PROCESS FOR PRODUCING A BIPHENYL METALLOCENE COMPLEX

Abstract

The invention relates to a process for preparing a boronic anhydride compound of formula (1), wherein, R.sup.1-R.sup.4 are substituents as defined in the disclosure and ‘B’ stands for the element boron. The invention also describes a process of using the boronic anhydride of formula (1), to prepare a biphenyl metallocene complex of formula (4), wherein, R.sup.1 to R.sup.10, are substituents as defined in the disclosure; and wherein ‘M’ is a transition metal element, ‘Q’ is an halide anion, and ‘P’ is the valency of the transition metal element ‘M’ and indicates the number of halide anion present. In addition, the invention further describes a process of purifying the metallocene complex of formula (4) so as to render the overall metallocene complex synthesis process environmentally sustainable as well as cost effective by minimizing waste effluents.

##STR00001##

Claims

1. A process for preparing a boronic anhydride compound of formula (1), ##STR00013## wherein, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are each independently selected from hydrogen, a halide, a linear or branched or cyclic hydrocarbyl group having one to twenty carbon atoms independently selected from an alkyl group, an alkenyl group, an aryl group, or an alkylaryl group; an alkylsulphide group having one to twenty carbon atoms, an alkoxy group having one to twenty carbon atoms, or an amine group; and ‘B’ stands for the element boron, the process comprising the steps of: a) providing a precursor mixture comprising (i) a biphenyl compound of formula (2), ##STR00014## wherein, R.sup.1 to R.sup.4 are as defined herein for formula (1) and wherein Z.sup.1 is hydrogen, and (ii) a tertiary amine compound; b) adding, at a temperature between 18° C. to 65° C., an alkyl and/or aryl lithium compound having one to ten carbon atoms, to the precursor mixture and forming a first lithiated reaction product; c) contacting the first lithiated reaction product with a boronate ester compound of formula (3)
B(OR.sup.11).sub.3  (3) and obtaining a boronate reaction product; wherein, R.sup.11 is independently selected from hydrogen, linear or branched or cyclic hydrocarbyl group having one to twenty carbon atoms independently selected from an alkyl group, alkenyl group, aryl group, an alkoxycarbonyl group, an alkylaryl group, or one or more combinations thereof; and d) hydrolyzing the boronate reaction product and forming the boronic anhydride compound of formula (1).

2. The process according to claim 1, wherein the tertiary amine compound is a bidentate tertiary amine.

3. The process according to claim 1, wherein the process further comprises the steps of preparing a reaction mixture comprising a metallocene complex of formula (4): ##STR00015## wherein, R.sup.1 to R.sup.4, are as defined for formula (1) in claim 1, and R.sup.5, R.sup.6,R.sup.7, R.sup.8, R.sup.9 and R.sup.10 are each independently selected from hydrogen, a halide, a linear or branched or cyclic hydrocarbyl group having one to twenty carbon atoms, independently selected from an alkyl group, an alkenyl group, an aryl group, or an alkylaryl group; an alkylsulphide group having one to twenty carbon atoms, an alkoxy group having one to twenty carbon atoms, an amine group, or one or more combinations thereof; and wherein ‘M’ is a transition metal element selected from Group 3, 4, or 5 of the Periodic System of Elements, ‘Q’ is an halide anion, and ‘P’ is the valency of the transition metal element ‘M’ and indicates the number of halide anion present, comprising the steps of: a) reacting in the presence of a palladium catalyst, the boronic anhydride of formula (1), with a 2-bromo indenyl compound of formula (6), ##STR00016## wherein, R.sup.5 to R.sup.10 are as defined herein for formula (4), and forming a metallocene complex precursor of formula (7); ##STR00017## wherein, R.sup.1 to R.sup.10 are as defined herein, b) reacting the metallocene complex precursor of formula (7), with the alkyl and/or aryl lithium compound having one to ten carbon atoms, and forming a second lithiated reaction product; and c) reacting for a time period ranging from 4 to 10 hours, the second lithiated reaction product, with a transition metal compound of formula (8),
MQ.sub.p  (8) and forming the reaction mixture comprising the metallocene complex of formula (4); wherein ‘M’ is a transition metal element selected from Group 3, 4, or 15 of the Periodic System of Elements, ‘Q’ is an halide anion, and ‘P’ is the valency of the transition metal element ‘M’ and indicates the number of halide anion.

