1,1,3,3-N,N,N′,N′-tetramethylguanidinium trifluoroacetate ionic liquid-promoted efficient one-pot synthesis of trisubstituted imidazoles

Article abstract of DOI:10.1080/00397910500328969

Trisubstituted imidazoles have been synthesized in very short reaction times with excellent yields in the presence of 1,1,3,3-N,N,N′,N′- tetramethylguanidinium trifluoroacetate as an ionic liquid at 100°C. The ionic liquid can be recycled for subsequent reactions without any appreciable loss of efficiency. Copyright Taylor & Francis LLC.

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1,1,3,3‐N,N,N′,N′‐Tetramethylguanidinium
Trifluoroacetate Ionic Liquid–Promoted
Efficient One‐Pot Synthesis of Trisubstituted
Imidazoles
Ahmad Shaabani a , Abbas Rahmati a , Behnaz Aghaaliakbari b & Javad
Safaei‐Ghomi b
a Department of Chemistry, Shahid Beheshti University, Tehran, Iran
b Department of Chemistry, University of Kashan, Kashan, Iran
Version of record first published: 21 Aug 2006.
To cite this article: Ahmad Shaabani, Abbas Rahmati, Behnaz Aghaaliakbari & Javad Safaei‐Ghomi (2006):
1,1,3,3‐N,N,N′,N′‐Tetramethylguanidinium Trifluoroacetate Ionic Liquid–Promoted Efficient One‐Pot Synthesis
of Trisubstituted Imidazoles, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 36:1, 65-70
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Synthetic Communicationsw, 36: 65–70, 2006
Copyright # Taylor & Francis LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500328969
1,1,3,3-N,N,N0,N0-Tetramethylguanidinium
Trifluoroacetate Ionic Liquid–Promoted
Efficient One-Pot Synthesis of Trisubstituted
Imidazoles
Ahmad Shaabani and Abbas Rahmati
Department of Chemistry, Shahid Beheshti University, Tehran, Iran
Behnaz Aghaaliakbari and Javad Safaei-Ghomi
Department of Chemistry, University of Kashan, Kashan, Iran
Abstract: Trisubstituted imidazoles have been synthesized in very short reaction times
with excellent yields in the presence of 1,1,3,3-N,N,N0,N0-tetramethylguanidinium
trifluoroacetate as an ionic liquid at 1008C. The ionic liquid can be recycled for
subsequent reactions without any appreciable loss of efficiency.
Keywords: Imidazole, ionic liquid, one-pot condensation reaction, 1,1,3,3-N,N,N0,N0-
tetramethylguanidinium trifluoroacetate
INTRODUCTION
Ionic liquids (ILs) are emerging as effective promoters and solvents for green
chemical reactions. During the past few years, a variety of catalytic reactions
have been successfully conducted using ILs as solvents. Many interesting
results have been obtained that demonstrate advantages of using ILs as
alternative for organic solvents. One of the most important advantages of
ILs is the behavior of solvophobic interactions that generate an internal
pressure, which promotes the association of the reactants in a solvent cavity
Received in the UK March 21, 2005
Address correspondence to Ahmad Shaabani, Department of Chemistry, Shahid
Beheshti University, P.O. Box 19396-4716, Tehran, Iran. Fax: þ98-21-2403041;
E-mail: a-shaabani@cc.sbu.ac.ir
65

66
A. Shaabani et al.
during the activation process and accelerates multicomponent reactions
(MCRs) in comparison with conventional solvents.[1–3]
Multisubstituted imidazoles are an important class of compounds in the
field of pharmaceuticals and exhibit a wide spectrum of biological activities.[4]
Owing to the versatile biological activities of these compounds, numerous
classical methods for their preparation have been reported.[4–10] In addition,
a few research groups have very recently reported one-pot condensation of
a-hydroxyketone, keto-oxime, or 1,2-diketone and aldehyde in the presence
of NH4OAc on solid supports under microwave irradiation.[11–14] However,
in spite of their potential utility, some of these methods not only involve
strongly acidic conditions (HOAc as a solvent and catalyst) and high tempe-
ratures (180–2008C) but also require special instruments.
During the course of our studies on the development of new routes to the
synthesis of highly substituted hetrocycles,[15] herein we report a valid and an
efficient procedure for the synthesis of trisubstituted imidazoles from a one-
pot condensation of 1,2-diketone 1 or a-hydroxyketone 2, aldehyde 3, and
NH4OAc in 1,1,3,3-N,N,N0,N0-tetramethylguanidinium trifluoroacetate
(TMGT) at 1008C (Scheme 1). To the best of our knowledge, this is the
first report of an ionic liquid one-pot condensation reaction synthesis of trisub-
stituted imidazoles.
RESULTS AND DISCUSSION
The successful results of the synthesis of trisubstituted imidazoles in TMGT
are given in Table 1. Using TMGT as promoter and solvent for the
synthesis of trisubstituted imidazoles not only represents a dramatic improve-
ment (15–40 min, 81–94%) over conventional thermal heating,[4–10] but
the reaction times are also comparable to the recently reported microwave
irradiation (20 min at HOAc, 180–2008C).[12–14]
Decreased reaction times are also realized because the solvophobic inter-
action behavior of TMGT generates an internal pressure, which promotes the
association of the reactants in the solvent cavity.
Scheme 1.

