Synthesis and antioxidant properties of sodium S-[3-(hydroxyaryl)propyl] thiosulfates and [3-(hydroxyaryl)propane]-1-sulfonates

Article abstract of DOI:10.1007/s11172-007-0172-3

Sodium S-[3-(hydroxyaryl)propyl] thiosulfates and [3-(hydroxyaryl)propane]- 1-sulfonates with various spatial hindrance of their phenolic OH groups were synthesized from dialkylphenols via a number of intermediate products. On a model reaction of oxidation of methyl oleate in aqueous sodium dodecyl sulfate, the rate constants of the interaction of the synthesized compounds with lipoperoxide radicals were determined.

Full text of DOI:10.1007/s11172-007-0172-3

Russian Chemical Bulletin, International Edition, Vol. 56, No. 6, pp. 1135—1143, June, 2007
1135
Synthesis and antioxidant properties of sodium Sꢀ[3ꢀ(hydroxyaryl)propyl]
thiosulfates and [3ꢀ(hydroxyaryl)propane]ꢀ1ꢀsulfonates*
а
а
а
а
А. S. Oleynik,а Т. S. Kuprina, N. Yu. Pevneva, А. F. Markov, N. V. Kandalintseva,
ꢀ
А. Е. Prosenko,а and I. А. Grigor'evb
aResearch Institute of Chemistry of Antioxidants, Novosibirsk State Pedagogical University,
28 ul. Vilyuiskaya, 630126 Novosibirsk, Russian Federation.
Fax: +7 (383) 268 1856. Eꢀmail: chemistry@ngs.ru
bN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry,
Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383) 330 9752. Eꢀmail: grig@nioch.nsc.ru
Sodium Sꢀ[3ꢀ(hydroxyaryl)propyl] thiosulfates and [3ꢀ(hydroxyaryl)propane]ꢀ1ꢀsulfonates
with various spatial hindrance of their phenolic ОН groups were synthesized from dialkylphenols
via a number of intermediate products. On a model reaction of oxidation of methyl oleate in
aqueous sodium dodecyl sulfate, the rate constants of the interaction of the synthesized comꢀ
pounds with lipoperoxide radicals were determined.
Key words: phenols, thiosulfates, sulfonates, antioxidants, free radicals, the Bunte salts.
A creation of hydrophilic "hybrid" compounds with
several antioxidantꢀactive centers in the molecule, which
can inhibit a peroxidation of lipids in different ways, is
one of the priorities in a search of new antioxidants to be
used in biology and medicine. Derivatives of spatially
hindered phenols, in which paraꢀsubstituent contains
alkylammonium,1—4 isothiuronium,3,4 and thiosulfate4,5
groups, are among such compounds. In particular, it was
earlier shown that sodium Sꢀ[3ꢀ(3,5ꢀdiꢀtertꢀbutylꢀ4ꢀ
hydroxyphenyl)propyl] thiosulfate (1а) is characterized
by a high antioxidant activity due to a concerted action of
the phenol and thiosulfate groups5 and shows hepatoꢀ
protecting,4 cardioprotecting,6 and immunomodulating7
activities.
The present work is aimed on the synthesis of strucꢀ
tural analogs of compound 1а, viz., thiosulfates 1 and
sulfonates 2, and on the comparative study of their antiꢀ
radical activity.
Compounds 1 and 2 were obtained from 2,6ꢀdialkylꢀ
phenols via the intermediate transformation of the latter
to (3ꢀhydroxypropyl)phenols and halogen derivatives 3a—i
and 4a—i, respectively.
According to the known method,8 alkylation of 2,6ꢀdiꢀ
tertꢀbutylphenol with allyl alcohol in the presence of
NaOH gave alcohol 3а, which upon treatment with PBr3
was converted to bromide 4а,9 upon treatment with HBr,
R1 = R2 = But (а); R1 = R2 = cycloꢀC6H11 (b); R1 = R2 = Me (c);
R
1 = R2 = H (d); R1 = Me, R2 = But (e); R1 = Me, R2
=
cycloꢀC6H11 (f); R1 = H, R2 = But (g); R1 = Н, R2 = cycloꢀC6H11 (h)
to bromide 4d, and by thermolysis, to alcohol 3g.10 Treatꢀ
ment of the latter with PBr3 led to bromide 4g (Scheme 1).
