SYNTHESIS OF FUNCTIONALLY SUBSTITUTED PYRIMIDINE DERIVATIVES BASED ON (E)-3- (4,5-DICHLOROISOTHIAZOL-3-YL)-1-FERROCENYLPROP-2-EN-1-ONE
Abstract
3-(4,5-Dichloroisothiazol-3-yl)-1-ferrocenylprop-2-en-1-one was synthesized by condensation of acetyl ferro-cene with 4,5-dichloroisothiazole-3-carbaldehyde. The reaction of isothiazolylferrocenyl ketone obtained with guanidine resulted in amino substituted ferrocenylisothiazolyl pyrimidine. The interaction of isothiazolylferrocenyl ketone with thiourea proceeded by heterocyclization, leading to the formation of ferrocenylisothiazolyl-3,4-dihydropyrimidin-2(1H)-thione. Hybrid derivatives of azaheterocycles and ferrocene are of interest for biotesting as antitumor agents.
About the Authors
V. I. PotkinBelarus
Corresponding Member, D. Sc. (Chemistry), Professor, Head of the Department
A. V. Kletskov
Belarus
Researcher
S. K. Petkevich
Belarus
Ph. D. (Chemistry), Senior researcher
I. A. Kolesnik
Belarus
Junior researcher
F. I. Zubkov
Russian Federation
Ph. D. (Chemistry), Assistant Professor
E. A. Kvyatkovskaya
Russian Federation
K. K. Borisova
Russian Federation
Assistant
A. V. Popov
Russian Federation
Ph. D. (Chemistry), Researcher
I. B. Rozentsveig
Russian Federation
D. Sc. (Chemistry), Assistant Professor, Deputy Director
References
1. Koroleva E. V., Gusak K. N., Ignatovich Zh. V. Synthesis and applications of 2-aminopyrimidine derivatives as key intermediates in chemical synthesis of biomolecules. Russian Chemical Reviews, 2010, vol. 79, no. 8, pp. 655–681. doi.org/10.1070/ rc2010v079n08abeh004116
2. Gouhar R. S., Youns M. Novel Series of Substituted Heterocycles derived from α,β-Unsaturated Ketones for Anticancer Evaluation. Research Journal of Pharmaceutical, Biological and Chemical Sciences, 2014, vol. 5, no. 2, pp. 680–692.
3. Al-Issa S. A. Synthesis and anticancer activity of some fused pyrimidines and related heterocycles. Saudi Pharmaceutical Journal, 2013, vol. 21, no. 3, pp. 305–316. doi.org/10.1016/j.jsps.2012.09.002
4. Huggins D. J., Sherman W., Tidor B. Rational Approaches to Improving Selectivity in Drug Design. Journal of Medicinal Chemistry, 2012, vol. 55, no. 4, pp. 1424–1444. doi.org/10.1021/jm2010332
5. Snegur L. V., Simenel A. A., Nekrasov Yu. S., Morozova E. A., Starikova Z. A., Peregudova S. M., Kuzmenko Yu. V., Babin V. N., Ostrovskaya L. A., Bluchterova N. V., Fomina M. M. Synthesis, structure and redox potentials of biologically active ferrocenylalkyl azoles. Journal of Organometallic Chemistry, 2004, vol. 689, no. 15, pp. 2473–2479. doi.org/10.1016/j. jorganchem.2004.05.001
6. Popova L. V., Babin V. N., Belousov Yu. A., Nekrasov Yu. S., Snegireva A. E., Borodina N. P., Shaposhnikova G. M., Bychenko O. B., Raevskii P. M., Morozova N. M., Ilyina A. I., Shitkov K. G. Antitumor effects of binuclear ferrocene derivatives. Applied Organometallic Chemistry, 1993, vol. 7, no. 2, pp. 85–94. doi.org/10.1002/aoc.590070203
7. Van Staveren D. R., Metzler-Nolte N. Bioorganometallic Chemistry of Ferrocene. Chemical Reviews, 2004, vol. 104, no. 12, pp. 5931–5986. doi.org/10.1021/cr0101510
