladium methanesulfonate was 1:1.2.

[0109] Example 8 Pd(Cl)(C 12 H8NH2)(BerttPhos) The preparation method of palladium complex is as follows: Weigh 2.19 g (10.0 mmol) of o-iodoaniline and dissolve it in 40 mL of tetrahydrofuran. Then slowly add 0.44 g (12 mmol) of hydrochloric acid in 10 mL of diethyl ether to obtain a mixture. Stir at 25 °C to carry out the salt formation reaction for 45 min. Then filter the reaction solution, wash with diethyl ether, and dry under vacuum to obtain solid 2-bromo-aminophenyl hydrochloride. 2-Bromo-aminophenyl hydrochloride, 2.35 g (15 mmol) of 2-chlorophenylboronic acid, and 231 mg (0.2 mmol) of tetratetraphenylphosphine palladium were dissolved in 75 mL of 1,4-dioxane. The mixture was purged with argon three times under stirring. Then, 6.52 g (20.0 mmol) of cesium carbonate aqueous solution (30 mL) was slowly added. The mixture was heated to 80 °C for a coupling reaction. After the reaction was completed by TCL monitoring, it was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 80:20 to 60:40) to obtain crystalline 2'-chloro-[1,1'-biphenyl]-2-aminohydrochloride. The molar ratio of 2-bromo-aminophenyl hydrochloride to 2-chlorophenylboronic acid was 1:1.5, and the molar ratio of tetratetraphenylphosphine palladium to 2-bromo-aminophenyl hydrochloride was 0.02:1. 1.77 g (10 mmol) of palladium chloride was dissolved in 50 mL of toluene, and 0.97 mL (20 mmol) of hydrazine hydrate was added. The mixture was then heated to 50 °C for cyclopalladiumation for 35 min, followed by cooling to room temperature. Then, 5.9 g (11 mmol) of Bertt Phos was added to the system for coordination reaction at room temperature for 45 min. 90% of the solvent was then removed under vacuum. The crude product was ground with pentane to obtain a palladium complex with a yield of 91% and a purity of 99.4%. The molar ratio of 2'-chloro-[1,1'-biphenyl]-2-aminohydrochloride to palladium chloride was 1:1.0.

[0110] Example 9 Pd (OTs) (C 12 H8NH2)(BerttPhos) The preparation method of palladium complex is as follows: 1.72 g (10.0 mmol) of o-bromoaniline was dissolved in 55 mL of toluene, followed by the addition of 2.24 g (13 mmol) of p-toluenesulfonic acid to obtain a mixture. The mixture was stirred at 30 °C for 1 h to form a salt, and then the reaction solution was filtered. After washing with diethyl ether, the solution was dried under vacuum to obtain solid 2-bromo-aminobenzene-p-methylbenzenesulfonate. 2-Bromo-aminobenzene-p-methylbenzenesulfonate, 4.01 g (20 mmol) of 2-bromophenylboronic acid, and 347 mg (0.3 mmol) of tetrakis(triphenylphosphine)palladium were dissolved in 90 mL of toluene. The mixture was purged with argon three times under stirring. Then, 2.24 g (20.0 mmol) of potassium tert-butoxide in 10 mL of toluene was slowly added. The mixture was heated to 90 °C for a coupling reaction. After the reaction was completed by TCL monitoring, it was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 80:20 to 60:40) to obtain crystalline 2'-chloro-[1,1'-biphenyl]-2-amino-p-methylbenzenesulfonate. The molar ratio of 2-bromo-aminobenzene-p-methylbenzenesulfonate to 2-bromophenylboronic acid was 1:2.0; the molar ratio of tetrakis(triphenylphosphine)palladium to 2-bromo-aminobenzene-p-methylbenzenesulfonate was 0.03:1. Crystalline 2'-chloro-[1,1'-biphenyl]-2-amino-p-toluenesulfonate and 5.82 g (13 mmol) of palladium p-toluenesulfonate were dissolved in 50 mL of 1,4-dioxane. CO was introduced at a gas flow rate of 10 mL / min for 60 min, and the mixture was heated to 60 °C for 1 h for cyclopalladiumization. The mixture was then cooled to room temperature. Next, 8.05 g (15 mmol) of Bertt Phos was added to the system for coordination reaction at room temperature for 1 h. Then, 90% of the solvent was removed under vacuum. The crude product was ground with pentane to obtain a palladium complex with a yield of 89% and a purity of 99.5%. The molar ratio of 2'-chloro-[1,1'-biphenyl]-2-amino-p-toluenesulfonate to palladium p-toluenesulfonate was 1:1.3.

