One-pot synthesis of 2,4,5-triarylimidazoles catalyzed by copper (II) trifluoroacetate under solvent-free conditions

Article abstract of DOI:10.1080/15533171003629055

A simple, efficient and eco-friendly procedure has been developed using copper(II) trifluoroacetate as catalyst for the synthesis of 2,4,5-triarylimidazoles by one-pot condensation of benzil, aldehydes and ammonium acetate under solvent-free conditions. Compared with traditional methods, the present methodology offers several advantages such as excellent yields, and environmentally benign milder reaction conditions. Moreover, the catalyst exhibits reusable activity.

Full text of DOI:10.1080/15533171003629055

Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 40:145–147, 2010
Copyright © Taylor & Francis Group, LLC
ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533171003629055
One-Pot Synthesis of 2,4,5-Triarylimidazoles Catalyzed by
Copper (II) Trifluoroacetate Under Solvent-Free Conditions
Dailei Song, Chunsheng Liu, Shaohua Zhang, and Genxiang Luo
Department of Chemistry, School of Chemistry and Materials Science, Liaoning Shihua University,
Fushun, Liaoning, P. R. China
Recently, trifluoroacetates have received considerable at-
tention as inexpensive, non-toxic, and readily available Lewis
acids catalysts for various organic transformations. For exam-
ple, Fe(TFA)3[13] and Bi(TFA)3,[14] were utilized as powerful
catalysts to synthesize multifarious compounds.
Previously, copper(II) trifluoroacetate as an efficient catalyst
was used in synthesizing 3,4-dipyrimidin-2(1H)-ones[15] and
α, αꢀ-bis(benzylidene substituted)cycloalkanones[16] and the re-
sults were satisfying in our study.
A simple, efficient and eco-friendly procedure has been devel-
oped using copper(II) trifluoroacetate as catalyst for the synthesis
of 2,4,5-triarylimidazoles by one-pot condensation of benzil, alde-
hydes and ammonium acetate under solvent-free conditions. Com-
pared with traditional methods, the present methodology offers
several advantages such as excellent yields, and environmentally
benign milder reaction conditions. Moreover, the catalyst exhibits
reusable activity.
Keywords catalyst, copper(II) trifluoroacetate, synthesis, triarylimi-
Encouraged by these successes, the reaction of benzil, aro-
matic aldehydes and ammonium acetate catalyzed by copper(II)
trifluoroacetate to synthesize 2,4,5-triarylimidazoles was stud-
ied (Scheme 1).
dazoles.
H
Ph
Ph
Ph
Ph
O
O
N
INTRODUCTION
Cu(TFA)2
R
Substituted imidazoles and their derivatives are receiving
growing attention for their pharmacologically properties such as
herbicidal, fungicidal, analgesic, antiinflammatory and antithro-
mobotic activities.[1] During the course of studies on the devel-
opment of new procedures to synthesize substituted imidazoles,
a number of catalysts, such as copper (II) acetate,[2] Cu2O,[3]
Yb(OTf)3,[4] elemental iodine,[5] ZrCl4,[6] HClO4-SiO2,[7] ze-
olite HY and silica gel,[8] NiCl26H2O,[9] were screened. Some
procedures also involve ionic liquid-promoted[10] or microwave-
assisted synthesis.[11,12] However, many of the synthesis proto-
cols for imidazoles reported so far suffer from one or more
disadvantages, such as harsh reaction conditions, poor yields,
long reaction times, and the use of hazardous and often expen-
sive catalysts. Thus, the development of a simple, efficient, and
versatile approach for the preparation of 2,4,5-triarylimidazoles
is an active area of research for further improvements towards
milder reaction conditions and higher product yields.
RCHO
+
+ NH4 OAc
neat100 o
C
N
1
2
3
4
SCH. 1. Synthesis of 2,4,5-triarylimidazoles catalyzed by Cu(TFA)2 under
solvent-free condition.
