Yaroslavl, Yaroslavl, Russian Federation
Yaroslavl, Yaroslavl, Russian Federation
student
Yaroslavl, Yaroslavl, Russian Federation
The paper examines the applicability limits of the intramolecular reductive cyclisation reaction of ortho-nitroarenes containing various limiting azagetherocycles for the synthesis of condensed benzimidazole derivatives with a nodal nitrogen atom. The process of intramolecular heterocyclisation occurred during the reduction of 4-(2-nitroaryl)-4-morpholine and 1-(2-nitroaryl)-4-methylpiperidine. At the same time, the presence of the 4-methyl-piperazine cycle in the substrate prevented the formation of a condensed polyazaheterocycle.
reductive intramolecular heterocyclisation, ortho-nitro-tert-anilines, condensed benzimidazole derivatives
1. Demirayak S., Mohsen U.A., Karaburun A.C. Synthesis and anticancer and anti-HIV testing of some pyrazino[1,2-a]benzimidazole derivatives. Eur. J. Med. Chem., 2002, 37(3), 255–260. DOI:https://doi.org/10.1016/S0223-5234(01)01313-7.
2. Nowicka A., Liszkiewicz H., Nawrocka W.P., Wietrzyk J., Kempińska K., Dryś A. Synthesis and antiproliferative activity in vitro of new 2-aminobenzimidazole derivatives. Reaction of 2 arylideneaminobenzimidazole with selected nitriles containing active methylene group. Cent. Eur. J. Chem., 2014, 12, 1047-1055. DOI:https://doi.org/10.2478/s11532-014-0533-3.
3. Sondhi S.M., Rani R., Singh J., Roy P., Agrawal S.K., Saxena A.K. Solvent free synthesis, anti-inflammatory and anticancer activity evaluation of tricyclic and tetracyclic benzimidazole derivatives. Bioorg. Med. Chem. Lett., 2010, 20(7), 2306-2310. DOI:https://doi.org/10.1016/j.bmcl.2010.01.147.
4. Moriarty E., Carr M., Bonham S., Carty M. P., Aldabbagh F. Synthesis and toxicity towards normal and cancer cell lines of benzimidazolequinones containing fused aromatic rings and 2-aromatic ring substituents. Eur. J. Med. Chem., 2010, 45(9), 3762-3769. DOI:https://doi.org/10.1016/j.ejmech.2010.05.025.
5. O’Donovan L., Carty M. P., Aldabbagh F. First synthesis of N-[(aziridin-2-yl)methyl]benzimidazolequinone and analysis of toxicity towards normal and Fanconi anemia cells. Chem. Commun., 2008, (43), 5592–5594. DOI:https://doi.org/10.1039/B814706J.
6. Fahey K., O'Donovan L., Carr M., Carty M. P., Aldabbagh F. The influence of the aziridinyl substituent of benzimidazoles and benzimidazolequinones on toxicity towards normal and Fanconi anaemia cells. Eur. J. Med. Chem., 2010, 45(5), 1873–1879. DOI:https://doi.org/10.1016/j.ejmech.2010.01.026.
7. Thummanagoti S., Yellol G. S., Sun C. Microwave-Assisted Tandem Transformation on an Ionic-Liquid Support: Efficient Synthesis of Pyrrolo/Pyridobenzimidazolones and IsoindolinoneFused Benzimidazoles. Chem. Asian J., 2011, 6(9), 2471 – 2480. DOI:https://doi.org/10.1002/asia.201100277.
8. Enumula S., Pangal A., Gazge M., Shaikh J. A. Diverse Pharmacological aspects of Benzimidazole Derivatives: A Review. Res. J. Chem. Sci., 2014, 4, 78-88. Available at: https://isca.me/rjcs/Archives/v4/i4/12.ISCA-RJCS-2014-032.pdf
9. Lynch M., Hehir S., Kavanagh P., O`Shaughnessy J., Carty M.P., Aldabbagh F. Synthesis by radical cyclization and cytotoxicity of highly potent bioreductive alicyclic ring fused [1,2-a]benzimidazolequinones. Chemistry, 2007, 13(11), 3218-3226. DOI:https://doi.org/10.1002/chem.200601450.
