A general halide-to-anion switch for imidazolium-based ionic liquids and oligocationic systems using anion exchange resins (A- form)

Article abstract of DOI:10.1039/c0cc05350c

Further studies on the application of an AER (A^- form) method broadened the anion exchange scope of representative ionic liquids and bis(imidazolium) systems. Depending on the hydrophobicity nature of the targeted imidazolium species and counte

Full text of DOI:10.1039/c0cc05350c

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COMMUNICATION
A general halide-to-anion switch for imidazolium-based ionic liquids and
oligocationic systems using anion exchange resins (Aꢀ form)wz
´
Ermitas Alcalde,* Immaculada Dinares,* Anna Ibanez and Neus Mesquida
Received 3rd December 2010, Accepted 18th January 2011
DOI: 10.1039/c0cc05350c
Further studies on the application of an AER (Aꢀ form) method
broadened the anion exchange scope of representative ionic
liquids and bis(imidazolium) systems. Depending on the hydro-
phobicity nature of the targeted imidazolium species and counter-
anions, different organic solvents were used to swap halides for
assorted anions, proceeding in excellent to quantitative yields.
azolate betaines showed that the method of choice makes
use of a strongly basic anion exchange resin (AER) converted
to the hydroxide form.13 From 1986 onwards, this procedure
was then conveniently applied to a variety of N-azolylimid-
azolium salts with several interannular linkers, including
aza-analogues of sesquifulvalene with a betaine character.14
Exploiting our standard anion exchange procedure, AER
(OHꢀ form), the counteranions of different types of bis-
(imidazolium) cyclophanes, protophanes and calix[4]arenes
were exchanged.15,16 Recently, Rogers and co-workers have
reported an imidazolium-based platform for ILs built up from
a methyleneimidazolium tetrazolate subunit, and using an
AER (OHꢀ form) to prepare the betaine structural motif.17
There are only a few reports on the application of anion
exchange resins to imidazolium-based ILs using either an AER
(OHꢀ form) or AER (Aꢀ form) for the counteranion exchange
(Scheme S1, ESIz). Taking advantage of the anion exchange
resin (OHꢀ form) method, Ohno and co-workers prepared
Bio-ILs.18 Likewise, several ionic liquid buffers were prepared.19
To the best of our knowledge, there are very few examples
in open chemistry literature, applying the AER
(Aꢀ form) protocol in water or aqueous methanol. Thus,
non-aqueous ionic liquids (NAILs) have been prepared using
The incorporation of imidazolium quaternary salts in a wide
array of cationic and oligocationic systems situate them at the
crossroads of multidisciplinary fields in chemistry.2–4 The role
of ionic liquids (ILs), besides their increasing importance as
green solvents, has been broadened to ionic liquid salt forms of
active pharmaceutical ingredients (APIs),5 energetic ionic
liquids (EILs)6 and tuneable aryl alkyl ionic liquids
(TAAILs).7 Their industrial applications have also been
reviewed.8 Chemical aspects of imidazolium-based ILs
concern their preparation, counteranion exchange and
purity.2,9–12
The common synthetic route to imidazolium-based systems
is a subclass of the Menschutkin reaction and gives the
targeted imidazolium system in which the counteranions,
halide ions, can be exchanged by different methods. A habitual
method is to swap the halide ion for another anion using an
inorganic salt (MA) that is also used to remove halide ions in
ILs. The halide-containing by-product salts can then be elimi-
nated by extraction or precipitation followed by filtration.
Overcoming the purification complexity remains a challenging
issue with the aim of obtaining pure IL salts, especially halide-
free ion pairs.
an AER (PO4 form).20 In a likewise manner with an AER
3ꢀ
ꢀ
(R/Ar–SO3 form), several N,N0-dialkylpyrrolidinium iodides have
been transformed to the corresponding mesylate and tosylate
salts.21 Using an AER (CSꢀ form) loaded with camphor-
sulfonate anion, both ILsꢁOTs22 and following a worthless
protocol from ILsꢁBr23 gave the corresponding ILsꢁ[CS].