In contrast to 2,6ꢀdiꢀtertꢀbutylphenol, its less hindered
analogs react with allyl alcohol not that straightforward:
a remarkable amount of byꢀproducts is formed, resulting
* Dedicated to the memory of Academician N. N. Vorozhtsov
on the 100th anniversary of his birth.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1094—1101, June, 2007.
1066ꢀ5285/07/5606ꢀ1135 © 2007 Springer Science+Business Media, Inc.

1136
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 6, June, 2007
Oleynik et al.
were obtained via the intermediate conversion of 2,6ꢀdiꢀ
alkylphenols to their allyl derivatives 5 and 6 (Scheme 2).
Chloride 4i was similarly synthesized from 2,4ꢀdiꢀtertꢀ
butylphenol (Scheme 3).
The final transformation of 3ꢀarylpropylhalides 4 to
thiosulfates 1 or sulfonates 2 was carried out by treatment
with Na2S2O3 or Na2SO3, respectively (Scheme 4).
Looking forward on practical utilization of syntheꢀ
sized compounds 1 and 2 (the inhibition of peroxidation
of lipids in biological subjects), their antiradical activity
in a model oxidation of methyl oleate in aqueous sodium
dodecyl sulfate (SDS) was studied. This reaction can be
considered as a particular case of the unsaturated fatty
acid esters oxidation in aqueous solutions of surfaceꢀacꢀ
X = OH (3a—i), Br (4a—h), Cl (4i)
R1 = R2 = But (а); R1 = R2 = cycloꢀC6H11 (b); R1 = R2 = Me (c);
R
1 = R2 = H (d); R1 = Me, R2 = But (e); R1 = Me, R2
=
cycloꢀC6H11 (f); R1 = H, R2 = But (g); R1 = Н, R2 = cycloꢀC6H11 (h)
in a decrease of the target alcohols yields. In this connecꢀ
tion, the less hindered bromopropylꢀsubstituted phenols
Scheme 1
Scheme 2
Y = Cl, Br
R1 = R2 = cycloꢀC6H11 (b); R1 = R2 = Me (c); R1 = R2 = H (d); R1 = Me, R2 = But (e); R1 = Me, R2 = cycloꢀC6H11 (f)

Sulfurꢀcontaining phenols as antioxidants
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 6, June, 2007
1137
Scheme 3
W0•106/mol L–1 s–1
9
8
7
6
5
4
3
2
2
4
6
8
[APH]/mmol L–1
Fig. 1. The rate of the uninhibited oxidation of methyl
oleate (W0) in aq. SDS at 60 °С vs. concentration of the initiaꢀ
tor (APH).
(Fig. 1). Earlier,11 the similar phenomenon was found for
the kinetics of oxidation of methyl oleate in aq. micellar
solution of SDS.
A solution of the system of differential equations, corꢀ
responding to the kinetic scheme presented above, with
the quasiꢀstationary approximation for all the radicals and
with regard for the relation W0 = k1[RH]Wi/k2 leads to
the following expression:
tive compounds, which serves as a satisfactory model of
the oxidation of lipids in biomembranes.11
The oxidation of methyl oleate (RH) in aq. SDS in the
presence of 2,2´ꢀazobis(2ꢀmethylpropionamidine) diꢀ
hydrochloride (APH) as the initiator proceeds as a freeꢀ
radical chain process and can be described as the followꢀ
ing kinetic scheme:
APH
r•
R•,
W0/W = 1 + 2k3W0[ArOH]/(k1[RH]Wi),
R• + O2
RO2
,
•
where W is the rate of inhibited oxidation, [RH] is the
concentration of the substrate in a sample, [ArOH] is the
concentration of the inhibitor, k1—k3 are the rate conꢀ
stants of the corresponding reactions.
