Exploration of 4,5-dimethyl-1H-imidazole N-oxide derivatives in the synthesis of new achiral and chiral ionic liquids

Article abstract of DOI:10.1016/j.tetasy.2009.02.053

New 1-alkoxy-3-alkyl-4,5-dimethylimidazolium bromides were synthesized by alkylation of the corresponding 1-alkylimidazole 3-oxides, which were conveniently prepared via condensation of α-(hydroxyimino)ketones, primary aliphatic amines, and formaldehyde.

Full text of DOI:10.1016/j.tetasy.2009.02.053

Tetrahedron: Asymmetry 20 (2009) 1073–1080
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Exploration of 4,5-dimethyl-1H-imidazole N-oxide derivatives
in the synthesis of new achiral and chiral ionic liquids
a
a
a,
b,
*
*
´
´
´
Grzegorz Mloston , Jarosław Romanski , Marcin Jasinski , Heinz Heimgartner
a
´
´
Department of Organic and Applied Chemistry, University of Łódz, Narutowicza 68, PL-90-136 Łódz, Poland
b Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
a r t i c l e i n f o
a b s t r a c t
Article history:
New 1-alkoxy-3-alkyl-4,5-dimethylimidazolium bromides were synthesized by alkylation of the corre-
sponding 1-alkylimidazole 3-oxides, which were conveniently prepared via condensation of -(hydroxy-
Received 4 February 2009
Accepted 24 February 2009
Available online 22 April 2009
a
imino)ketones, primary aliphatic amines, and formaldehyde. By using enantiomerically pure chiral
amines, optically active imidazolium salts were obtained. Treatment with sodium tetrafluoroborate in
acetone yielded the corresponding imidazolium tetrafluoroborates. All these compounds, with only
one exception, were obtained as oils, which are considered as potential ionic liquids and ‘chiral ionic liq-
uids’. The reduction of the chiral or non-chiral 1-alkylimidazole 3-oxides with Raney-Ni, followed by
alkylation with alkyl bromides and subsequent ion exchange to tetrafluoroborates, gave the correspond-
ing 1,3-dialkylimidazolium salts, most of them showing properties of ionic liquids. The alkylation of 1-
butyl-4,5-dimethylimidazole 3-oxide and the corresponding imidazole, respectively, with 1,3-dibromo-
propane led to the first bis-imidazolium dibromides and bis-tetrafluoroborates.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
after deoxygenation with Raney-Nickel, delivered the corresponding
imidazoles 4. Starting with easily available
a-(hydroxyimi-
The rapidly increasing number of books,1 review articles,2 and
original papers3–5 dealing with the preparation, properties, and
applications of ionic liquids (ILs) documents the growing impor-
tance of this class of compounds in almost all fields of chemistry
and related disciplines. For the purpose of modern organic synthe-
sis, chiral ionic liquids (CILs) and especially ‘room temperature chi-
ral ionic liquids’ (RTCILs) are of interest. The 1,3-disubstituted
imidazolium salts are by far the most frequently used group of sub-
stances displaying the required properties.
no)ketones 1, primary aliphatic amines 2, and paraformaldehyde,
achiral10 and chiral imidazoles11 were prepared in good yields
(Scheme 1).
R2
OH
N
R2
O
R2
R3
N
a) EtOH
reflux
N
Raney-Ni
EtOH, r.t.
R1NH2
+
CH2O
+
R3
R3
or
b) AcOH
r.t.
N
N
O
R1
R1
1
2
3
4
Chiral imidazolium ionic liquids (CIILs) can be prepared by alkyl-
ation of an achiral, 1-substituted imidazole with a chiral alkylating
agent (e.g., 1-methylimidazole and (ꢀ)-myrtanol tosylate6). How-
ever, the alternative and most frequently used method is the prepa-
ration of an imidazole bearing a chiral residue, which is then
alkylated with an achiral reagent. In this case, enantiomerically pure
1-phenylethylamine is often used as a starting material for the for-
mation of a 1-substituted imidazole with the stereogenic center lo-
cated at C(1) of the substituent (e.g., Refs. 7–9). Both approaches were
applied to prepare imidazoles without substituents at C(4) and C(5).
In a series of recent papers, we reported the synthesis of 2-unsub-
stituted 1-alkyl-4,5-dialkyl/aryl-1H-imidazole 3-oxides 3, which,
Scheme 1.
Using enantiomerically pure trans-cyclohexane-1,2-diamine,
the corresponding optically active bis-imidazole derivatives were
obtained.11b
In the published papers dealing with the preparation of ionic
liquids, imidazole N-oxides have not been explored either directly
or indirectly as imidazole building blocks. However, in a very re-
cent paper, 1-hydroxyimidazole and the corresponding 2-methyl
derivative were used for a stepwise preparation of a series of achi-
ral 3-alkoxy-1-alkylimidazolium salts, which displayed properties
of ‘room temperature ionic liquids’ (RTILs).12 In this context, an-
other paper deserves mentioning, in which 1-cyclohexyl-3-ethoxy-
imidazolium tetrafluoroborate was reported as the product of the
ethylation of the corresponding N-oxide with triethyloxonium
tetrafluoroborate.13
* Corresponding authors. Tel.: +48 42 635 5769; fax: +48 42 665 5162 (M.J.); tel.:
+41 44 635 4282; fax: +41 44 635 6812 (H.H.).
E-mail addresses: mjasinski@uni.lodz.pl (M. Jasin´ ski), heimgart@oci.uzh.ch (H.
Heimgartner).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.02.053

´
1074
G. Mloston et al. / Tetrahedron: Asymmetry 20 (2009) 1073–1080
Table 2
The goal of the study described in the present paper was the
1-Alkoxy-3-alkylimidazolium salts 5 and 6
application of diverse 1,4,5-trisubstituted 1H-imidazole 3-oxides
3 and the corresponding imidazoles 4 in the synthesis of new achi-
ral and chiral imidazolium salts with the properties of ‘room tem-
perature ionic liquids’ (RTILs).
No.
R1
R2
X
Yield
½
a 2D0
ꢁ
(c 0.2, CH2Cl2)
Mp (°C)
5a
5b
5c
5d
5e
5f
5g
5h
5i
6a
6b
6c
6d
6e
6f
6g
6h
6i
Bu
cHex
CH2CH2OH
CH2CH2OH
CH2CH(OH)CH3 (S)
CH(CH3)CO2Me (S)
CH(CH3)CO2Me (R)
CH(CH3)CO2Me (S)
CH(CH3)CO2Me (R)
Bu
cHex
CH2CH2OH
CH2CH2OH
CH2CH(OH)CH3 (S)
CH(CH3)CO2Me (S)
CH(CH3)CO2Me (R)
CH(CH3)CO2Me (S)
CH(CH3)CO2Me (R)
Bu
Bu
Bu
Hex
Bu
Bu
Bu
Hex
Hex
Bu
Bu
Bu
Hex
Bu
Bu
Bu
Hex
Hex
Br
Br
Br
Br
Br
Br
Br
Br
85
81
92
85
93
91
89
79
83
97
80
89
93
91
92
88
92
93
—
—
—
—
+13.7
+14.2
ꢀ15.8
+11.1
ꢀ12.0
—
—
—
—
+21.8
+14.7
ꢀ16.2
+9.5
ꢀ10.8
Oil
58–62
Oil
Oil
Oil
Oil
Oil
Oil
Oil
Oil
Oil
Oil
Oil
Oil
Oil
Oil
Oil
Oil
2. Results and discussion
For the present study, 4,5-dimethylimidazole 3-oxide was se-
lected as the basic structure, because it is easily available and it
was expected that the presence of two methyl groups does not
influence significantly the physico-chemical properties of imidazo-
lium salts expected as oily materials. For this reason, diac-
etylmonooxime 1a was reacted with primary amines,
aminoalcohols, and aminoesters in the presence of formaldehyde
or with the corresponding hexahydro-1,3,5-triazines according to
the reported protocols.10a,e,11c As a new example, 1-butyl-4,5-di-
methyl-1H-imidazole 3-oxide 3a was prepared by heating 1a and
1,3,5-tributylhexahydro-1,3,5-triazine (a trimer of methylidene
butylamine) in boiling ethanol (Scheme 2).
Br
BF4
BF4
BF4
BF4
BF4
BF4
BF4
BF4
BF4
During the storage of 5 and 6 at room temperature, no decom-
position was observed. Moreover, in the case of 5a, the thermal sta-
bility was tested by heating of a sample at 100 °C, and after 45 min,
the 1H NMR spectrum showed that no changes took place. The
compounds 5 and 6 were also stable when treated with diluted
HCl solution at room temperature. In an additional experiment, a
methanolic solution of 5a was treated with NaBH4 in order to test
the stability of the N–O bond. After ca. 1 h under mild conditions
(rt), 1-butyl-4,5-dimethylimidazole (4a) was isolated (33%,
50 min) accompanied by unchanged 5a. Complete reduction was
achieved after 16 h.
