Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Chemical Papers

IMPACT FACTOR 2016: 1.258

SCImago Journal Rank (SJR) 2016: 0.348
Source Normalized Impact per Paper (SNIP) 2016: 0.533

See all formats and pricing
More options …
Volume 68, Issue 5 (May 2014)


“Green synthesis” of benzothiazepine library of indeno analogues and their in vitro antimicrobial activity

Ashok Acharya / Rahul Kamble / Snehalkumar Patil / Shrikant Hese / Omprakash Yemul / Sudhakar Patil / Shivshankar Halale / Bhaskar Dawane
Published Online: 2014-01-28 | DOI: https://doi.org/10.2478/s11696-013-0496-4


A novel series of indeno-benzothiazepine derivatives was synthesised via a “green” route. Synthesis of these compounds involves the treatment of dinucleophiles such as 2-aminobenzenethiols with α,β-unsaturated ketones in poly(oxyethylene) (poly(ethylene glycol), PEG-400) catalysed by acetic acid. The synthone α,β-unsaturated ketones were obtained by Claisen-Schmidt condensation of indan-1-one with substituted pyrazole-2-carbaldehydes prompted by bleaching earth (pH 12.5) as catalyst and PEG-400 as “green” reaction solvent. Screening of all the synthesised compounds for antimicrobial activity revealed that most of these compounds exhibited moderate to significant antimicrobial activity.

Keywords: indeno-benzothiazepine; PEG-400; bleaching earth; antimicrobial activity

  • [1] Ballini, R., Bosica, G., Maggi, R., Ricciutelli, M., Righi, P., Sartori, G., & Sartorio, R. (2001). Clay-catalysed solventless synthesis of trans-chalcones. Green Chemistry, 3, 178–180. DOI: 10.1039/b101355f. http://dx.doi.org/10.1039/b101355fCrossrefGoogle Scholar

  • [2] Baag, M. M., Sahoo, M. K., Puranik, V. G.,& Argade, N. P. (2007). Reactions of o-aminothiophenol and o-aminophenyl disulfide with itaconic anhydride and (-)-dimenthyl itaconate: Access to enantiomerically pure 1,5-benzothiazepines and benzothiazolyl-2-methylacrylic acid. Synthesis, 2007, 457–463. DOI: 10.1055/s-2006-958977. http://dx.doi.org/10.1055/s-2006-958977Web of ScienceCrossrefGoogle Scholar

  • [3] Chandrasekhar, S., Narsihmulu, C., Sultana, S. S.,& Reddy, N. R. (2002). Poly(ethylene glycol) (PEG) as a reusable solvent medium for organic synthesis. Application in the Heck reaction. Organic Letters, 4, 4399–4401. DOI: 10.1021/ol0266976. http://dx.doi.org/10.1021/ol0266976CrossrefGoogle Scholar

  • [4] Chandrasekhar, S., Narsihmulu, C., Sultana, S. S., & Reddy, N. R. (2003). Osmium tetroxide in poly(ethylene glycol) (PEG): a recyclable reaction medium for rapid asymmetric dihydroxylation under Sharpless conditions. Chemical Communication, 2003, 1716–1717. DOI: 10.1039/b305154b. CrossrefGoogle Scholar

  • [5] Chen, J., Spear, S. K., Huddleston, J. G., & Rogers, R. D. (2005). Polyethylene glycol and solutions of polyethylene glycol as green reaction media. Green Chemistry, 7, 64–82. DOI: 10.1039/b413546f. http://dx.doi.org/10.1039/b413546fCrossrefWeb of ScienceGoogle Scholar

  • [6] Chobe, S. S., Dawane, B. S., Tumbi, K. M., Nandekar, P. P.,& Sangamwar, A. T. (2012). An ecofriendly synthesis and DNA binding interaction study of some pyrazolo[1,5-a]pyrimidines derivatives. Bioorganic & Medicinal Chemistry Letters, 22, 7566–7572. DOI: 10.1016/j.bmcl.2012.10.027. http://dx.doi.org/10.1016/j.bmcl.2012.10.027CrossrefWeb of ScienceGoogle Scholar

  • [7] Chobe, S. S., Kamble, R. D., Patil, S. D., Acharya, A. P., Hese, S. V., Yemul, O. S.,& Dawane, B. S. (2013). Green approach towards synthesis of substituted pyrazole-1,4-dihydro,9-oxa,1,2,6,8-tetrazacyclopentano[b]naphthalene-5-one derivatives as antimycobacterial agents. Medicinal Chemistry Research, 22, 5197–5203. DOI: 10.1007/s00044-013-0487-6. http://dx.doi.org/10.1007/s00044-013-0487-6CrossrefGoogle Scholar

