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Theoretical and experimental solid state studies of Ethyl 1-benzyl-2-(thiophen-3-yl)-1H-benzo[d]imidazole-5-carboxylate

  • Shankar Madan Kumar EMAIL logo , Vasantha Kumar , Mohammed Al-Ghorbani , Bantwala Shivaram Holla , Boja Poojary , Padikkaruvanth Praveen , Siddaiah Chandra Nayak , Janani S. Mohan , Subbiah Thamotharan , Varija Raghu Shamprasad , Neratur Krishnappagowda Lokanath , Nabil Al-Zaqri and Ali Alsalme


The title compound Ethyl 1-benzyl-2-(thiophen-3-yl)-1H-benzo[d]imidazole-5-carboxylate (BI) is prepared and characterized using spectroscopic methods. The theoretical optimization and three dimensional molecular structure are confirmed by X-ray diffraction method (single crystal). The C–H…π intermolecular interactions stabilize the crystal structure. The intermolecular contacts in the crystal structure are quantified using Hirshfeld surfaces and the crystal packing is elucidated using 3D energy frameworks analysis. In the frameworks, the dispersion energy term is dominated over the electrostatic energy term. The structural optimization was carried out with B3LYP/6-311++G (d, p) level of theory. The visual representations of positive and negative potentials (electrostatic potential) are mapped on the electron density isosurface. The band gap energy (HOMO-LUMO) of the molecule is calculated to be 4.36 eV. Structural conformation of BI is compared with similar structures.

Corresponding author: Shankar Madan Kumar, IOE, Vijnana Bhavan, University of Mysore, Mysore 570006, India, E-mail:


Authors thank IOE and DST PURSE Lab, Vijnana Bhavan, University of Mysore, Mysore, and SDM College (Autonomous), Ujire. Researchers supporting project (RSP-2020/78), King Saud University, Riyadh, Saudi Arabia.

  1. Author contribution: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.


1. Goker, H., Kus, C., Boykin, D. W., Yildiz, S., Altanlar, N. Synthesis of some new 2-substituted-phenyl-1H-benzimidazole-5-carbonitriles and their potent activity against Candida species. Bioorg. Med. Chem. 2002, 10, 2589–2596; in Google Scholar

2. Evans, D., Hicks, T. A., Williamson, W. R. N., Dawson, W., Meacock, S. C. R., Kitchen, E. A. Synthesis of a group of 1H-benzimidazoles and their screening for anti-inflammatory activity. Eur. J. Med. Chem. 1996, 31, 635–642; in Google Scholar

3. Nakano, H., Inoue, T., Kawasaki, N., Miyataka, H., Matsumoto, H., Taguchi, T., Inagaki, N., Nagai, H., Satoh, T. Synthesis of benzimidazole derivatives as antiallergic agents with 5-lipoxygenase inhibiting action. Chem. Pharm. Bull. 1999, 47, 1573–1578; in Google Scholar

4. Kus, C., Ayhan-Kilcigil, G., Can-Eke, B., Iscan, M. Synthesis and antioxidant properties of some novel benzimidazole derivatives on lipid peroxidation in the rat liver. Arch. Pharm. Res. 2004, 27, 156–163; in Google Scholar

5. Mohamed, B. G., Hussein, M. A., Abdel-Alim, A. M., Hashem, M. Synthesis and antimicrobial activity of some new 1-alkyl-2-alkylthio-1,2,4-triazolobenzimidazole derivatives. Arch. Pharm. Res. 2006, 29, 26–33; in Google Scholar

6. Denny, W. A., Rewcastle, G. W., Baguley, B. C. Potential antitumor agents, 59: structure–activity relationships for 2-phenylbenzimidazole-4-carboxamides, a new class of minimal DNA-intercalating agents which may not act via topoisomerase II. J. Med. Chem. 1990, 33, 814–819; in Google Scholar

7. Mavrova, A. T., Anichina, K. K., Vuchev, D. I., Tsenov, J. A., Denkova, P. S., Kondeva, M. S., Micheva, M. K. Antihelminthic activity of some newly synthesized 5(6)-(un) substituted-1H-benzimidazol-2-ylthioacetylpiperazine derivatives. Eur. J. Med. Chem. 2006, 41, 1412–1420; in Google Scholar

8. Victor, F., Brown, T. J., Campanale, K., Heinz, B. A., Shipley, L. A., Su, K. S., Tang, J., Vance, L. M., Spitzer, W. A. Synthesis, antiviral activity, and biological properties of vinylacetylene analogs of enviroxime. J. Med. Chem. 1997, 40, 151–1518; in Google Scholar