[0111] Example 10 Pd (OMs) (C 12 H8NH2)(RuPhos) The preparation method of palladium complex is as follows: Weigh 1.72 g (10.0 mmol) of o-bromoaniline and dissolve it in 50 mL of diethyl ether. Then add 2.24 g (13 mmol) of p-toluenesulfonic acid to obtain a mixture. Stir at 30 °C for 45 min to form a salt. Then filter the reaction solution, wash with diethyl ether, and dry under vacuum to obtain solid 2-bromo-aminobenzoic acid salt. 2-Bromo-aminobenzylsulfonate, 1.72 g (11 mmol) of 2-chlorophenylboronic acid, and 231 mg (0.2 mmol) of tetratriphenylphosphine palladium were dissolved in 100 mL of tetrahydrofuran. The mixture was purged with argon three times under stirring. Then, 2.76 g (20.0 mmol) of potassium carbonate solution (25 mL) was slowly added. The mixture was heated to 60 °C for a coupling reaction. After the reaction was completed by TCL monitoring, it was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 80:20 to 60:40) to obtain crystalline 2'-chloro-[1,1'-biphenyl]-2-aminomethanesulfonate. The molar ratio of 2-bromo-aminobenzylsulfonate to 2-chlorophenylboronic acid was 1:1.1, and the molar ratio of tetratriphenylphosphine palladium to 2-bromo-aminobenzylsulfonate was 0.02:1. 3.12 g (12 mmol) of palladium methanesulfonate and crystalline 2'-chloro-[1,1'-biphenyl]-2-aminomethanesulfonate were dissolved in 50 mL of tetrahydrofuran. CO was introduced at a gas flow rate of 10 mL / min for 30 min, and then the temperature was raised to 40 °C for a cyclopalladium reaction for 30 min, followed by cooling to room temperature. Then, 12 mmol of RuPhos was added to the system for a coordination reaction at room temperature for 30 min. 90% of the solvent was then removed under vacuum. The crude product was ground with pentane to obtain a palladium complex with a yield of 92% and a purity of 99.7%. The molar ratio of 2'-chloro-[1,1'-biphenyl]-2-aminomethanesulfonate to palladium methanesulfonate was 1:1.2.

[0112] Example 11 Pd(Cl)(C 12 H8NH2)(RuPhos) The preparation method of palladium complex is as follows: Weigh 2.19 g (10.0 mmol) of o-iodoaniline and dissolve it in 40 mL of tetrahydrofuran. Then slowly add 0.44 g (12 mmol) of hydrochloric acid in 10 mL of diethyl ether to obtain a mixture. Stir at 25 °C to carry out the salt formation reaction for 45 min. Then filter the reaction solution, wash with diethyl ether, and dry under vacuum to obtain solid 2-bromo-aminophenyl hydrochloride. 2-Bromo-aminophenyl hydrochloride, 2.35 g (15 mmol) of 2-chlorophenylboronic acid, and 231 mg (0.2 mmol) of tetratetraphenylphosphine palladium were dissolved in 75 mL of 1,4-dioxane. The mixture was purged with argon three times under stirring. Then, 6.52 g (20.0 mmol) of cesium carbonate aqueous solution (30 mL) was slowly added. The mixture was heated to 80 °C for a coupling reaction. After the reaction was completed by TCL monitoring, it was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 80:20 to 60:40) to obtain crystalline 2'-chloro-[1,1'-biphenyl]-2-aminohydrochloride. The molar ratio of 2-bromo-aminophenyl hydrochloride to 2-chlorophenylboronic acid was 1:1.5, and the molar ratio of tetratetraphenylphosphine palladium to 2-bromo-aminophenyl hydrochloride was 0.02:1. 1.77 g (10 mmol) of palladium chloride was dissolved in 50 mL of toluene, 20 mmol of hydrazine hydrate was added, and the mixture was heated to 50 °C for 35 min to carry out a cyclopalladium reaction, followed by cooling to room temperature. Then, 5.13 g (11 mmol) of RuPhos was added to the system and the mixture was coordinated at room temperature for 45 min. 90% of the solvent was then removed under vacuum. The crude product was ground with pentane to obtain a palladium complex with a yield of 90% and a purity of 99.5%. The molar ratio of 2'-chloro-[1,1'-biphenyl]-2-aminohydrochloride to palladium chloride was 1:1.0.

