One-pot and solventless synthesis of ionic liquids under ultrasonic irradiation

Article abstract of DOI:10.1055/s-2007-984881

A novel method is described for the one-pot synthesis of various ionic liquids in a competitive time. By using ultrasonic irradiation, different families of nitrogen-bearing ionic liquids can be obtained in a solvent-free or in aqueous medium, which gives a greener touch to the overall process. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-984881

LETTER
2065
One-pot and Solventless Synthesis of Ionic Liquids under Ultrasonic
Irradiation
One-pot
a
u
ndSolventle
l
ss Synt
i
hesisof
e
I
onic Liqu
n
idsunder
U
ltrason
E
ic Irradiation stager,a Jean-Marc Lévêque,*a Giancarlo Cravotto,b Luisa Boffa,b Werner Bonrath,c Micheline Drayea
a
Laboratoire de Chimie Moléculaire et Environnement, Polytech Savoie, Université de Savoie, 73376 Le Bourget du Lac cedex, France
Fax +33(479)758674; E-mail: jean-marc.leveque@univ-savoie.fr
b
c
Dipartimento di Scienza e Tecnologia del Farmaco, Universita di Torino, Via Giuria 9, 10125 Torino, Italy
DSM Nutritional Products, Research and Development, VFCR, Building 214/071, Grenzacherstr. 124, 4070 Basel, Switzerland
Received 13 April 2007
C4H9
C4H9
Cl–
Abstract: A novel method is described for the one-pot synthesis of
various ionic liquids in a competitive time. By using ultrasonic irra-
diation, different families of nitrogen-bearing ionic liquids can be
obtained in a solvent-free or in aqueous medium, which gives a
greener touch to the overall process.
N
N
N
toluene
reflux
acetone, r.t.
NH4PF6
–
PF6
C4H9Cl
+
N
N
N
Scheme 1 Classical synthesis of BmimPF6
Key words: ionic liquids, ultrasound, solvent-free reaction
already been improved by using non-conventional activa-
tion methods such as microwave in a solventless proce-
dure.8 Sonochemistry can also be a tool for improving this
synthesis. Indeed, it is known to enhance some processes
through a physical phenomenon called cavitation, which
is the formation, growth and collapse of bubbles in an
elastic liquid.9 By imploding, these bubbles create local
high pressure (up to 1000 bar) and high temperature (up to
5000 K) that lead to high-energy radical mechanisms10
and also create some interesting physical effects such as
micromixing, mass transport or reduction of particle
size.11 As the metathesis using ammonium salt is a hetero-
geneous process, the ultrasound methods could be of great
benefit since they are able to reduce ammonium salt
particles and, thus, increase their reactivity.12
The use of volatile organic compounds (VOCs) in synthe-
sis is becoming more and more inconvenient in terms of
ecological impact. Thus, room-temperature ionic liquids
(RTILs) that have aroused a great interest because of their
unusual physicochemical properties have been designed
to solve this problem. Thanks to their purely ionic nature,
RTILs possess a negligible vapor pressure; in addition
they can be recycled by distillation, making them interest-
ing candidates for avoiding both air pollution and waste
production. Moreover, they can be used in a large variety
of chemical transformations owing to their tunable polar-
ity, high thermal stability, high liquid range and good sol-
vating ability.1 In this way, many applications have been
described in organic chemistry,2 catalysis,3 inorganic
chemistry4 or electrochemistry.5 Mainly because of the
lack of thermodynamic and toxicological data,6 the possi-
bility to use ionic liquids on a large scale is still unex-
plored. Their conventional synthesis includes two steps,
the quaternarization of a heteroatom by an alkyl halide
followed by the metathesis of the resulting anion with its
corresponding salt. An example of this synthesis for the
well-known 1-butyl-3-methylimidazolium hexafluoro-
phosphate (BmimPF6) with ammonium salt is given in
Scheme 1.
