Int J Curr Pharm Res, Vol 8, Issue 1, 36-39Original Article


SYNTHESIS OF TETRA-SUBSTITUTED IMIDAZOLE DERIVATIVES BY CONDENSATION REACTION USING ZEOLITE H-ZSM 22 AS A HETEROGENEOUS SOLID ACID CATALYST

SAMI ULLAH BHAT*, RAWOOF AHMAD NAIKOO, MUZZAFFAR AHMAD MIR, RADHA TOMAR

School of Studies in Chemistry, Jiwaji University, Gwalior (M. P.) 474011
Email: profsamibhat92@gmail.com

Received: 29 Oct 2015, Revised and Accepted: 30 Dec 2015

ABSTRACT

Objective: The present work deals with the synthesis of tetrasubstituted imidazoles using environmentally benign and green catalyst H-ZSM-22.

Methods: The synthesized catalyst was characterized by FTIR, XRD and the products by FTIR and NMR.

Results: H-ZSM-22 has been used as an efficient catalyst for an improved and rapid synthesis of 1,2,4,5 tetrasubstituted imidazoles derivatives using reactants: Benzil, Aldehydes, Amines and Ammonium acetate having excellent yield under solvent conditions. Different derivatives of aldehyde have been used in this reaction. For all the synthesized derivatives, ambient reaction time was found to be of 15-30 min.

Conclusion: The main advantage of this reaction is small reaction time, high purity yield, easy work-up and pollution free.

Keywords: H-ZSM-22, One-pot synthesis, Multi-component reaction, Tetra-substituted imidazoles.

© 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

INTRODUCTION

Imidazole and its derivatives represent an important class of Heterocyclic organic compounds that provides important applications of both biological and pharmacological activities. They are having fungicidal [1-2], analgesic [3], anti-inflammatory, [4], antibacterial [5] and antitumor activities [6]. Some members of this family have been widely used as selective inhibitors of P 38 mitogen-activated protein (MAP) kinase [7-8] and B-Raf kinase [9]. In transition metals such as iron, copper and zinc imidazoles derivatives provide main role in potential corrosion inhibitors [10]. Several methods have been used for the synthesis of tetrasubstituted imidazole derivatives; these methods include condensation of diones, aldehydes, primary amines and ammonia [11], condensation of benzoin or benzoin acetate with aldehydes, primary amines and ammonia in the presence of copper acetate [12], four-component condensations of diones, aldehydes, primary amines, and ammonium acetate in HOAc under reflux conditions [13] and conversion of N-(2-oxo) amides with ammonium trifluoro acetate under neutral conditions [14].

Here we have presented a novel, and efficient method for the synthesis of 1,2,4,5 tetrasubstituted imidazoles using H-ZSM-22 as a heterogeneous solid acid catalyst.

MATERIALS AND METHODS

Synthesis of catalyst H-ZSM-22

Take SiO2 and Al2O3 at a ratio of 90: 1 in a 100 ml beaker; dissolve 1.0 g of KOH in 4.55 g of deionized water. Add an aqueous solution of 0.44 g Al2 (SO4)3.16H2O prepared in 4.55 g of deionized water. Mix thoroughly. Dissolve separately 2.6 g of 1, 8-diaminooctane in 18.2 g of deionized water and add into the beaker under constant stirring using a magnetic stirrer. Stire the mixture for 30 min until a clear solution is obtained. Add 11.9 g of colloidal silica into 6.74 g of deionized water and add it to the solution under constant stirring. Continue stirring for 90 min until a gel is obtained. Keep the gel in a polypropylene bottle for 24 h for aging. Now keep the gel in a Teflon-lined autoclave for 2 to 3 d at 160 °C for crystallization. The solid phase is then separated by filtration, washed with deionized water, and dried for 12 h. In an oven at 353 K. The conversion of Na-ZSM-22 Zeolite into H-form involves the following procedure:

Mix 9.0 of Na-ZSM-22 g, 7.23 g of NH4Cl and 13.80 ml of deionized water with 0.1 M HCl solution (5 ml) to reach pH 4. Stire the mixture at 60 °C for 6 h. Filter the material under suction and wash with deionized water. After the removal of chloride, the resulting material NH4+-Zeolite is then placed in an oven at 60 0c for 24 h. The ammonium form of Zeolite is converted into H-form by calcination over 60 min at 500 °C

Synthesis of tetrasubstituted imidazoles using ZSM-22 in refluxing ethanol

General procedure

A mixture of Benzil (1 mmol), Amine (1 mmol), Aldehyde (1 mmol), Ammonium acetate (5 mmol), and catalyst (0.08g) in ethanol (5 mL) was heated on the oil bath at 140 °C. After completion of the reaction monitored by TLC. The reaction mixture was cooled at room temperature. Add ethanol to remove catalyst and gives the pure product.

