Transition-metal-free synthesis of perdeuterated imidazolium ionic liquids by alkylation and H/D exchange

Article abstract of DOI:10.1002/ejoc.200700784

Economic, transition-metal-free syntheses of partially or completely deuterated imidazolium ionic liquids (ILs) were developed. Double alkylation starting from imidazole afforded side-chain deuterated imidazolium ionic liquids, which subsequently were ful

Full text of DOI:10.1002/ejoc.200700784

FULL PAPER
DOI: 10.1002/ejoc.200700784
Transition-Metal-Free Synthesis of Perdeuterated Imidazolium Ionic Liquids
by Alkylation and H/D Exchange
[a]
[a]
Ralf Giernoth* and Dennis Bankmann
Keywords: Ionic liquids / Imidazole / Deuterium exchange
Economic, transition-metal-free syntheses of partially or
completely deuterated imidazolium ionic liquids (ILs) were
developed. Double alkylation starting from imidazole af-
forded side-chain deuterated imidazolium ionic liquids,
which subsequently were fully deuterated by H/D-exchange
on the cation ring. Isotopic exchange was studied for a range
of ionic liquids, solvents and bases. Here, the presence of
small amounts of basic impurities was found to significantly
affect the exchange behaviour.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
Introduction
were able to deuterate all three ring positions. Also for
[
C mim]Cl, Seddon, Welton et al. reported exchange in all
2
The imidazolium cation is a prominent building block
for many room-temperature ionic liquids (ILs). Alongside
properties such as low resultant melting point, high thermal
stability and easy preparation, considerable evidence has
accumulated regarding the “non-innocent” or non-inert na-
ture of imidazolium cations in ionic liquids.
[3]
positions in D O without addition of base. Lin et al.
2
found exchange only in the 2-position of the homologous
series [C mim]...[C mim]Br in D O and CD OD, with the
2
8
2
3
rate decreasing with increasing side chain length. BF4–
and PF6– salts were reported not to undergo exchange.
Handy et al. found no exchange for [C mim]BF in D O
[2]
4
4
2
The ease of deprotonation of the NCHN position of the
ring is of course a long-known fact and is commonly used
in the formation of imidazol-2-ylidene complexes and free
without base, whereas [C mim]N(CN) was found to ex-
4
2
[5]
change in the 2-position. This was attributed to the fact
that the dicyanamide IL formed slightly basic solutions.
So far, very few syntheses of deuterated ionic liquids have
appeared in the literature. The groups of Dymek and of
[
1]
carbenes. The IL stability can therefore be assumed to be
limited by the reactivity of the 2-position of the imid-
azolium moiety.
Hardacre have reported experimental details for the synthe-
Furthermore, all the protons on the imidazolium ring are
prone to H/D-exchange, as was demonstrated repeatedly:
exchange in the 2-position was observed in several protic
[4,9,10]
sis of perdeuterated ILs.
Dymek prepared [D1]-
[
C mim] and[D ][C mim], using K CO for the second
2 3 2 2 3
compound, whereas Hardacre employed a Pd/C suspension
[
2]
[3–5]
solvents for a variety of ILs. Upon addition of bases,
in D O in the preparation of perdeuterated methylimidazole
2
[
6]
[7]
Lewis acids or metal clusters, exchange in all positions
was found. Even small amounts of a weak base like potas-
sium carbonate facilitated a complete H/D-exchange, inter-
estingly, with different rates for the three ring positions. The
relative exchange rates have already been studied for a range
from [D ]methylimidazole, which was obtained by ruthe-
3
nium catalysed alkylation of imidazole. Subsequent alky-
lation with [D ]methyl chloride or [D ]ethyl iodide afforded
3
5
the perdeuterated salts. The authors pointed out that a se-
lective 4,5-deuteration should be possible by reprotiation of
the 2-position, and that either side chain or the whole of
the ring may be left protonated.
[
2,5,8]
of substances,
and the 4- and 5-position rates were in-
creasingly disparate in our work as side chain length in-
creased.
There are, however, some contradictory reports on the
exchange behaviour. Dymek et al. prepared [D ][C mim]Cl
In addition, Arduengo et al. have published a transition-
metal-free route to [D ]-1,3,4,5-tetramethylimidazolium
12
[11]
1
2
chloride, which is not an ionic liquid. Furthermore, this
case is different, for exchange cannot be studied here due
to the absence of protons in the 4- and 5-positions.