RO2• + RH
ROOH + R•,
(1)
(2)
•
RO2
Molecular products,
The relation k3/k1, which characterizes the reactivity
of the synthesized compounds with respect to the peroxo
radicals of methyl oleate, was found from the given equaꢀ
tion with the use of experimentally determined values of
W0 and W. The k3/k1 values, averaged from several exꢀ
periments (3—8), are given in Table 1. In all the cases, the
average square error of the measurement did not exꢀ
ceed 25%.
•
ArOH + RO2
ROOH + ArO•,
(3)
RO2• + ArO•
Molecular products,
•
where r• is a radical of the initiator, R• and RO2 are
alkyl and alkylperoxide radicals of methyl oleate, respecꢀ
tively, ArOH and ArO• are a molecule and a radical of
the inhibitor.
The difference between this scheme and the classic
one, which describes an oxidation of hydrocarbons in
homogeneous solutions, consists in the linear terminaꢀ
tion step in accordance with reaction (2).11,12 This is conꢀ
firmed by the fact that the rate of the uninhibited oxidaꢀ
tion (W0) is proportional to the rate of initiation (Wi)
The k1 value derived during the oxidation of methyl
oleate in aq. SDS at 60 °C and necessary for the calculaꢀ
tion of the absolute values of k3, is not reported in the
literature. At the same time, it is known12 that the k3 value
only slightly depends on the RO2• nature. This allowed us
to estimate the k1 value on the basis of the k3 value,
Scheme 4

1138
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 6, June, 2007
Oleynik et al.
Table 1. Parameters of antiradical activity of compounds
1a,b,d—i and 2a,c,h
celles, formed from methyl oleate and SDS molecules),
undoubtedly should lead to a decrease of the k3 constant
value.
Comꢀ
pound
k3/k1
k3•10–3
/L mol–1 s–1
Naturally, the importance of these factors increases
with a decrease of spatial hindrance of the phenol OH
group, though they remain actual for the case of 2,6ꢀdiꢀ
tertꢀbutylphenol derivatives, too. Earlier,4 it was shown
that ionol and compound 1а and 2а in homogeneous
solution of methyl oleate in chlorobenzene are
charachterized by close k3 values, viz., (2.3—2.8)•104
L mol–1 s–1. This allows us to believe that the difference
in the k3 values, observed for ionol and salts 1а and 2а in
the model system under consideration, is connected not
to the influence of various paraꢀsubstituents on the elecꢀ
tron density of the aromatic ring, but rather involves the
different localization of these compounds in aqueous miꢀ
cellar solution: ionol as lipophilic antioxidant, apparently,
is inside the micelles, while hydrophilic derivatives 1а
and 2а are in the aqueous media.
1a
1b
1d
1e
1f
1g
1h
1i
270
608
9.2
495
736
83
5.6
12.6
0.19
10.2
15.2
1.7
2.0
7.2
3.5
3.1
95
350
168
150
88
2a
2c
2h
1.8
determined for 2,6ꢀdiꢀtertꢀbutylꢀ4ꢀmethylphenol (ionol)
in the oxidation of methyl oleate in aq. SDS (1.9•104
L mol–1 s–1 at 40 °C).11 According to the known data,12
the activation energy for the reaction of ionol with perꢀ
oxide radicals is equal to ~4.5 kcal mol–1, then for the
case of 60 °C from the Arrhenius equation it follows that
k3 = 2.9•104 L mol–1 s–1. In the used by us model sysꢀ
tems, the k3/k1 parameter for ionol is equal to 1400, conꢀ
sequently, k1 = 20.7 L mol–1 s–1. The k3 values for comꢀ
pounds 1 and 2 were calculated based on this parameter.
