Scholarly article on topic 'One-pot synthesis of 1,2,4,5-tetra substituted imidazoles using sulfonic acid functionalized silica (SiO2-Pr-SO3H)'

One-pot synthesis of 1,2,4,5-tetra substituted imidazoles using sulfonic acid functionalized silica (SiO2-Pr-SO3H) Academic research paper on "Chemical sciences"

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Arabian Journal of Chemistry
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{"Sulfonic acid functionalized silica" / SiO2-Pr-SO3H / "Tetrasubstituted imidazoles" / Benzil / "1 / 2-Diketones" / "One-pot reaction"}

Abstract of research paper on Chemical sciences, author of scientific article — Ghodsi Mohammadi Ziarani, Zeinab Dashtianeh, Monireh Shakiba Nahad, Alireza Badiei

Abstract SiO2-Pr-SO3H has been used as an efficient catalyst for an improved and rapid synthesis of 1,2,4,5-tetrasubstituted imidazoles, by four-component, one-pot reaction of 1,2-diketones, aryl aldehydes, ammonium acetate and substituted aromatic amines in excellent yields under solvent-free conditions.

Academic research paper on topic "One-pot synthesis of 1,2,4,5-tetra substituted imidazoles using sulfonic acid functionalized silica (SiO2-Pr-SO3H)"

Arabian Journal of Chemistry (2014) xxx, xxx-xxx

King Saud University Arabian Journal of Chemistry


One-pot synthesis of 1,2,4,5-tetra substituted imidazoles using sulfonic acid functionalized silica (SiO2-Pr-SO3H)

Ghodsi Mohammadi Ziarani a'*, Zeinab Dashtianeh a, Monireh Shakiba Nahad a, Alireza Badiei b

a Department of Chemistry, Alzahra University, P.O. Box 19938939973, Tehran, Iran b School of Chemistry, College of Science, University of Tehran, P.O. Box 14155-6455, Tehran, Iran

Received 12 October 2012; accepted 16 November 2013


Sulfonic acid functionalized silica;

SiO2-Pr-SO3H; Tetrasubstituted imidazoles; Benzil;

1,2-Diketones; One-pot reaction

Abstract SiO2-Pr-SO3H has been used as an efficient catalyst for an improved and rapid synthesis of 1,2,4,5-tetrasubstituted imidazoles, by four-component, one-pot reaction of 1,2-diketones, aryl aldehydes, ammonium acetate and substituted aromatic amines in excellent yields under solventfree conditions.

© 2013 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.

1. Introduction

The imidazoles constitute an important class of compounds with profound interest to medicinal chemists, as these compounds exhibit diverse biological properties such as antiallergic, analgesic (Chary et al., 2008), antifungal (Ballard et al., 1988), antibacterial, antiprotozoal, anthelmintic (Venkatesan et al., 2009), anti-tuberculosis, and anti-inflammatory (Gupta et al., 2004). They act as glucagon receptor, kinas inhibitor, antagonist of CB1 cannabinoid (Nshimyumukiza et al., 2010)

* Corresponding author. Tel./fax: +98 21 88041344. E-mail addresses:, gmohammadi@alzahra. (G. Mohammadi Ziarani), (A. Badiei). Peer review under responsibility of King Saud University.

and possess many other activities (Bellina et al., 2008). A large class of imidazoles emerges as ionic liquid in green chemistry and organometallic catalysis (Zang et al., 2010). They also have optical absorption and bright luminescence (Kumar and Thomas, 2011). They have been applied as ligands in coordination chemistry (Fulwa et al., 2009). They are also an active backbone in existing drugs such as candesartan (Alonen et al., 2008), losartan (Polevaya et al., 2001) and eprosartan (Grange et al., 2008) (Scheme 1).

1,2,4,5-Tetra-substituted imidazoles are synthesized by four-component condensation of a 1,2-diketone, a hydroxyke-tone or a ketomonoxime with an aldehyde, primary amine and ammonium acetate using HY zeolite (Balalaei and Arabanian, 2000), silica gel/NaHSO4 (Karimi et al., 2006), HClO4-SiO2 (Kantevari et al., 2007), molecular iodine (Kidwai et al., 2007), BF3-SiO2 (Sadeghi et al., 2008), InCl33H2O (Das Sharma et al., 2008), potassium dodecatugstocobaltatetrihy-drate (K5CoW12O40-3H2O) (Nagarapu et al., 2007), and

1878-5352 © 2013 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.


2 G. Mohammadi Ziarani et al.

Losartan Candesartan Eprosartan

Scheme 1 Some drugs with imidazole structure.

