PROCEEDINGS OF THE SHEVCHENKO SCIENTIFIC SOCIETY

Chemical Sciences

Archive / Volume LXXV 2024

Yuriy HORAK, Roman LYTVYN, Andrii VAKHULA, Mykola OBUSHAK

Ivan Franko National University of Lviv, Kyryla i Mefodiya Str., 6, 79005 Lviv, Ukraine
e-mail: mykola.obushak@lnu.edu.ua

DOI: https://doi.org/10.37827/ntsh.chem.2024.75.073

SYNTHESIS OF 2-[(5-ARYL-2-FURYL)METHYLENE]-5,6-DIPHENYLIMIDAZO[2,1-B][1,3]THIAZOL-3-ONES

Condensed five-membered nitrogen- and sulfur-containing heterocycles continues to attract the attention of synthetic chemists with high reactivity and a variety of chemical transformations. Due to a wide range of biological activity azole derivatives are proposed for use in modern medicine and biotechnology. It is known that compounds which contains imidazole fragment are part of a number of drugs such as: naphthizine, dibasole, metronidazole. 5-Arylfuran derivatives also have the broad spectrum of biological activity. Convenient method for preparation of arylfuran compounds is a catalytic arylation of furan derivatives with arenediazonium salts under the conditions of Meerwein reaction.
In this work the initial 5-arylfuran-2-carbaldehyde were obtained by furan-2-carbaldehyde arylation in the presence of CuCl2 as a catalyst. These aldehydes can be involved in three-component reaction with derivatives of azoles which were described above.
Tandem and domino reactions, as well as multicomponent reactions, are increasingly used in the practice of organic synthesis. Multicomponent reactions make possible to synthesize target compounds with greater efficiency, atom economy and contribute to the introduction of the concept of "green" chemistry.
We investigated the interaction of 5-aryl-2-furancarbaldehydes with chloroacetic acid and 4,5-diphenyl-1,3-dihydro-2H-imidazole-2-thione. Experiments have shown that this reaction occurs when the reagents are heated in glacial acetic acid and in the presence of fused sodium acetate. In these conditions, chloroacetic acid is cyclized with 4,5-diphenyl-1,3-dihydro-2H-imidazole-2-thione. Under the same conditions, the active methylene group of the thiazolidinone ring formed reacts with aldehydes. As a result 2-[(5-aryl-2-furyl)methylene]-5,6-diphenylimidazo[2,1-b][1,3]thiazol-3-ones are formed.
Thus, a synthetic way is proposed for the construction of hybrid structures in which the imidazo [2,1-b][1,3]thiazole fragment is coupled with arylfuran, which makes them perspective objects for screening for biological activity.

Keywords: 5-aryl-2-furancarbaldehydes, Meerwein reactions, multicomponent reactions, imidazo[2,1-b][1,3]thiazoles.

References:

    1. Grimmett M.R. Imidazole and benzimidazole synthesis. London: Academic Press, 1997. 265 p. (https://doi.org/10.1016/B978-0-12-303190-7.X5012-2).
    2. Agarwal S. Imidazole-Based Drug Discovery. Elsevier Inc., 2022. 352 p. (https://doi.org/10.1016/B978-0-323-85479-5.10000-0).
    3. Furstner A., Castanet A. S., Radkowski K., Lehmann C. W. Total Synthesis of (S)-(+)-Citreofuran by Ring Closing Alkyne Metathesis. J. Org. Chem. 2003. Vol. 68. P. 1521–1528. (https://doi.org/10.1021/jo026686q).
    4. Volynets G. P., Bdzhola V. G., Golub A. G. et al. Rational design of apoptosis signal-regulating kinase 1 inhibitors: Discoveringnovel structural scaffold. Eur. J. Med. Chem. 2013. Vol. 61. P.104–115. (https://doi.org/10.1016/j.ejmech.2012.09.022).
    5. Kort M. E., Drizin I., Gregg R. J., et al. Discovery and Biological Evaluation of 5-Aryl-2-furfuramides, Potent and Selective Blockers of the Nav1.8 Sodium Channel with Efficacy in Models of Neuropathic and Inflammatory Pain. J. Med. Chem. 2008. Vol. 51. P. 407–416. (https://doi.org/10.1021/jm070637u).
    6. Lee S., Yi K. Y., Hwang S. K., Lee B. H., Yoo S., Lee K. (5-Arylfuran-2-ylcarbonyl)guanidines as cardioprotectives through the inhibition of Na+/H+ exchanger isoform-1. J. Med. Chem. 2005. Vol. 48. P. 2882–2891. (https://doi.org/10.1021/jm0492305).
    7. Qing-Qing Huang, Min Huang, Fa-Jun Nan, Qi-Zhuang Ye. Metalloform-selective inhibition: Synthesis and structure–activity analysis of Mn(II)-form-selective inhibitors of Escherichia coli methionine aminopeptidase. Bioorg. Med. Chem. Lett. 2005. Vol. 15. P. 5386–5391. (https://doi.org/10.1016/j.bmcl.2005.09.019).
    8. Inuki S., Miyamoto J., Hashimoto N., Shimizu H., Tabuchi H., Kawai A., Greiner L.C., Kimura I., Ohno H. Structure-activity relationship studies of tetrahydroquinolone derivatives as GPR41 modulators. Bioorg. Med. Chem. Lett. 2024. 129758. (https://doi.org/10.1016/j.bmcl.2024.129758).
    9. Lesyuk O., Karpyak V., Obushak M. Synthesis of substituted tetrahydropyrimidinones сontaining arylfuran moiety. Visnyk Lviv Univ. Ser. Chem. 2023. Vol. 64. P. 265–269. (in Ukrainian). (https://doi.org/10.30970/vch.6401.265).
    10. Vakhula A. R., Horak Y. I., Lytvyn R. Z., Lesyuk A. I., Kinzhybalo V., Zubkov F. I., Obushak M. D. 5-Aryl-2-furaldehydes in the synthesis of tetrahydropyrimidinones by Biginelli reaction. Chem. Heterocycl. Compd. 2018. Vol. 54(5). P. 545–549. (https://doi.org/10.1007/s10593-018-2301-3).
    11. Obushak N. D., Lesyuk A. I., Ganushchak N. I., Mel'nik G. M., Zavalii P. Yu. Catalytic arylation of furfural by arenediazonium salts. Zh. Org. Khim. 1986. Vol. 22(11). P. 2331–2336; engl. P. 2093–2097; ChemInform. 1987. Vol. 18(15). Р. 83. (https://doi.org/10.1002/chin.198715186).
    12. Obushak N. D., Gorak Yu. I., Matiichuk V. S., Lytvyn R. Z. Synthesis of heterocycles based on arylation products of unsaturated compounds: XVII. Arylation of 2-acetylfuran and synthesis of 3-R-6-(5-Aryl-2-furyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines. ChemInform. 2009. Vol. 40(21). (https://doi.org/10.1002/chin.200921170).
    13. Gorak Yu. I., Obushak N. D., Matiichuk V. S., Lytvyn R. Z. Synthesis of heterocycles from arylation products of unsaturated compounds: XVIII. 5-Arylfuran-2-carboxylic acids and their application in the synthesis of 1,2,4-thiadiazole, 1,3,4-oxadiazole, and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives. ChemInform. 2009. Vol. 40(50). (https://doi.org/10.1002/chin.200950029).
    14. Obushak N.D., Ganushchak N.I., Lesyuk A.I., Dzikovskaya L.M., Kisilitsa P.P. Arylation of Furan Compounds by Arenediazonium Salts. Zh. Org. Chem. 1990. Vol. 26(4). P. 873–880.
    15. Obushak M., Horak Y., Lytvyn R., Matiychuk V., Lesyuk O. Arylation of furan derivatives by arenediazonium salts. Proc. Shevchenko Sci. Soc.Chem. Sci. 2007. Vol. 18. P. 69–86. (http://dspace.nbuv.gov.ua/bitstream/handle/123456789/73962/08-Obushak.pdf?sequence=1).
    16. Zhu J., Wang Q., Wang M. Multicomponent Reactions in Organic Synthesis. Weinheim: Wiley, 2014. 494 p. 17. Anastas P. T., Warner J. C. Green chemistry: Theory and practice. New York: Oxford University Press, 2000. 152 p.

How to Cite

HORAK Yu., LYTVYN R., VAKHULA A., OBUSHAK M. SYNTHESIS OF 2-[(5-ARYL-2-FURYL)METHYLENE]-5,6-DIPHENYLIMIDAZO[2,1-B][1,3]THIAZOL-3-ONES. Proc. Shevchenko Sci. Soc. Chem. Sci. 2024. Vol. LXXV. P. 73-77.

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