10. Fagan V., Bonham S., Carty M.P., Aldabbagh F. One-pot double intramolecular homolytic aromatic substitution routes to dialicyclic ring fused imidazobenzimidazolequinones and preliminary analysis of anticancer activity. Org. Biomol. Chem., 2010, 8(14), 3149-3156. DOI:https://doi.org/10.1039/c003511d.
11. Suleman A., Skibo E.B. A comprehensive study of the active site residues of DT-Diaphorase: rational design of benzimidazolediones as DT-Diaphorase substrates. J. Med. Chem., 2002, 45 (6), 1211-1220. DOI:https://doi.org/10.1021/jm0104365.
12. A. Ts. Mavrova. Synthesis and antitrichinellosis activity of some 2-substituted-[1,3]thiazolo[3,2-a]benzimidazol-3(2H)-ones. Org. Biomol. Chem., 2005, 13, 5550–5559. DOI:https://doi.org/10.1016/j.bmc.2005.06.046.
13. Pridvorov G.V., Mukha O.Yu., Lipatov V.A. Protivosudorozhnye svoistva kondensirovannykh proizvodnykh imidazobenzimidazola: tezisy dokladov Rossiiskoi konferentsiya po meditsinskoi khimii s mezhdunarodnym uchastiem «MedKhim-Rossiya 2021», 2021, 439. DOI:https://doi.org/10.19163/medchemrussia2021-2021-439 (in Russian).
14. Dolzhenko A.V., Chui W.K., Dolzhenko A.V., Chan L.W. Synthesis and biological activity of fluorinated 2 amino-4-aryl-3,4-dihydro[1,3,5]triazino[1,2-a]benzimidazoles. J. Fluorine Chem., 2005, 126(5), 759–763. DOI:https://doi.org/10.1016/j.jfluchem.2005.02.009.
15. Kaur P., Wakode S. R. Antimicrobial properties of benzimidazole and Mannich bases of benzimidazole: A review. Int. J. Sci. Res., 2016, 5(3), 762-772. Available at: https://www.ijsr.net/archive/v5i3/NOV161972.pdf (accessed 11.11.2024).
16. Badawey E.S.A., Rida S.M., Soliman F.S., Kappe T. Benzimidazole condensed ring systems, VI: Organic azides in heterocyclic synthesis, X: Synthesis of some substituted pyrimido[1,6-a]-benzimidazoles as potential antimicrobial agents. Monatsh Chem., 1989, 120, 1159–1164.
17. Villa P., Arumugam N., Almansour A.I., Kumar R.S., Mahalingam S.M., Maruoka K., Thangamani S. Benzimidazole tethered pyrrolo[3,4-b]quinoline with broad-spectrum activity against fungal pathogens. Bioorg. Med. Chem. Lett., 2019, 29(5), 729-733. DOI:https://doi.org/10.1016/j.bmcl.2019.01.006.
18. Mohamed B.G., Abdel-Alim A.M., Hussein M.A. Synthesis of 1-acyl-2-alkylthio-1,2,4-triazolobenzimidazoles with antifungal, anti-inflammatory and analgesic effects. Acta Pharm.56(1 31. Available at: https://core.ac.uk/download/pdf/14378832.pdf (accessed 11.11.2024).
19. Chernyshov V.V., Yarovaya O.I., Fadeev D.S., Gatilov Y.V., Esaulkova Y.L., Muryleva A.S., Sinegubova K.O., Zarubaev V.V., Salakhutdinov N.F. Single-stage synthesis of heterocyclic alkaloid-like compounds from (+)-camphoric acid and their antiviral activity. Mol Divers, 2020, 24, 61–67. DOI:https://doi.org/10.1007/s11030-019-09932-9.
20. De Palma, A.M., Heggermont, W., Leyssen, P., Pürstinger, G., Wimmer, E., De Clercq, E., Rao A., Monforte A.M., Chimirri A., Neyts J. Antienterovirus activity and structure–activity relationship of a series of 2,6-dihalophenyl-substituted 1H,3H-thiazolo[3,4-a]benzimidazoles. Biochem. Biophys. Res. Commun., 2007, 353 (3), 628-632. DOI:https://doi.org/10.1016/j.bbrc.2006.12.063.
21. Gaba M., Sing S., Mohan C. Benzimidazole: An emerging scaffold for analgesic and anti-inflammatory agents. Eur. J. Med. Chem., 2014, 76, 494-505. DOI:https://doi.org/10.1016/j.ejmech.2014.01.030.
