A simple halide-to-anion exchange method for heteroaromatic salts and ionic liquids

Article abstract of DOI:10.3390/molecules17044007

A broad and simple method permitted halide ions in quaternary heteroaromatic and ammonium salts to be exchanged for a variety of anions using an anion exchange resin (A- form) in non-aqueous media. The anion loading of the AER (OH- form) was examined using two different anion sources, acids or ammonium salts, and changing the polarity of the solvents. The AER (A- form) method in organic solvents was then applied to several quaternary heteroaromatic salts and ILs, and the anion exchange proceeded in excellent to quantitative yields, concomitantly removing halide impurities. Relying on the hydrophobicity of the targeted ion pair for the counteranion swap, organic solvents with variable polarity were used, such as CH₃OH, CH₃CN and the dipolar nonhydroxylic solvent mixture CH₃CN:CH₂Cl ₂ (3:7) and the anion exchange was equally successful with both lipophilic cations and anions.

Full text of DOI:10.3390/molecules17044007

Molecules 2012, 17, 4007-4027; doi:10.3390/molecules17044007
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
A Simple Halide-to-Anion Exchange Method for
Heteroaromatic Salts and Ionic Liquids
Ermitas Alcalde *, Immaculada Dinarès *, Anna Ibáñez and Neus Mesquida
Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Joan XXIII s/n,
08028 Barcelona, Spain; E-Mails: aibaneji7@alumnes.ub.edu (A.I.); neusmesquida@ub.edu (N.M.)
* Authors to whom correspondence should be addressed; E-Mails: ealcalde@ub.edu (E.A.);
idinares@ub.edu (I.D.); Tel.: +34-934-024-540 (E.A.).
Received: 29 February 2012; in revised form: 20 March 2012 / Accepted: 23 March 2012 /
Published: 2 April 2012
Abstract: A broad and simple method permitted halide ions in quaternary heteroaromatic
and ammonium salts to be exchanged for a variety of anions using an anion exchange resin
(A− form) in non-aqueous media. The anion loading of the AER (OH− form) was examined
using two different anion sources, acids or ammonium salts, and changing the polarity of
the solvents. The AER (A− form) method in organic solvents was then applied to several
quaternary heteroaromatic salts and ILs, and the anion exchange proceeded in excellent to
quantitative yields, concomitantly removing halide impurities. Relying on the hydrophobicity
of the targeted ion pair for the counteranion swap, organic solvents with variable polarity
were used, such as CH3OH, CH3CN and the dipolar nonhydroxylic solvent mixture
CH3CN:CH2Cl2 (3:7) and the anion exchange was equally successful with both lipophilic
cations and anions.
Keywords: imidazolium salts; pyridinium salts; ammonium salts; anion exchange resin;
counteranion exchange; ionic liquids
1. Introduction
Besides their recognized value as an alternative to conventional solvents, ionic liquids (ILs) are
becoming increasingly useful in a widening range of fields in chemistry leaning toward biology.
Indeed, ILs have featured extensively in recent scientific open literature and patents, which reflects
their importance in research and development (R&D) [1–9]. The greenness of commonly used IL

Molecules 2012, 17
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syntheses and purification procedures has been analyzed and evaluated [10] as well as their
environmental acceptability and their role in sustainable development [11]. Simple imidazolium
quaternary salts with a low melting point are a long-standing IL family and at the same time
imidazolium-based systems have continued their progress in anion recognition chemistry and
N-heterocyclic carbenes (NHCs) [12].
Chemical aspects of imidazolium-based ILs dealing with their preparation, counteranion exchange
and purity have been the subject of numerous studies and are currently being investigated with the aim
of obtaining pure IL salts, especially halide-free ion pair compounds [4,10,12–16]. A widespread
synthesis of imidazolium ILs makes use of a subclass of the Menschutkin reaction, a nucleophilic
substitution carried out under neutral conditions between N-substituted imidazoles and an alkyl or
benzylhalides, affording the targeted imidazolium system in which the counteranion, that is, the halide
ion, can be exchanged by different methods. The most frequent method is the classical halide ion
exchange with an inorganic salt (MA) that is also used to remove halide ions in ILs. The halide-containing
byproduct salts can then be removed by extraction or precipitation followed by filtration. The
challenging issue of purification can be addressed by several IL clean-up protocols to eliminate the
unwanted halide and/or metal species, among other byproducts [13–16]. The isolation and purification
of pure heteroaromatic quaternary systems can be troublesome, especially if the different ionic species
present in the solution-phase have a similar solubility. In this context, a comparative study of the
transformation of N-azolylpyridinium salts to the corresponding pyridinium azolate betaines showed
that the method of choice makes use of a strongly basic anion exchange resin, AER (OH− form) [17].
From 1986 onwards, the AER (OH− form) method has been applied to a variety of N-azolylimidazolium
and N-azolylpyridinium salts with several interanular linkers. Exploiting our standard AER (OH− form)
method, the halide-to-anion exchange of different types of bis(imidazolium) cyclophanes, protophanes
and calix[4]arenes was carried out using a column chromatography packed with a strongly basic AER
(OH− form) followed by immediate collection of the eluates in diluted aqueous acid solution [12,18–22].
The few examples of anion exchange resin application to ILs reported in the open literature use: (a)
the AER (OH− form) method, involving the swap of halides for OH−, and then to the [IL][OH]
aqueous or hydroalcoholic solution was slowly added a slight excess of an aqueous acid solution and
displacement of the OH− anion by the selected A− anion; or (b) the AER (A− form) method, involving
the incorporation of the anion in the resin (OH− form) before the anion is exchanged in ILs. Taking
advantage of the AER (OH− form) method, Ohno and co-workers prepared Bio-ILs using strong basic
Amberlite (OH− form) to exchange a halide ion for OH−, and organic acids or natural aminoacids were
added to the aqueous solution of [IL][OH] to prepare examples of imidazolium-based [IL][A] [23,24].
Choline cations were similarly transformed to the corresponding ionic liquids [25]. In the same way,
several ionic liquid buffers were prepared by treatment of the aqueous solution of [IL][OH] with
organic acids [26]. There are only a few reports exploiting the AER (A− form) method in water or
aqueous methanol. Thus, several examples of non-aqueous ionic liquids (NAILs) have been prepared
using an AER (PO43− form) [27]. An AER (OH− form) was loaded with mesylate or tosylate anions by
−
treatment with the corresponding sulfonic acid and the prepared AER (R/Ar-SO3 form) was then used
to transform several N,N’-dialkylpyrrolidinium iodides to the corresponding sulfonate cations [28].
Loading the anion exchanger with camphorsulfonate anion, AER (CS− form) gave the corresponding
[IL][CS]from either [IL][OTs] [29] or [IL]Br [30], the latter following a worthless protocol.

Molecules 2012, 17
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Treatment of [bmim]Cl with the AER (A− form) -acetate, lactate and nitrate- produced the anion
exchange giving [bmim][A] [31]. Recently, we examined the preparation of an AER (A− form)
conveniently loaded with a selected anion by treatment with either acids or ammonium salts in water
or hydroalcoholic media. The anion exchange was carried out in methanol, providing a pure ionic
liquid in quantitative yield. This simple procedure not only offers a convenient way to replace halide
anions by a broad range of anions in ILs, including task-specific and chiral ILs, but also eliminates
halide impurities [32]. Further studies have been directed towards expanding the scope of the
halide-for-anion swap in non-aqueous media to representative imidazolium ILs and known examples
of bis(imidazolium)-based frameworks for anion recognition. Both lipophylic imidazolium systems
and low hydrophilic anions proceeded in excellent to quantitative yields [33].
In this paper we report how the AER (A− form) method can be exploited for a halide-to-anion
exchange in several illustrative examples from IL families. The anion source and solvent selection for
loading the AER (OH− form) were first examined using different acids or ammonium salts and organic
solvent mixtures with variable polarity. The halide-to-anion exchange was then studied using
imidazolium-based ILs, random examples of quaternary azolium and pyridinium salts as well as
quaternary ammonium salts from the APIs family (Figure 1).
Figure 1. The AER (A− form) method applied to representative quaternary heteroaromatic
salts and quaternary ammonium salts.
2. Results and Discussion
2.1. AER (A− Form) Method. Anion Loading
Anion source. Two methods were used to load the anions: Via A, from acids, or via B, involving the
corresponding ammonium salt (Scheme 1 and Table 1).
The AER (OH− form) was packed in a column and treated with an aqueous or hydromethanolic
solution of the acid or ammonium salt. The loading effectiveness was then checked by passing a
methanolic solution of [bmim]I through the AER column loaded with the target anion and the halide
ion to another anion exchange proceeded in quantitative yield.

