Ionic liquids are compatible with on-water catalysis

Article abstract of DOI:10.1039/c3cc44150d

A major limitation of on-water catalysis has been the need for liquid reactants to enable emulsification. We demonstrate that ionic liquids are compatible with on-water catalysis, enabling on-water catalysed reactions for otherwise unreactive solid-solid systems. The unique solvation properties of ionic liquids dramatically expands the scope of on-water catalysis.

Full text of DOI:10.1039/c3cc44150d

ChemComm
View Article Online
View Journal | View Issue
COMMUNICATION
Ionic liquids are compatible with on-water catalysis†
Kaitlin D. Beare, Alexander K. L. Yuen, Anthony F. Masters, Thomas Maschmeyer
and Christopher S. P. McErlean*
Cite this: Chem. Commun., 2013,
49, 8347
Received 3rd June 2013,
Accepted 2nd August 2013
DOI: 10.1039/c3cc44150d
www.rsc.org/chemcomm
A major limitation of on-water catalysis has been the need for
liquid reactants to enable emulsification. We demonstrate that
ionic liquids are compatible with on-water catalysis, enabling on-
water catalysed reactions for otherwise unreactive solid–solid
systems. The unique solvation properties of ionic liquids dramati-
cally expands the scope of on-water catalysis.
The social imperative for sustainability has led to a re-evaluation of
traditional chemical methods, and provided impetus for a move
towards green chemistry. Solvent replacement and catalysis have been
identified as complementary approaches that may help mitigate the
impact of chemical synthesis.1 Possessing negligible vapour pressures,
ionic liquids are solvents that can theoretically be recycled indefinitely,
minimizing waste generation.2,3 Increasing the green credentials of
ionic liquids are their unique solvation properties that allow for a wide
range of otherwise insoluble materials, such as biomass, to participate
in chemical transformations.4–6 Aside from ionic liquids, water is
perhaps the most obvious green solvent. It has no toxicity, no
flammability, and is readily available, albeit in low purity (e.g. seawater).
Crucially, water can function as more than just a solvent. In 2005
Sharpless observed that the rate of reaction between certain insoluble
organic compounds increased when the reactions were performed as
aqueous emulsions.7 Driven by the unique reactivity of interfacial
water,8,9 this mode of reactivity is known as on-water catalysis.10,11
Scheme 1 Butler’s solid vs. liquid dipolar cycloadditions.
Scheme 2 Solid vs. liquid aromatic Claisen rearrangement.
We recently reported similar trends for the unimolecular aromatic
A factor limiting the widespread application of on-water chemi- Claisen rearrangement (Scheme 2).13 The insoluble compound 4
stry is the requirement for at least one reagent to be liquid in order failed to undergo rearrangement until it was converted into a liquid.
to generate the oil-in-water emulsion that is critical for catalysis. For We wondered if ionic liquids would serve as the liquid phase and
example, Butler and co-workers12 reported that when the dipolar still allow on-water catalysis to occur. Given that the ion pairs could
cycloadditions involving phthalazinium-2-dicyanomethanide (1) themselves interact with the interface, it was not obvious that ionic
were performed at temperatures below the melting points of the liquids would be compatible with interfacial reactivity. We now
dipolarophiles 2 and 3 (Scheme 1), there was essentially no reac- detail initial outcomes of our investigations.
tion. At temperatures above their melting points, 2 and 3 formed
Our first efforts focussed on the Diels–Alder cycloaddition of
aqueous emulsions and the reaction gave the products in high yield. anthracene-9-carbinol (6). Compound 6 is a solid with only sparing
aqueous solubility, but one that is known to undergo a hydrogen-
bond-accelerated cycloaddition.14,15 As detailed in Table 1, com-
pound 6 does not participate in a thermal Diels–Alder reaction with
School of Chemistry F11, University of Sydney, Sydney 2006, Australia.
E-mail: christopher.mcerlean@sydney.edu.au; Fax: +61 2 9351 3329;
solid dimethyl fumarate (7) under neat conditions at 80 1C (entry 1).