22. Srikanth L., Raj V.V., Raghunandan N., Venkateshwerlu L. Recent advances and potential pharmacological activities of benzimidazole derivatives. Der Pharma Chem., 2011, 3(2), 172-193. DOI:https://doi.org/10.5555/20113163843.
23. Jain K.S., Shah A.K., Bariwal J., Shelke S.M., Kale A.P., Jagtap J.R., Bhosale A.V. Recent advances in proton pump inhibitors and management of acid-peptic disorders. Bioorg. Med. Chem., 2007, 15(3), 1181-1205. DOI:https://doi.org/10.1016/j.bmc.2006.07.068.
24. Vandyshev D.Yu., Kovygin Y.A., Khmelevskaya T.N., Shcherbakov K.A., Shikhalieva K.D., Smoliannikova M.Yu., Shikhaliev H.S. Synthesis of 3,4-dihydropyrimido[1,2-a]benzimidvzols, promising CRF1 receptor antagonists. Russian Chemical Buelletin, 2024, 73(4), 994-1004.
25. Aso K., Kobayashi K., Takai T., Kojima T., Tokumaru K., Mochizuki M. U.S. Patent No. 8901141, 2009.
26. Tan K.L., Bergman R.G., Ellman J.A. Annulation of alkenyl-substituted heterocycles via rhodium-catalyzed intramolecular C-H activated coupling reactions. J. Am. Chem. Soc., 2001, 123(11), 2685-2686. DOI:https://doi.org/10.1021/ja0058738.
27. Tan K.L., Park S., Ellman J.A., Bergman R.G. Intermolecular coupling of alkenes to heterocycles via C-H bond activation. J. Org. Chem., 2004. 69(21), 7329-7335. DOI:https://doi.org/10.1021/jo048666p.
28. Haque M.R., Rasmussen M. Ambident heterocyclic reactivity: Intramolecular alkylations of 2,4-disubstituted benzimidazoles. Tetrahedron, 1997, 53(20), 6937-6958. DOI:https://doi.org/10.1016/S0040-4020(97)00394-3.
29. Bastug G., Eviolitte C., Marko I.E. Functionalized orthoesters as powerful building blocks for the efficient preparation of heteroaromatic bicycles. Org. Lett., 2012, 14(13), 3502-3505. DOI:https://doi.org/10.1021/ol301472a.
30. Allin S.M., Bowman W.R., Karim R., Rahman S.S. Aromatic homolytic substitution using solid phase synthesis. Tetrahedron, 2006, 62(18), 4306-4316. DOI:https://doi.org/10.1016/j.tet.2006.02.071.
31. Begunov R.S., Sakulina V.O., Syroeshkin M.A., Saverina E.A., Sokolov A.A., Minyaev M.E. Electroreductive heterocyclization of ortho-piperidino substituted nitro(het)arenas. Mendeleev Commun., 2020, 30(5), C. 633 635. DOI:https://doi.org/10.1016/j.mencom.2020.09.027.
32. Begunov R.S., Sokolov A.A., Filimonov S.I. Synthesis of Quinone’s Derivatives of Benzannelated Heterocycles with a Bridgehead Nitrogen. ZhOrKh., 2020, 56(8), 1222-1232. DOI:https://doi.org/10.31857/S051474922008008X (in Russian).
33. Hubbard J.W., Piegols A.M., Söderberg B.C.G. Palladium-catalyzed N-heteroannulation of N-allyl- or N benzyl-2-nitrobenzenamines: synthesis of 2-substituted benzimidazoles. Tetrahedron, 2007, 63(30), 7077-7085. DOI:https://doi.org/10.1016/j.tet.2007.05.010.
34. Meth-Cohn O., Suschitzky H. Heterocycles by ring closure of ortho-substituted t-anilines (The t-amino effect). Adv. Heterocycl. Chem., 1972, 14, 211-278. DOI:https://doi.org/10.1016/S0065-2725(08)60954-X.
35. Tong S., Xu Z., Mamboury M., Wang Q., Zhu J. Aqueous Titanium Trichloride Promoted Reductive Cyclization of o‐Nitrostyrenes to Indoles: Development and Application to the Synthesis of Rizatriptan and Aspidospermidine. Angew. Chem., Int. Ed., 2015, 54(40), 11809-11812. DOI:https://doi.org/10.1002/anie.201505713.
