Transition-metal free ring deuteration of imidazolium ionic liquid cations

Article abstract of DOI:10.1016/j.tetlet.2006.04.032

A simple, low-cost and transition-metal free ring deuteration procedure applicable to ionic liquids (ILs) with imidazolium cations has been developed. Reaction profiles for the exchange have been measured.

Full text of DOI:10.1016/j.tetlet.2006.04.032

Tetrahedron Letters 47 (2006) 4293–4296
Transition-metal free ring deuteration of imidazolium ionic
liquid cations
Ralf Giernoth* and Dennis Bankmann
Institute of Organic Chemistry, University of Cologne, Greinstrasse 4, D-50939 Ko¨ln, Germany
Received 14 February 2006; revised 30 March 2006; accepted 4 April 2006
Available online 5 May 2006
Abstract—A simple, low-cost and transition-metal free ring deuteration procedure applicable to ionic liquids (ILs) with imidazolium
cations has been developed. Reaction profiles for the exchange have been measured.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
allows for in situ reaction and monitoring and tracking
of the deuterium labels. Deuterium NMR in ionic liq-
uids was previously described.9 The procedure presented
here may also find application as one step in the prepa-
ration of perdeuterated ionic liquids for use with NMR
spectroscopy in cases where solvent signals cannot be
tolerated at all as opposed to NMR-based solvent filter-
ing techniques.10
The recent surge in ionic liquid (ILs)1 research and their
application in both academia and industry have left
chemists with questions regarding structure and reactiv-
ity of reaction systems contained in these new solvents.
Repeatedly it has been found that several ionic liq-
uids—especially those based on imidazolium ions—are
not really inert solvents.2
In contrast to prior efforts described in the litera-
ture,11,12 we focussed on labelling room temperature
common ionic liquids themselves, not their precursors
like alkylimidazoles or imidazolium halide salts. To
the best of our knowledge, we report here for the first
time the full ring deuteration of ionic liquids with anions
apart from halides. For halides, this has been done by
Dymek Jr. et al.11 with potassium carbonate base. The
2-position of dicyanamide and chloride 1-butyl-3-methyl-
imidazolium salts has been deuterated by Handy et al.3
who also determined the respective rate constants. How-
ever, the authors do not observe exchange in 4- and 5-
position or give deuterium contents for their products
presumably because their experiments were not designed
with preparation of deuterated ILs in mind. In one
paper, exchange of the 2-position was observed in
CD3OD and D2O with imidazolium bromides but not
with other anions.13
The most discussed reactivity pattern of ILs has been the
formation of N-heterocyclic carbenes or carbene-com-
plexes from imidazolium cations,3–6 which may influ-
ence reactivity—be it advantageously or adversely. The
ease of abstraction of the proton in the 2-position of
the imidazolium ring is expected to largely determine
the electrochemical and chemical stability of ILs.7
To further the possibility for investigations on reaction
systems in which cation acidity may play a role, we
developed a deuteration procedure for common ionic
liquids with imidazolium cations. The ILs obtained are
useful labelled compounds in conjunction with NMR
spectroscopy and mass spectrometry. The aforemen-
tioned analytical techniques possess the potential to
answer questions regarding the participation of the solvent
by simply tracing the incorporation of the labels into
products. Furthermore, as recently demonstrated by
our group,8 high-resolution NMR spectroscopy is possi-
ble in ionic liquids in spite of strong solvent signals and
2. Deuteration procedures
Water-miscible and water-stable ionic liquids with the
BF4 anion may be readily deuterated by stirring the IL
with a threefold volume excess of D2O and 15 mol %
Keywords: Ionic liquids; Isotopic labelling; Spectroscopy.
*
Correspondingauthor. Fax:+492214705102; e-mail:Ralf.Giernoth@
uni-koeln.de
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.04.032

