U.S. patent application number 09/912926 was filed with the patent office on 2002-04-18 for synthesis and isomerization of 1,2-bis (indenyl) ethanes.
This patent application is currently assigned to Boulder Scientific Company. Invention is credited to Gately, Daniel A..
Application Number | 20020045789 09/912926 |
Document ID | / |
Family ID | 22881569 |
Filed Date | 2002-04-18 |
United States Patent
Application |
20020045789 |
Kind Code |
A1 |
Gately, Daniel A. |
April 18, 2002 |
Synthesis and isomerization of 1,2-bis (indenyl) ethanes
Abstract
A method for producing 1,2-bis(indenyl)ethanes in good yield is
described. An agent and its application for isomerizing kinetic EBI
to thermodynamic EBI and for isomerizing meso TMS-EBI to rac
TMS-EBI are exemplified.
Inventors: |
Gately, Daniel A.;
(Berthoud, CO) |
Correspondence
Address: |
EDWARD S. IRONS
3945 - 52ND STREET, N.W.
WASHINGTON
DC
20016
US
|
Assignee: |
Boulder Scientific Company
|
Family ID: |
22881569 |
Appl. No.: |
09/912926 |
Filed: |
July 25, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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09912926 |
Jul 25, 2001 |
|
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09234481 |
Jan 21, 1999 |
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Current U.S.
Class: |
585/477 |
Current CPC
Class: |
C07C 5/22 20130101; C07C
2602/08 20170501; C07F 7/083 20130101; C07C 31/30 20130101; C07F
17/00 20130101; C07C 13/465 20130101 |
Class at
Publication: |
585/477 |
International
Class: |
C07C 005/22 |
Claims
I claim:
1. A method for isomerization of a compound of Formula I 10wherein
said Formula I compound is unsubstituted or identically substituted
at one or more of the available ring positions 2 to 7 and 2' to 7',
which comprises treating said Formula I compound with an
isomerization agent comprising a solution of an alkali metal
alkoxide having the formula MOR, wherein M is an alkali metal and R
is a hydrocarbyl group having one to ten carbon atoms in a
non-interfering solvent and wherein said solution contains from
about 10 mol percent to about 20 mol percent of said alkali metal
alkoxide.
2. The claim 1 method, wherein said isomerization is accomplished
at a temperature of 10.degree. C. to 25.degree. C.
3. The claim 1 method wherein said Formula I compound is kinetic
EBI and wherein said isomerization converts said kinetic EBI to a
thermodynamic EBI.
4. The claim 1 method wherein said Formula I compound is kinetic
EBI and wherein said isomerization converts said kinetic EBI to
thermodynamic EBI.
5. A method for converting a kinetic EBI to thermodynamic EBI which
comprises: (i) providing a solution of a kinetic EBI in a
hydrocarbon solvent first solution; (ii) combining said first
solution with a second solution of potassium tertiary butoxide in a
non-interfering ether solvent, wherein a third solution of kinetic
EBI in a combined hydrocarbon and a non-interfering solvent is
produced; (iii) refluxing said step (ii) third solution, wherein at
least a portion of said kinetic EBI contained therein is converted
to thermodynamic EBI.
6. The claim 5 method, wherein said non-interfering ether solvent
is tetrahydrofuran.
7. The claim 5 method further comprising steps (iv) and (v): (iv)
exchanging said combined hydrocarbon and non-interfering ether
solvent for a hydrocarbon solvent wherein a fourth solution of said
kinetic EBI in said hydrocarbon solvent is produced; and (v)
separating said kinetic EBI from said step (iv) fourth
solution.
8. The claim 5 method, wherein said hydrocarbon solvent is
hexane.
9. A method which comprises: (i) providing a solution of kinetic
EBI in a non-interfering solvent, (ii) converting said step (i)
solution to a mixture containing solid kinetic EBI in a mother
liquor solution of kinetic EBI, (iii) separating said solid kinetic
EBI from said mother liquor solution of EBI, and (iv) treating said
mother liquor solution of EBI with an isomerization agent wherein
at least a portion of said kinetic EBI in solution in said mother
liquor is converted to thermodynamic EBI.
