Boehmite nanoparticles, an efficient green catalyst for the multi-component synthesis of highly substituted imidazoles

Article abstract of DOI:10.1016/j.apcata.2013.07.027

Boehmite nanoparticles (AlOOH NPs) was found to be a highly active and green catalyst for the synthesis of highly substituted imidazoles under solvent-free conditions. This one-pot procedure is very simple, and affords good to excellent yields. Furthermore, the catalyst shows good thermal stability and recyclability. The catalyst was recycled for five runs without an appreciable loss in its catalytic activity.

Full text of DOI:10.1016/j.apcata.2013.07.027

Accepted Manuscript
Title: Boehmite nanoparticles, an efficient green catalyst for
the multi-component synthesis of highly substituted
imidazoles
Author: Ali Keivanloo Mohammad Bakherad Elahe Imanifar
Mahdi Mirzaee
PII:
S0926-860X(13)00425-0
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.apcata.2013.07.027
APCATA 14343
To appear in:
Applied Catalysis A: General
Received date:
Revised date:
Accepted date:
19-1-2013
13-7-2013
14-7-2013
Please cite this article as: A. Keivanloo, M. Bakherad, E. Imanifar, M. Mirzaee,
Boehmite nanoparticles, an efficient green catalyst for the multi-component
synthesis of highly substituted imidazoles, Applied Catalysis A, General (2013),
http://dx.doi.org/10.1016/j.apcata.2013.07.027
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Boehmite nanoparticles, an efficient green catalyst for the multi-component
synthesis of highly substituted imidazoles
Ali Keivanloo*, Mohammad Bakherad, Elahe Imanifar, Mahdi Mirzaee
School of Chemistry, Shahrood University of Technology, Shahrood,
Ph
O
O
Ph
Ph
O
N
AlOOH NPs
R
NH2
NH4OAc
+
+
+
Ar
H
solvent free
120 °C
Ph
Ar
N
R
20 - 90 min
R= aryl, alkyl
13 examples
Ph
Ph
Ph
O
O
O
N
AlOOH NPs
2 NH4OAc
+
+
Ar
H
solvent free
120 °C
Ph
Ar
N
H
10 - 75 min
8 examples
1
Page 1 of 25

Highlights
► Boehmite nanoparticles was prepared and used as a catalyst for synthesis of highly
substituted imidazoles. ► Boehmite nanoparticles is an efficient and reusable catalyst for
this process. ► This protocol is green, solvent-free and advantageous with high yields.
2
Page 2 of 25