Keggin-type heteropolyacids (Heravi et al., 2007). In addition, they can also be synthesized by N-alkylation of tri-substituted imidazoles (Ucucu et al., 2001), hetero-Cope rearrangement (Lantos et al., 1993), condensation of 1,2-diketone with an aryl nitrile and primary amine under microwave irradiation (Balalaie et al., 2003).

In this paper, we want to report the application of SiO2-Pr-SO3H as a highly active heterogeneous solid acid catalyst in the preparation of 1,2,4,5-tetrasubstituted imidazoles.

2. Result and discussion

The condensation reaction of benzil (1), aromatic aldehydes (2), ammonium acetate as ammonia source (3) and substituted amine (4) in the presence of SiO2-Pr-SO3H produced 1,2,4,5-tetra-substituted imidazoles (5) in excellent yields under solvent-free conditions at 140 0C (Scheme 2) in 10 min to 2.5 h. The results are demonstrated in Table 1. After completion of the reaction (monitored by TLC), water was added for removing any excess ammonium acetate, then the crude product was dissolved in ethyl acetate and the heterogeneous solid acid catalyst was removed easily by simple filtration, and after cooling of the filtrate, the pure crystals of products were obtained. It can be seen when the electron-withdrawing substituents exist in the aromatic ring of the aldehydes, increased yields of products were observed, whereas the effect was reverse with the electron-donating substituent.

For the preparation of catalyst, at first, the surface of silica was grafted with (3-mercapto-propyl)trimethoxysilane (MPTS) and then the thiol functionalities were oxidized into sulfonic acid groups by hydrogen peroxide to give SiO2-Pr-SO3H as solid heterogeneous catalyst (Scheme 3) (Mohammadi Ziarani et al., 2011a,b).

The suggested mechanism for the SiO2-Pr-SO3H catalyzed transformation is shown in Scheme 4. Concerning the reaction mechanism, we suggest that initially, the solid acid catalyst

protonates the carbonyl group of aromatic aldehyde which then condenses with ammonium acetate and substituted aromatic amine (4) to produce the adduct products (7). Nucleo-philic reaction of compound (7) with protonated benzil (1) creates intermediate (8). In the presence of catalyst, ring closure followed by dehydration, gives 1,2,4,5-tetra-substituted imidazoles (5). The product structure was confirmed by IR, *H NMR and GC-Mass data.

The efficiency of various catalysts in the synthesis of imid-azole derivatives has been compared in Table 2. The mentioned method has several advantages, such as excellent yields, simple procedure, and use of an eco-friendly and recyclable catalyst.

3. Experimental section: general information

IR spectra were recorded from KBr disk using a FT-IR Bruker Tensor 27 instrument. The NMR was run on a Bruker DPX, 250 MHz. Melting points were measured using the capillary tube method with an electro thermal 9200 apparatus.

3.1. Preparation of catalyst

To SiO2 (20 g) in dry toluene (50 ml), (3-mercaptopropyl)tri-methoxysilane (25 ml) was added and the reaction mixture was refluxed for 24 h. After this period, the mixture was filtered to obtain 3-mercaptopropylsilica which was washed with acetone and dried. 3-mercaptopropylsilica (MPS) (20 g) was oxidized with H2O2 (50 ml) and one drop of H2SO4 in methanol (20 ml) for 24 h at room temperature and then the mixture was filtered and washed with H2O and acetone to obtain SiO2-Pr-SO3H catalyst. The modified SiO2-Pr-SO3H was dried and used as solid acid catalyst in the synthesis of 1,2,4,5-tetra substituted imidazoles.

Scheme 2 Synthesis of 1,2,4,5-tetra-substituted imidazoles (5) in the presence of SiO2-Pr-SO3H.

One-pot synthesis of 1,2,4,5-tetra substituted imidazoles using SiO2 -Pr-SO3H

Table i SiO2-Pr-SO3H catalyzed synthesis of 1,2,4,5-tetrasubstituted imidazoles (5).

Entry Product

Time (min) Yield (%) Mp (°C) Mp (Lit)

156-158 157-159 Shoar et al. (2010)

248-250 249-250 Shoar et al. (2010)

181-183 181-183 Shoar et al. (2010)

Ph ^ —


189-190 188-190 Shoar et al. (2010)

158-162 163-165 Shoar et al. (2010)

132-133 131-132 Davoodnia et al. (2010)

N /=\ /

149-150 155-157 Ucucu et al. (2001)

4 G. Mohammadi Ziarani et al.

Table 1 SiO2-Pr-SO3H catalyzed synthesis of 1,2,4,5-tetrasubstituted imidazoles (5).

