Phosphorus-containing derivatives of 2,6-di(tert-butyl)phenol: The antioxidant activity and properties of the corresponding phenoxyl radicals

Abstract

The properties of phenoxyl radicals generated by the oxidation of mono , di , and triphosphorus derivatives of 2,6 di(tert butyl) 4 methylphenol (ionol) were studied by ESR. These compounds exist as conformers that are interconvertible with a temperature dependent rate. Numerical processing of the ESR spectra gave the thermodynamic and activation param eters that characterize the interconversion of the conformers. The antioxidant activities of the compounds were studied in a model oxidation of oleic acid and with biological objects. These phenols efficiently inhibited radical oxidation reactions.Derivatives of 2,6 di(tert butyl) 4 methylphenol (ionol) are efficient antioxidants. 1 They are biologically active compounds capable of inhibiting lipid peroxidation and lowering the oxidative stress of the organism. In re cent years, we have proposed a convenient route to a number of ionol derivatives with one, two, or three phos phorus containing groups, starting from easily accessible 3,5 di(tert butyl) 4 hydroxybenzaldehyde and trimethyl silyl esters of phosphorus(III) acids. 2-4 Here we studied the antioxidant properties of phosphorus containing ionol derivatives 1-4.A comparative analysis of the antioxidant activity was performed against reference compound 5 containing no 2,6 di(tert butyl)phenol fragment.The antioxidant activities of 2,6 di(tert butyl)phenols are determined by the stability of the corresponding phenoxyl radicals. 1 We generated phenoxyl radicals from compounds 1-4 and studied their properties by ESR.Experimental 1 H, 13 C, and 31 P NMR spectra were recorded on a Bruker Avance 400 spectrometer (400, 100, and 162 MHz, respectively) in CDCl 3 for compounds 2 and 3, DMSO d 6 for 1, and D 2 O for 4 with Me 4 Si ( 1 H, 13 C) and 85% H 3 PO 4 in D 2 O ( 31 P) as standards. All reactions were carried out in anhydrous solvents under dry argon. ESR spectra were recorded on a Bruker ER 200 D SRC instrument fitted with an ER 4105 DR double resonator (~9.5 GHz) and an ER 4111 VT thermocontroller and on a Bruker EMX 8/2.7 instrument. Diphenylpicrylhydrazyl (DPPH, g = 2.0037) was used as a standard in the determination of the g factor. Spectra were simulated with the WinEPR SimFonia v 1.25 program (Bruker).Compounds 1-5 were prepared according to our proce dure 3,4 by reactions of trimethylsilyl esters of phosphorus(III) acids with 3,5 di(tert butyl) 4 hydroxybenzaldehyde and 3,5 di(tert butyl) 4 hydroxybenzoyl chloride. The physico chemical constants of compounds 2-4 (see Ref.3) and 5 (see Ref. 4) were identical with the literature data.O,O Diethyl [3,5 di(tert butyl) 4 hydroxyphenyl(trimethyl silyloxy)methyl]phosphonate (1) was obtained from diethyl

Synthesis of mono‐ and bisorganophosphorus substituted amides of unsaturated carboxylic acids with PCHNC(O) and antioxidant fragments

“…The 1 H, 13 C, and 31 P NMR spectra were registered on a Bruker Avance-400 spectrometer (400, 100, and 162 MHz, respectively) in CDCl 3 (1)(2)(3)(4)(5)7,11), CD 3 OD (6) or (CD 3 ) 2 SO (8-10,12-14) against TMS ( 1 H and 13 C) and 85% H 3 PO 4 in D 2 O ( 31 P). All reactions were performed under dry argon in anhydrous solvents.…”

“…Also recently, we have proposed the convenient methods for the synthesis of new functionalized mono-and bisorganophosphorus compounds including ionol fragments [6], which were used by us for preparation of stable phenoxyl radicals [7] and were possessed of antioxidative activity [8]. In this work, we propose the unique way for the synthesis of new monoand bisorganophosphorus substituted amides of unsaturated carboxylic acids with PCHNC(O) and antioxidant fragments (cf.…”

Synthesis of new functionalized mono‐ and bisphosphinates with 2,6‐di‐tert‐butyl‐4‐methylphenol fragments

“…The 1 H, 13 C, and 31 P NMR spectra were registered on a Bruker Avance-400 spectrometer (400, 100, and 162 MHz, respectively) in CDCl 3 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) …”

“…These compounds were used by us for the preparation of stable phenoxyl radi-cals and were interesting as biological active compounds [2]. In this work, we propose the convenient methods for the synthesis of new functionalized mono-and bisphosphinates including of ionol fragments, starting from the readily accessible 3,5-di-tert-butyl-4-hydroxybenzaldehyde (A), 3,5-di-tertbutyl-4-hydroxybenzalchloride (B), and 3,5-di-tertbutyl-4-hydroxybenzoyl chloride (C), which were prepared by the procedures described in [3][4][5], and trimethylsilyl esters of functionalized trivalent phosphorus acids which were prepared by us early as unique organophosphorus synthons [6][7][8].…”

Synthesis of Organophosphorus‐Substituted Amides of Carbonic Acids with PCHNC(O) and 2,6‐Di‐tert‐butyl‐4‐methylphenol Fragments

“…Also recently, we have proposed the convenient methods for synthesis of new functionalized organophosphorus compounds including of ionol fragments [3,4], which were used by us for preparation of stable phenoxyl radicals and were possessed of antioxidative activity [5]. In this work, we propose the unique way for synthesis of new organophosphorus-substituted amides of various carbonic acids with PCHNC(O) and ionol fragments, which was based on available imines [6,7], acyl chlorides [8], and trimethylsilyl esters of trivalent organophosphorus acids [9].…”