Method for producing biphenyl metallocene complex

Abstract

The present invention relates to a method for preparing a boric anhydride compound of formula (1), wherein R 1 ‑R 4 is a substituent as defined in the present invention, and 'B' represents the element boron. The present invention also describes a method for preparing a biphenyl metallocene complex of formula (4) using boric anhydride of formula (1), wherein R 1 ‑R 10 is a substituent as defined in the present invention; and wherein 'M' is a transition metal element, 'Q' is a halogen anion, 'P' is the valence of the transition metal element 'M', and represents the number of halogen anions present. In addition, the present invention further describes a method for purifying the metallocene complex of formula (4) to render the entire metallocene complex synthesis process environmentally sustainable and cost-effective by minimizing waste effluents.

Description

[0001] The present invention relates to the field of metallocene complexes, in particular to a method suitable for synthesizing biphenyl ligands with high yield and their metallocene complexes.

[0002] In the past, it has been demonstrated that catalyst systems containing metallocene complexes with biphenyl ligands such as 2,2'-bis(2-indenyl)biphenyl are suitable for the polymerization of alpha-olefins. Since the production of metallocene ligands and complexes is relatively expensive compared to conventional polymerization catalysts such as Ziegler-Natta catalysts, it has been considered to use cheaper starting materials / reagents and to develop production methods that can produce metallocene complexes and their intermediate compounds in high yields while maintaining sufficient purity. Specifically, the use of biphenyl as a starting material is particularly attractive for the production of metallocene catalysts because it achieves relative cost effectiveness while providing suitable properties such as stereospecificity for metallocene catalyst systems.

[0003] Typically, as described in US6342622B1, the synthetic route for preparing metallocene complexes includes preparing a mixture of alkyl lithium compounds such as butyl lithium and tertiary amines such as tetramethylethylenediamine (TMEDA). The mixture is prepared by adding TMEDA to butyl lithium under ice bath temperature conditions. Thereafter, a biphenyl compound is added to the mixture to form a dilithium salt of biphenyl, which is then used to prepare a ligand based on boric anhydride and 2,2'-bis(2-indenyl)biphenyl, which are key intermediates for preparing metallocene ligands.

[0004] However, there are several disadvantages in this known synthetic route. For example, the dilithium salt is highly pyrophoric and difficult to mass produce. In addition, the yield of producing this dilithium salt is unstable, and undesirable by-products such as monoisomers are formed, while having a low conversion rate to the dilithium salt. In addition, the purification of the dilithium salt is difficult, and it is necessary to wash the dilithium salt with hexane or other suitable solvents for multiple times to obtain a suitable product purity for further reaction. Because the dilithium salt yield is low, the overall yield (which depends on the yield and purity of the dilithium salt) of the intermediate product synthesized by the metallocene ligand is also low, which leads to the high cost of producing metallocene complexes. In addition, because the overall yield of the metallocene ligand is low, the production of the metallocene complex and the ligand produces significant material waste and produces poisonous effluents, which not only increases the production cost and makes the entire production method inefficient, but also has an adverse effect on the environmental and sustainability parameters of the industrial-scale metallocene catalyst production.

[0005] Although some synthetic routes described in the existing open literature are promising, some of the above-mentioned shortcomings are not fully resolved. For example, IJpeij et al. described (Journal of Organic Chemistry, 2002, Vol. 67, pp. 169-176) a method of double Suzuki coupling. However, the method described in Ijpeij involves high capital and operating costs because the method involves the use of a homogeneous catalyst that is difficult to recover from the final product. In addition, the method described in US6342622B1, particularly the method described in Example VIII, involves a synthetic scheme that is difficult to scale up at the industrial production level, which results in relatively low product yields and undesirable waste of materials.

[0006] Therefore, for the foregoing reasons, there remains a need to develop a cost-effective method for synthesizing metallocene complexes and having the benefits of producing one or more of metallocene complexes and their intermediate products in high yields suitable for industrial scale production while maintaining optimal utilization of resources and raw materials.

[0007] Therefore, in one aspect of the present invention, as one of the objects of the present invention, the present invention relates to a process for producing metallocene complexes in high yield. Another object of the present invention is to provide a process for producing boric anhydride in high yield, which is a key intermediate in the process for producing metallocene complexes. Yet another object of the present invention is to provide an environmentally sustainable process for industrial scale production of metallocene complexes and their intermediate compounds, with optimal utilization of raw materials.

[0008] One or more objects of the present invention are achieved by providing a method for preparing a boronic anhydride compound of formula (1).