Molecules 2012, 17
4010
Scheme 1. AER (A− form) method: The loading.
Table 1. Loading AER (OH− form): Anion source and solvents.
Anion
AcO−
Cl−
Source
Solvent
(a)
(a)
(a)
(a)
(a)
(a)
(a)
(a)
Anion
AcO−
Cl−
Source
AcOH
HCl
HPF6
HBF4
BzOH
Solvent
(b)
(a), (b)
(b)
(b)
(b)(g)
+
NH4 AcO−
+
NH4 Cl−
−
+
−
−
PF6
BF4
NH4 PF6
PF6
−
+
−
−
NH4 BF4
BF4
−
+
−
CF3SO3
NH4 CF3SO3
BzO−
SCN−
F¯
NH4 SCN−
(S)-Lactate−
(S)-Lactic acid (b)
+
+
−
NH4 F−
MeSO3
MeSO3H
Bu2PO4H
HClO4
HNO3
Ibuprofene
(b)
−
+
−
−
H2PO4
NH4 H2PO4
Bu2PO4
(b), (c)
(a), (b)
(a), (b)
(d), (e)
−
+
−
−
HSO4
NH4 HSO4
(a)
(d), (e)
ClO4
+
−
Ph4B−
NH4 Ph4B−
NO3
Ibu−
Solvent: (a) H2O; (b) CH3OH:H2O; (c) CH3OH; (d) CH3CN:H2O (9:1); (e) CH3CN:CH3OH
(9.5:0.5); (f) THF:H2O (1:1); (g) THF:CH3OH (4:1).
Thus, following via A, the resin was charged with organic oxoanions derived from carboxilate
−
−
−
(R-CO2 ), including chiral (S)-lactate, sulfonate (MeSO3 ) or phosphate (Bu2PO4 ), together with
inorganic anions such as Cl−, NO3 or ClO4 , by treatment with the corresponding 1% aqueous acidic
solutions. When the loading was performed with the aqueous solution of CF3SO3H, HF, H3PO4 or
H2SO4, the polymeric matrix was partially denaturalized by overheating. For this reason, anions such
−
−
as CF3SO3 , F−, H2PO4 or HSO4 were loaded in the resin using aqueous solutions of their ammonium
−
−
−
salts (via B). In order to confirm the efficiency of the method, both procedures were used to load
−
−
AcO−, Cl−, PF6 or BF4 anions, and identical results were obtained. A few attempts to load anions
from their corresponding Na+, K+ or Li+ salt showed, however, that the replacement of OH− in the
AER was incomplete, as evidenced by an observed mixture of anions in the checking, and this was not
further studied.
Solvent selection. We extended our studies to the loading of hydrophobic anions, and explored
alternative solvents and solvent mixtures. Benzoic acid was selected to prepare the AER (BzO− from)

Molecules 2012, 17
4011
and then a methanolic solution of [bmim]I was used to check the iodide-to-benzoate anion switch. The
resin was first packed in a column and generously washed with the solvent, which was used afterwards
to load the benzoate anion. Pure solvents such as distilled CH3OH, CH3CN, THF and CH2Cl2 were
assayed, but only CH3OH provided the optimal loading. Then, several solvent mixtures containing
CH3CN or THF with H2O or CH3OH were applied. Among the successful loading solvent mixtures
that provided the AER in the BzO− form, those with the lowest proportions of water or methanol were
CH3CN:H2O (9:1), CH3CN:CH3OH (9.5:0.5), THF:H2O (1:1) or THF:CH3OH (4:1) (Scheme 1 and
Table 1).
These results indicated that a non-aqueous mixture can be used to incorporate lipophylic anions,
although the presence of a protic solvent was necessary for the OH− replacement in the AER. Once the
suitable solvent conditions were found, acetonitrile solvent mixtures were used to load representative
hydrophobic anions: The anti-inflammatory acid ibuprofen to explore via A and ammonium
tetraphenylborate to explore via B.
In order to check the loading effectiveness, a methanolic solution of [bmim]I was passed through
the AER (Ibu− form) or AER (Ph4B− form) and the pure [bmim][Ibu] [34] or [bmim][Ph4B] [35] was
obtained (see later). These results confirmed that lipophylic anions replace the OH− anion in resin
when using the appropriate solvent and the corresponding AER (A¯ form) obtained can then be used
for the halide-to-anion switch.
Loading and exchange ability. The anion amount that the AER can load and the amount of halide
that can then be exchanged were examined. Thus, 2.5 g (~3 cm3) of commercial wet A-26 (OH form)
was treated with a 1% NH4AcO aqueous solution until the pH value of the eluates indicated that
loading was complete. Thus, 14.54 mmol of AcO− was loaded with a maximum loading of 5.8 mmol
of AcO− per 1 g of this AER. In this context, the synthesis and characterization of resin-supported
organotrifluoroborates have recently been reported and the loading was quantified by a UV/Vis
spectroscopic analysis [36].
A 50 mM methanolic solution of [bbim]Br was passed through the packed column and aliquots
1
were collected periodically and examined by H-NMR. The related integration of signals
corresponding to the anion and imidazolium cation indicated that the exchange process was
quantitative up to nearly 14.54 mmol of ionic liquid, suggesting that the Br− exchange could take place
as long as there was enough AcO− anion (Scheme 2).
Scheme 2. AER (A− form) method. (i) Maximum anion loading. (ii) Checking anion
exchange capacity.

Molecules 2012, 17
4012
Additionally, it should also be considered that the AER used in the exchange can be recycled by
treatment with 10% NaOH aqueous solution, and the recovered AER (OH− form) can be re-utilized for
a new anion loading. In the present study, the chosen resin was Amberlyst A-26, given that it allows
the use of aqueous mixtures and non-aqueous solvents, but other similar strongly basic anion exchange
resins can be used instead.
2.2. AER (A− Form) Method. Anion Exchange
Having achieved the loading of several anions in the AER, we examined their efficiency in the
counterion exchange in imidazolium-based ILs, including [bmim]I or Br, [bbim]I or Br or [mmim]I
as well as [bm2im]Br. Thus, a methanolic solution of IL was passed through a column packed with the
AER (A− form) previously prepared, and the solvent was removed from the collected eluates.
Following this simple method, in almost all cases I− or Br−  95% halide-for-anion swapping was
obtained except for the hydrophobic anions Ph4B− and Ibu−, which gave for example, from [bmim]I in
65% and 95% yield, respectively (Table 2 and Scheme 3).
Table 2. Results of the iodide or bromide exchange in imidazolium ionic liquids.
[bmim]I or Br [bbim]I or Br
Yield Yield
I− I−
[mmim]I
Yield
[bm2im]Br
Yield
Br−
I−
Anion
AcO−
BzO−
Solvent (%) a (ppm) b (%) a (ppm) b (%) a (ppm) b (%) a (ppm) b
CH3OH 100
CH3OH 100
<20
<20
20–40
<20
100
100
100
100
―
100
100
100
100
―
<20
<20
<20
<20
100
95
100
95
―
100
―
100
100
―
100
100
100
100
100
100
100
―
<20
<20
<20
<20
98
100
100
92
100
100
―
―
91
100
―
―
97
―
―
100
100
―
91
―
<13
<13
<13
<13
<13
<13
(S)-Lactate− CH3OH
100
−
MeSO3
MeSO3
CH3OH 100
CH3CN
CH3OH 100
CH3OH 82
−
―
−
Bu2PO4
<20
ND c
ND
<20
ND c
ND
<20
F−
Cl−
PF6
PF6
NO3
ClO4
BF4
CH3OH 100
CH3OH 100
ND
<20
−
20–40
<20
ND
13–26
−
CH3CN
―
−
CH3OH 100
CH3OH 100 100–120 100
<20
100
<20
20–40
<20
20–40
20–40
<20
ND
<20
<20
20–40
20–40
20–40
<20
<20
<20
−
−
CH3OH 100
CH3OH 100
CH3OH 100
CH3OH 100
CH3OH 100
<20
<20
<20
<20
ND
<20
<20
<20
<20
100
100
100
100
100
45
100
―
―
13–26
−
H2PO4
−
HSO4
−
CF3SO3
SCN−
Ph4B−
Ph4B−
Ibu−
<13
ND
ND
CH3OH
CH3CN
CH3OH
CH3CN
65
95
95
―
―
―
<13
<13
Ibu−
100
96
ND: Not Determined. a Recovered new ion pair. Yields ≥95% in CH3OH were not further examined
b
in CH3CN; Halide contents after anion exchange determined by the silver chromate test;
c Analyzed by HPLC/IC from exchange of Br− by F−: Presence of Br− anion was not observed.

