|Title of Invention||
A METHOD OF PREPARING A TRIFLUOROVINYL METAL COMPLEX
|Abstract||A,ββ-Trifluorostyrene and derivatives thereof synthesized in two steps from 1, 1, 1, 2-tetrafluoroethylene. In the first step, 1, 1, 1, 2- tetrafluoroethylene is reacted with a base, a metal salt such as zinc chloride and an optionally amine to form a trifluorovinyl metal complex. In the second step, the trifluorostyrene or derivative is obtained by reacting the trifluorovinyl metal complex with an aryl transfer agent such as, for example, an aryl triflate or an aryl halide, in the presence of a metal catalyst and optionally a coordinating ligand. Both steps may be carried out in one reactor.|
|Full Text||A METHOD OF PREPARING A TRIFLUOROVINYL METAL COMPLEX
BACKGROUND OF THE INVENTION
The present invention relates to a method of preparing a trifluorovinyl metal
complex and related monomers via the in-situ formation of a trifluorovinyl metal
Description of the Related Art
a,p,P-Trifluorostyrenes ('TFS") can be used as monomers in the
production of polymers that, in turn, can be used to produce membranes with favorable
chemical and mechanical properties. In addition, if the resultant polymers are
functionalized with an ion-exchange group, they can be used to form ion-exchange
membranes. A polymer membrane comprising TFS and/or substituted TFS monomer
units may be suitable for a wide variety of applications and, in particular, such polymer
membranes containing ion-exchange functionality have been used in electrochemical
applications such as fuel cells as disclosed in U.S. Patent Nos. 5,422,411, 5,602,185 and
The synthesis of a,P,P-trifluorostyrene was initially reported in the late
1940's and early 1950's. While several methods have since been reported, none of the
methods are economically viable in the large scale synthesis of TFS and related
monomers. Typical conditions that could render methodologies generally unsuitable for
large scale synthesis include low yields, high or low temperatures, high pressures, the
use of toxic chemicals and the use of environmentally damaging chemicals such as
U.S. Patent No. 2,612,528 discloses a multi-step synthesis of TFS via a
Friedal-Crafts acylation to produce an overall TFS yield of about 30%. In addition to
the low yield obtained, the method also requires the use of a toxic fluorinatuig agent,
namely antimony pentafluoride, and the isolation of CFC intermediates.
U.S. Patent Nos. 2,651,627 and 2,752,400 report a synthesis of TFS from
chlorotrifluoroethylene and benzene by pyrolysis at 550-600°C. Not only does this
method require high temperatures and the use of a CFC as a starting material, but this
method only results in low yields of less than 30%. Pyrolysis at 600-800°C was also
reported in U.S. Patent No. 3,489,807 in the synthesis of TFS from β,β-
chlorofluoroethylbenzene and 2-chloro-1,1-difluoroethylene, though, relatively low
yields were similarly reported. Low yields also result from the synthesis of TFS via the
reaction of phenyl lithium with tetrafluoroethylene as disclosed in U.S. Patent No.
2,874,166. Cryogenic temperatures of
-30 to -100°C are disclosed in U.S. Patent No. 3,449,449 for the reaction of solid
phenylsodium with tetrafluoroethylene under high pressure (i.e., 70-1400 kPa) to form
Relatively high yields at mild temperatures are described in Heinze and
Burton (Journal of Organic Chemistry 55:2714-2720, 1998) for the synthesis of TFS.
However, this synthesis requires the use of either iodotrifluoroethylene or
bromotrifluoroethylene as a starting material. Bromo- and iodotrifluoroethylene are
class 2 ozone-depleters that are both relatively expensive and currently commercially
available in large volumes from only one source in North America, namely Halocarbon
Accordingly, there remains a need for improved synthetic methods for
making TFS and related monomers, particularly methods that provide for relatively
high yields under mild conditions using commercially available and relatively
environmentally benign starting materials.