Treatment of [bmim][Cl] with several AER (Aꢀ form) pro-
duced the anion exchange giving [bmim][A].24 Recently, we
examined the preparation of an AER (Aꢀ form) conveniently
loaded with a variety of anions in water and hydromethanolic
media. The counteranion exchange of representative ILs was
carried out in aqueous methanol or methanol, providing a
pure ionic liquid in quantitative yield.1 Among different
purification protocols of imidazolium ILs,2,9–13 ion exchange
resins should be a plausible method of choice although few
reports have examined this.9,12,25
The apparent directness of the counteranion exchange
process does not imply that it is either simple or trivial since
isolation and purification of pure heteroaromatic quaternary
systems, e.g. imidazolium salts, is sometimes difficult and can
be a serious problem when the solubility of the different ionic
species present in the solution mixture is similar (Scheme S1,
ESIz).4
A comparative study of the transformation of
N-azolylpyridinium salts to the corresponding pyridinium
Laboratori de Quı´mica Orga`nica, Facultat de Farma`cia, Universitat
de Barcelona, Avda. Joan XXIII s/n, 08028, Barcelona, Spain.
E-mail: ealcalde@ub.edu
w Imidazolium-based frameworks. 22. Part 21: ref. 1.
z Electronic supplementary information (ESI) available: Scheme S1,
Tables S1–S5, Fig. S1, experimental procedures and spectral data. See
DOI: 10.1039/c0cc05350c
In this communication, we report our studies focused on
extending the scope of the AER (Aꢀ form) method to swap the
halide ion for another anion in water or hydromethanolic
media to dipolar nonhydroxylic organic solvents, e.g. CH3CN
and CH3CN : CH2Cl2 (3 : 7), for halide-free synthesis of
c
3266 Chem. Commun., 2011, 47, 3266–3268
This journal is The Royal Society of Chemistry 2011

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hydrophobic ILs. The usefulness of this procedure has been
further developed to hydrophobic bis(imidazolium) systems.
We first examined the AER (OHꢀ form) loading with acids
or ammonium salts using solvent mixtures with different
polarities. The column was packed with resin Amberlyst
A-26 (OHꢀ form)26 and loaded with a 1% benzoic acid
solution in different solvents, Scheme 1. The successful loading
of solvent mixture CH3CN : CH3OH (9.5 : 0.5) afforded AER
(Bzꢀ form) with the lowest proportion of a protic solvent,
indicating that a non-aqueous solvent mixture allowed low
water-soluble anions to be loaded and only a small proportion
of a protic solvent was necessary for the OHꢀ interchange in
the AER. The loading with two selected hydrophobic anions
was examined: via A, with the anti-inflammatory acid ibuprofen
and via B, with ammonium tetraphenylborate. The anion
loading effectiveness was then checked by passing a methanolic
solution of [bmim][I] through the AER column loaded with Bzꢀ
anion and the iodide-to-benzoate anion switch proceeded in
Next, in order to extend the protocol to less hydrophilic
cationic systems, a random of recently reported ILs allowed
us to evaluate if the anion exchange was equally successful.
Thus, a methanolic solution of [bm2im][Br] or [bmpy][I] was
passed through a column packed with the convenient AER
(Aꢀ form), affording the corresponding pure [bm2im][A] or
[bmpy][A], characterized by 1H NMR and ESI(ꢀ)-MS. The
anion exchange was effective in all cases although in a few
assays the yield of the new quaternary salts was only 88%,
which was then improved to 100% when the anion exchange
was performed in CH3CN (Scheme 2 and Table S2 in ESIz).
The AER (Aꢀ form) procedure was then applied to represen-
tative hydrophobic ILs such as [hmim][Cl] and [dmim][Cl]
together with the quaternary ammonium salt [d2m2N][Br] to
swap the halide for the ibuprofenate anion (Scheme 2 and
Table S3 in ESIz). A solution of the corresponding quaternary
salt in CH3CN was used to perform the anion exchange but
the yields were fairly moderate, 64%, 85% and 61% respec-
tively. A more lipophilic solvent mixture of CH3CN : CH2Cl2
(3 : 7) permitted the halide-to-ibuprofenate switch quantita-
tively, giving the targeted hydrophobic new ibuprofenate
imidazolium salts [hmim][Ibu] and [dmim][Ibu], and the
ꢀ
quantitative yield. Using AER (Ibuꢀ form) or (BPh4 form),
the anion exchange in methanol proceeded in 95% and 65%
yields, respectively. The test to check anion exchange in
acetonitrile for the lipophilic Ibuꢀ or BPh4 ꢀ a28nions improved
ꢀ
the yield of [bmim][Ibu]27 and [bmim][BPh4
]
to 100% and
95%, respectively (Scheme 1 and Table S1 in ESIz). Parallel to
this work, Viau et al.27 have also reported the preparation of
[bmim][Ibu] in 94% yield following the classic precipitation
procedure from [bmim][Cl] (Table S1, ESIz).