10. The claim 9 method further comprising a step (v) isolating said
thermodynamic EBI produced in step (iv).
11. The claim 9 method, wherein said isolating step (v) is
accomplished by subjecting said mother liquor to conditions
effective to cause solid thermodynamic EBI to precipitate and
separating said precipitated solid thermodynamic EBI.
12. The claim 1 method wherein said Formula I compound has
substituents at the 3 and 3'ring positions with consequent meso and
rac isomers and wherein said isomerization converts a Formula I
meso isomer to a meso:rac mixture.
13. A method for isomerizing meso EBI to racemic EBI which
comprises treating said meso EBI with an isomerization agent
comprising a solution of an alkali metal alkoxide having the
formula MOR, wherein M is an alkali metal and R is a hydrocarbyl
group having one to ten carbon atoms in a non-interfering solvent
and wherein said solution contains from about 10 mol percent to
about 20 mol percent of said alkali metal alkoxide.
14. A method which comprises: (i) providing meso
bis-1,2(3-trimethylsilyl indenyl-1) ethane; (ii) treating said step
(i) meso bis-1,2-(3-trimethylsilyl indenyl-l)ethane with potassium
tertiary butoxide, wherein the product of said treating step (ii)
comprises a mixture of said meso bis-1,2-(3-trimethylsilyl
indenyl-1)ethane and rac bis-1,2-(3-trimethylsilyl indenyl-1)
ethane.
15. The claim 14 method, wherein said treating step (ii) is
accomplished at a temperature of from about 10.degree. C. to about
25.degree. C. with a 10 mol percent to 20 mol percent selection of
said potassium tertiary butoxide in a non-interfering ether
solvent.
16. The claim 14 method wherein said non-interfering solvent is
tetrahydrofuran.
17. The claim 14 method where said step (i)
bis-1,2-(3-trimethylsilyl indenyl-1)ethane is substantially free of
the corresponding rac isomer and wherein the product of said
treating step (ii) contains substantially equal amounts of meso and
rac bis-1,2-(3-trimethylsilyl indenyl-l)ethane.
18. A method which comprises: (i) reacting lithium indenide with
1,2-dibromoethane in a non-interfering, non-hydrocarbon solvent,
wherein a first reaction mixture containing kinetic EBI in solution
is produced; (ii) exchanging said solvent of said first reaction
mixture with a hydrocarbon solvent, wherein a first hydrocarbon
solvent solution of kinetic EBI is produced; (iii) reducing the
temperature of said step (ii) solution to a level effective to
cause precipitation of solid kinetic EBI from a second hydrocarbon
mother liquor solution of kinetic EBI; (iv) separating said solid
kinetic EBI from said second mother liquor solution thereof; (v)
treating said mother liquor solution of kinetic
1,2-bisbindenyl(l))ethane with an isomerization agent comprising a
solution of an alkali metal alkoxide having the formula MOR,
wherein M is an alkali metal and R is a hydrocarbyl group having
one to ten carbon atoms in a non-interfering solvent and wherein
said solution contains from about 10 mol percent to about 20 mol
percent of said alkali metal alkoxide, wherein a mother liquor
solution of thermodynamic EBI is produced; and (vi) subjecting said
step (v) mother liquor solution to conditions effective to cause
precipitation of said thermodynamic EBI therefrom.
19. The claim 18 method wherein (i) said step (i) solvent comprises
tetrahydrofuran, and (ii) said hydrocarbon solvent is a hexane.
20. The claim 18 or claim 19 method further comprising a step (vii)
separating said step (vi) precipitated thermodynamic EBI.
21. The claim 18 or claim 19 method further comprising a step
(viii) combining said solid kinetic EBI separated in step (iv) with
said solid thermodynamic EBI separated in step (vii).