4. The process according to claim 3, wherein the reaction mixture comprising the metallocene complex of formula (4) is further purified using solvent extraction and filtration, to obtain: (i) a purified metallocene complex of formula (4a) ##STR00018## wherein, R.sup.1 to R.sup.10, M′, ‘Q’ and ‘P’ are as defined in claim 3; and (ii) a product effluent comprising a mixture of metallocene complex of formula 4a, metallocene complex precursor of formula 7, partially complexed metallocene complex, and lithium based inorganic salts.

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

6. The process according to claim 3, wherein the transition metal element ‘M’ is selected from zirconium, hafnium, or titanium.

7. The process according to claim 3, wherein the transition metal compound of formula (8) is zirconium tetrachloride (ZrCl.sub.4).

8. The process according to claim 1, wherein the alkyl and/or aryl lithium compound is selected from methyl lithium, butyl lithium, or phenyl lithium.

9. A process comprising one or more steps comprising: a) providing a precursor mixture comprising (i) a biphenyl compound of formula (2) ##STR00019## wherein, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are each independently selected from hydrogen, a halide, a linear or branched or cyclic hydrocarbyl group having one to twenty carbon atoms independently selected from an alkyl group, an alkenyl group, an aryl group, an alkoxycarbonyl group, or an alkylaryl group; an alkylsulphide group having one to twenty carbon atoms, an alkoxy group having one to twenty carbon atoms, an amine group, or combinations thereof; and wherein Z.sup.1 is hydrogen; and (ii) a tertiary amine compound; and/or b) adding at a temperature between 18° C. to 65° C., an alkyl and/or aryl lithium compound having one to ten carbon atoms, to the precursor mixture and forming a first lithiated reaction product; and/or c) contacting the first lithiated reaction product with a boronate ester compound of formula (3)
B(OR.sup.11).sub.3  (3) and obtaining a boronate reaction product; wherein R.sup.11 is independently selected from hydrogen, linear, branched or cyclic hydrocarbyl group having one to twenty carbon atoms, independently selected from an alkyl group, an alkenyl group, an aryl group, an alkoxycarbonyl group, or an alkylaryl group, or one or more combinations thereof; and/or d) hydrolyzing the boronate reaction product and forming the boronic anhydride compound of formula (1) ##STR00020## wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are each independently selected from hydrogen, a halide, a linear or branched or cyclic hydrocarbyl group having one to twenty carbon atoms independently selected from an alkyl group, an alkenyl group, an aryl group, or an alkylaryl group; an alkylsulphide group having one to twenty carbon atoms, an alkoxy group having one to twenty carbon atoms, or an amine group; and ‘B’ stands for the element boron; and/or e) reacting the boronic anhydride compound of formula (1) with a 2-bromo indenyl of formula (6) ##STR00021## wherein R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9 and R.sup.10 are each independently selected from hydrogen, a halide, a linear or branched or cyclic hydrocarbyl group having one to twenty carbon atoms, independently selected from an alkyl group, an alkenyl group, an aryl group, or an alkylaryl group; an alkylsulphide group having one to twenty carbon atoms, an alkoxy group having one to twenty carbon atoms, and an amine group, or one or more combinations thereof, in the presence of a palladium catalyst and forming a metallocene complex precursor of formula (7), ##STR00022## wherein, R.sup.1 to R.sup.10 are as defined herein; and/or f) reacting the metallocene complex precursor of formula (7) with the alkyl and/or aryl lithium compound having one to ten carbon atoms, and forming a second lithiated reaction product; and/or g) reacting for a time period ranging from 4 to 10 hours, the second lithiated reaction product with a transition metal compound of formula (8),
MQ.sub.p  (8) wherein, ‘M’ is a transition metal element selected from Group 3, 4, or 5 of the Periodic System of Elements, ‘Q’ is an halide anion, and ‘P’ is the valency of the transition metal element ‘M’ and indicates the number of halide anion present, and forming a reaction mixture comprising a metallocene complex of formula (4), ##STR00023## wherein, R.sup.1 to R.sup.10, ‘M’, ‘Q’ and ‘P’ are as defined herein; and/or h) purifying the reaction mixture comprising the metallocene complex of formula (4), using solvent extraction and filtration, and obtaining (i) a purified metallocene ligand of formula (4a), ##STR00024## wherein, R.sup.1 to R.sup.10, ‘M’, ‘Q’ and ‘P’ are as defined herein, and (ii) a product effluent comprising a mixture of metallocene complex of formula 4a, metallocene complex precursor of formula 7, partially complexed metallocene complex, and lithium based inorganic salts.