[0009]

[0010] Where R 1 , R 2 , R 3 and R 4 Each independently selected from hydrogen, halogen, linear or branched or cyclic hydrocarbon group having 1-20 carbon atoms, which is independently selected from alkyl, alkenyl, aryl, alkylaryl; alkyl sulfide group having 1-20 carbon atoms, alkoxy group having 1-20 carbon atoms, and amine group; 'B' represents elemental boron, which comprises the steps of:

[0011] a) providing a precursor mixture, the mixture comprising:

[0012] (i) a biphenyl compound of formula (2),

[0013]

[0014] Where R1 -R 4 As defined herein, and wherein Z 1 is hydrogen, and

[0015] (ii) a tertiary amine compound;

[0016] b) adding an alkyl and / or aryl lithium compound having 1 to 10 carbon atoms to the precursor mixture at any temperature between 18°C ​​and 65°C, alternatively between 21°C and 45°C, or alternatively between 25°C and 35°C, and forming a first lithiation reaction product;

[0017] c) contacting the first lithiation reaction product with a borate ester compound of formula (3):

[0018] B(OR 11 )3(3)

[0019] The borate ester reaction product is obtained; wherein R 11 independently selected from hydrogen, linear or branched or cyclic hydrocarbon groups having 1 to 20 carbon atoms, independently selected from alkyl, alkenyl, aryl, alkoxycarbonyl, alkylaryl and one or more combinations thereof; and

[0020] d) hydrolyzing the boric acid ester reaction product to form a boronic acid anhydride compound of formula (1).

[0021] In a preferred embodiment of the present invention, R 11 In some preferred embodiments, R 1 -R 4 is hydrogen. In some embodiments of the present invention, the alkyl and / or aryl lithium compound is an alkyl lithium compound having 2-8 carbon atoms, preferably 4 carbon atoms. In some embodiments of the present invention, the alkyl and / or aryl lithium compound is selected from methyl lithium, butyl lithium, phenyl lithium, preferably the alkyl and / or aryl lithium compound is butyl lithium. In some embodiments of the present invention, the first lithiation reaction product is a dilithium salt of the formula:

[0022]

[0023] Where R 1 -R 4 As defined herein. In some preferred embodiments of the present invention, the tertiary amine compound is a bidentate tertiary amine, preferably tetramethylethylenediamine (TMEDA). In some embodiments of the present invention, the molar ratio of biphenyl to the alkyl and / or aryl lithium compound is 0.5-5, preferably 1-4, more preferably 2-4. In some embodiments of the present invention, the molar ratio of biphenyl to the alkyl and / or aryl lithium compound is 0.5-5, preferably 1-4, or more preferably 2-3.

[0024] As demonstrated in Example 1, in some preferred embodiments of the present invention, the process of the present invention for producing the boronic anhydride of formula (1) produces a yield improvement of nearly 140% compared to the process described in US Pat. No. 6,342,622 B1. A key aspect to be mentioned in the process of the present invention for preparing boronic anhydride is the order of addition of the reactants, wherein the alkyl and / or aryl lithium compound is added to a precursor mixture comprising a biphenyl compound of formula (2) and a tertiary amine compound at a suitable temperature of 18° C. to 65° C. In contrast, patent US Pat. No. 6,342,622 B1 describes a process wherein the tertiary amine compound is first added to the alkyl and / or aryl lithium compound under ice bath conditions, and thereafter the biphenyl is added to the resulting mixture. Without wishing to be bound by any particular theory, it is speculated that the order of addition and mixing of the reactants described in the present invention ensures minimal moisture contamination by removing any moisture present in the reactants and the alkyl and / or aryl lithium compound, which results in a high conversion of the biphenyl compound to the lithiation reaction product and thus results in a high yield of the boronic anhydride of formula (1). Furthermore, the method for synthesizing boric anhydride of the present invention enables those skilled in the art to carry out the synthesis method at ambient temperature, e.g., room temperature conditions of 20°C-25°C, rather than the low temperature or ice bath temperature conditions described in US6342622B1, which would require special capital-intensive equipment and devices to carry out such temperature conditions on an industrial production scale.

[0025] In some aspects of the present invention, the present invention relates to the use of a boric anhydride of formula (1) for preparing a biphenyl metallocene complex in high yield. In some aspects of the present invention, the present invention further relates to a method comprising the steps of preparing a reaction mixture comprising a metallocene complex of formula (4):

[0026]

[0027] Where R 1 -R 4 As defined herein, and R 5 , R 6 , R 7 , R 8 , R 9 and R 10 Each independently selected from hydrogen, halogen, linear or branched or cyclic hydrocarbon group having 1-20 carbon atoms, which is independently selected from alkyl, alkenyl, aryl, alkylaryl; alkyl sulfide groups having 1-20 carbon atoms, preferably having 1-10 carbon atoms, alkoxy groups having 1-20 carbon atoms, preferably having 1-10 carbon atoms, and amine groups, and one or more combinations thereof; and wherein 'M' is a transition metal element selected from Groups 3, 4, and 5 of the Periodic Table of Elements, 'Q' is a halogen anion, preferably a chloride anion, 'P' is the valence of the transition metal element 'M', and represents the number of halogen anions present, which comprises the steps of:

[0028] a) reacting a boric anhydride of formula (1) with a 2-bromoindenyl compound of formula (6) in the presence of a palladium catalyst to form a metallocene complex precursor of formula (7);

[0029]

[0030] Where R 5 -R 10 As defined herein;

[0031]

[0032] Where R 1 -R 10 As defined herein,

[0033] b) reacting the metallocene complex precursor of formula (7) with an alkyl and / or aryl lithium compound having 1 to 10 carbon atoms to form a second lithiation reaction product; and

[0034] c) reacting the second lithiation reaction product with a transition metal compound of formula (8) for 4 to 10 hours, preferably 5 to 8 hours, to form a reaction mixture comprising a metallocene complex of formula (4), MQ p (8)

[0035] Wherein 'M' is a transition metal element selected from Groups 3, 4 and 5 of the periodic table, 'Q' is a halogen anion, preferably a chloride anion, and 'P' is the valence of the transition metal element 'M' and represents the number of halogen anions.

