Phosphonium ionic liquids as reaction media for strong bases

Article abstract of DOI:10.1039/b411646a

Phosphonium ionic liquids are compatible with strong bases; for example, solutions composed of commercially available phenylmagnesium bromide in THF are persistent in tetradecyl(trihexyl)phosphonium chloride for several hours-days: their stability appears to be couched in kinetic terms.

Full text of DOI:10.1039/b411646a

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Phosphonium ionic liquids as reaction media for strong bases
Taramatee Ramnial, Daisuke D. Ino and Jason A. C. Clyburne*
Received (in Columbia, MO, USA) 28th July 2004, Accepted 12th October 2004
First published as an Advance Article on the web 10th December 2004
DOI: 10.1039/b411646a
Phosphonium ionic liquids are compatible with strong bases;
for example, solutions composed of commercially available
phenylmagnesium bromide in THF are persistent in tetra-
decyl(trihexyl)phosphonium chloride for several hours–days:
their stability appears to be couched in kinetic terms.
solvent alternatives, namely H
2 2
O and supercritical CO , react with
strong bases.
Environmental pressure to reduce waste and re-use materials has
1
,2
driven studies into ‘‘Green’’ chemistry. Recent reviews have
3–5
covered these emerging fields and it is apparent that one of the
most difficult areas to make environmentally friendlier is solution
phase chemistry. Solvents play key roles in chemical reactions; they
serve to homogenize and mix reactants, and act as a heat sink for
exothermic processes. It is clear that one of the biggest industrial
We recently found that NHCs are persistent in phosphonium
18
6
concerns is replacement of volatile organic compounds (VOCs),
based ILs, such as tetradecyl(trihexyl)phosphonium chloride IL 2
22,23
2
1
particularly those that are toxic, such as CH Cl , and those that
2
a
(CYPHOSH IL 101). NHCs are highly basic (pK 5 22–24)
2
are hazardous to handle. Of the latter class of VOCs, the most
offensive are ethers, which are volatile, flammable, and form
explosive peroxides: they are, unfortunately, on the ‘‘A-list’’ of
solvents for reactions involving strong bases. Successful attempts
to replace or limit the use of VOCs have been made, and these
and we were surprised that deprotonation of the IL 2 to produce a
phosphorane 3 did not occur. This suggested to us to examine
whether stronger bases would be persistent and reactive in
phosphonium based ILs. Here we report: 1. Grignard reagents
are persistent in IL 2 and 2. a study examining the behaviour of
Grignard reagents in an ionic liquid.
7
include processes that use no solvent or new solvent systems such
11
8–10
O,
12
as supercritical H
2
supercritical CO
2
,
fluorous solvents,
IL 2 (mp 5 ca. 250 uC) can be dried by azeotropic distillation
with benzene or with Kmetal and a small amount (5%) of hexane
13,14
and ionic liquids (ILs).
ILs are particularly attractive because
of their low volatility, high thermal capacity, and resistance to
combustion. Here we report that phosphonium based ILs can
support chemistry involving strong bases and we use Grignard
reagents as illustrative examples.
(
added to reduce viscosity and facilitate stirring). Note that the
latter drying process is not feasible for IL 1. The lack of reactivity
of IL 2 with potassium portends well for the reaction of other
bases in this ionic liquid since, in theory, solid potassium is a
source of the strongest base, the electron.
Perhaps the most extensively studied class of ILs is based upon
1
5
the imidazolium ion 1 and the most popular example is the
ethylmethylimidazolium ion with anions such as [BF ] and [AlCl ].
Dry samples of IL 2 form clear solutions of low viscosity with
commercially available PhMgBr in THF. Grignard reagents
dissolved in IL 2 are air and moisture sensitive. These solutions
show no sign of degradation after one month as shown by
reactivity studies. Deprotonation of 2 to produce a phosphorane 3
was not observed. Quench of solutions composed of IL 2 and
4
4
Notwithstanding the sensitivity of the anions, these ILs have
garnered attention since they facilitate many unusual chemical
reactions. Solutions of IL 1 support reactions such as alkene
16
17
oligomerizations, alkylations and acylations. We note that
imidazolium based solvent systems are unsuitable for reactions
involving either active metals (i.e., Na or K) or in reactions
that involve strong bases (i.e. Grignards, organolithiums, and
amides) since these reagents react with the imidazolium-based
solvents. For instance, imidazolium ions react quantitatively
with Kmetal to produce imidazol-2-ylidenes (N-heterocyclic car-
PhMgBr with anhydrous Br
2
resulted in the exclusive formation of
PhBr, however 5% of biphenyl was detected when the one month
24
2
old IL 2 Grignard reagent solution was quenched with Br .
Benzene, the product of a deprotonation reaction, was not
observed. We also examined complete removal of THF from the
IL 2 Grignard solutions, but in general this resulted in the
formation of more biphenyl and hence reaction yields were
reduced. Good results were obtained when the ratio of THF : IL
was 1 : 3. Unfortunately, attempts to generate the Grignard
reagent in phosphonium based ionic liquids failed.
1
8
benes, NHCs), and treatment of imidazolium ions with bases,
such as lithium di-iso-propylamide or potassium tert-butoxide,
1
9
is the standard method for generation of NHCs. Even with
weaker bases, such as NR , Aggarwal showed that during the
3
Baylis–Hillman reaction in an imidazolium-based ionic liquid, the
We have found that since the ionic liquids have a high heat
capacity we do not need to cool the reaction solutions to the
extremely low temperatures often needed for ethereal solutions.
We performed a survey of reactions in IL 2, and these include
addition to carbonyls, benzyne reactions, halogenation and
low reported yields were the result of addition of the deprotonated
2
0
imidazolium cation to an aldehyde. Finally, the other ‘‘Greener’’
*clyburne@sfu.ca
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Chem. Commun., 2005, 325–327 | 325

