Convenient synthesis of various ionic liquids from onium hydroxides and ammonium salts

Article abstract of DOI:10.1016/j.tetlet.2009.05.015

Hydroxide ionic liquids, such as 1-alkyl-3-methylimidazolium hydroxides, undergo smooth anion metathesis with ammonium salts to produce a variety of ionic liquids in excellent yields. It is a practical supplement of traditional neutralization method due to the broader range of starting materials containing desired anions.

Full text of DOI:10.1016/j.tetlet.2009.05.015

Tetrahedron Letters 50 (2009) 4286–4288
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Convenient synthesis of various ionic liquids from onium hydroxides
and ammonium salts
*
Yanqing Peng , Guiyun Li, Jianguo Li, Shaojun Yu
Shanghai Key Lab of Chemical Biology, Institute of Pesticides and Pharmaceuticals, East China University of Science and Technology, Shanghai 200237, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 February 2009
Revised 5 May 2009
Accepted 8 May 2009
Available online 12 May 2009
Hydroxide ionic liquids, such as 1-alkyl-3-methylimidazolium hydroxides, undergo smooth anion
metathesis with ammonium salts to produce a variety of ionic liquids in excellent yields. It is a practical
supplement of traditional neutralization method due to the broader range of starting materials contain-
ing desired anions.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Ionic liquids
Synthesis
Onium hydroxide
Ammonium salts
Metathesis
In the past few years, the use of room temperature ionic liquids
as attractive solvents has blossomed in organic transformations
due to their unique properties (non-volatility, non-flammability,
reasonable stability, and excellent dissolving capacity) and the po-
tential in designing task-specific ionic liquids by the employment
of functional anions or cations.1 More recently, ionic liquids were
also found to be efficient solvents in material chemistry.2 Despite
the significant developments in the utility of ionic liquids, they
are still expensive solvents for many of the chemists. In order to
facilitate the general acceptance of ionic liquids, cost and availabil-
ity issues are necessary to be addressed. Ionic liquids are fre-
quently prepared by ion-exchange (metathesis) method.3 This
procedure involves two steps, namely, quaternization4 and anion
metathesis. Anion metathesis is performed by treating quaternary
ammonium halides with the salts containing desired anions in
large amounts of organic solvents such as acetone,5 methanol,6
and acetonitrile.7 Generally, however, the metathesis is exceed-
ingly slow (e.g., 72 h5c). Water is an appropriate solvent in the syn-
thesis of water-immiscible ionic liquids such as [bmim][PF6].8 In
these cases, hydrophobic ionic liquid phase can be isolated sponta-
neously from aqueous solution phase.
method has its own limitations. Some acids, such as thiocyanic acid
(HSCN), are unstable under reaction conditions. On the other hand,
some of the acids are highly corrosive and toxic. For example,
aqueous HBF4 and HPF6 are dangerous and unstable acids, both lib-
erating HF upon decomposition, and both acids must be kept at
low temperature to avoid rapid decomposition. It is difficult to find
‘pure’ lactic acid because concentrated aqueous solutions of lactic
acid (>30 wt %) contain a distribution of oligomers that arise via
intermolecular esterification.10 Thus, the development of alterna-
tive approaches to ionic liquids starting from omium hydroxides
is still in demand.
To increase the utility of onium hydroxides in the synthesis of
ionic liquids, we have developed a novel ‘ammonia elimination’
strategy using 1-alkyl-3-methylimidazolium hydroxide as versatile
intermediate, and report herein our preliminary results. The salient
feature of this method is the use of ammonium salts instead of free
acids (Scheme 1, route b), thus avoiding the inherent limitation of
H2O
HX
Ionic liquids with different anions can also be obtained by the
neutralization of basic hydroxide ionic liquids, such as [bmi-
m][OH], with the corresponding acid (Scheme 1, route a).9 It is a
very practical approach to halide-free ionic liquids with advanta-
ges such as high yields and rapid reactions. Unfortunately, this
(a)
OH
X
N
N
N
N
(b)
NH4X
NH3, H2O
* Corresponding author. Tel.: +86 21 64252945; fax: +86 21 64252603.