(i.e. 1-ethyl-3-methylimidazolium chloride; in our no-
menclature, C denotes the length of the alkyl chain) by
x
[
4]
dissolving [C mim]Cl in D O and evaporating the solvent.
2
2
The group of Dupont has used our previously published
For the synthesis of [D ][C mim]Cl, they added K CO and
[8]
3
2
2
3
procedure to synthesize imidazolium ILs in which only
the imidazolium ring protons are exchanged by deute-
rium.
Perdeuterated ILs may be used as solvents for NMR
studies. Furthermore, they may be used as isotopically lab-
[
a] Institute of Organic Chemistry, University of Cologne,
[12]
Greinstrasse 4, Köln, Germany
Fax: +49-221-470-5102;
E-mail: Ralf.Giernoth@uni-koeln.de
Eur. J. Org. Chem. 2008, 2881–2886
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2881

R. Giernoth, D. Bankmann
FULL PAPER
elled compounds to shed light on reaction mechanisms in Table 1. Results of selective deuteration experiments in deuterium
oxide.
ionic liquids where heterocyclic carbene formation or pro-
ton equilibria are suspected. Finally, neutron diffraction
measurements in ILs are aided by the availability of these
proton-free compounds, as demonstrated by Arduengo et
al.[
% Deuterium[a]
Product
Base
Yield
(%)
C-2
C-4
C-5
[
D
1
2
3
][C
][C
][C
4
4
4
mim]BF
mim]BF
mim]BF
4
4
4
2
3
4
–
80
41
90
96
0
94
0
95
94
0
95
94
11]
[D
[
CsOH, K
2
CO
3
D
CsOH
In this work, we present the facile and generic synthesis
1
of perdeuterated and partially deuterated ionic liquids by [a] Determined from H NMR integrals vs. NCH integral; error
2
margin around 5%.
application of isotopic exchange on imidazolium cations.
The syntheses were performed either in transition-metal-
free or completely metal-free ways.
only the 2-position exchanges measurably in slightly basic
solution. Monodeuterated species are obtained by stirring
Results and Discussion
in D O or, depending on the hydrophobicity of the IL, in
2
After investigations on H/D-exchange and the synthesis
CH OD. After 16 h at 60 °C (40 °C for methanol), the H/D-
3
[8]
of [D ][C mim]BF and -Tf N salts, we now present C-2
3
4
4
2
exchange equilibrium is reached for all ionic liquids studied.
and C-4/C-5-selective deuteration of the imidazolium ring
Figure 1 and Table 1). The method utilizes the fact that
Complete ring deuteration is achieved as described ear-
(
lier[8] by addition of 10 mol-% of a hydroxide base to the
D O solution of the IL and stirring.
2
The D O solutions are neutralized with the acid corre-
2
sponding to the IL anion and extracted with dichloro-
methane or ethyl acetate to recover the IL. Highly water
soluble ILs like [C mim]TfO can be prepared this way since
2
efficient extraction of [C mim]TfO from water fails. As a
2
consequence, when sodium carbonate is used as base, re-
moval of metal salts is not possible, leading to precipitation
of mixed imidazolium/sodium triflates (Figure 2). Bases on
solid support were considered to circumvent the introduc-
tion of metal salts into the ionic liquid and allow for base
removal. Here, Amberlite IRA-400(OH) (styrene-divinyl-
benzene matrix with ion quaternary ammonium groups) ex-
change resin loaded with hydroxide anions is effective.
Bis-deuterated compounds can be prepared by complete
deuteration of the imidazolium ring under basic conditions
followed by a second exchange step to reprotiate the 2-posi-
tion.
Ring deuteration can be employed as one step in the syn-
thesis of perdeuterated ionic liquids when these are built
from adequately deuterated alkylating agents and imid-
Figure 1. Synthesis of partially deuterated imidazolium salts.
Figure 2. Crystal structure of a mixed sodium imidazolium triflate.
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2881–2886

Perdeuterated Imidazolium Ionic Liquids
azole. (Perdeuterated imidazole as the starting material
would be extremely costly and could result in significant
loss of deuterium in the synthetic procedure – especially
during anion exchange, which is typically done in protic
solvents like water or octanol.) For economic reasons, the
side chain length here is limited to methyl and ethyl. We
synthesized both [D ]-1-methylimidazole and [D ]-1-ethyl-
3
5
imidazole, since the choice of the initial counterion deter-
mines (or rather limits) the availability of the corresponding
methylating and ethylating agents.
