Zinc (II) [tetra(4-methylphenyl)] porphyrin: A novel and reusable catalyst for efficient synthesis of 2,4,5-trisubstituted imidazoles under ultrasound irradiation

Article abstract of DOI:10.5012/jkcs.2011.55.5.787

An efficient three-component one-step synthesis of 2,4,5-trisubstituted imidazoles by condensation reaction of 1,2-diketones or a-hydroxyketones with aromatic aldehydes and ammonium acetate using Zinc (II) [tetra (4-methylphenyl)] porphyrin as a novel and reusable catalyst under ultrasound irradiation at ambient temperature is described. In this method, a-hydroxyketones as well as 1,2-diketones were converted to their corresponding 2,4,5-trisubstituted imidazoles in excellent yields. Copyright

Full text of DOI:10.5012/jkcs.2011.55.5.787

Journal of the Korean Chemical Society
2011, Vol. 55, No. 5
Printed in the Republic of Korea
http://dx.doi.org/10.5012/jkcs.2011.55.5.787
Zinc (II) [tetra(4-methylphenyl)] Porphyrin: a Novel and Reusable Catalyst
for Efficient Synthesis of 2,4,5-trisubstituted Imidazoles Under
Ultrasound Irradiation
†
*
Javad Safari , Shiva Dehghan Khalili, Sayed Hossein Banitaba, and Hossein Dehghani
Department of Organic Chemistry, College of Chemistry, University of Kashan, 87317-51167, Kashan, Iran.
*
E-mail: Safari_jav@yahoo.com, Safari@kashanu.ac.ir.
†
Department of Inorganic Chemistry, College of Chemistry, University of Kashan, 87317-51167, Kashan, Iran
(Received May 29, 2011; Accepted July 27, 2011)
ABSTRACT: An efficient three-component one-step synthesis of 2,4,5-trisubstituted imidazoles by condensation reaction of
1,2-diketones or α-hydroxyketones with aromatic aldehydes and ammonium acetate using Zinc (II) [tetra (4-methylphenyl)]
porphyrin as a novel and reusable catalyst under ultrasound irradiation at ambient temperature is described. In this method,
α-hydroxyketones as well as 1,2-diketones were converted to their corresponding 2,4,5-trisubstituted imidazoles in excellent
yields.
Key words: Three-component condensation, 2,4,5-Trisubstituted imidazoles, Zinc (II) [tetra (4-methylphenyl)] porphyrin,
Ultrasound irradiation
tuted imidazoles have received much attention because of
their wide range of pharmaceutical and biological prop-
INTRODUCTION
15
16,17
Multicomponent reactions (MCRs) have drawn great
interest enjoying an outstanding status in modern organic
synthesis and medicinal chemistry because they are one-
pot processes bringing together three or more compo-
erties such as antitumor, anti-inflammatory,
anti-
allergic, analgesic and antibacterial effects. Various
substituted imidazoles act as inhibitors of p38 MAP
18
19
20
21
kinase and B-Raf kinase and glucagon receptors.
22
23
1-4
nents and show high atom economy and high selectivity.
Accordingly, a number of synthetic methods have been
reported for the construction of this important structure.
Generally 2,4,5-trisubstituted imidazoles are synthesized
by three-component cyclocondensation of 1,2-diketone,
α-hydroxyketone or α-ketomonoxime with an aldehyde
and ammonium acetate. A variety of catalysts including
protonic and Lewis acid catalysts have been introduced
for synthesis of 2,4,5-trisubstituted imidazoles such as
MCRs have great contribution in convergent synthesis of
complex and important organic molecules from simple
and readily available starting materials, and have emerged
5-7
as powerful tools for drug discovery. Ultrasound has
increasingly been used in organic synthesis. A large num-
ber of ultrasonic reactions can be carried out in higher
8-11
yield, shorter reaction time or milder conditions. The
24
25
26
27
H2SO4, H3PO4, NiCl2·6H2O, Yb(OTf)3, InCl3·3H2O,
28
phenomenon responsible for the beneficial effects of
ultrasound on chemical reactions is cavitation. During the
rarefaction cycle of the wave, the molecules of the liquid
are separated, generating bubbles that subsequently col-
29
I2, polymer-supported ZnCl2, oxalic acid, boric
30
31
32
33
34
acid, p-toluenesulfonic acid, L-proline, L-proline tri-
35
flate, Cu(NO3)2-zeolite, and ionic liquids.
