Biaryl phenoxy group IV transition metal catalysts for olefin polymerization
11066488 · 2021-07-20
Assignee
Inventors
- Endre Szuromi (Lake Jackson, TX)
- David D. Devore (Midland, MI)
- Robert D. J. Froese (Midland, MI)
- Arkady L. Krasovskiy (Lake Jackson, TX)
- Lixin Sun (Lake Jackson, TX, US)
- Kevin A. Frazier (Midland, MI)
- Joseph S. Renny (London, GB)
Cpc classification
C08F4/65912
CHEMISTRY; METALLURGY
C08F2500/03
CHEMISTRY; METALLURGY
C08F2500/04
CHEMISTRY; METALLURGY
C08F210/16
CHEMISTRY; METALLURGY
C08F2500/03
CHEMISTRY; METALLURGY
C08F210/16
CHEMISTRY; METALLURGY
C08F2500/04
CHEMISTRY; METALLURGY
C08F210/14
CHEMISTRY; METALLURGY
C08F4/65908
CHEMISTRY; METALLURGY
Y02P20/582
GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
C08F210/14
CHEMISTRY; METALLURGY
International classification
C08F4/64
CHEMISTRY; METALLURGY
C08F4/659
CHEMISTRY; METALLURGY
C08F210/16
CHEMISTRY; METALLURGY
Abstract
Embodiments are directed to a catalyst system comprising metal-ligand complexes and processes for polyolefin polymerization using the metal-ligand complex having the following structure: ##STR00001##
Claims
1. A catalyst system comprising a metal-ligand complex according to formula (I): ##STR00048## where M is a metal selected from the group consisting of titanium, zirconium, hafnium, the metal having a formal oxidation state of +2, +3, or +4; each X is a monodentate or bidentate ligand independently selected from the group consisting of unsaturated (C.sub.2-C.sub.20)hydrocarbon, unsaturated (C.sub.2-C.sub.50)heterohydrocarbon, (C.sub.1-C.sub.50)hydrocarbyl, (C.sub.6-C.sub.50)aryl, (C.sub.6-C.sub.50)heteroaryl, cyclopentadienyl, substituted cyclopentadienyl, (C.sub.4-C.sub.12)diene, halogen, —N(R.sup.N).sub.2, and —NCOR.sup.C; n is 1, 2 or 3; m is 1 or 2; the metal-ligand complex has 6 or fewer metal-ligand bonds; each Y is independently selected from oxygen or sulfur; each R.sup.1, R.sup.2, R.sup.3, and R.sup.4 is independently selected from the group consisting of (C.sub.1-C.sub.50)hydrocarbyl, (C.sub.1-C.sub.50)heterohydrocarbyl, (C.sub.6-C.sub.50)aryl, (C.sub.4-C.sub.50)heteroaryl, —Si(R.sup.C).sub.3, —Ge(R.sup.C).sub.3, —P(R.sup.P).sub.2, —N(R.sup.N).sub.2, —OR.sup.C, —SR.sup.C, —NO.sub.2, —CN, —CF.sub.3, R.sup.CS(O)—, R.sup.CS(O).sub.2—, (R.sup.C).sub.2C═N—, R.sup.CC(O)O—, R.sup.COC(O)—, R.sup.CC(O)N(R)—, (R.sup.C).sub.2NC(O)—, halogen, and —H; each R.sup.5 is independently chosen from (C.sub.1-C.sub.50)hydrocarbyl, (C.sub.1-C.sub.50)heterohydrocarbyl, (C.sub.6-C.sub.50)aryl, (C.sub.4-C.sub.50)heteroaryl, —Si(R.sup.C).sub.3, and —Ge(R.sup.C).sub.3, and, when m is 2, two R.sup.5 are optionally covalently linked; for each individual ring containing groups z.sub.1, z.sub.2, and z.sub.3, each of z.sub.1, z.sub.2, and z.sub.3 is independently selected from the group consisting of sulfur, oxygen, —N(R.sup.R)—, or —C(R.sup.R)—, provided that at least one and not more than two of z.sub.1, z.sub.2, and z.sub.3 are —C(R.sup.R)—, where R.sup.R is —H or (C.sub.1-C.sub.30)hydrocarbyl, wherein any two R.sup.R groups bonded to neighboring atoms are optionally linked; each R.sup.C, R.sup.N, and R.sup.P in formula (I) is independently a (C.sub.1-C.sub.30)hydrocarbyl.
2. The catalyst system according to claim 1, wherein: M is zirconium or hafnium; each X is independently selected from the group consisting of (C.sub.6-C.sub.20)aryl, (C.sub.4-C.sub.20)heteroaryl, (C.sub.4-C.sub.12)diene, and a halogen; each Y is oxygen; each R.sup.1 is independently selected from the group consisting of (C.sub.1-C.sub.50)aryl and (C.sub.4-C.sub.50)heteroaryl; and each R.sup.2, R.sup.3 and R.sup.4 is independently selected from the group consisting of (C.sub.1-C.sub.50)hydrocarbyl, (C.sub.1-C.sub.40)heterohydrocarbyl, (C.sub.6-C.sub.40)aryl, (C.sub.4-C.sub.50)heteroaryl, halogen, and —H.
3. The catalyst system according to claim 1, wherein for each individual ring containing groups z.sub.1, z.sub.2, and z.sub.3, one of z.sub.1, z.sub.2, and z.sub.3 is a sulfur atom, and two of z.sub.1, z.sub.2, and z.sub.3 are —C(H)—.
4. The catalyst system according to claim 1, wherein each R.sup.1 is carbazolyl, each R.sup.2 is methyl, and each R.sup.3 is methyl.
5. The catalyst system according to claim 1, wherein each R.sup.1 is 3,6-di-tert-butylcarbazol-9-yl.
6. The catalyst system according to claim 1, wherein each R.sup.1 is 3,5-di-tert-butylphenyl.
7. The catalyst system according to claim 1, wherein R.sup.2 is tert-octyl.
8. The catalyst system according to claim 1, wherein m is 2 and the metal-ligand complex has a structure according to formula (II): ##STR00049## where R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, z.sub.1, z.sub.2, z.sub.3, Y, and X are as defined in formula (I); and n is 1 or 2.
9. The catalyst system according to claim 8, wherein: M is zirconium or hafnium; each X is independently selected from the group consisting of (C.sub.6-C.sub.50)aryl, (C.sub.6-C.sub.50)heteroaryl, (C.sub.4-C.sub.12)diene, and halogen; each Y is oxygen; each R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is independently selected from the group consisting of (C.sub.1-C.sub.50)hydrocarbyl, (C.sub.1-C.sub.50)heterohydrocarbyl, (C.sub.6-C.sub.50)aryl, (C.sub.4-C.sub.50)heteroaryl, halogen, and hydrogen.
10. The catalyst system according to claim 8, wherein for each individual ring containing groups z.sub.1, z.sub.2, and z.sub.3, one of z.sub.1, z.sub.2, and z.sub.3 is a sulfur atom, and two of z.sub.1, z.sub.2, and z.sub.3 are —C(H)—.
11. The catalyst system according to claim 9, wherein n is 2 and each X is benzyl.
12. The catalyst system according to claim 8, wherein each R.sup.1 is carbazolyl, each R.sup.2 is methyl, and each R.sup.3 is methyl.
13. The catalyst system according to claim 8, wherein each R.sup.1 is 3,6-di-tert-butylcarbazol-9-yl or 2,7-di-tert-butylcarbazol-9-yl.
14. The catalyst system according to claim 8, wherein each R.sup.3 is tert-octyl.
15. The catalyst system according to claim 8, wherein each R.sup.1 is 3,5-di-tert-butylphenyl.
16. The catalyst system according to claim 8, wherein the two groups R.sup.5 are covalently linked, whereby the metal-ligand complex comprises a divalent radical Q consisting of the two covalently linked groups R.sup.5, and the metal-ligand complex has a structure according to formula (III): ##STR00050## where: Q is (C.sub.1-C.sub.12)alkylene, (C.sub.1-C.sub.12)heteroalkylene, (—CH.sub.2Si(R.sup.C).sub.2CH.sub.2—), (—CH.sub.2CH.sub.2Si(R.sup.C).sub.2CH.sub.2CH.sub.2—), (—CH.sub.2Ge(R.sup.C).sub.2CH.sub.2—), or (—CH.sub.2CH.sub.2Ge(R.sup.C).sub.2CH.sub.2CH.sub.2—), where R.sup.C is (C.sub.1-C.sub.30)hydrocarbyl; R.sup.1-4, Y, X, M, z.sub.1, z.sub.2, and z.sub.3 are defined in formula (I); and n is 1, or 2.