EXPERIMENTAL
Melting points were measured on X-6 micro-melting point
apparatus and uncorrected. IR spectra were measured on spec-
1
trum GX spectrometer (KBr). HNMR spectra were recorded
on Bruker AVANCE 600 spectrometer (600MHz for 1HNMR),
using CDCl3 as solvent and tetramethylsilane (TMS) as internal
reference.
Preparation of Copper(II) Trifluoroacetate
Copper(II) trifluoroacetate was prepared according to known
procedure.[17] An excess of copper monoxide reacted with tri-
fluoroacetic acid in water. The mixture was stirred for 20–30
min at room temperature and then the mixture was filtered. Af-
ter that the filtrate was evaporated to be dry in water bath. The
obtained crude product was recrystallized twice with water.
Received 13 September 2009; accepted 17 January 2010.
Address correspondence to Genxiang Luo, Department of Chem-
istry, School of Chemistry and Materials Science, Liaoning Shi-
hua University, Fushun, Liaoning 113001, P. R. China. E-mail:
genxiangluo@yahoo.com.cn
145

146
D. SONG ET AL.
TABLE 1
General Procedure for the Synthesis of
Condensation of benzil, benzaldehyde and ammonium acetate
2,4,5-Triaubatituted Imidazoles Catalyzed by Copper(II)
Trifluoroacetate
in the different solventsa
Benzil (1 mmol), ammonium acetate (4 mmol), aldehyde
(1 mmol) and copper(II) trifluoroacetate (0.01 mmol) were
mixed in a round bottom flask. The mixture was stirred for
a few hours at 100◦C. When TLC indicated the completion of
the reaction, the mixture was cooled to room temperature, and
then some pieces of ice were added into this system. The solid
was filtered and washed with ice-cold water and purified further
by recrystallization (hot ethanol). The structure of the product
was characterized by IR and 1H NMR.
Entry Molar ratio of Catalyst Solvent
Yield (%)b
1c
2
3
4
5
6
7
—
Solvent-free
H2O
EtOH
trace
trace
66
68
93
0.01
0.01
0.01
0.01
0.02
0.04
MeOH
Solvent-free
Solvent-free
Solvent-free
93
93
aThe condensation reaction of benzil (1 mmol), benzaldehyde (1
mmol) and ammonium acetate (4 mmol) were carried out at 100◦C for
4 h.; bIsolated yields; cno catalyst.
Selected Product Characterization Data
2,4,5-Triphenylimidazole 4a: m.p. 279◦C; IR (KBr)
ν =3413, 3038, 1596, 1488 cm−1; 1H NMR (CDCl3, 600 MHz):
δ =12.69 (s, 1H), 7.37–7.52 (m, 15H) ppm.
Prompted by this success, we extended this reaction of ben-
zil, ammonium acetate with a range of other aldehydes under
the same conditions; the results were shown in Table 2. It is
found that the reaction of benzil, ammonium acetate with other
aldehydes can be carried out smoothly for 4 h in the experiment
procedure. The yields are all above 90%.
Table 2 showed that aromatic aldehydes containing both elec-
tron donating and withdrawing groups underwent the conversion
smoothly and gave the products with excellent yields (Entry 1–
9). But this reaction does not occur even in a prolonged reaction
time when aromatic aldehydes are replaced by aliphatic aldehy-
des.
It is important to note that one of the advantages of Cu(TFA)2
is its ability to be recyclable as catalyst. When Cu(TFA)2 was
separated from the products, it can be reused in subsequent
reactions. As shown in Table 2, it was found that the catalyst
can be reused four times without a significant loss of catalytic
2-(4-Chlorophenyl)-4, 5-diphenylimidazole 4b: m.p. 266–
268; IR (KBr) ν = 3204, 1613, 1492 cm−1; 1H NMR (CDCl3,
600 MHz): δ =12.77 (s, 1H), 7.24–7.54 (m, 12H), 8.09 (d, 2H)
ppm. 2-(4-Hydroxyphenyl)-4, 5-diphenylimidazole 4c: m.p.
