One Pot Synthesis, Characterization of Benzothiazole/ Benzimidazole Tethered Imidazole Derivatives using Clay as Catalyst.

Introduction

The development of economical andenvironmentally viable catalyst has a great importance in the field of organic synthesis and is extensively needed for industrial processes. In recent years heterogeneous catalysts have attracted huge interest due to their magnificent properties in organic synthesis.Heterogeneous catalyst exhibits excellent catalytic activity with ability of easy separation from the synthesized product and reusability.Current reports on the heterogeneous catalysts have highlighted their tremendous arena of modifications and applications on the new fronts of organic synthesis. The magnetic nanophotocatalyst WO₃ZnO/Fe₃O₄ developed forthe  synthesis of benzimidazole derivatives¹. The nanocomposite W–ZnO@NH₂–CBB successfully used as a photocatalyst for the photochemical synthesis of benzimidazoles induced by UV-visible light².The magneticcatalyst H₃PW₁₂O₄₀@Fe₃O₄/EN-MIL-101 used for synthesis ofindazolo phthalazine-triones³.Ananoporous basic catalyst developed by grafting amine on UiO‐66 and used for the synthesis of 2‐aminithiophenes⁴.Themesoporous catalyst Nb-Zr/KIT-6 successfully used for benzylpyrazolylcoumarins synthesis⁵. The synthesisof 3-substituted indoleswere reported by using H₅PW₁₀V₂O₄₀@VO_x/SBA-15-NH₂asa  catalyst⁶.Heterogeneous catalysts exhibit properties like low toxicity, recyclability, easy separation, great diversity at structural level and stability at high temperatures^7-10.

The clay material forms an important part of heterogeneous catalysts due their vast availability and interesting catalytic properties. In recent times, these are heavily explored for their catalytic potential in organic synthesis¹¹. The naturally occurring clays are mostly acidic in nature and exhibit high surface area. The clay catalysts found their prominent applications in the field of refining of petroleum and transformation of bio-ethanol into hydrocarbons^12,13. The need for cheap, non-toxic and reusable catalysts is very high in industrial processes. Red brick clay which is easily available and non-hazardous is a perfect catalytic material^14,15. Red brick clay is composed of mainly SiO₂ (12.36%), Fe₂O₃ (5.28%) and Al₂O₃ (5.23%). The red brick clay has been used as an efficient catalyst in many reactions and it also showed selective 1,4-butanediol dehydration with an excellent yield^16,17. The photo-catalytic oxidative degradation of dyes like malachite green (MG) is efficiently catalyzed by iron and zinc supported on red brick nanocomposites^{18, 19}.

Nitrogen containing heterocyclic moieties has a huge importance in organic synthesis²⁰. Imidazole moiety has significance in synthetic and medicinal fields due to its crucial role as building blocks in products of natural origin²¹. Imidazole derivatives attracted significant attention by their prominent biological activities that include antihypertensive, antimicrobial and anticancer^22-25. Benzimidazole is a crucial moiety in the field of medicinal chemistry owing to a wide variety of pharmacological and biological activities, which include anticancer, antimicrobial and anti-inflammatory^26-29. Benzothiazole is another prominent moiety which possesses a broad range of biological activities. The benzothiazole derivatives incorporating imidazole moiety exhibited tremendous antifungal activity. Benzothiazole derivatives were also known for their anticancer activity. The magnificent activities of these moieties inspired us to synthesize the imidazole derivatives with benzimidazole and benzothiazole. The benzimidazole / benzothiazole tethered imidazole derivatives definitely provide leads for further drug development^30,31