Synthesis of tetrasubstituted imidazoles

Characterization

X-Ray diffraction (XRD)

For X-ray diffraction analysis, the samples were placed in aluminum sample holder equipment. Copper Kα radiation at the speed of 20/min gives 2θ range scanning from 0 ° to 60 °. The only d-spacing of interest in X-ray patterns were the basal spacing’s along c axis.

Fourier-transform infrared (FT-IR) spectroscopy

In FTIR analysis, ZSM-22 was treated with KBr method which consists of mixing 0.007 g of the sample and 0.1 g of KBr in order to form pellet that allows the passage of light. In FTIR analysis wavelength ranges from 3000 to 400 cm−1, with increments of 500 cm−1. Again Characterization of the products was performed on SHIMADZU FT-IR spectrometer, and the sample was prepared with KBr method and form pellet. The wavelength of spectra ranges from 500–4000 cm−1. NMR of the products was performed on BRUKER ADVANCE II 400 NMR spectrometer.

Table 1: Synthesis of tetra-substituted imidazole derivatives using H-ZSM-22 through a condensation reaction between Benzil, Aldehyde, Amine and Ammonium acetate

Entry Benzil Aldehyde Amine Ammonium Acetate Product

Time

min

Yield

%
1. NH4OAc 30 81
2. NH4OAc 15 86
3. NH4OAc 17 87
4. NH4OAc 20 76

Spectral data of tetra-substituted imidazole derivatives

Entry 1: 1, 2, 4, 5-Tetraphenyl-1H-imidazole (C27H20N2) White powder; m. p. 210–2150c FT-IR (KBr): υmax (in Cm−1) 3058 (C-H aromatic), 1589 (C=C aromatic), 1448 (C=N) 1H NMR (400 MHz, CDCl3): δ (ppm) 7.11–7.58 (m, 20H, H–Ar) (fig. 3-4)

Entry 2: 2-(4-Chlorophenyl)-1, 4, 5-triphenyl-1H-imidazole (C27H19ClN2): Cream crystal; m. p. 151-156 ◦C; FT-IR (KBr): υmax (in Cm−1) 3050 (C-H aromatic), 1589 (C=C aromatic), 1448 (C=N) 1065 (C–Cl) 1H NMR (400 MHz, CDCl3): δ (ppm) 7.15–7.37 (m, 17H, H-Ar), 7.5 (d,2H, H-Ar) (fig. 5-6)

Entry 3: 2-(4-Nitrophenyl)-1,4,5-triphenyl-1H-imidazole (C27H19NO2N2): m. p. 185-1900c; FT-IR (KBr): υmax (in Cm−1) 3056 (C-H aromatic), 1591 (C=C aromatic), 1515 (C=N) 1338 (C–NO2) 1H NMR (400 MHz, CDCl3): δ (ppm) 6.6-7.8 (m, 17H, H-Ar),8.2(d,2H, H-Ar) (fig. 7-8)

Entry 4: 2-(4-Hydroxyphenyl)-1, 4, 5-triphenyl-1H-imidazole (C27H19OHN2): m. p. 278-2800c; FT-IR (KBr): υmax (in Cm−1) 3006 (C-H aromatic), 1577 (C=C aromatic), 1442 (C=N)1085 (C–OH) 1H NMR (400 MHz, CDCl3): δ (ppm) 6.5-7.8 (m, 17H, H-Ar),7.9(d,2H, H-Ar) (fig. 9-10)

RESULTS AND DISCUSSION

Characterization of Zeolites and products

The x-ray diffraction patterns of H-ZSM-22 are shown in fig. 1. The XRD analysis shows that the synthesized materials are crystalline in nature. Further, it was found that in diffraction signals, the sharp peak value (2 θ) for H-ZSM-22 is 23.6 are already reported [15]. FT-IR spectrum of H-ZSM-22 is shown in fig 2. In FT-IR analysis, H-form of ZSM-22 shows absorption band at 450 cm-1 which corresponds due to Si, Al-O bond and those at around 1000 and 790 cm-1 were respectively due to asymmetric and symmetric stretches of the Zeolite framework.