These alkylated imidazoles can then be quaternized
either by [D ]methyl iodide or [D ]ethyl bromide and sub-
3
5
sequently be subjected to anion exchange or alkylated with
2
Figure 4. Synthesis of perdeuterated [D11][C mim]TfO.
other agents like e.g. [D ]methyl triflate.
3
With these imidazolium salts that are deuterated in the
side-chains, an exchange of the ring protons can be carried
out, yielding the perdeuterated compounds in the fashion
described above. We have synthesized two example sub-
stances, [D ][C mim]Tf N (Figure 3) and [D ][C mim]TfO
Imidazole can also be alkylated using [D ]methyl iodide
3
and [D ]ethyl bromide under deprotonation/phase transfer
5
[
13]
conditions in CH Cl .
With potassium tert-butoxide,
2
2
1
1
2
2
11
2
imidazole is deprotonated and subsequently alkylated by
means of the alkyl halide. Our yields are, however, some-
what below those reported in the literature, and the prod-
ucts were always contaminated with tert-butyl alcohol after
kugelrohr distillation.
(Figure 4).
A screening experiment was set up to evaluate the appli-
cability to various commercial and synthesized IL samples
(Table 2) and to assess which ILs are prone to exchange on
the imidazolium cation. The ionic liquids were treated with
D O or CH OD and shaken for 16 h at 60 °C or 40 °C,
2
3
respectively. 20 mol-% CsOH·H O or 20 vol.-% of a
2
CH OD solution saturated with K CO were used as bases
3
2
3
and an additional screening was run without base.
–
It sould be noted that, although it is known that BF -
4
ILs are prone to produce HF in the presence of water, our
final samples were all free of fluoride – probably a result of
our workup procedure (see Exp. Sect.).
Very low water solubility in the longer side chain ionic
liquids led to low exchange in initial experiments in D O.
2
Figure 3. Synthesis of perdeuterated [D11][C
2
mim]Tf
2
N.
Therefore, [D ]methanol was chosen as a solvent for the
1
Table 2. Screening of the substrate scope.
IL
Solvent
t / h
T / °C
No base
0.2 Equiv. of CsOH·H
2
O
K
2
CO
3
solution
Deuterium[
a]
% Deuterium
[a]
% Deuterium
[a]
%
C-2
C-4/5
C-2
C-4/5
C-2
C-4/5
[
C
2
mim]Br
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
3
3
3
3
3
3
3
3
OD
OD
OD
OD
OD
OD
OD
OD
OD
OD
OD
OD
OD
OD
16
16
16
16
16
16
16
16
16
16
16
16
16
16
40
40
40
40
40
40
40
40
40
40
40
40
40
40
89
86
16
42
12
87
76
92
2
6
8
11
3
10
0
0
0
24
0
10
10
3
0
5
0
5
precipitation
(exp. not done)
[
C
C
2
[
C
C
2
mim]EtSO
mim]Tf
mim]MeSO
mim]Br
mim]Tf
10mim]Tf
4
77
62
82
83
82
85
79
85
51
86
64
60
[
C
2
2
N
84
72
75
82
[
3
C
4
precipitation
[
[
4
2
N
88
90
80
70
74
73
74
65
71
86
86
79
78
76
78
79
75
77
2
N
(exp. not done)
[
[
[
[
[
[
[
C
4
5
7
8
9
mim]BF
4
4
4
4
4
82
45
3
4
6
6
85
0
C
C
C
C
C
C
mim]BF
mim]BF
mim]BF
mim]BF
88
86
79
78
83
79
10mim]BF
11mim]BF
4
4
0
0
1
[
2
a] Determined from H NMR integrals vs. NCH integral; error margin around 5%.
Eur. J. Org. Chem. 2008, 2881–2886
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2883

R. Giernoth, D. Bankmann
FULL PAPER
screening. Apart from economic reasons, [D ]methanol can change observed in [C mim]Tf N, [C mim]Br, [C mim]BF
4
1
2
2
4
5
be used as a universal method, since water-soluble ILs can and additional results for other substrates, it can be con-
also be deuterated in [D ]methanol with comparable results. cluded that ionic liquids with these anions do not exchange
1
Upon addition of cesium hydroxide, all ILs were found significantly unless contaminated by basic impurities.
to exchange in all three ring positions in CH OD, proving
3
the generic scope of the method described here. Interest-
ingly, some of the ionic liquids showed significant exchange Experimental Section
in the 2-position without any added base whereas others
General Methods: The ionic liquids were either obtained from Sol-
did not. This kind of discrepancy was discussed in the intro-
vent Innovation GmbH or synthesized according to established lit-
duction and can be attributed to basic impurities (see be-
erature procedures. Deuterium oxide (99.9%D) and [D
99.0%D) were obtained from Deutero GmbH and used without
further purification. [D ]Methyl iodide, [D ]methyl triflate and
1
]methanol
low).