[0113] Example 12 Pd (OTs) (C 12 H8NH2)(RuPhos) The preparation method of palladium complex is as follows: 1.72 g (10.0 mmol) of o-bromoaniline was dissolved in 55 mL of toluene, and then 2.24 g (13 mmol) of p-toluenesulfonic acid was added to obtain a mixture. The mixture was stirred at 30 °C for 1 h to form a salt. The reaction solution was then filtered, washed with diethyl ether, and dried under vacuum to obtain solid 2-bromo-aminobenzene-p-methylbenzenesulfonate. 2-Bromo-aminobenzene-p-methylbenzenesulfonate, 4.01 g (20 mmol) of 2-bromophenylboronic acid, and 347 mg (0.3 mmol) of tetrakis(triphenylphosphine)palladium were dissolved in 90 mL of toluene. The mixture was purged with argon three times under stirring. Then, 2.24 g (20.0 mmol) of potassium tert-butoxide in 10 mL of toluene was slowly added. The mixture was heated to 90 °C for a coupling reaction. After the reaction was completed by TCL monitoring, it was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 80:20 to 60:40) to obtain crystalline 2'-chloro-[1,1'-biphenyl]-2-amino-p-methylbenzenesulfonate. The molar ratio of 2-bromo-aminobenzene-p-methylbenzenesulfonate to 2-bromophenylboronic acid was 1:2.0; the molar ratio of tetrakis(triphenylphosphine)palladium to 2-bromo-aminobenzene-p-methylbenzenesulfonate was 0.03:1. 5.82 g (13 mmol) of crystalline 2'-chloro-[1,1'-biphenyl]-2-amino-p-toluenesulfonate and 5.82 g (13 mmol) of palladium p-toluenesulfonate were dissolved in 50 mL of 1,4-dioxane. CO was introduced, and the mixture was heated to 60 °C for a cyclopalladium reaction for 1 h, followed by cooling to room temperature. Then, 15 mmol of RuPhos was added to the system for a coordination reaction at room temperature for 1 h. After that, 90% of the solvent was removed under vacuum. The crude product was ground with pentane to obtain a palladium complex with a yield of 87% and a purity of 99.3%. The molar ratio of 2'-chloro-[1,1'-biphenyl]-2-amino-p-toluenesulfonate to palladium p-toluenesulfonate was 1:1.3.

[0114] Application Example 1 1.05 mL (10.0 mmol) of bromobenzene, 1.45 mL (11.0 mmol) of 4-methylstyrene, and 0.1 mmol of the palladium complex from Example 1 were dissolved in 30 mL of 1,4-dioxane. Then, 2.07 g (15.0 mmol) of potassium carbonate was added, and the mixture was heated to 80 °C and reacted for 9 h. After the reaction was completed, the mixture was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 100:0 to 80:20) to give a white solid with a yield of 98%.

[0115] The reaction equation in Application Example 1 is as follows: .

[0116] Application Example 2 1.01 mL (10.0 mmol) of chlorobenzene, 1.45 mL (11.0 mmol) of 4-methylstyrene, and 84.6 mg (0.1 mmol) of the palladium complex from Example 1 were dissolved in 30 mL of N,N-dimethylformamide. Then, 2.07 g (15.0 mmol) of potassium carbonate was added, and the mixture was heated to 100 °C and reacted for 10 h. After the reaction was completed, the mixture was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 100:0 to 80:20) to give a white solid with a yield of 95%.

