Ярославль, Ярославская область, Россия
Ярославль, Ярославская область, Россия
студент
Ярославль, Ярославская область, Россия
В работе изучены границы применимости реакции внутримолекулярной восстановительной циклизации орто-нитроаренов, содержащих различные предельные азагетероциклы, для синтеза конденсированных производных бензимидазола с узловым атомом азота. Процесс внутримолекулярной гетероциклизации наблюдался при восстановлении 4-(2-нитроарил)-4-морфолина и 1-(2-нитроарил)-4-метилпиперидина, в то время как наличие в субстрате 4-метил-пиперазинового цикла препятствовало образованию конденсированного полиазагетероцикла
восстановительная внутримолекулярная гетероциклизация, орто-нитро-трет-анилины, конденсированные производные бензимидазола
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. URL: 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. Mavrova A.Ts. 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. Придворов Г.В., Муха О.Ю., Липатов В.А. Противосудорожные свойства конденсированных производных имидазобензимидазола: тезисы докладов Российской конференция по медицинской химии с международным участием «МедХим-Россия 2021», 2021, 439. DOI:https://doi.org/10.19163/medchemrussia2021-2021-439.
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: А review. Int. J. Sci. Res., 2016, 5(3), 762-772. URL: https://www.ijsr.net/archive/v5i3/NOV161972.pdf.
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., 2006, 56(1), 31. URL: https://core.ac.uk/download/pdf/14378832.pdf.
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. Вандышев Д.Ю., Ковыгин Ю.А., Хмелевская Т.Н., Щербаков К.А., Шихалиева К.Д., Смольянникова М.Ю., Шихалиев Х.С. Синтез 3,4-дигидропиримидо[1,2-а]бензимидвзолов, перспективных антагонистов CRF1 рецепторов. Изв. АН. Серия Химическая, 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), С. 633-635. DOI:https://doi.org/10.1016/j.mencom.2020.09.027.
32. Бегунов Р. С., Соколов А. А., Филимонов С. И. Синтез хиноидных производных бензаннелированных гетероциклов с узловым атомом азота. ЖОрХ., 2020, 56(8), 1222-1232. DOI:https://doi.org/10.31857/S051474922008008X.
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. Бегунов Р.С., Соколов А.А. Однореакторное восстановление и галогенирование N-(2,4-динитрофенил)пиперидина. От химии к технологии шаг за шагом, 2022, 3(2), 30-36. DOI:https://doi.org/10.52957/27821900_2022_02_30.
48. Zhurko G.A. Chemcraft. Version 1.6. URL: http://www.chemcraftprog.com