[0036] Advantageously, the method of the present invention enables those skilled in the art to carry out the second lithiation reaction product and the transition metal compound (MQ) in a shorter time than the method described in US6342622B1. p ). As shown in the results of Example 3, the reaction time of the present invention is particularly suitable for maximizing the conversion yield of the metallocene complex of formula (4). As a result, the method of the present invention becomes effective and suitable for large-scale industrial applications. In one aspect of the present invention, the second lithiation reaction product has the structure shown below:

[0037]

[0038] In some embodiments of the present invention, the alkyl and / or aryl lithium compound is an alkyl lithium compound having 2-8 carbon atoms, preferably 4 carbon atoms. In some embodiments of the present invention, the alkyl and / or aryl lithium compound is selected from methyl lithium, butyl lithium, phenyl lithium, preferably the alkyl and / or aryl lithium compound is butyl lithium. In some aspects of the present invention, the palladium catalyst is selected from tetrakis (triphenylphosphine) (Pd (PPh3) 4), Pd (OAc) 2, Pd2 (dba) 3, PdCl2, PdCl2 (PPh3) 2. In some preferred embodiments of the present invention, the palladium catalyst is tetrakis (triphenylphosphine) (Pd (PPh3) 4).

[0039] In some embodiments of the present invention, the transition metal element 'M' is selected from zirconium, hafnium, titanium, preferably the transition metal element 'M' is zirconium. In some embodiments of the present invention, the transition metal compound (MQ) of formula (8) p ) is zirconium tetrachloride (ZrCl4).

[0040] The reaction mixture contains the desired metallocene complex of formula (4) and a mixture of products, which are considered to be impurities and need to be separated from the reaction mixture to obtain a purified metallocene complex of formula (4a), which is suitable for use in a catalyst system. In some aspects of the invention, the reaction mixture containing the metallocene complex of formula (4) is further purified using solvent extraction and filtration to obtain:

[0041] (i) a purified metallocene complex of formula (4a),

[0042]

[0043] Where R 1 -R 10 , 'M', 'Q' and 'P' are as defined herein; and

[0044] (ii) A product effluent comprising a mixture of the metallocene complex of formula (4a), the metallocene complex precursor of formula (7), the partially complexed metallocene complex and a lithium-based inorganic salt.

[0045] In some embodiments of the present invention, the purification / ligand recovery method includes the steps of: (a) dissolving a reaction mixture containing a metallocene complex of formula (4) in an organic solvent selected from dichloromethane, toluene, pentane, acetonitrile, hexane or preferably dichloromethane at a temperature of 18°C-110°C, preferably at a temperature of 25°C-35°C, to obtain a suspension, (b) filtering the suspension to obtain a first filtrate, (c) concentrating the filtrate under moderate heating to obtain a precipitate, (d) filtering the precipitate to obtain a solid residue product and a second filtrate, (e) washing the solid residue product with an organic solvent and then filtering to obtain a purified metallocene complex of formula (4a) and a third filtrate, and (f) mixing the second filtrate and the third filtrate to form a product effluent. In one aspect of the present invention, the purity of the metallocene complex of formula (4a) is 95% to 99.5 wt%, preferably 98% to 99.5 wt%, relative to the total weight of the metallocene complex of formula (4a). In the present invention, the purity can be determined using any known spectroscopic technique, for example 1 H NMR Spectroscopy. Although the above cleanup / ligand recovery methods have been shown to be useful in the process of the present invention, the cleanup / ligand recovery methods described herein can be used with any biphenyl system that is useful in metallocene complex preparation.

[0046] In some aspects of the invention, the product effluent is recovered for use in preparing a reaction mixture comprising the metallocene complex of formula (4).

[0047] In some embodiments of the present invention, the product effluent is distilled to remove the solvent and other volatiles, and the solid material thus obtained is then further treated with methanolic hydrochloric acid to obtain the metallocene complex precursor of formula (7).

[0048] As can be appreciated by those skilled in the art, the method for purifying the metallocene complex (4) enables those skilled in the art to obtain a purified metallocene complex (4a) of high purity, while recycling the produced effluent back to produce a metallocene complex precursor of formula (7), which is then used to synthesize the metallocene complex of formula (4), which results in an improvement in the overall yield of producing a high-purity metallocene complex (4a) while mitigating the generation of toxic effluents. As can be appreciated by those skilled in the art, the method for purifying the metallocene complex of formula (4) described in the present invention enables purification to be carried out at a lower temperature than that described in US6342622B1, which describes the use of a heated volatile solvent such as boiling toluene for purification. As a result, the method of the present invention can be scaled up for large-scale industrial applications while ensuring operational safety and risk.