  • [8] Cox, D. A., & Matlib, M. A. (1993). Modulation of intramitochondrial free Ca2+ concentration by antagonists of Na+ -Ca2+ exchange. Trends in Pharmacological Sciences, 14, 408–413. DOI: 10.1016/0165-6147(93)90063-p. http://dx.doi.org/10.1016/0165-6147(93)90063-PCrossrefGoogle Scholar

  • [9] Dawane, B. S., Konda, S. G., Mandawad, G. G.,& Shaikh, B. M. (2010a). Poly(ethylene glycol) (PEG-400) as an alternative reaction solvent for the synthesis of some new 1-(4-(4′-chlorophenyl-2-thiazolyl)-3-aryl-5-(2-butyl-4-chloro-1Himidazol-5-yl)-2-pyrazolines and their in vitro antimicrobial evaluation. European Journal of Medicinal Chemistry, 45, 387–392. DOI: 10.1016/j.ejmech.2009.10.015. http://dx.doi.org/10.1016/j.ejmech.2009.10.015Web of ScienceCrossrefGoogle Scholar

  • [10] Dawane, B. S., Shaikh, B. M., Khandare, N. T., Kamble, V. T., Chobe, S. S.,& Konda, S. G. (2010b). Eco-friendly polyethylene glycol-400: a rapid and efficient recyclable reaction medium for the synthesis of thiazole derivatives. Green Chemistry Letters and Reviews, 3, 205–208. DOI: 10.1080/17518251003709506. http://dx.doi.org/10.1080/17518251003709506Web of ScienceCrossrefGoogle Scholar

  • [11] De Sarro, G., Chimirri, A., De Sarro, A., Gitto, R., Grasso, S., & Zappalà, M. (1995). 5H[1,2,4]Oxadiazolo[5,4-d][1,5]benzothiazepines as anticonvulsant agents in DBA/2 mice. European Journal of Medicinal Chemistry, 30, 925–929. DOI: 10.1016/0223-5234(96)88311-5. http://dx.doi.org/10.1016/0223-5234(96)88311-5CrossrefGoogle Scholar

  • [12] Di Santo, R., & Costi, R. (2005). 2H-Pyrrolo[3,4-b][1,5]benzothiazepine derivatives as potential inhibitors of HIV-1 reverse transcriptase. II Farmaco, 60, 385–392. DOI: 10.1016/j.farmac.2005.03.006. http://dx.doi.org/10.1016/j.farmac.2005.03.006Google Scholar

  • [13] El-Bayouki, K. A. M. (2013). Benzo[1,5]thiazepine: Synthesis, reactions, spectroscopy, and applications. Organic Chemistry International, 2013, 210474. DOI: 10.1155/2013/210474. http://dx.doi.org/10.1155/2013/210474CrossrefGoogle Scholar

  • [14] Grandolini, G., Perioli, L.,& Ambrogi, V. (1999). Synthesis of some new 1,4-benzothiazine and 1,5-benzothiazepine tricyclic derivatives with structural analogy with TIBO and their screening for anti-HIV activity. European Journal of Medicinal Chemistry, 34, 701–709. DOI: 10.1016/s0223-5234(99)00223-8. http://dx.doi.org/10.1016/S0223-5234(99)00223-8CrossrefGoogle Scholar

  • [15] Heldebrant, D. T., & Jessop, P. G. (2003). Liquid poly(ethylene glycol) and supercritical carbon dioxide: a benign biphasic solvent system for use and recycling of homogeneous catalysts. Journal of the American Chemical Society, 125, 5600–5601. DOI: 10.1021/ja029131l. http://dx.doi.org/10.1021/ja029131lCrossrefGoogle Scholar

  • [16] Jain, R., Yadav, T., Kumar, M.,& Yadav, A. K. (2011). Facile ionic liquid-mediated protocol for the regioselective synthesis of 1,5-benzothiazepines. Synthetic Communications, 41, 1889–1900. DOI: 10.1080/00397911.2010.493626. http://dx.doi.org/10.1080/00397911.2010.493626CrossrefGoogle Scholar

  • [17] Konda, S. G., Humne, V. T., & Lokhande, P. D. (2011). Rapid and selective deallylation of allyl ethers and esters using iodine in polyethylene glycol-400. Green Chemistry, 13, 2354–2358. DOI: 10.1039/c1gc15153c. http://dx.doi.org/10.1039/c1gc15153cCrossrefWeb of ScienceGoogle Scholar

  • [18] Kurokawa, J., Adachi-Akahane, S.,& Nagao, T. (1997). Effects of a novel, potent benzothia-zepine Ca2+ channel antagonist, DTZ323, on guinea-pig ventricular myocytes. European Journal of Pharmacology, 325, 229–236. DOI: 10.1016/s0014-2999(97)00119-2. http://dx.doi.org/10.1016/S0014-2999(97)00119-2CrossrefGoogle Scholar