The data obtained (see Table 1) show that in the oxiꢀ
dation of methyl oleate in aq. SDS, the synthesized comꢀ
pounds considerably differ in their reactivity toward acꢀ
tive radicals: the describing them k3 values range between
In general, the obtained results show that a number
of the synthesized compounds (thiosulfate derivatives
1b,e,f,i) surpass the prototype 1а in their antiradical acꢀ
tivity and as hydrophilic bioantioxidants are of interest for
further study.
Experimental
2,6ꢀDimethylꢀ, 2,6ꢀdiꢀtertꢀbutylꢀ, 2,4ꢀdiꢀtertꢀbutylꢀ, and
6ꢀtertꢀbutylꢀ2ꢀmethylphenols (Merck), as well as 2,6ꢀdicycloꢀ
hexylꢀ and 2ꢀmethylꢀ6ꢀcyclohexylphenols, prepared by alkylaꢀ
tion of phenol and оꢀcresol with cyclohexene according to the
Kolka13 method, were used as the starting materials for the
synthesis of compounds 1 and 2.
1Н NMR spectra of salts 1 and 2 were recorded on a Bruker
DRXꢀ500 spectrometer (500.13 MHz) in D2O (SiМе4 as the
standard), of all the other compounds, in СDСl3 (СHСl3 as the
standard). The melting points were determined in the capillary
tubes with a PTP apparatus or with the Kofler heating table.
Sodium Sꢀ[3ꢀ(3,5ꢀdicyclohexylꢀ4ꢀhydroxyphenyl)propyl]
thiosulfate (1b). A solution of Na2S2O3•5H2O (9.2 g, 37 mmol)
in water (15 mL) was added to bromopropane 4b (11.4 g,
30 mmol) in ethanol (30 mL), the mixture was refluxed for 6 h
under argon, then cooled down and extracted with Et2O. The
extract was dried with Na2SO4 and the solvent was evaporated.
The residue was washed with warm (~40 °C) hexane to give the
target thiosulfate 1b (10.7 g, 82%).
Sodium [3ꢀ(3,5ꢀdicyclohexylꢀ4ꢀhydroxyphenyl)propane]ꢀ1ꢀ
sulfonate (2b). Bromopropane 4b (5.7 g, 15 mmol), Na2SO3
(2.8 g, 22 mmol), propanꢀ2ꢀol (15 mL), and water (15 mL) were
placed into a 50ꢀmL tube. The tube was sealed, placed into a
thermostat, equipped with a shaking device, and kept for 5 h
at 120 °C. After cooling down, the tube was opened, the organic
phase was separated, the solvent was evaporated, the residue was
washed with warm (~40 °C) hexane and then treated with acꢀ
etone under heating (~50 °C). The undissolved in hot acetone
residue was filtered off, the filtrate was concentrated to give
sulfonate 2b (3.1 g, 51%).
190 and 1.5•104 L mol–1 s–1
.
In the series of orthoꢀdisubstituted thiosulfates 1а, 1е,
1b, 1f, when going from diꢀtertꢀbutyl derivative to methylꢀ
tertꢀbutyl and further to dicyclohexyl and methylcycloꢀ
hexyl derivative, an increase of the k3 values was obꢀ
served, which obviously can be explained by the decrease
of sterical hindrance for reaction (3) to occur. Apparently
the same factor causes the difference in the reactivity of
isomers 1а and 1i.
