3-Alkoxymethyl-1-(1R,2S,5R)-(-)-menthoxymethylimidazolium salts-based chiral ionic liquids

Article abstract of DOI:10.1016/j.tetasy.2010.10.029

A new group of imidazolium salt-based chiral ionic liquids have been prepared and characterized. The chiral ionic liquids obtained are stable in air, in contact with water and popular organic solvents. Their physicochemical properties, single-crystal X-ray structures, antimicrobial activities, and antielectrostatic effects have been determined. The chiral ionic liquids synthesized have proven to represent not only potential new solvents in asymmetric synthesis but also effective disinfectants with antielectrostatic activity.

Full text of DOI:10.1016/j.tetasy.2010.10.029

Tetrahedron: Asymmetry 21 (2010) 2709–2718
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
3-Alkoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylimidazolium salts-based
chiral ionic liquids
Joanna Feder-Kubis a, , Maciej Kubicki b, Juliusz Pernak c
⇑
a
_
´
Wrocław University of Technology, Faculty of Chemistry, Wybrzeze Wyspianskiego 27, 50-370 Wrocław, Poland
b Poznan´ Adam Mickiewicz University, Faculty of Chemistry, Grunwaldzka 6, 60-780 Poznan´, Poland
c Poznan´ University of Technology, Department of Chemical Technology, pl. Skłodowskiej-Curie 2, 60-965 Poznan´, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
A new group of imidazolium salt-based chiral ionic liquids have been prepared and characterized. The
chiral ionic liquids obtained are stable in air, in contact with water and popular organic solvents. Their
physicochemical properties, single-crystal X-ray structures, antimicrobial activities, and antielectrostatic
effects have been determined. The chiral ionic liquids synthesized have proven to represent not only
potential new solvents in asymmetric synthesis but also effective disinfectants with antielectrostatic
activity.
Received 30 September 2010
Accepted 28 October 2010
Available online 22 November 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
were determined. First, the 1-alkoxymethylimidazoles shown in
Table 1 were prepared in toluene, according to Scheme 2. In the
Ionic liquids are organic salts (built with an organic cation and
organic or inorganic anion) that are generally liquid at ambient
temperatures or melt below 100 °C. This general definition makes
the cation–anion combinations enormous. The popularity of ionic
liquids has resulted in the emergence of new groups such as room
temperature ionic liquids,1–4 energetic ionic liquids,5–7 task-specificity
ionic liquids,8,9 and chiral ionic liquids,10–16 among others.
There are a growing numbers of papers indicating that chiral
ionic liquids may be useful in many areas of science and technology
but the synthesis and use of these liquids are still in their infancy.
Chiral pool material may be located in the cation or anion or in
both the cation and anion. Obviously, the chirality arising from
the starting material is kept in the ionic liquids. Numerous groups
have selected strategies to prepare chiral ionic liquids from chiral
starting materials including chiral cations by metathesis reactions.
Cations can be constructed without modification17,18 or with mod-
ification of the side chain.19–21 We have already described chiral
ionic liquids obtained directly from the natural chiral pool of
(1R,2S,5R)-(ꢀ)-menthol based. Herein we report the synthesis
and properties of new imidazolium chiral ionic liquids with two
substituents in the imidazolium ring: (1R,2S,5R)-(ꢀ)-menthoxy-
methyl and alkoxymethyl.
first step, triethylamine was reacted with the appropriate chloro-
methyl alkyl ether to give (alkoxymethyl)triethylammonium chlo-
rides. The second step consisted of the N-alkoxymethylation of the
imidazole with the appropriate (alkoxymethyl)triethylammonium
chloride. The 1-alkoxymethylimidazoles, which were formed in
74–82% yields, were distilled from the reaction mixture.
Quaternization was achieved using freshly distilled 1-alkoxyme-
thylimidazole and distilled chloromethyl (1R,2S,5R)-(ꢀ)-menthyl ether,
which was obtained from (1R,2S,5R)-(ꢀ)-menthol, an inexpensive
and commercially available (ꢀ)-isomer. This ether is an excellent
reagent for quaternization, but it is readily hydrolyzed to HCl,
CH2O, and menthol. As a result of this, these reactions should be
conducted under strictly anhydrous conditions. Herein, a suitable
solvent proved to be anhydrous hexane; from which the product
precipitated.
Quaternization takes place immediately and proceeds readily at
room temperature according to an SN1 mechanism.22–24 Table 2
contains a list of the chiral 3-alkoxymethyl-1-(1R,2S,5R)-(ꢀ)-men-
thoxymethylimidazolium chlorides 1, which have been prepared
by this procedure. The chlorides used as precursors of the new
chiral ionic liquids were obtained in very good yields and their
specific rotations were measured. The synthesized 3-alkoxymethyl-
1-(1R,2S,5R)-(ꢀ)-menthoxymethylimidazolium chlorides 1, which
are presented in Table 2, are colorless oils, except for 1a which is
a low melting crystal chloride.
2. Results and discussion
The purities of these salts were determined by a direct two-
phase titration technique (EN ISO 2871-2: 1994) and ranged from
97.1% to 99.9% (Table 2). The remainder was essentially water, since
the chlorides are hygroscopic. All of these precursors of chiral ionic
liquids 1 are soluble at room temperature in acetone, chloroform,
Several 3-alkoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylimi-
dazolium salts were prepared (Scheme 1) and their properties
⇑
Corresponding author. Tel.: +48 71 320 29 75; fax: +48 71 328 04 75.
E-mail address: joanna.feder-kubis@pwr.wroc.pl (J. Feder-Kubis).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.10.029

2710
J. Feder-Kubis et al. / Tetrahedron: Asymmetry 21 (2010) 2709–2718
Cl
O
RO
RO
N
N
N
N
+
O
Cl-
1
MX
RO
N
N
+
O
X-
2-5
Scheme 1.
DMF, THF, methanol, ethanol, 1-propanol, 2-propanol, and water.
Aqueous solutions of chlorides 1d–1k were observed to form a
foam. At elevated temperatures, the chlorides 1 were found to dis-
solve in ethyl acetate but not in hexane or ether.
Table 1
1-Alkoxymethylimidazoles prepared
R
Yield (%)
Bp (°C)
C2H5
C3H5
C4H9
C5H11
C6H13
C7H15
C8H17
C9H19
80
82
81
79
81
78
78
76
78
78
74
97–98 at 20 mmHg
In the asymmetric part of the unit cell of 1a, there are two cat-
ions, two chloride anions, and two water molecules. Interestingly,
both symmetry-independent cations have quite similar geome-
tries: bond lengths and bond angles but their conformations differ
fundamentally. Figure 1 shows the anisotropic ellipsoid represen-
tation of one of the molecules, while Figure 2 shows the compari-
son of both molecules. It is evident that the orientation of
substituents with respect to the imidazole ring plane is opposite
by the comparison of the appropriate torsion angles. For instance,
C2–N1–C11–O12 is 67.6(5)° in A and ꢀ77.9(4)° in B, C2–N3–C31–
O32: ꢀ81.3(4)° in A, 73.8(4)°. The absolute values of the angles are
115–116 at 17 mmHg
138–139 at 21 mmHg
155–156 at 18 mmHg
168–169 at 20 mmHg
178–179 at 19 mmHg
184–185 at 23 mmHg
177–178 at 13 mmHg
232–234 at 43 mmHg
205–206 at 17 mmHg
215–216 at 13 mmHg
C
C
C
10H21
11H23
12H25
+
(C2H5)3N
+
ROCH2N(C2H5)3 Cl-
ClCH2OR
+
+
(C2H5)3NH Cl-
+
ROCH2N(C2H5)3 Cl-
+
N
N
N
N
ROCH2
H
Scheme 2.
Table 2
3-Alkoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylimidazolium chlorides 1
Specific rotationb a 2D0
½ ꢁ
Chloride
R
Yield (%)
Mp (°C)
Surfactant content (%)
1a
1b
1c
1d
1e
1f
1g
1h
1i
C2H5
C3H5
C4H9
C5H11
C6H13
C7H15
C8H17
C9H19
98.5
98.0
99.0
97.5
97.5
96.0
95.0
94.5
94.0
95.0
94.5
55–58a
Oil
Oil
Oil
Oil
Oil
Oil
Oil
Oil
ꢀ137.6 (c 0.45)
ꢀ86.1 (c 0.9)
ꢀ59.7 (c 1.0)
ꢀ76.0 (c 1.7)
ꢀ71.6 (c 0.8)
ꢀ72.0 (c 0.7)
ꢀ67.6 (c 1.4)
ꢀ60.65 (c 0.9)
ꢀ59.9 (c 1.5)
ꢀ61.5 (c 1.2)
ꢀ65.2 (c 0.95)
99.8
99.9
99.8
99.7
98.5
98.1
98.4
98.2
97.5
97.1
97.9
C
C
C
10H21
11H23
12H25
1j
1k
Oil
Oil
a
From ethyl acetate + acetone + ethanol; needles.
c in ethanol.
b

J. Feder-Kubis et al. / Tetrahedron: Asymmetry 21 (2010) 2709–2718
2711
Table 3
Selected torsion angles
quite similar but the signs are opposite, and as there are no sym-
metry elements which can reverse these signs, this means that
there are two different conformers in the crystal structure.