Trisubstituted Imidazoles
67
Table 1. One-pot synthesis of trisubstituted imidazoles in 1,1,3,3-N,N,N0,N0-
tetramethylguanidinium trifluoroacetate as an ionic liquid at 1008C
MP (8C)
Entry
Y
Time (min)
Yield (%)
Found
Reported
4a
4b
–H
–CH3
15
20
92
94, 93,a 87,a
88,a 84a
94
89
.300
226–228
—
233b
4c
4d
4e
4f
–OCH3
–Cl
20
20
20
25
30
30
40
40
227–230
259–261
227 dec.
.300
226–227
225–230
256–259
227 dec.
230–232c
261–263c
—
–NO2
–H
84
84
—
233b
230–232c
261–263c
—
4g
4h
4i
–CH3
–OCH3
–Cl
87
86
82
81
4j
–NO2
aThe same catalyst was used for each of the four runs.
bRef.[4]
cRef.[16]
.
.
In
a typical experiment, aldehyde (1 mmol), 1,2-diketone, or
a-hydroxyketone compound (1 mmol) and ammonium acetate (2 mmol) in
TMGT (0.6 mmol) were successively charged into a screw-capped vial con-
taining a magnetic stirring bar. The reaction proceeded at 1008C for 15–40
min during which time a solid product gradually formed. After the completion
of reaction (TLC), the resulting solid product was washed with cold water,
filtered, and dried to afford the product.
Experiments were conducted to study the reaction of para-methylbenzal-
dehyde and NH4OAc with the mixture of benzil or benzoin at 1008C in the
absence of TMGT. The yield of product was only 41% and 38% after
30 min, respectively.
To explore the scope and limitations of this reaction, we extended
the reaction of 1,2-diketo with various aromatic aldehydes carrying either
electron-releasing or electron-withdrawing substituents in the para
positions. We found that the reaction proceeds very efficiently.
It is important to note that because direct use of benzoin rather than benzil
in the synthesis of imidazoles represents a significant improvement in greener
chemical synthesis, we repeated the reaction with benzoin instead of benzil,
and as indicated in Table 1 the desired product was efficiently produced.
One of the other advantages of these ILs is their ability to be recyclable as
reaction media. We were easily able to separate TMGT from the reaction
medium by washing it with water and evaporating the solvent under
vacuum, and reused it for subsequent reactions. As indicated in Table 1,

68
A. Shaabani et al.
there was no considerable loss of efficiency with regard to reaction time and
yield after four times (Entry 4b). However, fresh IL can be added after four
uses for subsequent runs.
CONCLUSIONS
We have developed an efficient and environmentally friendly method for the
synthesis of trisubstituted imidazoles in excellent yield within short reaction
times. Using TMGT as a promoter and solvent for the synthesis of trisubsti-
tuted imidazoles not only represents a dramatic improvement (15–40 min,
81–94%) over conventional thermal heating, but the reaction time is
comparable to the recently reported microwave irradiation.[12,14]
EXPERIMENTAL
Melting points were measured on an Electrothermal 9100 apparatus and are
uncorrected. Elemental analyses were performed using a Heraeus CHN-
O-Rapid analyzer. Mass spectra were recorded on a Finnigan-MAT 8430
mass spectrometer operating at an ionization potential of 70 eV. IR spectra
were recorded on a Shimadzu IR-470 spectrometer. 1H and 13C NMR
spectra were recorded on a Bruker DRX-300 Avance spectrometer at
300.13 and 75.47 MHz, respectively. NMR spectra were obtained on
solutions in DMSO-d6. All the products (except 4e and 4j) are known
1
compounds, which were characterized by IR and H NMR spectral data,
and their melting points were compared with literature reports.
Typical Procedure for the Preparation of 4a
A mixture of benzaldehyde (0.106 g, 1 mmol), benzil (0.210 g, 1 mmol),
ammonium acetate (0.154 g, 2 mmol), and 1,1,3,3-N,N,N0,N0-tetrmethylguani-
dinium trifluoroacetate (0.137 g, 0.6 mmol) was heated with stirring at 1008C
for 20 min. After cooling, the reaction mixture was washed with cold water
(2 ꢀ 25 mL) and the residue crystallized from water and acetone to afford
the pure product 4a (0.272 g, 0.92 mmol, 92%).
Data
2,4,5-Triphenylimidazole (4a or 4f). White powder. IR (KBr) n: 3425, 3053,
1629, 1586, 696 cm21. 1H NMR (DMSO-d6) d 7.17–7.49 (m, 3C6H5), 12.69
(s, NH) ppm. 13C NMR (DMSO-d6) d 125.6, 127.0, 127.5, 128.2, 128.6, 128.7,
128.9, 129.1, 130.0, 130.8, 131.5, 135.6, 137.5, 145.9 ppm.