8. Kulchitsky V. A., Potkin V. I., Zubenko Yu. S., Chernov A. N., Talabaev M. V., Demidchik Yu. E., Petkevich S. K., Kazbanov V. V., Gurinovich T. A., Roeva M. O., Grigoriev D. G., Kletskov A. V., Kalunov V. N. Cytotoxic Effects of Chemotherapeutic Drugs and Heterocyclic Compounds at Application on the Cells of Primary Culture of Neuroepithelium Tumors. Medicinal Chemistry, 2012, vol. 8, no. 1, pp. 22–32. doi.org/10.2174/157340612799278298
9. Potkin V. I., Petkevich S. K., Kletskov A. V., Zubenko Yu. S., Kurman P. V., Pashkevich S. G., Gurinovich T. A., Kul- chitsky V. A. The synthesis of isoxazolyl- and isothiazolylcarbamides. Russian Journal of Organic Chemistry, 2014, vol. 50, no. 11, pp. 1667–1676. doi.org/10.1134/s1070428014110219
10. Potkin V. I., Kletskov A. V., Petkevich S. K., Pashkevich S. G., Kazbanov V. V., Denisov A. A., Kulchitsky V. A. Synthesis of water soluble isoxazol-3-yl(isothiazol-3-yl) carboxamides and ureas containing amino acid residues – potential anticancer agents. Heterocyclic Letters, 2015, vol. 5, no. 1, pp. 11–19.
11. Chebanov V. A., Desenko S. M. Dihydroazines based on α,β-unsaturated ketones reactions. Current Organic Chemistry, 2006, vol. 10, no. 3, pp. 297–317. doi.org/10.2174/138527206775473904
12. Kaberdin R. V., Potkin V. I., Petkevich S. K. Synthesis and properties of chlorovinyl ketones. Vestsi Natsyyanal’nai akademii navuk Belarusi. Seriya chimicheskih nauk = Proceeding of the National Academy of Sciences of Belarus, chemical series, 2006, no. 2, pp. 100–120 (in Russian).
13. Potkin V. I., Petkevich S. K., Kletskov A. V., Dikusar E. A., Zubenko Yu. S., Zhukovskaya N. A., Kazbanov V. V., Pashkevich S. G. Synthesis of functionally substituted isoxazole and isothiazole derivatives. Russian Journal of Organic Chemistry, 2013, vol. 49, no. 10, pp. 1523–1533. doi.org/10.1134/s1070428013100205
14. Varga L., Nagy T., Kovesdi I., Benet-Buchholz J., Dorman G., Urge L., Darvas F. Solution-phase parallel synthesis of 4,6-diaryl-pyrimidine-2-ylamines and 2-amino-5,5-disubstituted-3,5-dihydro-imidazol-4-ones via a rearrangement. Tetrahedron, 2003, vol. 59, no. 5, pp. 655–662. doi.org/10.1016/s0040-4020(02)01560-0
15. Borodina E. A., Orlova N. A., Gatilov Yu. V., Sal’nikova O. I. Reaction of polyfluorinated chalcones with guanidine. Russian Journal of Organic Chemistry, 2015, vol. 51, no. 12, pp. 1745–1752. doi.org/10.1134/s1070428015120143
16. Potkin V. I., Petkevich S. K., Kletskov A. V., Kolesnik I. A., Zvereva T. D., Zhukovskaya N. A., Levkovskaya G. G., Rozentsveig I. B. New derivatives of 4,5-dihydro-1H-pyrazole, 4,5-dihydro-1,2-oxazole, and pyrimidine prepared proceeding from (E)-3-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-1-ferrocenylprop-2-en-1-one. Russian Journal of Organic Chemistry, 2017, vol. 53, no. 2, pp. 240–245. doi.org/10.1134/s1070428017020178
17. Yan Zou, Qiong Zhang, A.M. Showkot Hossain, Sheng-Li Li, Jie-Ying Wu, Wei-Zai Ke, Bao-Kang Jin, Jia-Xiang Yang, Sheng-Yi Zhang, Yu-Peng Tian. Synthesis, crystal structures, electrochemistry and nonlinear optical properties of a novel (D–A–D) biferrocenyl derivative: 2-Amino-4,6-diferrocenylpyrimidine. Journal of Organometallic Chemistry, 2012, vol. 720, pp. 66–72. doi.org/10.1016/j.jorganchem.2012.08.036