E-mail address: yqpeng@ecust.edu.cn (Y. Peng).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.05.015

Y. Peng et al. / Tetrahedron Letters 50 (2009) 4286–4288
4287
Table 1
traditional neutralization method. Firstly, many of the ammonium
Synthesis of various ionic liquids from onium hydroxides and ammonium salts
salts are commercially available in high purities. Secondly, most of
them are safe, stable, and non-corrosive in comparison with their
parent acids. During the anion metathesis between hydroxide ionic
liquids and ammonium salts, NH4OH can be removed readily by ro-
tary evaporation under reduced pressure, with the non-volatile
residue as the component of desired ionic liquids. Undoubtedly,
gaseous ammonia will not contaminate the final products.
1-Alkyl-3-methylimidazolium salts are a class of commonly
used ionic liquids.11 As a starting point for the development of
our methodology, the synthesis of [bmim][OH] was initially inves-
tigated. Two processes have been reported for the synthesis of
hydroxide ionic liquids. In the first process, hydroxide ionic liquids
were prepared from halide ionic liquid precursors by anion ex-
change using hydroxide-type ion exchange resin such as Amberlite
IRA-400 (OHÀ).9 The ion exchange resin method routinely affords
hydroxide ionic liquids that are much pure, although large amount
of ion exchange resin is necessary in order to obtain halide-free
products. In the second process, hydroxide ionic liquids were syn-
thesized by direct anion exchange between halide ionic liquids and
alkali hydroxide (KOH or NaOH) in appropriate organic solvents.12
Indeed, direct anion metathesis in organic solvents is a simple pro-
cedure; however, the ionic liquid thus obtained is often contami-
Entry
1
Cations
Anions
Yielda (%)
BF4
99
N
N
N
N
N
N
N
N
N
N
2
3
4
5
PF6
98
99
99
96
p-TsO
MsO
PhCOO
HO
Me
SCN
COO
6
7
97
96
99
N
N
N
N
N
N
H
8
BF4
nated by
a small quantity of halides which remains from
a
incomplete metathesis reaction.
Isolated yields.
In the present work, a hybrid two-step procedure modified from
literature methods has been developed as shown in Figure 1.13
Crude ionic liquid was prepared by a classic anion metathesis pro-
cedure ( Fig. 1, a). In the literature procedure, solid potassium
hydroxide was added to a solution of [bmim][Br] in dry methylene
chloride and the mixture was stirred vigorously at room tempera-
ture for 10 h to give [bmim][OH].12a It was found in our investiga-
tion that, however, the use of methylene chloride often led to a
brownish product. So we decided to screen a range of organic sol-
vents for anion metathesis. Among them, THF was found to be a
much appropriate solvent by which a colorless or yellowish crude
ionic liquid could be obtained.
The presence of halide could be confirmed by adding aqueous
silver nitrate into a sample solution pre-treated with HNO3
(Fig. 1, b). To remove the halide impurities, the aqueous solution
of crude [bmim][OH] was then passed through a column charged
with anion-exchange resin to afford halide-free [bmim][OH] ionic
liquid, which gives negative result in the silver nitrate test
(Fig. 1, c). [C5mim][OH] could also be prepared by a similar syn-
thetic procedure. It has been reported that omium hydroxides
are not particularly stable and cannot be used as concentrated
aqueous solutions, but 40% aqueous solution of certain omium
hydroxides is stable.14 In our experiments, as-synthesized omium
hydroxides were stored and used as 30–40 wt % aqueous solutions.
With the desired precursors in hand, several anions were then
introduced by ammonia elimination strategy.15 In this study, eight
ionic liquids were selected as examples to demonstrate the utility
of our synthetic route (Table 1). Treatment of various ammonium
salts with equimolar amount of omium hydroxides immediately
resulted in ammonia evolution. The mixture was degassed and
dehydrated under reduced pressure to afford desired ionic liquids.