258–259◦C; IR (KBr) ν = 3630, 3411, 3058, 1602, 1485 cm−1
;
1H NMR (CDCl3, 600 MHz): δ = 12.45 (s, 1H), 7.35–7.51 (m,
10H), 6.84 (d, 2H), 7.89 (d, 2H), 9.69 (s, 1H) ppm.
2-(2-Chlorophenyl)-4, 5-diphenylimidazole 4e: m.p. 194–
196◦C; IR (KBr) ν = 3436, 3063, 1602, 1637, 1202 cm−1
;
1H NMR (CDCl3, 600 MHz): δ =12.62 (s, 1H), 7.79–7.81 (d,
1H), 7.59–7.62 (d, 2H), 7.46–7.49 (d, 1H), 7.23–7.43 (m, 10H)
ppm.
2-(4-Methoxyphenyl)-4, 5-diphenylimidazole 4f: m.p. 233–
235◦C; IR (KBr) ν = 3409, 3029, 1613, 1493 cm−1; 1H NMR
(CDCl3, 600 MHz): δ = 12.52 (s, 1H), 8.00 (d, 2H), 7.51 (d,
4H), 7.33 (t, 4H), 7.27 (t, 2H), 7.03 (d, 2H), 3.79 (s, 3H) ppm.
2-(2,4-Dichlorophenyl)-4, 5-diphenylimidazole 4h: m.p.
177–178◦C; IR (KBr) ν = 3439, 3067, 1594, 1552, 1101 cm−1
;
TABLE 2
1H NMR (CDCl3, 600 MHz): δ = 12.7 (s, 1H), 7.83 (s, 1H),
The synthesis of 2, 4, 5-triarylimidazoles catalyzed by
copper(II) trifluoroacetate
7.78 (d, 1H), 7.23–7.58 (m, 12H) ppm.
Yield
(%)a
Mp (◦C) Mp (◦C)
Found Reported
Entry R
Product
RESULTS AND DISCUSSION
Firstly, the mixture of benzil, benzaldehyde and ammonium
acetate was chosen as the model to determine the optimal reac-
tion conditions for the synthesis of 2, 4, 5-triarylimidazoles. Sev-
eral solvents were tested in this reaction (Table 1). As shown in
Table 1, among the tested solvents such as H2O, EtOH, MeOH
and solvent-free system, the condensation reaction of benzil,
benzaldehyde and ammonium acetate gave highest yield in the
presence of a catalytic amount of Cu(TFA)2 at 100◦C for 4h
under solvent-free condition. Meanwhile, the molar ratio of cat-
alyst was also studied in this reaction. The results indicated that
the best yield is 93% in the presence of 0.01 mmol Cu(TFA)2
(Entry 5). However, in the absence of Cu(TFA)2, the reaction
didn’t yield any product after 4h (Entry 1).
1
H
4a 93,90b, 88b, 279 276–277[12]
85b,87b
2
3
4
5
6
7
8
9
4-ClC6H4
4-OHC6H4
4-CH3C6H4
2-ClC6H4
4b
4c
4d
4e
97
91
92
95
92
91
97
92
266–268 263–264[12]
258–259 260–261[18]
239–240 232–235[19]
194–196 196–197[19]
233–235 228–231[20]
316–318 313–315[9]
177–178 176–178[4]
224–226 227[10]
4-CH3OC6H4 4f
3-NO2C6H4
2,4-Cl2C6H3
4-NO2C6H4
4g
4h
4i
aIsolated yield; The same catalyst was used for each of the four
b
runs.

SYNTHESIS OF 2,4,5-TRIARYLIMIDAZOLES
147
activity, yielding the corresponding product with 90, 88, 85, and
87% isolated yields respectively.
A probable mechanism for the synthesis of 2, 4, 5-
triarylimidazoles was proposed in Scheme 2.
Preparation and N-alkylation studies of 2,4(5)-disubstituted imidazoles.