Tel: +61 2 9351 3970
This removes any contribution of the background thermal reaction
† Electronic supplementary information (ESI) available: Additional rate studies,
experimental details and compound characterisation. See DOI: 10.1039/c3cc44150d to the observed yields of subsequent cycloadditions. When 6 and 7
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 8347--8349 8347

View Article Online
Communication
ChemComm
Table 1 On-water Diels–Alder reaction between two solids
Table 2 Effect of ionic liquid on a liquid-containing on-water reaction
Entry
Solventa
Conversionb (%)
Entry
Solventa
Conversionb (%)
1
2
3
4
5
6
7
On-water
At-water
Neat
Toluene
Ethanol
[BMIM][NTf2]
On-water–[BMIM][NTf2]
83
50
49
54
57
64
85
1
2
3
4
5
6
7
8
9
Neat
At-water
On-water
Toluene
0
0
0
66
76
27
47
61
31
n-Butanol
[BMIM][NTf2]
On-water–toluene
On-water–[BMIM][NTf2]
Hexadecane–[BMIM][NTf2]
a
Reaction conditions: 7 (0.5 mmol), 9 (0.5 mmol) solvent (4 mL),
co-solvent (0.5 mL), rt, 45 min. Based on 1H NMR integration.
b
a
10% v/v ionic liquid-in-water emulsion leads to optimal results, but
that the on-water effect is observed at substantially lower concentra-
tions of ionic liquid, which may be beneficial for large scale reactions.
If the ionic liquid is merely acting as a ‘liquefier’ in these on-water
reactions then it ought to exert no influence on reactions that already
contain a liquid reagent. This is indeed the case. As detailed in Table 2,
the Diels–Alder reaction between the liquid diene 9 and the solid
dienophile 7 is accelerated on-water (compare entry 1 with entries 2–6).
Performing the reaction in an ionic liquid-in-water emulsion gave the
same conversion as the reaction performed without the ionic liquid
(entries 1 and 7). The ionic liquid had no influence on the rate.
The beneficial impact of ionic liquids lies not in using them as
substitutes for organic solvents, but in harnessing their unique
properties to dissolve typically insoluble compounds. As such we
examined the dipolar cycloaddition between the highly insoluble
phthalazinium compound 1 and various dipolarophiles.
As shown in Table 3, the solid–liquid dipolar cycloaddition between
1 and the liquid phthalimide 11 was monitored at short and long
reaction times. At short reaction times the level of conversion correlates
with the solubility of compounds 1 and 11. Whilst it is not visible to the
eye, compound 1 must have some solubility in the liquid dipolarophile
11 such that the cycloaddition occurs under neat reaction conditions
(entry 1). Although 1 is not soluble in water,12 compound 11 is slightly
Reaction conditions: 6 (0.5 mmol), 7 (0.5 mmol) solvent (4 mL),
co-solvent (0.5 mL), 80 1C, 16 h. Based on 1H NMR integration.
b
were added to water and gently stirred (conditions we have pre-
viously termed ‘at-water’8) the solid remained in contact with the
walls of the reaction vessel and no reaction occurred (entry 2). When
the mixture was vigorously stirred in the manner commonly
employed to generate an emulsion for on-water reactions (entry 3),
no emulsion was formed and the solid remained visible against the
surface of the vessel. Unsurprisingly, no reaction occurred. However,
when the reagents were dissolved in either non-polar or polar, protic
organic solvents (entries 4 and 5) the reaction smoothly gave the
desired cycloadduct. This demonstrates that it is not an inherent
lack of reactivity that stops the two compounds from reacting under
neat or on-water conditions, but rather it is a consequence of their
physical state. When the substrates were dissolved in the common
ionic liquid [BMIM][NTf2]16 the reaction proceeded sluggishly (entry
6). Could we add a small amount of solvent to the mixture of solid
reagents to dissolve them and provide for emulsion formation?
The answer is yes. Adding a small amount of an organic solvent to
the reaction mixture (entry 7) enabled emulsion formation and the
cycloaddition occurred. Of course, it may be that the product was
formed only in the organic solvent and that interfacial water played
no role. In any event, the addition of organic solvents to generate the
emulsion is unsatisfactory as it does not correspond to the ethos of
solvent replacement. In contrast, the addition of ionic liquid to the
solid reagents (entry 8) not only allowed for easy emulsion forma-
tion, but resulted in a much higher level of conversion than was seen
in the ionic liquid itself. The cause of this acceleration is not merely
physical in origin. Generation of an emulsion using [BMIM][NTf2]
and hexadecane (entry 9) gave conversion rates that corresponded to
the background reaction occurring in the ionic liquid phase. The
cycloaddition of the solid reagents 6 and 7 is accelerated when the
reaction is performed as an ionic liquid-in-water emulsion. Ionic
liquids are compatible with on-water catalysis.
