Novosibirsk State Pedagogical University Bulletin, 2015, vol. 5, no. 3, pp. 112–123
542.06 547.56 547.1'123

Synthesis and Antioxidant Activity of Dodecyl-(3-(4-hydroxyaryl)propyl)selenides

Kholshin S. 1 (Novosibirsk, Russian Federation), Cheblukova V. P. 1 (Novosibirsk, Russian Federation), Yagunov S. E. 1 (Novosibirsk, Russian Federation), Oleynik A. S. 1 (Novosibirsk, Russian Federation), Kandalintseva N. V. 1 (Novosibirsk, Russian Federation), Prosenko A. E. 1 (Novosibirsk, Russian Federation)
1 Novosibirsk State Pedagogical University, Novosibirsk, Russian Federation

The paper presents a synthesis of structurally related series of dodecyl-(3-(4-hydroxyaryl)propyl)selenides with different number and different structure of the ortho-alkyl substituents. Corresponding 3-(4-hydroxyaryl)-1-bromopropanes, 1-chlorododecane, selenium, and sodium sulfite were used as synthons. The synthesis of the target compounds were carried out via preparation of the bis-dodecyldiselenide as intermediate. The synthesized dodecyl-(3-(4-hydroxyaryl) propyl)selenides were active in reactions with peroxide radicals and peroxides, hence it work like hybrid antioxidants. Antiradical activity of these compounds studied in the model reaction of initiated cumene oxidation at 60 °C. Experimentally measured rate constant interaction with cumylperoxyde radicals ranged from 2.6 ∙ 104 M-1 s-1 ∙ for ortho-unsubstituted dodecyl-(3-(4-hydroxyphenyl)propyl)selenide to 1.3 ∙ 105 ∙ M-1 s-1 for its 3,5-dimethylated analogue. It has been shown, that replacement of selenium in the molecules of dodecyl-(3-(4-hydroxyaryl)propyl)selenides to sulfur does not lead to significant changes in antiradical properties of the compounds. However, the study of the kinetics of decomposition of cumene hydroperoxide in acetic acid at 60 °C in the presence of dodecyl-(3-(4-hydroxyaryl)propyl)selenides and corresponding dodecyl-(3-(4-hydroxyaryl)propyl)sulfides revealed significant differences in peroxide destruction activity these classes of compounds. In conditions of the experiment sulfides were reacted with equimolar amounts of cumene hydroperoxide, while selenides exhibited higher activity and digested whole peroxide (6-fold excess).


selenides, polyfunctional phenolic antioxidants, selenium-containing antioxidants