It should be noted that the addition of K CO only af-
(
2
3
3
3
forded exchange in the 2-position of the ILs that did not [D ]ethyl bromide were obtained from Aldrich (manufactured at
5
exchange significantly without added base. The ILs that do Cambridge Isotope Labs) and used from fresh ampoules without
exchange under these conditions show significant exchange further purification. Steps including methyl triflate were performed
1
2
13
under an argon atmosphere. H, D and C NMR spectra were
measured at 298 K on Bruker AC-300, DPX-300 and DRX-500
at C-4 and C-5 when K CO is added. Therefore, selective
C-2 deuteration should only be attempted with ILs that are
known to be free of basic impurities.
Differences in exchange behaviour noted above appear
between samples of similar ionic liquids, especially regard-
ing the 2-position. Assuming that basic impurities are the
source of the more ready exchange in some IL samples, we
considered methylimidazole to be the most likely basic con-
taminant in imidazolium ILs. NMR experiments on undi-
luted samples accordingly revealed the presence of up to
2
3
2 6
instruments. [D ]Dichloromethane and [D ]DMSO were taken
from fresh bottles and dried with 3-Å molecular sieves in septum-
capped bottles. ESI-HRMS data were obtained with a Finnigan
MAT 900S spectrometer.
1
1
-Butyl-3-methyl-[D ]imidazolium Tetrafluoroborate (2): 1-Butyl-3-
methylimidazolium tetrafluoroborate (1.00 g, 4.42 mmol) and deu-
terium oxide (2.73 mL, 3.00 g, 150 mmol) were mixed and stirred
for 16 h at 60 °C. The mixture was extracted twice with dichloro-
methane (3 mL each), and the solvent of the combined organic
layers was removed in vacuo. The residue was dried for 2 h at 60 °C
1
% of methylimidazole.
To assess whether such a concentration would be able to
under high vacuum to obtain the product as a colourless oil (0.8 g,
1
influence the exchange, a series of experiments was per- 80%, 96% D at C-2). H NMR (300 MHz, [D ]DMSO): δ = 9.06
6
formed using a clean (not exchanging) IL and mixtures of (s, 0.04 H), 7.74 (m, 1 H), 7.67 (m, 1 H), 4.14 (t, J = 7.2 Hz, 2 H),
that IL with increasing amounts of methylimidazole 3.83 (s, 3 H), 1.75 (quint, J = 7.6 Hz, 2 H), 1.25 (sext, J = 7.5 Hz,
2
2
H), 0.89 (t, J = 7.5 Hz, 3 H) ppm. H NMR (46 MHz, [D
6
]-
(
Table 3). The results demonstrate very significant exchange
DMSO): δ = 9.06 (s) ppm. 13C NMR (75 MHz, [D
36.5 (m, J = 34.2 Hz), 123.6, 122.2, 48.5, 35.7, 31.3, 18.8,
]DMSO): δ =
6
in the 2-position even with 1 mol-% of base. Interestingly,
it was reported that the addition of water to imidazolium-
ILs decreases the acidity of certain ILs and H O effectively
1
1
3.2 ppm.
2
[
14]
1
2
-Butyl-3-methyl-[D ]imidazolium Tetrafluoroborate (3): 1-Butyl-3-
behaves as a base. However, D O (and CH OD) are not
2
3
methylimidazolium tetrafluoroborate (1.00 g, 4.42 mmol) was dis-
solved in deuterium oxide (2.73 mL, 3.00 g, 150 mmol) and treated
with cesium hydroxide monohydrate (0.12 g, 0.71 mmol). The solu-
tion was stirred for 28 h at 60 °C, and after cooling, extracted twice
with dichloromethane (5 mL). The solvent of the combined organic
layers was removed in vacuo, yielding a clear, colourless oil (0.72 g),
which was dissolved in water (5 mL) and treated with potassium
carbonate (12.2 mg, 0.09 mmol). The solution was stirred for 24 h
at 60 °C, extracted four times with dichloromethane (5 mL each)
and washed with a small portion of water. The solvent of the com-
bined organic layers was removed in vacuo to obtain the product
basic enough for measurable effects under the conditions
presented here.