In a previous paper, Xu et al. described a one-pot three-
component synthesis of ionic liquids under thermal heat-
ing in heterogeneous conditions but the reaction time re-
mained significantly long (from 15 h with 1-alkyl bromide
to 35 h with 1-alkyl chloride) to obtain satisfactory yields
(up to 87%).13
In the present article, we report the first one-pot synthesis
of RTILs under ultrasonic irradiation. Our first experi-
ment was a solvent-free one-pot synthesis of BmimPF6
since it is one of the most used and known RTIL. Different
acoustic powers were utilized and the reaction conditions
are described in Table 1.
The metathesis step can also be performed using toxic
hexafluorophosphoric acid.7 Furthermore, a large volume
of volatile organic solvents (such as acetone, toluene,
acetonitrile) is involved in both steps which is quite prob-
lematic considering that one of the main goals in green
chemistry is to ban VOCs. Lastly, the time required to
obtain a ready-to-use ionic liquid can last up to a few days
if one considers synthesis and purification, avoiding a
larger-scale production. Consequently, this reaction has
Even if the results were not as good as expected, an in-
fluence of the power on the product yield was observed
(entries 1 and 2 in Table 1). In both sonication attempts,
the reaction mixture rapidly turned brown leading to low-
purity BmimPF6. Usually, the quaternarization occurs
with heat whereas metathesis takes place at room temper-
ature. The degradation observed is maybe due to this an-
tagonistic system. We then decided to check the thermal
stability of our reagents. 1-Methylimidazole was consid-
ered as stable since no degradation was observed by GC–
MS analysis after sonication. In our first few attempts of
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Advanced online publication: 12.07.2007
DOI: 10.1055/s-2007-984881; Art ID: G09907ST
© Georg Thieme Verlag Stuttgart · New York

2066
J. Estager et al.
LETTER
Table 1 Preliminary Results of Solvent-Free One-Pot Synthesis of
BmimPF6
phobic nature makes the workup easier. The results are
given in Table 3.
a
These results tend to prove that a rapid one-pot synthesis
of ionic liquids is possible as soon as starting materials are
designed for this objective. As expected, high thermally
stable salts are necessary to resist the harsh conditions
implied by sonication. Thus, only potassium hexafluoro-
phosphate seemed well suited for this synthesis.
Entry Activation
method
Temp Time
Yield
(°C)
(min) (%)
1
2
3
Ultrasound 20 kHz (37 W)
Ultrasound 20 kHz (50 W)
60
30
30
30
24
59
29
80
Magnetic stirring (ca 500 rpm) 140
However, the reaction conditions (temperature, time, etc.)
were not adequate when 1-chlorooctane was used; a much
longer reaction time would probably be required in that
case. In addition, 1-bromooctane would have to be used
for a swift synthesis even if the chloride compounds are
less expensive. Some tests concerning the level of purities
were performed on the obtained ionic liquid and 0.48%
w/w of bromide (ion-exchange chromatography) was ob-
tained and 0.26% w/w of water was observed with Karl-
Fischer titration. Moreover, no organic impurity was ob-
served in the 1H and 13C NMR data. These results tend to
prove that the purity of ionic liquids is acceptable, at least
for synthesis.
a Amine–NH4PF6–1-chlorobutane = 1:1:1.
‘one-pot’ reaction we noticed decomposition at an early
stage for ammonium hexafluorophosphate which stopped
the overall reaction. So, thermogravimetric analyses were
performed in the presence of air on four commercially
available hexafluorophosphate salts (NH4PF6, LiPF6,
NaPF6 and KPF6) to determine their stabilities. The results
of these analyses are given in Table 2.
Table 2 Thermogravimetric Data of Commercially Available
Hexafluorophosphate Salts
Different combinations of cations and alkyl halides were
then examined to generalize this procedure to different
families of hexafluorophosphate ionic liquids. The results
are given in Table 4.
Entry
Salt
Temp (°C) of decomposition
1
2
3
4
LiPF6
NaPF6
NH4PF6
KPF6
97
128
183
460
Average to good results were obtained for various combi-
nations of nitrogen-bearing heterocycles and alky halides.