Table 3 Ionic liquid on-water reaction of an insoluble solid and a liquid
Conversion at
20 minb,c (%)
Conversion
at 6 hb (%)
Entry
Solventa
1
2
3
4
5
6
7
8
Neat
At-water
Toluene
Ethanol
[BMIM][NTf2]
On-water
On-water–toluene
On-water–[BMIM][NTf2]
33
24
19
21
52
39
23
79
84
53
78
85
79
88
74
100
The amount of ionic liquid used to generate the emulsion displays
an effect on the efficacy of catalysis. With too little ionic liquid the
reagents will not necessarily be emulsified and reaction would occur
through Butler’s phase transitioning mechanism.12 On the other
hand, too much ionic liquid would result in reagent dilution and
reduce the likelihood of interaction with interfacial water. After
a
Reaction conditions: 1 (0.5 mmol), 11 (0.5 mmol) solvent (4 mL),
co-solvent (0.5 mL), rt. Based on 1H NMR integration. Only the endo
b
c
experimentation (see ESI†), we discovered that an approximately isomer was observed.
c
This journal is The Royal Society of Chemistry 2013
8348 Chem. Commun., 2013, 49, 8347--8349

View Article Online
ChemComm
Communication
soluble, such that when the reaction is performed at-water (entry 2)
some of the dipolarophile dissolves into the aqueous phase leaving less
to function as a solvent that facilitates the neat cycloaddition. Conse-
quently, the level of conversion decreases appreciably. The same trend
is apparent for organic solvents (entries 3 and 4) in which 11 is soluble,
but 1 is not. Both compounds 1 and 11 are soluble in [BMIM][NTf2]
(entry 5) and it is here that the rate of the background reaction can be
accurately assessed. The scene is now set to ascertain whether or not
the reaction is susceptible to on-water catalysis. Attempts to generate an
emulsion by vigorous stirring of the reactants in the presence of water
(entry 6) failed due to the low solubility of 1.
The rate of conversion mirrored the neat reaction (compare entries
1 and 6). Similarly, employing water–organic mixtures (entry 7) failed
to provide an oil-in-water emulsion due to the insolubility of 1. The
presence of the organic phase only aided dissolution of 11 and
consequently the level of conversion mirrored that of the organic
solvent (entry 3). Strikingly, the ionic liquid-in-water emulsion gener-
ated with [BMIM][NTf2] led to a large increase in conversion (compare
entries 5 and 8). The enhanced solubilising ability of the ionic liquid
enabled a previously inaccessible on-water catalysed transformation to
be conducted under exceedingly mild conditions.
The reaction between the insoluble 1 and a solid dipolarophile 13
gave similar results (see Table 4). Of note is the observation that low
purity water (i.e. sea water) can be used in the process with little
effect on catalysis (entry 8). The magnitude of the on-water effect was
evident in that the reactions of the imides 11 and 13 conducted as
ionic liquid-in-water emulsions reached completion in ca. 80 min,
whereas the on-water reactions and the reactions in organic solvents
required prolonged reaction times of 12–24 hours (see ESI†).17
Our attention then turned to the most challenging scenario, which
was highlighted in Scheme 1. When both reactants are solids with low
solubility in water and traditional solvents, then the only recourse has
been the thermal liquefaction of at least one of the reagents to access
the on-water mode of catalysis. As shown in Scheme 3, the ionic
liquid-on-water reaction of 1 and 3 gave the cycloadduct 5 in moderate
yield at 40 1C. The reaction was performed slightly above ambient
temperature to allow accurate measurement of endo :exo ratios.17
Scheme 3 Dipolar cycloaddition of insoluble solids.