Boehmite nanoparticles, an efficient green catalyst for the multi-component
synthesis of highly substituted imidazoles
Ali Keivanloo1, Mohammad Bakherad, Elahe Imanifar, Mahdi Mirzaee
School of Chemistry, Shahrood University of Technology, Shahrood, Iran
Abstract- Boehmite nanoparticles (AlOOH NPs) was found to be a highly active and green
catalyst for the synthesis of highly substituted imidazoles under solvent-free conditions. This
one-pot procedure is very simple, and affords good to excellent yields. Furthermore, the
catalyst shows good thermal stability and recyclability. The catalyst was recycled for five
runs without an appreciable loss in its catalytic activity.
Introduction
Multi-component reactions [1] (MCRs) have emerged as an efficient and powerful tool for
drug discovery [2] and modern synthetic organic chemistry due to their valued features such
as atom economy (describes the conversion efficiency of a chemical process in terms of all
atoms involved) and straightforward reaction design. They have also offered the opportunity
to construct target compounds by the introduction of diverse elements in a single chemical
event. Typically, purification of products resulting from these reactions is simple since all the
organic reagents employed are consumed and incorporated into the target compound [3].
MCRs leading to interesting heterocyclic scaffolds are particularly useful for the construction
of diverse chemical libraries of ‘drug-like’ molecules. The development of new MCRs and
1Corresponding Author. Fax: +98 2733395441.
E-mail addresses:akeivanloo@yahoo.com, keivanloo@shahroodut.ac.ir
3
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improving known multi-component reactions are an area of considerable current interest. One
such reaction is the synthesis of imidazoles.
The imidazole ring is a fertile source of biologically important molecules. Compounds
containing imidazole moiety have many pharmacological properties, and play important roles
in biochemical processes. They are well-known as inhibitors of P38MAP kinase, fungicides,
herbicides, anti-inflammatory agents, anti-thrombotic agents, plant growth regulators, and
therapeutic agents. In addition, they are used in photography as photosensitive compounds.
Some substituted triarylimidazoles are selective antagonists of the glucagon receptors and
inhibitors of the IL-1 biosynthesis [4].It is also the core structural skeleton in many important
biological molecules like histidine, histamine, and biotin, as well as several drug moieties
[5]such as trifenagrel, eprosartan, and losartan. Consequently, the development of novel
synthetic methods for their synthesis has attracted sustained interest in organic synthesis.
Numerous methods have been reported for the synthesis of highly substituted imidazoles
using various catalytic systems such as L-proline [6], ZrCl4 [7], InCl3-3H2O [8], HClO4–SiO2
[9], BF3SiO2 [10], K5CoW12O40-3H2O [11], heteropolyacids [12], silica gel, zeolite HY [13],
silica gel/NaHSO4 [14], molecular iodine [15], silica sulfuric acid [16], microwave irradiation
[17], ionic liquids [18], NiCl2-6H2O/Al2O3 [19], and cerium ammonium nitrate (CAN) [20].
However, the above-mentioned methods suffer from one or more disadvantages such as the
use of hazardous organic solvents, expensive moisture-sensitive catalysts, tedious work-up
conditions, long reaction time, and large volume of catalyst loadings. In the present work, we
used the boehmite nanoparticles (NPs) catalyst to contract these problems. Boehmite is
aluminum oxide hydroxide (γ-AlOOH) mineral, a component of aluminum ore bauxite
containing extra hydroxyl groups on its surface. Among different methods for the preparation
of boehmite NPs, a hydrothermal-assisted sol-gel technique was used here. It has some
advantages such as preparation in a one-pot process and processing at low temperature.
4
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Experimental
Preparation of the catalyst:
AlOOH NPs were prepared according to the following procedure: 10 ml of aluminum-2-
butoxide (2M) in 2-butanol was placed in a 300 ml stainless steel autoclave, which contained
50 ml of deionized water. The autoclave was then heated for 5 hours at 100˚C in an oven.
After cooling the autoclave, the powder produced was filtered off, and dried at 100˚C
overnight. This powder was used as the catalyst in the reactions.
All the reagents used were of general reagent grade. FT-IR spectra were obtained as
potassium bromide pellets in the range of 400-4000 cm-1 on a Bomem MB
1
seriesspectrometer. HNMR spectra were recorded on a Brucker BRX 400 AVANCE
spectrometer. Elemental analyses were performed on a Thermo Finnigan Flash EA
microanalyzer. TG/DSC measurements were performed using
a
STA-1500
thermogravimetric analyzer. Microscopic morphology of the products was visualized by
TEM (LEO 1455VP).
General procedure for the synthesis of 1,2,4,5-tetrasubstituted imidazoles:
Benzil (1 mmol), amine (1 mmol), aldehyde (1 mmol), ammonium acetate (1 mmol), and
AlOOH NPs (10 mol%) were placed in a test tube. The reactants were mixed and heated at
120°C for the appropriate time. The reaction progress was followed by TLC. After
completion of the reaction, the mixture was cooled down to room temperature. Hot ethanol
was then added to the mixture, which was subsequently filtered to remove the catalyst. After
evaporation of the solvent, the residue was crystallized from ethanol.
5
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General procedure for the synthesis of 2,4,5-trisubstituted imidazoles:
To a mixture of benzil (1 mmol) and aromatic aldehyde (1 mmol) in a test tube, was added
ammonium acetate (2.5 mmol) and AlOOH NPs (5 mol%). The reactants were mixed and
