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Applied Catalysis A: General 467 (2013) 291300

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Applied Catalysis A: General


journal homepage: www.elsevier.com/locate/apcata

Boehmite nanoparticles, an efcient 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, Iran

a r t i c l e

i n f o

a b s t r a c t
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 ve runs without an appreciable loss in its catalytic activity. 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Article history: Received 19 January 2013 Received in revised form 13 July 2013 Accepted 14 July 2013 Available online xxx

1. Introduction Multi-component reactions [1] (MCRs) have emerged as an efcient and powerful tool for drug discovery [2] and modern synthetic organic chemistry due to their valued features such as atom economy (describes the conversion efciency 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, purication 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 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-inammatory 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 3H2 O [8], HClO4 SiO2 [9], BF3 SiO2 [10], K5 CoW12 O40 3H2 O [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 -6H2 O/Al2 O3 [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 (-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 hydrothermalassisted solgel technique was used here. It has some advantages such as preparation in a one-pot process and processing at low temperature. 2. Experimental

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Corresponding author. Fax: +98 2733395441. E-mail addresses: akeivanloo@yahoo.com, keivanloo@shahroodut.ac.ir (A. Keivanloo).

2.1. Preparation of the catalyst AlOOH NPs were prepared according to the following procedure: 10 ml of aluminum-2-butoxide (2 M) in 2-butanol was placed in a 300 ml stainless steel autoclave, which contained 50 ml of

0926-860X/$ see front matter 2013 The Authors. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.apcata.2013.07.027

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A. Keivanloo et al. / Applied Catalysis A: General 467 (2013) 291300

Ph

+
Ph 1 R= aryl, alkyl Ph O O

O Ar 2 H

Ph

NH2 3

NH 4OAc

AlOOH NPs solvent free 120 C 20 - 90 min Ph N R

N Ar 4

+
Ph 1 O

O Ar 2 H

Ph

2 NH 4OAc

AlOOH NPs solvent free 120 C 10 - 75 min Ph N H

N Ar 5

Scheme 1. Synthesis of 1,2,4,5-tetrasubstituted/2,4,5-trisubstituted imidazoles by a multi-component reaction of benzil, aldehydes, NH4 OAc, and amine by boehmite NPs catalyst under solvent-free conditions.