10. A process according to claim 9, wherein the process comprises the steps for preparing a purified metallocene complex of formula (4a), comprising the steps of: a) providing a precursor mixture comprising (i) a biphenyl compound of formula (2); b) adding at a temperature between 18° C. to 65° C., an alkyl and/or aryl lithium compound having one to ten carbon atoms, to the precursor mixture and forming a first lithiated reaction product; c) contacting the first lithiated reaction product with a boronate ester compound of formula (3)
B(OR.sup.11).sub.3  (3) and obtaining a boronate reaction product; wherein R.sup.11 is independently selected from hydrogen, linear, branched or cyclic hydrocarbyl group having one to twenty carbon atoms, independently selected from alkyl, alkenyl, aryl, alkoxycarbonyl, or alkylaryl groups or one or more combinations thereof; and d) hydrolyzing the boronate reaction product and forming the boronic anhydride compound of formula (1); e) reacting the boronic anhydride compound of formula (1) with a 2-bromo indenyl of formula (6) in the presence of a palladium catalyst and forming a metallocene complex precursor of formula (7); f) reacting the metallocene complex precursor of formula (7) with the alkyl and/or aryl lithium compound having one to ten carbon atoms, and forming a second lithiated reaction product; g) reacting for a time period ranging from 4 to 10 hours, the second lithiated reaction product with a transition metal compound of formula (8),
MQ.sub.p  (8) wherein, ‘M’ is a transition metal element selected from Group 3, 4, or 5 of the Periodic System of Elements, ‘Q’ is an halide anion, and ‘P’ is the valency of the transition metal element ‘M’ and indicates the number of halide anion present, and forming a reaction mixture comprising a metallocene complex of formula (4); h) purifying the reaction mixture comprising the metallocene complex of formula (4), using solvent extraction and filtration, and obtaining (i) the purified metallocene ligand of formula (4a), and (ii) a product effluent comprising a mixture of metallocene complex of formula 4a, metallocene complex precursor of formula 7, partially complexed metallocene complex, and lithium based inorganic salts.

11. (canceled)

12. (canceled)

13. The process according to claim 1, wherein the tertiary amine compound is tetramethylethylene diamine (TMEDA).

14. The process according to claim 1, wherein the alkyl and/or aryl lithium compound is butyl lithium.

Description

Example 1

[0071] Purpose: To prepare a boronic anhydride compound of formula (1) (1, 1′-biphenyl-2, 2′-diyldiboronic anhydride) and compare the yield of production with that described in the reference U.S. Pat. No. 6,342,622B1. The general reaction scheme as practiced for Example 1 is shown below:

##STR00010##

[0072] Reactants used: For the purpose of Example 1 the following reactants were used:

TABLE-US-00001 TABLE 1 Reactants Reactant Chemical Supplier Biphenyl Biphenyl Aldrich Alkyl Lithium n-Butyl Lithium Aldrich Tertiary Amine Compound TMEDA Aldrich Boronate ester compound Trimethyl borate Aldrich

[0073] Process of synthesis: A biphenyl compound (25 g, 0.16 mole) charged under inert atmosphere, was added to a three neck flask, in the presence of dry hexane (100 ml). To this reaction mixture, TMEDA (60.8 ml, 0.40 mole) was added through a funnel at room temperature (˜25° C.). It was observed that the reaction mixture turned into a clear solution after complete addition of TMEDA. The mixture was stirred for 20 minutes at room temperature to form the precursor mixture. Thereafter, alkyl lithium compound, n-BuLi (243 ml, 0.38 mole; 1.6 M solution in hexane) was added through a cannula under inert atmosphere for over a 20 minute duration.