heated at 120°C for the appropriate time. The reaction progress was followed by TLC. After
completion of the reaction, the mixture was cooled down to room temperature. Hot ethanol
was then added to the mixture, which was subsequently filtered to remove the catalyst. After
evaporation of the solvent, the residue was crystallized from ethanol.
Characterization data for the new compounds are given below:
1-(3-chlorophenyl)-2,4,5-triphenyl-1H-imidazole (4e)
1
Mp = 205-207°C; HNMR (400 MHz, CDCl3): δ 6.85-6.87 (m, 1H, 1CH), 6.97-7.22 (m,
14H, 14CH), 7.35-7.37 (m, 2H, 2CH), 7.50-7.53 (m, 2H, CH); 13C NMR (100 MHz, CDCl3):
δ 126.75, 126.77, 127.37, 127.96, 128.20, 128.27, 128.55, 128.60, 128.89, 128.97, 129.99,
130.18, 130.29, 130.68, 131.10, 134.20, 134.58, 138.27, 138.49, 146.91. IR (KBr): 3050,
1585, 1478, 1560, 780, 765, 698 cm-1; Anal. Calcd. for C27H19ClN2: C, 79.70; H, 4.71; N,
6.88; Found: C, 79.68; H, 4.70; N, 8.90.
2,4,5-triphenyl-1-propyl-1H-imidazole (4i)
1
Mp = 75-77°C; HNMR (400MHz, CDCl3): δ 0.50 8 (t, J= 7.6, 3H, CH3), 1.29 (m, J= 7.6,
2H, CH2), 3.78 (t, J= 7.6, 2H, CH2), 7.03-7.14 (m, 3H, 3CH), 7.34-7.46 (m, 10H, 10CH),
7.62 (dd, J= 8.2, 1.6, 2H, 2CH); 13C NMR (100 MHz, CDCl3): δ 10.87, 23.90, 46.37, 126.19,
126.82, 127.77, 128.03, 128.62, 128.78, 129.04, 129.19, 129.67, 129.94, 131.03, 131.61,
134.63, 137.70, 147.70. IR (KBr): 3050, 2950, 2900, 1600, 1490, 1470, 1440, 770, 720, 693
cm-1; Anal. Calcd. for C24H22N2: C, 85.17; H, 6.55; N, 8.28; Found: C, 85.18; H, 6.56; N,
8.26.
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1-(2-methoxyethyl)-2,4,5-triphenyl-1H-imidazole (4k)
Mp = 121-123°C; 1HNMR (400 MHz, CDCl3): δ 2.96 (s, 3H, CH3), 3.14 (t, J=6.3, 2H, CH2),
4.04 (t, J=6.3, 2H, CH2), 7.04-7.14 (m, 3H, 3CH), 7.36-7.46 (m, 10H, 10CH), 7.67 (dd, J=
8.0, 1.6, 2H, 2CH); 13C NMR (100 MHz, CDCl3): δ 43.95, 58.73, 70.70, 126.28, 126.86,
127.86, 128.04, 128.62, 128.76, 128.90, 129.12, 129.46, 131.16, 131.29, 131.38, 134.47,
137.18, 148.12. IR (KBr): 3050, 2920, 1600, 1560, 1470, 1440, 1110, 1010, 780, 700 cm-1;
Anal. Calcd. for C24H22N2O: C, 81.33; H, 6.26; N, 7.90; Found: C, 81.30; H, 6.27; N, 7.92.
2,4,5-triphenyl-1-(propan-2-yl)-1H-imidazole(4l)
Mp = 159-161°C; 1HNMR (400 MHz, CDCl3): δ 1.26 (d, J= 6.8, 2H, CH2), 4.48 (m, J= 6.8,
1H, CH), 7.09-7.19 (m, 3H, 3CH), 7.45-7.50 (m, 10H, 10CH), 7.65 (dd, J=7.6, 2.0, 2H,
2CH); 13C NMR (100 MHz, CDCl3): δ 23.30, 49.38, 125.53, 126.04, 126.67, 127.93, 128.37,
128.74, 128.81, 128.92, 130.07, 132.23, 132.45, 132.52, 134.64, 137.89, 147.56. IR (KBr):
3050, 2950, 2900, 1650, 1595, 1440, 1338, 1210, 760, 720, 694 cm-1; Anal. Calcd. for
C24H22N2: C, 85.17; H, 6.55; N, 8.28; Found: C, 85.15; H, 6.56; N, 8.29.
1-butyl-2,4,5-triphenyl-1H-imidazole (4m)
1
Mp = 114-116°C; HNMR (400 MHz, CDCl3): δ 0.53 (t, J= 7.6, 3H, CH3), 0.90 (m, J= 7.6,
2H, CH2), 1.24 (m, J= 7.6, 2H, CH2), 3.81 (t, J= 7.6, 2H, CH2), 7.03-7.14 (m, 3H, 3CH),
7.34-7.46 (m, 10H, 10CH), 7.62 (dd, J= 8.0, 1.6, 2H, 2CH); 13C NMR (100 MHz, CDCl3): δ
13.27, 19.54, 32.54, 44.51, 126.20, 126.82, 128.04, 128.61, 128.81, 129.03, 129.22, 129.65,
130.99, 131.05, 131.54, 131.59, 134.61, 137.68, 147.67. IR (KBr): 3050, 2950, 2920, 1600,
1500, 1478, 1440, 768, 718, 696 cm-1; Anal. Calcd. for C25H24N2: C, 85.19; H, 6.86; N, 7.95;
Found: C, 85.21; H, 6.85; N, 7.97.
2,4,5-triphenyl-1-(tetrahydrofuran-2-ylmethyl)-1H-imidazole (4n)
7
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Mp = 142-144°C; 1HNMR (400 MHz, CDCl3): δ 1.42-1.58 (m, 4H, 2CH2), 3.30-3.33 (m, 1H,
CH), 3.40-3.46 (m, 1H, CH), 3.61-3.65 (m, 1H, CH), 3.85-3.99 (m, 2H, CH2), 7.04-7.14 (m,
3H, 3CH), 7.35-7.46 (m, 10H, 10CH), 7.67 (dd, J=7.6, 1.6, 2H, 2CH); 13C NMR (100 MHz,
CDCl3): δ 25.10, 28.29, 48.55, 67.63, 78.23, 126.21, 126.99, 127.97, 128.58, 128.72, 128.89,
129.05, 129.51, 139.73, 131.20, 131.51, 131.73, 134.59, 137.72, 148.29. IR (KBr): 3050,
2950, 2900, 2850, 1600, 1498, 1478, 1440, 1070, 770, 698 cm-1; Anal. Calcd. for C26H24N2O:
C, 82.07; H, 6.36; N, 7.36; Found: C, 82.10; H, 6.35; N, 7.34.
Results and discussion
In continuation of our studies on the synthesis of heterocyclic compounds [21] and their
methodology [22], we investigated the synthesis of highly substituted imidazoles in the
presence of heterogeneous catalysts under the thermal- and solvent-free conditions. Herein,
we report a mild and efficient one-pot protocol for the synthesis of highly substituted
imidazole derivatives by an MCR involving a benzil, an aldehyde, NH4OAc, and an amine
using a green and recyclable boehmite NPs catalyst under solvent-free conditions (Scheme
1). A thorough literature survey showed no reference concerning the use of boehmite NPs as
catalyst for the synthesis of heterocyclic compounds. Boehmite NPs were prepared via a
hydrothermal-assisted sol-gel process. The most promising property of this hydrothermally
processed boehmite NPs is the formation of a highly crystalline single-phase product with no
organic residue [23,24]. This was confirmed by the IR spectrum and XRD pattern, and also
the TG/DSC thermogram of this sample (Scheme 2). In the TG/DSC curve, there is no
exothermic peak at around 250˚C from ignition of the organic residue. There are also two
endothermic peaks below 100˚C and at around 450˚C in this thermogram. The first one is due
to the elimination of physically adsorbed water, and the other one is attributed to
dehydroxylation of boehmite. Calculation of particle size from the XRD pattern according to
8
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the Scherer equation shows 10 nm particles. This was confirmed by transmission electron
microscopy (TEM) image (Scheme 3). In this image, needle-shaped NPs are seen with over
50 nm long and up to 10 nm width. Efficient surface area of the boehmite NPs used in this