17. The catalyst system according to claim 16, wherein Q is —CH.sub.2Si(CH.sub.3).sub.2CH.sub.2—.
18. A polymerization process for producing an ethylene-based polymer, the polymerization process comprising: polymerizing ethylene and at least one additional α-olefin in the presence of a catalyst system according to claim 1 and at least one activator to form a polymer, wherein the polymer exhibits: a density from 0.860 g/cm.sup.3 to 0.973 g/cm.sup.3, measured according to ASTM D792; a molecular weight distribution from 1 to 20; and less than 20% octene incorporation.
19. The polymerization process according claim 17, wherein the density is from 0.880 g/cm.sup.3 to 0.920 g/cm.sup.3.
20. The polymerization process according claim 17, wherein the activator comprises MMAO, bis(hydrogenated tallow alkyl)methylammonium, tetrakis(pentafluorophenyl)borate, or tris(pentafluorophenyl)borane.
Description
EXAMPLES
(1) One or more features of the present disclosure are illustrated in view of the examples as follows:
Example 1
Synthesis of methyl 4-bromo-3-methoxythiophene-2-carboxylate 2
(2) ##STR00013##
(3) Compound 1 (1.000 g, 4.22 mmol) was dissolved in 40 mL of acetone. Potassium carbonate (2.915 g, 21.09 mmol) was added followed by iodomethane (2.36 mL, 37.96 mmol; d 2.28). The resulting mixture was heated at 60° C. for 14 hours. The reaction mixture was allowed to cool to 23° C. and then filtered through a pad of Celite, which was then rinsed with methylene chloride (20 mL). The filtrate was concentrated under vacuum and the residue was taken up in 80 mL of methylene chloride and the small amount of white solids was removed by filtration. The solvent was removed under vacuum giving a yellow solid (1.01 g, 95%).
(4) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.39 (s, 1H), 4.01 (s, 3H), 3.88 (s, 3H).
Example 2
Synthesis of 4-bromo-3-methoxythiophene-2-carboxylic acid 3
(5) ##STR00014##
(6) Compound 2 (1.000 g, 3.98 mmol) was dissolved in 15 mL THF, and mixed with a 1.0 M sodium hydroxide aqueous solution (5.2 mL, 5.18 mmol). The mixture was stirred at room temperature for 48 h.
(7) Aqueous HCl (1.0 M) was added dropwise to the mixture until pH was approximately 2. The acidic mixture was extracted with CH.sub.2Cl.sub.2 (60 mL×2). Brine was added to assist phase separation. The combined organic extracts were concentrated using a rotary evaporator to obtain a residue, which was mixed with 100 mL of CH.sub.2Cl.sub.2. Some white material stayed undissolved. These solids were filtered off (found to be water soluble). The filtrate was washed with water (60 mL×2), dried with Na.sub.2SO.sub.4, and concentrated under reduced pressure to a solid (0.55 g, 58%).
(8) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.51 (s, 1H), 4.08 (s, 3H).
Example 3: Synthesis of 3-bromo-4-methoxythiophene 4
(9) ##STR00015##
(10) Compound 3 (0.550 g, 2.32 mmol) was treated with 15 mL of conc. H.sub.2SO.sub.4 at 65° C. for 5 hours in a scintillation vial equipped with a pressure-relief septum cap. (Note: it was important to use a vent needle or some other way to relieve pressure as this reaction produces CO.sub.2 gas.) After cooling to room temperature, the mixture was poured into 20 mL of crushed ice, and extracted with methylene chloride (3×100 mL). The organic extracts were combined, washed successively with sat. aqueous NaHCO.sub.3 (2×80 mL), and water (2×100 mL). The organic layer was passed through a plug of silica gel and concentrated under vacuum to a dark brown oil (0.3 g, 67%). Solvent removal needed to be done quickly due to volatility of the product. GC/MS confirmed pure desired product (m/z=193).
(11) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.20 (d, J=3.5 Hz, 1H), 6.25 (d, J=3.5 Hz, 1H), 3.88 (s, 3H).
Example 4
Synthesis of Ligand L1
(12) ##STR00016##
(13) Compound 4 (0.080 g, 0.41 mmol) and compound 5 (0.200 g, 0.41 mmol, purchased from Boulder Scientific) were dissolved in 4 mL THF. Na.sub.2CO.sub.3 (0.264 g, 2.49 mmol) was dissolved in 1 mL of deionized water and added to the THF solution forming a biphasic solution, which was then sparged with N.sub.2 for 30 min. Pd(P.sup.tBu3).sub.2 (0.011 g, 0.021 mmol) was dissolved in 0.5 mL degassed THF in a nitrogen-filled drybox, and then added to the reaction mixture via syringe. The biphasic mixture was stirred vigorously at 65° C. for 14 hours. The reaction mixture was allowed to cool to 25° C. and the aqueous phase was separated and discarded. The organic phase was diluted with 30 mL THF and the solution was passed through a short plug of silica gel. The filtrate was concentrated on a rotary evaporator. The crude protected product was used in the next step without further purification.
(14) .sup.1H NMR (400 MHz, C.sub.6D.sub.6) δ 8.09 (dt, J=7.6, 0.9 Hz, 2H), 7.37-7.21 (m, 7H), 7.03 (d, J=3.5 Hz, 1H), 6.84 (d, J=1.9 Hz, 1H), 6.27 (s, 1H), 5.72 (d, J=3.5 Hz, 1H), 3.01 (s, 3H), 2.06 (s, 3H).
(15) The crude protected product was dissolved in 4 mL of a ca 1:2 mixture of MeOH and THF, concentrated HCl (4 drops from a Pasteur pipette) was added and the solution stirred at 23° C. for 5 hours. The solution was evaporated to dryness under vacuum and the residue was dissolved in 40 mL of Et.sub.2O, passed through a short plug of silica gel and the solvent was removed under vacuum. The brown crude product was purified using a Biotage (EtOAc/hexane gradient: 5% to 10% EtOAc over 8 column volume (CV), then held at 10%). Fractions containing the pure product were combined and concentrated on a rotary evaporator. The product was further dried under high vacuum overnight to obtain L1 as a white solid (0.130 g, 81%).
(16) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.20-8.11 (m, 2H), 7.45-7.38 (m, 3H), 7.36 (d, J=1.8 Hz, 1H), 7.31-7.28 (m, 3H), 7.27-7.26 (m, 1H), 6.46-6.41 (m, 2H), 3.90 (s, 3H), 2.40 (s, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 154.84, 147.78, 141.12, 131.41, 130.52, 129.35, 129.31, 125.80, 125.37, 124.30, 123.77, 123.36, 120.23, 119.72, 110.31, 98.19, 57.97, 20.55.
Example 5
Synthesis of Ligand L2
(17) ##STR00017##
(18) Compound 4 (0.100 g, 0.52 mmol) and compound 6 (0.262 g, 0.52 mmol, purchased from Boulder Scientific) were dissolved in 4 mL THF. Na.sub.2CO.sub.3 (0.329 g, 3.11 mmol) was dissolved in 1 mL of deionized water and added to the THF solution forming a biphasic solution, which was then sparged with N.sub.2 for 30 min. Pd(Pt-Bu.sub.3).sub.2 (0.013 g, 0.026 mmol) was dissolved in 0.5 mL degassed THF in a nitrogen-filled drybox, and then added to the reaction mixture via syringe. The biphasic mixture was stirred vigorously at 65° C. for 14 hours. The reaction mixture was allowed to cool to 25° C. and the aqueous phase was separated and discarded. The organic phase was diluted with 30 mL THF and the solution was passed through a short plug of silica gel. The filtrate was concentrated on a rotary evaporator. The crude protected product was dissolved in 16 mL of a ca 1:1 mixture of Me0H and THF, concentration HCl (4 drops from a Pasteur pipette) was added and the solution stirred at 23° C. for 4 hours. The solution was evaporated to dryness under vacuum and the residue was dissolved in 100 mL of EtOAc/hexane (10% EtOAc), passed through a short plug of silica gel and the solvent was removed under vacuum to afford L2 as a beige solid in quantitative yield.
(19) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.45 7.41 (m, 2H), 7.39 (d, J=1.8 Hz, 2H), 7.32 (d, J=3.4 Hz, 1H), 7.14 (d, J=2.7 Hz, 2H), 6.42 (d, J=3.4 Hz, 1H), 6.17 (s, 1H), 3.90 (s, 3H), 2.36 (s, 3H), 1.37 (s, 18H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 155.32, 150.63, 147.98, 137.35, 131.21, 130.92, 130.56, 130.06, 129.62, 123.89, 123.80, 122.16, 121.28, 97.72, 57.86, 34.94, 31.53, 31.48, 20.56.