36
37-39
Despite
12
lapse in the compression cycle. These rapid and violent
their potential utility, most of these methods have a num-
ber of drawbacks including poor yields, high temperature,
use of toxic catalyst, strongly acidic conditions and the
requirement for harsh reaction conditions. Therefore, the
development of facile and environmentally benign method
for the synthesis of biologically active 2,4,5-trisubstituted
imidazoles is the necessary part of organic synthesis.
implosions generate short-lived regions with tempera-
o
tures of roughly 5000 C, pressures of about 1000 atm and
o
heating and cooling rates above 10 billion C per sec-
13
ond. Such localized hot spots can be thought as microre-
actors in which the energy of sound is transformed into a
useful chemical form.
The imidazole ring system is one of the most important
substructures found in a large number of natural products
Electron-deficient metalloporphyrins have been used as
40-44
mild and non-toxic Lewis acid catalysts.
In continu-
14
and pharmacologically active compounds. Multisubsti-
ation of our interest on the synthesis of 2,4,5-trisubsti-
-787-

788
Javad Safari, Shiva Dehghan Khalili, Sayed Hossein Banitaba, and Hossein Dehghani
Scheme 1. One-pot synthesis of 2,4,5-trisubstituted imidazoles catalyzed by [ZnT(4-CH3)PP] under ultrasound irradiation at ambient
temperature.
45,46
tuted imidazoles,
we decided to explore ability of
output power of 350 W. The reaction ask was located in
the maximum energy area in the cleaner, where the sur-
face of reactants (reaction vessel) is slightly lower than the
level of the water and the temperature of the water bath
metalloporphyrins in the synthesis of 2,4,5-trisubstituted
imidazoles for the first time. Therefore, Zinc (II) [tetra (4-
methylphenyl)] porphyrin was used as a mild Lewis acid
catalyst for the three-component one-step synthesis of
2,4,5-trisubstituted imidazoles by condensation reaction
of 1,2-diketones or α-hydroxyketones with aromatic alde-
hydes and ammonium acetate under ultrasound irradia-
tion at ambient temperature (Scheme 1).
o
was controlled at 25 C.
General procedure for the synthesis of 2,4,5-trisub-
stituted imidazoles catalyzed by [ZnT(4-CH3)PP] under
ultrasound irradiation
A mixture of benzoin or benzil derivatives (1 mmol),
aldehyde (1 mmol), ammonium acetate (0.31 g, 4 mmol)
and [ZnT(4-CH3)PP] (3 µmol %) in 10 ml ethanol was
taken in a 50 ml conical flask and the reaction mixture was
irradiated in the water bath of the ultrasonic cleaner at
EXPERIMENTAL
Chemical reagents in high purity were purchased from
the Merck Chemical Company. All materials were of
commercial reagent grade. Zinc (II) [tetra (4-methylphe-
o
25 C for a period as indicated in Table 2 and Table 3. The
nyl)] porphyrin was prepared and metallated according to
progress of reaction was followed by TLC. After com-
pletion of reaction, the solvent was evaporated, then the
solid residue was purified by column chromatography
(eluent petroleum ether: ethyl acetate=9:2) on silica gel to
give analytically pure products in good to excellent yield
and were fully characterized by spectroscopic methods
47,48
the literature.