deionized water. The autoclave was then heated for 5 h at 100 C in an oven. After cooling the autoclave, the powder produced was ltered 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 4004000 cm1 on a Bomem MB seriesspectrometer. 1 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). 2.2. 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 ltered to remove the catalyst. After evaporation of the solvent, the residue was crystallized from ethanol. 2.3. 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 ltered to remove the catalyst. After evaporation of the solvent, the residue was crystallized from ethanol. Characterization data for the new compounds are given below: 2.3.1. 1-(3-chlorophenyl)-2,4,5-triphenyl-1H-imidazole (4e) Mp = 205207 C; 1 HNMR (400 MHz, CDCl3 ): 6.856.87 (m, 1 H, 1CH), 6.977.22 (m, 14H, 14CH), 7.357.37 (m, 2H, 2CH), 7.507.53 (m, 2H, CH); 13 C NMR (100 MHz, CDCl3 ): 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 cm1 ; Anal. Calcd. for C27 H19 ClN2 : C, 79.70; H, 4.71; N, 6.88; Found: C, 79.68; H, 4.70; N, 8.90. 2.3.2. 2,4,5-triphenyl-1-propyl-1H-imidazole (4i) Mp = 7577 C; 1 HNMR (400 MHz, CDCl3 ): 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 ), 7.037.14 (m, 3H, 3CH), 7.347.46 (m, 10H, 10CH), 7.62 (dd, J = 8.2, 1.6, 2H, 2CH); 13 C NMR (100 MHz, CDCl3 ): 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 cm1 ; Anal. Calcd. for C24 H22 N2 : C, 85.17; H, 6.55; N, 8.28; Found: C, 85.18; H, 6.56; N, 8.26. 2.3.3. 1-(2-methoxyethyl)-2,4,5-triphenyl-1H-imidazole (4k) Mp = 121123 C; 1 HNMR (400 MHz, CDCl3 ): 2.96 (s, 3H, CH3 ), 3.14 (t, J = 6.3, 2H, CH2 ), 4.04 (t, J = 6.3, 2H, CH2 ), 7.047.14 (m, 3H, 3CH), 7.367.46 (m, 10H, 10CH), 7.67 (dd, J = 8.0, 1.6, 2H, 2CH); 13 C NMR (100 MHz, CDCl ): 43.95, 58.73, 70.70, 126.28, 126.86, 3 127.86, 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 cm1 ; Anal. Calcd. for C24 H22 N2 O: C, 81.33; H, 6.26; N, 7.90; Found: C, 81.30; H, 6.27; N, 7.92. 2.3.4. 2,4,5-triphenyl-1-(propan-2-yl)-1H-imidazole(4l) Mp = 159161 C; 1 HNMR (400 MHz, CDCl3 ): 1.26 (d, J = 6.8, 2H, CH2 ), 4.48 (m, J = 6.8, 1H, CH), 7.097.19 (m, 3H, 3CH), 7.457.50 (m, 10H, 10CH), 7.65 (dd, J = 7.6, 2.0, 2H, 2CH); 13 C NMR (100 MHz, CDCl3 ): 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 cm1 ; Anal. Calcd. for C24 H22 N2 : C, 85.17; H, 6.55; N, 8.28; Found: C, 85.15; H, 6.56; N, 8.29. 2.3.5. 1-butyl-2,4,5-triphenyl-1H-imidazole (4m) Mp = 114116 C; 1 HNMR (400 MHz, CDCl3 ): 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 ), 7.037.14 (m, 3H, 3CH), 7.347.46 (m, 10H, 10CH), 7.62 (dd, J = 8.0, 1.6, 2H, 2CH); 13 C NMR (100 MHz, CDCl3 ): 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,

A. Keivanloo et al. / Applied Catalysis A: General 467 (2013) 291300 Table 1 Condensation of benzil, benzaldehyde, benzylamine and ammonium acetate using different catalysts and solventsa .

293

Ph Ph O NH2 N 2 NH4OAc Catalyst solvent 4b Ph N Ph O Ph H

+
Ph O

Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Catalyst AlOOH (NPs) AlOOH (NPs) AlOOH (NPs) AlOOH (NPs) AlOOH (NPs) AlOOH (NPs) AlOOH (NPs) AlOOH (NPs) ZnO (NPs) ZnO (NPs) ZnBr2 ZnBr2 NiCl2 NiCl2
c

Catalyst loading (mol%) 10 10 10 10 10 10 5 20 10 20 10 20 10 20

Solvent EtOH CH3 CN H2 O Neat Neat Neat Neat Neat H2 O Neat Neat EtOH Neat EtOH

Temp ( C) 80 80 100 140 120 100 120 120 100 120 120 80 120 80

Time (min) 120 120 120 50 50 100 100 50 120 120 150 150 120 120

Yieldb (%) 50 20 35 96 96 83 91 71 10 10 65 25 46 11

Bold indicate the optimum conditions. a Reaction conditions: benzil (1.0 mmol), benzaldehyde (1.0 mmol), benzylamine (1.0 mmol), NH4 OAc (1.0 mmol), catalyst and solvent (10 ml), or neat. b Isolated yield. c Nonoparticles.