When 1-bromobutane was used, water had to be added to
solubilize the solid bromide intermediate resulting from
quaternarization and to avoid precipitation. Indeed, this
precipitation could be very problematic since a solid me-
dium is able to reflect the ultrasonic waves, as it is well
known, for example in medical diagnostic,14 leading to a
possible damage to the ultrasonic probe by reflecting too
much energy on the ultrasound source. As our objective
was to develop an ‘as green as possible process’, water
was chosen. Unfortunately, results were poorer when 1-
bromobutane was used probably because of the dilution of
the medium by the additional water. Also, when 1-methyl-
pyrrolidine was used, a natural precipitation of the final
product was observed. As the yield was high enough for
N-octyl-N-methylpyrrolidinium hexafluorophosphate, no
Thus, the potassium salt was chosen for the synthesis of
hexafluorophosphate RTILs. Lastly, the alkyl halide was
changed in order to improve the overall reactivity. As the
first step involves a SN2 mechanism, the nature of the
halide is of great importance as already observed for
conventional ionic liquids synthesis.13 Since a too high
temperature resulted in the degradation of some reactants,
more reactive compounds were chosen to make the exper-
imental conditions milder. Some experiments were tried
with 1-octyl-3-methylimidazolium hexafluorophosphate
(OmimPF6) as model reactant since it is, like BmimPF6,
one of the most common ionic liquids, and its hydro-
Table 3 One-Pot Synthesis of OMImPF6 under Ultrasonic Irradiationa
Entry
Amine
PF6 salt
LiPF6
Alkyl halide
Temp (°C)b
Time (min)
120
Yield (%)c
1
2
3
4
5
1-methylimidazole
1-methylimidazole
1-methylimidazole
1-methylimidazole
1-methylimidazole
1-bromooctane
1-bromooctane
1-bromooctane
1-chlorooctane
1-bromooctane
85
85
80
80
85
0
NaPF6
NH4PF6
KPF6
120
0
120
trace
trace
85
120
KPF6
120
a Amine–PF6 salt–alkyl halide = 1:1:1’, ultrasonic irradiation: 30 kHz, acoustic power of 0.86 W/mL.
b Temperature increased because of ultrasound; a cryostat was used to control this heating phenomenon.
c Isolated yield.
Synlett 2007, No. 13, 2065–2068 © Thieme Stuttgart · New York

LETTER
One-pot and Solventless Synthesis of Ionic Liquids under Ultrasonic Irradiation
2067
Table 4 Ultrasound-Assisted Syntheses of PF6 Ionic Liquidsa
Entry
Amine
Alkyl halide
Temp (°C)d
Time (min)
180
Yield (%)e
1
2
3
4
5
6
7
8
9
1-methylimidazole
1-methylimidazole
1-methylimidazole
pyridine
1-bromohexane
1-bromopentane
1-bromobutaneb
1-bromooctane
1-bromohexanec
1-bromopentanec
1-bromobutaneb
1-bromooctane
1-bromobutaneb
88
87
84
81
90
80
80
80
80
96
87
61
86
70
75
55
86
68
180
180
180
pyridine
80
pyridine
75
pyridine
180
1-methylpyrrolidine
1-methylpyrrolidine
40
120
a Amine–PF6 salts–alkyl halide = 1:1:1; ultrasonic irradiation: 20 kHz, acoustic power of 0.99 W/mL.
b Water was added to avoid precipitation.
c Reaction stopped because of precipitation of the medium.
d Temperature naturally increased because of ultrasound. Cryostat was used to control this heating phenomenon.
e Isolated yield.
