Preparation of functionalized imidazolium salts under microwave irradiation

Article abstract of DOI:10.1080/00397910600634464

A direct alkylation of a substituted imidazole to prepare the corresponding functionalized ionic liquid has been developed in excellent yields under microwave irradiation. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600634464

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Preparation of Functionalized Imidazolium
Salts under Microwave Irradiation
Shih‐Kang Fu a & Shiuh‐Tzung Liu a
a Department of Chemistry, National Taiwan University, Taipei, Taiwan
Published online: 20 Aug 2006.
To cite this article: Shih‐Kang Fu & Shiuh‐Tzung Liu (2006): Preparation of Functionalized Imidazolium Salts
under Microwave Irradiation, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 36:14, 2059-2067
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Synthetic Communicationsw, 36: 2059–2067, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600634464
Preparation of Functionalized Imidazolium
Salts under Microwave Irradiation
Shih-Kang Fu and Shiuh-Tzung Liu
Department of Chemistry, National Taiwan University, Taipei, Taiwan
Abstract: A direct alkylation of a substituted imidazole to prepare the corresponding
functionalized ionic liquid has been developed in excellent yields under microwave
irradiation.
Keywords: Imidazolium, ionic liquid, microwave irridiation
From an environmental perspective, ionic liquids provide an alternative reaction
medium for chemical reactions.[1] Among various ionic liquids, simple alkyl
substituted 1,3-dialkyl-imidazolium cations associated with weakly coordinat-
ing anions are the most popular used in biphasic catalysis because of their
distinct physical–chemical properties.[1,2] More recently, developments of the
presence of appropriate functional groups as part of ionic liquid molecules to
increase the immobilization of catalysts or facilitate the separation process
represent a new area of interest.[3] Thus, a few of this type of ionic liquids,
such as imidazolium-based ones with amine,[4] amido,[5] hydroxy,[6] carboxy-
late,[7] urea,[8] perfluoro-chains,[9] and nitriles,[3] are known.
Conventional heating in refluxing solvents is a typical way to prepare 1,3-
dialkylimidazolium halides. Compared to the time-consuming processes of
conventional methods, a microwave-assisted chemical reaction has been
applied to synthesize ionic liquids.[10,11] In the past two decades, the use of
microwave ovens in chemical synthesis and analysis has grown because of
the advantages in reducing reaction times, improving yield, and simplifying
procedures. The preparation of functionalized ionic liquids using a solvent-
free approach has not reported in literature.[4–9]
Received in Japan March 7, 2006
Address correspondence to Shiuh-Tzung Liu, Department of Chemistry, National
Taiwan University, Taipei 106, Taiwan. E-mail: stliu@ntu.edu.tw
2059

2060
S.-K. Fu and S.-T. Liu
RESULTS AND DISCUSSION
The microwave-assisted reaction was conducted in a round-bottom flask using
a Discovery microwave heating apparatus with a thermal controller (CEM
Corp., Matthews, NC). This apparatus allows the reaction flask to be
equipped with condenser fitted into a microwave-irradiation chamber (see
the experimental section). Typically, a mixture of equal molar amounts
(6.5 mmol) of 1-methylimidazole and g-bromobutyonitrile in a 20-mL flask
was irradiated at 180 W at 1808C for 30 s. Upon completion of the reaction,
the pale yellow, viscous oil was washed with dichloromethane (20 mL ꢀ 2)
to remove the unreacted starting materials. The residue was dried under
vacuum overnight, and the obtained material was analytical pure.
All reactions studied in this work are shown in Scheme 1. As a starting
point, we studied the microwave-assisted coupling of 1-methylimidazole
with 3-triethoxysilylpropyl chloride. Entries 1–5 of Table 1 show the
results of this optimization. It appeared that the period of irradiation and
reaction temperature were critical for the reaction. The best conditions for
the preparation of 1 is irradiation at microwave power of 245 W for 40 s.
Either a higher or a lower power of irradiation in this reaction gave decompo-
sition or poorer yield. The scale for the reaction is irrelevant to the irradiation
period employed. Because of the moisture sensitivity of the triethoxy silyl
group, the reaction had to be carried out under a dry nitrogen atmosphere;
otherwise the condensation leading to Si-O-Si took place, which caused
a decrease in the yield of 1. However, it can be carried out under aerobic
Scheme 1. Preparation of functionalized 1,3-disubstituted imidazolium–based ionic
liquids.