22. The claim 18 or claim 19 method further comprising a step (ix)
converting said step (viii) combined solid kinetic EBI and solid
thermodynamic EBI to a Group IV metal metallocene olefin
polymerization catalyst.
23. A method for synthesizing a 1,2-bis(indenyl)ethane which
comprises: (i) reacting indene with an alkali metal alkyl in a
non-interfering solvent at a temperature below 0.degree. C.,
wherein a first reaction mixture containing an alkali metal
indenide and said solvent is produced; (ii) raising the temperature
of said first reaction mixture from 20.degree. C. to 40.degree. C.;
(iii) combining said step (ii) first reaction mixture at 20.degree.
C. to 40.degree. C. with dibromoethane, wherein a second reaction
mixture is produced and thereafter (iv) adding tetrahydrofuran to
said second reaction mixture wherein a third reaction mixture
containing EBI is produced; (v) adding water to said third reaction
mixture, wherein an organic phase and an aqueous phase form; (vi)
separating said step (v) aqueous and organic phases; (vii)
exchanging the solvent of said organic phase separated in step (v)
with a hydrocarbon solvent from which kinetic EBI is separated.
24. The claim 23 method, wherein said step (i) non-interfering
solvent is tetrahydrofuran.
25. A method for synthesizing EBI which comprises: (i) reacting
n-butyl lithium with indene at a temperature of 40.degree. C. to
50.degree. C. wherein a reaction mixture containing lithium
indenide is produced; (ii) cooling said step (i) reaction mixture
to -10.degree. C. to -30.degree. C.; (iii) adding dibromomethane to
provide a second reaction mixture; (iv) adding tetrahydrofuran to
said second reaction mixture at a temperature of -15.degree. C. to
-20.degree. C. with agitation, wherein a third reaction mixture
containing solid EBI a mother liquor is produced; and (v)
separating solid EBI from said third reaction mixture, wherein a
mother liquor solution of kinetic EBI is produced.
26. A method which comprises: (i) reacting lithium indenide with
1,2-dibromoethane in a diethyl ether and tetrahydrofuran solvent
mixture, wherein a first reaction mixture containing kinetic EBI in
solution in said solvent mixture is produced; (ii) exchanging said
solvent mixture of said first reaction mixture with a hexane
solvent, wherein a first hexane solution of kinetic EBI is
produced; (iii) reducing the temperature of said step (ii) solution
to a level effective to cause precipitation of solid kinetic EBI
from a second hexane solution of said kinetic EBI; (iv) separating
said solid kinetic EBI from said second hexane solution thereof;
(v) treating said second hexane solution of kinetic EBI with
potassium tertiary butoxide, wherein a hexane solution of the
thermodynamic EBI is produced; and (vi) subjecting said step (v)
hexane solution to conditions effective to cause crystallization of
said thermodynamic EBI therefrom.
27. The claim 26 method further comprising a step (vii) separating
said step (vi) crystallized thermodynamic EBI.
28. The claim 26 or claim 27 method further comprising a step
(viii) combining said kinetic EBI separated in step (iv) with the
thermodynamic EBI separated in step (vii).
29. The claim 26 or claim 27 method further comprising a step (ix)
converting said step (viii) combined kinetic EBI and thermodynamic
EBI to a Group IV metal metallocene olefin polymerization
catalyst.
30. A composition of matter having the formula A.sub.2M).sub.2
wherein A is a mixture of kinetic and thermodynamic EBI, M is
zirconium, titanium or hafnium, and X is a halogen.
31. The claim 30 compound wherein M is zirconium and X is chlorine.
Description
[0001] This application is a division of U.S application Ser. No.
09/234,481 filed Jan. 21, 1999.
FIELD OF INVENTION
[0002] This invention relates to the synthesis and isomerization of
1,2-bis(indenyl)ethanes (EBI). BACKGROUND OF THE INVENTION
[0003] In this specification, the expression 1,2-bis(indenyl)ethane
or EBI means collectively all isomers of Formula I: 1
[0004] in which the symbol "(" indicates a 1,2-bis(indenyl-1)ethane
which has a 1,2, 1,2'double bond (thermodynamic EBI, BRN No.