J. Org. Chem. 1983, 48,745–3750.
3. Kanazawa, C., Kamijo, S., and Yamamoto, Y. Synthesis of imidazoles
through the copper-catalyzed cross-cycloaddition between two different
isocyanides. J. Am. Chem. Soc. 2006, 128, 10662–10663.
4. Wang, L.M., Wang, Y.H., and Tian, H. Ytterbium triflate as an eficient cat-
alyst for one-pot synthesis of substituted imidazoles through three- compo-
nent condensation of benzil, aldehydes and ammonium acetate. J. Fluorine.
Chem. 2006, 127,1570–1573.
NH4OAc
Cu(TFA)2
NH3 + HOAc
5. Kidwai, M., Mothsra, P., Bansal, V., and Goyal, R. Efficient elemental
iodine catalyzed one-pot synthesis of 2,4,5-triarylimidazoles. Monatsh.
Chem. 2006, 137, 1189–1194.
6. Sharma, G.V.M., Jyothi, Y., and Lakshmi, P. S. Efficient room-temperature
synthesis of tri- and tetrasubstituted imidazoles catalyzed by ZrCl4. Synth.
Commun. 2006, 36, 2991–3000.
7. Srinivas, K., Vuppalapati, S.V.N., Biradar, D.O., and Nagarapu, L. Highly
efficient, one-pot, solvent-free synthesis of tetrasubstituted imidazoles using
HClO4-SiO2 as novel heterogeneous Catalyst. J. Mol. Catal. A: Chem.
2006, 266, 109–113.
8. Balalaie, S., and Arabanian, A. One-pot synthesis of tetrasubstituted imida-
zoles catalyzed by zeolite HY and silica gel under microwave irradiation.
Green Chem. 2000, 2, 274–276.
..
NH3
O
..
-H2O
R-CH NH
R-C-H
a
b
Cu(TFA)2
O
OH
..
NH3
Ph
O
O
Ph
Ph
Ph
Ph
H+
+
NH-CH-R
NH
NH
Ph
..
c
d
e
Cu(TFA)2
9. Heravi, M.M., Bakhtiari, K., Oskooie, H.A., and Taheri, S. Synthesis of
2, 4, 5-triaryl-imidazoles catalyzed by NiCl2·6H2O under heterogeneous
system. J. Mol. Catal. A: Chem. 2006, 263, 279–281.
10. Shaabani, A., and Rahmati, A. 1, 1, 3, 3-N, N, N’, N’-tetramethyl-
guanidinium trifluoroacetate ionic liquid–promoted efficient one-pot syn-
thesis of trisubstituted imidazoles. Synth. Commun. 2006, 36, 65–70.
11. Balalaie, S., Hashemi, M.M., and Akhbari, M. A novel one-pot synthesis
of tetrasubstituted imidazoles under solvent-free conditions and microwave
irradiation. Tetrahedron Lett. 2003, 44, 1709–1711.
OH
H
N
H
Ph
Ph
Ph
Ph
N
HC-R
N
-H+
-H2O
HC-R
C-R
N
Ph
NH
Ph
NH
+
+
h
g
f
SCH. 2. The possible mechanism for the synthesis of triarylimidazoles cat-
alyzed by Cu(TFA)2
12. Kidwai, M., Saxena, S., Ruby, and Rastogi, S. An efficient synthesis of
2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted-1h-imidazoles. Bull. Ko-
rean Chem. Soc. 2005, 26, 2051–2053.
13. Adibi, H., Samimi, H.A., and Beygzadeh, M. Iron(III) trifluoroacetate
and trifluoromethanesulfonate: Recyclable Lewis acid catalysts for one-
pot synthesis of 3,4-dihydropyrimidinones or their sulfur analogues and
1,4-dihydropyridines via solvent-free Biginelli and Hantzsch condensation
protocols. Catal. Commun. 2007, 8, 2119–2124.