718, 696 cm1 ; Anal. Calcd. for C25 H24 N2 : C, 85.19; H, 6.86; N, 7.95; Found: C, 85.21; H, 6.85; N, 7.97. 2.3.6. 2,4,5-triphenyl-1-(tetrahydrofuran-2-ylmethyl)-1H-imidazole (4n) Mp = 142144 C; 1 HNMR (400 MHz, CDCl3 ): 1.421.58 (m, 4H, 2CH2 ), 3.303.33 (m, 1H, CH), 3.403.46 (m, 1H, CH), 3.613.65 (m, 1H, CH), 3.853.99 (m, 2H, CH2 ), 7.047.14 (m, 3H, 3CH), 7.357.46 (m, 10H, 10CH), 7.67 (dd, J = 7.6, 1.6, 2H, 2CH); 13 C NMR (100 MHz, CDCl3 ): 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 cm1 ; Anal. Calcd. for C26 H24 N2 O: C, 82.07; H, 6.36; N, 7.36; Found: C, 82.10; H, 6.35; N, 7.34. 3. 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 efcient one-pot protocol for the synthesis of highly substituted imidazole derivatives by an MCR involving a benzil, an aldehyde, NH4 OAc, 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 conrmed 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 rst 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 the Scherer equation shows 10 nm particles. This was conrmed 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. Efcient surface area of the boehmite NPs used in this work was 326 m2 /g.

Scheme 2. TG/DSC thermogram of nano-boehmite prepared by hydrothermal assisted solgel proceesing at 100 C.

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A. Keivanloo et al. / Applied Catalysis A: General 467 (2013) 291300

Scheme 3. TEM image of nano-boehmite prepared by hydrothermal assisted solgel proceesing at 100 C.

To optimize the reaction conditions for the synthesis of 1,2,4,5tetrasubstituted 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 rst 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, CH3 CN, 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 efciently 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 1,2,4,5tetrasubstituted 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 electrondonating and electron-withdrawing substituents present on both the aromatic aldehydes and aromatic amines, resulting in good-tohigh yields of the corresponding imidazoles. Aliphatic amines also reacted efciently, affording the desired products in 7890% 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

Table 2 Condensation of benzil, benzaldehyde, ammonium acetate using different catalysts and solventsa .

Ph

+
Ph O
Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14

O Ph H

Ph

2 NH4OAc

Catalyst solvent Ph N H

N Ph 5a
Temp ( C) 80 80 100 120 120 120 100 140 100 120 80 120 80 120 Time 120 120 120 80 80 80 80 80 180 180 180 180 180 180 Yieldb (%) 56 67 50 98 94 72 85 98 5 10 22 38 25 60

Catalyst AlOOH (NPs) AlOOH (NPs) AlOOH (NPs) AlOOH (NPs) AlOOH (NPs) AlOOH (NPs) AlOOH (NPs) AlOOH (NPs) ZnO (NPs) ZnO (NPs) ZnBr2 ZnBr2 NiCl2 NiCl2
c

Catalyst loading (mol%) 5 5 5 5 10 20 5 5 10 5 10 5 10 5

Solvent EtOH CH3 CN H2 O Neat Neat Neat Neat Neat H2 O Neat EtOH Neat EtOH Neat

Bold indicate the optimum conditions. a Reaction conditions: benzil (1.0 mmol), benzaldehyde (1.0 mmol), NH4 OAc (2.5 mmol), catalyst and solvent (10 ml), or neat. b Isolated yield. c Nanoparticles.

A. Keivanloo et al. / Applied Catalysis A: General 467 (2013) 291300 Table 3 Boehmite NPs catalyzed synthesis of 1,2,4,5-tetrasubstituted imidazolesa .

295

Ph

+
Ph O

O Ar H

Ph

NH2

NH4OAc

AlOOH NPs 120 C Ph N R

N Ar

Entry

Aldehyde

Amine

Product

Time (min)

Yieldb (%)

Reference

CHO
1

NH2

N N

50

94

4a

CHO
2

NH2

N N

50

96

4b
CHO
NH2
3
N N

H3C

60

86

12

CH3

4c

CHO

NH2
Cl

N N

20

92

Cl

4d

CHO
5

NH2

N N

20

93

New

Cl
Cl

4e

296 Table 3 (Continued) Entry Aldehyde Amine

A. Keivanloo et al. / Applied Catalysis A: General 467 (2013) 291300

Product

Time (min)