A
B
C2–N1–C11–O12
C5–N1–C11–O12
N1–C11–O12–C13
C11–O12–C13–C14
C2–N3–C31–O32
C4–N3–C31–O32
N3–C31–O32–C33
C31–O32–C33–C34
C36–C35–C34–C341
C33–C38–C37–C371
67.6(5)
ꢀ77.9(4)
ꢀ109.8(5)
100.4(5)
82.8(4)
ꢀ75.9(4)
175.2(3)
ꢀ81.3(4)
93.6(4)
ꢀ89.2(3)
158.1(3)
177.1(3)
178.3(3)
ꢀ174.6(3)
73.8(4)
ꢀ100.9(4)
74.2(4)
124.2(3)
177.3(3)
174.9(3)
Figure 1. A perspective view of the cation
A with the labeling scheme; the
ellipsoids are drawn at the 33% probability level, hydrogen atoms are shown as
spheres of arbitrary radii.25
Figure 3. The crystal packing as seen along [0 1 0] direction.26
Figure 2. A comparison of the two symmetry-independent cations; the imidazo-
lium planes were fitted one onto another.25
The cyclohexane rings are very close to an ideal chair conforma-
tion, with all substituents in equatorial positions (Table 3 lists the
relevant torsion angles). In the crystal structure the chloride anions
and water molecules make isolated helices (Fig. 3) around the two-
fold screw axes along y. It should be noted that there are two types
of helices; one made by O1W water and Cl1A, and the other by
O2W and Cl1B (Fig. 4, Table 4). These helices have different types
of screw features: one kind is left-handed and the other is right-
handed. Hence, the same feature: the presence of pseudo-enantio-
meric pairs, which were observed at the level of conformation of
the cations, is also observed at the level of the crystal packing.
The cations and ion-water helices are linked by electrostatic inter-
actions and some weak, hydrogen-bond-type C–Hꢂ ꢂ ꢂO, and C–
Hꢂ ꢂ ꢂClꢀ interactions (cf. Table 4).
Figure 4. The neighboring hydrogen-bonded helices of different screw senses.26
tory yield. All of the [BF4]ꢀ 2, [ClO4]ꢀ 3, and [PF6]ꢀ 4 salts are
solid and the majority of them crystallized easily to form plates
or needles with a sharp melting point. All of the new 3-alkoxy-
methyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylimidazolium salts are
insoluble in water. Thus, by changing the counter anion, all of
the hydrophilic oil chlorides (with the exception 1a) are trans-
formed to hydrophobic crystal salts. All of the salts that were pre-
pared would qualify as ionic liquids. Table 5 contains the melting
points, specific rotations, and surfactant contents as estimated by
a direct two-phase titration technique, using ethanol as the solvent
for 2–4. These chiral ionic liquids are not soluble in water, hexane,
The final synthesis step involves the metathesis of the chlorides
with an appropriate inorganic salt in water or water/menthol solu-
tion. The ion exchange reaction proceeds smoothly, with satisfac-

2712
J. Feder-Kubis et al. / Tetrahedron: Asymmetry 21 (2010) 2709–2718
Table 4
Hydrogen bond data (Å, °)
tact with water and popular organic solvents. These chiral room
temperature ionic liquids can be made anhydrous by heating at
80 °C in vacuo and storing them over P4O10. The water content
was determined to be less than 500 ppm by coulometric Karl–Fisher
titration. After 41 days, these anhydrous chiral ionic liquids ab-
sorbed water from the atmosphere to a maximum level of about
1.0%.
We noticedthat 3-alkoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxyme-
thylimidazolium bis(trifluoromethanesulfonyl)imides absorbed less
water than the analogous alkylimidazolium bis(trifluoromethane-
sulfonyl)imides.24 For example after 41 days, 1-(1R,2S,5R)-(ꢀ)-
menthoxymethyl-3-octylimidazolium [Tf2N]ꢀ absorbed 1.51% of
water whereas its corresponding 1-(1R,2S,5R)-(ꢀ)-menthoxymeth-
yl-3-hexyloxymethylimidazolium [Tf2N]ꢀ 5e just 0.89%, which is
about 41% less.
The specific rotation, density, viscosity, thermal degradation,
and glass transition temperature for anhydrous and chloride-free
room temperature ionic liquids have been measured. The results
are presented in Table 6. The chiral ionic liquids are more dense
than water (1.29–1.15 g mLꢀ1) and decrease with increasing molar
mass. Figure 5 shows that there is a linear relationship between the
molar volume (calculated from the equation Vm = M/d where
d = density) and the number of carbon atoms in the alkoxy group.
The density of the dry chiral ionic liquids studied is weakly temper-
ature dependent. As the temperature is varied from 35 to 45 °C,
the density decreased by about 3%. Ionic liquids are inherently
D
H
A
D–H
Hꢂ ꢂ ꢂA
Dꢂ ꢂ ꢂA
D–Hꢂ ꢂ ꢂA
O1W
O1W
O2W
O2W
C31A
C5A
H1W1
H1W2
H2W2
H2W2
H31A
H5A
Cl1A
0.85
0.85
0.85
0.85
0.97
0.93
0.93
2.33
2.30
2.36
2.34
2.42
2.32
2.56
3.144(2)
3.113(2)
3.201(3)
3.140(3)
3.304(4)
3.198(5)
3.389(4)
161
161
169
156
151
158
148
Cl1Ai
Cl1B
Cl1Bii
O1Wiii
O1Wiv
Cl1B
C2B
H2B
Symmetry codes: (i) ꢀx, 1/2 + y, ꢀz; (ii) 1 ꢀ x, 1/2 + y, ꢀz; (iii) 1 + x, y, z; (iv) x,
y ꢀ 1, z.
and ether but are soluble in acetone, chloroform, DMF, THF, tolu-
ene, and low molecular weight alcohols. At elevated temperatures,
salts 2–4 have been found to dissolve in ethyl acetate.
On the other hand, room temperature ionic liquids can be ob-
tained by converting the anion from chloride into [Tf2N]ꢀ. Removal
of chloride ions from the hydrophobic ionic liquid was carried out
by rinsing them with distilled water. In Table 6, eleven chiral ionic
liquids 5 are presented, including 8 which are room temperature
ionic liquids. All room temperature ionic liquids are colorless liq-
uids, which are non-volatile, non-flammable, and miscible with
acetone, chloroform, ethyl acetate, DMF, THF, toluene, and low
molecular weight alcohols. They are not soluble in hexane or ether
and are immiscible with water. They are stable in air, and in con-
Table 5
3-Alkoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylimidazolium salts 2–4
Specific rotationd a 2D0
½ ꢁ
Chiral ionic liquids
R
Anion
Yield (%)
Mp (°C)
Surfactant content (%)
2a
2b
2c
2d
2e
2f
2g
2h
2i
C2H5
C3H5
C4H9
C5H11
C6H13
C7H15
C8H17
C9H19
[BF4]ꢀ
[BF4]ꢀ
[BF4]ꢀ
[BF4]ꢀ
[BF4]ꢀ
[BF4]ꢀ
[BF4]ꢀ
[BF4]ꢀ
[BF4]ꢀ
[BF4]ꢀ
[BF4]ꢀ
[ClO4]ꢀ
[PF6]ꢀ
99.5
99.5
99.5
99.0
99.0
98.0
98.5
98.5
99.0
97.0
87.5
99.0
99.5
80–82a
78–79a
91–92b
93–95b
72–74b
58–61c
46–47c
48–49c
32–33
ꢀ83.7 (c 0.6)
ꢀ98.3 (c 0.9)
ꢀ104.9 (c 0.6)
ꢀ75.2 (c 0.7)
ꢀ78.6 (c 0.6)
ꢀ66.2 (c 1.5)
ꢀ62.1 (c 1.6)
ꢀ67.6 (c 1.4)
ꢀ55.4 (c 1.1)
ꢀ54.3 (c 1.9)
ꢀ52.6 (c 1.4)
ꢀ80.8 (c 0.6)
ꢀ75.1 (c 0.5)
99.1
99.7
99.7
98.3
98.5
99.5
99.1
99.3
97.2
98.5
98.1
99.1
99.6
C
C
C
10H21
11H23
12H25
2j
2k
3
36–38
47–48c
63–64a
76–81a
CH3
CH3
4
a
b
c
From water + ethanol; needles.