[0049] In some aspects of the invention, the invention relates to a method comprising one or more steps, preferably in the following order:

[0050] a) providing a precursor mixture comprising (i) a biphenyl compound of formula (2), wherein R 1 , R 2 , R 3 and R 4 Each is independently selected from hydrogen, halogen, linear or branched or cyclic hydrocarbon groups having 1 to 20 carbon atoms, which are independently selected from alkyl, alkenyl, aryl, alkoxycarbonyl, alkylaryl; alkyl sulfide groups having 1 to 20 carbon atoms, alkoxy groups having 1 to 20 carbon atoms, amine groups, and combinations thereof; and wherein Z 1 is hydrogen; and

[0051] (ii) a tertiary amine compound;

[0052] and / or

[0053] b) adding an alkyl and / or aryl lithium compound having 1 to 10 carbon atoms to the precursor mixture at any temperature of 18°C ​​to 65°C, optionally at 21°C to 45°C, or optionally at 25°C to 35°C to form a first lithiation reaction product;

[0054] and / or

[0055] c) contacting the first lithiation reaction product with a borate ester compound of formula (3):

[0056] B(OR 11 )3(3)

[0057] The borate ester reaction product is obtained; wherein R 11 independently selected from hydrogen, linear, branched or cyclic hydrocarbon groups having 1 to 20 carbon atoms, independently selected from alkyl, alkenyl, aryl, alkoxycarbonyl or alkylaryl and one or more combinations thereof;

[0058] and / or

[0059] d) hydrolyzing the boric acid ester reaction product to form a boronic acid anhydride compound of formula (1);

[0060] and / or

[0061] e) reacting a boronic acid anhydride compound of formula (1) with a 2-bromoindenyl compound of formula (6) in the presence of a palladium catalyst to form a metallocene complex precursor of formula (7);

[0062] and / or

[0063] f) reacting the metallocene complex precursor of formula (7) with an alkyl and / or aryl lithium compound having 1 to 10 carbon atoms to form a second lithiation reaction product;

[0064] and / or

[0065] g) reacting the second lithiation reaction product with a transition metal compound of formula (8) for 4 to 10 hours, preferably 5 to 8 hours, to form a reaction mixture comprising a metallocene complex of formula (4), MQ p (8)

[0066] wherein 'M' is a transition metal element selected from Groups 3, 4, and 5 of the Periodic Table, 'Q' is a halogen anion, and 'P' is the valence of the transition metal element 'M' and represents the number of halogen anions present;

[0067] and / or

[0068] h) purifying the reaction mixture comprising the metallocene complex of formula (4) using solvent extraction and filtration to obtain (i) purified metallocene ligand of formula (4a), and (ii) a product effluent comprising a mixture of the metallocene complex of formula 4a, a metallocene complex precursor of formula 7, a partially complexed metallocene complex and a lithium-based inorganic salt.

[0069] In some aspects of the invention, the invention relates to a method comprising the following steps, preferably in the following order:

[0070] a) providing a precursor mixture comprising (i) a biphenyl compound of formula (2), wherein R 1 , R 2 , R 3 and R 4 Each is independently selected from hydrogen, halogen, linear or branched or cyclic hydrocarbon groups having 1 to 20 carbon atoms, which are independently selected from alkyl, alkenyl, aryl, alkoxycarbonyl, alkylaryl; alkyl sulfide groups having 1 to 20 carbon atoms, alkoxy groups having 1 to 20 carbon atoms, amine groups, and combinations thereof; and wherein Z 1 is hydrogen; and (ii) a tertiary amine compound;

[0071] b) adding an alkyl and / or aryl lithium compound having 1 to 10 carbon atoms to the precursor mixture at any temperature of 18°C ​​to 65°C, optionally at 21°C to 45°C, or optionally at 25°C to 35°C to form a first lithiation reaction product;

[0072] c) contacting the first lithiation reaction product with a borate ester compound of formula (3):

[0073] B(OR 11 )3(3)

[0074] The borate ester reaction product is obtained; wherein R 11 independently selected from hydrogen, linear, branched or cyclic hydrocarbon groups having 1 to 20 carbon atoms, independently selected from alkyl, alkenyl, aryl, alkoxycarbonyl or alkylaryl and one or more combinations thereof;

[0075] d) hydrolyzing the boric acid ester reaction product to form a boronic acid anhydride compound of formula (1); reacting the boronic acid anhydride compound of formula (1) with a 2-bromoindenyl compound of formula (6) in the presence of a palladium catalyst to form a metallocene complex precursor of formula (7);

[0076] e) reacting the metallocene complex precursor of formula (7) with an alkyl and / or aryl lithium compound having 1 to 10 carbon atoms to form a second lithiation reaction product;

[0077] f) reacting the second lithiation reaction product with a transition metal compound of formula (8) for 4 to 10 hours, preferably 5 to 8 hours, to form a reaction mixture comprising a metallocene complex of formula (4),

[0078] (MQ p )(8)

[0079] wherein 'M' is a transition metal element selected from Groups 3, 4, and 5 of the Periodic Table, 'Q' is a halogen anion, and 'P' is the valence of the transition metal element 'M' and represents the number of halogen anions present;

[0080] g) purifying the reaction mixture comprising the metallocene complex of formula (4) using solvent extraction and filtration to obtain (i) purified metallocene ligand of formula (4a), and (ii) a product effluent comprising a mixture of the metallocene complex of formula 4a, a metallocene complex precursor of formula 7, a partially complexed metallocene complex and a lithium-based inorganic salt.