Table 5 Effect of ionic liquid composition on the reaction between 1 and 13
Water
miscibility
Conversion Conversion
in ILb (%) on-IL–waterb (%)
Entry Ionic liquida
1
2
3
4
5
[EMIM][FAP]
[BMIM][NTf2]
[EMIM][B(CN)4] Immiscible 77
[HMIM][BF4]
[BMIM][BF4]
Immiscible 10
Immiscible 32
18
64
98
6
Miscible
Miscible
45
25
9
a
Reaction conditions: 1 (0.5 mmol), 13 (0.5 mmol) solvent (4 mL),
co-solvent (0.5 mL), rt. Based on 1H NMR integration.
b
There was no increase in endo selectivity for this reaction, confirming
the on-water nature of the process (see ESI†).18 This result represents a
significant advance on existing, energy intensive methods.
Given that emulsion formation is an absolute requirement for
on-water catalysis, the emulsifying properties of the ionic liquids
ought to exert an effect on the level of conversion.19 As expected,
water immiscible ionic liquids facilitate on-water chemistry,
whereas water miscible ionic liquids do not (Table 5).
In summary, we have shown for the first time that ionic liquids
are compatible with on-water catalysis. Due to the unique solubilizing
properties of ionic liquids, this opens new vistas for ionic liquid-on-
water catalysis.
This work was funded by the Australian Research Council
(DP120102466).
Notes and references
1 P. Anastas and N. Eghbali, Chem. Soc. Rev., 2010, 39, 301–312.
2 M. Petkovic, K. R. Seddon, L. P. N. Rebelo and C. S. Pereira, Chem.
Soc. Rev., 2011, 40, 1383–1403.
3 J. P. Hallett and T. Welton, Chem. Rev., 2011, 111, 3508–3576.
4 H. Wang, G. Gurau and R. D. Rogers, Chem. Soc. Rev., 2012, 41, 1519–1537.
5 M. M. Hossain and L. Aldous, Aust. J. Chem., 2012, 65, 1465–1477.
6 M. E. Zakrzewska, E. Bogel-Lukasik and R. Bogel-Lukasik, Chem.
Rev., 2011, 111, 397–417.
Table 4 Ionic liquid on-water reaction of an insoluble solid and a solid
7 S. Narayan, J. Muldoon, M. G. Finn, V. V. Fokin, H. C. Kolb and
K. B. Sharpless, Angew. Chem., Int. Ed., 2005, 44, 3275–3279.
8 J. K. Beattie, C. S. P. McErlean and C. B. W. Phippen, Chem.–Eur. J.,
2010, 16, 8972–8974.
9 K. D. Beare and C. S. P. McErlean, Org. Biomol. Chem., 2013, 11, 2452–2459.
10 R. N. Butler and A. G. Coyne, Chem. Rev., 2010, 110, 6302–6337.
11 A. Chanda and V. V. Fokin, Chem. Rev., 2009, 109, 725–748.
12 R. N. Butler, A. G. Coyne and E. M. Moloney, Tetrahedron Lett., 2007,
48, 3501–3503.
13 K. D. Beare and C. S. P. McErlean, Tetrahedron Lett., 2013, 54, 1056–1058.
14 D. C. Rideout and R. Breslow, J. Am. Chem. Soc., 1980, 102, 7816–7817.
15 R. Breslow, U. Maitra and D. Rideout, Tetrahedron Lett., 1983, 24,
1901–1904.
Entry
Solventa
Conversion at 20 minb,c (%)
1
2
3
4
5
6
7
8
9
Neat
At-water
Toluene
Ethanol
[BMIM][NTf2]
On-water
On-water–toluene
On-water–[BMIM][NTf2]
On-sea water–[BMIM][NTf2]
0
0
10
9
32
0
15
64
52
16 H. Deng, C. Yuan, J. He and J.-P. Cheng, J. Org. Chem., 2012, 77, 7291–7298.
17 R. N. Butler, A. G. Coyne, W. J. Cunningham and L. A. Burke,
J. Chem. Soc., Perkin Trans. 2, 2002, 1807–1815.
18 R. N. Butler, A. G. Coyne, W. J. Cunningham and E. M. Moloney,
J. Org. Chem., 2013, 78, 3276–3291.
a
Reaction conditions: 1 (0.5 mmol), 13 (0.5 mmol) solvent (4 mL),
co-solvent (0.5 mL), rt. Based on 1H NMR integration. Only the endo 19 P. J. Scammells, J. L. Scott and R. D. Singer, Aust. J. Chem., 2005, 58,
b
c
isomer was observed.
155–169.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 8347--8349 8349