Table 1. Results for the reactions of 1-methylimidazole with various alkyl halidesa
Quantity of
reactant (mmol)
Power of
MW (W)
Temp.
(8C)
Entry
Product
T (s)
Atm.
Yieldb
Physical property
Ref.
[12]
1
2
6.5
60
1
1
245
245
245
185
245
185
180
100
100
100
180
250
250
30
40
40
25
40
40
25
30
25
35
35
30
90
90
20
20
20
245
245
140
145
185
180
180
175
180
168
180
185
185
110
170
170
N2
air
N2
N2
N2
air
air
air
air
air
air
air
air
air
air
air
95%
49%
trace
trace
93%
90%
95%
92%
90%
90%
81%
90%
85%
45%
dec.
0
Pale yellow liquid
Pale yellow liquid
—
3
6.5
6.5
6.5
11.3
6.5
6.5
6.5
3.4
4.6
5.0
2.9
1.5
1.5
1.5
1
4
1
—
5
1
Pale yellow liquid
Pale yellow liquid
Pale yellow liquid
Lemon yellow liquid
Colorless liquid
Pale yellow liquid
Lemon yellow liquid
Colorless liquid
Colorless liquid
White powder solid
—
6
2
[13]
[3]
7
3
8
4
[14]
[15]
[16]
9
5
10
11
12
13
14
15
16
6
7
8
9
10
10
10
100
5
—
aReaction conditions: an equal molar amount of 1-methylimidazole and RX in flask without using any solvent.
bIsolated yield and characterized by 1H NMR.

2062
S.-K. Fu and S.-T. Liu
1
conditions for other substrates. All products were characterized by H NMR
and elemental analysis. The optimum reaction conditions for reactions of
1-methylimidazole with various alkyl halides are summarized in Table 1.
As shown in Table 1, various alkyl halides were able to react with
imidazole to give the corresponding ionic liquid in excellent yields (entries
6–13). For example, the production of 10 was achieved by adopting 30 W
at 1108C, whereas the compound 8 was with 250 W at 1858C. For the acetyl-
ated glucose derivative, the reaction provided a moderate yield by using
30 W of microwave at 1108C. Attempts to improve the yield by varying the
microwave powers and temperatures failed, indicating an intrinsic property
of this substrate.
All functionalized imidazolium halides except 10 are in liquid phase at
room temperature. Compound 10 is in a solid form, which becomes liquid at
temperatures greater than 90–938C. As for solubility, those containing 22OH
of polyether groups are water- and methanol-soluble materials. In fact,
compound 8 is completely miscible with water. Of course, the halide anions
of this series of ionic liquids also increase their solubility toward water.
Similarly, the alkylation of 1-propyl-2-methylimidazole proceeded smoothly
to give the corresponding ionic liquid in excellent yield (Scheme 2). The
reaction conditions employed are comparable to the preparation of the
related 1,3-disubstituted imidazolium-based ionic liquids (Table 2).
Reaction of 1-bromo-3-chloropropane with 1-methylimidazole under
microwave irradiation yielded a mixture of 14, 15,[17] and 16[18] (Scheme 3).
It shows that the poor selectivity of nucleophilic substitution of imidazole
toward alkyl bromide versus chloride under microwave-assisted conditions
even with a lower power irradiation. Even under mild conditions with lower
power (30 W), this reaction still provided a mixture of products. However, the
reaction proceeded poorly at the temperature lower than 1008C. All these
compounds were not able to be obtained in pure form because of the anion.
3-Aminopropyl chloride was also tested as a substrate for the alkylation.
A mixture of an equalmolar amount of 3-aminopropyl chloride hydrochloride
Scheme 2. Preparation of functionalized 1,2,3-trisubstituted imidazolium–based
ionic liquids.