R1NH2
or
+
CH O
2
OH
N
OR2
O
N
N
R2Br
R1
R1
X
+
CHCl3, r.t.
- H2O
N
N
N
N
O
1
/
R1
3
R1
N
R1
5a-i X = Br
NaBF4
acetone
r.t.
1a
3a-f
for R1 and R2 see Tables 1 and 2
6a-i X = BF4
It is worth mentioning that in the case of enantiomerically pure
amino components, that is, (S)-1-aminopropan-2-ol or methyl (R)-
and (S)-alaninate, the known optically active imidazole N-oxides
3d, 3e, and 3f were converted to the corresponding optically active
3-alkoxyimidazolium salts 5e–i in good yields (Table 2). Their con-
venient preparation opens up access to a new type of optically ac-
tive ionic liquids (RTCILs).
The deoxygenation of imidazole N-oxides 3a–f to give 4a–f was
easily achieved by treatment with Raney-Ni in ethanol at room
temperature (Scheme 3).10e,11a,c All of these compounds were used
in alkylation reactions with n-butyl and n-hexyl bromide to give
1,3-dialkylimidazolium bromides 7 (Table 3). In this series, the
reactions were carried out in boiling benzene, and after ca. 6 h,
the conversions were complete. However, in the cases of 4e and
4f, partial decomposition was observed under the applied condi-
tions and, for this reason, the alkylations with butyl bromide were
performed at room temperature in CH2Cl2 solution using excess of
the alkylating agent (3 equiv). The imidazolium bromides 7 were
obtained as liquids in the case of 7c–f and as solids in the case of
7a,b,g,h.
Scheme 2.
The imidazole N-oxides 3a–f (Table 1) were used for O-alkyla-
tions using n-butyl and n-hexyl bromide, respectively. As already
reported, 2-unsubstituted imidazole N-oxides 3 undergo a thermal
isomerization to give imidazol-2-ones even at 80 °C (boiling ben-
zene).14 For this reason, the alkylation reactions were carried out
in chloroform solution at room temperature. After three days, the
3-alkoxyimidazolium bromides 5a–i were obtained in very good
yields as pale yellow oils, with the exception of 5b, which was a
colorless solid (Table 2).
Table 1
1-Substituted 4,5-dimethylimidazole N-oxides 3 and the corresponding imidazoles 4
No.
R1
Yield
½
a 2D0
ꢁ
(c 0.2, CH2Cl2)
Mp (°C)
3a
3b
3c
3d
3e
3f
4a
4b
4c
4d
4e
4f
Bu
cHex
CH2CH2OH
CH2CH(OH)CH3 (S)
CH(CH3)CO2Me (S)
CH(CH3)CO2Me (R)
Bu
cHex
CH2CH2OH
81
63
82
82
67
72
91
86
74
75
77
65
—
—
—
Oil
199–201
105–10710e
119–12010e
144–14611c
142–14511c
Oil
Oil
94–98
Oil
+42.0a
+47.1
ꢀ48.5
—
O
R2
—
—
+69.2
ꢀ9.9
+10.4
N
N
N
R2Br
Raney-Ni
EtOH, r.t.
X
CH2CH(OH)CH3 (S)
CH(CH3)CO2Me (S)
CH(CH3)CO2Me (R)
benzene
80 ºC
N
N
N
Oil
Oil
R1
R1
R1
a 1D7
ꢁ
(c 1, MeOH).
a
½
7a-h X = Br
NaBF4
acetone
r.t.
3a-f
4a-f
The exchange of the bromide ion against the tetrafluoroborate
for R1 and R2 see Table 3
8a-h X = BF4
ion was easily achieved by treatment of solutions of 5a–i in ace-
tone with a slight excess of solid NaBF4 at room temperature. All
of the prepared 3-alkoxyimidazolium tetrafluoroborates 6a–i (Ta-
ble 2) were well soluble not only in acetone but also in ethanol,
chloroform, and water. On the other hand, they were insoluble in
ether.
Scheme 3.
After the anion exchange Brꢀ?BF4ꢀ, the salts 8a–f were ob-
tained as liquids, but 8g,h were still solid materials with melting
points below 100 °C (Table 3).

´
1075
G. Mloston et al. / Tetrahedron: Asymmetry 20 (2009) 1073–1080
Table 3
rate 10 was easily achieved under standard conditions and affor-
ded the oily product in high yield (91%).
Similarly, the alkylation of 4a with 1,3-dibromopropane in boil-
ing benzene gave the bis-imidazolium salt 11 as an oily material,
and the tetrafluoroborate 12 prepared from this was obtained as
a semi-solid substance.
1,3-Dialkylimidazolium salts 7 and 8
No.
R1
R2
X
Yield
½ ꢁ (c 0.2, CH2Cl2)
a 2D0
Mp (°C)
7a
7b
7c
7d
7e
7f
7g
7h
8a
8b
8c
8d
8e
8f
Bu
Bu
cHex
cHex
CH2CH2OH
CH2CH(OH)CH3 (S)
CH(CH3)CO2Me (S)
CH(CH3)CO2Me (R)
Bu
Bu
cHex
cHex
CH2CH2OH
CH2CH(OH)CH3 (S)
CH(CH3)CO2Me (S)
CH(CH3)CO2Me (R)
Bu
Hex
Bu
Hex
Bu
Bu
Bu
Bu
Bu
Hex
Bu
Hex
Bu
Bu
Bu
Bu
Br
Br
Br
Br
Br
Br
Br
Br
BF4
BF4
BF4
BF4
BF4
BF4
BF4
BF4
94
89
95
91
97
84
53
44
95
87
97
94
98
92
95
75
—
—
—
—
—
+13.8
+11.2
ꢀ11.0
—
—
—
—
—
83–86
118–120
Oil
Oil
Oil
3. Conclusions
Oil
96–99
99–103
Oil
Oil
Oil
Oil
Oil
Oil
64–66
67–68
The results presented here show that 1-substituted 4,5-di-
methyl-1H-imidazole 3-oxides 3 can be used for the preparation
of a new type of imidazole-based ionic liquids containing alkoxy
residues at the N atom. All of the prepared bromides 5 and tetra-
fluoroborates 6 are oily materials at room temperature or solids
with melting points below 100 °C. Similar properties were ob-
served in the case of the bis-imidazolium salts 9 and 10. Deoxygen-
ation of the N-oxides 3 opens access to the corresponding 1,4,5-
trisubstituted imidazoles 4, which via alkylation were converted
into the corresponding salts 7 and 8. These materials displayed
similar properties as 5 and 6 and, therefore, can be considered as
potentially useful RTILs. It is worth pointing out that the described
procedures open a relatively simple and efficient access to optically
active RTCILs using enantiomerically pure 1-aminopropan-2-ol
and methyl alaninate, respectively, as the amino component. Sim-
ilar to the alkylimidazolium salts 7/8, the 3-alkoxy analogues 5/6
proved to be stable at enhanced temperature. In addition, the pres-
ence of the oxygen atom enhances their ability to form liquid prod-
ucts. These properties are of crucial importance for potential
applications of the new materials as a medium for organic
reactions.
+21.2
+10.3
ꢀ8.2
8g
8h
Some spectroscopic properties of the imidazolium salts of type
5/6 and 7/8 deserve a short comment. In the 1H NMR spectra of
bromides 5, the diagnostic signal of H–C(2) appeared always
downfield-shifted in comparison with the corresponding tetra-
fluoroborates 6 (Dd ca. 1–2 ppm). The same tendency was ob-
served in the series of bromides 7 and tetrafluoroborates 8.
Whereas in the 13C NMR spectra of 7 and 8 the signals of C(2) were
registered at 135–132 ppm, the corresponding signals of the alk-
oxyimidazolium salts 5 and 6 were observed between 132 and
129 ppm. This trend of a high-field shift in the alkoxy-substituted
imidazolium salts fits well with the data reported earlier.13 In addi-
tion, the signals of the CH2–O groups in 5 and 6 were located at 82–
75 ppm.