Example 6: Synthesis of Ligand L3
(20) ##STR00018##
(21) Compound 4 (0.055 g, 0.28 mmol) and compound 7 (0.198 g, 0.28 mmol, purchased from Boulder Scientific) were dissolved in 4 mL THF. Na.sub.2CO.sub.3 (0.181 g, 1.71 mmol) was dissolved in 1 mL of deionized water and added to the THF solution forming a biphasic solution, which was then sparged with N.sub.2 for 20 min. Pd(P.sup.tBu.sub.3).sub.2 (0.007 g, 0.014 mmol) was dissolved in 0.8 mL degassed THF in a nitrogen-filled drybox, and then added to the reaction mixture via syringe. The biphasic mixture was stirred vigorously at 65° C. for 14 hours. The reaction mixture was allowed to cool to 25° C. and the aqueous phase was separated and discarded. The organic phase was diluted with 30 mL THF and the solution was passed through a short plug of silica gel. The filtrate was concentrated on a rotary evaporator. The crude protected product was dissolved in 16 mL of a ca 1:1 mixture of MeOH and THF, concentration HCl (4 drops from a Pasteur pipette) was added and the solution stirred at 25° C. for 14 hours. The solution was evaporated to dryness under vacuum and the residue was dissolved in 100 mL of EtOAc/hexane (10% EtOAc), passed through a short plug of silica gel and the solvent was removed under vacuum to afford L3 as a beige solid (0.165 g, 97%). LC/MS confirmed pure desired product (m/z=596).
(22) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.02 (d, J=8.2 Hz, 2H), 7.59 (d, J=2.4 Hz, 1H), 7.45 (d, J=3.4 Hz, 1H), 7.37 (d, J=2.6 Hz, 1H), 7.34 (d, J=1.7 Hz, 1H), 7.32 (d, J=1.7 Hz, 1H), 7.20 (d, J=1.4 Hz, 2H), 6.45 (d, J=3.4 Hz, 1H), 6.11 (s, 1H), 3.94 (s, 3H), 1.76 (s, 2H), 1.40 (s, 6H), 1.37 (s, 18H), 0.84 (s, 9H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 155.36, 149.09, 147.68, 142.59, 141.57, 129.74, 128.82, 126.66, 124.66, 124.23, 122.72, 121.09, 119.64, 119.43, 118.21, 117.66, 106.63, 106.29, 97.81, 57.90, 57.20, 38.24, 35.14, 32.51, 31.90, 31.80, 31.73, 31.58.
Example 7
Synthesis of Ligand L4
(23) ##STR00019##
(24) Compound 4 (0.059 g, 0.31 mmol) and compound 8 (0.212 g, 0.31 mmol, purchased from Boulder Scientific) were dissolved in 4 mL THF. Na.sub.2CO.sub.3 (0.194 g, 1.83 mmol) was dissolved in 1 mL of deionized water and added to the THF solution forming a biphasic solution, which was then sparged with N.sub.2 for 15 min. Pd(P.sup.tBu.sub.3).sub.2 (0.008 g, 0.015 mmol) was dissolved in 0.8 mL degassed THF in a nitrogen-filled drybox, and then added to the reaction mixture via syringe. The biphasic mixture was stirred vigorously at 65° C. for 14 hours. The reaction mixture was allowed to cool to 25° C. and the aqueous phase was separated and discarded. The organic phase was diluted with 30 mL THF and the solution was passed through a short plug of silica gel. The filtrate was concentrated on a rotary evaporator. The crude protected product was dissolved in 16 mL of a 1:1 mixture of MeOH and THF, concentrated HCl (4 drops from a Pasteur pipette) was added and the solution stirred at 25° C. for 14 hours. The solution was evaporated to dryness under vacuum and the residue was dissolved in 100 mL of EtOAc/hexane (10% EtOAc), passed through a short plug of silica gel and the solvent was removed under vacuum to afford L4 as a beige solid (0.170 g, 93%). LC/MS confirmed pure desired product (m/z=596).
(25) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.17 (d, J=1.8 Hz, 2H), 7.56 (d, J=2.4 Hz, 1H), 7.48 (d, J=1.9 Hz, 1H), 7.46 (d, J=1.9 Hz, 1H), 7.43 (d, J=3.4 Hz, 1H), 7.38 (d, J=2.4 Hz, 1H), 7.17 (s, 1H), 7.14 (s, 1H), 6.43 (d, J=3.4 Hz, 1H), 6.27 (s, 1H), 3.90 (s, 3H), 1.75 (s, 2H), 1.48 (s, 18H), 1.39 (s, 6H), 0.84 (s, 9H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 155.19, 147.53, 142.65, 142.53, 139.64, 129.70, 128.70, 126.66, 124.95, 124.19, 123.56, 123.29, 122.68, 116.27, 109.55, 97.90, 57.87, 57.06, 38.21, 34.72, 32.44, 32.06, 31.88, 31.58.
Example 8
Synthesis of 2-bromo-3-methoxythiophene 10
(26) ##STR00020##
(27) The synthesis of compound 10 was based on JACS 2012, 134(46), 19070. A solution of N-bromosuccinimide (1.840 g, 10.34 mmol) in dry DMF (6 mL) has been added dropwise to a solution of 3-methoxythiophene (1.180 g, 10.34 mmol) in dry DMF (4 mL). After 1 h, the reaction mixture was partitioned between water and dichloromethane (30 mL each). The aqueous layer was washed with dichloromethane (30 mL) and then the combined dichloromethane layers were washed with brine (2×30 mL), dried over Na.sub.2SO.sub.4, and the solvent was removed under reduced pressure. The crude product was dissolved in 100 mL of hexane and passed through a plug of silica gel. Solvent removal afforded the pure product as a pale yellow liquid (1.500 g, 75%).
(28) Important note: the pure product was not stable at 25° C. on air. Significant decomposition took place within an hour. Stability at low temperature and/or under inert atmosphere was not tested.
(29) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.21 (d, J=6.0 Hz, 1H), 6.77 (d, J=6.0 Hz, 1H), 3.90 (s, 3H).
Example 9
Synthesis of Ligand L5
(30) ##STR00021##
(31) Compounds 5 (0.228 g, 0.47 mmol) and 10 (0.091 g, 0.47 mmol) were dissolved in 10 mL THF. Na.sub.2CO.sub.3 (0.300 g, 2.83 mmol) was dissolved in 5 mL of deionized water and added to the THF solution forming a biphasic solution, which was then sparged with N.sub.2 for 20 min. Pd(P.sup.tBu.sub.3).sub.2 (0.012 g, 0.024 mmol) was dissolved in 2 mL degassed THF in a nitrogen-filled drybox, and then added to the reaction mixture via syringe. The reaction mixture was stirred vigorously at 65° C. for 14 hours. The reaction mixture was allowed to cool to 25° C. The aqueous phase was separated and discarded. The organic phase was mixed with 30 mL of Et.sub.2O, and the solution was passed through a plug of silica gel. The solvent was removed under vacuum to give a yellow residue—a protected product.
(32) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.20-8.13 (m, 2H), 7.46-7.36 (m, 3H), 7.34 (d, J=5.6 Hz, 1H), 7.32-7.27 (m, 3H), 7.26-7.23 (m, 2H), 6.92 (d, J=5.6 Hz, 1H), 3.92 (s, 3H), 2.40 (s, 3H).
(33) The yellow residue, the protected product, was dissolved in 20 mL of a 1:1 (v/v) mixture of MEOH and THF, concentrations HCl (5 drops from a Pasteur pipette) was added and the solution stirred at 25° C. for 3 hours. The reaction mixture was evaporated to dryness, the residue was dissolved in a mixture of 50 mL diethyl ether and 50 mL hexane, and the solution was passed through a plug of silica gel. Solvent removal under vacuum afforded ligand L5 (0.150 g, 83%).
(34) .sup.1H NMR (400 MHz, C.sub.6D.sub.6) δ 8.11 (dt, J=7.7, 1.1 Hz, 2H), 7.48 (dd, J=2.2, 0.7 Hz, 1H), 7.38-7.20 (m, 7H), 6.87 (dt, J=2.2, 0.6 Hz, 1H), 6.69 (d, J=5.6 Hz, 1H), 6.21 (d, J=5.6 Hz, 1H), 2.94 (s, 3H), 2.02 (s, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 151.34, 147.93, 141.19, 130.88, 130.53, 129.51, 126.04, 125.69, 125.11, 123.25, 121.87, 120.19, 119.54, 118.31, 116.46, 110.32, 59.43, 20.52
Example 10
Synthesis of propane-1,3-diyl bis(trifluoromethanesulfonate) 13
(35) ##STR00022##
(36) A solution of 1,3-propanediol (2.9 mL, 40.0 mmol) and pyridine (6.5 mL, 80 mmol; d 0.978) in dry dichloromethane (100 mL) was cooled to −78° C. under nitrogen and Tf.sub.2O (13.5 mL, 80.0 mmol; d 1.677) was added dropwise. The reaction mixture was warmed to 25° C. and stirred for 1 h to give a pink solution with a white precipitate. The reaction mixture was washed with deionized water quickly (3×20 mL), dried over anhydrous Na.sub.2SO.sub.4 and filtered through silica gel quickly. The silica gel was washed with dichloromethane (50 mL) and the filtrate was combined with the first washing. The solvent was removed under vacuum to afford compound 13 as a pale red oil (7.5 g, 55%). The product should be stored under inert atmosphere.