Functionalized Imidazolium Salts
2063
Table 2. Results for preparation of 1,2,3-trisubstituted imidazolium–based ionic
liquids
Product
Power (W)
T (s)
Temp. (8C)
Yield (%)
Physical property
11
12
13
235
180
105
40
50
30
185
180
180
75
89
85
Pale yellow liquid
Pale yellow liquid
Pale yellow liquid
salt, 1-methylimidazole, and triethylamine was irradiated at 1708C with the
power setting of 180 W for 90 s to provide the desired ionic liquid 17 in
65% yield accompanied by the formation of azetidine Eq. (1). This outcome
shows that the alkylation takes place with imidazole nitrogen superior to the
amine site. However, the use of excess 3-aminopropyl chloride salt can
provide 17 in a high yield.
Scheme 3. Reaction of imidazole with 3-chloro-1-bromopropane.

2064
S.-K. Fu and S.-T. Liu
In summary, we have demonstrated a much faster and more efficient
method for the preparation of functionalized imidazolium-based ionic liquid
in high yields. Work on these functionalized ionic liquids continues and is
expected to illustrate interesting new results.
EXPERIMENTAL
Nuclear magnetic resonance spectra were recorded in CDCl3 or acetone-d6 on
either a Bruker AM-300 or Avance 400 spectrometer. Chemical shifts are
1
given in parts per million relative to Me4S for H and 13C NMR. Infrared
spectra were measured on a Nicolet Magna-IR 550 spectrometer (series-II)
as KBr pallets, unless otherwise noted. Microwave irradiation was carried
out in a Discovery microwave heating apparatus with temperature controller
(CEM Corp., Matthews, NC). The reaction temperature reported was based
on this readout. Chemicals and solvents were of analytical grade and used
as received unless otherwise stated. a-Bromotetraacetyl-L-glucose was
prepared from the earlier reported procedures.[19]
General Procedure
An equal molar amount of 1-methylimidazole and alkyl halides in a 20-mL
flask was set up as shown in Fig. 1 and was irradiated at a certain level of
power with programming the temperature for a certain period of reaction
time. Upon completion of the reaction, the pale yellow, viscous oil was
washed with dichloromethane (20 mL ꢀ 2) to remove the unreacted starting
materials and was dried under vacuum overnight. Spectroscopic data of
the obtained compounds 1–6 are essentially identical to the literature
reported.[3,12–16]
Figure 1. Microwave-assisted heating apparatus.