Scheme 2 AER (Aꢀ form) procedure in organic solvents: the anion
exchange. (a) In CH3OH or CH3CN, imidazolium and pyridinium
salts: [bm2im][Br], [bmpy][I]. (b) In CH3CN or CH3CN : CH2Cl2
(3 : 7), imidazolium and quaternary ammonium salts: [hmim][Cl],
[dmim][BrCl], [d2m2N][Br].
Scheme 1 AER (Aꢀ form) procedure: the loading. (i) Loading the
AER (resin (OHꢀ form) with acids or ammonium salts in different
solvent mixtures. (ii) Checking the anion loading. (iii) Testing the
anion exchange in CH3CN.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 3266–3268 3267

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antibacterial–anti-inflammatory salt [d2m2N][Ibu], an example
of APIs reported by Rogers and co-workers.5
3 Recent reviews on anion recognition chemistry include:
C. Caltagirone and P. A. Gale, Chem. Soc. Rev., 2009, 38, 520;
Z. Xu, S. K. Kim and J. Yoon, Chem. Soc. Rev., 2010, 39, 1457.
4 E. Alcalde, I. Dinares and N. Mesquida, Top. Heterocycl. Chem.,
2010, 24, 267.
5 J. Stoimenovski, D. R. MacFarlane, K. Bica and R. D. Rogers,
Pharm. Res., 2010, 27, 521; W. L. Hough, M. Smiglak,
´
H. Rodrıguez, R. P. Swatloski, S. K. Spear, D. T. Daly,
J. Pernak, J. E. Grisel, R. D. Carliss, M. D. Soutullo,
J. H. Davis, Jr. and R. D. Rogers, New J. Chem., 2007, 31, 1429.
6 M. Smiglak, A. Metlen and R. D. Rogers, Acc. Chem. Res., 2007,
40, 1182.
7 S. Ahrens, A. Peritz and T. Strassner, Angew. Chem., Int. Ed.,
2009, 48, 7908.
8 N. V. Plechkova and K. R. Seddon, Chem. Soc. Rev., 2008, 37, 123.
9 B. Clare, A. Sirwardana and D. R. MacFarlane, Top. Curr. Chem.,
2009, 290, 1.
10 P. J. Scammells, J. L. Scott and R. D. Singer, Aust. J. Chem., 2005,
58, 155; S. Chowdhury, R. S. Mohan and J. L. Scott, Tetrahedron,
2007, 63, 2363.
Application of our simple halide-to-anion exchange
procedure with both lipophilic cations and low hydrophilic
anions confirmed its efficiency. Hence, further studies were
centered on four examples of less polar imidazolium-based
systems (see Fig. S1, ESIz): the (anthrylmethyl)imidazolium
fluorescent chloride 1ꢁCl;29 the known dicationic fluorescent
protophane anion receptor 2ꢁ2Cl;4,30 the bis(imidazolium)
cyclophane prototype 3ꢁ2Cl,4,16 and the new calix[4]arene
4ꢁ2Br (Table S1, ESIz).
The (anthrylmethyl)imidazolium chloride 1ꢁCl was trans-
ꢀ
formed to several fluorescent salts 1ꢁA, e.g. 1ꢁPF6ꢀ, 1ꢁBF4
,
1ꢁCF3SO3ꢀ, in yields from 70% to 89%, following the classic
counteranion exchange with inorganic salts (MA). Accord-
ingly, the ion pair 1ꢁCl recently reported by Dyson and
co-workers,29 could be an illustrative example of a less
polar simple imidazolium salt to test the efficiency of the
AER (Aꢀ form) procedure in organic solvents. When thꢀe
11 M. Smiglak, C. C. Hines and R. D. Rogers, Green Chem., 2010, 12,
491.