Due to the facts mentioned above, it is difficult to find ‘pure’ lactic
acid in laboratories because of the presence of oligomers. However,
pure ammonium lactate could be obtained readily by fed-batch
fermentation of Rhizopus oryzae from corncob hydrolysate.16 Sed-
don and co-workers have introduced the synthesis of [bmim][lac-
tate] ionic liquid by the metathesis between sodium lactate and
[bmim][Cl] in acetone.17 In our procedure, [bmim][lactate] was
obtained in 97% yield by the reaction of aqueous [bmim][OH] with
ammonium
L-(+)-lactate (Table 1, entry 6). Other ionic
liquids (e.g., [bmim][benzoate]18 and [bmim][SCN]19), which had
been synthesized previously through traditional anion metathesis,
were also prepared successfully by our method. To broaden the
scope of substrates, [C5mim][OH] has also been tested as a starting
material. Aqueous solution of [C5mim][OH] was treated with
NH4BF4 to give ionic liquid [C5mim][BF4] in excellent yields
(Table 1, entry 8).
Anion metathesis is an equilibrium reaction. In the cases using
onium halides as starting materials, the equilibrium could be bro-
ken by the precipitation of insoluble silver halides with soluble sil-
ver salts (e.g., AgBF4),20 or by using a suitable organic co-solvent
from which the formed alkali halides can be precipitated.5 In the
present method, metathesis occurred irreversibly due to the elim-
ination of gaseous ammonia. In contrast to traditional anion
metathesis, this procedure yields ionic liquids without any non-
volatile impurities after the removal of ammonia and water under
reduced pressure.21
NaOH
OH
Cl
THF
N
N
N
N
NaCl
(a)
halide-free
[bmim][OH]
[bmim][OH]
[bmim][Cl]
(c)
HNO3
[bmim][NO3]
[bmim][Cl]
NMe3 OH
(b)
AgNO3
metathesis by ion-exchange
chromatography
AgCl
Hydroxide ionic liquid, such as tetrabutyl phosphonium
hydroxide, is now commercially available as a concentrated aque-
ous solution.14 Recently, Wasserscheid’s group has revealed the
precipitation
Figure 1. Synthesis of onium hydroxide.

4288
Y. Peng et al. / Tetrahedron Letters 50 (2009) 4286–4288
C.-G. Tetrahedron Lett. 2006, 47, 7723–7726; (d) Xu, J.-M.; Liu, B.-K.; Wu, W.-B.;
Qian, C.; Wu, Q.; Lin, X.-F. J. Org. Chem. 2006, 71, 3991–3993; (e) Ranu, B. C.;
Jana, R.; Sowmiah, S. J. Org. Chem. 2007, 72, 3152–3154.
production of 5% aqueous solutions of [emim]OH at the kilogram
scale by electrodialysis from the non-toxic bulk ionic liquid
[emim][EtOSO3].22 This environmentally benign process could be
modified for the efficient and economical synthesis of various
onium hydroxide intermediates. This fact implies that hydroxide
ionic liquids might be a new series of readily available reagents
on the catalog of chemical suppliers in the near future. Hence,
ammonia elimination method described in this Letter provides
an attractive and practical route to access various ionic liquids in
chemical laboratories.
In summary, we have demonstrated that ammonium salts are
practical alternatives to the corresponding acids for the synthesis
of ionic liquids when onium hydroxides are employed as precur-
sors. In comparison with direct neutralization method, the present
approach is less eco-friendly because of the release of ammonia
gas, which should be treated before final disposal. However, it is
very suitable when the parent acids are unstable, dangerous, or
could not be obtained in pure form. In other words, it is a valuable
supplement of direct neutralization method due to the broader
range of anion sources.