(37) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 4.67 (t, J=5.8 Hz, 4H), 2.36 (p, J=5.8 Hz, 2H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 118.54 (q, J=320.0 Hz), 71.43, 29.27.
Example 11
Synthesis of butane-1,4-diyl bis(trifluoromethanesulfonate) 15
(38) ##STR00023##
(39) A solution of 1,4-butanediol (1.000 g, 11.10 mmol) and pyridine (2.69 mL, 33.30 mmol; d 0.978) in dry dichloromethane (60 mL) was cooled to −78° C. under nitrogen and Tf.sub.2O (4.67 mL, 27.74 mmol; d 1.677) was added dropwise. The reaction mixture was warmed to 25° C. and stirred for 14 hours to give a pink solution with a white precipitate. The reaction mixture was washed with deionized water quickly (3×50 mL), dried over anhydrous Na.sub.2SO.sub.4 and filtered through Celite. The solvent was removed under vacuum to give the desired product as an oil. Pentane (30 mL) was added forming a separate phase over the oil, so it was removed under vacuum. As the system cooled while under vacuum the oil turned into an off-white solid (2.3 g, 59%). The product was stored under inert atmosphere at −30° C.
(40) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 4.59 (m, 4H), 2.02 (m, 4H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 118.57 (q, J=319.4 Hz), 75.74, 25.37. .sup.19F NMR (376 MHz, CDCl.sub.3) δ −74.62 (non-calibrated).
Example 12
Synthesis of Compound 16
(41) ##STR00024##
(42) Compound 1 (0.100 g, 0.42 mmol) was dissolved in 5 mL of acetone (solvent dried over MgSO.sub.4). Potassium carbonate (0.291 g, 2.11 mmol) was added followed by compound 13 (0.070 g, 0.21 mmol). The resulting mixture was heated at 65° C. for 14 hours. The mixture was filtered and the filter cake rinsed with dichloromethane (30 mL). The combined filtrate was concentrated under vacuum. Dichloromethane (50 mL) was added (some of the material was insoluble) and the mixture was filtered through a Celite pad. The filtrate was evaporated to dryness under vacuum (0.100 g, 94%). LC/MS confirmed the product as a sodiated adduct (m/z=537).
(43) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.38 (s, 2H), 4.47 (t, J=6.2 Hz, 4H), 3.87 (s, 6H), 2.34 (p, J=6.2 Hz, 2H).
Example 13
Synthesis of Compound 17
(44) ##STR00025##
(45) Compound 1 (0.500 g, 2.11 mmol) was dissolved in 50 mL of acetone (solvent was dried over MgSO.sub.4). Potassium carbonate (1.457 g, 10.55 mmol) was added followed by compound 15 (0.366 g, 1.03 mmol). The resulting mixture was heated at 65° C. for 14 hours. The mixture was filtered and the filter cake rinsed with dichloromethane (100 mL). The combined filtrate was concentrated under vacuum. Dichloromethane (50 mL) was added and the mixture was filtered through a Celite pad. The filtrate was evaporated to dryness under vacuum to give an orange oil (0.526 g, 48%).
(46) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.38 (s, 2H), 4.26 (m, 4H), 3.87 (s, 6H), 2.09 (m, 4H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 160.76, 157.92, 127.07, 127.01, 116.91, 108.83, 75.22, 52.11, 26.64.
Example 14
Synthesis of Compound 18
(47) ##STR00026##
(48) The synthesis was based on WO2002038572A1 for 3-bromo-4-hexyloxythiophene-2-carboxylic acid. To a solution of compound 16 (0.220 g, 0.43 mmol) in 5 mL of ethanol (containing 2 mL THF to improve solubility) was added a solution of NaOH (0.510 g, 12.84 mmol) in 3 mL of water. The mixture was stirred vigorously at 70° C. for 14 hours. After allowing the reaction mixture to cool to 25° C., it was acidified with concentration HCl to pH 1 and extracted with Et.sub.2O (2×30 mL). The organic phase was washed with water (3×50 mL), dried over Na.sub.2SO.sub.4 and the solvent was removed under reduced pressure to give a white solid (0.200 g, 96%). The solubility of the product in CDCl.sub.3 was low, however, it slowly dissolved in acetone-d.sub.6.
(49) .sup.1H NMR (400 MHz, acetone-d.sub.6) δ 7.82 (s, 2H), 4.52 (t, J=6.3 Hz, 4H), 2.32 (p, J=6.3 Hz, 2H). .sup.13C NMR (101 MHz, acetone-d.sub.6) δ 161.49, 158.42, 128.67, 118.19, 108.97, 73.44, 31.80.
Example 15
Synthesis of Compound 19
(50) ##STR00027##
(51) To a solution of compound 17 (0.510 g, 0.97 mmol) in a mixture of 10 mL of ethanol and 8 mL THF was added a solution of NaOH (1.16 g, 28.96 mmol) in 6 mL of water. The mixture was stirred vigorously at 70° C. for 14 hours. After allowing the reaction mixture to cool to 25° C., it was acidified with concentration HCl to pH=1 and extracted with Et.sub.2O (2×80 mL). The organic phase was washed with water (3×60 mL), dried over Na.sub.2SO.sub.4, filtered through Celite, and the solvent was removed under reduced pressure to give an off-white solid (0.440 g, 91%). The product was taken into the next step (decarboxylation) without further purification.
(52) .sup.1H NMR (400 MHz, acetone-d.sub.6) δ 7.81 (s, 2H), 4.31 (m, 4H), 2.07 (m, 4H).
Example 16
Synthesis of Compound 20
(53) ##STR00028##
(54) The synthesis was based on PCT Int. Appl., 2004033440. In a 40 mL scintillation vial equipped with a pressure-release septum cap compound 18 (0.200 g, 0.41 mmol) was treated with 5 mL of conc. H.sub.2SO.sub.4 at 65° C. for 5 hours. During this time a vent needle was used to relieve pressure caused by CO.sub.2 release.
(55) After allowing the reaction mixture to cool to room temperature, it was poured into 50 mL of crushed ice and extracted with dichloromethane (3×40 mL). The combined organic phase was washed successively with H.sub.2O (2×30 mL), saturated aqueous NaHCO.sub.3 (2×30 mL), and brine (2×40 mL). The organic layer was passed through a short plug of silica gel and concentrated under vacuum (0.135 g, 82%). NMR showed slightly impure product. It was taken into the next step without further purification.
(56) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.18 (d, J=3.5 Hz, 2H), 6.30 (d, J=3.5 Hz, 2H), 4.21 (t, J=6.0 Hz, 4H), 2.34 (p, J=6.0 Hz, 2H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 153.40, 122.05, 103.26, 97.66, 67.00, 28.90.
Example 17
Synthesis of Compound 21
(57) ##STR00029##
(58) In a 40 mL scintillation vial equipped with a pressure-release septum cap compound 19 (0.440 g, 0.88 mmol) was treated with 10 mL of conc. H.sub.2SO.sub.4 at 65° C. for 5 hours. During this time a vent needle was used to relieve pressure caused by CO.sub.2 release. After allowing the reaction mixture to cool to room temperature, it was poured into 100 mL of crushed ice and extracted with dichloromethane (3×60 mL). The combined organic phase was filtered through Celite and then washed successively with H.sub.2O (2×60 mL), sat. aq. NaHCO.sub.3 (2×60 mL), and brine (2×60 mL). The organic layer was passed through a short plug of silica gel (some product was lost due to a minor spill at this stage) and concentrated under vacuum (0.075 g).
(59) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.18 (d, J=3.5 Hz, 2H), 6.25 (d, J=3.5 Hz, 2H), 4.09 (m, 4H), 2.05 (m, 4H).