[0081] In some aspects of the invention, the present invention relates to the use of the method of the present invention for improving the yield of metallocene complexes. In some aspects of the present invention, the present invention relates to the use of the method of the present invention for improving the purity of metallocene complexes. In one aspect of the present invention, the metallocene complex thus obtained is combined with a donor and an activator to prepare a metallocene catalyst suitable for polymerizing olefins. It is apparent that the present invention now enables those skilled in the art to use the method of the present invention to prepare high purity metallocene complexes in high yield and on an industrial scale while minimizing the discharge of harmful effluents and by-products.

[0082] The following includes specific examples of some embodiments of the present invention. The examples are for illustrative purposes only and are not intended to limit the present invention. It should be understood that the embodiments and aspects disclosed herein are not mutually exclusive, and such aspects and embodiments can be combined in any manner.

[0083] Example 1

[0084] Purpose: To prepare the boronic anhydride compound of formula (1) (1,1'-biphenyl-2,2'-diyl diboronic anhydride) and compare the yield with that described in reference US6342622B1. The general reaction scheme practiced in Example 1 is shown below:

[0085]

[0086] Reactants used: The following reactants were used in Example 1:

[0087] Table 1: Reactants

[0088] Reactants Chemicals supplier Biphenyl Biphenyl Aldrich Alkyl lithium n-Butyllithium Aldrich Tertiary amine compounds TMEDA Aldrich Boric acid ester compounds Trimethyl borate Aldrich

[0089] Synthesis method: The biphenyl compound (25g, 0.16mol) loaded under an inert atmosphere is added to a three-necked flask in the presence of anhydrous hexane (100ml). TMEDA (60.8ml, 0.40mol) is added to the reaction mixture with a funnel at room temperature (~25°C). It is observed that the reaction mixture becomes a clear solution after TMEDA is added. The mixture is stirred at room temperature for 20 minutes to form a precursor mixture. Thereafter, an alkyl lithium compound, n-BuLi (243ml, 0.38mol; 1.6M hexane solution) is added by cannula in an inert atmosphere over a duration of 20 minutes.

[0090] The color of the reaction mixture then changed from pale yellow to orange and then to dark red, and the temperature increased from 24° C. to 35° C. The reaction mixture was then heated to 50-52° C. for 1 hour and then cooled to room temperature. After stirring at room temperature for 1 hour, 500 ml of hexane was added to the reaction mixture and the temperature was cooled to -50° C. [1 h] and settled [0.5 h] to precipitate orange crystalline 2,2' dilithium biphenyl bisTMEDA adduct (first lithiation reaction product), and the residual mother liquor was sucked out through a cannula.

[0091] Finally, 250 ml of tetrahydrofuran was added to the 2,2' dilithium biphenyl bisTMEDA adduct (the first lithiation reaction product, which was placed in a flask in solid form), followed by dropwise addition of trimethyl borate (51.5 ml, 0.464 mol) (boric acid ester compound) at a temperature of -50°C. The reaction mixture formed was stirred at room temperature for 1 hour, followed by addition of dilute hydrochloric acid (10% until pH reached -1.5) at a temperature of 0°C, followed by stirring at room temperature for 1 hour. Layer separation was observed, and the organic layer was washed with a saline solution and then dried and concentrated over anhydrous sodium sulfate to obtain the crude desired product. The crude residue was crystallized from toluene and hexane to obtain the biphenyl boronic anhydride compound.

[0092] Comparative Example: Synthesis Procedure (Example 1A): The procedure practiced was as described in patent US Pat. No. 6,342,622 B1 under Example VIII and the reported results were compared with those obtained carrying out Example 1.

[0093] Results: Table 2 below provides a detailed comparison between the yields obtained from Example 1 of the present invention and the results of Comparative Example 1A. The amount of product formed was determined using conventional 1 H-NMR spectroscopy is performed, for example, using a BRUKER 300 MHz instrument to record the spectra and using CDCl3 as solvent.

[0094] Table 2: Product results

[0095] Biphenyl weight (g) Weight of boric anhydride / boric acid product obtained (g) Yield % Example 1 25(0.16) 20(0.09) 55％ Example 1A 103(0.67mol) 37.68(0.15mol) 23％

[0096] It is evident that the product yield obtained by carrying out the present invention is significantly higher (-140% higher) than the yield obtained from Comparative Example 1 A. From the experimental section, it can be noted that the reaction time of the process carried out in Example 1 of the present invention is less than the reaction time described in Example 1A, thereby making the process of the present invention more efficient and suitable for industrial scale production.