Over the years, researchers have introduced wide variety of catalyst for the synthesis of imidazole derivatives. Reports have revealed that zeolite³², p-dodecylbenzenesulfonic acid (DBSA)³³, DABCO³⁴,  HNO₃@ nano-SiO₂³⁵,L-proline³⁶, HClO₄-SiO₄³⁷, PEG-400³⁸, MgAl₂O₄³⁹,nano TiCl₄-SiO₂⁴⁰, nano-crystalline sulfated zirconia⁴¹, NH₄Fe(SO₄)₂ KOH⁴², Phenoxyl Spacer⁴³, nanocrystalline silica supported tin oxide (SiO₂:SnO₂)⁴⁴, Sodium lauryl sulfate⁴⁵, Cu@imine/Fe₃O₄ magnetic nanoparticles ⁴⁶, sulfamic acid functionalized hollow magnetic spheres⁴⁷ have significantly improved the efficiency but environmental aspects remain overlooked. The novelty of this work lies in the fact that we have reported a greener catalyst in the form of brick derived clay which is very economical due to easy availability with simple workup and we have successfully utilized it for the synthesis of benzothiazole/ benzimidazoletethered imidazole derivatives with very good efficiency. The synthesized benzothiazole/ benzimidazoletethered imidazole derivatives can provide important leads for further drug development.  Brick derived clay proved itself as a promising catalyst in this synthesis with additional benefits of its cheapness, easy availability with simple workup, reusability and most importantly it is environmentally favorable material as compared to other alternatives. 

Herein, we report inexpensive, reusable and non-toxic brick derived catalyst for the synthesis of benzothiazole /benzimidazole tethered imidazole derivatives by one pot condensation reaction with terrific yields.

Material and Methods

The reagents used in this research work were obtained from Sigma Aldrich, Merck and Loba-chemie. The brick derived clay material used in this synthesis was obtained by grinding the red brick to fine powder. The reaction progress was monitored usingTLC Silica gel 60 aluminum plates (Merck). Melting points of all the derivatives wereobserved in thermal apparatus formelting point. FT-IR spectra were recorded by using Bruker FT-IR spectrophotometer.JEOL JNM-ECX500 spectrometer was used for¹HNMR and ¹³CNMR analysis of derivatives.

Synthesis of brick derived clay catalyst

The clay material was obtained by grinding the brick to fine powder. This grinded powder is then heated in the oven for 24 hours at 120 °C to make it moisture free.

Figure 1: Brick derived clay. Click here to View figure

Figure 2: FT-IR Spectra of brick derived clay. Click here to View figure

Synthesis of benzothiazole / benzimidazole tethered imidazole derivatives.

General procedure

All the four components namelybenzil, 2-aminobenzimidazole / 2-amino-6-nitrobenzothiazole, selected aldehyde, ammonium acetate were taken in  one millimolar quantity along with brick derived clay catalyst (50 mg) in ethanol and refluxed for 45-60 minutes at 70°C. The progression of the reaction is observed by thin layer chromatography (Ethyl acetate- n-hexane 2:3). When the reaction reaches its completion the product filtered for separating the catalyst and cooled at room temperature. The recrystallization has done with ethanol and product obtained with optimum purity.

Scheme 1: Reaction scheme for the synthesis of benzothiazole tethered imidazole derivatives. Click here to View scheme

Scheme 2: Reaction scheme for the synthesis of benzimidazole tethered imidazole derivatives Click here to View scheme

N,N-dimethyl-4-(1-(6-nitrobenzo[d]thiazol-2-yl)-4,5-diphenyl-1H-imidazol-2-yl)aniline (HP-1)

yellow solid; yield 89% ; mp210-213 °C; IR(υ max, cm−¹) :3025 (=C–H), 1648 (C=C,  imidazole), 1540(C=N, imidazole); 1H NMR (400 MHz, DMSO-d6) δ8.01-8.67(d, 3H,  Ar-H), 6.70-7.6 (d, 4H, Ar-H), 7.27-7.40 (d, 10H, Ar-H), 3.04 (s, 6H, C-H); 13C NMR (100 MHz, DMSO-d6) δ 172, 158, 157, 153, 144, 141, 138, 135, 133, 131.8, 130, 126, 125, 123, 122, 121, 120,  119, 117, 112, 111, 110, 49, 48, 42, 40, 39, 38, 37.