From water + 2-propanol; needles.
From water + 2-propanol; plates.
c in ethanol.
d
Table 6
3-Alkoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylimidazolium bis(trifluoromethanesulfonyl)imides 5
d
e
Specific rotationb a 2D0
½ ꢁ
Chiral ionic liquids
R
Yield (%)
Mp (°C)
Densityc (g mLꢀ1
)
Viscosityc (mm2/s)
Tonset (°C)
Tg (°C)
5a
5b
5c
5d
5e
5f
5g
5h
5i
C2H5
C3H5
C4H9
C5H11
C6H13
C7H15
C8H17
C9H19
99.5
99.0
99.0
93.5
91.5
90.0
92.0
92.5
95.5
93.0
96.0
45–46a
ꢀ55.2 (c 1.1)
ꢀ54.1 (c 0.7)
ꢀ51.2 (c 0.95)
ꢀ49.3 (c 1.1)
ꢀ47.6 (c 0.9)
ꢀ45.7 (c 1.1)
ꢀ44.4 (c 1.2)
ꢀ41.3 (c 1.4)
ꢀ40.7 (c 2.2)
ꢀ34.4 (c 1.1)
ꢀ32.1 (c 1.0)
—
—
—
—
—
—
—
—
—
—
—
—
58–59a
33–35
—
—
—
—
—
—
—
—
1.29
1.27
1.25
1.23
1.21
1.18
1.16
1.15
600
612
630
666
703
728
756
779
230
225
225
230
230
230
230
230
ꢀ60.6
ꢀ61.2
ꢀ61.9
ꢀ61.8
ꢀ63.5
ꢀ66.4
ꢀ67.4
ꢀ68.2
C10H21
C11H23
C12H25
5j
5k
a
b
c
From water + 2-propanol; plates.
c in ethanol.
At 35 °C.
Decomposition temperature determined from onset to 50% mass loss.
Glass transition temperature.
d
e

J. Feder-Kubis et al. / Tetrahedron: Asymmetry 21 (2010) 2709–2718
2713
Comparing the differences between values of the chemical shifts,
the anions can be ordered according to their increasing shielding
capacities as follows:[Cl]ꢀ < [ClO4]ꢀ < [BF4]ꢀ < [Tf2N]ꢀ < [PF6]ꢀ.
The most pronounced shielding abilities were noted for the
[PF6]ꢀ and [Tf2N]ꢀ anions.
650
600
550
500
450
Additionally, the 13C NMR spectra indicated notable differences
in the chemical shifts depending on the anion used. These shifts
were most evident for carbon C12. For example: the difference
between 3-ethoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylim-
idazolium chloride 1a and its corresponding [NTf2]ꢀ 5a is
2.6 ppm. Significant differences in the chemical shifts were also ob-
served for carbon C9. In this case, the differences between the cor-
responding [Cl]ꢀ and [PF6]ꢀ salts achieve nearly 1 ppm.
The antielectrostatic effect was determined following the crite-
ria listed in Table 8. The antielectrostatic effect of salts 1–5 and 7
reflects two quantities: the surface resistance and the half-charge
decay time. The surface resistance Rs was calculated from the
formula:
5
6
7
8
9
10
11
12
Number of Carbon Atoms in the Alkoxy Group
Figure 5. Molar volume as a function of the number of carbon atoms in the alkoxy
group in chiral ionic liquids 5.
700
600
500
400
300
200
100
Ul
is
Rs ¼
½Xꢁ
where U is the applied voltage (U = 100 V), l is the length of the
electrode (l = 100 mm), i is the measured current intensity, and s is
the distance between the electrodes (s = 10 mm).
The half-charge decay time has been calculated as follows:
rffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
65
35
40
45
50
55
60
Temperature [°C]
sþ2
þ
sꢀ2
s1=2
¼
½sꢁ
2
Figure 6. Viscosity of dry chiral ionic liquid 5g as
temperature.
a function of increasing
where s+ and sꢀ are the mean half decay times of positive and neg-
ative charges, respectively.
The reported antielectrostatic effects are presented in Table 9.
All synthesized chlorides 1a–1k demonstrated excellent antielec-
trostatic effects. Their ability to drain the surface charge reflected
their strong hygroscopic properties. On the other hand, the
[BF4]ꢀ, [ClO4]ꢀ and [PF6]ꢀ salts lost their capacity to drain surface
electric charge, while, [Tf2N]ꢀ salts 5a–5k, even if strongly hydro-
phobic, demonstrated a strong tendency to drain the surface
charge. Bis(trifluoromethanesulfonyl)imides penetrate the poly-
mer surface because they have unique solvent capabilities and
are better able to discharge the electric charge.
The chiral chlorides prepared were tested for antimicrobial
activity against rods, cocci, and fungi. The minimum inhibitory
concentration (MIC) and minimum bactericidal or fungicidal con-
centration (MBC or MFC) determined for chiral chlorides 1h and
1i are given in Table 10. Additionally, MIC, MBC, and MFC values
are presented for benzalkonium chloride (BAC, in which alkyl rep-
resents a mixture of alkyls from C8H17 to C18H37).
Our previous biological research on 3-alkyl-1-(1R,2S,5R)-(ꢀ)-
menthoxymethylimidazolium chlorides has given us the best re-
sults for nonyl, decyl, undecyl, and dodecyl substituents.24 Those
chlorides should be regarded as superactive. This is why in order
to check the antimicrobial activities of 3-alkoxymethyl-1-
(1R,2S,5R)-(ꢀ)-menthoxymethylimidazolium chlorides we have
selected chlorides with nonylmethyl 1h and decylmethyl 1i sub-
stituents. Similarly as for alkylimidazolium chlorides, these two
alkoxymethylimidazolium chlorides 1h and 1i should be regarded
as superactive. The MIC and MBC values of each alkoxymethylim-
idazolium chloride are comparable, indicating not only a strong
biostatic effect but also high biocidal activity. Furthermore, the
activities for the majority of examples were higher than the ones
shown by BAC and these alkoxymethylimidazolium chlorides
broaden the range of activities against microbes. The results
achieved are in agreement with the literature data. Both alkyl27
and alkoxymethyl28,29 substituents in the imidazolium ring influ-
enced the antimicrobial activity.
much more viscous than popular organic solvents. Increases in
molar mass were accompanied by increases in viscosity, while
increasing the temperature resulted in a decrease in viscosity, as
shown in Figure 6 for 5g.
All room temperature ionic liquids have shown no measurable
vapor pressure. The thermal properties for the chiral ionic liquids
5 were established by DSC and TGA analyses. The glass transition
temperatures (Tg) are very low and oscillate between ꢀ60 °C and
ꢀ68 °C (depends of number of carbon atoms in the alkoxymeth-
ylimidazolium substituent). All synthesized liquids [Tf2N]ꢀ—5d–k
were thermally stable up to ca. 230 °C (a similar thermal stability
was observed earlier for 1-alkyl-3-(1R,2S,5R)-(ꢀ)-menthoxyme-
thylimidazolium [Tf2N]ꢀ24). The [Tf2N]ꢀ 5 could not be estimated
by a direct two-phase titration technique, because the [Tf2N]ꢀ an-
ion in this salt is not interchangeable.
The synthesized salts were characterized by 1H NMR, 13C NMR,
and elemental analysis. Protons of the H2C13 group, which links
the two rings, appear in the spectrum in the form of two doublets.
The manifestation of the diasteroisotopic protons was typical for
all the studied salts, for example, for 1a 5.74 and 5.93 (d,
J = 10.4 Hz, 2H, AB system, H13).
The 1H NMR spectra of the chlorides and the other salts indicate
different chemical shifts particularly for the imidazolium ring pro-
tons and methylene protons adjacent to the oxygen atoms. Table 7
shows a comparison of the 1H NMR spectra of the 3-ethoxymethyl-
1-(1R,2S,5R)-(ꢀ)-menthoxymethylimidazolium chloride 1a with
the following [BF4]ꢀ 2a, [ClO4]ꢀ 3, [PF6]ꢀ 4, and [NTf2]ꢀ 5a. A strong
anion effect was evident. Substitution of the [Cl]ꢀ anion with the
other anions named above resulted in changes in the imidazolium
ring electron density. A shift of nearly 3 ppm between the [Cl]ꢀ salt
and the [PF6]ꢀ salt in the case of the HC12 group shows the
dramatic effect of the change in electron density resulting from
changing the anion. Similar results were noticed earlier for 1-alky-
limidazolium salts,24 but a shift of 2 ppm for the same anions (in
the same conditions) has been observed there.