BRIEF SUMMARY OF THE INVENTION
The present method provides for the two-step synthesis of TFS or a
derivative thereof from 1,1,1,2-tetrafluoroethane ("HFC-134a")-
In the first step, a trifluorovinyl metal complex is formed by effecting a
reaction between HFC-134a, an amine, a base and a metal salt This is shown in the
following reaction wherein MX1n is the metal salt:
The amine may be added to the reaction mixture as a free amine or with the metal salt in
a preformed metal salt-amine complex. Alternatively, the amine may be generated in
situ. For example, if lithium diisopropylamide is used as the base, diisopropylamine
will be generated in situ.
In another embodiment of the first step, a trifluoro vinyl metal complex is
formed by effecting a reaction between HFC-134a, a base and a metal salt, wherein the
reaction temperature is greater than -68°C. In a more specific embodiment, the reaction
temperature is from about 15°C to about 25°C.
The second step involves reacting the trifluorovinyl metal complex, as
prepared above, with an aromatic transfer agent (ArX2) in the presence of a metal
catalyst and a coordinating ligand to form TFS or a derivative thereof. This is shown in
the following reaction:
The X2 group of the aromatic transfer agent can be any of a variety of
suitable transfer agent leaving groups, such as halogen, triflate (i.e., -OSO2CF3), or
other suitable groups known to those skilled in the art. In this regard, higher yields
have been observed with aromatic iodides. Typically, the aromatic group will be a
carbocyclic aromatic group, such as phenyl or naphthyl, although heterocyclic aromatic
groups, such as thienyl, may also be used. As discussed in greater detail below, the
aromatic transfer agent may be optionally substituted.
To form TFS, the aromatic transfer agent is a phenyl halide (such as
phenyl iodide). The metal catalyst may be palladium, nickel or platinum, in either the
zero oxidation state or reduced to this oxidation state in situ. Palladium(0)
bis(dibenzyiidene acetone) is an example of a metal catalyst that is easy to handle and
both temperature and air stable. The coordinating ligand can be a mono- or
multidentate phosphine, arsine or other ligand known to those skilled in the art. The
ligand may be, for example, triphenylphosphine.
The two steps in the synthesis of TFS or derivative thereof can be
performed without isolating the trifluorovinyl metal complex intermediate. Further, a
mixture of two or more TFS monomers (or derivatives thereof) can be synthesized by
adding a second aromatic transfer agent along with the first aromatic transfer agent.
These and other aspects of the invention will be evident upon reference
to the following detailed description.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
α,β,β-Trifluorostyrene (TFS) has the following structure (I):
As used herein, "derivatives" of TFS include compounds having the
following structure (II):
wherein Ar represents an aromatic carbocyclic or heterocylic moiety, optionally
substituted with one or more substituents, but not including structure (I).
Representative aromatic carbocylic moieties include phenyl and 1- and 2-naphthyl,
while representative aromatic heterocyclic moieties include thienyl, furyl and pyrrolyl.
When substituted by two or more substituents, the substituents may be the same or
different. Substituents include any moiety not having acidic hydrogens. Representative
substituents include, but are not limited to, hydroxy, cyano, nitro, halo, halogenated
alkyl such as trifluoromethyl, halogenated alkenyl such as -CF=CF2, alkoxy such as
methoxy, and aryloxy such as phenoxy.
As used herein, "alkyl" means a straight chain or branched, noncyclic or
cyclic, unsaturated or saturated aliphatic hydrocarbon containing from 1 to 10 carbon
atoms. Representative saturated straight chain alkyls include methyl, ethyl, n-propyl, n-
butyl, n-pentyl, n-hexyl, and the like; while saturated branched alkyls include isopropyl,
sec-butyl, isobutyl, tert-butyl, isopentyl, and the like. Representative saturated cyclic
alkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -CH2cyclopropyl,
-CH2cyclobutyl, -CH2cyclopentyl, -CH2cyclohexyl, and the like; while unsaturated
cyclic alkyls include cyclopentenyl and cyclohexenyl, and the like. Cyclic alkyls, also
referred to as "homocyclic rings," and include di- and poly-homocyclic rings such as
decalin and adamantyl. Unsaturated alkyls contain at least one double or triple bond
between adjacent carbon atoms (referred to as an "alkenyl" or "alkynyl", respectively).