Functionalized Imidazolium Salts
Data
2065
Compound 7. ymax KBr/cm21 3164, 2952, 2866, 1726 (yC55O), 1653 (yC55C),
1573; 1H NMR (300 MHz, CDCl3): d 9.99 (s, 1H), 7.53 (s, 1H), 7.47 (s, 1H),
4.20 (t, 2H, J ¼ 7.31 Hz), 3.93 (s, 3H), 3.91 (q, 2H, J ¼ 7.05 Hz), 2.16
(t, J ¼ 7.29 Hz), 1.80 (m, 2H), 1.50 (m, 2H), 1.24 (m, 2H), 1.07 (t, 3H,
J ¼ 7.18 Hz). MS found [M-Br]þ 239 for C13H23N2O2; anal. calcd. for
C13H23BrN2O2: C, 48.91; H, 7.26; N, 8.78. Found for C, 45.45; H, 7.15;
N, 9.46.
Compound 8. ymax KBr/cm21 3552 (yO22H), 3164, 2872, 1653 (yC55C), 1587,
1
1116; H NMR (300 MHz, D2O): d 8.75 (s, 1H), 7.52 (s, 1H), 7.45 (s, 1H),
4.39 (t, 2H, J ¼ 4.6 Hz), 3.91 (s, 3H), 3.89 (m, 2H), 3.72 (m, 6H), 3.60
(m, 2H). MS found [M-Cl]þ 215 for C10H19N2O3; anal. calcd. for
C10H19ClN2O3: C, 47.9; H, 7.64; N, 11.19. Found: C, 47.21; H, 7.83; N, 11.37.
Compound 9. ymax KBr/cm21 3164, 2873, 1646, 1566, 1103; 1H NMR
(300 MHz, CDCl3): d 9.81 (s, 1H), 7.66 (s, 1H), 7.47 (s, 1H), 3.97 (s, 3H),
3.79 (t, 2H, J ¼ 4.58 Hz), 3.52 (m, 8H), 3.25 (s, 3H). MS found [M-Br]þ
229 for C11H21N2O3; anal. calcd. for C11H21BrN2O3: C, 42.73; H, 6.85; N,
9.06. Found: C, 42.59; H, 7.19; N, 8.98.
Compound 10. Mp: 90–938C; ymax KBr/cm21 3171, 2939, 2879, 1726
(yC55O), 1653, 1587, 1089; H NMR (300 MHz, CDCl3): d 10.05 (s, 1H),
1
7.38 (s, 1H), 7.31 (s, 1H), 5.15 (t, 1H, J ¼ 9.6 Hz), 5.02 (t, 1H, J ¼ 9.9 Hz),
4.85 (t, 1H, J ¼ 8.0 Hz), 4.50 (d, 1H, J ¼ 8.0 Hz), 4.39 (m, 2H), 4.20
(m, 1H), 4.06 (s, 3H), 3.71 (m, 2H), 3.62 (m, 2H), 2.20 (m, 2H), 2.05
(s, 1H), 2.02 (s, 1H), 2.00 (s, 1H), 1.95 (s, 1H). MS found [M-Br]þ 472 for
C20H29N2O10; anal. calcd. for C20H29BrN2O10: C, 44.70; H, 5.44; N, 5.21.
Found: C, 44.26; H, 5.45; N, 4.99.
Compound 11. ymax KBr/cm21 3144, 2980, 2933, 2849, 1640, 1586, 1076;
1H NMR (300 MHz, CDCl3): d 7.66 (s, 1H), 7.51 (s, 1H), 4.27 (t, 2H,
J ¼ 7.3 Hz), 4.08 (t, 6H, J ¼ 7.3 Hz), 3.92 (q, 2H, J ¼ 7.2 Hz), 2.65 (s, 3H),
2.34 (t, 2H, J ¼ 7.2 Hz), 1.97 (m, 2H), 1.72 (m, 2H), 0.82 (t, 9H,
J ¼ 7.3 Hz). MS found [M-Cl]þ 287 for C13H27N2O3Si; anal. calcd. for
C13H27ClN2O3Si: C, 48.35; H, 8.43; N, 8.68. Found: C, 47.21; H, 7.83;
N, 11.37.
Compound 12. ymax KBr/cm21 3403 (yO22H), 3144, 2952, 2886, 1653, 1593,
1
1129; H NMR (300 MHz, CDCl3): d 7.81 (s, 1H), 7.49 (s, 1H), 4.43 (t, 2H,
J ¼ 4.5 Hz), 4.10 (t, 2H, J ¼ 7.2 Hz), 3.81 (t, 2H, J ¼ 4.5 Hz), 3.52
(m, 8H), 2.65 (s, 3H), 1.75 (m, 2H), 0.88 (t, 3H, J ¼ 5.2 Hz). MS found
[M-Cl]þ 257 for C13H25ClN2O3; anal. calcd. for C13H25ClN2O3: C, 53.33;
H, 8.61; N, 9.57. Found: C, 53.18; H, 8.98; N, 9.44.

2066
S.-K. Fu and S.-T. Liu
Compound 13. ymax KBr/cm21 3139, 2974, 2883, 1727, 1640, 1587;
1H NMR (300 MHz, CDCl3): d 7.65 (s, 1H), 7.54 (s, 1H), 4.19 (t, 2H,
J ¼ 11.2 Hz), 3.43 (s, 9H), 2.72 (s, 3H), 1.79 (m, 2H), 0.84 (t, 3H,
J ¼ 18.4 Hz), 0.54 (t, 3H, J ¼ 12.6 Hz). MS found [M-Br]þ 239 for
C13H23BrN2O2; anal. calcd. for C13H23BrN2O2: C, 48.91; H, 7.26; N, 8.78.
Found for C, 48.96; H, 7.93; N, 8.96.
Compound 17. ymax KBr/cm21 3455 (yN22H), 3157, 2963, 2753, 1634, 1579;
1H NMR (300 MHz, D2O): d 8.65 (s, 1H), 7.39 (s, 1H), 7.32 (s, 1H), 4.19
(t, 2 H, J ¼ 7.3 Hz), 3.75 (s, 3H), 2.93 (m, 2H), 2.16 (m, 2H). MS found
[M–Cl]þ 140 for C7H14N3; anal. calcd. for C7H14ClN3: C, 47.86; H, 8.03.
Found for C, 47.66; H, 7.83.
ACKNOWLEDGMENT
This research was supported by the National Science Council (NSC93-2113-
M002-004), Taiwan, China.
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