Melting points were determined in open
capillaries using an Electrothermal Mk3 apparatus and are
uncorrected. FT-IR spectra were obtained with potassium
-1
bromide pellets in the range 400-4000 cm with a Perkin-
1
13
Elmer 550 spectrometer. H NMR and C NMR spectra
were recorded with a Bruker DRX-400 spectrometer at
400 and 100 MHz respectively. NMR spectra were obtained
in DMSO-d6 solutions and are reported as parts per mil-
lion (ppm) downfield from tetramethylsilane as internal
standard. The abbreviations used are: singlet (s), doublet
(d), triplet (t) and multiplet (m). Elemental analysis (C, H,
N) was performed with a Carlo Erba Model EA 1108 ana-
lyzer or a Perkin-Elmer 240c analyzer, and results agreed
favorably with calculated values. The UV-vis measurements
were obtained with a GBC cintra 6 UV-vis spectropho-
1
13
such as IR, H NMR, C NMR and element analyses (C,
H, N) and have been identified by the comparison of the
reported spectral data. The spectral data for new com-
pounds are presented below.
Spectroscopic data for new 2,4,5-trisubstituted imi-
dazoles
3-[4,5-bis(4-methoxyphenyl)-1H-imidazol-2-yl]phe-
-1
nol (5n). Cream solid. IR (KBr) (υmax/cm ): 3415 (N-H),
1
3338 (O-H), 1613 (C=C), 1500 (C=N), 1247 (C-O); H
®
tometer. Ultrasonication was performed in a EUROSONIC
NMR (400 MHz, DMSO-d6): δH 12.42 (s, 1H, NH), 9.52
(s, 1H, OH), 7.38-7.49 (m, 6H, Ar-H), 7.23 (t, 1H, J=8.0
4D ultrasound cleaner with a frequency of 50 kHz and an
Journal of the Korean Chemical Society

Synthesis of Triaryl Imidazoles Using [ZnT(4-CH3)PP] as catalyst under Ultrasound Irradiation
789
1
Hz, Ar-H), 7.00 (d, 2H, J=8.4 Hz, Ar-H), 6.86 (d, 2H, J=
8.4 Hz, Ar-H), 6.74 (dd, 1H, J=8.0, 2.8 Hz, Ar-H), 3.78 (s,
(N-H), 1604 (C=C), 1519 (C=N), 1248 (C-O); H NMR
(400 MHz, DMSO-d6): δH 12.50 (s, 1H, NH), 7.45 (d, 2H,
J=7.6 Hz, Ar-H), 7.40 (d, 2H, J=8.0 Hz, Ar-H), 7.26 (s,
2H, Ar-H), 7.0 (d, 2H, J=8.0 Hz, Ar-H), 6.87 (d, 2H, J=
8.0 Hz, Ar-H), 6.48 (s, 1H, Ar-H), 3.80 (s, 3H, OMe), 3.79
13
3H, OMe), 3.73 (s, 3H, OMe) ppm; C NMR (100 MHz,
DMSO-d6): δC 159.2, 158.4, 158.0, 145.4, 136.7, 132.2,
130.2, 130.1, 128.6, 128.4, 127.5, 124.0, 116.4, 115.6, 114.5,
114.1, 112.5, 55.6, 55.5 ppm; Anal. Calcd. for C23H20N2O3: C,
74.18; H, 5.41; N, 7.52 %. Found: C, 74.16; H, 5.39; N,
7.49%.
13
(s, 3H, OMe), 3.73 (s, 6H, OMe), ppm; C NMR (100
MHz, DMSO-d6): δC 161.2, 158.9, 158.1, 145.1, 137.0, 134.3,
132.8, 130.1, 128.8, 128.6, 124.0, 114.3, 114.1, 103.4,
100.8, 55.8, 55.5 ppm; Anal. Calcd. for C25H24N2O4: C,
72.10; H, 5.81; N, 6.73%. Found: C, 72.09; H, 5.79; N,
6.72%.