Representative straight chain and branched alkenyls include ethylenyl, propylenyl, 1-
butenyl, 2-butenyl, isobutylenyl, 1-pentenyl, 2-pentenyl, 3-methyl-l-butenyl, 2-methyl-
2-butenyl, 2,3-dimethyl-2-butenyl, and the like; while representative straight chain and
branched alkynyls include acetylenyl, propynyl, 1-butynyl, 2-butynyl, 1-pentynyl, 2-
pentynyl, 3-methyl-l butynyl, and the like.
Furthermore, "aryl" means an aromatic carbocyclic moiety, such as
phenyl and naphthyl, while "alkoxy" and "aryloxy"- mean -O-alkyl and -O-aryl,
In the present approach, 1,1,1,2-tetrafluoroethane ("HFC-134a") is used
as a starting material in the synthesis of TFS, or a derivative thereof, under relatively
mild conditions. As a starting material, HFC-134a is economical and environmentally
benign. HFC-134a has been reported as a starting material for perfluorovinyl-metal
derivatives in Banger et al. (Chemical Communications 1997, 139-140). However,
Banger et al. use very low temperatures (i.e., -78°C) for the synthesis of the
perfluorovinyl metal derivatives as it was understood that trifluorovinyl lithium
decomposes at higher temperatures (see, e.g., D.J. Burton et al., Tetrahedron, 2993,
In an embodiment of the present method, TFS monomers and derivatives
thereof can be synthesized in two steps. In the first step, a trifluorovinyl metal complex
is formed by reacting HFC-134a with a base, an amine and a metal salt. In the second
step, an aromatic transfer agent, a metal catalyst and a coordinating ligand are combined
and heated. After cooling to room temperature, TFS monomers, or derivatives thereof,
can typically be isolated in yields of about 75-85%.
It should be understood that various bases may be used in this first step,
provide that the base is capable of deprotonating HFC-134a. Representative bases
include, but are not limited to, alkyl and aryl lithium reagents (such as lithium
diisopropylamide or t-butyllithiurn), alkyl and aryl Grignard reagent, and sodium or
Representative metal salts, M(X1)n, include, but are not limited to, zinc
salt, mercuric salt, indium salt, magnesium salt, cadmium salt, thalium salt, alkyl tin
salt, aryl tin salt, alkyl lead salt or aryl lead salt. The metal salt may be a metal halide
(i.e., X1 = halide) wherein the halide is a chloride, bromide or iodide, although other
metal salts such as a metal acetate (X1 = acetate) or a metal triflate (X1 = triflate) may
also be used. Also, the X1 groups need not be the same, although they typically are the
same, and n represents the number of electron donating X1 groups are associated with
the metal M. The metal salt is preferably anhydrous, though small amounts of water
may be present. Nevertheless, higher yields tend to be observed in the absence of water
during the first step. Anhydrous zinc chloride is a representative reagent as it reacts
efficiently, and it is more economical and/or more environmentally benign than the
other salts mentioned above.
Suitable amines include alkyl, aryl and heteroaromatic amines as
understood by those skilled in the art. In this regard, "heteroaromatic amine" means an
aromatic heterocycle ring of 5 to 10 members and having at least one nitrogen atom and
containing at least 1 carbon atom, including both mono- and bicyclic ring systems.
Representative heteroaromatic amines include (but are not limited to) pyrrole, indole,
azaindole, pyridine, quinoline, isoquinoline, pyrazole, imidazole, benzimidazole,
pyridazine, pyrimidine, pyrazine, cinnoline, phthalazine, and quinazoline.
Further, the amine may be mono- or multi-dentate. Without limiting the
generality of the foregoing, the amine may be, for example, tetramethylethylenediamine
("TMEDA"), diisopropylamine, triethylamine, or 2,2'-bi-pyridyl. Alternatively, the
amine need not be independently added to the reaction mixture, though either lower
yields tend to be observed or the reaction must be operated at lower temperatures.