Molecules 2012, 17
Scheme 3. AER (A− form) method applied to imidazolium-based ILs.
4013
Moreover, no evidence of N-heterocyclic carbenes (NHCs) and/or dealkylation by-product
formation was observed despite the basic environment, e.g., anion basicity [13,37,38]. The purity of
1
the ionic liquids obtained by this method was qualitatively determined using H-NMR spectra, and/or
ESI(−)-MS experiments, and according to the silver chromate test, most analyses indicated low halide
contents (<20 ppm for I− or <13 ppm for Br−). Further quantification of possible halide impurity was
restricted by instrumental limitation [32].
Although the halide exchange occurred with lipophylic anions such as Ph4B−, when the process was
carried out in methanol the yield of the recovered compound decreased to 65%, due to the change of
solubility of the new ion pair, which caused their partial retention in the resin. Hence, organic solvents
such as CH3CN or CH2Cl2 or CH3CN:CH2Cl2 solvent mixtures were then selected to perform the
halide switch, the treatment of [bmim]I with AER (BzO− form) being used to check the process. The
results indicated that the exchange was successful in both aprotic organic solvents, while the use
of pure CH2Cl2 as a solvent in our usual exchange procedure was discarded due to experimental
difficulties, after testing several combinations, the mixture with the highest proportion of
dichloromethane that was workable was found to be CH3CN:CH2Cl2 (3:7). This enabled a quantitative
iodide-for-benzoate swap and afforded the possibility for those exchanges of hydrophobic ionic species.
Accordingly, the preparation of [bmim][Ph4B] or [bbim][Ph4B] from their corresponding iodide
salts using the AER (Ph4B¯ form) in CH3OH provided the corresponding ion pair in 65% and 45%
yield, respectively. The yield increased to 95% and 100% when CH3CN was used, confirming that less
polar solvents in the exchange process substantially improved the recovery of the less hydrophilic ion
pair (Scheme 4). Similarly, [bm2im]Br was directly studied in CH3CN and the exchange of Ph4B− and
Ibu− anions proceeded in 91% and 96% yields, respectively (Table 2).
Hydrophobic salts such as hexylmethylimidazolium chloride [hmim]Cl or decylmethylimidazolium
chloride [dmim]Cl were used to swap the chloride for the ibuprofenate anion. A solution of the
corresponding ionic liquid in CH3CN was passed through the AER (Ibu− form) affording the anion
exchange in 95% yields. A more lipophylic solvent was then used and quantitative results were

Molecules 2012, 17
4014
obtained with the dipolar nonhydroxylic organic solvent mixture CH3CN:CH2Cl2 (3:7) (Scheme 4 and
Table 3).
Scheme 4. AER (A− form) method. Halide to lipophylic anion exchange.
Table 3. Comparative results of chloride exchange in [hmim]Cl and [dmim]Cl.
Cation
hmim
Anion
Ibu−
Solvent
CH3CN
CH3CN:CH2Cl2 (3:7)
CH3CN
CH3CN:CH2Cl2 (3:7)
Yield (%) a Cl− (ppm) b
90
100
87
<6
<6
<6
<6
Ibu−
dmim
Ibu−
Ibu−
100
a Yield of the recovered new ion pair; b Halide contents after anion exchange determined by silver chromate test.
Next, the AER (A− form) method was extended to other anions. Thus, a methanolic solution of
−
[bmim]Cl was passed through the AER (PF6 form) packed column and the eluates were analyzed
1
after the solvent was removed. The H-NMR spectrum coincided with that of [bmim][PF6], which
indicated a successful exchange confirmed by the silver chromate test (<6 ppm of Cl−). Similarly, a
methanolic solution of [bmim][PF6] was passed through the AER (Cl− form) packed column and the
1H-NMR spectrum also showed the quantitative exchange (Scheme 5). Thus, a conveniently loaded
AER can be used to carry out the swapping from a range of anions other than halides. The process was
1
followed by H-NMR, since the signal corresponding to the C(2)-H of the imidazolium moiety is
generally the most influenced by the nature of the anion (see Experimental section); for example, the
chemical shift value measured in CDCl3 (0.02 M) is 9.07 ppm in [bmim][PF6] while in the same
conditions this value is 10.99 ppm in [bmim]Cl.
Scheme 5. AER (A− form) method: Chloride to hexafluorophosphate exchange and vice versa.

Molecules 2012, 17
4015
Regarding other heteroaromatic cationic systems, pyridinium ([bmpy]I) or benzimidazolium (2·I)
nuclei were chosen as examples to carry out the anion swap, together with the well known NHC
precursor 1,3-dimesitylimidazolium salt (1·Cl) (Figure 1 and Scheme 6). A methanolic solution of
[bmpy]I was passed through a column packed with the convenient AER (A− form), and the
corresponding pure [bmpy][A] were obtained in  98% yield, except for the acetate anion, which was
recovered in 84% yield. Changing to a more hydrophobic solvent, the iodide-for-acetate swap in
acetonitrile proceeded in quantitative yield. In the treatment of [bmpy]I with the AER (A− form), there
was no evidence in any case of the formation of decomposition byproducts, despite the basicity of
some anions, e.g., acetate (Table 4).
Scheme 6. Halide-to-anion exchange in quaternary azolium and pyridinium salts.
Following the same procedure, a methanolic solution of the new benzimidazolium salt 2·I was used
to obtain the corresponding ion pair 2·A, with excellent yields. The iodide exchange of the white solid
2·I (m.p. 150–1 °C) led to oily ion pairs at room temperature or solids with a low melting point
(see Experimental section). The new benzimidazolium salts 2·A are related to previously reported
benzimidazolium salts with potential use as new materials, e.g., ionic liquid crystals [39] and
crystalline metal-containing ILs [40–42]. Likewise, the chloride anion in 1,3-dimesitylimidazolium salt
1·Cl can be successfully displaced by a wide range of anions using the AER (A− form). When the
swapping took place in methanol, the recovery of 1·A was between 80 to 95%, but in acetonitrile
yields were nearly quantitative (Table 4). In all cases the silver chromate test revealed the low chloride
content after the exchange (<6 ppm), which confirmed the easy swapping of Cl− anion. These
examples demonstrated that the method is also effective with non IL cationic systems, and is a general
method for preparing tuneable quaternary heteroaromatic salts. Accordingly, the well-known catalyst
precursor 1·Cl [43] was easily transformed in 1·A, and the presence of different counteranions could
potentially modulate the formation of organometallic complexes due to their improved solubility and
the stabilizing effect of anion participation.