Table 3. Influence of 1-methylimidazole (mim) on H/D exchange.
Product
Solvent
Equiv. of mim % Deuterium[a]
C-2
C-4/5
[C
5
[C
5
[C
5
[C
5
[C
5
[C
5
mim]BF
mim]BF
mim]BF
mim]BF
mim]BF
mim]BF
4
4
4
4
4
4
CD
CD
CD
CD
CD
CD
3
3
3
3
3
3
OD
OD
OD
OD
OD
OD
0
2
0
0
0
7
8
3
0.01
0.025
0.05
0.1
74
86
88
85
84
1
as a colourless oil (0.41 g, 41%, 95% D at C-4 and C-5). H NMR
0.2
(
0
7
300 MHz, [D
6
]DMSO): δ = 9.03 (s, 1 H), 7.71 (s, 0.05 H), 7.65 (s,
.05 H), 4.14 (t, J = 7.2 Hz, 2 H), 3.83 (s, 3 H), 1.76 (quint, J =
.6 Hz, 2 H), 1.25 (sext, J = 7.5 Hz, 2 H), 0.89 (t, J = 7.5 Hz, 3 H)
1
[
a] Determined from H NMR integrals vs. NCH
2
integral; error
margin around 5%.
2
ppm. H NMR (77 MHz, [D
6
]DMSO): δ = 7.75 (s), 7.70 (s) ppm.
]DMSO): δ = 136.4, 123.3 (m, J =
1.5 Hz), 122.0 (m, J = 31.0 Hz), 48.5, 35.7, 31.4, 18.8, 13.3 ppm.
1
3
C NMR (75 MHz, [D
6
3
Conclusions
1
-Butyl-3-methyl-[D ]imidazolium Tetrafluoroborate (4): 1-Butyl-3-
3
The protocols presented here are reasonably economic
routes to perdeuterated ILs that may be combined in a de-
sired manner to afford partially or fully deuterated ionic
liquids or, more generally, imidazolium salts. The substrate
methylimidazolium tetrafluoroborate (1.00 g, 4.42 mmol), deute-
rium oxide (3.00 mL, 3.30 g, 165 mmol) and cesium hydroxide
monohydrate (0.12 g, 0.71 mmol) were mixed and stirred for 12 h
at 60 °C. After cooling, the mixture was neutralized with 48%
scope was probed by screening experiments and the pro- aqueous tetrafluoroboric acid and extracted twice with dichloro-
cedures were found to be very generic. From the low ex- methane (5 mL each). The solvent of the combined organic layers
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Eur. J. Org. Chem. 2008, 2881–2886

Perdeuterated Imidazolium Ionic Liquids
was removed in vacuo, and the residue was dried for 2 h at 60 °C
between dichloromethane (5 mL) and deuterium oxide (3 mL), the
layers were separated, and the water layer was extracted with
dichloromethane (5 mL). The combined organic layers were
washed with deuterium oxide (3 mL), and the solvent was removed
in vacuo. The resulting oil was dried for 2 h at 60 °C under high
under high vacuum to obtain the product as a very slightly yellow
1
oil (0.92 g, 90%, 94%D at C-2, C-4 and C-5). H NMR (300 MHz,
[D
6
]DMSO): δ = 9.04 (s, 0.04 H), 7.73 (m, 0.04 H), 7.65 (m, 0.04
H), 4.15 (t, J = 7.2 Hz, 2 H), 3.83 (s, 3 H), 1.75 (quint, J = 7.6 Hz,
H), 1.25 (sext, J = 7.5 Hz, 2 H), 0.89 (t, J = 7.5 Hz, 3 H) ppm.
2
2
vacuum to obtain the product as a colourless oil (0.76 g, 85%). H
2
13
H NMR (46 MHz, [D
NMR (126 MHz, [D ]DMSO): δ = 136.2 (m, J = 33.9 Hz), 123.2 (s), 3.79 (s), 1.35 (s) ppm. C NMR (75 MHz, [D
m, J = 30.5 Hz), 121.9 (m, J = 30.5 Hz), 48.5, 35.7, 31.4, 18.8,
6
]DMSO): δ = 9.06 (s), 7.74 (s) ppm.
C
6
NMR (46 MHz, [D ]DMSO): δ = 9.07 (s), 7.74 (s) 7.68 (s), 4.12
1
3
6
6
]DMSO): δ =
(
136.1 (m), 123.3 (m), 121.7 (m), 119.5 (q, J = 322 Hz), 43.4 (m),
+
13.3 ppm.