Nevertheless, acceptable yields may still be observed at temperatures higher than -68°C
even without any amine being present in the reaction mixture. However, if lithium
diisopropylamide ("LDA") is used as the base, relatively high yields are observed at
higher temperatures even without amine being independently added to the reaction
mixture. Without being bound by theory, it is believed that higher yields are observed
due to an amine, namely diisopropylamine, being generated in situ as LDA reacts with
The amine and the metal salt can be added to the reaction mixture as
separate components, or in the form of a preformed metal salt-amine complex, such as,
for example, a ZnCl2•TMEDA complex.
THF is used as a solvent in the above embodiment though it is
understood that other solvents may be used.
Dependent on the base chosen, the temperature of the reaction to form
the trifluorovinyl metal complex may be varied without significantly affecting the yield.
For example, the reaction may be performed at room temperature (i.e. 15-25°C) and
also at low temperatures, such as, for example -90°C without significantly impacting
the yield. However, an advantage of the present method is that it allows more practical
conditions to be used in the synthesis of TFS monomers and derivatives thereof.
The aromatic transfer agent (ArX2) may be an aromatic halide (i.e., X2 =
fluoro, chloro, bromo or iodo), triflate (i.e. X2 = -OSO2CF3), or other aromatic transfer
agent known to those skilled in the art. The aryl group is phenyl to yield TFS.
Alternatively, to yield TFS derivatives, the aromatic group may be substituted phenyl,
naphthyl, substituted naphthyl, heteroaryl or substituted heteroaryl. To this end,
"heteroaryl" means an aromatic heterocycle ring of 5 to 10 members and having at least
one heteroatom selected from nitrogen, oxygen and sulfur, and containing at least 1
carbon atom, including both mono- and bicyclic ring systems. Representative
heteroaryls include (but are not limited to) furyl, benzofuranyl, thiophenyl,
benzothiophenyl, pyrrolyl, indolyl, isoindolyl, azaindolyl, pyridyl, quinolinyl,
isoquinolinyl, oxazolyl, isooxazolyl, benzoxazolyl, pyrazolyl, imidazolyl,
benzimidazolyl, thiazolyl, benzothiazolyl, isothiazolyl, pyridazinyl, pyrimidinyl,
pyrazinyl, triazinyl, cinnolinyl, phthalazinyl, and quinazolinyl.
Furthermore, a combination of different aromatic transfer agents may be
added to the reaction mixture to yield a mixture of TFS monomers and/or derivatives
thereof. For example, if the aromatic transfer agent is iodophenyl and iodophenyl
substituted with trifiuoromethyl (at either the ortho, meta or para position), and such
transfer agents are added together as the aromatic transfer agents, a mixture of TFS and
F3CC6H4CF=CF2 will be generated.
The metal catalyst can be any palladium, nickel or platinum metal
catalyst wherein the metal is in the zero oxidation state. Alternatively, the metal
catalyst may be in the +2 or +4 oxidation state and then reduced in situ, to the zero
oxidation state. For example, the metal catalyst may be palladium bis(dibenzylidene
The coordinating ligand may be any ligand selected from the group of
mono or multidentate phosphines and arsines. High yields of TFS and derivatives
thereof may still be observed if the coordinating ligand is not added to the reaction
mixture. Triphenylphosphine as the coordinating ligand allows high yields of TFS and
derivatives thereof, is cost effective and relatively environmentally benign.
A small amount of bis trifluorometal complex may be formed in the first
step along with the "mono-complex". This is shown in the following schematic:
The formation of the "bis complex" is not significant as it reacts with the aromatic
transfer agent, similarly to the mono complex in the second step of the reaction to
produce TFS or derivative thereof.
The isolation and purification of TFS and derivatives can be
accomplished by, for example, first flash distilling the reaction mixture under vacuum
to separate the solvents and product from the metal salts produced during the reaction.
The TFS monomer may then be isolated by fractional distillation under partial pressure.
Depending on the relative volatility of the solvent, the TFS or related monomer may be
isolated directly from the reaction mixture by fractional distillation.