2-(3-nitrophenyl)-4,5-bis(4-methoxyphenyl)-1H-imi-
-1
dazole (5o). Yellow solid. IR (KBr) (υmax/cm ): 3428 (N-
H), 1615 (C=C), 1523 (C=N), 1460 (N=O), 1348 (N-O),
1
1249 (C-O); H NMR (400 MHz, DMSO-d6): δH 12.92 (s,
2-(4-methoxyphenyl)-4,5-bis(4-fluorophenyl)-1H-imi-
-1
dazole (5s). White solid. IR (KBr) (υmax/cm ): 3427 (N-
1H, NH), 8.92 (s, 1H, Ar-H), 8.50 (d, 1H, J=8.2 Hz, Ar-
H), 8.20 (d, 1H, J=8.2 Hz, Ar-H), 7.75 (t, 1H, J=8.2 Hz,
Ar-H), 7.47 (d, 2H, J=8.4 Hz, Ar-H), 7.43 (d, 2H, J=8.4
Hz, Ar-H), 7.00 (d, 2H, J=8.4 Hz, Ar-H), 6.90 (d, 2H, J=
8.4 Hz, Ar-H), 3.80 (s, 3H, OMe), 3.75 (s, 3H, OMe) ppm;
1
H), 1613 (C=C), 1504 (C=N), 1248 (C-O); H NMR (400
MHz, DMSO-d6): δH 12.53 (s, 1H, NH), 8.0 (d, 2H, J=8.4
Hz, Ar-H), 7.48-7.53 (m, 4H, Ar-H), 7.28 (t, 2H, J=8.8
Hz, Ar-H), 7.14 (t, 2H, J=8.8 Hz, Ar-H), 7.03 (d, 2H, J=
13
13
8.4 Hz, Ar-H), 3.80 (s, 3H, OMe) ppm; C NMR (100
C NMR (100 MHz, DMSO-d6): δC 159.4, 158.6, 148.8,
143.1, 137.5, 132.5, 131.4, 130.8, 130.2, 128.8, 128.7, 127.9,
123.5, 122.7, 119.7, 114.6, 114.1, 55.7, 55.5 ppm; Anal.
Calcd. for C23H19N3O4: C, 68.82; H, 4.77; N, 10.47%.
Found: C, 68.79; H, 4.75; N, 10.44%.
MHz, DMSO-d6): δC 163.0 (C-F, d, J=243.0 Hz), 160.6
(C-F, d, J=241.0 Hz), 159.0, 146.2, 146.2, 133.5 (d, J=
10.0 Hz), 130.2 (d, J=9.0 Hz), 129.5, 129.3, 127.5, 123.5,
117.2 (d, J=22.0 Hz), 115.8 (d, J=21.0 Hz), 114.5, 112.3,
55.6 ppm; Anal. Calcd. for C22H16F2N2O: C, 72.92; H,
4.45; N, 7.73%. Found: C, 72.89; H, 4.43; N, 7.71%.
3-[4,5-bis(4-fluorophenyl)-1H-imidazol-2-yl]phenol
2-(3-methoxyphenyl)-4,5-bis(4-methoxyphenyl)-1H-
-1
imidazole (5p). White solid. IR (KBr) (υmax/cm ): 3430
1
(N-H), 1608 (C=C), 1519 (C=N), 1246 (C-O); H NMR
-1
(5t). Golden crystalline solid. IR (KBr) (υmax/cm ): 3437
(400 MHz, DMSO-d6): δH 12.50 (s, 1H, NH), 7.64 (d, 1H,
J=8.0 Hz, Ar-H), 7.62 (s, 1H, Ar-H), 7.36-7.46 (m, 5H,
Ar-H), 7.00 (d, 2H, J=8.4 Hz, Ar-H), 6.91 (dd, 1H, J=8.4,
1
(N-H), 3300 (O-H), 1605 (C=C), 1517 (C=N); H NMR
(400 MHz, DMSO-d6): δH 12.62 (s, 1H, NH), 9.54 (s, 1H,
OH), 7.45-7.58 (m, 6H, Ar-H), 7.30 (t, 2H, J=7.6 Hz, Ar-
H), 7.24 (d, 1H, J=8.0 Hz, Ar-H), 7.15 (t, 2H, J=8.3 Hz,
2.2 Hz, Ar-H), 6.87 (d, 2H, J=8.4 Hz, Ar-H), 3.82 (s, 3H,
13
OMe), 3.79 (s, 3H, OMe), 3.74 (s, 3H, OMe) ppm;
C
13
Ar-H), 6.78 (d, 1H, J=8.0 Hz, Ar-H) ppm; C NMR (100
NMR (100 MHz, DMSO-d6): δC 160.0, 158.9, 158.2, 145.1,
136.2, 132.3, 130.2, 130.2, 128.6, 128.2, 127.2, 124.1,
117.0, 115.5, 114.4, 114.3, 110.5, 55.6, 55.5, 55.5 ppm;
Anal. Calcd. for C24H22N2O3: C, 74.59; H, 5.74; N, 7.25%.