Example 18
Synthesis of Ligand L6
(60) ##STR00030##
(61) Compounds 5 (0.291 g, 0.60 mmol) and 20 (0.120 g, 0.30 mmol) were dissolved in 10 mL THF. Na.sub.2CO.sub.3 (0.383 g, 3.62 mmol) was dissolved in 2 mL of water and added to the THF solution forming a biphasic solution, which was then sparged with N.sub.2 for 20 min. Pd(P.sup.tBu.sub.3).sub.2 (0.015 g, 0.030 mmol) was dissolved in 0.8 mL degassed THF in a nitrogen-filled drybox, and then added to the reaction mixture via syringe. The reaction mixture was stirred vigorously at 65° C. for 14 hours. The reaction mixture was allowed to cool to 25° C. The aqueous phase was separated and discarded. The organic phase was diluted with 30 mL THF and the solution was passed through a short plug of silica gel. The filtrate was concentrated on a rotary evaporator and the residue was dissolved in 16 mL of a 1:1 (v/v) mixture of MEOH and THF, 4 drops of conc HCl were added and the solution was stirred at 25° C. for 4 hours. The solution was evaporated to dryness under vacuum and the residue was dissolved in 150 mL of EtOAc/hexane (30% v/v EtOAc), passed through a short plug of silica gel and the solvent was removed under vacuum to give a beige solid (0.220 g). Biotage purification was performed using a gradient of EtOAc in hexane as the eluent (2% to 20% EtOAc over 11 CV, then held at 20%). The desired product fractions (first main eluted material) were combined and evaporated to dryness under vacuum to give a white solid (0.140 g, 61%). Since acetone was used to rinse the Biotage tubes, residual acetone showed up in the NMR spectra, otherwise the product was pure. The solids were taken up in 5 mL of dichloromethane and solvent was removed under vacuum. High vacuum was applied on the solids overnight, but dichloromethane still showed up in the NMR. The product did not dissolve completely in CDCl.sub.3, however, it slowly dissolved in C.sub.6D.sub.6.
(62) .sup.1H NMR (400 MHz, C.sub.6D.sub.6) δ 8.15 8.09 (m, 4H), 7.27 (pd, J=7.1, 1.4 Hz, 8H), 7.21-7.17 (m, 4H), 7.07 (dd, J=2.2, 0.5 Hz, 2H), 6.82 (d, J=3.4 Hz, 2H), 6.79 (dd, J=2.3, 0.6 Hz, 2H), 6.00 (s, 2H), 5.40 (d, J=3.4 Hz, 2H), 3.52 (t, J=5.9 Hz, 4H), 2.02 (s, 6H), 1.47 (p, J=5.9 Hz, 2H). .sup.13C NMR (101 MHz, C.sub.6D.sub.6) δ 154.26, 149.15, 142.40, 132.40, 130.73, 130.16, 129.95, 126.52, 125.83, 124.61, 124.57, 124.51, 121.07, 120.58, 111.03, 99.27, 66.95, 28.94, 20.67.
Example 19
Synthesis of Ligand L7
(63) ##STR00031##
(64) Compounds 5 (0.291 g, 0.60 mmol) and 21 (0.120 g, 0.30 mmol) were dissolved in 10 mL THF. Na.sub.2CO.sub.3 (0.383 g, 3.62 mmol) was dissolved in 4 mL of water and added to the THF solution forming a biphasic solution, which was then sparged with N.sub.2 for 20 min. Pd(P.sup.tBu.sub.3).sub.2 (0.015 g, 0.030 mmol) was dissolved in 0.8 mL degassed THF in a nitrogen-filled drybox, and then added to the reaction mixture via syringe. The reaction mixture was stirred vigorously at 65° C. for 14 hours. The reaction mixture was allowed to cool to 25° C. The aqueous phase was separated and discarded. The organic phase was diluted with 30 mL THF and the solution was passed through a short plug of silica gel. The filtrate was concentrated on a rotary evaporator and the residue was dissolved in 20 mL of a 1:1 (v/v) mixture of MEOH and THF, 5 drops of concentrated HCl were added and the solution was stirred at 25° C. for 3 hours. The solution was evaporated onto silica gel for Biotage purification, which was performed using a gradient of EtOAc in hexane as the eluent (2% to 20% EtOAc over 11 CV, then held at 20%). The desired product fractions (eluted last) were combined and evaporated to dryness under vacuum to give a dark orange solid (0.072 g, 50%). LC/MS confirmed the desired product in form of a sodiated adduct (m/z=820). The product was taken up in diethyl ether (6 mL) and solvent was removed under vacuum. NMR still showed ether present.
(65) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.13 (dt, J=7.6, 0.9 Hz, 4H), 7.38 (d, J=3.4 Hz, 2H), 7.36 (d, J=1.2 Hz, 1H), 7.33 (m, 6H), 7.24 (br s, 2H), 7.22 (d, J=1.0 Hz, 1H), 7.20 (m, 6H), 6.41 (s, 2H), 6.24 (d, J=3.4 Hz, 2H), 3.95 (s, 4H), 2.35 (s, 6H), 1.84 (s, 4H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 153.60, 147.86, 141.22, 131.54, 130.51, 129.55, 129.41, 125.72, 125.33, 124.08, 123.85, 123.35, 120.24, 119.66, 110.16, 98.93, 70.44, 25.83, 20.50.
Example 20
Synthesis of Ligand L8
(66) ##STR00032##
(67) Compounds 8 (0.286 g, 0.41 mmol) and 22 (0.085 g, 0.21 mmol) were dissolved in 10 mL THF. Na.sub.2CO.sub.3 (0.262 g, 2.47 mmol) was dissolved in 4 mL of water and added to the THF solution forming a biphasic solution, which was then sparged with N.sub.2 for 15 min. Pd(P.sup.tBu.sub.3).sub.2 (0.011 g, 0.021 mmol) was dissolved in 0.8 mL degassed THF in a nitrogen-filled drybox, and then added to the reaction mixture via syringe. The reaction mixture was stirred vigorously at 65° C. for 14 hours. The reaction mixture was allowed to cool to 25° C. The aqueous phase was separated and discarded. The organic phase was concentrated on a rotary evaporator and the resulting wet residue was dissolved in 50 mL Et.sub.2O and the small amount aqueous layer was removed with a pipette. The solution was passed through a short plug of silica gel. The filtrate was concentrated on a rotary evaporator and the residue was dissolved in 20 mL of a 1:2 (v/v) mixture of MEOH and THF, 5 drops of concentrated HCl were added and the solution was stirred at 25° C. for 14 hours. The reaction mixture was evaporated to dryness, redissolved in 50 mL of THF and evaporated onto silica gel. Biotage purification was performed using a gradient of EtOAc in hexane as the eluent (2% to 18% EtOAc over 10 CV). The desired product fractions (eluted last) were combined and evaporated to dryness under vacuum (0.080 g, 32%).
(68) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.16 (d, J=1.6 Hz, 4H), 7.53 (d, J=2.4 Hz, 2H), 7.44 (d, J=1.9 Hz, 2H), 7.41 (m, 4H), 7.35 (d, J=2.4 Hz, 2H), 7.11 (d, J=8.6 Hz, 4H), 6.29 (d, J=3.4 Hz, 2H), 6.10 (s, 2H), 4.01 (m, 4H), 1.91 (m, 4H), 1.70 (s, 4H), 1.45 (s, 36H), 1.35 (s, 12H), 0.80 (s, 18H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 154.16, 147.58, 142.58, 139.66, 129.64, 128.59, 126.66, 124.76, 124.09, 123.51, 123.33, 122.70, 116.28, 109.48, 98.60, 70.22, 57.08, 38.20, 34.71, 32.44, 32.05, 31.89, 31.56, 25.89.
Example 21
Synthesis of Compound 23
(69) ##STR00033##
(70) Compounds 5 (1.599 g, 3.31 mmol) and 22 (0.800 g, 3.31 mmol) were dissolved in 20 mL of THF. Na.sub.2CO.sub.3 (2.103 g, 19.84 mmol) was dissolved in 10 mL of water and added to the THF solution forming a biphasic solution, which was then sparged with N.sub.2 for 30 min. Pd(P.sup.tBu.sub.3).sub.2 (0.068 g, 0.13 mmol) was dissolved in 1 mL of degassed THF in a nitrogen-filled drybox, then added to the reaction mixture via syringe. The reaction mixture was stirred vigorously at 65° C. overnight. The reaction mixture was allowed to cool to 25° C. and the aqueous phase was separated and discarded. The THF phase was dried over Na.sub.2SO.sub.4 and then evaporated onto silica gel for Biotage purification, which was performed using 5% (v/v) EtOAc in hexane as the eluent. The product fractions (second eluted material) were combined and the solvents were removed on a rotary evaporator. Et.sub.2O used to transfer the product from a flask into a vial was seen in the product NMR even after drying under vacuum. Yield: 0.701 g, 41%.