The monomer may then be polymerized to form a polymer suitable for
use in such applications as a membrane in electrochemical fuel cells. The polymer may
be a homopolymer or a copolymer. Copolymers may be random, block or graft
TRIFLUOROVINYL ZINC CHLORIDE
A 250 mL three-necked round bottom flask fitted with a dry
ice/isopropanol condenser, septum and a low temperature thermometer were assembled
while hot and flushed with nitrogen gas. It was charged with ZnCl2 (3.42g, 25.0 mmol)
and THF (15.0 ml). The solution was cooled to 12-15°C using a cold water bath and
gaseous HFC-134a (2.5 ml, 30.0 mmol) was condensed in the saturated solution. LDA
was added to the reaction mixture slowly over 35 min. through a cannula while
maintaining the temperature between 15 and 20°C. The tip of the cannula was dipped
below the surface of the solution to avoid decomposition of the intermediate vinyl
lithium at the tip by the reaction of gaseous HFC-134a with LDA. The reaction mixture
was stirred for lh at 20°C and then allowed to settle for 2h. The 19F NMR of the zinc
reagent was recorded at this stage and showed formation of the trifluorovinyl zinc
complex along with traces of unreacted HFC-134a. Small amounts of bis trifluorovinyl
zinc product was also formed along with mono trifluorovinyl zinc complex as seen by
the shoulder peaks in the up field direction to the mono complex. The ratio of mono/bis
was approximately 90:10. The estimated yield of the trifluorovinyl zinc chloride was
Following the general procedure as provided for in Example 1, the
reaction was repeated varying the base, the metal salt, the amine and/or the temperature
as provided for in the following table.
a The metal salt and amine were added as a preformed ZnCl2•TMEDA
b LTMP is lithium-2,6-tetramethyl-4-methoxy piperide. The structure of
GENERAL PROCEDURE FOR TFS AND DERIVATIVES
Trifluorovinyl zinc chloride was prepared according to Example 1. The
dry ice/isopropanol condenser and the thermometer from the reaction described in
Example 1 were replaced with a stopcock and stopper. The trifluorovinyl zinc chloride
solution was concentrated under vacuum to almost half its original volume. During this
concentration, excess HFC-134a was evaporated off. After careful displacement of the
vacuum with nitrogen, a condenser fitted with a nitrogen inlet replaced the stopcock.
Iodobenzene (approx. 0.8 eq) and tetrakistriphenylphosphine palladium (Pd(PPh3)4)
(approx. 1.5 mol%) were then added. The reaction mixture was heated at 60°C using an
oil bath. The reaction progress was monitored using 19F NMR by sampling small
aliquots of the reaction mixture. After the complete conversion of the trifluorovinyl
zinc chloride to the TFS, the reaction mixture was triturated several times with pentane
or hexane and the combined extracts evaporated on a rotary evaporator after the
addition of silica gel. Silica gel was added prior to evaporation of the solvent to absorb
the TFS product and thereby prevent loss of product due to its volatile nature. After
evaporation of the solvent, column chromatography on silica gel was then carried out
with either pentane or hexane as eluent depending on the volatility of the TFS.
Following the general procedure as provided for in Example 10, the
reaction was repeated varying the aryl halide.
While particular steps, elements, embodiments and applications of the
present invention have been shown and described, it will be understood, of course, that
the invention is not limited thereto since modifications may be made by persons skilled
in the art, particularly in light of the foregoing teachings. It is therefore contemplated
by the appended claims to cover such modifications as incorporate those steps or
elements that come within the spirit and scope of the invention.
WE CLAIM :
1. A method for preparing a trifluorovinyl metal complex comprising effecting
a reaction between 1,1,1,2-tetrafluoroethane, an amine, a base, and a metal
salt, wherein the amine is an alkyl amine, an aryl amine or an heteroaromatic
2. The method as claimed in claim 1 wherein the amine is a multidentate
3. The method as claimed in claim 2 wherein the amine is
4. The method as claimed in claim 1 wherein the amine is generated in situ.
5. The method as claimed in claim 1 wherein the base is lithium
diisopropylamide, t-butyl lithium or lithium-2,6-tetramethyl-4-methoxy piperide.
6. The method as claimed in claim 5 wherein the base is lithium
7. The method as claimed in claim 1 wherein the metal salt is a metal halide.
8. The method as claimed in claim 7 wherein the metal halide is a zinc
9. The method as claimed in claim 8 wherein the zinc halide is anhydrous
10. The method as claimed in claim 1 wherein the metal salt and the amine
are in a preformed metal salt-amine complex.