Found: C, 74.58; H, 5.75; N, 7.24%.
MHz, DMSO-d6): δC 162.2 (C-F, d, J=243.0 Hz), 161.6
(C-F, d, J=243.0 Hz), 160.1, 145.9, 136.7, 132.0, 131.9,
131.1 (d, J=7.0 Hz), 130.3, 129.4 (d, J=7.0 Hz), 127.8,
127.6, 118.1, 116.1 (d, J=21.0 Hz), 115.6 (d, J=22.0 Hz),
114.7, 110.7 ppm; Anal. Calcd. for C21H14F2N2O: C, 72.41;
H, 4.05; N, 8.04%. Found: C, 72.38; H, 4.04; N, 8.02%.
5-[4,5-bis(4-methoxyphenyl)-1H-imidazol-2-yl]-2-
-1
methoxyphenol (5q). Ash-gray solid. IR (KBr) (υmax/cm ):
3424 (N-H), 3320 (O-H), 1615 (C=C), 1504 (C=N), 1249
1
(C-O); H NMR (400 MHz, DMSO-d6): δH 12.26 (s, 1H,
RESULTS AND DISCUSSION
NH), 9.11 (s, 1H, OH), 7.52 (s, 1H, Ar-H), 7.37-7.46 (m,
6H, Ar-H), 6.98 (d, 2H, J= 8.4 Hz, Ar-H), 6.86 (d, 2H, J=
8.4 Hz, Ar-H), 3.80 (s, 3H, OMe), 3.78 (s, 3H, OMe), 3.73
To achieve suitable conditions for the synthesis of 2,4,5-
trisubstituted imidazoles, various reaction conditions have
been investigated in the reaction of 4-methoxybenzalde-
hyde 3b, benzil 1a, and ammonium acetate as a model
reaction. We examined the effect of different solvents
such as water, EtOH, THF, DMF, CH3CN, and CHCl3 on a
13
(s, 3H, OMe) ppm; C NMR (100 MHz, DMSO-d6): δC
159.1, 158.7, 148.4, 146.9, 145.6, 129.8, 129.2, 128.4, 126.3,
126.0, 123.5, 124.1, 116.8, 114.3, 114.0, 113.2, 112.5, 56.1,
55.5, 55.1 ppm; Anal. Calcd. for C24H22N2O4: C, 71.63; H,
5.51; N, 6.96%. Found: C, 71.61; H, 5.49; N, 6.95%.