(71) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.15 8.08 (m, 2H), 7.46 7.41 (m, 8H), 7.38 (d, J=3.5 Hz, 1H), 7.35 7.32 (m, 1H), 7.31-7.27 (m, 2H), 7.25 7.23 (m, 1H), 4.42 4.30 (m, 1H), 2.75 2.64 (m, 1H), 2.42 (s, 3H), 1.18 0.80 (m, 8H), 0.63 (d, J=13.3 Hz, 1H).
Example 22
Synthesis of Ligand L9
(72) ##STR00034##
(73) In a nitrogen-filled glove box, compound 23 (0.400 g, 0.77 mmol) was dissolved in Et.sub.2O (5 mL) and cooled to −35° C. The pentane solution of t-BuLi (0.95 mL, 1.62 mmol; 1.70 M) was added to the cold solution of 23 and the reaction mixture was allowed to warm to 0° C. while stirring, then cooled to −35° C. for 30 min. Trimethylene di(thiotosylate) (0.145 g, 0.35 mmol) was added to the solution, which was then allowed to warm to 25° C. and stirred for 14 hours. The reaction mixture was washed with 20 mL saturated NH.sub.4Cl (aq) and extracted into EtOAc (30 mL). Some white solids were present in the biphasic mixture, which were removed by filtration. The organic phase was dried over Na.sub.2SO.sub.4 and passed through a plug of silica gel. Solvent was removed under vacuum. The crude THP-protected product was subjected to Biotage purification (EtOAc/hexane gradient: 1% to 10% EtOAc over 11.5 CV, then held at 10%).
(74) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.14 (dt, J=7.7, 0.9 Hz, 4H), 7.41-7.36 (m, 4H), 7.35 (d, J=3.3 Hz, 2H), 7.31-7.27 (m, 4H), 7.24-7.23 (m, 2H), 7.21-7.14 (m, 4H), 7.05 (d, J=3.3 Hz, 2H), 5.09 (s, 2H), 2.79 (t, J=7.0 Hz, 4H), 2.34 (s, 6H), 1.80 (p, J=7.0 Hz, 2H).
(75) The purified protected product was dissolved in 16 mL of a 1:1 (v/v) mixture of THF and MEOH, concentration HCl (3 drops from a Pasteur pipette) was added and the solution was stirred at 25° C. for 2 hours. Solvent removal under vacuum gave a white residue, which was dissolved in 15 mL Et.sub.2O, passed through a plug of silica gel, and evaporated to dryness under vacuum. The product was dried overnight under high vacuum (0.182 g, 64%).
(76) .sup.1H NMR (400 MHz, C.sub.6D.sub.6) δ 8.05 (dt, J=7.7, 1.0 Hz, 4H), 7.37-7.29 (m, 4H), 7.29-7.19 (m, 8H), 7.05 (dd, J=2.3, 0.6 Hz, 2H), 6.87 (d, J=3.3 Hz, 2H), 6.71 (dd, J=2.2, 0.7 Hz, 2H), 6.61 (d, J=3.3 Hz, 2H), 4.93 (s, 2H), 2.47 (t, J=7.1 Hz, 4H), 1.98 (s, 6H), 1.55 (p, J=7.1 Hz, 2H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 147.80, 140.97, 138.39, 131.99, 131.66, 130.30, 129.27, 126.09, 125.41, 124.60, 124.23, 124.02, 123.64, 120.35, 120.16, 110.20, 33.56, 28.25, 20.49.
Example 23
Synthesis of Ligand L10
(77) ##STR00035##
(78) In a nitrogen-filled glove box, compound 23 (0.293 g, 0.57 mmol) was dissolved in Et.sub.2O (5 mL) and cooled to −35° C. The pentane solution of t-BuLi (0.70 mL, 1.19 mmol; 1.70 M) was added to the cold solution of 23 and the reaction mixture was allowed to warm to 0° C. while stirring, then cooled to −35° C. for 30 min. Tetramethylene di(thiotosylate) (0.117 g, 0.27 mmol) was added to the solution, which was then allowed to warm to 25° C. and stirred for 14 hours. The reaction mixture was washed with 20 mL saturated NH.sub.4Cl (aq) and extracted into EtOAc (30 mL). The organic phase was passed through a plug of silica gel and the solvent was removed under vacuum. The crude THP-protected product was dissolved in 20 mL of a 1:1 (v/v) mixture of THF and MEOH, conc HCl (5 drops from a Pasteur pipette) was added and the solution was stirred at 25° C. for 3 hours. Solvent removal under vacuum gave a white residue, which was dissolved in 100 mL of a 1:1 (v/v) mixture of EtOAc and hexane, passed through a plug of silica gel, and evaporated to dryness under vacuum to afford L10 as a beige solid in quantitative yield.
(79) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.14 (d, J=7.7 Hz, 4H), 7.44-7.37 (m, 4H), 7.35 (d, J=3.3 Hz, 2H), 7.31-7.29 (m, 2H), 7.29-7.26 (m, 4H), 7.22-7.17 (m, 4H), 7.06 (d, J=3.3 Hz, 2H), 5.18 (s, 2H), 2.75-2.64 (m, 4H), 2.35 (s, 6H), 1.69-1.60 (m, 4H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 147.81, 141.00, 138.21, 131.95, 130.28, 129.29, 126.04, 125.43, 124.30, 124.10, 124.00, 123.61, 120.44, 120.33, 120.11, 110.22, 34.22, 27.84, 20.49.
Example 24
Synthesis of Compound 25
(80) ##STR00036##
(81) A 50 mL nitrogen-purged round bottom flask was charged with Turbo Grignard solution (1.70 mL, 2.18 mmol; 1.30 M in THF) and cooled to −40° C. in an acetonitrile dry ice bath. To this cold solution was added 3,4-dibromofuran (0.447 g, 1.98 mmol) dissolved in THF (1 mL) dropwise to prevent the reaction from undergoing an exotherm. The reaction mixture was allowed to warm to 25° C. The reaction mixture was then cooled to 0° C. and trimethylene di(thiotosylate) (370 mg, 0.89 mmol) dissolved in THF (2 mL) was added dropwise at 0° C. The reaction mixture was then allowed to warm to ambient temperature overnight. A significant amount of precipitate had formed. Saturated aqueous ammonium chloride solution (15 mL) was added to the reaction mixture and the resultant was extracted into ethyl acetate (20 mL). The organics were washed with saturated aqueous ammonium chloride solution (2×15 mL), dried over sodium sulfate, filtered and absorbed onto Celite under vacuum. This material was purified via flash column chromatography (0 to 20% EtOAc in hexanes) yielding the product as a colorless oil (0.145 g, 41%).
(82) .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.48 (dd, J=1.7, 0.4 Hz, 2H), 7.42 (dd, J=1.7, 0.4 Hz, 2H), 2.81 (t, J=7.1 Hz, 4H), 1.78 (p, J=7.1 Hz, 2H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ 145.68, 142.00, 117.46, 106.23, 33.22, 28.44.
Example 25
Synthesis of Ligand L11
(83) ##STR00037##
(84) In a nitrogen-filled drybox a vial containing a stirbar was charged with compound 5 (0.237 g, 0.49 mmol), compound 25 (0.065 g, 0.16 mmol) and Cs.sub.2CO.sub.3 (0.319 g, 0.98 mmol). Deoxygenated dioxane (2 mL) and PdCl (crotyl)(P.sup.tBu.sub.3) (0.0033 g, 0.01 mmol) were added and the vial was sealed with a septum cap and removed from the drybox. Deoxygenated, deionized water (0.6 mL) was added via syringe. The reaction mixture was heated to 80° C. and stirred vigorously for 14 hours. The reaction mixture was allowed to cool to 25° C. and the aqueous phase was separated and discarded. The organic phase was evaporated to dryness under vacuum. The residue was deprotected in a mixture of CHCl.sub.3 and MEOH (6:1 v/v) using 10 mol % of pyridinium p-toluenesulfonate at 60° C. over 2.5 hours. The solvents were removed under vacuum and the residue was taken up in Et.sub.2O (ca 5 mL), passed through a plug of silica gel and evaporated to dryness under vacuum (0.070 g, 56%).
(85) .sup.1H NMR (500 MHz, CDCl.sub.3) δ 8.14 (dt, J=7.7, 0.9 Hz, 1H), 7.73 (d, J=1.7 Hz, 0H), 7.54 (d, J=1.9 Hz, 1H), 7.46 (d, J=1.7 Hz, 0H), 7.38 (ddd, J=8.2, 7.2, 1.0 Hz, 1H), 7.28 (ddd, J=7.9, 7.4, 0.8 Hz, 1H), 7.21 (dt, J=7.9, 0.8 Hz, 1H), 7.14 (d, J=1.8 Hz, 0H), 5.36 (s, 0H), 5.30 (s, 0H), 2.66 (t, J=7.0 Hz, 1H), 2.35 (s, 1H), 1.76 (p, J=7.0 Hz, 1H). .sup.13C NMR (126 MHz, CDCl.sub.3) δ 147.87, 145.19, 142.85, 140.94, 131.33, 130.48, 128.84, 126.17, 124.05, 123.68, 122.85, 120.39, 120.29, 119.75, 115.85, 110.12, 109.70, 33.57, 28.29, 20.55.