2-(2-(3,4-dimethoxyphenyl)-4,5-diphenyl-1H-imidazol-1-yl)-6-nitrobenzo[d]thiazole(HP-2)

Pale yellow solid; yield 86% ; mp196-199 °C; IR(υ max, cm−¹) :3030 (=C–H), 1674 (C=C, imidazole), 1583(C=N, imidazole); 1H NMR (400 MHz, DMSO-d6) δ8.01-8.06(d, 3H,  benzothiazole), 7.5-7.9(d, 10H, C-H), 7.01-7.04 (d, 3H, C-H), 3.8 (d, 6H, O-CH3); 13C NMR (100 MHz, DMSO-d6) δ 196, 192, 172, 171, 156, 149, 142,  138, 137, 136, 135, 132, 131, 130, 129, 128, 127, 125, 123, 115, 112, 109, 98, 95, 58, 56, 42, 40, 38.

4-(1-(1H-benzo[d]imidazol-2-yl)-4,5-diphenyl-1H-imidazol-2-yl)-N,N-dimethylaniline(HP-3)

White solid; yield 88% ; mp205-208 °C; IR(υ max, cm−¹) : 3248(NH)3015 (=C–H), 1675 (C=C, imidazole), 1533(C=N, imidazole); 1H NMR (400 MHz, DMSO-d6) δ9.4-7.9(d, 4H,  Ar-H), 6.7-7 (d, 4H, Ar-H, Benzimidazole), 7.6-7.9 (t, 10H, C-H), 6.02 (d, 1H, N-H), 3.04 (s, 6H, N-CH3); 13C NMR (100 MHz, DMSO-d6) δ 196, 194,193, 192, 190, 188, 185, 172, 170, 156, 154, 146, 139, 137, 133, 132, 131, 130, 128,  126, 125,  120, 112, 44, 42, 41, 40, 39, 38, 21.

2-(2-(3,4-dimethoxyphenyl)-4,5-diphenyl-1H-imidazol-1-yl)-1H-benzo[d]imidazole(HP-4)

White solid; yield 84% ; mp215-218 °C; IR(υ max, cm−¹) :3090 (=C–H), 1673 (C=C, imidazole), 1508(C=N, imidazole); 1H NMR (400 MHz, DMSO-d6) δ9.7-7.9(d, 10H,  Ar-H), 7.1-7.3(d, 4H, Benzimidazole), 7.01-7.04 (d, 3H, C-H), 6.02(d, 1H, N-H), 3.7 (d, 6H, O-CH3); 13C NMR (100 MHz, DMSO-d6) δ 194, 193, 191, 174, 170, 156, 154, 153, 149, 146, 139, 138, 136, 134, 133, 129, 128, 126, 119, 118, 117, 113, 112, 110, 56, 54, 42, 40, 39, 22.

Results and Discussion

Figure 3: FT-IR spectra of HP-3. Click here to View figure

In our investigation, the brick derived clay has emerged as a promising catalyst for the synthesis of benzothiazole /benzimidazole tethered imidazole derivatives. The work up is straight forward without any hectic procedure. All the four component reactions were carried out at 70°C and reached completion point within 45 to 60 minutes with very high efficiency. The yield of imidazole derivatives mainly depends on the functional group associated with aldehyde. An aldehyde with electron-withdrawing groups yields more in comparison to aldehyde with electron-donor groups. The FT-IR spectrum of the products showed characteristic vibrational bands of imidazole moiety at1596 cm⁻¹ for C=N and 1675 cm⁻¹ for C=C groups.

The catalyst has exhibited excellent efficiency in all the reactions and the product yield of various derivatives of benzothiazole /benzimidazole tethered imidazolewere84– 89 % as shown in Table-1.