2-(3,5-dimethoxyphenyl)-4,5-bis(4-methoxyphenyl)-
o
model reaction under ultrasound irradiation at 25 C
(Table 1, entry 1-6). The reaction using EtOH as solvent
gave the best result and 5b was obtained in 80% yield
-1
1H-imidazole (5r). White solid. IR (KBr) (υmax/cm ): 3420
2011, Vol. 55, No. 5

790
Javad Safari, Shiva Dehghan Khalili, Sayed Hossein Banitaba, and Hossein Dehghani
a
Table 1. Optimization of the reaction conditions for synthesis of 2,4,5-trisubstituted imidazoles
b
Yield (%)
Entry
1
Solvent
Water
EtOH
THF
Method
Ultrasound
Ultrasound
Ultrasound
Ultrasound
Ultrasound
Ultrasound
High speed stirring
Ultrasound
Ultrasound
Ultrasound
Ultrasound
Ultrasound
Ultrasound
Catalyst (µmol %)
Time (min)
2.0
2.0
2.0
2.0
2.0
2.0
2.0
None
1.0
1.5
2.5
3.0
70
70
70
70
70
70
120
70
70
70
70
70
70
20
80
42
35
40
53
35
42
70
77
88
96
96
2
3
4
DMF
5
CH3CN
CH3Cl
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
6
7
8
9
10
11
12
13
4.0
a
b
Benzil (1 mmol), 4-methoxybenzaldehyde (1 mmol), NH4OAc (4 mmol), Isolated yield based on aldehyde.
within 70 min (Table 1, entry 2). To demonstrate the effect
of ultrasound, the synthesis of 5b as a model was inves-
tigated under high speed stirring conditions. The reaction
failed to give low yield under high speed stirring condi-
tions (Table 1, entry 7). It was apparent that the ultrasound
irradiation accelerates this transformation under ambient
conditions. To delineate the role of catalyst, the reaction
was investigated with and without catalyst. As shown, in
the absence of catalyst the yield of the product was found
to be low (Table 1, entry 8). On the other hand, ultrasound
irradiation and the catalyst have a great influence on the
model reaction. As indicated (Table 1, entry 12) the best
result have been obtained with amount of 3 µmol% [ZnT
(4-CH3)PP] in EtOH under ultrasound irradiation at ambi-
ent temperature and the yield of reaction with increasing
the amount of [ZnT(4-CH3)PP] is not increased (Table 1,
Table 2. One-pot synthesis of of 2,4,5-trisubstituted imidazoles catalyzed by [ZnT(4-CH3)PP] under ultrasound irradiation at ambient tem-
a
perature
b
Yield (%)
Entry
1
Benzil
1a
R1, R2
H
Aldehyde
3a
R3
H
Time (min)
70
Product
5a
M.p. C (lit)
29
17
17
17
94
270-272 (272-273)
228-231 (230-232)
230-233 (232-235)
301-303 (303-304)
2
1a
H
3b
3c
p-OMe
70
5b
5c
96
3
1a
H
p-Me
70
95
4
1a
H
3d
3e
m-Br
70
5d
5e
93
37
5
1a
H
m-OH
70
92
259 (260-261)
29
46
46
46
6
1a
H
3f
m-NO2
70
5f
90
269-271 (265-267)
259-262 (259-261)
214-216 (215-216)
256-257 (254-256)
7
1a
H
3g
3h
3i
m-OMe
m-OH, p-OMe
m-OMe, m-OMe
H
70
5g
5h
5i
92
8
1a
H
70
97
9
1a
H
70
93
17
10
11
12
13
14
15
16
17
18
19
20
1b
1b
1b
1b
1b
1b
1b
1b
1b
1c
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
F
3a
80
5j
90
201.5-203 (202-204)
17
3b
3c
p-OMe
80
5k
5l
93
183-185 (184-186)
186-188 (185-187)
248-251 (250-252)
230-232
17
17
p-Me
80
93
3d
3e
m-Br
80
5m
5n
5o
5p
5q
5r
90
m-OH
80
91
3f
m-NO2
80
88
240-242
3g
3h
3i
m-OMe
m-OH, p-OMe
m-OMe, m-OMe
p-OMe
80
91
234-236
80
95
132-134
80
92
195-197
3b
3e
50
5s
98
248-250
1c
F
m-OH
50
5t
95
271-273
a
b
Benzil (1 mmol), Aldehyde (1 mmol), NH4OAc (4 mmol), [ZnT(4-CH3)PP] (3 µmol %), Isolated yield based on aldehyde.