[0074] The color of reaction mixture thereafter changed from pale yellow to orange to crimson red and the temperature was increased from 24° C. to 35° C. Thereafter the reaction mixture was heated to 50-52° C. for one hour and subsequently cooled to room temperature. After stirring at room temperature for one hour, 500 ml of hexane was added to the reaction mixture and the temperature was cooled to −50° C. [1 hr.] and settled [0.5 hr.] to precipitate out orange crystals of 2, 2′dilithio biphenyl.bis TMEDA adduct (first lithiated reaction product) and the residual liquor was siphoned off through the cannula.

[0075] Finally to the 2, 2′dilithiobiphenyl.bis TMEDA adduct (first lithiated reaction product), which was left in the flask in the form of a solid, was charged with 250 ml tetrahydrofuran and was followed by dropwise addition of trimethyl borate (51.5 ml, 0.464 mole) (boronate ester compound) under a temperature condition of −50° C. The resultant reaction mixture was stirred at room temperature for an hour followed by the addition of dilute hydrochloric acid (10%, until pH reaches −1.5) under a temperature condition of 0° C. followed by stirring over 1 hour at room temperature. It was observed that the layers were separated, organic layer was washed with brine solution and subsequently dried over anhydrous sodium sulphate and concentrated to get the crude desired product. The crude residue was crystallized from toluene and hexane to obtain the biphenyl boronic anhydride compound.

[0076] Comparative Example: Procedure of Synthesis (Example 1A): The procedure practiced was as described in the U.S. Pat. No. 6,342,622B1 under Example VIII and the reported results were compared with the results obtained from the practice of Example 1.

[0077] Results: Table 2 below provides a detail comparison between the production yield of the results obtained from inventive Example 1 and comparative Example 1A. The amount of product formed was determined using a standard .sup.1H-NMR spectroscopic technique such as a BRUKER 300 MHz instrument was used for recording the spectra and CDCl.sub.3 was used as solvent.

TABLE-US-00002 TABLE 2 Product results Weight of boronic anhydride/boronic Weight of acid based product biphenyl (g) obtained (g) Yield % Example 1 25 (0.16) 20 (0.09) 55% Example 1A 103 (0.67 mol) 37.68 (0.15 mol) 23%

[0078] As is evident, the product yield obtained by the practice of the present invention is significantly higher (˜140% higher) than that obtained from the comparative Example 1A. From the experimental section it may be noted that the process practiced in the inventive Example 1 has a lesser reaction time over the reaction time described in Example 1A, thereby making the inventive process more efficient and suitable for industrial scale production.

Example 2

[0079] Purpose: To prepare a metallocene complex of formula (4a) (2, 2′-bis (2-indenyl) biphenyl zirconium dichloride complex) from the boronic anhydride compound of formula (1) obtained from Example 1, and compare the yield of production so obtained from the practice of Example 2 with that described by the reference U.S. Pat. No. 6,342,622B1. The general reaction scheme as practiced for Example 2 is shown below:

##STR00011## ##STR00012##

[0080] Reactants used: For the purpose of Example 2 the following reactants were used:

TABLE-US-00003 TABLE 3 Reactants Reactant Chemical Supplier 2-Bromo-Indenyl 2-Bromoindene Prepared compounds in-house Palladium Palladium-tetrakis(triphenylphosphine) Aldrich Catalyst (Pd(PPh.sub.3).sub.4)