3055002, CAS RN No. 18657-57-3) or a 2,3 2', 3'double bond (kinetic
EBI, BRN No. 3083835, CAS RN Nos. 15721-07-0, 18686-04-9,
18686-05-0). The two unnumbered fusion C atoms are asymmetric. The
1,1.degree. C. atoms are asymmetric in kinetic EBI compounds. The
3,3.degree. C. atoms are asymmetric when substituted.
[0005] Each of the ring substituents may be hydrogen or any one to
ten carbon atom hydrocarbyl group. Each ring substituent may be the
same as or different from any other ring substituent. One to ten
carbon atom alkyl groups are preferred. 2,2'methyl and 4,7,
4'7'dimethyl EBIs are representative.
[0006] The EBI 3,3'substituents may be any hydrocarbyl group or
hydrocarbyl silyl group, preferably having one to ten carbon atoms.
Useful alkyl silyl 3,3'substituents have the formula (R).sub.3-Si,
in which R is a one to ten carbon atom hydrocarbyl group, typically
an alkyl group. The methyl group is preferred. Each R may be the
same as or different from each of the other two R groups. Chiral
TMS-EBI is preferred.
[0007] Meso and rac (racemic) forms of kinetic EBI and thermal
isomerization of kinetic to thermodynamic EBI are known phenomena.
Marechal, et al, Bulletin de la Societe Chimicue de France (1967)
8:2954-2961.
[0008] Kinetic and thermodynamic EBI are interchangeably useful
separately and in mixtures as ligands for metallocene olefin
polymerization catalysts. However, the large-scale production of
kinetic EBI is constrained because the thermodynamic isomer is
produced at temperatures below about -70.degree. C.; whereas, at
higher temperatures low yields of kinetic EBI consequent from Spiro
indene and vinylidene impurities may result. See, e.g., Yang, et
al., SYNLETT (1996) 147 and Collins, et al., J. Organometallic
Chem. (1988) 342:21 (thermodynamic EBI synthesized at -78.degree.
C. stirred overnight and warmed to room temperature). See also ,
Ewen, J., et al., J. Am. Chem. Soc. (1987) 109:6544-6545 and
Grossman, R., et al., Organometallics (1991) 10:1501-1505 (50% to
80% arecrystallized yields of thermodynamic isomer because of the
formation of spiroindene by-product).
[0009] 3,3'C substitution imparts chirality to some Formula I
compounds with consequent achiral meso and chiral racemic forms.
Metallocene isotactic polypropylene catalysts may require
substantially pure rac EBI ligands; for example, rac
1,2-bis(3,3'trimethylsilyl indenyl-1)ethane (hereinafter rac
TMS-EBI). Typically, TMS-EBI may be produced by reaction of EBI
with two equivalents of BuLi to produce dilithio EBI. Dilithio EBI
is treated with two equivalents of TMSCl to produce 3,3'-bis
TMS-EBI. Synthesis of substituted EBI compounds, including TMS-EBI,
typically yields a mixture of meso and rac forms. Separation of the
rac form from such mixtures may not be practical for industrial
applications.
SUMMARY OF THE INVENTION
[0010] The invention may comprise a method for producing EBI from
an indene in good yield at moderate temperatures.
[0011] Pursuant to one aspect of the invention, a method is
provided for the moderate temperature synthesis of kinetic EBI
substantially free of by-product impurities.
[0012] Important embodiments of the invention include isomerization
agents effective to convert kinetic EBI to thermodynamic EBI and
also to convert meso 3,3'substituted EBI to a meso/rac mixture. The
invention may include isomerization protocols implemented by these
reagents.