35.0 (m), 13.9 (m) ppm. HRMS (ESI): calcd. [M] 121.1539; found
1
21.154.
]-1-Ethylimidazole: Imidazole (5.97 g, 87.7 mmol) was dissolved
in dry dichloromethane (50 mL) and treated with 18-crown-6
2.32 g, 8.77 mmol) and potassium tert-butoxide (9.84 g,
7.7 mmol). The resulting slurry was stirred for 40 min at room
temp. during which a brownish colour evolved. [D ]Ethyl bromide
6.58 mL, 10.0 g, 87.7 mmol) was added dropwise and the mixture
1
-[D ]Methylimidazole: Imidazole (4.42 g, 65.0 mmol) was dis-
3
[D
5
solved in dry dichloromethane (150 mL) and treated with 18-
crown-6 (1.64 g, 6.20 mmol) and potassium tert-butoxide (7.85 g,
(
8
7
0.0 mmol). The resulting slurry was stirred for 20 min at room
temp., during which time a brownish colour evolved. Methyl iodide
10.0 g, 69.0 mmol) in dry dichloromethane (40 mL) was added
(
5
(
dropwise and the mixture then stirred for another 3 h at room
temp. The solution was filtered and the solvent of the filtrate was
removed in vacuo. The residual brown oil was distilled at 60–100 °C
then stirred overnight at room temp. The solution was filtered and
the solvent of the filtrate was removed in vacuo. The residual brown
oil was distilled at 85–115 °C (0.2 mbar) and subsequently dried at
150 mbar to obtain the product containing residual tert-butyl
alcohol as a colourless oil (4.59 g, 52%). H NMR (300 MHz, [D ]-
(0.2 mbar) to obtain the product containing residual tert-butyl
1
6
alcohol as a colourless oil (2.91 g, 53%). H NMR (300 MHz, [D ]
DMSO): δ = 7.55 (s, 1 H), 7.08 (s, 1 H), 6.87 (s, 1 H) ppm. H
1
2
6
2
13
DMSO): δ = 7.61 (s, 1 H), 7.15 (m, 1 H), 6.88 (m, 1 H) ppm. H
NMR (46 MHz, [D
75 MHz, [D ]DMSO): δ = 137.8, 128.4, 120.4, 32.0 (m, J =
0.75 Hz) ppm.
6
]DMSO): δ = 3.59 (s) ppm. C NMR
1
3
NMR (77 MHz, [D
75 MHz, [D ]DMSO): δ = 136.7, 128.3, 118.8, 28.8 (m), 15.1 (m)
ppm. HRMS (ESI): calcd. [M] 102.1074; found 102.108.
6
]DMSO): δ = 3.91 (s), 1.25 (s) ppm. C NMR
(
2
6
(
6
+
[D
8
]-1-Ethyl-3-methylimidazolium Bromide (6): [D
azole (2.91 g, 34.2 mmol) was added dropwise to [D ]ethyl bromide
2.82 mL, 4.29 g, 37.6 mmol). The mixture was stirred for 15 min
3
]Methylimid-
[D
8
]-1-Ethyl-3-methylimidazolium Trifluoromethanesulfonate (9):
5
[D ]-1-Ethylimidazole (4.50 g, 44.5 mmol) was dissolved in dry hex-
5
(
ane (40 mL) and cooled to 0 °C. The solution was treated dropwise
with trifluoromethanesulfonic acid [D ]methyl ester (5.08 mL,
.51 g, 44.9 mmol), instantaneosly leading to turbidity in the solu-
at 50 °C and for 2 h at 70 °C, until the initial turbidity disappeared.
Upon cooling, the mixture solidified to a yellowish mass, which
was minced and treated with ethyl acetate and stirred at –10 °C for
3
7
tion. After the addition was complete, the mixture was allowed to
reach room temperature over 30 min. The resulting biphasic mix-
ture was refluxed for 2 h and stirred for 18 h. The layers were sepa-
rated, and the lower layer dried in a rotary evaporator. The brown,
oily residue was partitioned between water (10 mL) and dichloro-
methane (10 mL), the layers were separated and the aqueous layer
was washed with dichloromethane (10 mL). The solvent of the
aqueous layer was removed in vacuo, and the residue was dried for
1
h. A colourless solid precipitated, which was filtered off in the
cold. The solid was dried in vacuo, and the product was obtained
as a colourless solid (5.02 g, 74%). 1H NMR (300 MHz, [D
]-
6
2
DMSO): δ = 9.23 (s, 1 H), 7.81 (m, 1 H), 7.72 (m, 1 H) ppm. H
NMR (46 MHz, [D ]DMSO): δ = 4.14 (s), 3.80 (s), 1.35 (s) ppm.
