Synthesis of new indole-containing derivatives of 3-acetyl-2H-chromen-2-ones under iodine catalysis and in silico analysis of the biological properties of the obtained compounds
DOI:
https://doi.org/10.33581/2520-257X-2026-1-%25pKeywords:
catalysis, indole, 3-acetyl-2H-chromen-2-ones, 7-azaindoleм, PASS Online electronic platform, in silico analysisAbstract
An efficient method for the preparation of 2-(1,1-di-1H-indol-3-ylethyl)-3H-benzo[f]chromen-3-one and 3-[1-(1H-indol-2-yl)-1-(1H-indol-3-yl)ethyl]-6-nitro-2H-chromen-2-one from the corresponding 3-acetyl-2H-chromen-2‑ones and indole in dichloromethane under iodine catalysis was developed. The presence of steric hindrance near the carbonyl group resulted in a mixture of products of unidentified composition. In silico calculations on the PASS Online electronic platform showed that 2-(1,1-di-1H-indol-3-ylethyl)-3H-benzo[f]chromen-3-one and 3-[1-(1H-indol-2-yl)-1-(1H-indol-3-yl)ethyl]-6-nitro-2H-chromen-2-one may have high structural similarity to known compounds exhibiting antiarthritic activity, and also acting as substrates of cytochrome CYP2F1, an enzyme involved in the metabolism of xenobiotics and some drugs.
References
Husain A, Alasmari AF, Azmi SNH, Ali N, Sarker MMR, Alharbi M, et al. Rational drug design, synthesis, and in vivo biological activity of new indolyl-imidazolone hybrids as potential and safer non-steroidal anti-inflammatory agents. Journal of King Saud University – Science. 2022;34(4):102023. DOI: 10.1016/j.jksus.2022.102023.
Gribble GW, editor. Heterocyclic scaffolds II: reactions and applications of indoles. Berlin: Springer; 2010. XIII, 488 p. (Maes BUW, editor. Topics in heterocyclic chemistry; volume 26). DOI: 10.1007/978-3-642-15733-2.
Praveen C, Dheenkumar P, Muralidharan D, Perumal PT. Synthesis, antimicrobial and antioxidant evaluation of quinolines and bis(indolyl)methanes. Bioorganic & Medicinal Chemistry Letters. 2010;20(24):7292–7296. DOI: 10.1016/j.bmcl.2010.10.075.
Keri RS, Sasidhar BS, Nagaraja BM, Santos MA. Recent progress in the drug development of coumarin derivatives as potent antituberculosis agents. European Journal of Medicinal Chemistry. 2015;100:257–269. DOI: 10.1016/j.ejmech.2015.06.017.
Shi L, Liu Y, Wang C, Yuan X, Liu X, Wu L, et al. Synthesis of 1-(β-coumarinyl)-1-(β-indolyl)trifluoroethanols through regioselective Friedel – Crafts alkylation of indoles with β-(trifluoroacetyl)coumarins catalyzed by Sc(OTf)3. RSC Advances. 2020;10(24):13929–13935. DOI: 10.1039/d0ra01237h.
Yuan X, Wu L, Xu C, Pan Z, Shi L, Yang G, et al. A consecutive one-pot two-step approach to novel trifluoromethyl-substituted bis(indolyl)methane derivatives promoted by Sc(OTf)3 and p-TSA. Tetrahedron Letters. 2019;60(52):151329. DOI: 10.1016/j.tetlet.2019.151329.
Wang W-B, Zhu Y-S, Guo S-Q, Wang Q-L, Bu Z-W. A FeCl3-catalyzed highly regioselective 1,2-addition/substitution sequence for the construction of coumarin-substituted bis(indolyl)methanes. Organic & Biomolecular Chemistry. 2016;14(19):4420–4425. DOI: 10.1039/C6OB00515B.
Минеева ИВ. 2-Замещенные аллилбромиды как электрофильные и нуклеофильные структурные блоки для создания фрагментов 1,3-дикарбонильных соединений. Применение в синтезе гетероциклических соединений. Журнал органической химии. 2022;58(9):936–950. DOI: 10.31857/S0514749222090038.