In two recent papers, we presented the synthesis of a series of
bis(imidazole N-oxides) based on the method depicted in Schemes
1 and 2. In this case, diamines were used for the reaction with
4. Experimental
4.1. General
formaldehyde and subsequent condensation with
a-(hydroxyimi-
no)ketones 1.10e,11b In the present study, we decided to investigate
whether bisimidazolium salts prepared via alkylation of imidazole
N-oxides and the corresponding imidazoles, respectively, with 1,3-
dibromopropane displayed properties of RTILs. As model com-
pounds, 1-butyl-4,5-dimethyl-1H-imidazole 3-oxide 3a and 1-bu-
tyl-4,5-dimethylimidazole 4a were selected. The twofold
alkylation with 3a using 0.5 equiv of the dibromide occurred under
typical conditions leading to the salt 9 as a pale yellow oil in 90%
yield (Scheme 4). The subsequent conversion to the tetrafluorobo-
Melting points were determined on a Melt-Temp. II apparatus
(Aldrich) and are uncorrected. IR Spectra were recorded on a
NEXUS FT-IR spectrophotometer in KBr, absorptions in cmꢀ1
.
1H
and 13C NMR Spectra were measured on a Tesla BS567A (80 and
20 MHz, resp.) or Bruker AC 300 instrument (300 and 75.5 MHz,
resp.) in CDCl3 or CD3OD, chemical shifts (d) in ppm (TMS = 0 ppm),
coupling constants J in hertz. The multiplicity of the 13C signals was
deduced from DEPT spectra. Optical rotations were determined on
an Automatic Digital Polarimeter Krüss P3002RS. HRMS Spectra
were measured on a Finnigan MAT-95 instrument.
O
O
O
N
4.2. Starting materials: imidazole N-oxides
(CH2)3
Br
Br
N
N
(CH2)3
2X
CHCl3
r.t.
N
N
N
Synthesis, properties, and spectroscopic data of imidazole N-
oxides 3b–f have been described previously.10a,b,e,11c
Bu
Bu
Bu
9
X = Br
3a
NaBF4
acetone
r.t.
4.2.1. Synthesis of 1-butyl-4,5-dimethyl-1H-imidazole 3-oxide
3a
10 X = BF4
A solution of diacetylmonooxime 1a (10 mmol) and 1,3,5-tribu-
tylhexahydro-[1,3,5]triazine (3.4 mmol) in EtOH (40 mL) was
heated at reflux for 3 h. Evaporation of the solvent under reduced
pressure yielded a red oil, which was washed twice with Et2O
(2 ꢂ 15 mL). The crude product 3a was purified by chromatogra-
phy (SiO2, AcOEt, then AcOEt:MeOH 1:1), and the viscous oily sub-
stance was used in the next step without further purification.
(CH2)3
N
(CH2)3
N
N
Br
Br
benzene
80 ºC
N
N
N
2X
Bu
Bu
Bu
Yield: 1.36 g (81%). Pale red oil. IR (film):
m 3358vs, 3139s, 2958s,
11 X = Br
4a
NaBF4
acetone
r.t.
2931s, 2873m, 1626m, 1456m (br), 1396m, 1381m, 1339s,
1255m, 1194m, 1150m, 1080m. 1H NMR (CDCl3): d 7.78 (s, 1H,
HC(2)); 3.77 (t, J = 7.6, 2H, CH2N); 2.16, 2.13 (2s, 6H, 2Me); 2.05–
1.11 (m, 4H, 2CH2); 0.95 (br t, 3H, MeCH2). 13C NMR (CDCl3): d
12 X = BF4
Scheme 4.

´
G. Mloston et al. / Tetrahedron: Asymmetry 20 (2009) 1073–1080
1076
125.2 (d, C(2)); 123.5, 120.1 (2s, C(4), C(5)); 44.6, 31.5, 18.6 (3t,
3CH2, Bu); 12.6 (q, CH3, Bu); 7.7, 6.3 (2q, 2Me). HRMS (EI): Calcd
for C9H16N2O (M+): 168.1263, found 168.1259.
4.3.6. Methyl (R)-2-(4,5-dimethyl-1H-imidazol-1-yl)propanoate
4f
Yield: 1.18 g (65%). ½a D20
¼ þ10:5 (c 0.2, CH2Cl2).
ꢁ
4.3. Synthesis of 1,4,5-trisubstituted imidazoles 4
4.4. Synthesis of 1-substituted 3-alkoxy-4,5-dimethylimidazolium
bromides 5 and bis-imidazolium bromide 9
To a magnetically stirred solution of the imidazole N-oxide 3
(10 mmol) in ethanol (20 mL), an ethanolic suspension of freshly
prepared Raney-Nickel was added in small portions, and the pro-
gress of the reaction was followed by TLC (SiO2, MeOH/AcOEt
1:3). After the starting N-oxide was completely reduced, the solu-
tion was filtered through a CeliteÒ plug (ca. 10 cm, EtOH), the fil-
trate was concentrated, and dried under reduced pressure. The
obtained highly pure product 4 was analyzed without further
purification.
The solution of imidazole N-oxide 3 (1.0 mmol) and excess of
the corresponding alkyl bromide (ca. 3–4 mmol) or 0.5 equiv of
1,3-dibromopropane (101 mg, 0.5 mmol) in CHCl3 (3 mL) was mag-
netically stirred at rt for 72 h. After the solvent was removed in va-
cuo, the oily residue was washed with Et2O (4 ꢂ 5 mL), dissolved in
CH2Cl2, filtered, and dried. If necessary, crude products can be puri-
fied by chromatography on a short column with neutral alumina
(CHCl3, then acetone in the case of 5, or acetone, then AcOEt:MeOH
1:1 in the case of 9).
4.3.1. 1-Butyl-4,5-dimethyl-1H-imidazole 4a
Yield: 1.43 g (91%). Colorless oil. IR (film):
m
2959s, 2932s,
4.4.1. 1-Butoxy-3-butyl-4,5-dimethylimidazolium bromide 5a
2873m, 1500s, 1451m, 1388m, 1380m, 1366m, 1233m, 1202m.
1H NMR (CDCl3): d 7.31 (s, 1H, HC(2)); 3.76 (t, J = 6.8, 2H, CH2N);
2.11, 2.10 (2s, 6H, 2Me); 1.82–1.05 (m, 4H, 2CH2); 1.93 (br t, 3H,
MeCH2). 13C NMR (CDCl3): d 133.5 (d, C(2)); 132.2, 120.6 (2s,
C(4), C(5)); 43.2, 31.5, 18.3 (3t, 3CH2, Bu); 12.2 (q, Me, Bu); 11.3,
6.9 (2q, 2Me). HRMS (EI): Calcd for C9H16N2 (M+): 152.1313, found
152.1313.
Yield: 259 mg (85%). Pale orange oil. IR (film): m 3089m, 2958s,
2934s, 2873s, 1631m, 1544m, 1466s (br), 1380m, 1340m, 1143m,
935m. 1H NMR (CDCl3): d 10.85 (s, 1H, HC(2)); 4.54 (t, J = 6.6, 2H,
CH2O); 4.34 (t, J = 6.8, 2H, CH2N); 2.27 (s, 6H, 2Me); 2.00–1.16
(m, 8H); 0.97 (t, J = 6.4, 6H, 2MeCH2). 13C NMR (CDCl3): d 132.3
(d, C(2)); 123.7, 123.6 (2s, C(4), C(5)); 82.9, 47.4, 31.9, 29.6, 19.4,
18.7 (6t, 6CH2, 2Bu); 13.6, 13.4 (2q, 2Me, 2Bu); 8.4, 7.0 (2q, 2Me).
4.3.2. 1-Cyclohexyl-4,5-dimethyl-1H-imidazole 4b
4.4.2. 1-Butoxy-3-cyclohexyl-4,5-dimethylimidazolium
bromide 5b
Yield: 1.53 g (86%). Pale yellow oil. IR (film):
m 2933vs, 2857s,
1592w, 1490s, 1451s, 1386m, 1314m, 1275m, 1242m, 1220s. 1H
NMR (CDCl3): d 7.39 (s, 1H, HC(2)); 3.88–3.43 (m, 1H, cHex);
2.15, 2.12 (2s, 6H, 2Me); 2.11–1.12 (m, 10H, cHex). 13C NMR
(CDCl3): d 132.0, 121.1 (2s, C(4), C(5)); 131.0 (d, C(2)); 53.8 (d,
CH, cHex); 33.4, 24.6, 23.9 (3t, 5CH2, cHex); 11.6, 7.8 (2q, 2Me).
HRMS (EI): Calcd for C11H18N2 (M+): 178.1470, found 178.1467.
Yield: 268 mg (81%). Colorless crystals. Mp 58–62 °C (Et2O). IR
(KBr):
m 3440vs, 3374s, 3114m, 3039m, 2929vs (br), 2861s,
1633m, 1608m, 1542m, 1453m, 1394m, 1221m, 1190m, 1030m,
959s, 902m. 1H NMR (CDCl3): d 10.91 (s, 1H, HC(2)); 4.63 (t,
J = 6.1, 2H, CH2O); 4.32–3.85 (m, 1H, cHex); 2.31, 2.27 (2s, 6H,
2Me); 2.19–1.26 (m, 14H); 0.96 (t, J = 6.4, 3H, MeCH2). 13C NMR
(CDCl3): d 130.7 (d, C(2)); 123.7, 123.5 (2s, C(4), C(5)); 82.8, 33.0,
29.6, 25.3, 24.2, 18.7 (6t, 8CH2, Bu, cHex); 58.4 (d, CH, cHex);
13.7 (q, Me, Bu); 9.0, 7.1 (2q, 2Me).