C NMR (75 MHz, [D ]DMSO): δ = 136.2, 123.5, 121.9 ppm.
6
13
6
+
HRMS (ESI): calcd. [M] 119.1416; found 119.142.
]-1-Ethyl-3-methylimidazolium Bis(trifluoromethylsulfonyl)amide
7): [D ]-1-Ethyl-3-methylimidazolium bromide (5.02 g, 25.2 mmol)
[D
8
(
3
h at 60 °C under high vacuum to obtain the product as a colour-
1
8
6
less oil (10.15 g, 85%). H NMR (300 MHz, [D ]DMSO): δ = 9.06
and lithium bis(trifluoromethylsulfonyl)amide (7.96 g, 27.7 mmol)
were stirred for 24 h at room temp. in water (10 mL). The biphasic
mixture was treated with ethyl acetate (20 mL), the layers were sep-
arated and the aqueous phase was extracted with ethyl acetate
2
(
s, 1 H), 7.75 (s, 1 H), 7.66 (s, 1 H) ppm. H NMR (46 MHz,
13
[
(
3
D
6
]DMSO): δ = 4.14 (s), 3.80 (s), 1.35 (s) ppm. C NMR
75 MHz, [D ]DMSO): δ = 136.2, 123.6, 121.9, 120.7 (q, J =
22 Hz), 43.4 (m), 35.0 (m), 14.0 (m) ppm. HRMS (ESI): calcd.
6
(10 mL). The solvent of the combined organic layers was removed
+
[
M] 119.1416; found 119.142.
11]-1-Ethyl-3-methylimidazolium Trifluoromethanesulfonate (10):
]-1-Ethyl-3-methylimidazolium trifluoromethanesulfonate
4.00 g, 14.9 mmol) was dissolved in deuterium oxide (25 mL) and
in vacuo, and the crude product was partitioned between ethyl ace-
tate (30 mL) and water (10 mL) to remove residual halides. The
solvent of the organic layer was removed in vacuo, and the residue
[D
[D
8
(
was dried for 2 h at 60 °C under high vacuum to obtain the product
treated with Amberlite IRA-400(OH) (2 g). The mixture was stirred
for 48 h at 45 °C and for 18 h at room temp. The polymer beads
were removed by filtration, and the filtrate was neutralized with
trifluoromethanesulfonic acid. The solvent was removed in vacuo,
and the resulting slightly yellow oil was dried for 2 h at 60 °C under
high vacuum. The residue was treated with deuterium oxide
1
as a yellowish oil (7.9 g, 78%). H NMR (300 MHz, [D
6
]DMSO):
δ = 9.07 (s, 1 H), 7.73 (m, 1 H), 7.65 (m, 1 H) ppm. 2H NMR
1
3
(
77 MHz, [D
NMR (75 MHz, [D
321 Hz), 43.5 (m, J = 22 Hz), 35.0 (m), 14.0 (m) ppm. HRMS
ESI): calcd. [M]+ 119.1416; found 119.142.
6
]DMSO): δ = 4.13 (s), 3.79 (s), 1.35 (s) ppm.
C
6
]DMSO): δ = 136.3, 123.5, 121.9, 119.6 (q, J
=
(
(
10 mL) and stirred for 3 d at 60 °C. The solvent was removed in
[
D
11]-1-Ethyl-3-methylimidazolium
amide (8): [D ]-1-Ethyl-3-methylimidazolium bis(trifluoromethyl-
sulfonyl)amide (0.97 g, 2.43 mmol) was dissolved in [D ]methanol
6.00 mL, 4.86 g, 147.1 mmol), treated with cesium hydroxide
Bis(trifluoromethylsulfonyl)- vacuo, and the residue was dried for 2 h at 60 °C under high vac-
2
8
uum to obtain the product as a yellowish oil (2.88 g, 71%).
NMR (77 MHz, [D
(s), 3.79 (s), 1.32 (s) ppm. C NMR (75 MHz, [D
H
1
6
]DMSO): δ = 9.11 (s), 7.78 (s), 7.69 (s), 4.13
1
3
(
4
]methanol): δ =
monohydrate (0.12 g, 0.71 mmol) and stirred for 24 h at 50 °C. The
mixture was neutralized with bis(trifluoromethylsulfonyl)amide,
and the solvent was removed in vacuo. The residue was partitioned
137.8 (m), 124.9 (m), 123.3 (m), 121.8 (q, J = 319 Hz), 45.4 (m),
35.9 (m), 14.4 (m) ppm. HRMS (ESI): calcd. [M]+ 122.16009;
found 122.161.