For citation:
Kholshin S., Cheblukova V. P., Yagunov S. E., Oleynik A. S., Kandalintseva N. V., Prosenko A. E. Synthesis and Antioxidant Activity of Dodecyl-(3-(4-hydroxyaryl)propyl)selenides. Novosibirsk State Pedagogical University Bulletin, 2015, vol. 5, no. 3, pp. 112–123. DOI:
  1. Tapiero H., Townsend D. M., Tew K. D. The antioxidant role of selenium and seleno-compounds. Biomed. Pharmacotherapy. 2003, vol. 57, pp. 134–144.
  2. Kohrle J., Brigelius-Flohe R., Bock A., Gartner R., Meyer O., Flohe L., Selenium in Biology: Facts and Medical Perspectives. Biol. Chem. 2000, vol. 381, pp. 849–864.
  3. Birringer M., Pilawa S., Flohe L. Trends in selenium biochemistry. Nat. Prod. Rep. 2002,
    vol. 19, pp. 693–718.
  4. Mugesh G., du Mont W.-W., Sies H. Chemistry of Biologically Important Synthetic Organoselenium Compounds. Chem. Rev. 2001, vol. 101, pp. 2125–2179.
  5. Nogueira C. W., Zeni G., Rocha J. B. T. Organoselenium and Organotellurium Compounds: Toxicology and Pharmacology. Chem. Rev. 2004, vol. 104, pp. 6255–6285.
  6. Parnham M. J., Graf E. Pharmacology of synthetic organic selenium compounds. Progr. Drug Res. 1991, vol. 36, pp. 9–47.
  7. Shi H., Liu S., Miyake M., Liu K. J. Ebselen Induced C6 Glioma Cell Death in Oxygen and Glucose Deprivation. Chem. Res. Toxicol. 2006, vol. 19, pp. 655–660.
  8. Bhabak K. P., Mugesh G. Synthesis, Characterization, and Antioxidant Activity of Some Ebselen Analogues. Chem. Eur. J. 2007, vol. 13, pp. 4594–4601.
  9. Luo Z., Sheng J., Sun Y., Lu C., Yan J., Liu A., Luo H., Huang L., Li X. Synthesis and Evaluation of Multi-Target-Directed Ligands against Alzheimer’s Disease Based on the Fusion of Donepezil and Ebselen. J. Med. Chem. 2013, vol. 56, pp. 9089–9099.
  10. Shanks D., Amorati R., Fumo M. G., Pedulli G. F., Valgimigli L., Engman L. Synthesis and Antioxidant Profili of of all-rac-α-Selenotocopherol. J. Org. Chem. 2006, vol. 71, pp. 1033–1038.
  11. Amorati R., Pedulli G. F., Valgimigli L., Johansson H., Engman L. Organochalcogen Substituents in Phenolic Antioxidants. Org. Lett. 2010, vol. 12, no. 10, pp. 2326–2329.
  12. Prosenko A. E., Dyubchenko O. I., Terakh E. I., Markov A. F., Gorokh E. A., Boiko M. A. Synthesis and Investigation of Antioxidant Properties of Alkylated Hydroxybenzyl Dodecyl Sulfides. Petroleum Chemistry. 2006, vol. 46, no. 4, pp. 283–288. (In Russian)
  13. Plotnikov M. B., Prosenko A. E., Smoljakova V. I., Ivanov I. S., Chernisheva G. A., Kandalintseva N. V. Synthesis and anti-oxidative activity of 3.5-dimethyl-4-hydroxybenzyltiododecane. Pharmaceutical Chemistry Journal.  2010, vol. 44, no. 3, pp. 65–67. (In Russian)
  14. Plotnikov M. B., Prosenko A. E., Smoljakova V. I., Ivanov I. S., Chernisheva G. A., Prosenko A. E., Gross M. A., Boiko M. A. Agents with antiplatelet, reduces blood viscosity and increased anti-thrombogenic activity. Russian patent No 2368376 (2009). (In Russian)
  15. Prosenko A. E., Gross M. A., Kandalintseva N. V., Tolstikova T. G., Sorokina I. V. Agent for correcting the cytotoxic effects of chemotherapy and paraneoplastic processes having antitumor activity. Russian patent No 2447888 (2012). (In Russian)
  16. Price T. S., Jones L. M. The Benzyl and Nitrobenzyl Selenosulphates and the Benxyl and Nityobenzyl Diselenides. J. Chem. Soc. 1909, vol. 95, pp. 1729–1738.
  17. Klayman D. L. The Synthesis of Aminoethyl-Substituted Selenium Compounds. J. Org. Chem. 1965, vol. 30, pp. 2454–2456.
  18. Gunther W. H., Mautner H. G. Analogs of Parasympathetic Neuroeffectors. Acetylselenocholine, Selenocholine, and Related Compounds. J. Med. Chem. 1964, vol. 7, pp. 229–232.
  19. Tsepalov V. F. Method of quantitative analysis using antioxidants model reaction initiated oxidation. The study of synthetic and natural antioxidants in vivo and in vitro. Collected articles.  Nauka Publ., 1992, pp. 16–26. (In Russian)
  20. Prosenko А. Е. Polyfunctional sulfur-, nitrogen-, phosphorus-containing antioxidants based on alkylated phenols: synthesis, properties and application prospects. Novosibirsk, 2010, 462 p. (In Russian)
  21. Denisov E. T., Denisova T. G. Handbook of Antioxidants: Bond Dissociation Energies, Rate Constants, Activation Energies and Enthalpies of Reactions. – CRC Press LLC Publ., 2000.
  22. Terakh E. I., Kandalintseva N. V., Nikulina V. V., Pinko P. I., Prosenko A. E. Study of the Reactivity of Thioalkylphenols toward Cumyl Peroxide Radicals and Cumene Hydroperoxide. Petroleum Chemistry. 2004, vol. 44,  pp. 211–214. (In Russian)
  23. Prosenko A. E., Markov A. F., Khomchenko A. S., Boiko M. A., Terakh E. I., Kandalintseva N. V. Synthesis and antioxidant activity of alkyl 3-(4-hydroxyaryl)propyl sulfides. Petroleum Chemistry. 2006, vol. 46, pp. 442–446. (In Russian)
  24. Prosenko A. E., Markov A. F., Pinko P. I., Krisin A. P., Koptyug V. A. A method for preparing 4-haloalkyl-2,6-di-tert-butylphenols. Russian patent No 1376511 (1993). (In Russian)
  25. Oleynik А. S., Kuprina T. S., Pevneva N. Yu., Markov A. F., Kandalintseva N. V., Prosenko A. E., Grigor’ev I. A. Synthesis and antioxidant properties of sodium S-[3-(hydroxyaryl)propyl]thiosulfates and [3-(hydroxyaryl)propane]-1-sulfonates. Russ. Chem. Bull. 2007, vol. 56, pp. 1135–1143. (In Russian)
  26. Armarego W. L. F., Chai C. L. L. Purification of Laboratory Chemicals. Elsevier, 2013.
  27. Roginsky V. A. Phenolic antioxidants. Reactivity and efficiency. Moscow, Nauka Publ., 1988. 247 p. (In Russian)
  28. Lyacovskaya Yu. N., Piul’skaya V. I. Methods of study of oxidative deterioration of fats. Moscow, GOSINTI Publ., 1960. 52 p. (In Russian)
Date of the publication 09.06.2015