Molecules 2012, 17
Table 4. Results of the halide exchange in pyridinium, benzimidazolium and imidazolium
4016
salts [bmpy][I], 1·Cl and 2·I.
[bmpy][I]
Solvent Yield
I−
(%) a (ppm) b (%) a (ppm) b (%) a (ppm) b
1·Cl
2·I
Yield
Cl−
Yield
I−
Anion
AcO−
AcO−
BzO−
BzO−
CH3OH
CH3CN
CH3OH
CH3CN
84
100
100
―
100
100
―
100
100
98
―
100
―
100
―
―
<20
<20
<20
95
―
92
100
98
91
100
95
100
79
100
88
95
<6
100
―
95
―
100
90
100
97
100
100
―
95
―
100
―
―
<20
<6
<6
<6
<6
<6
<6
<6
<6
<6
<6
<6
ND
ND
<6
<20
(S)-Lactate− CH3OH
<20
<20
<20
<20
−
MeSO3
MeSO3
CH3OH
CH3CN
CH3OH
CH3OH
CH3OH
CH3CN
CH3OH
CH3CN
CH3OH
CH3CN
−
−
Bu2PO4
<20
<20
<40
<20
<20
<20
−
PF6
−
BF4
−
BF4
−
CF3SO3
CF3SO3
SCN−
<20
ND
<20
ND
−
91
97
82
SCN−
Ph4B−
CH3CN
a
ND: Not Determined. Yield of the recovered new ion pair. Yields ≥95% in CH3OH were not
further examined in CH3CN; b Halide contents after anion exchange determined by silver chromate test.
Two examples of quaternary ammonium salts were selected from the API family to confirm
the efficiency of the method with this type of ILs. The choline lactate ([Cho][Lact]) [44] was
quantitatively prepared from the corresponding [Cho]I using the AER (Lact− form) in methanol.
Didecyldimethylammonium bromide ([d2m2N]Br) was transformed to the antibacterial-anti-
inflammatory didecyldimethylammonium ibuprofenate [d2m2N][Ibu] [45].
This hydrophobic ammonium salt required the lipophylic solvent mixture CH3CN:CH2Cl2 (3:7) to
afford the quantitatively iodide-to-ibuprofenate switch, since in acetonitrile the yield was only 61%
(Scheme 7 and Table 5).
Scheme 7. AER (A− form) method. Quaternary ammonium salts.

Molecules 2012, 17
Table 5. The halide exchange in quaternary ammonium salts [Cho]I and [d2m2N]Br.
4017
Cation Anion
Solvent
Yield (%) a
I− (ppm) b
<20
Cho
d2m2N
(S)-Lactate− CH3OH
100
61
100
Ibu−
Ibu−
CH3CN
CH3CN: CH2Cl2 (3:7)
<13
<13
a
b
Yield of the recovered new ion pair; Halide contents after anion exchange
determined by silver chromate test.
The quaternary heteroaromatic and ammonium ILs prepared taking advantage of the AER (A− form)
method in organic solvents were characterized by 1H-NMR, electrospray ionization mass spectrometry
in the negative mode and the halide content was determined by the silver chromate test. When the
recovery of the new ion pair [IL][A] was 95%, a new assay was performed using a less polar organic
solvent, which improved the yield in the range of 95% to 100%. As mentioned above, the use of an
anion exchange resin implies the possibility of sorbet contamination [13,46], so, nano-particulates may
be an issue to analyze. The analysis of possible nano-particulate contamination was, however, beyond
the scope of the present study.
Recapping the results, the AER (A− form) method applied to different examples of quaternary
heteroaromatic salts and ionic liquids permitted the halide to be swapped for assorted anions in
excellent yields of 95% when the appropriate organic solvent or solvent mixture was used. It was
confirmed that the AER (A− form) method is efficient with imidazolium-based ILs, improving the
currently operative procedures of classical counteranion exchange. Against a large pool of quaternary
heteroaromatic and ammonium salts, we limited ourselves to the eleven examples shown in Figure 1 to
validate the AER (A− form) method in non-aqueous media.
3. Experimental
3.1. General
Ion exchanger resin Amberlyst A-26 (Aldrich, OH− form), [hmim]Cl, [dmim]Cl, [Cho]I and
[d2m2N]Br together with all acids, ammonium salts, reagents and solvents were purchased from
commercial suppliers, unless mentioned otherwise, and used without further purification. All solvents
were reagent grade and methanol and THF were distilled prior to use. [bmim]I [32], [bmim]Br [32],
[bbim]I [32], [bbim]Br [32], [mmim]I [32], [bm2im]Br [47], [bmpy]I [48], and 1·Cl [49] were
1
13
prepared according with the literature. H-NMR and C-NMR spectra were recorded on a Varian
1
13
1
13
Gemini 300 (300 MHz for H and 75.4 MHz for C) spectrometer at 298 K. H and C chemical
shifts were referenced with TMS as an internal reference. Mass spectrometric analyses were performed
on a LC/MSD-TOF (2006) mass spectrometer with a pumping system HPLC Agilent 1100 from
Agilent Technologies at Serveis Científico-Tècnics of universitat de Barcelona. The pH was measured
with benchmeter pH1100 (Eutech Instrunments, Nijkerk, The Netherlands), using Hamilton Flushtrode
pH electrode for hydroalcoholic solutions.

Molecules 2012, 17
4018
3.2. Loading the AER (OH− Form) with Acids or Ammonium Salts
A glass column (1 cm diameter ) packed with 2.5 g (~3 cm3) of commercial wet strongly basic
anion exchange Amberlyst A-26 (OH− form) was washed with water, and the column bed was
equilibrated progressively with water-solvent mixtures until reaching the selected solvent media used
afterwards for anion loading (~25 mL of each solvent mixture). A 1% acid or ammonium salt solution
in the appropriate solvent was passed slowly through the resin until the eluates had the same pH value
as the original selected acid solution, and then the resin was washed generously with solvent until
constant pH. The process was carried out at room temperature, using gravity as the driving force.
3.3. Anion Exchange: General Procedure
A solution of the imidazolium salt (0.5–0.6 mmol) in 10 mL of the selected solvent was passed
slowly through a column packed with ~3 cm3 of Amberlyst A-26 (A– form), and then washed with
25 mL of solvent. The combined eluates were evaporated, and the residue obtained was dried in a
vacuum oven at 60 °C with P2O5 and KOH pellets.
3.4. Silver Chromate Test
The amount of halide contents was determined by a silver chromate test following a similar
protocol to that described by Sheldon and co-workers [31]. An aqueous solution (5 mL) of potassium
chromate (5% p/v in Milli-Q water, 0.257 M) was added to the sample (5–10 mg). To 1 mL of the
resulting dark yellow solution was added a minimum amount of silver nitrate aqueous solution (0.24%
p/v in Milli-Q water, 0.014 M). A persistent red suspension of silver chromate would be observed if
the sample was free of halide. The minimum measurable amount of silver nitrate aqueous solution was
0.011 mL; consequently, the detection limit is approx. 6 ppm for Cl−, 13 ppm for Br− or 20 ppm for I−.
The halide content was determined at least twice for each sample.
3.5. 1,3-Dibutyl-5,6-dimethylbenzimidazolium Iodide (2·I)
A suspension of 5,6-dimethyl-1H-benzimidazole (1.00 g, 6.84 mmol) and NaH (0.40 g, 16.66 mmol)
in dry THF (100 mL) was stirred under argon atmosphere at 60 °C for 1 h, and then 1-iodobutane (1.50 g,
8.15 mmol) was added. The reaction mixture was stirred at 65 °C for 48 h, and then 5 mL of ethanol
were added. The solvent was evaporated to dryness, and the residue was treated with water (50 mL)
and extracted with CH2Cl2 (3 × 50 mL). The organic solution was dried over anhydrous Na2SO4,
filtered and the solvent was eliminated under vacuum. A mixture of the previous yellow oil (1.34 g,
6.62 mmol) and 1-iodobutane (1.23 g, 6.70 mmol) was stirred under argon atmosphere at 85 °C for 20 h.
The reaction mixture was washed with dry diethyl ether (3 × 25 mL) in an ultrasonic bath, providing
the pure 2·I as a white solid (2.47 g, 93% yield). M.p. 150–1 °C. δH (300 MHz; CDCl3; Me4Si) 0.99
(6H, t, J = 7.4 Hz, N-C3H6-CH3), 1.45 (4H, m, N-C2H4-CH2-CH3), 2.02 (4H, m, N-CH2-CH2-C2H5),
2.47 (6H, s, C(5,6)-Me), 4.56 (4H, t, J = 7.4 Hz, N-CH2-C3H7), 7.42 (2H, s, C(4,7)-H) and 11.01
(1H, s, C(2)-H). δC (75.4 MHz, CDCl3) 13.5, 19.8, 20.7, 31.3, 47.3, 112.8, 129.8, 137.5, 140.4.
HRMS-ESI(+) Calcd for C17H27N2 [M]+ 259.2169, found 259.2167.