Table 1: Showingsynthesized benzothiazole / benzimidazole tethered imidazole  derivatives with reaction time and yield. Click here to View table

The quantity of catalyst which results in highest efficiency is tested by carrying out a sequence of reactions with similar reaction conditions but varied amount of the catalyst starting from 10mg. We have found that yield of the product significantly enhanced from 62 to 89% when we increased the amount of catalyst from 10 to 50 mg. The product yield does not change by further increase in the amount of catalyst. So for thefurther synthesis the amount of catalyst is fixed to50 mg.

Table 2: Showing efficiency of the brick derived clay catalyst at different amount.

Weight of catalyst (mg)	Reaction time (min)	Yield (%)
10	45	62
20	45	74
30	45	81
40	45	85
50	45	89

 

Reaction conditions

Substrate: Benzil, Aldehydes, Amines and Ammonium acetate, reaction temperature: 70°c, solvent: ethanol

The recovered catalyst is recycled with ethanol and ready for reuse in the next reaction run. The reused catalyst showed excellent efficiency without any appreciable loss in it. The efficiency of brick derived clay catalyst after successive reaction runs tabulated in Table 3

Table 3: Showing Efficiency of brick derived clay catalyst after successive reaction runs.

Reaction Runs	% Yield
1st	89
2nd	88
3rd	85
4th	84
5th	82

 

We have compared the efficiency of the brick derived clay catalyst with other reported catalysts that are predominantly used in the synthesis of imidazole derivatives like Zeolite, DABCO,  HNO₃@ nano-SiO₂and data tabulated in Table 4

Table 4: Showing comparison of the brick derived clay catalyst with other reported catalysts for imidazole derivatives synthesis

Catalysts	Solvent – Temp.	Reaction Time	Product Yield %
Zeolite32	Ethanol    100 °C	85 min	87
DABCO34	t-BuOH    70 °C	13–14 h	81
HNO3@nano-SiO235	solvent-free 100 °C	3.5 h	90
Brick derived clay	Ethanol     70 °C	45-60min	89

 

This work is primarily focused to enhance the greenness in the synthesis of imidazole derivatives. We have reported novel benzothiazole / benzimidazole tethered imidazole derivatives synthesized by utilizing brick derived clay catalyst. This catalyst is very economical and environmentally benign.

Conclusion

The brick derived clay used in this work qualifies itself on both the fronts, economically as well as environmentally.The yield of products clearly highlights the effectiveness of this catalyst for the synthesis of benzothiazole / benzimidazole tethered imidazole derivatives. This catalyst proves its efficiency by minimizing both the reaction time and waste material.It has delivered excellent yield of the product, moreover this catalyst shows reusability as an important edge over others. Therefore, the brick derived clay can act as a promising candidate for synthesis of benzothiazole / benzimidazole tethered imidazole derivatives with minimal impact on the environment.

Acknowledgment

We are highly grateful to the Dept. of Chemistry, DHSGU and SIC, DHSGU for valuable support in this research work.