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coupling reactions (Scheme 1). Product isolation is made easy since
phosphonium ionic liquids have remarkable solvent properties.
After reaction of the electrophile and the Grignard reagent,
addition of water and hexane to the reaction mixture results in the
formation of a three-phase system, with the organic layer on
the top, ionic liquid in the middle, and the aqueous layer on the
bottom. The products were isolated from the organic layer and
analyzed. The low yields reported in Scheme 1 reflect the
partitioning between the IL and organic phase, and isolated yields
can be markedly improved by successive extractions. In some
cases, due to the high thermal stability of the ILs and volatility of
the products, distillation could be used to remove the product from
the reaction mixtures. Analogous reactions were performed using
phenyllithium, but these reactions produced a variety of products
as yet unidentified. Finally, treatment of benzaldehyde with
Fig. 1 MM2 minimized structure of the tetradecyl(trihexyl)phospho-
nium cation showing acidic C–H site surrounded by non-rigid alkyl
groups.
thermodynamically favoured, reduction of the aldehyde occurs
because the faster reaction involves reduction of the carbonyl.
In summary, IL 2 is capable of supporting reactions involving
strong bases such as Grignard reagents. In this light, IL 2
complements IL 1 by supporting reagents (i.e., Grignards) that are
not viable in IL 1. The reactions between the Grignard reagent and
added reactants proceed cleanly, and there is no observed reaction
between the IL and the strongly basic reagents. The high thermal
capacity of IL 2 limits the need to cool the samples for reaction.
Use of phosphonium ILs also facilitates product separation due to
the triphasic nature of water, ionic liquid, and hexane combina-
tions. The identification of this chemistry opens up the possibility
of limiting the use of ethereal solvents in this class of reactions thus
allowing for a general ‘‘Greening’’ of Grignard chemistry.
Funding was provided by the Natural Sciences and Engineering
Council of Canada. We are grateful to CYTEC for donation of
ILs, and to Dr Al Robertson for encouraging this research. Dr
Neil Branda, Ms. Diane Dickie, and Ms. Lisa Langois provided
useful ideas and discussions.
NaBH in IL 2 produces benzyl alcohol as the only detectable
4
product. Again, this type of reaction is not feasible in IL 1. In
all cases, IL 2 can be washed with water and hexanes, dried, and
re-used.
The inertness of IL 2 towards reaction with bases appears to be
couched in kinetic arguments. It is reasonable that deprotonation
of a phosphonium ion to produce phosphorane 3 and a salt would
be thermodynamically favoured, but evidence for this reaction was
not observed. Contrast this with Wittig reagents, which are derived
from materials analogous to 2, but generally with significantly
shorter alkyl groups. Access to the reactive protic site on 2 (Fig. 1)
is difficult, and hence the Grignard reagents dissolve in the IL 2 but
fail to react with it. Further support for this kinetic argument is
3 2 3
provided by noting that [Ph PCH CH ][Br] is deprotonated to
form a phosphorane by IL 2/PhMgBr solutions as shown by
31 1
P{ H} NMR studies. Addition of electrophilic reagents to the
2
5
basic IL 2 solution allows for standard organometallic chemistry
A recent review highlighted the non-innocence of 1,3-dialkyl
imidazoliums. Our results suggest that phosphonium-based ionic
liquids may be more suitable for reactions involving strong bases.
to proceed. Sufficient steric protection of imidazolium ions to
2
prevent deprotonation at the acidic C site is not feasible, and thus
IL 1 can quench Grignard reagents. We note that such kinetic/
Taramatee Ramnial, Daisuke D. Ino and Jason A. C. Clyburne*
Department of Chemistry, Simon Fraser University, 8888 University
Drive, Burnaby, BC V5A 1S6, Canada. E-mail: clyburne@sfu.ca
thermodynamic control of solvent reactivity is common in
synthetic chemistry; consider, for example, NaBH reduction of
4
an aldehyde in an ethanolic solution. Whereas reaction of
4
NaBH with ethanol to produce a borate and hydrogen gas is
Notes and references
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Scheme 1 Survey of reactions explored in IL 2. Reaction conditions:
i. DMF; ii. NaBH ; iii. acetone; iv. benzaldehyde; v. 2,6-dibromoiodo-
benzene; vi. Br ; vii. CuCl . All reactions were followed by an aqueous
work-up and an extraction with hexanes.
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26 | Chem. Commun., 2005, 325–327
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24 Experimental procedure: Reactant (aldehyde, ketone, DMF, etc.) was
added to a stirred solution composed of IL 2 (15 mL) and 5 mL of
3
1
1
1
6 5
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1
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2
saturated aqueous ammonium chloride followed by the addition of
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1
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