work was 326 m2/g.
To optimize the reaction conditions for the synthesis of 1,2,4,5-tetrasubstituted imidazoles,
the reaction of benzil, benzaldehyde, ammonium acetate, and benzylamine was used as a
model reaction. Reactions at different solvents, temperatures, and various amounts of catalyst
revealed that the best conditions were solvent-free at 120°C and 10 mol% of boehmite NPs as
catalyst (Table 1, entry 5).
We then turned our attention toward screening of catalyst loading as 5, 10, and 20 mol%. At
the first stage, we selected 5 mol% boehmite NPs to catalyze the model reaction, and found
that the 1,2,4,5-tetrasubstituted imidazoles 4b were obtained in 91% yield within 100 min at
120°C. Furthermore, by loading 10 and 20 mol% successively, we found that the product 4b
was obtained in 96% and 71% yield, respectively. Increasing the loaded amount of catalyst
from 10 to 20 mol% decreased the yield of product. This indicates that 10 mol% of the
catalyst produces the best results with respect to the product yield, as shown in Table 1.
In order to examine the solvent effect, the reaction was explored in EtOH, CH3CN, and
water. The reaction in solvents required relatively longer reaction times, and afforded low
yields of the product (Table 1, entries 1, 2, and 3). The reaction proceeded efficiently under
solvent-free conditions, and the 2,4,5-trisubstituted imidazoles were produced in high yields.
Next, for the synthesis of 2,4,5-trisubstituted imidazoles, optimization was made in the same
fashion. The best conditions were solvent-free at 120°C and 5 mol% of boehmite NPs as the
catalyst (Table 2, entry 4).
After optimizing the reaction conditions, in order to explore the scope and generality of this
protocol, various aldehydes and amines were used as substrates for the synthesis of 1,2,4,5-
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tetrasubstituted imidazoles and 2,4,5-trisubstituted imidazoles. The results obtained are
shown in Tables 3 and 4. These results show that the reactions are equally facile with both
electron-donating and electron-withdrawing substituents present on both the aromatic
aldehydes and aromatic amines, resulting in good-to-high yields of the corresponding
imidazoles. Aliphatic amines also reacted efficiently, affording the desired products in 78-
90% yield.
Structures of the new compounds were characterized by spectroscopic and elemental analysis
data. The known products were characterized by comparing their physical properties with
those reported in the literature.
The plausible mechanism for the synthesis of highly substituted imidazoles in the presence of
boehmite NPs can be explained as shown in Scheme 4. The reaction proceeds via the diamine
intermediate [A], which is formed by the activation of aldehyde carbonyl group by the acidic
hydroxyl groups on the surface of boehmite NPs through intermolecular hydrogen bonding.
Condensation of diamine with 1,2-diketone followed by dehydration, and then rearrangement
through the imino intermediate [B] yielded the desired product.
One of the purposes for designing this heterogeneous catalyst is to enable recycling of the
catalyst for use in subsequent reactions. The reusability of the catalyst was tested upon the
reaction of benzil (1.0 mmol), benzaldehyde (1.0 mmol), NH4OAc (1.0 mmol), and
cyclohexylamine (1.0 mmol), as the representative reactants, and in the presence of recycled
catalyst (10 mol%) in order to study the recyclability of this heterogeneous catalyst
(Table 5, entries 1, 2, 3, and 4). After each run, hot ethanol was added, and the product was
filtered. Then the residue, catalyst, was washed with hot ethanol and reused. Apparently,
treatment with hot ethanol removes tars more efficiently from the catalyst surface. In this
way, the boehmite NPs catalyst was reusable, although a few gradual decline in its activity
was observed.
10
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Conclusion
We demonstrated a simple method for the synthesis of highly substituted imidazoles using
boehmite NPs as a reusable, eco-friendly, inexpensive, and efficient catalyst. Short reaction
times, high yields, simple operation, and easy work-up are some advantages of this method.
The system works equally well for a wide variety of amines and aldehydes, and tolerates a
variety of functional groups. Furthermore, the catalyst shows good thermal stability and
recyclability. The catalyst was recycled for five runs without an appreciable loss of its
catalytic activity. These advantages make the process highly valuable from the synthetic and
environmental points of view.
Acknowledgement
The authors would like to thank the Research Council of Shahrood University of Technology
for the financial support of this work.
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Table 1: Condensation of benzil, benzaldehyde , benzylamine and ammonium acetate using
different catalysts and solventsa
Ph
NH2
N
O
Ph
O
Ph
Ph
Catalyst
solvent
N
+
2 NH4OAc
+
+
H
Ph
Ph
O
4b
Entry
Catalyst
Catalyst
loading
(mol%)
Solvent
Temp
(°C)
Time
(min)
Yield b
(%)
1
2
AlOOH (NPs)c
AlOOH (NPs)
AlOOH (NPs)
AlOOH (NPs)
AlOOH (NPs)
AlOOH (NPs)
AlOOH (NPs)
AlOOH (NPs)
ZnO (NPs)
ZnO (NPs)
ZnBr2
10
10
10
10
10
10
5
EtOH
CH3CN
H2O
80
80
120
120
120
50
50
20
35
96
96
83
91
71
10
10
65
25
46
11
3
100
140
120
100
120
120
100
120
120
80
4
neat
5
neat
neat
50
6
100
100
50
7
neat
8
20
10
20
10
20
10
20
neat
9
H2O
120
120
150
150
120
120
10
11
12
13
14
neat
neat
ZnBr2
EtOH
neat
NiCl2
120
80
NiCl2
EtOH
a Reaction conditions: benzil (1.0 mmol), benzaldehyde (1.0 mmol), benzylamine (1.0 mmol),
NH4OAc (1.0 mmol), catalyst and solvent (10 mL), or neat.
b Isolated yield.
c Nonoparticles
14
Page 14 of 25