Molecules 2012, 17
4019
Melting points of compounds 2·A: 2·MeSO3, 62–3 °C; 2·Bu2PO4, 56–7 °C; 2·PF6, 85–6 °C; 2·BF4,
109–110 °C; 2·CF3SO3, 78–9 °C; 2·SCN, 64–5 °C; 2·AcO, 2·BzO and 2·Lact are oily compounds at
room temperature
3.6. 1H-NMR Data of Compounds [bmim][A] (Table 6), [bbim][A] (Table 7), [mmim][A] (Table 8),
[hmim][A] (Table 9), [dmim][A] (Table 9), [bm2im][A] (Table 10), [bmpy][A] (Table 11), 1·A
(Table 12), 2·A (Table 13), [Cho][A] (Table 14) and [d2m2N][A] (Table 14)
1
Table 6. H-NMR chemical shift values of 1-butyl-3-methylimidazolium salt [bmim][A]
(300 MHz) at 298 K a.
Anion
AcO−
BzO−
Solvent
CDCl3
CDCl3
H-2 H-4
H-5
Bu
Me A−
11.35 7.09 7.08 4.30; 1.86; 1.37; 0.96 4.06 1.99
11.00 7.09 7.09 4.29; 1.84; 1.33; 0.92 4.08 8.10; 7.33
11.19 7.17 7.17 4.31; 1.89; 1.38; 0.98 4.08 3.46; 1.41
10.21 7.25 7.20 4.28; 1.87; 1.38; 0.97 4.05 2.80
10.19 7.36 7.23 4.25; 1.80; 1.33; 0.88 4.00 3.80;1.54;1.33; 0.88
10.27 7.52 7.44 4.35; 1.93; 1.41; 0.99 4.14
10.41 7.46 7.37 4.35; 1.91; 1.40; 0.98 4.13
(c) 7.50 7.33 4.29; 1.87; 1.36; 0.95 4.06
10.99 7.31 7.24 4.33; 1.91; 1.40; 0.98 4.13
9.07 7.26 7.23 4.20; 1.88; 1.38; 0.97 3.98
10.02 7.35 7.30 4.25; 1.88; 1.38; 0.97 4.02
9.15 7.30 7.26 4.23; 1.89; 1.39; 0.98 4.02
8.98 7.28 7.24 4.21; 1.87; 1.39; 0.97 3.98
9.27 7.32 7.28 4.21; 1.88; 1.38; 0.97 3.99
9.59 7.36 7.31 4.32; 1.92; 1.41; 0.99 4.11
9.86 7.10 7.02 4.02; 1.66; 1.24; 0.87 3.71 7.26; 6.95; 3.53; 2.35;
1.75; 1.39; 0.82
9.25 7.35 7.32 4.14; 1.80; 1.31; 0.93 3.84 1.66
9.43 7.29 7.28 4.19; 1.80; 1.30; 0.92 3.86 7.93; 7.27
8.63 7.37 7.34 4.16; 1.80; 1.31; 0.94 3.83 2.43
8.56 7.39 7.35 4.14; 1.81; 1.31; 0.94 3.83
9.04 7.39 7.36 4.15; 1.80; 1.31; 0.93 3.84
8.42 7.35 7.31 4.11; 1.79; 1.30; 0.93 3.80
8.58 7.37 7.34 4.13; 1.81; 1.31; 0.94 3.82
8.43 7.37 7.35 4.12; 1.81; 1.32; 0.94 3.82
8.43 7.36 7.33 4.12; 1.82; 1.32; 0.94 3.81
8.43 7.36 7.33 4.12; 1.80; 1.32; 0.94 3.81
8.49 7.37 7.34 4.13; 1.80; 1.30; 0.94 3.82
4.54 6.01 5.84 3.16; 1.33; 1.13; 0.89 2.76 7.52; 6.97; 6.78
8.19 7.27 d 7.27 d 4.05; 1.77; 1.30; 0.93 3.74 7.27; 6.99; 6.84
(S)-Lactate− CDCl3
−
MeSO3
Bu2PO4
I− b
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
−
Br−
F−
Cl−
PF6
−
−
NO3
−
ClO4
−
BF4
−
CF3SO3
SCN−
Ibu−
AcO−
BzO−
CD3CN
CD3CN
CD3CN
CD3CN
CD3CN
CD3CN
CD3CN
CD3CN
CD3CN
CD3CN
CD3CN
CDCl3
−
MeSO3
I−
Cl−
PF6
−
−
NO3
−
ClO4
−
BF4
−
CF3SO3
SCN−
Ph4B−
Ph4B−
CD3CN
Ph4B−
DMSO-d6 9.06 7.74 7.67 4.13; 1.75; 1.24; 0.89 3.82 7.16; 6.91; 6.78
a
b
Solution concentrations are 0.02 M; Unambiguous assignments were made by NOESY-1D
(400 MHz); c Signal not observed; d Included in the phenyl signal.

Molecules 2012, 17
4020
1
Table 7. H-NMR chemical shift values of 1,3-dibutylimidazolium salt [bbim][A]
(300 MHz) at 298 K a.
Anion
AcO−
BzO−
Solvent
CDCl3
CDCl3
H-2 H-4,5 Bu
A−
11.32 7.14 4.35; 1.86; 1.39; 0.97 2.01
11.40 7.16 4.34; 1.87; 1.35; 0.93 8.10; 7.32
11.29 7.14 4.33; 1.87; 1.37; 0.96 4.02; 1.39
9.73 7.51 4.30; 1.88; 1.37; 0.96 2.75
11.05 7.11 4.37; 1.88; 1.40; 0.94 3.87; 1.62; 1.40; 0.94
10.34 7.38 4.38; 1.95; 1.42; 0.99
10.58 7.42 4.36; 1.90; 1.37; 0.95
(b) 7.17 4.30; 1.89; 1.40; 0.98
11.05 7.23 4.38; 1.92; 1.41; 0.98
9.05 7.23 4.24; 1.88; 1.39; 0.98
9.89 7.39 4.25; 1.86; 1.33; 0.94
9.24 7.38 4.26; 1.88; 1.37. 0.96
9.12 7.36 4.23; 1.87; 1.36; 0.95
10.59 7.31 4.40; 1.84; 1.34; 0.92
10.84 7.40 4.39; 1.84; 1.34; 0.91
9.49 7.28 4.26; 1.88; 1.38; 0.98
9.18 7.34 4.25; 1.88; 1.38; 0.97
(S)-Lactate− CDCl3
−
MeSO3
Bu2PO4
I−
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CD3CN
CDCl3
CDCl3
CDCl3
DMSO-d6
−
Br−
F−
Cl−
PF6
NO3
ClO4
−
−
−
−
BF4
−
H2PO4
−
HSO4
−
CF3SO3
SCN−
Ph4B−
Ph4B−
(b) 5.81 3.10; 1.30; 1.13; 0.89 7.50; 6.98; 6.82
9.19 7.79 4.15; 1.77; 1.26; 0.90 7.18; 6.92; 6.78
a Solution concentrations are 0.02 M. b Signal not observed.
1
Table 8. H-NMR chemical shift values of 1,3-dimethylimidazolium salt [mmim][A]
(300 MHz) at 298 K a.
Anion
Solvent H-2
H-4,5 Me
A−
1.69
7.93; 7.28
3.80; 1.38
2.43
AcO−
CD3CN
CD3CN
CDCl3
9.05 7.32 3.83
9.29 7.33 3.85
11.04 7.15 4.03
8.58 7.33 3.83
10.88 7.15 4.04
8.48 7.34 3.83
8.57 7.34 3.83
8.38 7.32 3.82
8.57 7.34 3.83
8.45 7.33 3.82
BzO−
(S)-Lactate−
−
MeSO3
CD3CN
CDCl3
−
Bu2PO4
3.86; 1.61; 1.39; 0.90
I−
CD3CN
CD3CN
CD3CN
CD3CN
CD3CN
Cl−
PF6
NO3
ClO4
−
−
−

