Synthesis and antiradical activity of sulfur-containing derivatives of 2,4-dimethylphenol

Alkylated phenols containing sulfide groups in substituents are effective antioxidants and, in vivo, exhibit protective properties under oxidative stress. The present study is devoted to the synthesis and comparative evaluation of the antioxidant properties of structurally related dimethylphenol derivatives containing bivalent sulfur in o-, n-substituents. By the reaction of 2,4-dimethylphenol with diethylaminomethyldodecyl sulfide in acetic acid with the yield of 73%, the synthesis of 2-dodecylthiomethyl-4,6-dime-thylphenol (I) was carried out. By the sequential interaction of the named phenol with N,N-diethyl amine (when boiling in acetic acid) and 2-mercaptoethanoic acid (boiling in m-xylene) S-(3,5-dimethyl-2-hydroxybenzy)lthioethanoic acid (II) was obtained, the yields of individual stages of these transformations were 87 % and 53 % accordingly. Isomers of the compounds I and II with dimethyl o-substitution - 4-dodecylthiomethyl-2,6-dimethylphenol (III) and 3,5-dimethyl-4-hydroxybenzylthioethanoic acid (IV) -were obtained by the methods previously described. The composition and structure of the newly synthesized compounds were confirmed by the elemental analysis and spectral data (IR and 'H NMR). The antiradical activity of compounds I-IV was studied in a model reaction of AIBN-initiated oxidation of cumene at 60 °C with the usage of a manometric method and a Warburg-type installation. In a kinetic experiment, the rate constants (k) of the interaction of synthesized compounds with cumene peroxide radicals were measured, and composed 6.6x10⁴, 7.5x10⁴, 2.8x10⁴ and 3.3x10⁴ M^-Uc^-1 respectively. The decrease of the k value during the transition from I to III and from II to IV can be associated with the formation of the intramolecular hydrogen bonds O№"S in the compounds III and IV containing bivalent sulfur in the o-position relative to the phenolic OH-group, which is confirmed by the spectral data. Thus, in the IR spectrum of the phenol III, there is an intense narrow absorption band in the region of 3619 cm^-1, corresponding to the valence vibrations of the free phenolic OH-group, while for the isomeric phenol I, there is a blurred absorption band in the region of 3333 cm^-1, which is characteristic for the valence vibrations of the phenolic OH-group involved in weak hydrogen bonding. Similarly, in the ¹H NMR spectrum of the phenol 1, there is a shift of the phenolic proton signal to the field weaker (6.50 ppm.) than with the similar signal for its isomer III (4.54 ppm.), which also corresponds to the formation of a weak hydrogen bond. Contribution of the authors: the authors contributed equally to this article. The authors declare no conflicts of interests.

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