11. The method as claimed in claim 1 wherein the reaction temperature is
from 15 to about 25°C.
12. A method for preparing a trifluorovinyl metal complex comprising effecting
a reaction between 1,1,1,2-tetrafluoroethane; a base; and a metal salt wherein
the reaction temperature is greater than -68°C.
13. The method as claimed in claim 12 wherein the base is lithium
diisopropylamide, t-butyl lithium or lithium-2,6-tetramethyl-4-methoxy piperide.
14. The method as claimed in claim 13 wherein the base is lithium
15. The method as claimed in claim 12 wherein the metal salt is a metal
16. The method as claimed in claim 15 wherein the metal halide is zinc halide.
17. The method as claimed in claim 16 wherein the zinc halide is anhydrous
18. The method as claimed in claim 12 wherein the effecting step further
comprises an amine, wherein the amine is an alkyl amine, an aryl amine or a
19. The method as claimed in claim 18 wherein the metal salt and the amine
are in a preformed metal salt-amine complex.
20. The method as claimed in claim 12 wherein the reaction temperature is
from 15 to 25°C.
21. A method for preparing an a,b,b-trifluorostyrene monomer or derivative
thereof, comprising the step of reacting the trifluorovinyl metal complex of any
one of claims 1 or 12 with a first aromatic transfer agent in the presence of a
22. The method as claimed in claim 21 wherein the first aryl transfer agent is
an aryl triflate, an aryl iodide, an aryl bromide or an aryl chloride.
23. The method as claimed in claim 22 wherein the first aryl transfer agent is
an aryl iodide.
24. The method as claimed in claim 23 wherein the aryl iodide is phenyl
25. The method as claimed in claim 21 wherein the reacting step further
comprises a second aryl transfer agent, wherein the second aryl transfer agent is
an aryl triflate, an aryl iodide, an aryl bromide or an aryl chloride.
26. The method as claimed in claim 21 wherein the metal catalyst is a
palladium metal catalyst, a nickel metal catalyst or a platinum metal catalyst.
27. The method as claimed in claim 26 wherein the metal catalyst is palladium
(0) bis(dibenzylidene acetone).
28. The method as claimed in claim 21 wherein the reacting step further
comprises a coordinating ligand selected from the group consisting of a
phosphine and an arsine.
29. The method as claimed in claim 28 wherein the coordinating ligand is
30. A method for preparing a polymer, comprising the steps of:
preparing an α,β,β-trifulurostyrene monomer or derivative thereof by
reacting the trifluorovinyl complex as claimed in any one of claims 1 or 12 with a
first aromatic transfer agent in the presence of a metal catalyst; and
polymerizing the a,b,b-trifluorostyrene monomer or derivative thereof.
31. The method as claimed in claim 30 wherein the polymer is a copolymer.
32. The method as claimed in claim 30 wherein the polymer is a random
33. The method as claimed in claim 30 wherein the polymer is a graft
A,ββ-Trifluorostyrene and derivatives thereof synthesized in two steps from
1, 1, 1, 2-tetrafluoroethylene. In the first step, 1, 1, 1, 2- tetrafluoroethylene is
reacted with a base, a metal salt such as zinc chloride and an optionally amine to
form a trifluorovinyl metal complex. In the second step, the trifluorostyrene or
derivative is obtained by reacting the trifluorovinyl metal complex with an aryl
transfer agent such as, for example, an aryl triflate or an aryl halide, in the
presence of a metal catalyst and optionally a coordinating ligand. Both steps may
be carried out in one reactor.
|Indian Patent Application Number||824/KOLNP/2004|
|PG Journal Number||23/2012|
|Date of Filing||15-Jun-2004|
|Name of Patentee||BDF IP HOLDINGS LTD.|
|Applicant Address||1700-666 BURRARD STREET, VANCOUVER, BRITISH COLUMBIA|
|PCT International Classification Number||C07C17/26|
|PCT International Application Number||PCT/CA2002/01861|
|PCT International Filing date||2002-12-04|