[0117] The reaction equation in Application Example 2 is as follows: .

[0118] Application Example 3 1.32 mL (10.0 mmol) of 2-chloro-1,3-xylene, 1.72 mL (15.0 mmol) of styrene, and 254 mg (0.3 mmol) of the palladium complex from Example 1 were dissolved in 50 mL of toluene. Then, 1.59 g (15.0 mmol) of sodium carbonate was added, and the mixture was heated to 110 °C and reacted for 12 h. After the reaction was completed, the mixture was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 100:0 to 80:20) to give a white solid in 89% yield.

[0119] The reaction equation in Application Example 3 is as follows: .

[0120] Application Example 4 1.73 g (10.0 mmol) of 2-chloro-m-phenylenediamine, 1.49 mL (15.0 mmol) of styrene, and 338.58 mg (0.4 mmol) of the palladium complex from Example 1 were dissolved in 50 mL of 1,4-dioxane. Then, 1.68 g (15.0 mmol) of potassium tert-butoxide was added, and the mixture was heated to 110 °C and reacted for 12 h. After the reaction was completed, the mixture was cooled to room temperature, extracted, dried, and purified by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate as eluent changed from 100:0 to 80:20) to give a white solid in 82% yield.

[0121] The reaction equation in Application Example 4 is as follows: .

[0122] As can be seen from the above embodiments, the preparation method provided by the present invention yields products with high purity and high yield.

[0123] 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 a palladium complex, comprising: The 2'-halo-[1,1'-biphenyl]-2-ammonium salt, palladium salt, reducing agent and solvent were mixed and then subjected to a cyclopalladium reaction. Then, a phosphine ligand was added to carry out a coordination reaction, and then post-processing was performed to obtain a palladium complex. The post-processing includes sequential solvent removal and purification.

2. The preparation method according to claim 1, characterized in that, The structural formula of the 2'-halo-[1,1'-biphenyl]-2-ammonium salt is shown in Formula I: Equation I; In formula I, R 1 It is methanesulfonate, chloride, or p-toluenesulfonate, and Y is chloride or bromide.

3. The preparation method according to claim 2, characterized in that, The preparation method of the 2'-halo-[1,1'-biphenyl]-2-ammonium salt includes the following steps: (1) After mixing o-haloaniline, acid and first solvent, a salt-forming reaction is carried out to obtain 2-halo-phenyl quaternary ammonium salt; (2) The 2-halo-phenyl quaternary ammonium salt, 2-halophenylboronic acid, palladium (0) catalyst, base and second solvent obtained in step (1) are mixed and coupled to obtain 2'-halo-[1,1'-biphenyl]-2-ammonium salt.

4. The preparation method according to claim 3, characterized in that, The acid in step (1) is methanesulfonic acid, hydrochloric acid or p-toluenesulfonic acid; the molar ratio of the o-haloaniline to the acid is 1:(1~1.5).

5. The preparation method according to claim 1, characterized in that, The molar ratio of the 2'-halo-[1,1'-biphenyl]-2-ammonium salt to the palladium salt is 1:(1.0~1.3).

6. The preparation method according to claim 1, characterized in that, The molar ratio of the palladium salt to the phosphine ligand is 1:(1.0~1.2).

7. The preparation method according to claim 1, characterized in that, The cyclopalladium reaction is carried out at a temperature of 40-60°C for 30-60 minutes.

8. The preparation method according to claim 1, characterized in that, The coordination reaction was carried out at room temperature for 30-60 minutes.

9. The palladium complex prepared by the preparation method according to any one of claims 1 to 8, wherein the palladium complex has the structural formula shown in Formula II: Formula II; In Equation I, R 1 It is an anion, and PR3 is a phosphine ligand.

10. The use of the palladium complex of claim 9 as a catalyst in the Heck coupling reaction.

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