Molecules 2012, 17
4021
Table 8. Cont.
Anion
BF4
Solvent
CD3CN
CDCl3
CDCl3
CD3CN
CD3CN
H-2 H-4,5 Me
8.43 7.33 3.82
10.26 7.30 4.09
10.19 7.34 4.09
8.45 7.33 3.82
8.44 7.33 3.83
A−
−
−
H2PO4
−
HSO4
−
CF3SO3
SCN−
a Solution concentrations are 0.02 M.
1
Table 9. H-NMR chemical shift values of imidazolium salts [hmim][A] and [dmim][A]
in CDCl3 (300 MHz) at 298 K a,b.
9
5
H5
H4
H5
H4
N
N
N
N
H2
A¯
H2
A¯
Me
[hmim][A]
Me
[dmim][A]
Cation Anion H-2 H-4 H-5 CnHn+1
Me
A−
–
hmim
Cl−
10.80 7.44 7.31 4.30; 1.89; 1.30; 0.86 4.11
Ibu−
9.72 7.08 7.01 4.05; 1.74; 1.26; 0.86 3.75 7.28; 7.01; 3.54;
2.37; 1.78; 1.41; 0.86
–
10.58 7.01 6.99 4.11; 1.78; 1.25; 0.87 3.81 7.31; 6.98; 3.60;
dmim
Cl−
10.82 7.38 7.27 4.32; 1.89; 1.27; 0.86 4.12
Ibu−
2.39; 1.79; 1.46; 0.87
a
b
Solution concentrations are in the range of 0.015 to 0.025 M; H-4 and H-5 assignments were
made according [bmim]I.
1
Table 10. H-NMR chemical shift values of 1-butyl-2,3-dimethylimidazolium salt
[bm2im][A] in CDCl3 (300 MHz) at 298 K a.
Bu
H5
N
Me
N
H4
A¯
Me
Anion
AcO−
BzO−
H-4
H-5 Me-2 Me-3 Bu
A−
7.58 7.36 2.59
7.54 7.27 2.50
3.82
3.71
3.92
3.94
3.92
4.04
3.98
3.90
3.88
3.86
3.96
4.06; 1.67; 1.26; 0.86 1.72
3.90; 1.58; 1.23; 0.85 7.97; 7.27
4.12; 1.79; 1.40; 0.98 3.87; 1.30
4.14; 1.80; 1.38; 0.98 2.74
4.13; 1.76; 1.37; 0.96 3.77; 1.56; 1.37; 0.89
4.24; 1.81; 1.40; 0.98
4.18; 1.80; 1.39; 0.94
4.11; 1.79; 1.40; 0.96
4.10; 1.79; 1.40; 0.97
4.09; 1.80; 1.40; 0.97
(S)-Lactate− 7.49 7.26 2.70
−
MeSO3
Bu2PO4
Br−b
7.47 7.27 2.69
7.55 7.27 2.68
7.76 7.56 2.83
7.60 7.46 2.80
7.46 7.30 2.70
7.40 7.27 2.68
7.32 7.22 2.66
7.43 7.32 2.77
−
I−
PF6
−
−
BF4
−
CF3SO3
NCS−
4.17; 1.83; 1.43; 0.98

Molecules 2012, 17
4022
Table 10. Cont.
Anion
Ph4B−
Ph4B−c
Ibu−
H-4
H-5 Me-2 Me-3 Bu
A−
6.38 6.28 2.39
7.63 7.60 2.56
7.30 7.07 2.37
2.98
3.73
3.57
3.36; 1.52; 1.25; 0.92 7.46; 6.99; 6.83
4.09; 1.68; 1.29; 0.90 7.17; 6.92; 6.78
3.88; 1.56; 1.22; 0.85 7.23; 6.94; 3.45; 2.33;
1.73; 1.33; 0.81
a
b
Solution concentrations are 0.02 M; Unambiguous assignments were made by NOESY-1D
(400 MHz); c In DMSO-d6.
Table 11. 1H-NMR chemical shift values of 1-butyl-4-methylpyridinium salt [bmpy][A] in
CDCl3 (300 MHz) at 298 K a.
Anion
AcO−
BzO−
H-2,6
9.35
8.94
H-3,5 Me Bu
A−
7.82
7.70
7.81
7.83
7.83
7.90
7.80
7.82
7.82
7.91
2.62 4.82; 1.96; 1.35; 0.94 1.96
2.47 4.67; 1.82; 1.25; 0.83 8.00; 7.31
2.57 4.65; 1.88; 1.35; 0.87 3.89; 1.26
2.57 4.65; 1.91; 1.32; 0.87 2.68
2.53 4.72; 1.89; 1.30; 0.83 3.78; 1.50; 1.30; 0.83
2.66 4.84; 2.00; 1.41; 0.95
2.66 4.54; 1.95; 1.39; 0.95
2.66 4.60; 1.95; 1.39; 0.95
2.65 4.60; 1.94; 1.38; 0.94
2.70 4.77; 2.03; 1.44; 0.99
(S)-Lactate− 9.05
−
MeSO3
Bu2PO4
I−
9.09
9.36
9.24
8.60
8.73
8.80
8.94
−
−
PF6
−
BF4
−
CF3SO3
NCS−
a Solution concentrations are 0.02 M.
Table 12. 1H-NMR chemical shift values of 1,3-bis(mesityl)imidazolium salt 1·A in CDCl3
(300 MHz) at 298 K a.
Anion
H-2
H-4,5
7.46
7.44
7.56
7.63
7.67
7.57
7.57
7.57
7.57
Me-2',6' Me-4' H-3' A−
AcO−
11.54
11.03
10.31
9.83
10.76
10.98
8.77
2.20
2.07
2.10
2.09
2.12
2.20
2.14
2.09
2.09
2.35
2.25
2.32
2.31
2.30
2.34
2.37
2.32
2.34
7.04 2.16
6.87 7.63; 7.14
7.00 3.65; 1.04
6.98 2.31
BzO−
(S)-lactate−
−
MeSO3
−
Bu2PO4
6.97 3.43; 1.32; 1.20; 0.79
Cl−
PF6
7.03
7.07
6.99
7.01
−
−
BF4
9.19
9.29
−
CF3SO3