[0013] The invention may include a series of moderate temperature
steps to produce a reaction mixture from which solid kinetic EBI
which may be substantially free of spiro indene impurities is
separated from a mother liquor. The solid kinetic EBI may be
separated in a single increment or in a plurality of increments,
each of said increments being separated from the mother liquor of
the preceding increment. Each mother liquor may comprise a solution
of additional kinetic EBI which may be isomerized to thermodynamic
EBI, preferably in solution in its mother liquor which is cooled
induce precipitation of solid thermodynamic EBI. The solid kinetic
and thermodynamic EBI products are useful separately or in
combination as metallocene catalyst ligands. This procedure for
synthesizing thermodynamic EBI, which includes an isomerization
step, is practiced and scalable, and is an improvement over the
lower yielding preparation of thermodynamic EBI which requires
starting the reactions at temperatures below -70.degree. C.
reported in the cited references.
[0014] The invention may include isomerization of a meso
3,3'substituted EBI, such as TMS-EBI to yield a meso and rac
mixture. Treatment of an existing mixture of meso and rac
3,3'substituted EBI with the isomerization agent yields a product
mixture enriched in the rac isomer. The stereospecific
transformation of racemic TMS-EBI to racemic metallocene is known.
See, e.g., Nifant'ev, I. A., et al. (1997) Organometallics
16:713-715. However, racemic TMS-EBI was isolated in only 34%
crystallized yield from the reaction of dilithio EBI and a
trimethyl silicon chloride. The isomerization of meso to meso-rac
TMS pursuant to this invention is an improvement over the prior art
because racemic TMS-EBI is used to synthesize racemic metallocene.
Iteration of the isomerization reaction with rac enrichment of the
product mixture at each iteration may yield an ultimate
substantially pure, e.g., 96% pure, rac product useful as a
stereospecific metallocene olefin polymerization catalyst
ligand.
DETAILED DESCRIPTION OF THE INVENTION
1. Synthesis of EBI
[0015] Formula I EBIs produced by any of the several known methods
may be used in any one or more of the embodiments of the
invention.
2. The Isomerization Agents
[0016] The isomerization agents useful in this invention are
solutions of alkali metal alkoxides having the formula MOR, wherein
M is any alkali metal and R is as defined. In the preferred
isomerization agents, R is t-butyl.
[0017] Useful isomerization agents are alkali metal alkoxide
solutions in a non-interfering, preferably ether, solvent. Suitable
solvents include tetrahydrofuran, 2-methyl tetrahydrofuran,
dioxane, and 1,2-dimethoxyethane. The isomerization agent solution
may contain any functional concentration, e.g., from 10 mol percent
to 20 mol percent, of alkali metal alkoxide. The preferred
isomerization agent is a 10 to 20 mol percent solution of potassium
tertiary butoxide in tetrahydrofuran.
3. The Isomerization Reactions
[0018] The isomerization reagents convert kinetic EBI to
thermodynamic EBI. They also convert meso 3,3'-substituted chiral
EBI to a mixture of the meso and rac forms.
[0019] In general, the isomerization reaction is accomplished by
treatment of a kinetic EBI or meso 3,3'-substituted EBI with the
isomerization reagent under conditions and for a time effective to
accomplish the desired reaction. Selection of the appropriate
conditions for a particular isomerization is determined by the
skilled man as a function of the particular isomerization involved
and of the degree of conversion desired. It is known that by going
from sodium methoxide to potassium t-butoxide, a substantial
increase in basic strength as well as more favorable solubility in
ether is achieved. See, Gilman (1953) Organic Chemistry Vol. III,
pp. 4-5, citing Gould, Jr., et al. (1935) J. Am. Chem. Soc. 57:340,
and Renfrow (1944) J. Am. Chem. Soc. 66:144.