2714
J. Feder-Kubis et al. / Tetrahedron: Asymmetry 21 (2010) 2709–2718
Table 7
The chemical shiftsa in 1H NMR
H
H
14
15
H
8
9
11
16-27
C 10
H
RO
N
N
+
12
O
6
5
H
1
4
C 13
H
H
H
2
X-
3
7
Salt
Anion
Characteristic protons
6
+
H
H
H
H
H
H
O
N
N
C
N
O
C 13
H
C 10
9
11
12
H
RO
+
N
N
N
H
H
1a
2a
3
4
5a
[Cl]ꢀ
11.88 (t)
7.66 (t)
7.55 (t)
7.56 (t)
7.46 (m)
7.57 (m)
7.58 (t)
7.53 (t)
5.74 and 5.93 (d)
5.62 (m)
5.65 (m)
5.58 (m)
5.57 i 5.64 (d)
5.85 (s)
3.41 (td)
3.41 (td)
3.37 (td)
3.32 (td)
3.31 (td)
[BF4]ꢀ
[ClO4]ꢀ
[PF6]ꢀ
[NTf2]ꢀ
9.12 (m)
9.24 (m)
8.92 (m)
9.05 (m)
7.45 (m)
5.58 (s)
a
Shift in ppm and J in Hertz.
Table 8
Criteria for the estimation of the antielectrostatic effect based on the surface
liquids include not only negligible vapor pressure, compatibility
with various organic compounds, ease of separation in aqueous-
liquid separations, antielectrostatic and antimicrobial activities
but also their potential application in asymmetric synthesis.
The proposed method of the synthesis of chiral ionic liquids
with chirality on the cation is effective and provides the possibility
to use chiral alcohols. The introduction of oxygen atoms to substit-
uents causes a fall in the thermal stability of synthesized salts but
at the same time improves susceptibility to biodegradation and
hydrolysis. The synthesized high biological active chlorides are po-
tential substitutes for benzalkonium chloride, which is used for
mouthwash.
resistance Rs
[X] and half-charge decay time s1/2 [s]
log Rs
s1/2
Antielectrostatic effect
<9
<0.5
Excellent
9–9.99
10–10.99
11–11.99
12–12.99
>13
0.51–2
2.1–10
10.1–100
>100
Very good
Good
Sufficient
Insufficient
>600
Lack of antielectrostatic properties
Table 9
Further research to fully evaluate the potential of these new
chiral compounds in synthetic and analytical applications is cur-
rently ongoing in our laboratories. We are currently studying the
use of chiral ionic liquids as solvents, as well as chiral catalysts
for a variety of asymmetric reactions. We envision that these
new ionic liquids will serve as effective solvents, especially since
a successful example in this area has already been reported in
the literature for a similar compound, with a (1R,2S,5R)-(ꢀ)-
menthoxymethyl substituent in a chiral ionic liquid.30 In 2005,
Ding et al. reported that several chiral ionic liquids have been suc-
cessfully used as chiral solvents in the photoisomerization of
dibenzobicyclo[2.2.2]octatriene diacid to induce enantiomeric ex-
cesses. The observed enantioselectivities, although modest in an
absolute sense, are among the highest achieved for unimolecular
photochemical reactions by the use of a chiral environment.
Surface resistance Rs
of the salts prepared
[
X
], half-charge decay time s1/2 [s], and antielectrostatic effects
Salt log Rs s1/2
Effect
Salt log Rs s1/2
Effect
1a
1b
1c
1d
1e
1f
1g
1h
1i
7.9
7.5
7.3
7.0
7.0
7.3
7.3
7.3
7.3
7.3
7.5
0.2
0.2
Excellent
Excellent
2h
2i
2j
2k
3
4
5a
5b
5c
5d
5e
5f
5g
5h
5i
12.9 >100
12.8 >100
12.9 >100
12.9 >100
Insufficient
Insufficient
Insufficient
Insufficient
Lack
0.25 Excellent
0.25 Excellent
0.2
0.2
0.2
0.2
0.2
0.2
Excellent
Excellent
Excellent
Excellent
Excellent
Excellent
>13
>13
9.9
>600
>600
Lack
0.8
Very good
Very good
Very good
Very good
Very good
Very good
9.5
9.8
9.7
9.5
9.3
8.9
8.9
8.8
8.8
8.9
0.9
1.0
1.0
1.0
0.2
1j
1k
2a
2b
2c
2d
2e
2f
0.25 Excellent
>13
>600
Lack
Lack
Lack
Lack
Insufficient 5j
Insufficient 5k
Insufficient
>13
>13
>13
12.3
12.8
12.8
>600
>600
>600
73
0.25 Excellent
0.2
0.2
0.25 Excellent
0.2 Excellent
Excellent
Excellent
4. Experimental
85
95
2g
4.1. General methods
1H NMR spectra were recorded on a Mercury Gemini 300 spec-
trometer at 300 MHz with tetramethylsilane as the standard; 13C
NMR spectra were recorded on the same instrument at 75 MHz.
Two-dimensional spectra were performed using standard pulse se-
quences from the Bruker Drx puls library at 600 MHz.
3. Conclusion
By applying Menschutkin reaction conditions, a number of chi-
ral alkoxymethylimidazolium-based ionic liquids were synthe-
sized, in which the chirality originates from the cation, which
was derivatized from the chiral pool of (1R,2S,5R)-(ꢀ)-menthol.
The type of anion determines the consistency and hygroscopic
character of the salt. Salts with a [Tf2N] anion are room tempera-
ture ionic liquids. The important attributes of the chiral ionic
´
Elemental analyses were performed at Poznan Adam Mick-
iewicz University. Melting points were determined by using an
electrothermal digital-melting-point apparatus model JA 9100. A
Mettler Toledo DA 110 M scale was used for the mass/density mea-
surements. A Mikro-Ostwald-Viskosimeter was used to viscosity

J. Feder-Kubis et al. / Tetrahedron: Asymmetry 21 (2010) 2709–2718
2715
Table 10
MIC and MBC values (
l
M) of 3-alkoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylimidazolium chlorides 1h and 1i
Strain
Chloride
Strain
Chloride
1h
1.2
19
0.2
0.5
2.3
2.3
4.7
1i
BACa
1h
1i
BAC
M. luteus
MIC
MBC
MIC
MBC
MIC
MBC
MIC
MBC
MIC
MBC
MIC
MBC
0.5
4.5
0.2
0.5
1.1
4.5
0.2
9
0.5
2.3
0.5
0.5
1.4
11
2.8
23
1.4
5.6
5.6
23
0.6
1.4
2.8
2.8
S. marcescens
P. vulgaris
P. aeruginosa
B. subtilis
MIC
MBC
MIC
MBC
MIC
MBC
MIC
MBC
MIC
MFC
MIC
MFC
145
145
37
37
145
145
2.3
2.3
19
72
9
282
282
18
175
175
88
88
175
175
2.8
2.8
11
88
23
88
S. aureus
18
S. epidermidis
E. faecium
M. catarrhalis
E. coli
282
565
1.1
2.3
4.5
36
19
1.2
1.2
1.2
2.3
C. albicans
R. rubra
9
19
18
a
Benzalkonium chloride.
measurements. Optical rotations were measured with a Perkin El-
mer 243B polarimeter. The water content was determined by using
an Aquastar volumetric Karl-Fischer titration with Composite 5
solution as the titrant and anhydrous methanol as solvent.
Elemental Anal. Calcd for C17H31ClN2O2 (330.5): C, 61.69; H, 9.46;
N, 8.47. Found: C, 61.39; H, 9.55; N, 8.59.
4.2.2.2.
1-(1R,2S,5R)-(ꢀ)-Menthoxymethyl-3-propoxymeth-
ylimidazolium chloride 1b. 1H NMR (CDCl3, 25 °C): d = 0.52 (d,
J = 6.9 Hz, 3H, H14 or H15), 0.90 (m, 12H, Ha-4, H7, H14 or H15,
Ha-2, Ha-1 and H18), 1.27 (m, 1H, H5), 1.44 (m, 1H, H3), 1.63
(m, 3H, Hb-1 and H17), 2.10 (m, 3H, Hb-4, H8 and Hb-2), 3.51
(m, 3H, H6 and H16), 5.77 (m, 4H, H10 and H13), 9.42 (m, 1H,
4.2. Syntheses
Chloromethyl (1R,2S,5R)-(ꢀ)-menthyl ether was prepared by
passing HCl through a mixture of formaldehyde and (1R,2S,5R)-
(ꢀ)-menthol.22 Chloromethyl alkyl ethers were prepared by pass-
ing HCl through a mixture of formaldehyde and the appropriate
alcohol. Imidazole was freshly recrystallized from benzene; mp
90–91 °C.