Molecules 2012, 17
4023
Table 12. Cont.
Anion
SCN−
Ph4B−
Ph4B−b
H-2
9.70
6.32
9.64
H-4,5 Me-2',6' Me-4' H-3' A−
7.63
7.06
8.25
2.19
2.02
2.11
2.37
2.20
2.35
7.08
6.77 7.30; 6.88; 6.77
7.20 7.18; 6.92; 6.78
a Solution concentrations are in the range of 0.01 to 0.02 M; b In DMSO-d6.
Table 13. 1H-NMR chemical shift values of 1,3-dibutyl-5,6-dimethylbenzimidazolium salt
2·A in CDCl3 (300 MHz) at 298 K a.
Anion
H-2 H-4,7 Me
Bu
A−
AcO−
11.86
11.91
11.39
10.63
11.52
10.98
9.25
7.37
7.37
7.36
7.40
7.36
7.43
7.43
7.48
7.42
7.43
2.46 4.55; 1.96; 1.42; 0.97 2.03
2.45 4.56; 2.00; 1.41; 0.93 8.11; 7.34
2.43 4.49; 1.92; 1.37; 0.93 4.03; 1.37
2.47 4.53; 1.98; 1.44; 0.99 2.84
2.45 4.57; 1.96; 1.41; 0.97 3.90; 1.62; 1.41; 0.90
2.46 4.55; 2.02; 1.46; 0.99
BzO−
(S)-lactate−
−
MeSO3
−
Bu2PO4
I−
PF6
−
2.48 4.41; 1.97; 1.43; 0.99
−
BF4
9.33
2.45 4.43; 1.94; 1.40; 0.94
−
CF3SO3
9.86
2.47 4.48; 1.97; 1.43; 0.98
SCN−
10.13
2.48 4.53; 2.02; 1.47; 1.00
a Solution concentrations are 0.02 M.
1
Table 14. H-NMR chemical shift values of quaternary ammonium salts [Cho][A] and
[d2m2N][A] (300 MHz) at 298 K.
Me
Me
OH
9
N
N
Me
Me
Me A¯
A¯
9
[Cho][A]
[d2m2N][A]
Cation Anion
Solvent Me N+-CH2-CH2-OH
CD3CN 3.12 3.95; 3.41; 3.59(OH) –
A−
Cho
I−
(S)-Lactate− CD3CN 3.13 3.95; 3.43; 3.67(OH) 3.78; 1.19
N+-CnHn+1
d2m2N
Br−
CDCl3 3.41 3.51; 1.65; 1.30; 0.88 –
CDCl3 3.01 3.10; 1.52; 1.26; 0.88 7.30; 7.00; 3.57;
2.39; 1.81; 1.42; 0.88
Ibu−
4. Conclusions
Faced with a large variety of quaternary imidazolium and ammonium salts, the present study using
an anion exchange resin (A− form) in non-aqueous media was based on a choice of eleven examples

Molecules 2012, 17
4024
taken from the IL pool [IL]X that could serve to evaluate the halide-for-anion swap. Significant
aspects of the reported AER (A− form) process are: (i) the anion loading of the AER (OH− form) with
acids and ammonium salts in solvent mixtures of different polarities according to the hydrophobicity
of the anion source; (ii) the anion exchange using the AER (A− form) method in organic solvents was
easily applied to several imidazolium, benzimidazolium, pyridinium and ammonium salts, the halide-
for-anion exchange progressing in excellent to quantitative yields. Depending on the hydrophobic
nature of the targeted organic salts, the counteranion exchange was accomplished in organic solvents
of variable polarity and dipolar nonhydroxylic organic solvent mixtures ranging from the lowest
proportions of water or methanol to lipophylic solvent mixtures such as CH3CN:CH2Cl2 (3:7).
On the whole, the AER (A− form) method in organic solvents is a method of choice for exchanging
the halide anions for a variety of anions in quaternary heteroaromatic and ammonium salts,
simultaneously removing halide impurities, which is often a troublesome task. This anion exchange
method could be adapted to a wide array of charged molecules crucial to advances in interdisciplinary
fields in chemistry.
Acknowledgments
The authors thank to the University of Barcelona for support, SCT-UB for the use of their
instruments, the D.G.I. (MICINN) Project CTQ2010-15251/BQU and the AGAUR (Generalitat de
Catalunya), Grup de Recerca Consolidat 2009SGR562. Thanks are also due to Lucy Brzoska for
helpful discussion on semantics and style.
References and Notes
1. Sowmiah, S.; Srinivasadesikan, V.; Tseng, M.-C.; Chu, Y.-H. On the chemical stabilities of ionic
liquids. Molecules 2009, 14, 3780–3813.
2. MacFarlane, D.R.; Pringle, J.M.; Howlett, P.C.; Forsyth, M. Ionic liquids and reactions at the
electrochemical interface. Phys. Chem. Chem. Phys. 2010, 12, 1659–1669.
3. Dupont, J.; Scholten, J.D. On the structural and surface properties of transition-metal
nanopartícules in ionic liquids. Chem. Soc. Rev. 2010, 39, 1780–1804.
4. Hallett, J.P.; Welton, T. Room-temperature ionic liquids: Solvents for synthesis and catalysis. 2.
Chem. Rev. 2011, 111, 3508–3576.
5. le Bideau, J.; Viau, L.; Vioux, A. Ionogels, ionic liquid based hybrid materials. Chem. Soc. Rev.
2011, 40, 907–925.
6. Plechkova, N.V.; Seddon, K.R. Applications of ionic liquids in the chemical industry. Chem. Soc.
Rev., 2008, 37, 123–150.
7. Stoimenovski, J.; MacFarlane, D.R.; Bica, K.; Rogers, R.D. Crystalline vs. ionic liquid salt forms
of active pharmaceutical ingredients: A position paper. Pharm. Res. 2010, 27, 521–526.
8. Deetlefs, M.; Seddon, K.R. Assessing the greenness of some typical laboratory ionic liquid
preparations. Green Chem. 2010, 12, 17–30.
9. Yau, H.M.; Chan, S.J.; George, S.R.D.; Hook, J.M.; Croft, A.K.; Harper, J.B. Ionic liquids: Just
molten salts after all? Molecules 2009, 14, 2521–2534.

Molecules 2012, 17
4025
10. Petkovic, M.; Seddon, K.R.; Rebelo, L.P.N.; Pereira, C.S. Ionic liquids: A pathway to
environmental acceptability. Chem. Soc. Rev. 2011, 40, 1383–1403.
11. Sun, N.; Rodríguez, H.; Rahmana, M.; Rogers, R.D. Where are ionic liquid strategies most suited
in the pursuit of chemicals and energy from lignocellulosic biomass? Chem. Commun. 2011, 47,
1405–1421.
12. Alcalde, E.; Dinarès, I.; Mesquida, N. Imidazolium-based receptors. Top. Heterocycl. Chem.
2010, 24, 267–300.
13. Clare, B.; Sirwardana, A.; MacFarlane, D.R. Synthesis and purification of ionic liquids.
Top. Curr. Chem. 2009, 290, 1–40.
14. Olivier-Bourbigou, H.; Magna, L.; Morvan, D. Ionic liquids and catalysis: Recent progress from
knowledge to applications. Appl. Catal. A 2010, 373, 1–56.
15. Smiglak, M.; Hines, C.C.; Rogers, R.D. New hydrogen carbonate precursors for efficient
and byproduct-free syntheses of ionic liquids based on 1,2,3-trimethylimidazolium and
N,N-dimethylpyrrolidinium cores. Green Chem. 2010, 12, 491–501.
16. Nockemann, P.; Thijs, B.; Driesen, K.; Janssen, C.R.; van Hecke, K.; van Meervelt, L.;
Kossmann, S.; Kirchner, B.; Binnemans, K. Choline saccharinate and choline acesulfamate: Ionic
liquids with low toxicities. J. Phys. Chem. B 2007, 111, 5254–5263.
17. Alcalde, E.; Dinarès, I.; Fayet, J.-P.; Vertut, M.-C.; Elguero, J. Synthesis of highly dipolar
betaines: Pyridinium azolates. J. Chem. Soc. Chem. Commun. 1986, 734–735.
18. Alcalde, E.; Alemany, M.; Pérez-García, L.; Rodríguez, M.L. Non-classical [14]metaheterophanes
containing betaine units. Synthesis, NMR spectroscopy, and X-ray crystallography. J. Chem. Soc.
Chem. Commun. 1995, 1239–1240.
19. Alcalde, E.; Alemany, M.; Gisbert, M. A direct synthetic approach to novel quadrupolar [14]
azolophanes. Tetrahedron 1996, 52, 15171–15188.
20. Alcalde, E.; Alvarez-Rúa, C.; García-Granda, S.; García-Rodriguez, E.; Mesquida, N.;
Pérez-García, L. Hydrogen bonded driven anion binding by dicationic [14] imidazoliophanes.
Chem. Commun. 1999, 295–296.
21. Alcalde, E.; Mesquida, N.; Vilaseca, M.; Alvarez-Rúa, C.; García-Granda, S. Imidazolium-based
dicationic cyclophanes. Solid-state aggregates with unconventional (C-H)+···Cl− hydrogen
bonding revealed by X-ray diffraction. Supramol. Chem. 2007, 19, 501–509.
22. Dinarès, I.; de Miguel, C.G.; Mesquida, N.; Alcalde, E. Bis(imidazolium)-calix[4]arene receptors
for anion binding. J. Org. Chem. 2009, 74, 482–485.
23. Ogihara, W.; Yoshizawa, M.; Ohno, H. Novel ionic liquids composed of only azole ions.
Chem. Lett. 2004, 33, 1022–1023.
24. Fukumoto, K.; Yoshizawa, M.; Ohno, H. Room temperature ionic liquids from 20 natural amino
acids. J. Am. Chem. Soc. 2005, 127, 2398–2399.
25. Fukaya, Y.; Iizuka, Y.; Sekikawa, K.; Ohno, H. Bio ionic liquids: Room temperature ionic liquids
composed wholly of biomaterials. Green Chem. 2007, 9, 1155–1157.
26. Ou, G.; Zhu, M.; Shea, J.; Yuan, Y. Ionic liquid buffers: A new class of chemicals with potential
for controlling pH in non-aqueous media. Chem. Commun. 2006, 4626–4628.