36. Joardar S., Bhattacharyya A., Das S. A palladium on carbon catalyzed one-pot synthesis of substituted benzimidazoles. Synthesis, 2014, 46(22), 3121-3132. DOI:https://doi.org/10.1055/s-0034-1378454.
37. Duchek J., Vasella A. Synthesis of Benzimidazoles by Phosphine‐Mediated Reductive Cyclisation of ortho Nitro‐anilides. Helv. Chim. Acta., 2011, 94(6), 977-986. DOI:https://doi.org/10.1002/hlca.201100123.
38. Alonso J., Halland N., Nazaré M., R'kyek O., Urmann M., Lindenschmidt A. A Direct, Regioselective Palladium‐Catalyzed Synthesis of N‐Substituted Benzimidazoles and Imidazopyridines. Eur. J. Org. Chem. 2011, 2011(2), 234–237. DOI:https://doi.org/10.1002/ejoc.201001423.
39. Nguyen T.B., Ermolenko L., Al-Mourabit A. Formic acid as a sustainable and complementary reductant: an approach to fused benzimidazoles by molecular iodine-catalyzed reductive redox cyclization of o-nitro-t-anilines. Green Chemistry, 2016, 18(10), 2966-2970. DOI:https://doi.org/10.1039/C6GC00902F.
40. Sun X., Lv X. H., Ye L. M., Hu Y., Chen Y. Y., Zhang X. J., Yan M. Synthesis of benzimidazoles via iridium-catalyzed acceptorless dehydrogenative coupling. Org. Biomol. Chem., 2015, 13(27), 7381-7383. DOI:https://doi.org/10.1039/C5OB00904A.
41. Xue D., Long Y.Q. Metal-free TEMPO-promoted C (sp3)–H amination to afford multisubstituted benzimidazoles. J. Org. Chem., 2014, 79(10), 4727-4734. DOI:https://doi.org/10.1021/jo5005179.
42. Fagan V., Bonham S., McArdle P., Carty M. P., Aldabbagh F. Synthesis and Toxicity of New Ring‐Fused Imidazo[5,4‐f]benzimidazolequinones and Mechanism Using Amine N‐Oxide Cyclizations. Eur. J. Org. Chem., 2012., 2012(10), 1967-1975. DOI:https://doi.org/10.1002/ejoc.201101687.
43. Baars H., Beyer A., Kohlhepp S. V., Bolm C. Transition-metal-free synthesis of benzimidazoles mediated by KOH/DMSO. Org. Lett, 2014, 16(2), 536-539. DOI:https://doi.org/10.1021/ol403414v.
44. Liubchak K., Nazarenko K., Tolmachev A. Synthesis of annulated benzimidazoles via amidine cyclization. Tetrahedron, 2012, 68(14), 2993-3000. DOI:https://doi.org/10.1016/j.tet.2012.02.027.
45. Chen J., Qu J., Zhang Y., Chen Y., Liu N., Chen B. Metal-free construction of tricyclic or tetracyclic compounds-acid-promoted synthesis of benzo[4,5]imidazo[2,1-a]isoindole and 1,2-dialkyl-2,3-dihydrobenzimidazoles. Tetrahedron, 2013, 69(1), 316-319. DOI:https://doi.org/10.1016/j.tet.2012.10.030.
46. Elder M. S., Melson G. A., Busch D. I. Reactions of coordinated ligands. XII. The synthesis of o-benzylene-2,1-benzimidazole in the presence of nickel (II) ions, and a study of some of its metal complexes. Inorg. Chem., 1966, 5(1), 74-77. DOI:https://doi.org/10.1021/ic50035a018.
47. Begunov R.S., Sokolov A.A. One-reactor reduction and halogenation of N-(2,4-dinitrophenyl)piperidine. From Chemistry Towards Technology Step-by-Step, 2022, 3(2), 30-36. DOI:https://doi.org/10.52957/27821900_2022_02_30 (in Russian).
48. Zhurko G.A. Chemcraft. Version 1.6. Available at: http://www.chemcraftprog.com (accessed at 12.02.2024).