[0020] Each type of isomerization may be accomplished to some
degree by treatment of the particular EBI isomer with an
isomerization reagent at a temperature of from about 20.degree. C.
to reflux for a time period of 30 minutes to 12 hours. The kinetic
to thermodynamic EBI isomerization appears to be facilitated by a
higher temperature and a longer time than the 3,3'-bis TMS-EBI meso
to meso:rac mixture isomerization. For example, 100% conversion of
kinetic to thermodynamic EBI may be accomplished by overnight
reflux in the reagent solvent such as THF. Less than 100%
isomerization occurs at lower temperatures or in a shorter reflux
time. In contrast, 100% meso TMS-EBI is converted in 30 minutes at
room temperature (20.degree. C.) by a similar isomerization agent
to a 50/50 rac-meso mixture.
4. Work-UP of Kinetic EBI Reaction Mixture
[0021] This aspect of the invention relates to the recovery of
kinetic EBI from a synthesis reaction mixture. An important step
entails exchange of any non-hydrocarbon reaction mixture solvent
for a hydrocarbon solvent from which kinetic EBI may be
precipitated, e.g., by cooling with consequent crystallization.
Appropriate hydrocarbon solvents are five to eight carbon atom
alkanes. Hexane and commercially available mixtures of hexanes
preferred. Aromatic hydrocarbon solvents including benzene,
toluene, and xylene may be used having due regard to conditions
requisite to crystallization from a particular solvent.
[0022] The hydrocarbon solution of kinetic EBI is cooled to cause
precipitation of at least a portion of solute. The quantity of
kinetic EBI precipitated is a function of the conditions imposed.
The solid kinetic EBI is separated, typically by filtration, from
the mother liquor solution of additional kinetic EBI. The separated
solid kinetic EBI is dried. A yield of 20% to 50% from indene is
typical.
5. Work-Up of Kinetic EBI Mother Liquor
[0023] This mother liquor or filtrate from the separation of solid
kinetic EBI is treated with an isomerization agent as described in
Sections 4 and 5, wherein the kinetic EBI solute is converted to
the thermodynamic isomer. The isomerization reaction mixture is
cooled or otherwise treated to induce precipitation of
thermodynamic EBI. The precipitate is recovered. The combined yield
of solid kinetic and thermodynamic EBI from indene may exceed
60%.
6. Conversion of EBI to a Metallocene
[0024] Either the separated kinetic EBI product of step 5, or the
separated thermodynamic product of step 6, or a mixture thereof may
be used in subsequent procedures to yield other products. An
important aspect of this invention is the substantial combined
yield of both EBI isomers from indene at relatively low reaction
temperatures. The EBI product mixture is used in known manner to
produce, inter alia, metallocene olefin polymerization catalysts
having the formula
A.sub.2ZX.sub.2
[0025] in which A is a mixture of kinetic and thermodynamic EBI, Z
is Zr, Ti or Hf, and X is a halogen. Z is typically Zr and X is
typically chlorine. (EBI).sub.2ZrCl.sub.2 is a typical catalyst.
Typically, such metallocenes are produced by the reaction of a
ligand lithenide with a Group IV tetrahalide. See, generally,
Spaleck (1994) Organometallics 13:954-963, Journal of
Organometallic Chem. 288 (1985) 63-67, and various Spaleck patents,
including U.S. Pat. Nos. 5,145,819 and 5,278,264.
EXEMPLIFICATION OF THE INVENTION
EXAMPLE I (Laboratory)
[0026] Indene in diethyl ether (1.25 equivalents) was treated with
BuLi in ethyl ether at -20.degree. C. to provide reaction mixture
containing lithium indenide pursuant to Equation 1, 2
[0027] The lithium indenide containing reaction mixture was warmed
to room temperature, was stirred for one hour, and then treated 0.5
mol of with dibromoethane. Ten minutes later tetrahydrofuran (THF)
(0.25 equiv.) was added. The temperature of the reaction slowly
warmed to 40.degree. C.
[0028] The .sup.1H NMR of the product mixture showed >95% yield
from indene of the kinetic isomer of EBI. No Spiro product was
observed. See Equation 2. 3
[0029] Water was added and the mixture separated into an aqueous
phase and an organic phase. The organic phase was separated and
dried with sodium sulfate.