Yieldb (%)

Reference

CHO
NH2
6
O2N N N

40

78

25

NO2

4f

CHO
7

NH2

N N

25

89

4g

CHO
8

NH2

N N

35

80

NO 2
O 2N

4h

CHO
NH2
9

N N CH 2 CH 2 CH 3

H3C

30

88

New

4i

CHO
10

NH2 O H3C

N
30 90 New

N CH2CH2OCH3

4k

A. Keivanloo et al. / Applied Catalysis A: General 467 (2013) 291300 Table 3 (Continued) Entry Aldehyde Amine Product Time (min) Yieldb (%)

297

Reference

CHO
11

H3C NH2 H3C

N N CH(CH3)2
90 85 New

4l

CHO
12

NH2 H3C

N N CH2CH2CH2CH3

30

86

New

4m

CHO

O
13

NH2
O

50

78

New

4n
a b

Reaction conditions: benzil (1.0 mmol), aldehyde (1.0 mmol), NH4 OAc (1.0 mmol), amine (1.0 mmol) and boehmite NPs (10 mol%) at 120 C. Isolated yield.

benzil (1.0 mmol), benzaldehyde (1.0 mmol), NH4 OAc (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 ltered. Then the residue, catalyst, was washed with hot ethanol and reused. Apparently, treatment with hot ethanol removes tars more efciently from the catalyst surface. In this way, the boehmite NPs catalyst was reusable, although a few gradual decline in its activity was observed.

Al H O

Al O

Al O

O H NH2

Al O
Ph

Al O

Al O

H O

H
O

Ph H N N
+

NH3 R NH2 - H2O

NH R (A)

Ph

-2H2O

Ph (B)

R = H, Alkyl, Aryl Ph N N R
Scheme 4. Proposed mechanism for the formation of 1,2,4,5-tetrasubstituted/2,4,5-trisubstituted imidazoles from benzil, aldehydes, NH4 OAc, and amine in the presence of boehmite NPs.

- H+

Ph

298

A. Keivanloo et al. / Applied Catalysis A: General 467 (2013) 291300

Table 4 Boehmite NPs catalyzed synthesis of 2,4,5-trisubstituted imidazolesa .

Ph

+
Ph
Entry

O Ar H

Ph

2 NH4OAc

AlOOH NPs 120 C Ph N H

N Ar

Aldehyde

Product

Time (min)

Yieldb , c (%)

CHO
1
N N H

40

98

5a

CHO
N

15

79

NO2
O 2N

N H

5b

CHO
N N H

3
H3C

45

88

CH3

5c

CHO
4

Cl

Cl

N N H

40

95

5d
CHO
N N H

10

86

Cl

Cl

5e

CHO
Cl N N H

75

83

Cl Cl
Cl

5f

A. Keivanloo et al. / Applied Catalysis A: General 467 (2013) 291300 Table 4 (Continued ) Entry Aldehyde Product Time (min)

299

Yieldb , c (%)

CHO
N N H

7
H3CO

50

85

OCH3

5g

CHO
8

H3CO

N N H

65

78

H3CO

5h
a b c

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Table 5 Condensation of benzil, benzaldehyde,ammonium acetate and benzylamine using recycled catalysts.a Entry 1 2 3 4 Number of cycles 1 2 3 5 Yieldb (%) 92 88 85 82

a Reaction conditions: benzil (1.0 mmol), benzaldehyde (1.0 mmol), NH4 OAc (1.0 mmol), cyclohexylamine (1.0 mmol) and recycled catalyst (10 mol%), 25 min. b Isolated yield.

4. Conclusion We demonstrated a simple method for the synthesis of highly substituted imidazoles using boehmite NPs as a reusable, ecofriendly, inexpensive, and efcient 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 ve 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 nancial support of this work. References
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