4294
R. Giernoth, D. Bankmann / Tetrahedron Letters 47 (2006) 4293–4296
Table 1. Yields and deuterium content of labelled ionic liquids
alkali metal hydroxide at 60 °C overnight (Scheme 1).
The solution is then neutralized with the corresponding
aqueous acid HBF4. Since the exchange reaction is
quenched on acidification, the use of HBF4/H2O does
not significantly compromise the deuterium content of
the product. Recovery of the ionic liquid is achieved
by extraction with dichloromethane and removal of
the organic solvent under vacuum and elevated temper-
ature. The deuterated product is obtained in yields of
90% and deuterium content of 95–98% in each position.
Ionic
liquid
Base
Solvent
t
T
Yielda Deuterium
(h) (°C) (%)
contentb
[bmim]BF4
[omim]BF4
[bmim]BF4
[bmim]BF4
[bmim]BF4
[bmim]BF4
CsOH D2O
CsOH D2O
KOH D2O
NaOH D2O
K2CO3 D2O
K2CO3 D2O
12 60 90
18 60 82
18 60 67
18 60 77
12 60 86
48 60 71
0.95, 0.95, 0.95
0.98, 0.98, 0.97
0.95, 0.95, 0.95
0.95, 0.95, 0.95
0.98, 0.47, 0.57
0.96, 0.65, 0.74
0.91, 0.84, 0.86
0.89, 0.90, 0.90
[bmim]Tf2N CsOH CH3OD 24 rt
87
[bmim]Tf2N CsOH CH3OD 48 60 98
a Subject to further optimization.
b Deuterium content determined from 1H NMR integration, ordered
from low to high field. For assignment, see Supplementary data.
Bistriflic amide salts as examples of water-immiscible
ILs may be deuterated by stirring in CH3OD with
30 mol % alkali metal hydroxide overnight at 60 °C
(Scheme 2). After neutralization with solid
(CF3SO2)2NH and removal of the organic solvent, the
IL is partitioned between water and ethyl acetate or
dichloromethane. Separation and removal of the organic
solvent affords the product in nearly quantitative yield
and with a deuterium content of about 90%.
3. Characterization of the products
1H NMR spectra of the products (Fig. 1) show no
decomposition by the bases. If the exchange is allowed
to run for a sufficient amount of time, integration of
the residual ring proton signals indicates equal deute-
rium content in all three positions, confirming that the
exchange reactions have reached equilibrium and
Except for cations with two very short side chains and
thus high water-miscibility like in [bmim]BF4, this
procedure is found to be generic, though sterically very
hindered ILs can be expected to require more fierce
reaction conditions. The aforementioned small cations
do undergo exchange, yet the recovery from the aqueous
phase is an unsolved issue.
Alkali metal hydroxides seem to be optimal bases due to
their low solubility in organic solvents, the negligible
catalytic activity of alkali metal cations and the fact that
neutralization of hydroxides yields only water and easily
separable salts.
10
9
8
ppm
Good results have been obtained in all cases with cae-
sium hydroxide as the base. However, sodium and
potassium hydroxides lead to comparable results. Potas-
sium carbonate affords a partially deuterated product
unless reaction times are increased significantly (Table
1). Again, no anion contamination of the ionic liquid
should take place, since on acidification and subsequent
heating CO2 is expelled.
9
8
7
6
5
4
3
2
ppm
Figure 1. Proton and deuterium (inset) spectra of [bmim]-d3BF4
(300 MHz, DMSO-d6).
5 H
N1
H2
D
H 4
D
N
-
-
BF4
R
BF4
D2O, base
3N
N
16-24h, 60 °C
H3C
H3C
R
D
R = Et, Bu, C8H15
D:H > 95:5
Scheme 1. Deuteration procedure for tetrafluoroborate ionic liquids.
9
8
ppm
H
D
H 4
D
N
5
Tf2N-
Tf2N-
MeOD, base
3N
N1
N
24-48h, 50 °C
H3C
R
H3C
R
H2
D
9
8
7
6
5
4
3
2
ppm
R = Bu
D:H > 90:10
Figure 2. Proton NMR spectrum of [bmim]-d3BF4 showing incom-
plete exchange (300 MHz, DMSO-d6).
Scheme 2. Deuteration procedure for bistriflic amide ionic liquids.