References

1. Li, B.; Tayebee, R.; Esmaeili, E.; Namaghi, MS.; Maleki, B.RSC Advances.2020,10, 40725-40738
   CrossRef
2. Chen, R.;  Jalili, Z.; Tayebee, R.  RSC Advances. 2021, 11,16359-16375.
   CrossRef
3. Hashemzadeh, A.; Amini, M.M.; Tayebee, R.; Sadeghian, A.; Durndell, L.J.; Isaacs, M.A.; Osatiashtiani, A.; Parlett, C.M.; Lee, A.F.  Molecular Catalysis. 2017,440,  96-106.
   CrossRef
4. Erfaninia, N.; Tayebee, R.; Dusek, M.; Amini, M.M. Applied Organometallic Chemistry.2018, 32(5), 4307.
   CrossRef
5. Ghohe, N.M.; Tayebee, R.; Amini, M.M.Materials Chemistry and Physics. 2019, 223, 268-276.
   CrossRef
6. Ghohe, N.M.; Tayebee, R.; Amini, M.M.; Osatiashtiani, A.; Isaacs, M.A.; Lee, A.F. Tetrahedron. 2017, 73(40), 5862-5871.
   CrossRef
7. Freire, C.; Pereira, C.; Rebelo, S. Catalysis.2012, 24, 116–203.
   CrossRef
8. Vedrine, J. C.Catalysts.2017, 7, 341.
   CrossRef
9. Climent, M. J.; Corma, A.; Iborra, S. RSC Adv.2012, 2, 16–58.
   CrossRef
10. Bhaskaruni, S. V. H. S.; Maddila, S.; Gangu, K.K.; Jonnalagadda, S. B. Arab. J. Chem. 2017, 13, 1142-1178.
    CrossRef
11. Takagaki, A.; Sugisawa, M.; Lu, D.; Kondo, J.N.; Hara, M.; Domen, K.; Hayashi, S.  J Am Chem Soc.2003,125, 5479–5485.
    CrossRef
12. Rownaghi, A.A.; Rezaei, F.; Hedlund, J. CatalCommun.2011, 14, 37–41.
    CrossRef
13. Rahimi, N.; Karimzadeh, R. Appl.Catal. A.2011, 398, 1–17.
    CrossRef
14. Zawrah, M.F.; Gado, R.A.; Feltin, N.; Ducourtieux, S.; Devoille, L. Process Saf Environ2016, 103, 237–251.
    CrossRef
15. Fort, J.; Vejmelkova, E.; Konakova,  D.; Alblova, N.; Cachova, M.; Keppert, M.; Rovnanikova, P.; Cerny, R.  J Clean Prod, 2018, 194, 714–725.
    CrossRef
16. Madduluri, V.R.; Katari, N.K.; Peddinti, N.; Velpula, V.K.; Burri, D.R.; Kamaraju, S.R.R.; Jonnalagadda, S.B.  Res ChemIntermed.2018, 44, 7619–7639.
    CrossRef
17. Madduluria, V.R.; Neelia, C.K.P.; Katari, N.K.; Ganjalaa, V.S.P.; Thirupataiaha, K.; Kamaraju, S.R.R.  CatalCommun.2018, 110, 38–41.
    CrossRef
18. Raizada, P.; Singh, P.; Kumar, A.; Pare, B.; Jonnalagadda, S.B.Sep Purif Technol.2014, 133, 429–437.
    CrossRef
19. Raizada, P.; Singh, P.; Kumar, A.; Sharma, G.; Pare, B.; Jonnalagadda,; S.B.; Thakur, P. ApplCatal A: General, 2014, 486, 159–169.
    CrossRef
20. Jiang, B.; Rajale, T.; Wever, W.; Tu, S.J.; Li, G.G.  Chem Asian J, 2010, 5, 2318–2335.
    CrossRef
21. Iinuma, Y.; Kozawa, S.; Ishiyama, H.; Tsuda, M.; Fukushi, E.; Kawabata, J.; Fromont, J.; Kobayashi, J.; Gesashidine, A. J Nat Prod.2005, 68, 1109–1110.
    CrossRef
22. Negi, A.; Alex, J.M.; Amrutkar, S.M.; Baviskar, A.T.; Joshi, G.; Singh, S.; Banerjee, U.C.; Kumar, R.   Bioorg Med Chem.2015, 23, 5654–5661.
    CrossRef