[0097] Example 2

[0098] Purpose: To prepare the metallocene complex (2,2'-bis(2-indenyl)biphenyl zirconium dichloride complex) of formula (4a) from the boric anhydride compound of formula (1) obtained in Example 1, and to compare the yield obtained in Example 2 with the yield described in reference US6342622B1. The general reaction scheme performed in Example 2 is shown below:

[0099]

[0100] Reactants used: The following reactants were used in Example 2:

[0101] Table 3: Reactants

[0102] Reactants Chemicals supplier 2-Bromo-indenyl compounds 2-Indene Bromide self made Palladium catalyst <![CDATA[Palladium(0) tetrakis(triphenylphosphine) (Pd(PPh3)4)]]> Aldrich

[0103] Method for synthesizing 2-bromoindane: To a mixture of indene (200 mmol), distilled water (15 ml) and dimethyl sulfoxide (70 ml) was added 210 mmol of N-bromosuccinimide in portions. The orange solution formed was stirred at room temperature for 10 hours, hydrolyzed with cold water (100 ml) and extracted with diethyl ether (3×100 ml). The combined extracts were dried over magnesium sulfate and concentrated by standing overnight at -24°C to produce crystals of 2-bromoindan-1-ol. The obtained 2-bromoindan-1-ol (120 mmol) was suspended in 100 ml of toluene and mixed with a catalytic amount of p-toluenesulfonic acid monohydrate. The mixture was heated at reflux for 12 hours and dehydrated with a reflux tube (Dean-Stark) apparatus. The dark brown suspension formed was filtered and the volatiles were removed under vacuum. The residue was passed through silica gel using pentane as the eluent, the solvent was then evaporated, and the crude product was vacuum distilled. 2-Indene bromide was finally obtained as yellow crystals with a yield of 55%.

[0104] Method for synthesizing metallocene complex: To tetra(n-butyl)ammonium hydroxide solution (191.25 ml, 1M methanol solution) were added the following reagents: toluene (150 ml), 2-bromoindene (24.68 gm), 2,2'-biphenyl diboronic anhydride (15.0 g) (boric anhydride compound obtained from Example 1) and palladium catalyst [Pd(PPh3)4] (0.765 g), and the resulting reaction mixture was heated to reflux. At the boiling point, the color of the reaction mixture changed from dark blue to dark brown, and the product immediately began to precipitate. The reaction mixture was then maintained at this temperature for 6 hours and then cooled to room temperature. Subsequently, dilute hydrochloric acid (10%, 130 ml) was added at a temperature of 5°C-10°C. Thereafter, the reaction mixture was filtered, washed with water, methanol (50 ml), and then washed with hexane (40 ml). The filtrates containing the hexane and methanol washings were combined, and the solvent mixture thus obtained was removed using a rotary evaporator. Methanol was added to the remaining residue, followed by cooling to 10° C. A precipitated product of 2,2′-bis(2-indenyl)biphenyl (metallocene complex precursor) was obtained, which was subsequently filtered off and washed with cold methanol and hexane. The dry weight of the compound thus obtained was ˜15 g.

[0105] A suspension of 2,2'-bis(2-indenyl)biphenyl (15 g) (metallocene complex precursor) was added to anhydrous diethyl ether (600 ml) under a nitrogen atmosphere and then cooled to 0° C. under an ice bath condition to obtain a suspension. A solution of n-butyllithium (alkyl lithium compound) (55 ml, 1.6 M hexane solution) was added to this suspension. After the addition, the solution thus obtained was warmed to room temperature and thereafter maintained at this temperature for 4 hours and then cooled to −78° C. to obtain a second lithiation reaction product.

[0106] Thereafter, zirconium tetrachloride (10.5g) is added in the second lithiation reaction product.The reaction mixture is warmed up to room temperature and the temperature is kept for 6 hours, which requires a longer time compared with the previous synthesis scheme.Subsequently, the crude reaction mixture is filtered to obtain a product (thick metallocene complex of formula 4), which is further purified.

[0107] For purification, the crude product obtained from the above method (crude metallocene complex of formula 4) was taken in dichloromethane (600 mL) and stirred at room temperature for 15 minutes to obtain a suspension. The suspension was then passed through a bed of cinnamate and concentrated to 75% of its volume. The solid was filtered (to obtain the first filtrate), then refluxed with hexane for 30 min, and finally the solid product and the filtrate (second filtrate) were filtered. The solid product was left and vacuum dried to obtain the desired 2,2'-bi(2-indenyl)biphenyl zirconium dichloride (~11 g) (pure metallocene complex of formula 4a).

[0108] Ligand recovery / purification from the product effluent (one recovery cycle): The filtrate and washings (first filtrate and second filtrate) thus obtained during the purification of crude 2,2'-bi(2-indenyl)biphenylzirconium dichloride (crude metallocene complex of formula 4) were collected (product effluent). Evaporation of the volatiles provided 9 g of tar-colored material. Further processing was carried out as follows: The residue (9 g) was vigorously stirred overnight as a suspension in methanolic HCl solution (200 mL, 6 M, prepared by adding 12 M HCl aqueous solution to methanol). The precipitated solid was filtered and washed with copious water. The final wash was carried out with methanol and then dried under water suction. 1 H NMR analysis showed that this compound was of sufficient purity. 4 g (53%) of the ligand (metallocene precursor) were obtained in this manner. 1 H NMR (CDCl3): δ7.41-7.09 (m, 16H), 6.32 (s, 2H), 3.35 (d, J=28.5Hz, 2H), 3.14 (d, J=28.5Hz, 2H).

[0109] Comparative Example: Procedure (Example 2A): The procedure was carried out as described in patent US6342622B1 under Example VIII.