Table 2:
Condensation of benzil, benzaldehyde ,ammonium acetate using different catalysts and
solventsa
Ph
O
O
Ph
O
N
Catalyst
solvent
2 NH4OAc
+
+
Ph
H
Ph
Ph
5a
Ph
N
H
Entry
Catalyst
Catalyst
loading
(mol%)
Solvent
Temp (°C)
Time
Yield b (%)
1
2
AlOOH (NPs)c
AlOOH (NPs)
AlOOH (NPs)
AlOOH (NPs)
AlOOH (NPs)
AlOOH (NPs)
AlOOH (NPs)
AlOOH (NPs)
ZnO (NPs)
ZnO (NPs)
ZnBr2
5
EtOH
CH3CN
H2O
80
80
120
120
120
80
56
67
50
98
94
72
85
98
5
5
3
5
100
120
120
120
100
140
100
120
80
4
5
neat
neat
5
10
20
5
80
6
neat
80
7
neat
80
8
5
neat
80
9
10
5
H2O
180
180
180
180
180
180
10
11
12
13
14
neat
10
22
38
25
60
10
5
EtOH
neat
ZnBr2
120
80
NiCl2
10
5
EtOH
neat
NiCl2
120
a Reaction conditions: benzil (1.0 mmol), benzaldehyde (1.0 mmol), NH4OAc (2.5 mmol),
catalyst and solvent (10 mL), or neat.
b Isolated yield.
c Nanoparticles
15
Page 15 of 25