12 P. Nockemann, B. Thijs, K. Driesen, C. R. Janssen, K. Van Hecke,
L. Van Meervelt, S. Kossmann, B. Kirchner and K. Binnemans,
J. Phys. Chem. B, 2007, 111, 5254; H. Mehdi, K. Binnemans,
K. Van Hecke, L. Van Meervelt and P. Nockemann, Chem.
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13 E. Alcalde, I. Dinares, J.-P. Fayet, M.-C. Vertut and J. Elguero,
Chem. Commun., 1986, 734; E. Alcalde, I. Dinares, J. Elguero,
J.-P. Fayet, M.-C. Vertut, C. Miravitlles and E. Molins, J. Org.
Chem., 1987, 52, 5009.
AER conveniently loaded with PF6ꢀ, BF4 or CF3SO3
ꢀ
anions was used, the anion swap in CH3OH proceeded in
yields from 73% to 93%, whereas a less polar solvent mixture,
CH3CN : CH3OH (9 : 1) gaveꢀnearly quantitative yields of
ꢀ
1ꢁPF6ꢀ, 1ꢁBF4 and 1ꢁCF3SO3 (Table S4, ESIz). Using the
same solvent mixture, CH3CN : CH3OH (9 : 1), excellent
results were obtained for the chloride-to-anion switch of
bis(imidazolium) protophane 2ꢁ2Cl and cyclophane 3ꢁ2Cl with
a variety of anions to afford 2ꢁ2A and 3ꢁ2A, respectively. The
less polar example, the new bis(imidazolium) calix[4]arene
4ꢁ2Br was directly examined in CH3CN solution and the
exchange with representative anions such as AcOꢀ, BzOꢀ
MeSO3ꢀ, Bu2PO4ꢀand PF6ꢀ proceeded in nearly quantitative
yields (Table S5, ESIz).
14 E. Alcalde, I. Dinares, J. Frigola, J. Rius and C. Miravitlles, Chem.
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´ ´ ´
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In summary, the reported anion exchange resin (Aꢀ form)
procedure in non-aqueous media is a simple method of choice to
swap the halide ions for a broad range of anions in ionic liquids,
concomitantly removing halide impurities. Depending on the
hydrophobic nature of the imidazolium salt, different solvents
were used, such as CH3CN and the mixture CH3CN : CH2Cl2
(3 : 7). The halide ion swap procedure progressed in excellent to
quantitative yields with both lipophilic imidazolium species and
low hydrophilic anions. This anion exchange procedure could be
adapted to a diversity of charged molecules such as oligocationic
imidazolium systems, along with quaternary heteroaromatic
and ammonium salts, thereby developing its performance in
fields with still broad scope and unexplored applications such as
ionic liquids and anion recognition chemistry.
17 D. M. Drab, J. L. Shamshina, M. Smiglak, C. C. Hines,
D. B. Cordesy and R. D. Rogers, Chem. Commun., 2010, 46, 3544.
18 W. Ogihara, M. Yoshizawa and H. Ohno, Chem. Lett., 2004, 33,
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Enzyme Microb. Technol., 2007, 40, 1095.
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26 In the present study, resin Amberlyst A-26 has been chosen
but other strongly basic anion exchange resins could be used
instead.
This research was supported by Vicerrectorat de Recerca,
Universitat de Barcelona and by the D.G.I. (MICINN) Project
CTQ2010-15251/BQU. Thanks are also due to the AGAUR
(Generalitat de Catalunya), Grup de Recerca Consolidat
2009SGR562.
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Commun., 2010, 46, 228.
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Notes and references
1 I. Dinares, C. Garcia de Miguel, A. Ibanez, N. Mesquida and
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E. Alcalde, Green Chem., 2009, 11, 1507.
2 Recent reviews on ILs include: M. Deetlefs and K. R. Seddon,
Green Chem., 2010, 12, 17; H. Olivier-Bourbigou, L. Magna and
D. Morvan, Appl. Catal., A, 2010, 373, 1.
29 Z. Fei, D.-R. Zhu, X. Yang, L. Meng, Q. Lu, W. H. Ang,
R. Scopelliti, C. G. Hartinger and P. J. Dyson, Chem.–Eur. J.,
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30 S. K. Kim, N. J. Singh, J. Kwon, I.-C. Hwang, S. J. Park,
K. S. Kim and J. Yoon, Tetrahedron, 2006, 62, 6065.
c
3268 Chem. Commun., 2011, 47, 3266–3268
This journal is The Royal Society of Chemistry 2011