[0081] Process of synthesis of 2-Bromoindene: To a mixture of indene (200 mmol), distilled water (15 ml) and dimethyl sulfoxide (70 ml) was added portion wise an amount of 210 mmol of N-bromosuccinimide. The resulting orange solution was stirred for 10 hours at room temperature, hydrolyzed with chilled water (100 ml), and extracted with diethyl ether (3×100 ml). The combined extracts were dried with magnesium sulphate and concentrated to give crystals of 2-bromoindan-1-ol upon standing overnight at −24° C. The obtained 2-bromoindan-1-ol (120 mmol) was suspended in 100 ml of toluene and mixed with a catalytic amount of para-toluenesulfonic acid monohydrate. The mixture was heated at reflux for 12 hours, and water was removed by a Dean-Stark apparatus. The resulting dark brown suspension was filtered and the volatiles were removed under vacuum. The residue was passed through silica gel using pentane as eluent, then the solvent was evaporated, and the crude product was distilled in vacuum. 2-Bromoindene was finally obtained as yellow crystals in 55% yield.

[0082] Process of synthesis of metallocene complex: To a solution of tetra(n-butyl)ammonium hydroxide (191.25 ml, 1M in methanol) the following reagents were added: toluene (150 ml), 2-Bromoindene (24.68 gm), 2,2′-Biphenyldiboronic anhydride (15.0 g) (boronic anhydride compound obtained from Example 1) and palladium catalyst [Pd(PPh.sub.3).sub.4] (0.765 g) and the resultant reaction mixture was heated to reflux. At the boiling point, the colour of the reaction mixture changed from deep blue to dark brown, and the product immediately started to precipitate. The reaction mixture was thereafter maintained at this temperature for six hours and then cooled to room temperature. Subsequently, dilute hydrochloric acid (10%, 130 ml) was added at a temperature between 5° C.-10° C. Thereafter, the reaction mixture was filtered, washed with water, methanol (50 ml), followed by a washing with hexane (40 ml). The filtrate comprising hexane and methanol washings were combined and the mixture of solvents so obtained, was removed by rotary evaporator. To the residue that was left, methanol was added 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 so obtained was ˜15 gm.

[0083] A suspension of 2,2′-bis(2-indenyl)biphenyl (15 g) (metallocene complex precursor) was added to dry diethyl ether (600 ml) under nitrogen atmosphere and was subsequently cooled to 0° C. under ice bath condition to obtain a suspension. To this suspension, a solution of n-butyl lithium (alkyl lithium compound) (55 ml, mole 1.6M in hexane) was added. After the addition, solution so obtained, was allowed to warm to room temperature and thereafter was maintained at this temperature for 4 hours and subsequently cooled to −78° C. to obtain the second lithiated reaction product.

[0084] Thereafter, zirconium tetrachloride (10.5 g) was added to the second lithiated reaction product. The reaction mixture was allowed to warm to room temperature and the temperature was maintained for six hours compared to previous synthetic protocols which required a longer time period. Subsequently, the crude reaction mixture was filtered and the product (crude metallocene complex of formula 4) was obtained which was further purified.

[0085] For the purification, the crude product as obtained from the above process (crude metallocene complex of formula 4) was taken in to dichloromethane (600 mL) and stirred for 15 minutes at room temperature to obtain a suspension. Then the suspension was passed through a celite bed and concentrated to 75% of its volume. The solid was filtered (to obtain first filtrate) and then refluxed with hexane for 30 min, and finally filtered a solid product and a filtrate (second filtrate). A solid product was left behind, which was dried with vacuum to obtain the desired 2, 2′-bi (2-indenyl) biphenyl zirconium dichloride (˜11 g) (Pure metallocene complex of formula 4a).

[0086] Ligand recovery/purification from product effluent (one cycle of recovery): Filtrates and washings (first filtrate and second filtrate) so obtained (product effluent) during purification of crude 2, 2′-bi (2-indenyl) biphenyl zirconium dichloride (crude metallocene complex of formula 4) were collected. Evaporation of the volatiles provided 9 g tarry dark brown material. Further treatments were conducted following a method as described below: The residue (9 g) was stirred vigorously as a suspension in a methanolic HCl solution (200 mL, 6M, prepared by adding aqueous 12M HCl in methanol) overnight. The precipitated solid was filtered and was washed with copious amounts of water. A final wash was given with methanol and was subsequently dried under water suction. .sup.1H NMR analysis showed sufficient purity of this compound. 4 g (53%) of ligand (metallocene precursor) was obtained in this method. .sup.1H NMR (CDC.sub.3): δ 7.41-7.09 (m, 16H), 6.32 (s, 2H), 3.35 (d, J=28.5 Hz, 2H), 3.14 (d, J=28.5 Hz, 2H).