13. Preparation of aqueous [bmim]OH: To a 500-mL Erlenmeyer flask equipped
with drying tube (CaCl2) were added commercially available [bmim][Cl]
(white crystalline solid, 17.45 g, 100 mol), KOH (5.60 g, 100 mol), and dry
THF (100 mL). The mixture was then sonicated in an ultrasonic clean bath
for 2 h. On completion of the reaction, the reaction mixture was allowed to
stand overnight and was filtered through a sintered funnel. The filtrate was
concentrated under vacuum for 0.5 h to afford 15.85 g of crude [bmim]OH as
a viscous liquid. The crude product was then diluted with 25 mL of deionized
water, and was treated by passing through a column charged with Amberlite
IRA-400 (OH) (type 717) anion exchange resin in order to remove residual
halide (confirmed by AgNO3 test after HNO3 neutralization). The
concentration of [bmim]OH was determined to be 38 wt % via acid-base
titration. It is better to store this intermediate solution in
a PTFE
(polytetrafluoroethylene) bottle. The resin material could be recycled by
washing with concentrated base.
14. Kagimoto, J.; Fukumoto, K.; Ohno, H. Chem. Commun. 2006, 2254–2256.
15. Representative procedure for the synthesis of [bmim][lactate]: At room
temperature, 1.07 g (10 mol) of ammonium L-lactate was added slowly into
an aqueous solution containing equimolar amount of [bmim]OH (4.11 g of
38 wt % solution) under vigorous stirring. Ammonia thus formed was gradually
removed at room temperature using a rotary evaporator (water-circulating
pump) until no ammonia evolution could be observed. The degassed solution
was then dried under vacuum at 60–70 °C for 24 h to eliminate the residual
water, leaving a clear, viscous ionic liquid (2.21 g, 97% yield). Structures of the
resulting ionic liquids were confirmed by proton NMR and FTIR spectroscopy.
[bmim][lactate]: FTIR (KBr): mmax 3410 (OH), 1726, 1728, 1597, 1599 cmÀ1 1H
;
Acknowledgments
NMR (CD3OD, 400 MHz): dH 1.01 (t, J = 7.5 Hz, 3H, CH3), 1.35 (d, J = 7.1 Hz, 3H,
Lac-b-CH3), 1.43–1.47 (m, 2H, CH2), 1.91–1.98 (m, 2H, CH2), 4.01 (s, 3H, NCH3),
The authors would like to thank the Shanghai Commission of
Science and Technology (08431901800) and the Shanghai Leading
Academic Discipline Project (B507) for support of this research.
4.17 (t, J = 7.3 Hz, 2H, NCH2), 4.26 (q, J = 7.1 Hz, 1H, Lac-
imid-H), 7.48 (s, 1H, imid-H), 9.72 (s, 1H, imid-H) ppm. [bmim][PF6]: FTIR (KBr):
mmax 3168, 3121, 2967, 2875, 1576, 1478, 851 (PF6), 744 cmÀ1 1H NMR
a-CH), 7.39 (s, 1H,
;
(CD3OD, 400 MHz): dH 0.91 (t, J = 7.4 Hz, 3H, CH3), 1.35–1.39 (m, 2H, CH2),
1.91–1.96 (m, 2H, CH2), 4.10 (s, 3H, NCH3), 4.45 (t, J = 7.3 Hz, 2H, NCH2), 7.91 (s,
1H, imid-H), 8.00 (s, 1H, imid-H), 9.25 (s, 1H, imid-H) ppm. [bmim][benzoate]:
References and notes
FTIR (KBr): mmax 3166, 3121, 2967, 2859, 1599, 1575, 1472 cmÀ1 1H NMR
;
(CD3OD, 400 MHz): dH 0.90 (t, J = 7.8 Hz, 3H, CH3), 1.01–1.16 (m, 2H, CH2),
1.59–1.71 (m, 2H, CH2), 3.72 (s, 3H, CH3), 4.05 (t, J = 8.0 Hz, 2H, CH2), 7.35–7.44
(m, 2H, Ph), 7.55–7.62 (m, 1H, Ph), 7.70 (s, 1H, imid-H), 7.75 (s, 1H, imid-H),
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solutions does not usually cause problems for humans and other mammals.
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