Journal of the Korean Chemical Society

Synthesis of Triaryl Imidazoles Using [ZnT(4-CH3)PP] as catalyst under Ultrasound Irradiation
791
entry 13).
In order to evaluate the generality of the process, sev-
eral diversified examples illustrating the present method
for the synthesis of 2,4,5-trisubstituted imidazoles 5a-t were
studied. The reaction of benzil with various aromatic alde-
hydes bearing electron-withdrawing groups or electron-
releasing groups and ammonium acetate was carried out
in the presence of [ZnT(4-CH3)PP] as catalyst under ultra-
sound irradiation at ambient temperature (Table 2). As
shown the process tolerates both electron withdrawing
and electron donating substituents on the aldehydes. The
aryl group substituted with different positions of the aro-
matic ring has not shown much effect on the formation of
the final product. We also concentrated our study on dif-
ferent benzils (4,4'-difluorobenzil, 4,4'-dimethoxybenzil)
(Table 2). The results illustrate the high ability of this
method for the synthesis of 2,4,5-triarylimidazoles with
different groups.
Scheme 2. Plausible mechanism.
activity. The nature of the recovered catalyst was moni-
tored by its UV-Vis spectrum Fig. 1, in which no change
was observed in its spectrum and since the catalyst
retained its activity in the condensation reaction.
The reusability of the [ZnT(4-CH3)PP] catalyst was stud-
ied using multiple synthesis of 2,4,5-trisubstituted imida-
zoles. The results showed that after reusing the catalyst for
several times, no change was observed in its catalytic
We have not established an exact mechanism for the for-
mation of 2,4,5-trisubstituted imidazoles, however, a rea-
sonable possibility is shown in Scheme 2. A plausible
mechanism for these reactions is that aldehyde and 1,2-
diketone are first activated by [ZnT(4-CH3)PP] to afford
A and B respectively. Then, imine intermediate (A), con-
denses further with the carbonyl carbon of 1,2 diketone
imine (B) and formation of carbocation (C) followed by
attack imine nitrogen to positive center and dehydration to
afford the iso-imidazole (E), which rearranges via [1,5]
sigmatropic shift to the required imidazole (Scheme 2).
The high catalytic activity of [ZnT(4-CH3)PP] catalyst
in the synthesis of trisubstituted imidazoles by conden-
sation reaction of benzil derivatives, aromatic aldehyde and
ammonium acetate under ultrasound irradiation, prompted
Fig. 1. UV-Vis spectrum of [ZnT(4-CH3)PP]: before reaction
(solid line) and after reaction (dashed line).
a
Table 3. Synthesis of 2,4,5-trisubstituted imidazoles using benzoin derivatives
b
Yield (%)
Entry
Benzoin
2a
R1, R2
H
Aldehyde
R3
H
Product
5a
Time (min)
90
1
2
3a
3b
3d
3h
3i
88
90
86
90
87
86
87
85
88
87
2a
H
p-OMe
5b
90
3
2a
H
m-Br
5d
90
4
2a
H
m-OH, p-OMe
m-OMe, m-OMe
H
5h
90
5
2a
H
5i
90
6
2b
OMe
OMe
OMe
OMe
OMe
3a
3b
3d
3h
3i
5j
100
100
100
100
100
7
2b
p-OMe
5k
8
2b
m-Br
5m
5q
9
2b
m-OH, p-OMe
m-OMe, m-OMe
10
2b
5r
a
b
Benzoin (1 mmol), Aldehyde (1 mmol), NH4OAc (4 mmol), [ZnT(4-CH3)PP] (3 µmol %), Isolated yield based on aldehyde.
2011, Vol. 55, No. 5

792
Javad Safari, Shiva Dehghan Khalili, Sayed Hossein Banitaba, and Hossein Dehghani
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The synthesis of different trisubstituted imidazoles with
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the corresponding trisubstituted imidazoles were obtained
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In summary an efficient and convenient procedure for
the three-component one-step synthesis of 2,4,5-trisub-
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efficiently converted to their corresponding 2,4,5-trisub-
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