[0087] Comparative Example: Procedure (Example 2A): The procedure practiced was as described in the U.S. Pat. No. 6,342,622B1 under Example VIII.

[0088] Results: Table 2 below provides a detail comparison between the production yield between Example 2 and comparative Example 2A. The amount of product formed was determined using a standard .sup.1H-NMR spectroscopic technique.

TABLE-US-00004 TABLE 4 Yield obtained for metallocene complex precursor Yield % (I) Weight of 2,2′- Weight of 2,2′- of 2,2′- biphenylboronic bis(2-indenyl) bis(2-indenyl) acid/anhydride (g) biphenyl (g) (7) biphenyl (g) (7) Example 15.3 g (0.066 mol) 15 g (0.039 mol) 59% 2 Example 12.2 g (0.045 mol) 5.98 g (15.6 mmol) 35% 2A

TABLE-US-00005 TABLE 5 Overall Yield of metallocene complex of formula (4) and formula (4)a Purified Overall Yield % Weight of 2, 2′-bis (2- Metallocene (starting from boronic Weight of 2,2′- indenyl) biphenyl complex of anhydride/acid bis(2-indenyl) zirconium dichloride formula 4a including ligand biphenyl (g) (7) complex (g) (4a) Yield % (II) recovery step) Example 2 15 g (0.039 mol) 11 g (0.020 mol) 51% 30% Example 2 13.55 g (0.025 mol) 64% 38% (with one cycle of ligand recovery and purification) Example 2A 3.84 g (0.01 mol) 3.95 g (0.007 mol) 70% 24%

[0089] As is evident, that the overall product yield obtained by the practice of the present invention is significantly higher (˜58% higher than the process described in U.S. Pat. No. 6,342,622) than that obtained from the comparative Example 2A (38% for the present invention versus 24%). It is to be noted that the inclusion of the ligand recovery process of at least 1 cycle as described in the present invention enhances the yield to 38% compared to 30% without the ligand recovery/purification process. This is because the inventive process is designed for the ligand recovered to be added back to the process for metallocene complex synthesis. In particular as the present invention results in higher yield of intermediate products (59% versus 35%) as shown in Table 4, the overall yield of metallocene complex is also increased over existing process known in literature.

[0090] Further, from the experimental section it may be noted that the complexation reaction between zirconium tetrachloride and the second lithiated reaction product was conducted at reduced time frame (6 hours as described versus a two day period described in the U.S. Pat. No. 6,342,622), thereby making the inventive process more efficient and suitable for industrial scale production.

[0091] For the purpose of calculation, it may be noted that the overall yield is calculated by multiplying Yield % (I) with Yield % (II). The yield is calculated using the mole number (mol), which in turn is calculated by dividing the weight of the compound used with respective molecular weight. For example, for boronic acid used in Example 2A, the mole number is calculated by dividing 12.2 by 269.

Example 3

[0092] Purpose: To demonstrate the dependence of conversion yield to the reaction time between zirconium tetrachloride and the second lithiated reaction product:

[0093] The table below gives a comparison of the conversion yield obtained when the reaction time between zirconium tetrachloride and the second lithiated reaction product was varied:

TABLE-US-00006 TABLE 5 Conversion yield Conversion yield (%) 2, 2′-bis (2-indenyl) Metallocene complex biphenyl zirconium Example precursor Time dichloride complex 1 0.501 3 hours 75% 2 0.435 6 hours >98%  3 0.496 16 hours  95%

[0094] From the table it is evident that a purposeful selection of time period of reaction of at least 6 hours of reaction is particularly suited for obtaining high conversion yield to obtain the metallocene complex as observed by 1H NMR spectroscopy (Comparison of peak-area). The reduced reaction time with enhanced yield comparison is particularly useful for industrial scale preparation of metallocene ligands and complexes.