Entry Product

Time (min) Yield (%) Mp (°C) Mp (Lit)

:<yo d

163-165 163-165 Davoodnia et al. (2010)

125-127 128-129 Ucucu et al. (2001)

182-184 188-190 Shaterian et al. 2011)

(MeO)3Si SH

Toluene, Re flux, 24 h

-O—Si /

H2O2, lt

CHjOH, 24 h

/1 —()

Q —O—Si

/ —O

Scheme 3 The preparation of SiO2-Pr-SO3H.

3.2. General procedure for the preparation of 1,2,4,5-tetra substituted imidazoles

The activated SiO2-Pr-SO3H (0.02 g), an aromatic aldehyde (2.5mmol), benzil (2.5mmol, 0.53 g), aniline or benzylamine (2.5mmol) and ammonium acetate (7.5mmol, 0.69 g) were placed in a flask and stirred at 140 0C under solvent free conditions for a suitable time (Table 1). The progress of the reaction was monitored by TLC (n-hexane:EtOAc, 1:4). After completion of the reaction, ethyl acetate was added to the reaction mixture, and the insoluble catalyst was separated by a simple filtration. The solvent of filtrate was evaporated, and pure products were obtained. The crystals of 1,2,4,5-tetra substituted imidazoles appeared after gradual evaporation of solvent at room temperature. The catalyst could be washed

subsequently with diluted acid solution, water and then acetone. After drying, it can be reused several times without noticeable loss of reactivity.

3.2.1. 1-Benzyl-2-(4-hydroxyphenyl)-4,5-diphenyl imidazole (5f)

IR (KBr): vmax = 3027, 1583, 1484, 1447; *H NMR (250 MHz, CDCl3) dH = 5.08 (s, 2H, CH2), 6.81-7.60 (m, 19 CH, arom) ppm; Mass (m/e): 402, 385, 325, 133, 77.

3.2.2. 1-Benzyl-2-(3,4-dimethoxyphenyl)-4,5-diphenyl imidazole (5j)

IR (KBr): vmax = 1594,1479,1418 cm"1; *H NMR (DMSO-d6) d = 3.62 (s, 6H, 2CH3), 5.19 (s, 2H, CH2), 6.79-7.47 (m, 18H), ppm; Mass (m/e): 461, 430, 385, 339, 282, 165, 136, 91, 55.

One-pot synthesis of 1,2,4,5-tetra substituted imidazoles using SiO2 -Pr-SO3H

O HO, /=\^R


NH4OAc 3

4 /=VK1 ^

R2NH2 4 -H2O

\\ // SiO2-Pr-SO3H Ph Ph


N^/H /=*Ri

oh y 8

Scheme 4 Proposed mechanism for the synthesis of 1,2,4,5-tetra-substituted imidazoles.

Table 2 The efficiency comparison of various catalysts in the synthesis of tetra substituted imidazoles.

Entry Catalyst Solvent Condition Yield (%) Time (h) Year Refs.

1 BF3-SiO2 - 140 °C 80-96 2 2008 Sadeghi et al. (2008)

2 InCl33H2O MeOH r.t. 47-84 6-9 2008 Das Sharma et al. (2008)

3 [(CH2)4SO3HMIM] - 140 °C 85-95 2-2.5 2010 Davoodnia et al. (2010)

4 MCM-41 - 140 °C 74-82 1.92-2.25 2010 Shoar et al. (2010)

5 MCM-41 AcOH Reflux 75-85 23-35 min 2010 Shoar et al. (2010)

6 p-TsOH - 140 °C 75-82 1.92-2.17 2010 Shoar et al. (2010)

7 p-TsOH EtOH Reflux 73-83 13-23 min 2010 Shoar et al. (2010)

8 - 1-Butyl-3-methylimidazolium bromide 140 °C 82-93 1.5-5 2010 Hasaninejad et al. (2010)

9 - 1-Butyl-3-methylimidazolium Bromide MW 82-93 3-8 min 2010 Hasaninejad et al. (2010)

10 P2O5/SiO2 - 100 °C 87-98 15-55 min 2011 Shaterian et al. (2011)

11 - - 140 °C 0 3 2010 Davoodnia et al. (2010)

12 SiO2-Pr-SO3H - 140 °C 85-98 10 min-3 h This work

[(CH2)4SO3HMIM]: 3-methyl-1-(4-sulfonic acid)-butyl imidazolium hydrogen sulfate.

4. Conclusion

In summary, we have demonstrated one-pot, four-component synthesis of 1,2,4,5-tetra substituted imidazoles, in the presence of sulfonic acid functionalized silica as an efficient solid acid catalyst in good to excellent yields under solvent free conditions. The attractive merit features of this protocol are the environmentally friendly conditions, simplicity of reaction, reasonable reaction times, very good yields, and simple workup procedure.


We gratefully acknowledge the financial support from the Research Council of Alzahra University and the University of Tehran.


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