4.3.3. 1-(2-Hydroxyethyl)-4,5-dimethyl-1H-imidazole 4c
Yield: 1.04 g (74%). Colorless solid. Mp 94–98 °C ([lit.15]: mp
103–106 °C). IR (KBr):
m 3096s (br), 2950–2700s, 1598m, 1509s,
1448m, 1249m, 1192m, 1073s, 849m. 1H NMR (CDCl3): d 7.25 (s,
1H, HC(2)); 6.35 (br s, 1H, OH); 3.92–3.77 (m, 4H, 2CH2); 2.10,
2.01 (2s, 6H, 2Me). 13C NMR (CDCl3): d 135.0 (d, C(2)); 132.1,
121.9 (2s, C(4); C(5)), 60.5, 47.7 (2t, 2CH2); 12.0, 8.2 (2q, 2Me).
HRMS (EI): Calcd for C7H12N2O (M+): 140.0950, found 140.0948.
4.4.3. 1-Butoxy-4,5-dimethyl-3-(2-hydroxyethyl)imidazolium
bromide 5c
Yield: 270 mg (92%). Yellow oil. IR (film):
m 3304vs, 3000–
2730s, 1632m, 1547m, 1456s, 1394m, 1343m, 1141m, 1073s. 1H
NMR (CDCl3): d 9.97 (s, 1H, HC(2)); 4.48 (t, J = 6.4, 2H, CH2O);
4.41 (t, J = 4.8, 2H, CH2O); 3.97 (t, J = 4.8, 2H, CH2N); 2.28 (s, 6H,
2Me); 2.16–1.23 (m, 4H, Bu); 0.97 (t, J = 6.4, 3H, MeCH2). 13C
NMR (CDCl3): d 129.4 (d, C(2)); 123.2, 122.1 (2s, C(4), C(5)); 81.0,
57.5, 48.0, 27.9, 17.0 (5t, 5CH2); 11.9 (q, Me, Bu); 7.1, 5.4 (2q, 2Me).
4.3.4. (S)-1-(2-Hydroxypropyl)-4,5-dimethyl-1H-imidazole 4d
Yield: 1.23 g (75%). Pale yellow oil. ½a D20
¼ þ69:2 (c 0.2, CH2Cl2).
ꢁ
IR (film):
m 3400vs (br), 3150–2550s, 1597m, 1505s, 1448s, 1389m,
1371m, 1335m, 1305m, 1240m, 1201m, 1179m, 1139m, 1092m,
1077m, 944m, 783m. 1H NMR (CDCl3): d 7.28 (s, 1H, HC(2)); 5.23
(br s, 1H, OH); 4.19–3.56 (m, 3H); 2.10, 2.00 (2s, 6H, 2Me); 1.25
(d, J = 6.4, 3H, MeCH2). 13C NMR (CDCl3): d 135.4 (d, C(2)); 132.3,
121.7 (2s, C(4), C(5)); 65.8 (t, CH2); 52.6 (d, CH); 20.5 (q, Me);
12.1, 8.4 (2q, 2Me). HRMS (EI): Calcd for C8H14N2O (M+):
154.1100, found 154.1098.
4.4.4. 4,5-Dimethyl-1-hexyloxy-3-(2-hydroxyethyl)imidazolium
bromide 5d
Yield: 273 mg (85%). Yellow oil. IR (film):
m 3319vs, 3000–
2750s, 1699m, 1633m, 1546m, 1456s, 1395m, 1380m, 1343m,
1142m, 1073s. 1H NMR (CDCl3): d 9.98 (s, 1H, HC(2)); 4.48 (t,
J = 6.7, 2H, CH2O); 4.44 (t, J = 5.4, 2H, CH2O); 3.98 (t, J = 5.4, 2H,
CH2N); 2.28 (s, 6H, 2Me); 2.19–1.08 (m, 8H, Hex); 0.92 (t, J = 6.8,
3H, MeCH2). 13C NMR (CDCl3): d 131.3 (d, C(2)); 124.9, 123.9 (2s,
C(4), C(5)); 83.2, 59.3, 49.8, 31.4, 27.8, 25.2, 22.4 (7t, 7CH2); 13.9
(q, Me, Hex); 8.9, 7.2 (2q, 2Me).
4.3.5. Methyl (S)-2-(4,5-dimethyl-1H-imidazol-1-yl)propanoate
4e
Yield: 1.40 g (77%). Pale yellow oil.
½
a 2D0
ꢁ
¼ ꢀ9:9 (c 0.2,
CH2Cl2). IR (film): 2950–2850s, 1747vs (C@O), 1596m, 1493s,
m
1451s, 1388m, 1330m, 1305s, 1207vs, 1065m, 736m. 1H NMR
(CDCl3): d 7.47 (s, 1H, HC(2)); 4.69 (q, J = 7.4, 1H); 3.74 (s, 3H,
MeO); 2.14, 2.09 (2s, 6H, 2Me); 1.74 (d, J = 7.4, 3H, MeCH2).
13C NMR (CDCl3): d 170.8 (s, C@O); 133.6, 121.9 (C(40), C(50));
133.0 (d, C(2)); 52.7 (q, MeO); 52.5 (d, CH); 17.6 (q, MeCH);
12.3, 8.2 (2q, 2Me). HRMS (EI): Calcd for C9H14N2O2 (M+):
182.1055, found 182.1059.
4.4.5. (S)-1-Butoxy-4,5-dimethyl-3-(2-hydroxypropyl)imida-
zolium bromide 5e
Yield: 285 mg (93%). Pale yellow oil. ½a D20
¼ þ13:7 (c 0.2,
ꢁ
CH2Cl2). IR (film):
m 3324vs, 3000–2850s, 1633m, 1546m, 1457m,
1376m, 1346m, 1323m, 1255m, 1140m, 1075m, 937m, 747m. 1H
NMR (CDCl3): d 10.01 (s, 1H, HC(2)); 4.9 (s, 1H, OH); 4.49 (t,
J = 6.8, 2H, CH2O); 4.38–4.09 (m, 3H); 2.27 (s, 6H, 2Me); 2.04–

´
1077
G. Mloston et al. / Tetrahedron: Asymmetry 20 (2009) 1073–1080
1.11 (m, 4H, Bu); 1.32 (d, J = 6.4, 3H, Me); 0.98 (t, J = 6.8, 3H,
MeCH2). 13C NMR (CDCl3): d 131.7 (d, C(2)); 124.7, 123.7 (2s,
C(4), C(5)); 82.8, 64.8, 29.7, 18.7 (4t, 4CH2); 53.6 (d, CH); 20.5 (q,
Me); 10.2 (q, Me, Bu); 8.8, 7.1 (2q, 2Me).
1381m, 1341m, 1058vs (br, BF4ꢀ), 936m. 1H NMR (CDCl3): d 9.05
(s, 1H, HC(2)); 4.41 (t, J = 6.4, 2H, CH2O); 4.13 (t, J = 8.7, 2H,
CH2N); 2.29 (s, 6H, 2Me); 1.97–1.15 (m, 8H); 1.09–0.83 (m, 6H,
2MeCH2). 13C NMR (CDCl3): d 130.3 (d, C(2)); 124.6, 124.4 (2s,
C(4), C(5)); 82.9, 47.6, 31.7, 29.7, 19.5, 18.8 (6t, 6CH2); 13.7, 13.4
(2q, 2Me, Bu); 8.4, 7.1 (2q, 2Me).
4.4.6. (S)-1-Butoxy-4,5-dimethyl-3-[1-(methoxycarbonyl)ethyl]-
imidazolium bromide 5f
Yield: 324 mg (91%). Pale yellow oil. ½a D20
ꢁ
¼ þ14:2 (c 0.2,
4.5.2. 1-Butoxy-3-cyclohexyl-4,5-dimethylimidazolium
tetrafluoroborate 6b
CH2Cl2). IR (film):
m 3432vs, 3050–2800vs (br), 1747vs (C@O),
1636m, 1544m, 1455m, 1440m, 1317m, 1240m, 1213s, 1063m,
935m. 1H NMR (CDCl3): d 10.86 (s, 1H, HC(2)); 5.72 (q, J = 7.7,
1H, MeCH); 4.62 (dt, J = 7.2, J = 0.9, 2H); 3.82 (s, 3H, MeO); 2.29,
2.24 (2s, 6H, 2Me); 2.03 (d, J = 7.7, 3H, MeCH); 1.95–1.37 (m,
4H); 0.97 (t, J = 6.0, 3H, MeCH2). 13C NMR (CDCl3): d 167.9 (s,
C@O); 130.8 (d, C(2)); 124.3, 123.4 (2s, C(4), C(5)); 82.0, 28.5,
16.4 (3t, 3CH2); 55.3 (d, CH); 52.6 (q, MeO); 17.6 (q, MeCH); 12.6
(q, Me, Bu); 8.4, 6.2 (2q, 2Me).