9. Camacho, J., Barazarte, A., Gamboa, N., Rodrigues, J., Rojas, R., Vaisberg, A., Gilman, R., Charris, J. Synthesis and biological evaluation of benzimidazole-5-carbohydrazide derivatives as antimalarial, cytotoxic and antitubercular agents. Bioorg. Med. Chem. 2011, 19, 2023–2029; in Google Scholar

10. Kumar, V., Poojary, B., Prathibha, A., Shruthi, N. Synthesis of some novel 1,2-disubstituted benzimidazole-5-carboxylates via one-pot method using sodium dithionite and its effect on N-debenzylation. Synth. Commun. 2014, 44, 3414–3425; in Google Scholar

11. Almansour, A. I., Arumugam, N., Kumar, R. S., Soliman, S. M., Altaf, M., Ghabbour, H. A. Synthesis, spectroscopic, X-ray diffraction and DFT studies of novel benzimidazole fused-1,4-oxazepines. Molecules 2016, 21, 724; in Google Scholar

12. Shivaprasad, C. M., Madan Kumar, S., Swaroop, T. R., Rangappa, K. S., Lokanath, N. K. 1-(4-Methylphenylsulfonyl)-2-{[3-methyl-4-(2,2,2-trifluoro-ethoxy)pyridin-2-yl]methylsulfanyl}-1H-1,3-benzimidazole. Acta Crystallogr. 2013, E69, 1846; in Google Scholar

13. Madan Kumar, S., Manasa, D., Kumar, V., Poojary, B., Byrappa, K., Abdoh, M. M. M. Ethyl 1-benzyl-2-(3-chlorophenyl)-1H-benzimidazole-5-carboxylate. IUCrData 2016, 1, 161068; in Google Scholar

14. Shivaprasad, C. M., Madan Kumar, S., Manjunath, B. C., Swaroop, T. R., Rangappa, K. S., Lokanath, N. K. Synthesis and structural studies of 2-((3-Methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl)methylthio)-1-(methylsulfonyl)-1H-benzo[d]imidazole. X-ray Struct. Anal. Online 2013, 29, 49, in Google Scholar

15. Usha, M. K., Madan Kumar, S., Vidyashree Jois, H. S., Kalluraya, B., Lokanath, N. K., Revannasiddaiah, D. 5-[(2-Methyl-4-nitro-1H-imidazol-1-yl)methyl]-1,3,4-thiadiazol-2-amine. Acta Crystallogr. 2013, E69, o1825; in Google Scholar

16. Mallappa, P., Shivapura, V., Madan Kumar, S., Nagaraju, G. K., Lokanath, N. K. 4-(4,5-Diphenyl-1H-imidazol-2-yl)-N,N-dimethylaniline. Acta Crystallogr. 2013, E69, o1006; in Google Scholar

17. Mallappa, P., Madan Kumar, S., Muneer, C. P., Shafi, P. M., Lokanath, N. K. 4-[Amino(3-methylphenyl)methylidene]-2-(3-methylphenyl)-1H-imidazol-5(4H)-one ethanol hemisolvate. Acta Crystallogr. 2013, E69, o174, in Google Scholar

18. Turner, M. M. J., Thomas, S. P., Shi, M. W., Jayatilaka, D., Spackman, M. A. Energy frameworks: insights into interaction anisotropy and the mechanical properties of molecular crystals. Chem. Commun. 2015, 51, 3735–3738; in Google Scholar

19. Madan Kumar, S., Lakshminarayana, B. N., Nagaraju, S., Sushma, Ananda, S., Manjunath, B. C., Lokanath, N. K., Byrappa, K. 3D energy frameworks of a potential nutraceutical. J. Mol. Struct. 2018, 1173, 300–306; in Google Scholar

20. Madan Kumar, S., Al-Ostoot Fares, H., Manjunath, B. C., Shamprasad, V. R., Yasser Hussein Eissa, Md., Mahesh, N., Zabiulla, Shaukath, A. K., Lokanath, N. K., Byrappa, K. Crystal packing analysis of 1-(3,4-dimethoxyphenyl)-3-(4-bromophenyl)prop-2-en-1-one exhibiting a putative halogen bond C–Br⋯O. J. Mol. Struct. 2018, 1156, 216–223; in Google Scholar

21. Rigaku Crystal Clear SM Expert 2.0 r15. Software for Data Collection and Processing; Rigaku Corporation: Tokyo, Japan, 2011.Search in Google Scholar

22. Sheldrick, G. M. A short history of SHELX. Acta Crystallogr. 2008, A64, 112–122; in Google Scholar

23. Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K., Puschmann, H. OLEX2: a complete structure solution, refinement and analysis program. J. Appl. Cryst. 2009, 42, 339–341; in Google Scholar

24. Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edging-ton, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J., Wood, P. A. Mercury CSD 2.0 – new features for the visualization and investigation of crystal structures. J. Appl. Crystallogr. 2008, 41, 466–470; in Google Scholar

25. Spackman, M. A., Jayatilaka, D. Hirshfeld surface analysis. Cryst. Eng. Comm. 2009, 11, 19–32; in Google Scholar

26. Spackman, M. A., McKinnon, J. J. Fingerprinting intermolecular interactions in molecular crystals. Cryst. Eng. Comm. 2002, 4, 378–392; in Google Scholar

27. Madan Kumar, S., Manjunath, B. C., Lingaraju, G. S., Abdoh, M. M. M., Sadashiva, M. P., Lokanath, N. K. A Hirshfeld surface analysis and crystal structure of 2′-[1-(2-fluoro-phenyl)-1H-tetrazol-5-]-4-methoxy-biphenyl-2carbaldehyde. Crystal. Struct. Theory Appl. 2013, 3, 124–131; in Google Scholar

28. McKinnon, J. J., Spackman, M. A., Mitchell, A. S. Novel tools for visualizing and exploring intermolecular interactions in molecular crystals. J. Acta. Crystallogr. 2004, B60, 627–668; in Google Scholar

29. Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D., Spackman, M. A. Crystal Explorer 17, 17; University of Western Australia: Australia, 2017.Search in Google Scholar

30. Turner, M. J., Grabowsky, S., Jayatilaka, D., Spackman, M. A. Accurate and efficient model energies for exploring intermolecular interactions in molecular crystals. J. Phys. Chem. Lett. 2014, 5, 4249–4255; in Google Scholar

31. Mackenzie, C. F., Spackman, P. R., Jayatilaka, D., Spackman, M. A. Crystal explorer model energies and energy frameworks: extension to metal coordination compounds, organic salts, solvates and open-shell systems. IUCrJ 2017, 4, 575–587; in Google Scholar

32. Madan Kumar, S., Hemraju, B. C., Anil, S. M., Manjunatha, N. K., Swamy, M. T., Lokanath, N. K., Al-Ghorbani, M., Al-Zaqri, N., Ali, A. Crystal structure, Hirshfeld surfaces, topology, energy frameworks and dielectric studies of 1-(2-chlorophenyl)-3,3-bis(methylthio)prop-2-en-1-one. Z. Kristallogr. 2019, 235, 85–93; in Google Scholar

33. Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Petersson, G. A., Nakatsuji, H., Li, X., Caricato, M., Marenich, A., Bloino, J., Janesko, B. G., Gomperts, R., Mennucci, B., Hratchian, H. P., Ortiz, J. V., Izmaylov, A. F., Sonnenberg, J. L., Williams-Young, D., Ding, F., Lipparini, F., Egidi, F., Goings, J., Peng, B., Petrone, A., Henderson, T., Ranasinghe, D., Zakrzewski, V. G., Gao, J., Rega, N., Zheng, G., Liang, W., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Throssell, K., Montgomery, J. A., Peralta, J. E., Ogliaro, F., Bearpark, M., Heyd, J. J., Brothers, E., Kudin, K. N., Staroverov, V. N., Keith, T., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J. C., Iyengar, S. S., Tomasi, J., Cossi, M., Millam, J. M., Klene, M., Adamo, C., Cammi, R., Ochterski, J. W., Martin, R. L., Morokuma, K., Farkas, O., Foresman, J. B., Fox, D. J. Gaussian 09, Revision A.02; Gaussian, Inc.: Wallingford CT, 2016.Search in Google Scholar

34. Kohn, W., Sham, L. J. Self-consistent equations including exchange and correlation effects. Phys. Rev. 1965, 140, A1133–A1138; in Google Scholar

35. Bulat, F. A., Toro-Labbe, A., Brinck, T., Murray, J. S., Politzer, P. Quantitative analysis of molecular surfaces: areas, volumes, electrostatic potentials and average local ionization energies. J. Mol. Model. 2010, 16, 1679–1691; in Google Scholar

36. Naven, S., Kumar, V., Poojary, B., Holla, B. S., Lokanath, N. K., Abdoh, M. M. M. Ethyl 1-benzyl-2-(4-methoxyphenyl)-1H-benzimidazole-5-carboxylate. IUCrDATA 2016, 1, x161759; in Google Scholar

Supplementary Material

Crystallographic data for the complex has been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 1538327 Copies of this information may be obtained free of charge via (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44-1223-336033; ).

The online version of this article offers supplementary material (

Received: 2020-04-30
Accepted: 2020-08-19
Published Online: 2020-09-17
Published in Print: 2020-11-26

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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