R. Giernoth, D. Bankmann / Tetrahedron Letters 47 (2006) 4293–4296
4295
that deuterium is statistically distributed between all
exchanging positions (cf. discussion below).
for 12 h with the weak base K2CO3 at 60 °C was 98%
deuterated at the 2-position, while the 4- and 5-position
were unevenly deuterated at 47% and 57% D, respectively
(Fig. 2), implying that the reaction had not reached
equilibrium. From the integration, a first semi-quantita-
tive statement on the relative exchange rates could be
made (assuming constant rates over the reaction time)
in that the ratio between the rates of the 2-, 4- and 5-
position is approximately 6.3:1:1.3.
The uniform incorporation of deuterium into all three
positions is confirmed by 2D NMR spectroscopy
(Fig. 1, inset). Since the 4- and 5-position are not indi-
vidually resolved, the two integrals exhibit a 1:2 ratio.
4. Reaction profiles
The exchange of [bmim]BF4 in D2O (Fig. 3) and
[bmim]Tf2N in CD3OD (Fig. 4) has been followed
in situ by means of 1H NMR spectroscopy at 45 °C
and with stoichiometries according to the preparative
If the exchange reaction is not allowed to run until equi-
librium is reached, unequal deuterium content can be
observed in the proton NMR spectra. A sample treated
100
4-pos
5-pos
90
80
70
60
50
40
30
20
10
100
10
0
100
200
300
400
0
200
400
600
800
1000
1200
1400
t / min
Figure 3. Reaction profile of the deuteration of 0.2 g [bmim]BF4 in 0.6 mL D2O with 24 mg caesium hydroxide at 45 °C. Curves show exponential
functions fitted to the first-order regime of the reactions. Inset shows data in logarithmic scale.
100
4-pos
5-pos
90
80
70
60
50
40
30
20
10
100
10
0
10
20
30
40
50
60
0
20
40
60
t / min
80
100
120
Figure 4. Reaction profile of the deuteration of 0.2 g [bmim]Tf2N in 0.6 mL CD3OD with 24 mg caesium hydroxide at 45 °C. Curves show
exponential functions fitted to the first-order regime of the reactions. Inset shows data in logarithmic scale.

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R. Giernoth, D. Bankmann / Tetrahedron Letters 47 (2006) 4293–4296
procedures. Though the latter reaction is considerably
faster, both exhibit common trends. In both cases, the
2-position was fully deuterated from the start of the
NMR measurements, indicating a very fast exchange.
In contrast, without the addition of base, exchange in
this position took 2 h to complete for the BF4 salt and
exchange of only 30% was observed after 4 h for the
Tf2N salt.
In conclusion, we could demonstrate an extremely sim-
ple and at the same time versatile deuteration procedure
for ionic liquids with imidazolium cations. The results
shown here are expected to be generic with respect to
imidazolium cation sidechain constitution and anion
type. Apart from simplicity, this procedure has further
conceptional advantages over known methods. If deu-
terated ILs are to be used for the study of reaction
mechanisms, exceptional purity is crucial. Since no tran-
sition metal is used, no metal contamination of the
product ionic liquid can occur. No decomposition of
the ionic liquid as a result of basic treatment could be
detected. Furthermore, direct deuteration of the IL to
be used in contrast to deuterating its precursors mini-
mizes loss of expensive labels in further preparative steps
and allows for deuteration on demand, with no need to
resynthesize ILs already available from prior syntheses
or commercial suppliers.
The reactions exhibit three domains. In the first, [bmim]-
d1 is abundant and a clean pseudo-first-order reaction is
found. The exchange rates of the 4- and 5-proton differ
by a factor of 1.3 (BF4 salt) and 1.2 (Tf2N salt), respec-
tively. This is in good agreement with the notion that the
exchange in the 4- and 5-position is mainly determined
by the nature of the 1- and 3-substituent, which are iden-
tical between both cases presented here. Variation of the
side chains will, in future kinetics investigations, provide
insight into whether the rate constants are determinated
mainly by sterical or electronic effects.
Supplementary data
With advancement of the exchange reaction, kinetics
deviate from exponential behaviour, suggesting increas-
ing exchange between species other than [bmim]-d1 and
D2O. As a multitude of deuterium bearing moieties exist
in the mixture at this point (thus rendering the kinetics
quite intricate), no analytical treatment of this region
was performed. The final region shows a steady decrease
in deuterium content difference between the 4- and
5-position, marking the path towards statistical (equilib-
rium) concentrations of deuterium in all exchanging
species. Further increase of deuterium content in the
product can then only be achieved by isolation and
repeated exchange with fresh deuterium source.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2006.
04.032.
References and notes
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5. Conclusions
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The fact that deuteration of all positions in the imidazol-
ium ring occurs even in the presence of a weak base
(and thus at low pH) clearly demonstrates the highly
noninert nature of ionic liquids containing this cation.
As significant exchange in the 2-position can be
observed even in the absence of added base, imidazolium
ionic liquids should in fact be considered to be protic
solvents. Catalytic amounts of base were shown to be
sufficient for complete proton exchange in all ring posi-
tions. This stresses on the fact that purity considerations
for ionic liquids should include the absence of contami-
nation with bases (such as the starting material
N-methylimidazole), which can be inferred to largely
influence reactivity on the imidazolium ring.
13. Lin, S.-T.; Ding, M.-F.; Chang, C.-W.; Lue, S.-S. Tetra-
hedron 2004, 60, 9441–9446.