Yield: 270 mg (80%). Pale yellow oil. IR (film): m 3136s, 3053m,
2937vs, 2865s, 1632m, 1541m, 1456s, 1398m, 1370m, 1338m,
1281m, 1217m, 1185m, 1058vs (BF4ꢀ), 937m. 1H NMR (CDCl3): d
9.17 (s, 1H, HC(2)); 4.43 (t, J = 6.2, 2H, CH2O); 4.29–3.85 (m, 1H,
cHex); 2.26, 2.23 (2s, 6H, 2Me); 2.15–1.25 (m, 14H); 0.98 (t,
J = 6.4, 3H, MeCH2). 13C NMR (CDCl3): d 128.3 (d, C(2)); 124.42,
124.37 (2s, C(4), C(5)); 82.7, 32.7, 29.7, 25.3, 24.3, 18.7 (6t, 8CH2,
Bu, cHex); 58.3 (d, CH, cHex); 13.7 (q, Me, Bu); 8.5, 6.9 (2q, 2Me).
4.4.7. (R)-1-Butoxy-4,5-dimethyl-3-[1-(methoxycarbonyl)ethyl]-
4.5.3. 1-Butoxy-4,5-dimethyl-3-(2-hydroxyethyl)imidazolium
tetrafluoroborate 6c
imidazolium bromide 5g
Yield: 298 mg (89%). ½a D20
ꢁ
¼ ꢀ15:8 (c 0.2, CH2Cl2).
Yield: 267 mg (89%). Pale yellow oil. IR (film): m 3307vs, 3142m,
3000–2850vs, 1699m, 1633m, 1548m, 1456m, 1395m, 1382m,
1360m, 1344m, 1240m, 1186m, 1142m, 1065vs (BF4ꢀ), 937m,
753m. 1H NMR (CDCl3): d 9.43 (s, 1H, HC(2)); 4.45 (t, J = 6.0, 2H,
CH2O); 4.39–4.26 (m, 2H, CH2O); 4.03–3.88 (m, 2H, CH2N); 2.26
(s, 6H, 2Me); 2.06–1.19 (m, 4H, Bu); 0.98 (t, J = 6.8 3H, MeCH2).
13C NMR (CDCl3): d 130.7 (d, C(2)); 125.0, 124.0 (2s, C(4), C(5));
82.7, 59.3, 49.6, 29.6, 18.6 (5t, 5CH2); 13.5 (q, Me, Bu); 8.5, 7.0
(2q, 2Me).
4.4.8. (S)-4,5-Dimethyl-1-hexyloxy-3-[1-(methoxycarbonyl)ethyl]-
imidazolium bromide 5h
Yield: 287 mg (79%). Pale yellow oil. ½a D20
¼ þ11:1 (c 0.2,
ꢁ
CH2Cl2). IR (film):
m 3424vs, 3050–2850vs (br), 1747vs (C@O),
1636m, 1544m, 1455m, 1440m, 1317m, 1298m, 1213s, 1107m,
1063m, 976m. 1H NMR (CDCl3): d 10.82 (s, 1H, HC(2)); 5.72 (q,
J = 7.5, 1H, MeCH); 4.61 (dt, J = 7.3, J = 0.8, 2H); 3.81 (s, 3H, MeO);
2.26, 2.22 (2s, 6H, 2Me); 2.04 (d, J = 7.5, 3H, MeCH); 2.05–1.11
(m, 8H); 0.91 (t, J = 6.0, 3H, MeCH2). 13C NMR (CDCl3): d 168.0 (s,
C@O); 130.9 (d, C(2)); 124.5, 123.6 (2s, C(4), C(5)); 82.4, 30.3,
26.6, 24.0, 16.5 (5t, 5CH2, Hex); 55.4 (d, CH); 52.7 (q, MeO); 21.3
(q, MeCH); 12.9 (q, Me, Hex); 8.5, 6.3 (2q, 2Me).
4.5.4. 4,5-Dimethyl-1-hexyloxy-3-(2-hydroxyethyl)imidazolium
tetrafluoroborate 6d
Yield: 305 mg (93%). Pale yellow oil. IR (film):
m 3316vs, 3144m,
3000–2850vs, 1634m, 1549m, 1456s, 1395m, 1343m, 1239m,
1186m, 1065vs (BF4ꢀ), 754vs, 666m. 1H NMR (CDCl3): d 9.19 (s,
1H, HC(2)); 4.38 (t, J = 6.2, 2H, CH2O); 4.27 (t, J = 4.8, 2H, CH2O);
3.93 (t, J = 4.8, 2H, CH2N); 2.28 (s, 6H, 2Me); 2.08–1.15 (m, 8H,
Hex); 0.89 (t, J = 6.8, 3H, MeCH2). 13C NMR (CDCl3): d 130.6 (d,
C(2)); 125.2, 124.2 (2s, C(4), C(5)); 83.1, 59.6, 49.7, 31.4, 27.7,
25.1, 22.4 (7t, 7CH2); 14.0 (q, Me, Hex); 8.6, 7.1 (2q, 2Me).
4.4.9. (R)-4,5-Dimethyl-1-hexyloxy-3-[1-(methoxycarbonyl)-
ethyl]imidazolium bromide 5i
Yield: 301 mg (83%). ½a D20
¼ ꢀ12:0 (c 0.2, CH2Cl2).
ꢁ
4.4.10. 1,10-(Propane-1,3-diyloxy)bis(4,5-dimethyl-3-butylimid-
azolium) dibromide 9
Yield: 242 mg (90%). Pale yellow oil. IR (film):
m
3100m, 2960s,
4.5.5. (S)-1-Butoxy-4,5-dimethyl-3-(2-hydroxypropyl)imidazolium
2934s, 2873s, 1632s, 1546m, 1467s, 1396m, 1379m, 1341m,
1144m, 1030m, 962m, 925m. 1H NMR (CDCl3): d 10.96 (s, 2H,
HC(2)); 4.88 (t, J = 6.8, 4H, 2CH2O); 4.12 (t, J = 7.9, 4H, 2CH2N);
2.68–1.19 (m, 14H); 2.38, 2.25 (2s, 12H, 4Me); 0.98 (br t, J = 5.9,
tetrafluoroborate 6e
Yield: 286 mg (91%). Pale yellow oil. ½a D20
¼ þ21:8 (c 0.2,
ꢁ
CH2Cl2). IR (film):
m 3532vs, 3146s, 3000–2850vs, 1633m, 1549m,
1459m, 1396m, 1382m, 1345m, 1320m, 1288m, 1255m, 1187m,
1065vs (br, BF4ꢀ), 938m, 763m. 1H NMR (CDCl3): d 8.88 (s, 1H,
HC(2)); 4.38 (t, J = 6.4, 2H, CH2O); 4.17–3.88 (m, 3H); 3.52 (br s,
1H, OH); 2.25 (s, 6H, 2Me); 2.03–1.22 (m, 4H, MeCH2); 1.28 (d,
J = 6.4, 3H, MeCH); 0.97 (t, J = 6.6, 3H, MeCH2). 13C NMR (CDCl3):
d 130.6 (d, C(2)); 125.3, 124.2 (2s, C(4), C(5)); 82.7, 53.8, 29.7,
18.8 (4t, 4CH2); 65.6 (d, CH); 20.3 (q, MeCH); 13.7 (q, Me, Bu);
8.6, 7.0 (2q, 2Me).
13
6H, 2MeCH2). C NMR (CDCl3): d 131.8 (d, C(2), C(20)); 124.2,
124.0 (2s, C(4), C(5), C(40), C(50)); 78.6, 47.1, 31.2, 26.0, 19.0 (5t,
9CH2); 13.0 (q, 2Me, Bu); 8.3, 7.1 (2q, 4Me).
4.5. Anion exchange reactions leading to compounds 6, 8, 10,
and 12
To the magnetically stirred solution of imidazolium bromides of
type 6 and 8 (1.0 mmol) or dibromides 9 and 11 (0.5 mmol) in ace-
tone (2 mL), solid NaBF4 (121 mg, 1.1 mmol) was added. After ca.