additional water was introduced and the reaction was ature ionic liquids. Different families of RTILs have been
stopped as soon as the precipitation occurred. However, obtained containing various cations, anions and lateral
the necessity of water with 1-bromobutane led once again alkyl chain length. This synthesis is in accordance with
to a decrease of the yield to 68%. Thus, this ultrasound- many principles of green chemistry.16 It was done under a
assisted method has proved its efficiency for the synthesis non-conventional activation method, it reduces the num-
of hexafluorophosphate ionic liquids for different cations ber of steps usually required for this kind of reaction, and
and lateral alkyl chains. However, several physicochemi- it is done without or with an environmentally benign sol-
cal key properties of ionic liquids depend on the nature of vent. Lastly, it enables a quick synthesis of room-temper-
their anions. Our methodology was consequently applied ature ionic liquids which are generally considered as
to other potassium salts to achieve tetrafluoroborate and green solvents. Our team is presently focusing its efforts
trifluoromethanesulfonate ionic liquids. The results are on generalizing this method to starting material with low-
given in Table 5.
er reactivity such as alkyl chloride or unreactive salts such
as lithium bis(trifluoromethanesulfonimide) in order to
synthesize ionic liquids with high hydrophobic character.
Average to good yields were obtained but a drawback still
remained for the synthesis of very hydrophilic ionic
liquids such as 1-butyl-3-methylimidazolium tetrafluoro-
borate. In fact, after the completion of the reaction, the hy-
drophilic ionic liquids were first dissolved in water and
then extracted from aqueous phase with dichloromethane
to remove this ionic liquid as well as the intermediate 1-
butyl-3-methylimidazolium bromide which was water-
soluble.13 There was, therefore, a necessity for the expect-
ed ionic liquid to be more soluble in dichloromethane than
in water. If not, the extraction failed, leading to yields that
were usually poorer for hydrophilic ionic liquid. Further-
more, the use of dichloromethane is not eco-friendly.
However, the one-pot synthesis remains interesting in
term of a green protocol since it removes the additional
purification of the quaternary nitrogen-bearing hetero-
cycle halide intermediate. The reduction of reaction time
won by the use of ultrasound is also of great benefit in
terms of economy and eco-chemistry. Moreover, no or-
ganic solvents were required during the process.
Acknowledgment
The authors would like to thank the Laboratoire de Catalyse et de
Synthèse Organique, University of Lyon I. This work was carried
out under the auspices of the European Union COST Action D32/
006/04.
References and Notes
(1) For review on ionic liquids, see: Welton, T. Chem. Rev.
1999, 99, 2071.
(2) Khandekar, A. C.; Khadilkar, B. M. Synlett 2002, 152.
(3) Estager, J.; Lévêque, J.-M.; Turgis, R.; Draye, M. J. Mol.
Catal. A: Chem. 2006, 256, 261.
(4) Price, B. K.; Hudson, J. L.; Tour, J. M. J. Am. Chem. Soc.
2005, 127, 14867.
(5) Zhang, S.; Hou, Y.; Huang, W.; Shan, Y. Electrochim. Acta
2005, 50, 4097.
(6) Ranke, J.; Müller, A.; Bottin-Weber, U.; Stock, F.; Stolte, S.;
Arning, J.; Störmann, R.; Jastorff, B. Ecotoxicol.
Environmen. Safety 2007, in press.
In this present work, we have developed a green protocol
to synthesize easily and directly non-halide room-temper-
Synlett 2007, No. 13, 2065–2068 © Thieme Stuttgart · New York