Eur. J. Org. Chem. 2008, 2881–2886
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2885

R. Giernoth, D. Bankmann
FULL PAPER
Exchange Screening: Exchange in deuterium oxide was performed
samples. We also thank Merck KGaA, especially Dr. Urs Wels-
Biermann, without whom we probably never would have carried
out this project so much in detail.
by mixing the IL (1 mmol) with D
0 °C. CH Cl (0.5 mL) was added to the solution (0.5 mL), and
the phases were separated. The organic phase (100–300 µL) was
2
O (1 g) and shaking for 16 h at
6
2
2
1
2 2
filled up to 500 µL with CD Cl and H NMR spectra were mea-
[
[
[
1] R. Singh, S. P. Nolan, Annu. Rep. Prog. Chem., Sect. B: Org.
Chem. 2006, 102, 168–196.
2] S.-T. Lin, M.-F. Ding, C.-W. Chang, S.-S. Lue, Tetrahedron
sured.
For exchange in [D
1
]methanol, the IL (1 mmol) was mixed with
2004, 60, 9441–9446.
CH OD (1 g), and the mixture was shaken for 16 h at 40 °C. The
3
3] A. G. Avent, P. A. Chaloner, M. P. Day, K. R. Seddon, T. Wel-
solutions were transferred to a desiccator, and the organic solvent
ton, J. Chem. Soc., Dalton Trans. 1994, 3405–3413.
was removed in vacuo. Samples (ca. 50 µL) were dissolved in
[4] K. M. Dieter, C. J. Dymek, N. E. Heimer, J. W. Rovang, J. S.
Wilkes, J. Am. Chem. Soc. 1988, 110, 2722–2726.
[5] S. T. Handy, M. Okello, J. Org. Chem. 2005, 70, 1915–1918.
1
CD
2
Cl
2
(200 µL) and CH
2
Cl
2
(300 µL) and H NMR spectra were
obtained.
[
6] P. C. Trulove, R. A. Osteryoung, Inorg. Chem. 1992, 31, 3980–
Exchange experiments with base were performed by mixing of
stock solutions of the base in [D ]methanol and solutions of IL in
]methanol to obtain a total of 1 g of solvent, 1 mmol IL and
3985.
1
[7] L. S. Ott, M. L. Cline, M. Deetlefs, K. R. Seddon, R. G. Finke,
J. Am. Chem. Soc. 2005, 127, 5758–5759.
[D
1
the amounts of base reported in the text. After cooling to room
temperature, neutralization was done with the acids corresponding
[8] R. Giernoth, D. Bankmann, Tetrahedron Lett. 2006, 47, 4293–
4296.
–
–
[9] C. Hardacre, J. D. Holbrey, S. E. J. McMath, Chem. Commun.
001, 367–368.
to the IL anions (HBF
4 3 4
was used also for MeSO and EtSO )
2
and then treated as for the mixtures without added base.
[
10] C. Hardacre, S. McMath, M. Nieuwenhuyzen, D. Bowron, A.
Soper, J. Phys.: Condens. Matter 2003, 15, S159–S166.
11] A. J. Arduengo, H. V. R. Dias, D. A. Dixon, R. L. Harlow,
W. T. Klooster, T. F. Koetzle, J. Am. Chem. Soc. 1994, 116,
Integrals were reported relative to NCH (however, this was equiva-
lent to using NCH , as no exchange was observed on any of the
side chain positions).
2
[
3
6
812–6822.
12] J. D. Scholten, G. Ebeling, J. Dupont, Dalton Trans. 2007,
554–5560.
[
5
Acknowledgments
[
[
13] W. C. Guida, D. J. Mathre, J. Org. Chem. 1980, 45, 3172–3176.
14] C. Thomazeau, H. Olivier-Bourbigou, L. Magna, S. Luts, B.
Gilbert, J. Am. Chem. Soc. 2003, 125, 5264–5265.
Received: August 24, 2007
We would like to thank Deutsche Forschungsgemeinschaft (DFG)
for financial support through the Emmy Noether programme and
Solvent Innovation GmbH for the donation of several ionic liquid
Published Online: April 25, 2008
2886
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2881–2886