2;10
H11), 10.12 (t, J1,2 = 1.8 Hz, J = 1.7 Hz, 1H, H9), 10.87 (m, 1H,
H12); 13C NMR (CDCl3): d = 10.3 (C18), 15.6 (C14 or C15), 20.9
(C7), 22.1 (C14 or C15), 22.4 (C1), 22.8 (C17), 25.4 (C8), 31.15
(C3), 34.0 (C4), 40.4 (C2), 47.8 (C5), 72.25 (C16), 76.6 (C6), 79.5
(C10), 80.0 (C13), 121.2 (C11), 136.1 (C9), 137.7 (C12). Elemental
Anal. Calcd for C18H33ClN2O2 (344.98): C, 62.66; H, 9.66; N, 8.12.
Found: C, 62.84; H, 9.71; N, 7.92.
4.2.1. Preparation of 1-alkoxymethylimidazoles
The appropriate chloromethyl alkyl ether (0.05 mol) was slowly
added to a stirred anhydrous solution of triethylamine (5.06 g,
0.05 mol) in toluene (50 mL), and stirring was continued at 80 °C
for 15 min. Imidazole (3.4 g, 0.05 mol) was then added. After
30 min, the mixture was refluxed. After cooling to room tempera-
ture, the triethylamine hydrochloride produced was filtered off and
the toluene was evaporated. The product was purified by vacuum
distillation.
4.2.2.3. 1-(1R,2S,5R)-(ꢀ)-Menthoxymethyl-3-pentyloxymethy-
limidazolium chloride 1d. 1H NMR (CDCl3, 25 °C): d = 0.51 (d, J =
6.9 Hz, 3H, H14 or H15), 0.90 (m, 12H, Ha-4, H7, H14 or H15, Ha-
2, Ha-1 and H20), 1,26 (m, 5H, H5, H18 and H19), 1.42 (m, 1H,
H3), 1.59 (m, 4H, Hb-1, Hb-4 and H17), 1.97 (sept d, J1,3 = 6.9 Hz,
J
J
1,2 = 2.5 Hz, 1H, H8), 2.10 (d, J = 11.8 Hz, 1H, Hb-2), 3.41 (td,
1,3 = 10.4 Hz, J1,2 = 4.1 Hz, 1H, H6), 3.59 (m, 2H, H16), 5.84 (s, 2H,
H10), 5.76 and 5.94 (m, 2H, H13), 7.71 (m, 1H, H11), 7.75 (m, 1H,
H9), 10.74 (m, 1H, H12); 13C NMR (CDCl3): d = 13.5 (C20), 15.2
(C14 or C15), 20.6 (C7), 21.8 (C19), 21.9 (C14 or C15), 22.4 (C1),
25.0 (C8), 27.6 (C18), 28.5 (C17), 30.7 (C3), 33.6 (C4), 40.0 (C2),
47.3 (C5), 70.3 (C16), 76.6 (C6), 79.0 (C10), 79.4 (C13), 121.4
(C11), 121.6 (C9), 137.1 (C12). Elemental Anal. Calcd for
4.2.2. General procedure for quaternization
Chloromethyl (1R,2S,5R)-(ꢀ)-menthyl ether (0.03 mol) was
added dropwise into a round-bottomed flask, which contained a
vigorously stirred mixture of 30 mL of dry hexane and 0.03 mol
of freshly distilled 1-alkoxymethylimidazole. The reaction mixture
was stirred at room temperature for 60 min. After 120 min, the
phases were separated and the crude product was washed with
dry hexane (3 ꢃ 30 mL). The volatile materials were removed un-
der reduced pressure at 60 °C overnight.
C20H37ClN2O2 (330.5): C, 64.39; H, 10.02; N, 7.51. Found: C,
64.48; H, 10.13; N, 7.35.
4.2.3. General procedure for ion exchange
Chiral 3-alkoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylimid-
azolium chlorides were dissolved in water or methanol and a sat-
urated aqueous stoichiometric solution of NaBF4, NaClO4, KPF6 or
Tf2NLi was added. The reaction mixture was stirred at room tem-
perature (for 24 h) producing a heterogeneous mixture. The crude
product was separated and washed with distilled water until the
chloride ions were no longer detected using AgNO3. The salt ob-
tained was dried at 80 °C for 24 h in vacuo. In the cases of water-
soluble salts, the water was first evaporated and the remnants
were dissolved in dry acetone. The inorganic salt was separated
and the solvent was evaporated to give the product.
4.2.2.1. 3-Ethoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylimi-
dazolium chloride 1a. 1H NMR (CDCl3, 25 °C): d = 0.51 (d, J =
6.9 Hz, 3H, H14 or H15), 0.91 (m, 9H, Ha-4, H7, H14 or H15, Ha-2
and Ha-1), 1.25 (m, 4H, H5 and H17), 1.46 (m, 1H, H3), 1.63 (m,
2H, Hb-1 and Hb-4), 1.97 (sept d, J1,3 = 7.1 Hz, J1,2 = 2.5 Hz, 1H,
H8), 2.08 (m, 1H, Hb-2), 3.41 (td, J1,3 = 10.4 Hz, J1,2 = 4.1 Hz, 1H,
H6), 3.68 (q, J = 7.1 Hz, 2H, H16), 5.85 (s, 2H, H10), 5.74 and
5.93 (d, J = 10.4 Hz, 2H, AB system, H13), 7.58 (t, J1,2 = 1.9 Hz,
0
2;10
J2;1 = 1.6 Hz, 1H, H11), 7.66 (t, J1,2 = 1.9 Hz, J = 1.6 Hz, 1H, H9),
11.88 (t, J = 1.4 Hz, 1H, H12); 13C NMR (CDCl3): d = 14.6 (C17),
15.4 (C14 or C15), 20.8 (C7), 22.0 (C14 or C15), 22.6 (C1), 25.3
(C8), 31.0 (C3), 33.8 (C4), 40.2 (C2), 47.5 (C5), 66.0 (C16), 76.6
(C6), 79.0 (C10), 79.8 (C13), 121.4 (C11), 122.5 (C9), 137.6 (C12).
4.2.3.1. 3-Ethoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylimi-
dazolium tetrafluoroborate 2a. 1H NMR (CDCl3, 25 °C): d = 0.51

2716
J. Feder-Kubis et al. / Tetrahedron: Asymmetry 21 (2010) 2709–2718
(d, J = 6.9 Hz, 3H, H14 or H15), 0.91 (m, 9H, Ha-4, H7, H14 or H15,
Ha-2 and Ha-1), 1.23 (m, 4H, H5 and H17), 1.42 (m, 1H, H3), 1.62
(m, 2H, Hb-1 and Hb-4), 1.97 (m, 2H, H8 and Hb-2), 3.41 (td,
(C4), 40.2 (C2), 47.8 (C5), 70.8 (C16), 76.6 (C6), 79.65 (C10), 80.0
(C13), 121.3 (C11), 121.7 (C9), 136.3 (C12). Elemental Anal. Calcd
for C21H39BF4N2O2 (438.42): C, 57.53; H, 8.98; N, 6.39. Found: C,
57.27; H, 9.19; N, 6.48.
J
1,3 = 10.4 Hz, J1,2 = 4.1 Hz, 1H, H6), 3.62 (q, J = 7.1 Hz, 2H, H16),
5.62 (m, 4H, H10 and H13), 7.53 (t, J = 1.6 Hz, 1H, H11), 7.55 (t,
J = 1.6 Hz, 1H, H9), 9.12 (m, 1H, H12); 13C NMR (CDCl3): d = 14.7
(C17), 15.4 (C14 or C15), 20.9 (C7), 22.1 (C14 or C15), 22.8 (C1),
25.4 (C8), 31.0 (C3), 34.0 (C4), 40.2 (C2), 47.7 (C5), 66.1 (C16),
76.6 (C6), 79.2 (C10), 79.9 (C13), 121.6 (C11), 121.8 (C9), 135.9
(C12). Elemental Anal. Calcd for C17H31BF4N2O2 (382.3): C, 53.41;
H, 8.19; N, 7.33. Found: C, 53.10; H, 8.27; N, 7.40.