[0030] The organic phase solvent (i.e., THF and hexanes) was
exchanged with hexanes in an amount such that the final volume was
concentrated to about 40 weight % of Kinetic EBI. The solution was
cooled to -20.degree. C. and filtered. The solid was dried to give
a 35% yield of the kinetic isomer of EBI.
EXAMPLE I(a) (Laboratory)
[0031] The Example I filtrate, a hexane solution of kinetic EBI,
was treated with 20 mol % potassium tertiary butoxide in THF and
refluxed overnight. .sup.1H NMR of the reaction mixture showed 100%
conversion of the kinetic EBI content to thermodynamic EBI. The
isomerization is illustrated by Equation 3: 4
[0032] The resulting hexane solution of thermodynamic EBI was
cooled to -20.degree.. The solid thermodynamic EBI precipitated and
was removed by filtration. The solid was dried to give an
additional 50% of thermodynamic EBI. Total yield of from indene was
85%.
EXAMPLE II
Meso to Rac Isomerization of TMS-EBI
[0033] 1.0 mol pure meso bis-1,2(3,3'TMS-EBI)ethane was dissolved
in THF (403 g) and 0.2 mol potassium tertiary butoxide (KOtbu) was
added in one portion to provide a THF solution containing 20 mol
percent of KOtbu. The solution changed color immediately from
yellow to green. The reaction mixture was stirred for 30 minutes.
.sup.1H NMR of the crude mixture showed rac/meso in a 50:50
ratio.
[0034] Upon addition of 3% aqueous NaCl, the reaction product
separated into an organic layer and an aqueous layer. The organic
layer was separated and washed with water; the THF solvent was
exchanged with heptane under conditions such that a heptane
solution containing about 35% bis-1,2(3,3'TMS-EBI-1) was obtained.
The heptane solution was cooled to -20.degree. C. and the meso
isomer crystallized. The solid meso was separated (198 g) by
filtration. The filtrate that contained rac was distilled, leaving
behind a sticky semi- solid that contained 200 g of 90%
diastereomerically pure rac.
EXAMPLE II(a)
[0035] The solid meso collected in Example II was converted to a 50
meso/50 rac mixture from which the rac was separated by reiteration
of the Example I work-up.
EXAMPLE III
[0036] Example II is repeated using 2,2T methyl substituted
TMS-EBI. An isomerization reaction mixture having a 65:35 meso:rac
ratio was produced: 5 6
EXAMPLE IV (Laboratory)
[0037] Example II is repeated using 4,4':7,7'methyl substituted
TMS-EBI. An isomerization reaction mixture having an 80:20 meso:rac
ratio was produced: 7
EXAMPLE V (Batch Record)
Synthesis of Rac-1,2-Ethylenebis
(3-trimethylsilyl-l-indenyl)ethane
Process Description
[0038] 1,2-Bis(indenyl)ethane, BSC-395 and THF are charged to a
reaction vessel. Butyllithium in hexanes is then added slowly. This
mixture is then slowly heated to room temperature and agitated. THF
and TMSC1 (trimethylsilyl chloride) are added to the vessel, and
the lithiated EBI is fed in cold. THF and unreacted TMSC1 are
distilled to the vessel. Heptane is added. The slurry is filtered
through a sparkler filter, collecting lithium salts. The filtrate
is cooled, and the meso product is collected on a filter. The meso
ligand is treated with potassium t-butoxide to isomerize to a
rac-:meso- mixture. The isomer mixture is separated. 8 9
Reaction 3
[0039] Meso product of reaction 2 is treated with potassium
t-butoxide in THF. Product of Reaction 3-50/50 rac and meso
1,2-ethylenebis(3-trimethyl- silyl-1-indenyl) ethane.