Example 26
Discrete Procatalysts 21-30
(86) In a nitrogen-filled drybox ZrCl.sub.4 or HfCl.sub.4 (0.05 mmol) was suspended in 2 mL of dry, degassed toluene and MeMgBr (0.140 mL, 0.21 mmol, 4.1 equiv; 1.5 M solution in Et.sub.2O) was added to the suspension at 25° C. Within 30 seconds the ligand solution (0.05 mmol) in 2 mL toluene was added and the mixture stirred for 2 hours at 25° C. (Ligands L6-L10 were used in the synthesis of these procatalysts.) The reaction mixture was evaporated to dryness under vacuum and toluene (5 mL) was added. The mixture was filtered (0.45 μm) and the filtrate was evaporated to dryness under vacuum. The toluene addition, filtration and solvent removal under vacuum was repeated one more time to afford the product. Individual yields and NMR data are provided in Table 1.
(87) TABLE-US-00001 TABLE 1 Yield and NMR data for Procatalysts 21-30 Yield Procatalyst (%) .sup.1H NMR data
Example 27
In Situ Procatalysts 1-20, 31, and 32
(88) In a nitrogen-filled drybox, appropriate volumes of 0.005 M solutions of ligands L1-L5 and L11 (0.1 μmol for procatalysts 1-10, 31, and 32; 0.2 μmol for procatalysts 11-20) were mixed with 0.010 M HfBn.sub.4 or ZrBn.sub.4 solutions (0.1 μmol) at 25° C., and injected into the PPR at the appropriate time from one-half hour to 3 hours later.
(89) The polymers resulting from Procatalysts 1-20 and 31-32 were prepared according to the PPR screening process, described above, using the following conditions: 120° C., 150 psig, 838 μL 1-octene, 500 nmol MMAO-3A, 100 nmol catalyst, 150 nmol bis(hydrogenated tallow alkyl)methylammonium tetrakis(pentafluorophenyl)borate, 5 mL total liquid volume. All polymerizations were performed with bis(hydrogenated tallow alkyl)methylammonium tetrakis(pentafluorophenyl)borate as the activator and MMAO as the scavenger. The data for the polymers resulting from Procatalysts 1-20 are reported in Table 2. The data for the polymers resulting from Procatalysts 31 and 32 are reported in Table 3.
(90) Catalyst activity (in terms of quench time and polymer yield) and resulting polymer characteristics were assessed for Procatalysts 1-20 and 31-32. The polymerizations were carried out in a parallel polymerization reactor (PPR).
(91) The selected data in Table 2 was obtained at 120° C. polymerization temperature. The activator was [HNMe(C.sub.18H.sub.37).sub.2][B(C.sub.6F.sub.5).sub.4] in an amount of 0.15 μmol. The quench times indicated the time required to reach 50 psi ethylene uptake. The quench times were measured based on the time at which the target uptake occurred or after 1800 seconds the polymerizations were quenched with CO, which ever occurred first.
(92) TABLE-US-00002 TABLE 2 Parallel Polymerization Reactor Data Procatalyst Quench Yield M.sub.w PDI Mol % No μmol time (s) (g) M.sub.n (g/mol) M.sub.n/M.sub.w Octene* 1 0.10 67 0.194 36,274 145,166 4.00 7.40 1 0.10 64 0.196 6,226 30,321 4.87 9.60 2 0.10 1,800 0.090 14,264 232,239 16.28 8.60 2 0.10 1,587 0.094 15,233 283,482 18.61 7.80 3 0.10 202 0.114 10,152 32,416 3.19 9.90 3 0.10 196 0.120 23,117 150,909 6.53 7.00 4 0.10 1,801 0.025 10,173 417,028 40.99 5.70 4 0.10 1,801 0.023 10,200 401,730 39.39 5.40 5 0.10 255 0.103 5,095 76,578 15.03 3.60 5 0.10 194 0.116 7,636 71,782 9.40 3.10 6 0.10 1,374 0.079 11,147 207,518 18.62 3.30 6 0.10 687 0.085 12,922 207,910 16.09 3.20 7 0.10 58 0.210 7,299 25,331 3.47 10.20 7 0.10 58 0.213 6,927 26,955 3.89 9.80 8 0.10 303 0.121 22,305 160,128 7.18 10.40 8 0.10 326 0.123 16,365 170,958 10.45 9.30 9 0.10 491 0.101 3,117 72,809 23.35 5.70 9 0.10 321 0.122 3,234 42,374 13.10 5.60 10 0.10 1,801 0.090 7,587 196,577 25.91 6.30 10 0.10 774 0.091 22,281 159,591 7.16 6.20 11 0.10 35 0.232 10,958 29,843 2.72 10.60 11 0.10 33 0.249 9,913 31,283 3.16 11.30 12 0.10 344 0.112 48,683 199,527 4.10 8.80 12 0.10 300 0.129 41,060 204,086 4.97 8.40 13 0.10 78 0.168 35,394 104,751 2.96 9.20 13 0.10 76 0.170 27,795 113,902 4.10 9.40 14 0.10 1,802 0.033 21,632 191,160 8.84 6.00 14 0.10 1,800 0.029 16,820 200,676 11.93 5.90 15 0.10 51 0.193 7,271 30,437 4.19 4.20 15 0.10 47 0.207 5,108 28,982 5.67 4.40 16 0.10 113 0.168 3,453 58,299 16.88 4.70 16 0.10 117 0.166 4,549 66,877 14.70 4.30 17 0.10 33 0.269 7,253 21,264 2.93 13.30 17 0.10 30 0.269 7,827 21,297 2.72 12.90 18 0.10 214 0.202 49,412 169,921 3.44 9.50 18 0.10 191 0.204 43,118 170,332 3.95 9.30 19 0.10 29 0.244 7,615 20,598 2.70 8.00 19 0.10 26 0.258 9,606 21,882 2.28 6.90 20 0.10 158 0.122 47,236 154,682 3.27 6.30 20 0.10 127 0.120 33,375 148,658 4.45 6.30 *Mol % Octene or C8/olefin is defined as: (moles 1-octene/(total moles 1-octene and ethylene)) × 100.
(93) Polymers prepared in polymerization systems including Procatalysts 1-20 yielded polymers with moderate octene incorporation; moderate octene incorporation is between 3 mol % and 15 mol % incorporation. Zirconium-containing Procatalyst 1, 3, 5, 7, 9, 11, 13, 15, 17, and 19 generally had higher efficiencies than that of hafnium-based Procatalyst 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20, as indicated by the shorter quench times and higher polymer yields. Hafnium-based procatalysts generally gave polymer with higher M.sub.w than corresponding zirconium analogues.
(94) The data in Table 3 was obtained at 120° C. or 150° C. polymerization temperature with varying amount of an activator (act) and procatalyst. The activator used to obtain the data in Table 3 was [HNMe(C.sub.18H.sub.37).sub.2][B(C.sub.6F.sub.5).sub.4]. The quench times indicated the time required to reach the target ethylene uptake (50 psi for 120° C. runs and 75 psi for 150° C. runs) and were measured as described above.