4 h, the resulting suspension was filtered through neutral alumina
(acetone or AcOEt:MeOH 1:1) and the solvent removed under re-
duced pressure. The residue was dissolved in CH2Cl2, filtered, and
dried (4 h/20 mm Hg). Some of the obtained products solidified
after trituration with Et2O.
4.5.6. (S)-1-Butoxy-4,5-dimethyl-3-[1-(methoxycarbonyl)ethyl]-
imidazolium tetrafluoroborate 6f
Yield: 317 mg (92%). Pale yellow oil. ½a D20
¼ þ14:7 (c 0.2,
ꢁ
CH2Cl2). IR (film):
m 3140m, 3050–2850vs (br), 1750vs (C@O),
1636m, 1545m, 1456m, 1442m, 1389m, 1317m, 1241m, 1213s,
1062vs (br, BF4ꢀ). 1H NMR (CDCl3): d 9.53 (s, 1H, HC(2)); 5.31 (q,
J = 7.4, 1H, MeCH); 4.48 (dt, J = 6.2, J = 2.1, 2H); 3.82 (s, 3H, MeO);
2.30, 2.24 (2s, 6H, 2Me); 1.94 (d, J = 7.4, 3H, MeCH); 1.91–1.69
(m, 2H); 1.60–1.42 (m, 2H); 0.97 (t, J = 7.3, 3H, MeCH2). 13C NMR
(CDCl3): d 168.5 (s, C@O); 129.7 (d, C(2)); 125.2, 124.2 (2s, C(4),
C(5)); 82.4, 29.0, 16.1 (3t, 3CH2); 55.3 (d, CH); 53.0 (q, MeO);
18.0 (q, MeCH); 13.0 (q, Me, Bu); 8.1, 6.3 (2q, 2Me).
4.5.1. 1-Butoxy-3-butyl-4,5-dimethylimidazolium tetrafluoro-
borate 6a
Yield: 303 mg (97%). Pale yellow oil. IR (film):
m 3140s, 3065m,
2964s, 2937s, 2876s, 1701m, 1633m, 1549m, 1468s, 1396m,

´
G. Mloston et al. / Tetrahedron: Asymmetry 20 (2009) 1073–1080
1078
4.5.7. (R)-1-Butoxy-4,5-dimethyl-3-[1-(methoxycarbonyl)ethyl]-
1202m, 1062vs (br, BF4ꢀ). 1H NMR (CDCl3): d 8.62 (s, 1H, HC(2));
4.21 (t, J = 6.5, 2H, CH2O); 4.08–3.81 (m, 4H); 2.24 (s, 6H, 2Me);
1.99–1.25 (m, 4H, Bu); 0.95 (t, J = 6.4, 3H, MeCH2). 13C NMR
(CDCl3): d 134.1 (d, C(2)); 127.2, 126.4 (2s, C(4), C(5)); 59.9, 49.0,
46.8, 31.3, 19.3 (5t, 5CH2); 13.2 (q, Me, Bu); 8.1 (q, 2Me).
imidazolium tetrafluoroborate 6g
Yield: 301 mg (88%). ½a D20
¼ ꢀ16:2 (c 0.2, CH2Cl2).
ꢁ
4.5.8. (S)-4,5-Dimethyl-1-hexyloxy-3-[1-(methoxycarbonyl)ethyl]-
imidazolium tetrafluoroborate 6h
Yield: 340 mg (92%). Pale yellow oil. ½a D20
ꢁ
¼ þ9:5 (c 0.2, CH2Cl2).
4.5.15. (S)-3-Butyl-4,5-dimethyl-1-(2-hydroxypropyl)imidazolium
IR (film):
m
3140m, 3050–2850vs (br), 1751vs (C@O), 1636m,
tetrafluoroborate 8f
1546m, 1455s, 1439s, 1389m, 1353m, 1316m, 1240s, 1213s,
1150m, 1062vs (BF4ꢀ), 977m. 1H NMR (CDCl3): d 9.39 (s, 1H,
HC(2)); 5.28 (q, J = 7.2, 1H, MeCH); 4.46 (dt, J = 6.4, J = 1.9, 2H);
3.82 (s, 3H, MeO); 2.30, 2.23 (2s, 6H, 2Me); 1.93 (d, J = 7.2, 3H,
MeCH); 1.88–1.74 (m, 2H); 1.48–1.26 (m, 6H); 0.90 (t, J = 6.5, 3H,
MeCH2). 13C NMR (CDCl3): d 168.6 (s, C@O); 129.7 (d, C(2));
125.4, 124.3 (2s, C(4), C(5)), 82.8, 30.8, 27.1, 24.5, 16.2 (5t, 5CH2,
Hex); 55.4 (d, CH); 53.2 (q, MeO); 21.8 (q, MeCH); 13.4 (q, Me,
Hex); 8.2, 6.5 (2q, 2Me).
Yield: 283 mg (92%). Pale yellow oil. ½a D20
¼ þ21:2 (c 0.2,
ꢁ
CH2Cl2). IR (film):
m 3533vs, 3160m, 3093m, 2966s, 2937s,
2877m, 1632m, 1567s, 1463s, 1400m, 1378m, 1285m, 1204s,
1062vs (br, BF4ꢀ). 1H NMR (CDCl3): d 8.67 (s, 1H, HC(2)); 4.22–
3.89 (m, 5H); 2.25 (s, 6H, 2Me); 2.03–1.19 (m, 4H, 2CH2); 1.25
(d, J = 5.9, 3H, MeCH); 0.96 (t, J = 6.2, 3H, MeCH2). 13C NMR (CDCl3):
d 134.7 (d, C(2)); 127.3, 126.3 (2s, C(4), C(5)); 65.6 (d, CH); 53.4,
47.0, 31.4, 19.5 (4t, 4CH2); 20.2 (q, MeCH); 13.4 (q, Me, Bu); 8.5,
8.3 (2q, 2Me).
4.5.9. (R)-4,5-Dimethyl-1-hexyloxy-3-[1-(methoxycarbonyl)ethyl]-
4.5.16. (S)-1-Butyl-3-[1-(methoxycarbonyl)ethyl]-4,5-dimethy-
limidazolium tetrafluoroborate 8g
imidazolium tetrafluoroborate 6i
Yield: 344 mg (93%). ½a D20
ꢁ
¼ ꢀ10:8 (c 0.2, CH2Cl2).
Yield: 310 mg (95%). Colorless solid. Mp 64–66 °C (Et2O).
½
a 2D0
ꢁ
¼ þ10:3 (c 0.2, CH2Cl2). IR (KBr):
m 3158m, 3089m, 2963s,
4.5.10. 1,3-Dibutyl-4,5-dimethylimidazolium tetrafluoroborate
8a
2938m, 2877m, 1751vs (C@O), 1635m, 1565s, 1456s, 1401m,
1386m, 1308m, 1258m, 1212s, 1058vs (BF4ꢀ), 975m. 1H NMR
(CDCl3): d 8.91 (s, 1H, HC(2)); 5.13 (q, J = 7.7, 1H); 4.24 (t, J = 7.6,
2H); 3.79 (s, 3H, MeO); 2.28, 2.18 (2s, 6H, 2Me); 1.92 (d, J = 7.7,
3H, MeCH); 1.92–1.24 (m, 4H); 0.95 (t, J = 6.4, 3H, MeCH2). 13C
NMR (CDCl3): d 169.1 (s, C@O); 134.0 (d, C(2)); 127.5, 126.8 (2s,
C(4), C(5)); 55.2 (d, CH); 53.6 (q, MeO); 47.3, 31.6, 19.3 (3t,
3CH2); 17.1 (q, MeCH); 13.4 (q, Me, Bu); 8.3, 8.1 (2q, 2Me).
Yield: 280 mg (95%). Pale yellow oil. IR (film):
m 3156m, 3091m,
2963s, 2936s, 2876m, 1632m, 1567m, 1467m (br), 1203m, 1054vs
(br, BF4ꢀ). 1H NMR (CDCl3): d 8.79 (s, 1H, HC(2)); 4.08 (t, J = 7.9, 4H,
2CH2N); 2.24 (s, 6H, 2Me); 2.02–1.13 (m, 8H, 4CH2); 0.95 (t, J = 7.2,
6H, 2MeCH2). 13C NMR (CDCl3): d 134.5 (d, C(2)); 126.7 (s, C(4),
C(5)); 47.1, 31.7, 19.5 (3t, 6CH2); 13.4 (q, 2Me, Bu); 8.4 (q, 2Me).