(i) Exemplification of Reaction 1
[0040] A nitrogen purged first reactor [190-241] was charged with
9.1 kgs of 1,2-bis(indenyl) ethane. 90.7 kgs of THF is charged to
the first reactor vessel. Thereafter, the pot temperature of the
first reactor vessel is reduced to the range of -25.degree. C. to
-20.degree. C. under 2-5 psig regulated nitrogen. 29.9 kgs of 1.6
molar n-butyl lithium in hexane is fed to first reactor vessel at a
rate effective to maintain the pot temperature in the range of
-25.degree. C. to -15.degree. C. Upon completion of n-butyl lithium
addition, the pot temperature of the first reactor is raised to a
temperature of 20.degree. C. to 25.degree. C. over a time period of
16 hours. The pot temperature is then raised to about 30.degree. C.
to dissolve the reactor product slurry and the contents of the
first reactor vessel are transferred from the first reactor vessel
to a dry, glass holding receiver ["receiver"]. The first reactor is
maintained wet with THF after the transfer of its contents to the
receiver.
(ii) Exerplification of Reaction 2
[0041] 11.5 kgs of trimethylsilyl chloride are charged to the THF
wet first reactor vessel. The pot temperature of the first reactor
vessel is lowered to the range of -20.degree. C. to -10.degree. C.
The contents of the glass holding receiver are added to the first
reactor vessel over a 30 minute time period while the pot
temperature is maintained in the range of -20.degree. C. to
-10.degree. C. The resulting reaction mixture is agitated under 2-5
psig regulated nitrogen as the pot temperature is slowly raised to
20.degree. C. to 25.degree. C. over a period of three hours.
Thereafter, the contents of the first reactor are stripped to a
paste by distillation of THF and TMSC1 to a temperature of
95.degree. C.
(iii) Exemplification of Reaction 3
[0042] The neutralized distillate which comprises a solution of
meso TMS is transferred to a second reactor [115-254]. 5.5 kgs of
heptane is added to the second reactor at a temperature of
20.degree. C. to 25.degree. C. THF content of the second reactor is
reduced to less than 2% by distillation of heptane/THF.
[0043] The temperature of the second reactor contents is adjusted,
if necessary, to 78.degree. C. to 82.degree. C., and that reactor
is emptied by filtration to remove lithium salts. The filtrate, a
solution of meso solids, is transferred to a nitrogen purged drum.
The second reactor is rinsed twice with heptane at 78.degree. C. to
82.degree. C. in an amount sufficient to provide a 35% solution of
meso solids when combined with the filtrate form the second reactor
contents.
[0044] The combined rinse heptane and the filtrate from the second
reactor are transferred to the first reactor at a temperature of
-30.degree. C. to -20.degree. C. The resulting meso solids
precipitate is removed by filtration and dried.
[0045] The dry meso solids are transferred to a third reactor
[95-252] which is charged with 13 kgs. of THF. 135 grams of
potassium t-butoxide are added by sprinkling to the contents of the
third reactor with agitation for 30 minutes. A 50:50 meso:rac
mixture is produced.
[0046] The third reactor is charged with 11.3 liters of water,
followed by 1.3 kgs. of sodium chloride which, in turn, is followed
by 5.4 kgs. of ethyl ether. The reaction mixture is agitated for 15
minutes, and settled for 15 minutes. A lower aqueous and an upper
organic layer form. The lower aqueous layer is removed. Pot
temperature of the third reactor is adjusted to less than
20.degree. C. 2 kgs. of sodium sulfate is added with agitation for
two hours. The agitated mixture is allowed to settle for 20
minutes, and filtered to a dry second reactor. Solvents are
distilled, the contents of the second reactor are cooled to
20.degree. C. to -20.degree. C., and charged with heptane in an
amount sufficient to provide a 35% solution of 50:50 rac:meso
solids. THF content is adjusted, if necessary, to less than 2%.
[0047] The first reactor [109-241] is cooled to -30.degree. C. to
-20.degree. C. The resulting solids are removed by filtration and
dried. The filtrate is retained for further processing.
* * * * *