(95) TABLE-US-00003 TABLE 3 Parallel Polymerization Reactor Data - Various Amounts of Activators Run Quench Procatalyst Temp Act time Yield M.sub.w PDI Mol % No μmol (° C.) (μmol) (s) (g) M.sub.n (g/mol) M.sub.n/M.sub.w Octene* 31 0.03 120 0.05 25 0.595 2,042 6,819 3.34 29.30 31 0.02 120 0.03 32 0.541 1,950 6,546 3.36 28.90 31 0.01 120 0.02 26 0.599 1,986 6,902 3.48 25.60 31 0.01 120 0.01 31 0.470 2,610 6,919 2.65 27.60 31 0.10 120 0.15 12 0.750 770 1,698 2.21 27.50 31 0.10 120 0.15 12 0.570 686 1,529 2.23 34.60 31 0.10 120 0.15 13 0.631 699 1,444 2.07 30.40 31 0.04 150 0.05 17 0.486 302 603 2.00 25.80 31 0.03 150 0.04 16 0.489 674 1,549 2.30 24.50 31 0.02 150 0.03 16 0.479 696 1,381 1.98 25.50 31 0.01 150 0.02 19 0.487 658 1,206 1.83 25.10 31 0.15 150 0.22 17 0.787 763 1,702 2.23 26.00 31 0.15 150 0.22 11 0.615 686 1,467 2.14 30.20 31 0.15 150 0.22 13 0.636 666 1,414 2.12 30.70 31 0.15 150 0.22 16 0.645 672 1,438 2.14 27.00 32 0.03 120 0.05 12 0.465 661 1,369 2.07 31.10 32 0.02 120 0.03 15 0.566 704 1,343 1.91 26.10 32 0.01 120 0.02 15 0.450 688 1,679 2.44 28.90 32 0.01 120 0.01 14 0.457 694 1,621 2.34 27.50 32 0.10 120 0.15 14 0.669 2,782 8,397 3.02 37.30 32 0.10 120 0.15 13 0.638 2,879 7,861 2.73 36.40 32 0.10 120 0.15 13 0.718 3,021 9,131 3.02 30.50 32 0.10 120 0.15 15 0.656 2,562 7,915 3.09 31.90 32 0.04 150 0.05 22 0.607 2,005 5,615 2.80 28.20 32 0.03 150 0.04 23 0.539 2,234 6,183 2.77 23.60 32 0.02 150 0.03 25 0.571 4,086 12,531 3.07 27.80 32 0.01 150 0.02 28 0.526 7,920 25,144 3.17 23.80 32 0.15 150 0.22 19 0.766 1,933 6,092 3.15 31.30 32 0.15 150 0.22 15 0.721 2,060 6,254 3.04 30.00 32 0.15 150 0.22 14 0.739 2,042 6,760 3.31 28.00 32 0.15 150 0.22 18 0.673 1,805 5,848 3.24 30.40 *Mol % Octene or C8/olefin is defined as: (moles 1-octene/(total moles 1-octene and ethylene)) × 100.
(96) Polymers prepared in polymerization systems including Procatalysts 31 and 32 exhibited very high efficiencies, as indicated by the shorter quench times and higher polymer yields. These procatalysts also produced polymers with low M.sub.w and high octene incorporation; high octene incorporation is at least 15 mol % incorporation.
(97) The data in Table 4 was obtained from the batch-reactor polymerizations at a 120° C. polymerization temperature with 1.2 eq. of [HNMe(C.sub.18H.sub.37).sub.2][B(C.sub.6F.sub.5).sub.4] as the activator. The run time was 10 minutes, and the scavenger was MMAO-3A.
(98) TABLE-US-00004 TABLE 4 Batch Reactor Ethylene and 1-Octene Copolymerization Data Efficiency M.sub.w 1-Octene Procatalyst (g poly/g metal) (g/mol) PDI mol % Procatalyst 21 6,577,500 29,500 1.9 18.2 Procatalyst 22 2,393,800 236,300 2.6 23.1 Procatalyst 23 6,961,200 31,000 2.1 17.5 Procatalyst 24 448,200 289,700 2.3 19.9 Procatalyst 25 2,718,700 25,100 1.9 15.9 Procatalyst 26 986,000 214,900 2.0 22.1 Procatalyst 27 7,673,800 1,500 3.5 13.0 Procatalyst 28 1,618,500 3,400 1.9 21.4 Procatalyst 29 3,672,400 5,500 2.3 16.3 Procatalyst 30 896,400 36,300 3.3 17.9 solvent: 1153 g of Isopar E, monomer: 280 psi of ethylene, comonomer: 568 g of 1-octene.
(99) Polymers prepared in the batch reactor as a result of Procatalysts 21 to 23 and 25 to 30 exhibited high efficiencies, all greater than 800,000 grams polymer per gram metal. Procatalysts 21 to 26 and 28 to 30 produced polymers having high mol % of octene incorporation (greater than 15 mol % incorporation). Procatalyst 27 produced polymer having moderate mol % of octene incorporation (greater than 10 mol % incorporation). The polymers produced from zirconium-based Procatalysts 21, 23, 25, and 27 to 29 exhibited higher efficiencies, but lower M.sub.w compared to polymers produced from corresponding hafnium-based Procatalysts 22, 24, 26, 28, and 30, respectively. Procatalysts 22, 24, and 26 yielded polymers with comparatively high molecular weights (all greater than 200,000 g/mol) and high octene incorporation of greater than 15 mol %, but had a lesser efficiency compared to the efficiencies of Procatalysts 21, 23, 25, and 27-30. Thioether-bridged Procatalysts 27 and 29 gave polymers with significantly lower M.sub.w compared to analogous ether-bridged Procatalysts 21 and 23. Similarly, thioether-bridged Procatalysts 28 and 30 gave polymers with significantly lower M.sub.w compared to analogous ether-bridged Procatalysts 22 and 24.
MEASUREMENT STANDARDS
(100) Density
(101) Samples that were measured for density were prepared according to ASTM D-1928, which is incorporated herein by reference in its entirety. Measurements were made within one hour of sample pressing using ASTM D-792, Method B, which is incorporated herein by reference in its entirety.
(102) Octene Content
(103) The mole % (mol %) of 1-octene within each sample was determined by taking a ratio of the CH.sub.3 area (1382.7-1373.5 wavenumbers) to the CH.sub.2 area (1525-1400 wavenumbers) and normalizing to a standard curve generated through NMR analysis of poly(ethylene-co-1-octene) standards.
(104) Gel Permeation Chromatography (GPC)
(105) The ethylene/alpha-olefin interpolymers were tested for their properties via GPC, according to the following procedure. The GPC system consists of a Waters (Milford, Mass.) 150° C. high temperature chromatograph (other suitable high temperatures GPC instruments include Polymer Laboratories (Shropshire, UK) Model 210 and Model 220) equipped with an on-board differential refractometer (RI). Additional detectors could include an IR4 infra-red detector from Polymer ChAR (Valencia, Spain), Precision Detectors (Amherst, Mass.) 2-angle laser light scattering detector Model 2040, and a Viscotek (Houston, Tex.) 150R 4-capillary solution viscometer. A GPC with the last two independent detectors and at least one of the first detectors was sometimes referred to as “3D-GPC”, while the term “GPC” alone generally refered to conventional GPC. Depending on the sample, either the 15-degree angle or the 90-degree angle of the light scattering detector was used for calculation purposes.
(106) Data collection was performed using Viscotek TriSEC software, Version 3, and a 4-channel Viscotek Data Manager DM400. The system was equipped with an on-line solvent degassing device from Polymer Laboratories (Shropshire, UK). Suitable high temperature GPC columns could be used such as four 30 cm long Shodex HT803 13 micron columns or four 30 cm Polymer Labs columns of 20-micron mixed-pore-size packing (MixA LS, Polymer Labs). The sample carousel compartment was operated at 140° C. and the column compartment was operated at 150° C. The samples were prepared at a concentration of 0.1 grams of polymer in 50 milliliters of solvent. The chromatographic solvent and the sample preparation solvent contain 200 ppm of butylated hydroxytoluene (BHT). Both solvents were sparged with nitrogen. The polyethylene samples were gently stirred at 160° C. for four hours (4 h). The injection volume was 200 microliters (IL). The flow rate through the GPC was set at 1 mL/minute.
(107) The GPC column set was calibrated before running the Examples by running twenty-one narrow molecular weight distribution polystyrene standards. The molecular weight (Mw) of the standards ranges from 580 to 8,400,000 grams per mole (g/mol), and the standards were contained in 6 “cocktail” mixtures. Each standard mixture had at least a decade of separation between individual molecular weights. The standard mixtures were purchased from Polymer Laboratories (Shropshire, UK). The polystyrene standards were prepared at 0.025 g in 50 mL of solvent for molecular weights equal to or greater than 1,000,000 g/mol and 0.05 g in 50 mL of solvent for molecular weights less than 1,000,000 g/mol. The polystyrene standards were dissolved at 80° C. with gentle agitation for 30 minutes. The narrow standards mixtures were run first and in order of decreasing highest molecular weight (Mw) component to minimize degradation. The polystyrene standard peak molecular weights were converted to polyethylene Mw using the Mark-Houwink constants. Upon obtaining the constants, the two values were used to construct two linear reference conventional calibrations for polyethylene molecular weight and polyethylene intrinsic viscosity as a function of elution column.
(108) Measurement for Efficiency
(109) The catalytic efficiency was measured in terms of amount of polymer produced relative to the amount catalyst used in solution polymerization process, wherein the polymerization temperature was at least 130° C.
(110) It should be apparent to those skilled in the art that various modifications can be made to the described embodiments without departing from the spirit and scope of the claimed subject matter. Thus, it is intended that the specification cover modifications and variations of the described embodiments provided such modification and variations come within the scope of the appended claims and their equivalences.