Molecules 2012, 17
4026
27. Lall, S.I.; Mancheno, D.; Castro, S.; Behaj, V.; Cohen, J.I.; Engel, R. Polycations. Part X. LIPs,
a new category of room temperature ionic liquid based on polyammonium salts. Chem. Commun.
2000, 2413–2414.
28. Golding, J.; Forsyth, S.; MacFarlane, D.R.; Forsyth, M.; Deacon, G.B. Methanesulfonate and
p-toluenesulfonate salts of the N-methyl-N-alkylpyrrolidinium and quaternary ammonium cations:
Novel low cost ionic liquids. Green Chem. 2002, 4, 223–229.
29. Machado, M.Y.; Dorta, R. Synthesis and characterization of chiral imidazolium salts. Synthesis
2005, 2473–2475.
30. Nobuoka, K.; Kitaoka, S.; Kunimitsu, K.; Iio, M.; Harran, T.; Wakisaka, A.; Ishikawa, Y.
Camphor ionic liquid: Correlation between stereoselectivity and cation-anion interaction.
J. Org. Chem. 2005, 70, 10106–10108.
31. Ruiz-Toral, A.; de los Ríos, A.P.; Hernández, F.J.; Janssen, M.H.A.; Schoevaart, R.;
van Rantwijk, F.; Sheldon, R.A. Cross-linked Candida antarctica lipase B is active in denaturing
ionic liquids. Enzyme Microb. Technol. 2007, 40, 1095–1099.
32. Dinarès, I.; de Miguel, C.G.; Ibáñez, A.; Mesquida, N.; Alcalde, E. Imidazolium ionic liquids:
A simple anion exchange protocol. Green Chem. 2009, 11, 1507–1510.
33. Alcalde, E.; Dinarès, I.; Ibáñez, A.; Mesquida, N. A general halide-to-anion switch for
imidazolium-based ionic liquids and oligocationic systems using anion exchange resins (A− form).
Chem. Commun. 2011, 47, 3266–3268.
34. Viau, L.; Tourné-Péteilh, C.; Devoisselle, J.-M.; Vioux, A. Ionogels as drug delivery system:
One-step sol-gel synthesis using imidazolium ibuprofenate ionic liquid. Chem. Commun. 2010,
46, 228–230.
35. Dupont, J.; Suarez, P.A.Z.; de Souza, R.F.; Burrow, R.A.; Kintzinger, J.-P. C-H—π interactions in
1-n-Butyl-3-methylimidazolium Tetraphenylborate molten salt: Solid and solution structures.
Chem.-Eur. J. 2000, 6, 2377–2381.
36. Yong, L.; Yao, M.-L.; Green, J.F.; Kelly, H.; Kabalka, G.W. Syntheses and characterization of
polymer-supported organotrifluoroborates: Applications in radioiodination reactions. Chem. Commun.
2010, 46, 2623–2625.
37. MacFarlane, D.R.; Pringle, J.M.; Johansson, K.M.; Forsyth, S.A.; Forsyth, M. Lewis base ionic
liquids. Chem. Commun. 2006, 1905–1917.
38. Rodríguez, H.; Gurau, G.; Holbreya, J.D.; Rogers, R.D. Reaction of elemental chalcogens with
imidazolium acetates to yield imidazole-2-chalcogenones: Direct evidence for ionic liquids as
proto-carbenes. Chem. Commun. 2011, 47, 3222–3224.
39. Lee, K.M.; Lee, C.K.; Lin, I.J.B. First example of interdigitated U-shape benzimidazolium ionic
liquid crystals. Chem. Commun. 1997, 899–900.
40. Wang, K.F.; Jian, F.F.; Zhuang, R.R.; Xiao, H.L. New ionic liquids of N,N'-dialkylbenzimidazolium
salt comprising copper(II) ions. Cryst. Growth Des. 2009, 9, 3934–3940.
41. Wang, K.F.; Jian, F.F.; Zhuang, R.R. A new ionic liquid comprising lanthanum(III) bulk-modified
carbon paste electrode: Preparation, electrochemistry and electrocatalysis. Dalton Trans. 2009,
4532–4537.
42. Zhuang, R.R.; Jian, F.F.; Wang, K.F. A new binuclear Cd(II)-containing ionic liquid: Preparation
and electrocatalytic activities. J. Organomet. Chem. 2009, 694, 3614–3618.

Molecules 2012, 17
4027
43. Arduengo, A.J., III. Looking for stable carbenes: The difficulty in starting anew. Acc. Chem. Res.
1999, 32, 913–921.
44. Vijayaraghavan, R.; Thompson, B.C.; MacFarlane, D.R.; Kumar, R.; Surianarayanan, M.;
Aishwarya, S.; Sehgal, P.K. Biocompatibility of choline salts as crosslinking agents for collagen
based biomaterials. Chem. Commun. 2010, 46, 294–296.
45. Hough, W.L.; Smiglak, M.; Rodríguez, H.; Swatloski, R.P.; Spear, S.K.; Daly, D.T.; Pernak, J.;
Grisel, J.E.; Carliss, R.D.; Soutullo, M.D.; et al. The third evolution of ionic liquids: Active
pharmaceutical ingredients. New J. Chem. 2007, 31, 1429–1436.
46. Clare, B.R.; Bayley, P.M.; Best, A.S.; Forsyth, M.; MacFarlane, D.R. Purification or
contamination? The effect of sorbents on ionic liquids. Chem. Commun. 2008, 2689–2691.
47. Burrell, A.K.; del Sesto, R.E.; Baker, S.N.; McCleskey, T.M.; Baker, G.A. The large scale
synthesis of pure imidazolium and pyrrolidinium ionic liquids. Green Chem. 2007, 9, 449–454.
48. Wang, J.; Cao, W.-F.; Su, J.-H.; Tian, H.; Huang, Y.-H.; Sun, Z.-R. Syntheses and nonlinear
absorption of novel unsymmetrical cyanines. Dyes Pigm. 2003, 57, 171–179.
49. Arduengo, A.J., III; Krafczyk, R.; Schmutzler, R. Imidazolylidenes, imidazolinylidenes and
imidazolidines. Tetrahedron 1999, 55, 14523–l4534.
Sample Availability: Samples of all compounds are available from the authors.
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