Trisubstituted Imidazoles
69
2-(4-Methylphenyl)-4,5-diphenylimidazole (4b or 4g). White powder.
IR (KBr) n: 3405, 3028, 1597 cm21
.
1H NMR (DMSO-d6) d 2.28
(s, OCH3), 7.21–7.49 (m, 2C6H5), 7.22 (d, 3J ¼ 7.3 Hz, C6H4), 7.92
3
(d, J ¼ 7.4 Hz, C6H4), 12.56 (s, NH) ppm. 13C NMR (DMSO-d6) d 21.3,
125.6, 126.9, 127.5, 128.0, 128.1, 128.4, 128.6, 128.8, 129.1, 129.7, 131.5,
135.6, 137.3, 138.1, 146.1 ppm.
2-(4-Metoxyphenyl)-4,5-diphenylimidazole (4c or 4h). White powder.
1
IR (KBr) n: 3405, 3053, 1626, 1249 cm21. H NMR (DMSO-d6) d 3.75
3
(s, OCH3), 6.99 (d, J ¼ 7.8 Hz, C6H4-OCH3), 7.15–7.51 (m, 2C6H5), 7.97
3
(d, J ¼ 7.8 Hz, C6H4-OCH3), 12.47 (s, NH) ppm. 13C NMR (DMSO-d6) d
55.6, 114.5, 123.6, 126.8, 127.1, 127.5, 128.0, 128.1, 128.6, 128.8, 129.0,
131.7, 135.7, 137.2, 146.1, 159.0 ppm.
2-(4-Cholorophenyl)-4,5-diphenylimidazole (4d or 4i). White powder.
IR (KBr) n: 3420, 3032, 1626, 1487 cm21. 1H NMR (DMSO-d6) d 7.00–7.51
3
3
(m, 2C6H5), 7.49 (d, J ¼ 8.5 Hz, C6H4Cl), 8.03 (d, J ¼ 8.3 Hz, C6H4Cl),
12.73 (s, NH) ppm. 13C NMR (DMSO-d6) d 127.1, 127.3, 127.5, 128.4,
128.7, 128.9, 129.0, 129.2, 129.3, 129.6, 129.9, 130.1, 131.3, 133.2,
144.8 ppm.
2-(4-Nitrophenyl)-4,5-diphenylimidazole (4e or 4j). Orange powder. IR
1
(KBr) n: 3420, 3090, 1592, 1507, 1336, 1102 cm21. H NMR (DMSO-d6) d
6.69 (d, 3J ¼ 7.4 Hz, C6H4NO2), 7.08–7.60 (m, 2C6H5), 8.03 (d, 3J ¼
7.5 Hz, C6H4NO2), 12.64 (s, NH) ppm. 13C NMR (DMSO-d6): d ¼ 101.1,
114.4, 127.5, 128.0, 128.2, 128.7, 128.8, 129.1, 130.8, 135.9, 145.5, 159.2,
166.1, 174.4 ppm. MS, m/e (%): 297 (60), 269 (20), 165 (100), 105 (25),
77 (50). Anal. calcd. for C21H15N3O2: C, 73.90; H, 4.39; N, 12.31. Found:
C, 73.83; H, 4.32; N, 12.39.
ACKNOWLEDGMENTS
We gratefully acknowledge financial support from the Research Council of
Shahid Beheshti University.
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