4.2.3.6. 1-(1R,2S,5R)-(ꢀ)-Menthoxymethyl-3-octyloxymethylim-
idazolium tetrafluoroborate 2g. 1H NMR (CDCl3, 25 °C): d = 0.51
(d, J = 7.0 Hz, 3H, H14 or H15), 0.90 (m, 12H, Ha-4, H7, H14 or H15,
Ha-2, Ha-1 and H23), 1.25 (m, 11H, H5, H18, H19, H20, H21 and
H22), 1.39 (m, 1H, H3), 1.59 (m, 4H, Hb-1, Hb-4 and H17), 1.99
(m, 2H, H8 and Hb-2), 3.35 (td, J1,3 = 10.5 Hz, J1,2 = 4.3 Hz, 1H,
H6), 3.54 (t, J1,2 = 6.3 Hz, 2H, H16), 5.62 (m, 4H, H10 and H13),
7.47 (m, 2H, H11 and H9), 9.16 (m, 1H, H12); 13C NMR (CDCl3):
d = 14.1 (C23), 15.5 (C14 or C15), 20.95 (C7), 22.1 (C14 or C15),
22.6 (C1), 22.8 (C22), 25.5 (C8), 25.9 (C21), 29.2 (C20), 29.25
(C19), 29.3 (C18), 31.0 (C3), 31.8 (C17), 34.1 (C4), 40.2 (C2), 47.9
(C5), 70.9 (C16), 76.6 (C6), 79.6 (C10), 80.0 (C13), 121.5 (C11),
121.75 (C9), 136.3 (C12). Elemental Anal. Calcd for C23H43BF4N2O2
(466.48): C, 59.21; H, 9.31; N, 6.01. Found: C, 58.90; H, 9.44; N,
6.12.
4.2.3.2. 1-(1R,2S,5R)-(ꢀ)-Menthoxymethyl-3-propoxymethylim-
idazolium tetrafluoroborate 2b. 1H NMR (CDCl3, 25 °C): d = 0.54
(d, J = 6.9 Hz, 3H, H14 or H15), 0.91 (m, 12H, Ha-4, H7, H14 or H15,
Ha-2, Ha-1 and H18), 1.26 (m, 1H, H5), 1.43 (m, 1H, H3), 1.61 (m,
4H, Hb-1, Hb-4 and H17), 2.01 (m, 2H, H8 and Hb-2), 3.36 (td,
J
1,3 = 10.5 Hz, J1,2 = 4.2 Hz, 1H, H6), 3.51 (m, 2H, H16), 5.63 (m,
4H, H10 and H13), 7.51 (m, 2H, H11 and H9), 9.19 (t, J = 1.6 Hz,
1H, H12); 13C NMR (CDCl3): d = 10.3 (C18), 15.7 (C14 or C15),
21.0 (C7), 22.1 (C14 or C15), 22.45 (C1), 22.8 (C17), 25.5 (C8),
31.1 (C3), 34.1 (C4), 40.2 (C2), 47.9 (C5), 72.2 (C16), 76.6 (C6),
79.6 (C10), 80.2 (C13), 121.5 (C11), 121.7 (C9), 136.4 (C12). Ele-
mental Anal. Calcd for C18H33BF4N2O2 (396.33): C, 54.54; H, 8.41;
N, 7.07. Found: C, 54.23; H, 8.57; N, 7.15.
4.2.3.7.
1-(1R,2S,5R)-(ꢀ)-Menthoxymethyl-3-nonyloxymethy-
limidazolium tetrafluoroborate 2h. 1H NMR (CDCl3, 25 °C): d =
0.50 (d, J = 6.9 Hz, 3H, H14 or H15), 0.91 (m, 12H, Ha-4, H7, H14
or H15, Ha-2, Ha-1 and H24), 1.25 (m, 13H, H5, H18, H19, H20,
H21, H22 and H23), 1.38 (m, 1H, H3), 1.58 (m, 4H, Hb-1, Hb-4
and H17), 1.99 (m, 2H, H8 and Hb-2), 3.35 (td, J1,3 = 10.4 Hz,
4.2.3.3. 3-Butoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylimi-
dazolium tetrafluoroborate 2c. 1H NMR (CDCl3, 25 °C): d = 0.51
(d, J = 7.0 Hz, 3H, H14 or H15), 0.89 (m, 12H, Ha-4, H7, H14 or H15,
Ha-2, Ha-1 and H19), 1.33 (m, 3H, H5 and H18), 1.60 (m, 4H, H3,
Hb-1 and H17), 1.91 (m, 1H, Hb-4), 1.98 (m, 2H, H8 and Hb-2),
3.36 (td, J1,3 = 10.5 Hz, J1,2 = 4.2 Hz, 1H, H6), 3.55 (t, J = 6.4 Hz, 2H,
H16), 5.63 (m, 4H, H10 and H13), 7.48 (m, 2H, H11 and H9), 9.16
(m, 1H, H12); 13C NMR (CDCl3): d = 13.7 (C19), 15.5 (C14 or C15),
19.0 (C7), 20.95 (C18), 22.1 (C14 or C15), 22.8 (C1), 25.5 (C8),
31.0 (C17), 31.2 (C3), 34.1 (C4), 40.2 (C2), 47.8 (C5), 70.5 (C16),
76.6 (C6), 79.6 (C10), 80.0 (C13), 121.4 (C11), 121.8 (C9), 136.3
J
1,2 = 4.1 Hz, 1H, H6), 3.53 (t, J1,2 = 6.6 Hz, 2H, H16), 5.64 (m, 4H,
2;10
H10 and H13), 7.57 (t, J1,2 = 1.9 Hz, J = 1.4 Hz, 1H, H11), 7.58 (t,
2;10
J
1,2 = 1.9 Hz, J = 1.4 Hz, 1H, H9), 9.14 (m, 1H, H12); 13C NMR
(CDCl3): d = 13.9 (C24), 15.2 (C14 or C15), 20.7 (C7), 21.9 (C14 or
C15), 22.4 (C1), 22.6 (C23), 25.1 (C8), 25.6 (C22), 29.0 (C21),
29.05 (C20), 29.1 (C19), 29.3 (C18), 30.8 (C3), 31.6 (C17), 33.8
(C4), 39.9 (C2), 47.5 (C5), 70.5 (C16), 76.6 (C6), 79.3 (C10), 79.6
(C13), 121.6 (C11), 121.9 (C9), 135.8 (C12). Elemental Anal. Calcd
for C24H45BF4N2O2 (480.51): C, 59.99; H, 9.46; N, 5.83. Found: C,
60.20; H, 9.52; N, 5.76.
(C12). Elemental Anal. Calcd for
C19H35BF4N2O2 (410.36): C,
55.61; H, 8.61; N, 6.83. Found: C, 55.30; H, 8.82; N, 6.79.
4.2.3.8. 3-Ethoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylimi-
dazolium perchlorate 3. 1H NMR (CDCl3, 25 °C): d = 0.51 (d, J =
6.9 Hz, 3H, H14 or H15), 0.91 (m, 9H, Ha-4, H7, H14 or H15, Ha-2
and Ha-1), 1.24 (m, 4H, H5 and H17), 1.44 (m, 1H, H3), 1.62 (m,
2H, Hb-1 and Hb-4), 1.98 (m, 2H, H8 and Hb-2), 3.37 (td,
4.2.3.4. 1-(1R,2S,5R)-(ꢀ)-Menthoxymethyl-3-pentyloxymethy-
limidazolium tetrafluoroborate 2d. 1H NMR (CDCl3, 25 °C):
d = 0.50 (d, J = 6.9 Hz, 3H, H14 or H15), 0.91 (m, 12H, Ha-4, H7,
H14 or H15, Ha-2, Ha-1 and H20), 1.25 (m, 5H, H5, H18 and
H19), 1.41 (m, 1H, H3), 1.59 (m, 4H, Hb-1, Hb-4 and H17), 1.98
(m, 2H, H8 and Hb-2), 3.35 (td, J1,3 = 10.4 Hz, J1,2 = 4.1 Hz, 1H,
H6), 3.53 (t, J = 6.6 Hz, 2H, H16), 5.59 (s, 2H, H10), 5.58 and 5.67
(d, J = 10.7 Hz, 2H, AB system, H13), 7.50 (m, 1H, H11), 7.51 (m,
1H, H9), 9.1 (m, 1H, H12); 13C NMR (CDCl3): d = 14.0 (C20), 15.5
(C14 or C15), 21.0 (C7), 22.1 (C19), 22.4 (C14 or C15), 22.8 (C1),
25.4 (C8), 28.0 (C18), 28.8 (C17), 31.0 (C3), 34.0 (C4), 40.2 (C2),
47.7 (C5), 70.7 (C16), 76.6 (C6), 79.5 (C10), 79.9 (C13), 121.3
(C11), 121.7 (C9), 136.0 (C12). Elemental Anal. Calcd for
J
1,3 = 10.4 Hz, J1,2 = 4.1 Hz, 1H, H6), 3.64 (q, J = 7.1 Hz, 2H, H16),
2;10
5.65 (m, 4H, H10 and H13), 7.56 (t, J1,2 = 1.9 Hz, J = 1.6 Hz, 2H,
H11 and H9), 9.24 (m, 1H, H12); 13C NMR (CDCl3): d = 14.7 (C17),
15.5 (C14 or C15), 20.9 (C7), 22.1 (C14 or C15), 22.7 (C1), 25.4
(C8), 31.0 (C3), 34.0 (C4), 40.2 (C2), 47.7 (C5), 66.2 (C16), 76.6
(C6), 79.3 (C10), 79.9 (C13), 121.6 (C11), 121.8 (C9), 135.9 (C12).