2068
J. Estager et al.
LETTER
Table 5 One-Pot Syntheses for Various Families of Ionic Liquidsa,15
Entry
1
Amine
Salt
Alkyl halide
Temp (°C)
Time (min)
180
Yield (%)d
1-methylimidazole
1-methylimidazole
1-methylimidazole
1-methylimidazole
pyridine
KOTf
KOTf
KOTf
KOTf
KOTf
KOTf
KOTf
KOTf
KOTf
KBF4
KBF4
KBF4
KBF4
KBF4
KBF4
1-bromooctane
1-bromohexane
1-bromopentane
1-bromobutaneb
1-bromooctane
1-bromohexane
1-bromobutaneb
1-bromooctanec
1-bromobutaneb
1-bromooctane
1-bromobutaneb
1-bromooctane
1-bromobutaneb
1-bromooctane
1-bromobutaneb
83
80
80
80
85
90
90
85
80
80
80
105
80
80
85
90
72
72
70
75
75
60
73
89
78
21
72
61
68
65
2
180
3
180
4
180
5
180
6
pyridine
180
7
pyridine
180
8
1-methylpyrrolidine
1-methylpyrrolidine
1-methylimidazole
1-methylimidazole
pyridine
50
9
180
10
11
12
13
14
15
180
180
180
pyridine
180
1-methylpyrrolidine
1-methylpyrrolidine
180
180
a Amine–PF6 salt–alkyl halide = 1:1:1; ultrasonic irradiation: 20 kHz, acoustic power of 0.99 W/mL.
b Water was added to avoid precipitation.
c Natural precipitation of product was observed after 50 min.
d Isolated yield.
(7) Holbrey, J. D.; Seddon, K. R. J. Chem. Soc., Dalton Trans.
1999, 2133.
(8) Namboodiri, V. V.; Varma, R. S. Tetrahedron Lett. 2002,
43, 5381.
(9) Neppiras, E. A. Phys. Rep. 1980, 61, 159.
(10) Suslick, K.; Schubert, P.; Goodale, J. J. Am. Chem. Soc.
1981, 103, 7342.
(11) Luche, J. L. In Synthetic Organic Sonochemistry; Plenum
Press: New York, 1998, 169.
(12) Lévêque, J.-M.; Luche, J.-L.; Pétrier, C.; Roux, R.; Bonrath,
W. Green Chem. 2002, 4, 357.
(13) Xu, D.-Q.; Liu, B.-Y.; Luo, S.-P.; Xu, Z.-Y.; Shen, Y.-C.
Synthesis 2003, 2626.
(14) Sonochemistry: Theory, Applications and Uses of
Ultrasound in Chemistry; Mason, T. J.; Lorimer, J. P., Eds.;
Ellis Harwood: Chichester, UK, 1988, 9.
(1 equiv) and nitrogen-bearing heterocycles were introduced
in a 25-mL cooling-jacket glass reactor. H2O was added
when 1-bromobutane was used as alkyl bromide. The
medium was sonicated at 20 kHz or 30 kHz for the times and
at the temperatures and acoustic powers listed in Tables 1
and 3–5. A heat-conducting fluid was used in the cooling
jacket to maintain the overall temperature at about 80 °C
during the experiments. The final mixture was then poured
into acetone and filtered through Celite. Acetone was
removed under vacuum. Hydrophobic ILs were washed with
H2O (4 × 20 mL) and Et2O (4 × 20 mL), to be finally dried
at 90 °C under vacuum (3 h). Hydrophilic ILs were dissolved
in H2O (50 mL) and extracted with CH2Cl2 (4 × 25 mL);
solvents were removed under vacuum and RTILs are washed
with Et2O (4 × 20 mL) to be finally dried at 90 °C under
vacuum (3 h). All products were checked by 1H and 13
C
(15) The used ultrasonic probe was a Branson 20 kHz digital
sonifer or a Ultrasons Annemasse S.A. 30 kHz probe.
Acoustic powers were determined by calorimetry.17 1H and
13C NMR spectra were recorded on a Bruker AMX 200 MHz
spectrometer. IR analyses were performed on an ATI
Mattson Genesis Series FTIR instrument. All precursor
products are commercially available and were used without
further purification. Potassium salts (1 equiv), alkyl bromide
NMR spectroscopy and no organic impurity was observed.
No significant trace of H2O was observed in the IR spectra.
(16) Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and
Practice; Oxford University Press: Oxford, 1998, 30.
(17) Kimura, T.; Sakamoto, T.; Lévêque, J.-M.; Sohmiya, H.;
Fujita, M.; Ikeda, S.; Ando, T. Ultrason. Sonochem. 1996, 3,
S157.
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