Table 3
Boehmite NPs catalyzed synthesis of 1,2,4,5-tetrasubstituted imidazolesa
Ph
O
O
Ph
Ph
O
N
AlOOH NPs
120 °C
R
NH2
NH4OAc
+
+
H
+
Ar
Ph
Ar
N
R
Entry Aldehyde
Amine
Product
Time Yield b reference
(min)
(%)
CHO
NH2
N
N
1
50
94
8
4a
NH2
CHO
N
N
2
50
96
8
4b
4c
NH2
CHO
N
N
3
60
20
H C
3
86
92
12
9
CH3
CHO
NH2
N
4
N
Cl
Cl
4d
16
Page 16 of 25

CHO
NH2
N
5
N
20
93
new
Cl
Cl
4e
CHO
NO2
NH2
N
6
N
40
25
78
89
25
O N
2
4f
CHO
NH2
N
7
8
N
9
4g
CHO
NH2
N
N
35
30
30
80
88
90
9
NO2
O N
2
4h
CHO
NH2
N
N
H3C
9
new
CH CH CH
3
2
2
4i
CHO
NH2
N
O
10
new
H3C
N
CH CH OCH
3
2
2
4k
17
Page 17 of 25

CHO
H3C
H3C
N
NH2
11
N
90
30
85
86
new
new
CH(CH )
3 2
4l
CHO
NH2
N
12
13
H3C
N
CH CH CH CH
3
2
2
2
4m
CHO
O
N
NH2
50
78
new
N
O
4n
a Reaction conditions: benzil (1.0 mmol), aldehyde (1.0 mmol), NH4OAc (1.0 mmol), amine
(1.0 mmol) and boehmite NPs (10 mol%) at 120 °C.
b Isolated yield.
18
Page 18 of 25