[0110] Results: Table 2 below provides a detailed comparison of the yields between Example 2 and Comparative Example 2A. The amount of product formed was calculated using the standard 1 Determined by H-NMR emission spectroscopy technique.

[0111] Table 4: Yields of metallocene complex precursors obtained

[0112]

[0113] Table 5: Overall yields of metallocene complexes of formula (4) and formula (4)a

[0114]

[0115] It is clear that the overall product yield obtained by carrying out the present invention is significantly higher (-58% higher than the method described in US6342622) than the yield obtained in Comparative Example 2A (38% for the present invention and 24% for the comparative example). It should be noted that as described in the present invention, the ligand recovery method including at least 1 cycle increases the yield to 38%, which is in contrast to 30% for the method without ligand recovery / cleanup. This is because the method design of the present invention adds the recovered ligand back to the metallocene complex synthesis method. Specifically, because the present invention produces a higher intermediate product yield (59% vs. 35%) as shown in Table 4, the overall yield of the metallocene complex is also increased over the existing methods known in the literature.

[0116] Furthermore, from the experimental part, it can be noted that the complexation reaction between zirconium tetrachloride and the second lithiation reaction product is carried out in a reduced period (six hours as opposed to two days as described in patent US6342622), thereby making the process of the present invention more efficient and suitable for industrial scale production.

[0117] For calculation, it can be noted that the overall yield is calculated by multiplying the yield % (I) by the yield % (II). The yield is calculated using moles (mol), which are then calculated by dividing the weight of the compound used by the respective molecular weight. For example, for the boric acid used in Example 2A, the moles are calculated by dividing 12.2 by 269.

[0118] Example 3

[0119] Objective: To demonstrate the correlation between conversion yield and reaction time between zirconium tetrachloride and the second lithiation reaction product:

[0120] The following table gives a comparison of the conversion yields obtained when the reaction time between zirconium tetrachloride and the second lithiation reaction product is varied:

[0121] Table 5: Conversion rate and yield

[0122]

[0123] It is clear from this table that a reaction time of at least 6 hours of reaction time is particularly suitable for obtaining high conversion yields to obtain metallocene complexes, such as by 1 H NMR spectroscopy (peak area comparison). The reduced reaction times and improved yield comparisons are particularly useful for the industrial-scale preparation of metallocene ligands and complexes.

Claims

1. A method for preparing a reaction mixture comprising a metallocene complex of formula (4): Where R 1 -R 4 Each is independently selected from hydrogen, halogen, linear or branched or cyclic hydrocarbon groups having 1 to 20 carbon atoms, which are independently selected from alkyl, alkenyl, aryl, alkylaryl; alkyl sulfide groups having 1 to 20 carbon atoms, alkoxy groups having 1 to 20 carbon atoms, and amine groups, and R 5 , R 6 , R 7 , R 8 , R 9 and R 10 each independently selected from hydrogen, halogen, linear or branched or cyclic hydrocarbon groups having 1 to 20 carbon atoms, independently selected from alkyl, alkenyl, aryl, alkylaryl; alkyl sulfide groups having 1 to 20 carbon atoms, alkoxy groups having 1 to 20 carbon atoms, and amine groups, and one or more combinations thereof; and wherein 'M' is a transition metal element selected from Groups 3, 4, and 5 of the Periodic Table of Elements, 'Q' is a halogen anion, 'P' is the valence of the transition metal element 'M', and represents the number of halogen anions present, It includes the steps of: a) providing a precursor mixture, the precursor mixture comprising (i) a biphenyl compound of formula (2), Where R 1 -R 4 As defined herein, and wherein Z 1 is hydrogen, and (ii) a tertiary amine compound; b) adding an alkyl and / or aryl lithium compound having 1 to 10 carbon atoms to the precursor mixture at any temperature of 18° C. to 65° C., and then reacting at 45° C. to 65° C. to form a first lithiation reaction product; c) contacting the first lithiation reaction product with a borate ester compound of formula (3): B(OR 11 )3(3) The borate ester reaction product is obtained; wherein R 11 independently selected from hydrogen, linear or branched or cyclic hydrocarbon groups having 1 to 20 carbon atoms, independently selected from alkyl, alkenyl, aryl, alkoxycarbonyl, alkylaryl and one or more combinations thereof; and d) hydrolyzing the boric acid ester reaction product to form a boronic acid anhydride compound of formula (1): Where R 1 -R 4 as defined herein; and 'B' represents the element boron, e) reacting a boronic anhydride compound of formula (1) with a 2-bromoindenyl compound of formula (6) in the presence of a palladium catalyst to form a metallocene complex precursor of formula (7), Where R 5 -R 10 As defined herein; Where R 1 -R 10 As defined herein, f) reacting the metallocene complex precursor of formula (7) with an alkyl and / or aryl lithium compound having 1 to 10 carbon atoms to form a second lithiation reaction product; and g) reacting the second lithiation reaction product with a transition metal compound of formula (8) at room temperature for 5 to 8 hours to form a reaction mixture comprising a metallocene complex of formula (4), MQ p (8) wherein 'M' is a transition metal element selected from Groups 3, 4, and 5 of the periodic table, 'Q' is a halogen anion, and 'P' is the valence of the transition metal element 'M' and represents the number of halogen anions.