Zhou X-Y, Chen X. Halogen bond-catalyzed Friedel – Crafts alkylation of indole with ketones and aldehydes for the synthesis of symmetrical 3,3′-diindolylmethanes using simple halogen donor catalyst. Letters in Organic Chemistry. 2021;18(8):604–610. DOI: 10.2174/1570178617999201012181016.
Bandgar BP, Shaikh KA. Molecular iodine-catalyzed efficient and highly rapid synthesis of bis(indolyl)methanes under mild conditions. Tetrahedron Letters. 2003;44(9):1959–1961. DOI: 10.1016/S0040-4039(03)00032-7.
Singh N, Singh KN. Iodine-catalyzed highly efficient synthesis of 3-alkylated/3-alkenylated indoles from 1,3-dicarbonyl compounds. Synlett. 2012;23(14):2116–2120. DOI: 10.1055/s-0032-1316684.
Yadav RN, Banik I, Banik BK. A novel method for the synthesis of bis-indole under microwave irradiation. Journal of the Indian Chemical Society. 2018;95(11):1397–1399.
Wang S-Y, Ji S-J, Loh T-P. The Michael addition of indole to α,β-unsaturated ketones catalyzed by iodine at room temperature. Synlett. 2003;14(15):2377–2379. DOI: 10.1055/s-2003-42105.
Pal R, Das Gupta A, Mallik AK. Facile iodine-catalyzed Michael addition of indoles to α,α′-bis(arylmethylene)cyclopentanones: an efficient synthesis of E-2-(3-indolylphenylmethyl)-5-phenylmethylenecyclopentanones. ISRN Organic Chemistry. 2012;2012:674629. DOI: 10.5402/2012/674629.
von der Heiden D, Bozkus S, Klussmann M, Breugst M. Reaction mechanism of iodine-catalyzed Michael additions. The Journal of Organic Chemistry. 2017;82(8):4037–4043. DOI: 10.1021/acs.joc.7b00445.
Ko S, Lin C, Tu Z, Wang Y-F, Wang C-C, Yao C-F. CAN and iodine-catalyzed reaction of indole or 1-methylindole with α,β-unsaturated ketone or aldehyde. Tetrahedron Letters. 2006;47(4):487–492. DOI: 10.1016/j.tetlet.2005.11.058.
Yin G, Fan L, Ren T, Zheng C, Tao Q, Wu A, et al. Synthesis of functionalized 2-aryl-4-(indol-3-yl)-4H-chromenes via iodine-catalyzed domino Michael addition – intramolecular cyclization reaction. Organic & Biomolecular Chemistry. 2012;10(44):8877–8883. DOI: 10.1039/C2OB26642C.
Rao VR, Muthenna P, Shankaraiah G, Akileshwari C, Babu KH, Suresh G, et al. Synthesis and biological evaluation of new piplartine analogues as potent aldose reductase inhibitors (ARIs). European Journal of Medicinal Chemistry. 2012;57:344–361. DOI: 10.1016/j.ejmech.2012.09.014.
Banik BK, Fernandez M, Alvarez C. Iodine-catalyzed highly efficient Michael reaction of indoles under solvent-free condition. Tetrahedron Letters. 2005;46 (14):2479–2482. DOI: 10.1016/j.tetlet.2005.02.044.
Feofanov MN, Anokhin MV, Averin AD, Beletskaya IP. The Friedel – Crafts reaction of indoles with Michael acceptors catalyzed by magnesium and calcium salts. Synthesis. 2017;49(22):5045–5058. DOI: 10.1055/s-0036-1589068.
Downloads
Additional Files
Published
Issue
Section
License
Copyright (c) 2026 Journal of the Belarusian State University. Chemistry
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The authors who are published in this journal agree to the following:
- The authors retain copyright on the work and provide the journal with the right of first publication of the work on condition of license Creative Commons Attribution-NonCommercial. 4.0 International (CC BY-NC 4.0).
- The authors retain the right to enter into certain contractual agreements relating to the non-exclusive distribution of the published version of the work (e.g. post it on the institutional repository, publication in the book), with the reference to its original publication in this journal.
- The authors have the right to post their work on the Internet (e.g. on the institutional store or personal website) prior to and during the review process, conducted by the journal, as this may lead to a productive discussion and a large number of references to this work. (See The Effect of Open Access.)