The main point is to consider the synthesis of tetrasubstituted imidazole derivatives. The reaction was carried out by using H-Form of ZSM-22 through a condensation reaction between Benzil, Aldehydes, Amines and Ammonium acetate using ethanol as solvent at 140 oC and the products are shown in table 1. It was found that the catalyst is highly selective resulting 87% isolating yield of tetra-substituted imidazole derivative. It was found that without catalyst the reaction could not occur, thus, catalyst plays an important role in this reaction. The synthesis of tetra-substituted imidazole derivatives was carried out by using different amounts of H-Form of Zeolite ZSM-22 at temperature 140oc which occurs at a reaction time of 30 min and the results are shown in table 2. It was noticed that the yield increases from 56%-87% with an increase in the weight of the catalyst from 20 to 80 mg respectively. The product yield remains constant with further increase in the amount of catalyst. For the rest of the studies, we used the weight of catalyst as 80 mg. Also, it was noticed that with further increasing the amount of catalyst, there is an increase in the yield of product, but there is no effect on the reaction time which remains same for all the cases as shown in table 2.

Table 2: Effect of weight of H-ZSM-22 on the synthesis of tetrasubstituted imidazole derivatives

Weight of catalyst Mg Reaction time min Yield %
20 30 56
40 30 62
60 30 68
80 30 87

Reaction conditions: substrate

Benzil, Aldehydes, Amines and Ammonium acetate, reaction temperature: 1400c, solvent: ethanol.

The result and catalytic efficiency of H-ZSM-22 for the synthesis of tetrasubstituted imidazoles using various derivatives of Aldehydes, Benzil, Amines and Ammonium acetate are shown in table 1. In all these cases the reactions are highly efficient and completed within 20-30 min. The catalyst shows a good performance in all these cases and the product yield of various derivatives of tetrasubstituted imidazoles are 76%-87%. The product yield of tetra-substituted imidazole derivatives depends on the nature of the functional group on the aromatic ring of the aldehyde. Aldehydes with electron-withdrawing groups afford more pure products compared with electron-donor groups. In all these cases the reaction work is very simple and easy. The catalyst was recycled using ethanol as a solvent which was evaporated. The efficiency of the recovered catalyst was verified by the reaction of Aldehydes, Benzil, Amine and Ammonium acetate and was found between 79-87 % as shown in table 3. The efficiency of the recovered catalyst decreased after three reaction cycles due to the loss of catalyst or catalyst structure during recovering process.

Table 3: Effect of catalyst recycling on percentage yield of tetra-substituted imidazole derivative

Runs % Yield
1st run 87
2nd run 86.4
3rd run 83.3
4th run 79.6

Fig. 1: XRD spectrum of H-ZSM-22


Fig. 2: FTIR spectrum of H-ZSM-22


Fig. 3: FTIR spectrum of 1, 2, 4, 5-tetra phenyl 1H-imidazole


Fig. 4: 1H-NMR spectrum of 1, 2, 4, 5-tetraphenyl-1H-imidazole


Fig. 5: FTIR spectrum of 2-(4-chlorophenyl) 1, 4, 5-triphenyl-1H-imidazole


Fig. 6: 1H-NMR spectrum of 2-(4-chlorophenyl) 1, 4, 5-triphenyl imidazole


Fig. 7: FTIR spectrum of 2-(4-nitrophenyl) 1, 4, 5-triphenyl 1H-imidazole


Fig. 8: 1H-NMR spectrum of 2-(4-nitrophenyl) 1, 4, 5-triphenyl 1H-imidazole


Fig. 9: FTIR spectrum of 2-(4-Hydroxyphenyl) 1, 4, 5-triphenyl 1H-imidazole


Fig. 10: 1H-NMR spectrum of 2-(4-Hydroxyphenyl) 1, 4, 5-triphenyl 1H-imidazole

CONCLUSION

H-ZSM-22 has been introduced as an efficient catalyst for the synthesis of tetrasubstituted imidazoles. This catalyst provides an alternate way for the above synthesis in terms of small reaction time, better product yield, minimum waste production, reusability of the catalyst as compared to other catalysts. In conclusion, we have demonstrated a simple method for the synthesis of tetrasubstituted imidazoles using H-ZSM-22 as an eco-friendly, inexpensive and efficient catalyst.