4.5.11. 1-Butyl-4,5-dimethyl-3-hexylimidazolium
tetrafluoroborate 8b
4.5.17. (R)-1-Butyl-3-[1-(methoxycarbonyl)ethyl]-4,5-
dimethylimidazolium tetrafluoroborate 8h
Yield: 271 mg (87%). Pale yellow oil. IR (film):
m
3155m, 3090m,
Yield: 244 mg (75%). Colorless solid. Mp 67–68 °C (Et2O).
¼ ꢀ8:2 (c 0.2, CH2Cl2).
2960s, 2934s, 2873s, 1632m, 1567m, 1467m, 1201m, 1058vs (br,
BF4ꢀ). 1H NMR (CDCl3): d 8.82 (s, 1H, HC(2)); 4.09 (t, J = 7.6, 4H,
2CH2N); 2.25 (s, 6H, 2Me); 2.08–1.13 (m, 10H, 5CH2); 1.10–0.73
(m, 6H, 2MeCH2). 13C NMR (CDCl3): d 134.0 (d, C(2)); 126.68,
126.62 (2s, C(4), C(5)); 47.0, 46.8, 31.4, 30.8, 29.5, 25.7, 22.2, 19.2
(8t, 8CH2); 13.7, 13.2 (2q, 2Me, Hex, Bu); 8.1 (q, 2Me).
½
a 2D0
ꢁ
4.5.18. 1,10-(Propane-1,3-diyloxy)bis(4,5-dimethyl-3-
butylimidazolium) tetrafluoroborate 10
Yield: 251 mg (91%). Colorless oil. IR (film):
m 3142m, 1964s,
1936s, 2876m, 1633m, 1549m, 1468 m (br), 1341m, 1187m,
1054vs (br, BF4ꢀ), 917m, 730s. 1H NMR (CDCl3): d 9.23 (s, 2H,
HC(2)); 4.61 (t, J = 6.0, 4H, 2CH2O); 4.08 (t, J = 7.9, 4H, 2CH2N);
2.46–1.14 (m, 14H); 2.31, 2.27 (2s, 12H, 4Me); 0.94 (t, J = 6.4, 6H,
2MeCH2). 13C NMR (CDCl3): d 130.2 (d, C(2), C(20)); 124.76,
124.69 (2s, C(4), C(5), C(40), C(50)); 78.6, 47.4, 31.2, 26.0, 19.3 (5t,
9CH2); 13.2 (q, 2Me, Bu); 8.2, 6.8 (2q, 4Me).
4.5.12. 3-Butyl-1-cyclohexyl-4,5-dimethylimidazolium
tetrafluoroborate 8c
Yield: 312 mg (97%). Pale yellow oil. IR (film):
m 3153m, 3084m,
2937s, 2864m, 1630m, 1560m, 1456m, 1374m, 1235m, 1054vs (br,
BF4ꢀ). 1H NMR (CDCl3): d 8.81 (s, 1H, HC(2)); 4.12 (t, J = 7.5, 2H,
CH2N); 4.23–3.71 (m, 1H, cHex); 2.24 (s, 6H, 2Me); 2.39–1.15 (m,
14H); 0.93 (t, J = 6.6, 3H, MeCH2). 13C NMR (CDCl3): d 132.1 (d,
C(2)); 126.3 (s, C(4), C(5)); 57.3 (d, CH, cHex); 46.9, 32.7, 31.7,
25.4, 24.3, 19.2 (6t, 8CH2); 13.2 (q, Me, Bu); 8.3, 8.0 (2q, 2Me).
4.5.19. 1,10-(Propane-1,3-diyl)bis(4,5-dimethyl-3-butylimidazolium)
tetrafluoroborate 12
Yield: 213 mg (84%). Orange semi-solid. IR (film):
m 3156m,
3091m, 2963s, 2935s, 2875m, 1632m, 1567s, 1466s (br), 1201m,
1050vs (br, BF4ꢀ), 920m, 730s. 1H NMR (CDCl3): d 9.35 (s, 2H,
HC(2)); 4.42 (t, J = 7.3, 4H, 2CH2N); 4.05 (t, J = 7.8, 4H, 2CH2N);
2.70–1.14 (m, 14H); 2.37, 2.27 (2s, 12H, 4Me); 0.95 (t, J = 6.7, 6H,
4.5.13. 1-Cyclohexyl-4,5-dimethyl-3-hexylimidazolium
tetrafluoroborate 8d
Yield: 329 mg (94%). Pale yellow oil. IR (film):
m 3153m, 3084m,
13
2934s, 2861s, 1630m, 1559m, 1456m, 1231m, 1197m, 1058vs (br,
BF4ꢀ). 1H NMR (CDCl3): d 8.83 (s, 1H, HC(2)); 4.12 (t, J = 7.4, 2H,
CH2N); 4.22–3.73 (m, 1H, cHex); 2.21, 2.22 (2s, 6H, 2Me); 2.17–
1.08 (m, 18H); 0.86 (br t, 3H, MeCH2). 13C NMR (CDCl3): d 132.1
(d, C(2)); 126.34, 126.28 (2s, C(4), C(5)); 57.3 (d, CH, cHex); 47.1,
32.7, 30.8, 29.7, 25.6, 25.1, 24.3, 22.1 (8t, 10CH2); 13.7 (q, Me,
Hex); 8.3, 8.0 (2q, 2Me).
2MeCH2). C NMR (CDCl3): d 134.0 (d, C(2), C(20)); 127.3, 126.4
(2s, C(4), C(5), C(40), C(50)); 46.8, 43.5, 31.2, 29.7, 19.2 (5t, 9CH2);
13.1 (q, 2Me, Bu); 8.2, 8.1 (2q, 4Me).
4.6. Synthesis of 1,3-disubstituted 4,5-dimethylimidazolium
bromides 7 and bis-imidazolium bromide 11
The solution of imidazole 4 (1.0 mmol) and excess of the corre-
sponding alkyl bromide (1.5 mmol) or 0.5 equiv of 1,3-diaminopro-
pane (101 mg, 0.5 mmol) in benzene (5 mL) was heated at reflux
for 6 h. Then, the solvent was removed (evaporated or decanted),
the resulting product was washed with Et2O (3 ꢂ 5 mL), and dried
4.5.14. 3-Butyl-4,5-dimethyl-1-(2-hydroxyethyl)imidazolium
tetrafluoroborate 8e
Yield: 278 mg (98%). Pale yellow oil. IR (film):
m 3544vs, 3161m,
3095m, 3050–2850vs, 1633m, 1567s, 1458m, 1400m, 1358m,

´
1079
G. Mloston et al. / Tetrahedron: Asymmetry 20 (2009) 1073–1080
under high vacuum for 4 h. The products 7a, 7b, 7g, and 7h solid-
4.6.7. (S)-1-Butyl-3-[1-(methoxycarbonyl)ethyl]-4,5-dimethy-
limidazolium bromide 7g
ified after trituration with Et2O. If necessary, the crude products
can be purified by chromatography on a short column of neutral
alumina (CHCl3, then acetone in the case of 7; or acetone, then
AcOEt:MeOH 1:1 in the case of 11).
Yield: 169 mg (53%, modified procedure: 3 equiv of butyl bro-
mide, CH2Cl2, rt, 48 h). Colorless solid. Mp 96–99 °C (Et2O).
½
a 2D0
ꢁ
¼ þ11:2 (c 0.2, CH2Cl2). IR (film):
m 3050–2850vs (br),
1740vs (C@O), 1636m, 1565s, 1475m, 1464m, 1449m, 1419m,
1383m, 1293m, 1274s, 1246s, 1212s, 1095m, 1063m, 1022m,
954m. 1H NMR (CDCl3): d 10.53 (s, 1H, HC(2)); 5.48 (q, J = 7.7,
1H, MeCH); 4.41 (dt, J = 7.6, J = 3.2, 2H); 3.79 (s, 3H, MeO); 2.26,
2.19 (2s, 6H, 2Me); 2.02 (d, J = 7.7, 3H, MeCH); 1.99–1.64 (m,
2H); 1.60–1.18 (m, 2H); 0.96 (t, J = 7.2, 3H, MeCH2). 13C NMR
(CDCl3): d 168.9 (s, C@O); 135.6 (d, C(2)); 126.8, 126.4 (2s, C(4),
C(5)); 55.5 (d, CH); 53.3 (q, MeO); 47.0, 31.5, 19.1 (3t, 3CH2, Bu);
17.1 (q, MeCH); 13.2 (q, Me, Bu); 8.8, 8.2 (2q, 2Me).