Table 4:
Boehmite NPs catalyzed synthesis of 2,4,5-trisubstituted imidazolesa
Ph
O
Ph
O
N
AlOOH NPs
120 °C
2 NH4OAc
+
+
Ar
H
Ph
Ar
Ph
O
N
H
Entry
Aldehyde
Product
Time
(min)
Yield b, c
(%)
CHO
1
N
40
98
N
H
5a
CHO
2
3
N
15
45
79
88
N
H
NO2
O
N
2
5b
5c
CHO
N
N
H
H C
3
CH3
CHO
Cl
Cl
4
5
N
40
10
95
86
N
H
5d
CHO
N
N
H
Cl
5e
Cl
19
Page 19 of 25

CHO
N
Cl
6
Cl
75
83
N
H
Cl
Cl
5f
CHO
N
7
8
50
65
85
78
N
H
H CO
3
OCH3
5g
CHO
H3CO
N
N
H
H CO
3
5h
a Reaction conditions: benzil (1.0 mmol), aldehyde (1.0 mmol), NH4OAc (2.5 mmol), and
boehmite NPs (5 mol%) at 120 °C.
b Isolated yield.
c Reference 6
20
Page 20 of 25

Table 5:
Condensation of benzil, benzaldehyde ,ammonium acetate and benzylamine using recycled
catalysts.
Entry
Nomber of cycles
Yield b (%)
1
2
1
2
92
88
3
4
3
5
85
82
a Reaction conditions: benzil (1.0 mmol), benzaldehyde (1.0 mmol), NH4OAc (1.0 mmol),
cyclohexylamine (1.0 mmol) and recycled catalyst (10 mol%), 25 min.
b Isolated yield.
21
Page 21 of 25

Scheme 1:
Synthesis of 1,2,4,5-tetrasubstituted/2,4,5-trisubstituted imidazoles by a multi-component
reaction of benzil, aldehydes, NH4OAc, and amine by boehmite NPs catalyst under solvent-
free conditions.
Ph
O
O
Ph
Ph
O
N
AlOOH NPs
R
NH2
NH4OAc
+
+
+
Ar
H
solvent free
120 °C
Ph
Ar
N
R
20 - 90 min
3
2
1
4
R= aryl, alkyl
Ph
Ph
Ph
O
O
O
N
AlOOH NPs
2 NH4OAc
+
+
Ar
H
solvent free
120 °C
Ph
Ar
N
H
10 - 75 min
5
2
1
22
Page 22 of 25

Scheme 2:
TG/DSC thermogram of nano-boehmite prepared by hydrothermal assisted sol-gel proceesing
at 100˚C.
23
Page 23 of 25

Scheme 3:
TEM image of nano-boehmite prepared by hydrothermal assisted sol-gel proceesing at
100˚C.
24
Page 24 of 25

Scheme 4:
Proposed mechanism for the formation of 1,2,4,5-tetrasubstituted/2,4,5-trisubstituted imidazoles
from benzil, aldehydes, NH4OAc, and amine in the presence of boehmite NPs.
O
O
H
O
O
O
H
O
Al
O
Al
O
Al
O
Al
O
Al
O
Al
O
H
H
O
H
H
O
Ph
Ph
NH2
NH
N
H
NH3
Ph
O
H
N+
R
Ph
R
- H2O
NH2
R
-2H2O
(B)
(A)
R = H, Alkyl, Aryl
- H+
Ph
N
Ph
N
R
25
Page 25 of 25