14. Khosropour, A.R., Mohammadpoor-Baltork, I., and Ghorbankhani, H.
Bi(TFA)3 immobilized in [nbpy]FeCl4: An efficient catalyst system for
the one-pot synthesis of 4,6-diarylpyrimidin-2(1H)- ones. Catal. Commun.
2006, 7, 713–716.
15. Song, D.L., Wang, R.X., Chen, Y.L., Zhang, S.H., Liu, C.S., and Luo, G.X.
Copper(II) trifluoroacetate catalyzed synthesis of 3,4-dihydropyrimidin-
2(1H)-ones under solvent-free conditions. React. Kinet. Catal. Lett. 2008,
95, 385–390.
16. Song, D.L., Chen, Y.L., Wang, R.X., Liu, C.S., Jiang, H., and Luo, G.X.
Crossed-Aldol condensation of cycloalkanones with aromatic aldehydes
catalysed by copper(II) trifluoroacetate. Prep. Biochem. Biotechnol. 2009,
39, 201–207.
17. Yanagihara, N., Goton, T., and Ogura, T. Complex formations of silver(I)
trifluoroacetate and trifluoromethanesulfonate with benzene and cyclohex-
ene. Polyhedron, 1996, 15, 4349–4354.
18. Kidwai, M., Mothsra, P., Bansal, V., Somvanshi, R.K., Ethayathulla, A.S.,
Dey, S., and Singh, T.P. One pot synthesis of highly substituted imidazoles
using molecular iodine: a versatile catalyst. J. Mol. Catal. A: Chem., 2007,
265, 177–182.
In this procedure, ammonium acetate can be decomposed
into ammonia and acetate acid. Ammonia is the nitrogen source.
Copper (II) trifluoroacete becomes a strong Lewis acid because
cupric ion has empty 3d orbit and trifluoroacetate has strong
eletron-withdrawing function. It can activate the carbonyl group
(C=O) of aldehyde and decrease the energy of transition state.
So the reaction proceeded more easily. Lone-pair electrons of
nitrogen attacked activated carbonyl group of aldehyde (a) and
obtained aryl aldimine (b). The similar reaction can occur to
one carbonyl group of benzil (c) resulting in formation of α-
imino ketone (d). And then, α-imino ketone (d) attacked another
carbonyl group of α-imino ketone (d) and obtained intermediate
(e). This intermediate (e) transformed into the final product (g)
through internal cyclization, dehydration and dehydrogenation.
In conclusion, we have developed a simple method for syn-
thesizing 2, 4, 5-triarylimidazoles using copper(II) trifluoroac-
etate as an efficient Lewis acid catalyst. This method offers sev-
eral advantages including high yields and simple experimental
work-up procedure, which is proven to be a useful method for
the synthesis of 2, 4, 5-triarylimidazoles.
REFERENCES
19. Zhou, J.F., Song, Y.Z., Yang, Y.L., Zhu, Y.L., and Tu, S.J. One-step syn-
thesis of 2-Aryl-4,5-diphenylidazoles under microwave irradiation. Synth.
Commun. 2005, 35, 1369–1373.
20. Shaabani, A., and Rahmati, A. Silica sulfuric acid as efficient and recover-
able catalyst for the synthesis of trisubstituted imidazoles. J. Mol. Catal. A:
Chem. 2006, 249, 246–248.
1. Xia, M., and Lu, Y.D. A novel neutral ionic liquid-catalyzed solvent-free
synthesis of 2,4,5-trisubstituted imidazoles under microwave irradiation.
J. Mol. Catal. A: Chem. 2007, 265, 205–208.
2. Lipshutz, B.H., and Morey, M.C. An approach to the cyclopeptide alka-
loids (phencyclopeptines) via heterocyclic diamide/dipeptide equivalents.

Copyright of Synthesis & Reactivity in Inorganic, Metal-Organic, & Nano-Metal Chemistry is the property of
Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv
without the copyright holder's express written permission. However, users may print, download, or email
articles for individual use.