2. The method according to claim 1, wherein in formulas (4) and (8), 'Q' is a chloride anion.

3. The method according to claim 1, wherein the tertiary amine compound is tetramethylethylenediamine (TMEDA).

4. The method according to any one of claims 1 to 3, wherein the reaction mixture comprising the metallocene complex of formula (4) is further purified using solvent extraction and filtration to obtain: (i) Purified metallocene complex of formula (4a) Where R 1 -R 10 , 'M', 'Q' and 'P' are as defined herein; and (ii) A product effluent comprising a mixture of the metallocene complex of Formula 4a, the metallocene complex precursor of Formula 7, a partially complexed metallocene complex and a lithium-based inorganic salt.

5. The process according to claim 4, wherein the product effluent is recycled for use in preparing a reaction mixture comprising the metallocene complex of formula (4).

6. The method according to any one of claims 1-3, wherein the transition metal element 'M' is selected from zirconium, hafnium, titanium.

7. The method according to claim 6, wherein the transition metal element 'M' is zirconium.

8. The method according to any one of claims 1 to 3, wherein the transition metal compound of formula (8) is zirconium tetrachloride (ZrCl4).

9. The method according to any one of claims 1 to 3, wherein the alkyl and / or aryl lithium compound is selected from methyl lithium, butyl lithium, phenyl lithium.

10. The process according to claim 9, wherein the alkyl and / or aryl lithium compound is butyl lithium.

11. A method comprising the steps in the following order: a) providing a precursor mixture comprising (i) a biphenyl compound of formula (2) Where R 1 , R 2 , R 3 and R 4 Each is independently selected from hydrogen, halogen, linear or branched or cyclic hydrocarbon groups having 1 to 20 carbon atoms, which are independently selected from alkyl, alkenyl, aryl, alkoxycarbonyl, alkylaryl; alkyl sulfide groups having 1 to 20 carbon atoms, alkoxy groups having 1 to 20 carbon atoms, amine groups, and combinations thereof; and wherein Z 1 is hydrogen; and (ii) a tertiary amine compound; b) adding an alkyl and / or aryl lithium compound having 1 to 10 carbon atoms to the precursor mixture at any temperature of 18° C. to 65° C., and then reacting at 45° C. to 65° C. to form a first lithiation reaction product; c) contacting the first lithiation reaction product with a borate ester compound of formula (3): B(OR 11 )3(3) The borate ester reaction product is obtained; wherein R 11 independently selected from hydrogen, linear, branched or cyclic hydrocarbon groups having 1 to 20 carbon atoms, independently selected from alkyl, alkenyl, aryl, alkoxycarbonyl or alkylaryl and one or more combinations thereof; d) hydrolyzing the boric acid ester reaction product to form a boronic acid anhydride compound of formula (1): Where R 1 , R 2 , R 3 and R 4 each independently selected from hydrogen, halogen, a linear or branched or cyclic hydrocarbon group having 1 to 20 carbon atoms, independently selected from alkyl, alkenyl, aryl, alkylaryl; an alkyl sulfide group having 1 to 20 carbon atoms, an alkoxy group having 1 to 20 carbon atoms, and an amine group; 'B' represents the element boron; e) reacting a boronic anhydride compound of formula (1) with a 2-bromoindenyl compound of formula (6) in the presence of a palladium catalyst to form a metallocene complex precursor of formula (7), Where R 5 , R 6 , R 7 , R 8 , R 9 and R 10 each independently selected from hydrogen, halogen, linear or branched or cyclic hydrocarbon groups having 1 to 20 carbon atoms, independently selected from alkyl, alkenyl, aryl, alkylaryl; alkyl sulfide groups having 1 to 20 carbon atoms, alkoxy groups having 1 to 20 carbon atoms, and amine groups, and one or more combinations thereof, Where R 1 -R 10 As defined herein; f) reacting the metallocene complex precursor of formula (7) with an alkyl and / or aryl lithium compound having 1 to 10 carbon atoms to form a second lithiation reaction product; g) reacting the second lithiation reaction product with a transition metal compound of formula (8) at room temperature for 5 to 8 hours to form a reaction mixture comprising a metallocene complex of formula (4), MQ p (8) wherein 'M' is a transition metal element selected from Groups 3, 4, and 5 of the Periodic Table of Elements, 'Q' is a halogen anion, 'P' is the valence of the transition metal element 'M', and represents the number of halogen anions present, Where R 1 -R 10 , ‘M’, ‘Q’ and ‘P’ are as defined herein; and h) purifying the reaction mixture comprising the metallocene complex of formula (4) using solvent extraction and filtration to obtain (i) a purified metallocene ligand of formula (4a), Where R 1 -R 10 , 'M', 'Q' and 'P' are as defined herein, and (ii) a product effluent comprising a mixture of the metallocene complex of Formula 4a, the metallocene complex precursor of Formula 7, the partially complexed metallocene complex, and a lithium-based inorganic salt.

12. Use of the method according to any one of claims 1 to 11 for improving the yield in the production of metallocene complexes.

13. Use of the method according to any one of claims 1 to 11 for improving the purity of metallocene complexes.

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