  • [19] Miyata, O., Hinada, T., Ninomiya, I., & Naito, T. (1997). Asymmetric construction of two contiguous stereocenters by diastereoface differentiating addition reaction of thiols to chiral imides: Formal synthesis of (+)-diltiazem. Tetrahedron, 53, 2421–2438. DOI: 10.1016/s0040-4020(96)01191-x. http://dx.doi.org/10.1016/S0040-4020(96)01191-XCrossrefGoogle Scholar

  • [20] Prakash, O., Kumar, A. Sadana, A., Prakash, R., Singh, S. P., Claramunt, R. M., Sanz, D., Alkorta, I.,& Elguero, J. (2005). Study of the reaction of chalcone analogs of dehydroacetic acid and o-aminothiophenol: synthesis and structure of 1,5-benzothiazepines and 1,4-benzothiazines. Tetrahedron, 61, 6642–6651. DOI: 10.1016/j.tet.2005.03.035. http://dx.doi.org/10.1016/j.tet.2005.03.035CrossrefGoogle Scholar

  • [21] Rao, D. M., Giridhar, T., Reddy, R. B.,& Mouli, G. V. P. C. (1995). A novel synthesis of benzothiazepines. Indian Journal of Heterocyclic Chemistry, 5, 145–148. Google Scholar

  • [22] Sindler-Kulyk, M., & Neckers, D. C. (1982). Photochemistry of 2-phenylbenzothiazole with ethoxyacetylene and ethoxypropyne. Synthesis of 1,5-benzothiazepines The Journal of Organic Chemistry, 47, 4914–4919. DOI: 10.1021/ jo00146a018. CrossrefGoogle Scholar

  • [23] Upadhyay, K. Manvar, A., Rawal, K., Joshi, S., Trivedi, J., Chaniyara, R., & Shah, A. (2012). Evaluation of structurally diverse benzoazepines clubbed with coumarins as Mycobacterium tuberculosis agents. Chemical Biology & Drug Design, 80, 1003–1008. DOI: 10.1111/j.1747-0285.2012.01436.x. http://dx.doi.org/10.1111/j.1747-0285.2012.01436.xWeb of ScienceCrossrefGoogle Scholar

  • [24] Urbanski, M. J., Chen, R. H., Demarest, K. T., Gunnet, J., Look, R., Ericson, E., Murray, W. V., Rybczynski, P. J.,& Zhang, X. (2003). 2,5-Disubstituted 3,4-dihydro-2Hbenzo[b][1,4]thiazepines as potent and selective V2 arginine vasopressin receptor antagonists. Bioorganic & Medicinal Chemistry Letters, 13, 4031–4034. DOI: 10.1016/j.bmcl.2003.08.051. http://dx.doi.org/10.1016/j.bmcl.2003.08.051CrossrefWeb of ScienceGoogle Scholar

  • [25] Yadav, J. S., Reddy, B. V. S., Eshwaraiah, B., & Anuradha, K. (2002). Amberlyst-15®: a novel and recyclable reagent for the synthesis of 1,5-benzodiazepines in ionic liquids. Green Chemistry, 4, 592–594. DOI: 10.1039/b206558b. http://dx.doi.org/10.1039/b206558bCrossrefGoogle Scholar

  • [26] Yang, X., Buzon, L., Hamanaka, E.,& Liu, K. K. C. (2000). Enzymatic resolution of benzothiazepine for the preparation of squalene synthetase inhibitors. Tetrahedron Asymmetry, 11, 4447–4450. DOI: 10.1016/s0957-4166(00)00458-4. http://dx.doi.org/10.1016/S0957-4166(00)00458-4CrossrefGoogle Scholar

  • [27] Zhong, W., Chen, X.,& Zhang, Y. (2000). Low-valent titanium induced simultaneous reduction of nitro group and S-S bond in nitrodisulfides: A novel method for the synthesis of benzothiazoline, benzothiazoles and 2,3-dihydro-1,5-benzothiazepines. Synthetic Communications, 30, 4451–4460. DOI: 10.1080/00397910008087072. http://dx.doi.org/10.1080/00397910008087072CrossrefGoogle Scholar

About the article

Published Online: 2014-01-28

Published in Print: 2014-05-01

Citation Information: Chemical Papers, ISSN (Online) 1336-9075, DOI: https://doi.org/10.2478/s11696-013-0496-4.

Export Citation

© 2013 Institute of Chemistry, Slovak Academy of Sciences. Copyright Clearance Center

Comments (0)

Please log in or register to comment.
Log in