23. Schemeth, D.; Kappacher, C.; Rainer, M.; Thalinger, R.; Bonn, G.K. Talanta.2016, 153, 177–185.
    CrossRef
24. Wen, S.Q.; Jeyakkumar. P.; Avula, S.R.; Zhang, L.; Zhou, C.H. Bioorg Med ChemLett.2016, 26, 2768–2773.
    CrossRef
25. Vazquez, G.N.; Figueroa, S.H.; Piedra, M.T.; Galicia, J.V.; Leyva, J.C.R,; Soto, S.E.; Rivera, I.L.; Guardarrama, B.A.; Gomez, Y.R.; Molina, R.V.; Barajas, M.I.  Bioorg Med Chem.2010, 18, 3985–3991.
    CrossRef
26. Sontakke, V. A.; Kate, A. N.; Ghosh, S.; More, P.; Gonnade, R.; Kumbhar, N. M.; Kumbhar, A. A.; Chopade, B. A.; Shinde, V. S. New J. Chem. 2015,  39, 4882-4890.
    CrossRef
27. Arulmurugan, S.; Kavitha, H.P. Orient. J. Chem. 2020, 36(4), 672-679
    CrossRef
28. Gaba, M.; Mohan, C.  Med. Chem. 2015,  5(2), 58-63.
29. Ajani, O.O.; Aderohunmu, D.V.; Olorunshola, S.J.;Ikpo, C.O.; Olanrewaju, I.O.Orient. J. Chem.2016, 32(1), 109-120
    CrossRef
30. Zhao, S.; Zhao, L.; Zhang, X.; Liu, C.; Hao, C.; Xie, H.; Sun, B.; Zhao, D.; Cheng, M. Eur. J. Med. Chem.2016, 123, 514-522
    CrossRef
31. Sadhasivam, G.; Kulanthai, K.; Natarajan, A. Orient. J. Chem.2015, 31(2), 819-826. 
    CrossRef    
32. Teimouri, A.; Chermahini, A.N.  J MolCatal A,2011, 346, 39–45.
    CrossRef
33. Das, B.; Kashanna, J.; Kumar, R.A.; Jangili, P. MonatshChem, 2013, 144, 223–226.
    CrossRef
34. Murthy, S.N.; Madhav, B.; Nageswar, Y.V.D.,  TetrahedronLett, 2010, 51, 5252–5257.
    CrossRef
35. Nikoofar, K.; Dizgarani, S.M.   J Saudi ChemSoc, 2017, 21, 787–794.
    CrossRef
36. Samai, S.; Nandi, G.C.; Singh, P.; Singh, .S.;Tetrahedron,2009,65,10155–10161.
    CrossRef
37. Kantevari, S.; Vuppalapati, S.V.N.; Biradar, D.O.; Nagarapu, L.;J. Mol. Catal. A: Chem.2007,266, 109–113.
    CrossRef
38. Wang, X.C.; Gong, H.P.; Quan, Z.J.; Li, L.; Ye, H.L.;Chinese Chem. Lett., 2009, 20, 44-47.
    CrossRef
39. Safari, J.; Ravandi, S.G.; Akbari, Z. J. Adv. Res. 2013, 4, 509–514.
    CrossRef
40. Mirjalili, B.F.; Bamoniri, A.H.; Zamani, L. Sci. Iran., 2012, 19, 565–568.
    CrossRef
41. Alikarami, M.; Amozad, M. Bull ChemSoc Ethiop.2017, 31, 177.
    CrossRef
42. Hashmi, S.Z.; Kishore, D. ARKIVOC.2016,318.
    CrossRef
43. Hashmi, S.Z.; Kishore, D.J.;  Heterocyclic Chem. 2017, 54, 2912
    CrossRef
44. Borhade, A. V.; Tope, D. R.;Gite S.G. Arabian J Chem.2017, 10, S559.
    CrossRef
45. Bansal, R.; Soni, P.K.; Halve, A.K. J. Heterocyclic Chem.2018, 55, 1308-1312
    CrossRef
46. Thwin, M.; Mahmoudi, B.; Ivaschukc, O.A.;Yousif, Q.A.RSC Adv.2019, 9, 15966
    CrossRef
47. Arora, G.; Gupta, R.; Yadav, P.; Dixit, R.; Srivastava, A.; Sharma, R.K. Current Research in Green and Sustainable Chemistry.2021, 4, 100050
    CrossRef

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