ACKNOWLEDGMENT

We are highly thankful to IIT Delhi and Jammia Milia University for the characterization of the synthesized materials.

CONFLICT OF INTERESTS

Declare none

REFERENCES

  1. Sathe BS, Jaychandran E, Jagtap VA, Deshmukh SD. Synthesis and antifungal screening of fluoro benzothiazole imidazole derivatives. Pharm Chem 2011;3:305–9.
  2. Roongpisuthipong A, Chalermchockcharoenkit A, Sirimai K, Wanitpongpan P, Jaishuen A, Foongladda S, et al. Safety and efficacy of a new imidazole fungicide, Sertaconazole, in the treatment of fungal vulvovaginitis: a comparative study using Fluconazole and Clotrimazole. Asian Biomed 2010;4:443–8.
  3. Sondhi SM, Jain S, Dinodia M, Kumar A. Synthesis of some thiophene, imidazole and pyridine derivatives exhibiting good anti-inflammatory and analgesic activities. Med Chem 2008;4:146–54.
  4. Amir M, Ahsan I, Akhter W, Khan SA, AliI. Design and synthesis of some azole derivatives containing 2, 4, 5-triphenyl imidazole moiety as anti-inflammatory and antimicrobial agents. Indian J Chem Sect B: Org Chem Incl Med Chem 2011;50:207–13.
  5. Ganguly S, Vithlani VV, Kesharwani AK, Kuhu R, Baskar L, Mitramazumder P, et al. Synthesis, antibacterial and potential anti-HIV activity of some novel imidazole analogs. Acta Pharm 2011;61:187–201.
  6. Wittine K, Stipkovic Babic M, Makuc D, Plavec J, Kraljevic´ Pavelic´ S, Sedic´ M, et al. Novel 1,2,4-triazole and imidazole derivatives of l-ascorbic and imino-ascorbic acid: synthesis, anti-HCV and antitumor activity evaluations. Bioorg Med Chem 2012;20:3675–85.
  7. Scior T, Domeyer DM, Cuanalo-Contreras KA, Laufer S. Pharmacophore design of p38 MAP kinase inhibitors with either 2,4,5-trisubstituted or 1,2,4,5-tetrasubstituted imidazole scaffold. Curr Med Chem 2011;18:1526–39.
  8. Laufer S, Hauser D, Stegmiller T, Bracht C, Ruff K, Schattel V, Albrecht W, et al. Tri-and tetra substituted imidazoles as p38 a mitogen-activated protein kinase inhibitors. Bioorg Med Chem Lett 2010;20:6671–5.
  9. Scior T, Domeyer DM, Cuanalo-Contreras KA, Laufer S. Pharmacophore design of p38 MAP kinase inhibitors with either 2,4,5-trisubstituted or 1,2,4,5-tetrasubstituted imidazole scaffold. Curr Med Chem 2011;18:1526–39.
  10. Takle AK, Brown MJB, Davies S, Dean DK, Gaiba G, Francis A, et al. The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett 2006;16:378–81.
  11. Bhargava G, Ramanarayanan TA, Gouzman I, Abelev E, Bemasek SL. Inhibition of iron corrosion by imidazole: an electrochemical and surface science study. Corrosion 2009;65:308–17.
  12. Stoeck V, Schunack W. N-Substituierte Imidazole aus Aldehyden, 1,2-Diketonen, primären Aminen und flüssigem Ammoniak. Arch Pharm 1974;307:922.
  13. Krieg B, Manecke GZ. Sythese und halbleitereigenschaften aryl substituierter imidazole. Naturforschung B 1967;22:132.
  14. Claiborne CF, Liverton NJ, Nguyen KT. An efficient synthesis of tetrasubstituted imidazoles from N-(2-Oxo)-amides. Tetrahedron Lett 1998;39:8939-42.
  15. Valyocsik WE, US Pat; 1990;4:902406.