4.6.1. 1,3-Dibutyl-4,5-dimethylimidazolium bromide 7a
Yield: 272 mg (94%). Pale brown solid. Mp 83–86 °C (Et2O). IR
(KBr):
m 3010m, 2962vs, 2935s, 2876m, 1630m, 1567m, 1459m,
1245m, 1197m. 1H NMR (CDCl3): d 10.39 (s, 1H, HC(2)); 4.22 (t,
J = 8.4, 4H, 2CH2N); 2.25 (s, 6H, 2Me); 2.13–1.18 (m, 8H, 4CH2);
0.99 (br t, 6H, 2MeCH2). 13C NMR (CDCl3): d 135.6 (d, C(2)); 126.1
(s, C(4), C(5)); 46.8, 31.7, 19.3 (3t, 6CH2); 13.3 (q, 2Me, Bu); 8.4
(q, 2Me).
4.6.2. 1-Butyl-4,5-dimethyl-3-hexylimidazolium bromide 7b
4.6.8. (R)-1-Butyl-3-[1-(methoxycarbonyl)ethyl]-4,5-dimethylimida-
zolium bromide 7h
Yield: 282 mg (89%). Colorless solid. Mp 118–120 °C (Et2O). IR
(KBr):
m
2960s, 2931s, 2872m, 1630m, 1565m, 1468m, 1458m,
Yield: 140 mg (44%, modified procedure: 3 equiv of butyl bro-
1199m. 1H NMR (CDCl3): d 10.48 (s, 1H, HC(2)); 4.22, 4.21 (2t,
J = 6.4, 4H, 2CH2N); 2.24 (s, 6H, 2Me); 2.12–1.12 (m, 12H, 6CH2);
1.07–0.69 (m, 6H, 2MeCH2). 13C NMR (CDCl3): d 136.3 (d, C(2));
126.0 (s, C(4), C(5)); 47.3, 47.1, 32.0, 31.1, 30.1, 26.0, 22.4, 19.6
(8t, 8CH2); 13.9, 13.5 (2q, 2Me, Hex, Bu); 8.5 (q, 2Me).
mide, CH2Cl2, rt, 48 h). Mp 99–103 °C (Et2O). ½a D20
¼ ꢀ11:0 (c 0.2,
ꢁ
CH2Cl2).
4.6.9. 1,10-(Propane-1,3-diyl)bis(4,5-dimethyl-3-butylimidazoli-
um) dibromide 11
Yield: 227 mg (89%). Pale yellow oil. IR (film):
m 3136m, 2960s,
4.6.3. 3-Butyl-1-cyclohexyl-4,5-dimethylimidazolium bromide
7c
2933s, 2872m, 1698m, 1632s, 1564s, 1464s, 1399m, 1377m,
1
1246m, 1200s. H NMR (CDCl3): d 10.29 (s, 2H, HC(2), 7HC(20));
Yield: 301 mg (95%). Pale yellow oil. IR (film):
m
2933vs (br),
4.66 (t, J = 6.7, 4H, 2CH2N); 4.07 (t, J = 6.8, 4H, HC(2), CH2N);
2.91–1.14 (m, 14H); 2.50, 2.23 (2s, 12H, 4Me); 0.98 (br t, J = 5.6,
2860m, 1629m, 1557m, 1454m, 1233m, 1212m, 1196m. 1H NMR
(CDCl3): d 10.46 (s, 1H, HC(2)); 4.38 (t, J = 6.8, 2H, CH2N); 4.27–
3.60 (m, 1H, cHex); 2.27 (s, 6H, 2Me); 2.39–1.13 (m, 14H, 7CH2);
0.95 (t, J = 6.4, 3H, MeCH2). 13C NMR (CDCl3): d 135.0 (d, C(2));
125.9, 125.4 (2s, C(4), C(5)); 58.0 (d, CH, cHex); 47.2, 33.3, 32.3,
25.5, 24.4, 19.6 (6t, 8CH2); 13.6 (q, Me, Bu); 8.8, 8.4 (2q, 2Me).
13
6H, 2MeCH2). C NMR (CDCl3): d 134.4 (d, C(2), C(20)); 127.0,
125.6 (2s, C(4), C(5), C(40), C(50)); 46.4, 43.2, 30.8, 29.5, 18.8 (5t,
9CH2); 12.7 (q, 2Me, Bu); 8.5, 7.9 (2q, 4Me).
4.7. Reaction of 5a with NaBH4
4.6.4. 1-Cyclohexyl-4,5-dimethyl-3-hexylimidazolium bromide
7d
To the solution of 5a (3.01 g, 10.5 mmol) in MeOH (15 mL), solid
NaBH4 (1.03 g, 27 mmol) was added in small portions at 0 °C. After
30 min, the ice-bath was removed and stirring was continued for
20 min at rt, the solution was diluted with 10% HCl (15 mL) and
stirred for another 20 min. Then, the organic solvents were re-
moved under reduced pressure and the resulting aqueous solution
extracted with Et2O (3 ꢂ 20 mL). The organic layer was flash chro-
matographed (SiO2, AcOEt:MeOH 2:1), the solvents removed, and
the product dried in vacuum to give pure 4a (0.51 g, 33%). Then,
the water layer was treated with excess of solid NaHCO3, extracted
with CH2Cl2 (2 ꢂ 20 mL), dried with anhyd. Na2SO4, and filtered.
The solvent was removed and pure 5a (1.65 g) was isolated.
Note: Complete reduction of 5a (0.83 g, 2.7 mmol) was achieved
using 10 equiv of NaBH4 in MeOH/H2O mixture (rt, 16 h) to give 4a
in 75% yield.
Yield: 312 mg (91%). Pale yellow oil. IR (film):
m 2931vs, 2858m,
1629m, 1557m, 1467m, 1454m, 1232m, 1199m, 730m. 1H NMR
(CDCl3): d 10.44 (s, 1H, HC(2)); 4.32 (t, J = 7.2, 2H, CH2N); 4.25–
3.68 (m, 1H, cHex); 2.28, 2.27 (2s, 6H, 2Me); 2.39–1.08 (m, 18H,
9CH2); 1.05–0.71 (m, 3H, MeCH2). 13C NMR (CDCl3): d 134.5 (d,
C(2)); 125.8, 125.5 (2s, C(4), C(5)); 57.6 (d, CH, cHex); 47.0, 33.0,
30.9, 30.0, 25.7, 25.2, 24.1, 22.1 (8t, 10CH2); 13.6 (q, Me, Hex);
8.6, 8.2 (2q, 2Me).
4.6.5. 3-Butyl-4,5-dimethyl-1-(2-hydroxyethyl)imidazolium
bromide 7e
Yield: 269 mg (97%). Pale yellow oil. IR (film):
m 3288vs, 3050–
2760s, 1632m, 1564s, 1459s, 1399m, 1375m, 1355m, 1200s,
1077s. 1H NMR (CDCl3): d 9.65 (s, 1H, HC(2)); 4.38 (t, J = 5.2, 2H,
CH2O); 4.09 (t, J = 7.6, 2H, CH2N); 3.98 (t, J = 5.2, 2H, CH2N); 2.24,
2.22 (2s, 6H, 2Me); 2.07–1.18 (m, 4H, 2CH2); 0.96 (t, J = 6.4, 3H,
MeCH2). 13C NMR (CDCl3): d 133.7 (d, C(2)); 125.1, 124.2 (2s,
C(4), C(5)); 57.5, 47.5, 45.3, 29.9, 17.8 (5t, 5CH2); 11.7 (q, Me,
Bu); 6.9, 6.3 (2q, 2Me).
Acknowledgments
The authors thank the Polish Ministry for Science and Higher Edu-
cation (G.M.) for the Grant (PBZ-KBN-126/T09/2004) and F. Hoff-
mann-La Roche AG (H.H.), Basel, for financial support. The help by
Dr. E. Röcker (JLU Giessen) in the registration of some HRMS spec-
tra is acknowledged.
4.6.6. (S)-3-Butyl-4,5-dimethyl-1-(2-hydroxypropyl)imidazolium
bromide 7f
Yield: 253 mg (84%). Colorless oil. ½a D20
¼ þ13:8 (c 0.2, CH2Cl2).
ꢁ
References
IR (film):
m 3274vs, 2964s, 2933s, 2874m, 1632m, 1564m, 1463m,
1374m, 1200m, 1139m, 1084m, 730m. 1H NMR (CDCl3): d 9.77 (s,
1H, HC(2)); 4.41–4.05 (m, 3H); 4.09 (t, J = 7.2, 2H, CH2N); 2.24 (s,
6H, 2Me); 2.07–1.15 (m, 4H, 2CH2); 1.30 (d, J = 6.4, 3H, MeCH);
0.96 (t, J = 8.0, 3H, MeCH2). 13C NMR (CDCl3): d 136.0 (d, C(2));
126.5, 125.6 (2s, C(4), C(5)); 64.7 (d, CH); 53.0, 46.9, 31.4, 19.3
(4t, 4CH2); 20.4 (q, MeCH); 13.2 (q, Me, Bu); 8.4, 8.3 (2q, 2Me).
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