Elemental Anal. Calcd for C17H31ClN2O6 (394.95): C, 51.69; H,
7.93; N, 7.09. Found: C, 52.01; H, 7.75; N, 7.05.
4.2.3.9. 3-Ethoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylimi-
dazolium hexafluorophosphate 4. 1H NMR (CDCl3, 25 °C): d =
0.55 (d, J = 6.6 Hz, 3H, H14 or H15), 0.93 (m, 9H, Ha-4, H7, H14
or H15, Ha-2 and Ha-1), 1.24 (m, 4H, H5 and H17), 1.45 (m, 1H,
H3), 1.63 (m, 2H, Hb-1 and Hb-4), 2.00 (m, 2H, H8 and Hb-2),
3.32 (td, J1,3 = 7.1 Hz, J1,2 = 3.8 Hz, 1H, H6), 3.60 (kw, J = 7.1 Hz,
2H, H16), 5.58 (m, 4H, H10 and H13), 7.45 (m, 1H, H11), 7.46 (m,
1H, H9), 8.92 (m, 1H, H12); 13C NMR (CDCl3): d = 14.7 (C17), 15.4
(C14 or C15), 21.0 (C7), 22.1 (C14 or C15), 22.8 (C1), 25.5 (C8),
31.0 (C3), 34.1 (C4), 40.2 (C2), 47.9 (C5), 66.2 (C16), 76.6 (C6),
79.3 (C10), 80.1 (C13), 121.3 (C11), 121.6 (C9), 135.6 (C12). Ele-
mental Anal. Calcd for C17H31F6N2O2P (440.47): C, 46.35; H, 7.11;
N, 6.36. Found: C, 46.10; H, 7.03; N, 6.51.
C
20H37BF4N2O2 (424.39): C, 56.60; H, 8.81; N, 6.60. Found: C,
56.37; H, 8.72; N, 6.77.
4.2.3.5.
3-Hexyloxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethy-
limidazolium tetrafluoroborate 2e. 1H NMR (CDCl3, 25 °C):
d = 0.51 (d, J = 7.0 Hz, 3H, H14 or H15), 0.90 (m, 12H, Ha-4, H7,
H14 or H15, Ha-2, Ha-1 and H21), 1.27 (m, 7H, H5, H18, H19 and
H20), 1.62 (m, 5H, H3, Hb-1, Hb-4 and H17), 1.99 (m, 2H, H8 and
Hb-2), 3.35 (td, J1,3 = 10.55 Hz,
J
1,2 = 4.3 Hz, 1H, H6), 3.53 (t,
J = 6.5 Hz, 2H, H16), 5.62 (m, 4H, H10 and H13), 7.47 (m, 2H, H11
and H9), 9.16 (m, 1H, H12); 13C NMR (CDCl3): d = 14.0 (C21), 15.5
(C14 or C15), 21.0 (C7), 22.1 (C20), 22.5 (C14 or C15), 22.8 (C1),
25.5 (C8), 25.55 (C19), 29.1 (C18), 31.0 (C3), 31.5 (C17), 34.1

J. Feder-Kubis et al. / Tetrahedron: Asymmetry 21 (2010) 2709–2718
2717
Table 11
4.2.3.10. 3-Ethoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylim-
idazolium bis(trifluoromethanesulfonyl)imide 5a. 1H NMR
(CDCl3, 25 °C): d = 0.50 (d, J = 7.1 Hz, 3H, H14 or H15), 0.93 (m,
9H, Ha-4, H7, H14 or H15, Ha-2 and Ha-1), 1.26 (m, 4H, H5 and
H17), 1.43 (m, 1H, H3), 1.63 (m, 2H, Hb-1 and Hb-4), 1.95 (m,
2H, H8 and Hb-2), 3.31 (td, J1,3 = 10.7 Hz, J1,2 = 4.4 Hz, 1H, H6),
3.59 (q, J = 7.1 Hz, 2H, H16), 5.58 (s, 2H, H10), 5.57 and 5.64 (d,
J = 10.7 Hz, 2H, AB system, H13), 7.57 (m, 2H, H11 and H9), 9.05
(m, 1H, H12); 13C NMR (CDCl3): d = 14.3 (C17), 15.1 (C14 or C15),
20.6 (C7), 21.7 (C14 or C15), 22.6 (C1), 25.2 (C8), 30.9 (C3), 33.8
(C4), 40.0 (C2), 47.5 (C5), 66.0 (C16), 76.6 (C6), 79.1 (C10), 80.0
(C13), 122.0 (C11), 122.2 (C9), 135.0 (C12); anion: 113.2, 117.5,
121.7, 126.0. Elemental Anal. Calcd for C19H31F6N3O6S2 (575.73):
C, 39.63; H, 5.44; N, 7.30. Found: C, 39.54; H, 5.56; N, 7.43.
Crystal data, data collection and structure refinement
1a
Formula
Formula weight
Crystal system
Space group
a (Å)
(C17H33N2O2)+ꢂClꢀꢂH2O
348.90
Monoclinic
P21
13.838(3)
9.132(2)
17.367(4)
110.46(3)
2056.2(8)
4
1.13
760
0.20
b (Å)
c (Å)
b (°)
V (Å3)
Z
dx (g cmꢀ3
F(0 0 0)
)
l
(mmꢀ1
)
H
Range (°)
2.45–25.00
ꢀ16 6 h 6 15
ꢀ10 6 k 6 10
ꢀ13 6 l 6 20
hkl Range
4.2.3.11. 1-(1R,2S,5R)-(ꢀ)-Menthoxymethyl-3-propoxymethy-
limidazolium bis(trifluoromethanesulfonyl)imide 5b. 1H NMR
(CDCl3, 25 °C): d = 0.51 (m, 3H, H14 or H15), 0.91 (m, 12H, Ha-4,
H7, H14 or H15, Ha-2, Ha-1 and H18), 1.27 (m, 1H, H5), 1.44 (m,
1H, H3), 1.62 (m, 3H, Hb-1 and H17), 1.95 (m, 2H, Hb-4 and H8),
2.20 (m, 1H, Hb-2), 3.32 (td, J1,3 = 10.6 Hz, J1,2 = 4.3 Hz, 1H, H6),
3.50 (q, J = 6.6 Hz, 2H, H16), 5.63 (m, 4H, H10 and H13), 7.51 (m,
2H, H11 and H9), 9.20 (m, 1H, H12); 13C NMR (CDCl3): d = 10.1
(C18), 15.5 (C14 or C15), 20.9 (C7), 21.9 (C14 or C15), 22.4 (C1),
22.8 (C17), 25.5 (C8), 31.1 (C3), 34.0 (C4), 40.2 (C2), 47.7 (C5),
72.4 (C16), 76.6 (C6), 79.7 (C10), 80.4 (C13), 121.65 (C11), 121.8
(C9), 135.6 (C12); anion: 113.2, 117.6, 121.7, 126.0. Elemental
Anal. Calcd for C20H33F6N3O6S2 (589.76): C, 40.73; H, 5.65; N,
7.13. Found: C, 40.99; H, 5.51; N, 7.04.
Reflections
Collected
Unique (Rint
With I > 2
No. of parameters
R(F) [I > 2 (I)]
wR(F2) [I > 2
(I)]
11266
6778 (0.042)
2436
423
0.036
)
r(I)
r
r
0.029
R(F) [all data]
0.145
0.034
0.67
0.10/ꢀ0.13
wR(F2) [all data]
Goodness of fit
Max/min
D
q
(e Åꢀ3
)
fractometer with Sapphire CCD-detector with graphite-monochro-
4.2.3.12. 3-Butoxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethylim-
idazolium bis(trifluoromethanesulfonyl)imide 5c. 1H NMR
(CDCl3, 25 °C): d = 0.50 (d, J = 7.0 Hz, 3H, H14 or H15), 0.91 (m,
12H, Ha-4, H7, H14 or H15, Ha-2, Ha-1 and H19), 1.33 (m, 3H,
H5 and H18), 1.60 (m, 5H, H3, Hb-1, H17 and Hb-4), 1.97 (m, 2H,
H8 and Hb-2), 3.32 (td, J1,3 = 10.5 Hz, J1,2 = 4.3 Hz, 1H, H6), 3.53 (t,
J = 6.5 Hz, 2H, H16), 5.63 (m, 4H, H10 and H13), 7.50 (m, 2H, H11
and H9), 9.21 (m, 1H, H12); 13C NMR (CDCl3): d = 13.6 (C19), 15.4
(C14 or C15), 18.95 (C7), 20.9 (C18), 21.95 (C14 or C15), 22.8
(C1), 25.5 (C8), 31.0 (C17), 31.1 (C3), 34.0 (C4), 40.2 (C2), 47.7
(C5), 70.6 (C16), 76.6 (C6), 79.6 (C10), 80.4 (C13), 121.6 (C11),
121.9 (C9), 135.7 (C12); anion: 117.6, 121.7, 121.8, 122.1 Elemen-
tal Anal. Calcd for C21H35F6N3O6S2 (603.79): C, 41.77; H, 5.85; N,
6.96. Found: C, 41.98; H, 5.79; N, 7.08.
matized Mo Ka radiation (k = 0.71073 Å). The data were corrected
for Lorentz-polarization as well as for absorption effects.31 Accu-
rate unit-cell parameters were determined by a least-squares fit
of 2137 reflections of highest intensity, chosen from the whole
experiment. The structures were solved with SIR9232 and refined
with the full-matrix least-squares procedure on F2 by SHELXL97.33
Scattering factors incorporated in SHELXL97 were used. The function
P
2
2 2
wðjFoj ꢀ jFcj Þ was minimized, with wꢀ1 = [
r
2(Fo)2 + (0.001ꢂP)2]
(P = [Max (F2o, 0) + 2F2c ]/3). All non-hydrogen atoms were refined
anisotropically. The hydrogen atoms were placed geometrically,
in idealized positions, and refined as rigid groups with their Uiso’s
as 1.2 (OH) or 1.5 (methyl) times Ueq of the appropriate carrier
atom. Relevant crystal data are listed in Table 11, together with
refinement details.
Crystallographic data (excluding structure factors) for the struc-
tural analysis have been deposited with the Cambridge Crystallo-
graphic Data Centre, No. CCDC-786077. Copies of this information
may be obtained free of charge from: The Director, CCDC, 12 Union
Road, Cambridge, CB2 1EZ, UK. Fax: +44(1223)336-033, e-mail:
deposit@ccdc.cam.ac.uk, or www: www.ccdc.cam.ac.uk.
4.2.3.13. 3-Decyloxymethyl-1-(1R,2S,5R)-(ꢀ)-menthoxymethy-
limidazolium bis(trifluoromethanesulfonyl)imide 5i. 1H NMR
(CDCl3, 25 °C): d = 0.49 (d, J = 6.9 Hz, 3H, H14 or H15), 0.89 (m,
12H, Ha-4, H7, H14 or H15, Ha-2, Ha-1 and H25), 1.32 (m, 16H,
H5, H18, H19, H20, H21, H22, H23, H24 and H3), 1.61 (m, 4H,
Hb-1, Hb-4 and H17), 1.99 (m, 2H, H8 and Hb-2), 3.34 (m, 1H,
H6), 3.51 (m, 2H, H16), 5.61 (m, 4H, H10 and H13), 7.56 (t,
4.4. Thermal analysis
2;10
2;10
J
1,2 = 1.9 Hz, J = 1.6 Hz, 1H, H11), 7.58 (t, J1,2 = 1.9 Hz, J
=
1.6 Hz, 1H, H9), 9.06 (m, 1H, H12); 13C NMR (CDCl3): d = 14.0
(C25), 15.2 (C14 or C15), 20.7 (C7), 21.8 (C14 or C15), 22.6 (C1),
25.3 (C24), 25.7 (C8), 25.7 (C23), 29.0 (C22), 29.1 (C21), 29.2
(C20), 29.4 (C19), 29.45 (C18), 31.0 (C3), 31.8 (C17), 33.9 (C4),
40.0 (C2), 47.5 (C5), 70.6 (C16), 76.6 (C6), 79.3 (C10), 79.9 (C13),
121.8 (C11), 122.1 (C9), 135.0 (C12); anion: 113.1, 117.4, 121.6,
125.9. Elemental Anal. Calcd for C27H47F6N3O6S2 (687.97): C,
47.13; H, 6.90; N, 6.11. Found: C, 46.92; H, 6.69; N, 6.28.
Glass temperature was determined by DSC, Mettler Toledo DSC
Instruments model cooled with a intracooler. The calorimeter was
calibrated for temperature and cell constants using indium (melt-
ing point 156.61 °C, D
H 28.71 J gꢀ1). Data were collected at constant
atmospheric pressure, using samples between 10 and 40 mg in alu-
minum sample pans. Experiments were performed heating at the
rate of 10 °C minꢀ1. An empty sample pan was used as reference.
Thermal decomposition temperatures were measured in the dy-
namic heating regime using a TGA (TA Instruments 2950) under air
atmosphere. Samples between 2 and 10 mg were heated from 40 to
500 °C under constant heating at 10 °C minꢀ1. Decomposition tem-
peratures (Tonset5% and Tonset) were determined from onset to 5
mass loss and 50% mass loss, respectively, under nitrogen.
4.3. X-ray structure determination
Diffraction data for 1a were collected at room temperature by
the
x-scan technique on an Oxford Diffraction KM4 four-circle dif-

2718
J. Feder-Kubis et al. / Tetrahedron: Asymmetry 21 (2010) 2709–2718
4.5. Antielectrostatic properties
of the studied salt supporting no colony formation was defined as
the MBC (minimal bactericidal concentration) or MFC (minimal
fungicifal concentration).
The antielectrostatic effect was measured on a Wigofil polyeth-
ylene film with a density of 150 g/m2 that did not contain any
lubricants or antioxidants. From this 0.25 mm film, 12.5 mm diam-
eter disks were cut. The disks were washed in acetone and then
dried by placing them in an air-conditioned room. A disk was
rubbed on the surface with a cotton-swab soaked with a 0.5% chlo-
roform solution of each studied salt. Next, the disk was hung up so
that the chloroform could evaporate spontaneously.
The disks, covered with chiral imidazolium salts, were stored
for 24 h in an air-conditioned room at 20 2 °C and a relative
humidity of 55 5%. Finally, the surface resistance and half-life de-
cay time were measured. The measuring apparatus and the meth-
od have recently been described elsewhere.34 The relative error in
the determination of these two quantities did not exceed 5%.
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4.7. Antimicrobial activity test procedure
Antimicrobial activity was determined by the tube dilution
method and described earlier.35 Bacteria strains were cultured on
a Müller-Hinton broth for 24 h. and fungi on Sabouraud agar for
48 h. A suspension of the microorganisms at a concentration of
106 cfu mLꢀ1 was prepared from each culture. This suspension
was then used to inoculate each dilution of the broth medium at
a 1:1 ratio. Growth of the microorganisms (or lack thereof) was
determined visually after incubation for 24 h at 37 °C (bacteria)
or 48 h at 29 °C (fungi).
The lowest concentration at which there was no visible growth
(turbidity) was taken as the MIC (minimal inhibitory concentra-
tion). Then an aliquot taken from each tube in a sample loop was
cultured in an agar medium with inactivates (0.3% lecithin. 3%
´
34. Pernak, J.; Czepukowicz, A.; Pozniak, R. Ind. Eng. Chem. Res. 2001, 40, 2379–
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´
35. Cybulski, J.; Wisniewska, A.; Kulig-Adamiak, A.; Lewicka, L.; Cieniewska-
polysorbate 80. and 0.1% cysteine
L) and incubated for 48 h at
Rosłonkiewicz, A.; Kita, K.; Fojutowski, A.; Nawrot, J.; Materna, K.; Pernak, J.
Chem. Eur. J. 2008, 14, 9305–9311.
37 °C (bacteria) or for 5 d at 29 °C (fungi). The lowest concentration