According to the known data,12 in oxidation of the
model hydrocarbons, 2,6ꢀdimethylꢀ and monoꢀоꢀtertꢀbuꢀ
tylꢀsubstituted phenols surpass the corresponding 2,6ꢀdiꢀ
tertꢀbutylphenols in their k3 constant values. At the same
time, in the model system under consideration, the
k3 values for monoꢀorthoꢀsubstituted phenols 1g,h yield
to those of their disubstituted analogs 1a,b from 3.3 to
6.3 times, while 2,6ꢀdimethylphenol 2с is less effective
than the corresponding 2,6ꢀdiꢀtertꢀbutylphenol 2а. Apꢀ
parently a hydration of the phenol ОН groups in comꢀ
pounds 1 and 2 is responsible for such results. The formaꢀ
tion of hydrogen bonds, such as ArOH...OH2, as well as
•
the spatial separation of ArOH and RO2 (hydrophilic
molecules of the antioxidant mainly are in aqueous
•
medium, while lipophilic radicals RO2 are in the miꢀ

Sulfurꢀcontaining phenols as antioxidants
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 6, June, 2007
1139
Sodium Sꢀ[3ꢀ(3,5ꢀdimethylꢀ4ꢀhydroxyphenyl)propyl] thiosulꢀ
fate (1c), Sꢀ[3ꢀ(5ꢀtertꢀbutylꢀ4ꢀhydroxyꢀ3ꢀmethylphenyl)propyl]
thiosulfate (1e), Sꢀ[3ꢀ(5ꢀcyclohexylꢀ4ꢀhydroxyꢀ3ꢀmethylpheꢀ
nyl)propyl] thiosulfate (1f), Sꢀ[3ꢀ(3ꢀcyclohexylꢀ4ꢀhydroxyꢀ
phenyl)propyl] thiosulfate (1h), Sꢀ[3ꢀ(3,5ꢀdiꢀtertꢀbutylꢀ2ꢀhydrꢀ
oxyphenyl)propyl] thiosulfate (1i), [3ꢀ(4ꢀhydroxyꢀ3,5ꢀdimethylꢀ
phenyl)propane]ꢀ1ꢀsulfonate (2c), [3ꢀ(5ꢀtertꢀbutylꢀ4ꢀhydroxyꢀ3ꢀ
methylphenyl)propane]ꢀ1ꢀsulfonate (2e) and [3ꢀ(3ꢀcyclohexylꢀ4ꢀ
hydroxyphenyl)propane]ꢀ1ꢀsulfonate (2h) were obtained similarly.
The syntheses of thiosulfates 1а,d,g and sulfonates 2а,d,g were
described earlier.5
4ꢀ(3ꢀBromopropꢀ1ꢀyl)ꢀ2,6ꢀdicyclohexylphenol (4b). A mixꢀ
ture of alcohol 3b (20 g, 63.2 mmol) and 40.5% aq. HBr (55 mL,
0.38 mol) was refluxed for 8 h with distillation of azeotrope,
then it was cooled down and extracted with toluene
(3×(10—15) mL). The extract was washed with water, dried
with Na2SO4, the solvent was evaporated. The residue was disꢀ
tilled in vacuo to obtain bromo derivative 4b (16.9 g, 70%).
4ꢀ(3ꢀBromopropꢀ1ꢀyl)ꢀ2ꢀtertꢀbutylꢀ6ꢀmethylphenol (4е). Alꢀ
cohol 3e (8.5 g, 38 mmol) and DMF (3.6 mL, 46 mmol) were
dissolved in toluene (40 mL), then PBr3 (2 mL, 21 mmol) was
added dropwise at 40—50 °C and the mixture was stirred for 2 h
at 80 °C. Then the reaction mixture was cooled down to 60 °C,
water (10 mL) was added and this was heated with stirring for
0.5 h at 80 °C. Then it was cooled down and extracted with
toluene. The extract was washed with water, dried with Na2SO4,
the solvent was evaporated. The residue was recrystallized from
light petroleum to give bromo derivative 4e (8.4 g, 77%).
Bromo derivatives 4c,f, were obtained similarly by the reacꢀ
tion of alcohols 3c,f with HBr, bromo derivative 4d, by the
reaction of alcohol 3а with HBr. Bromides 4а,g were obtained
similarly to 4e.
(2×50 mL), then neutralized with HCl, washed with water, dried
with Na2SO4, the solvent was evaporated. The residue was disꢀ
tilled in vacuo to give compound 4h (37.2 g, 50%).
1ꢀAllyloxyꢀ2,4ꢀdiꢀtertꢀbutylbenzene (5i). 2,4ꢀDiꢀtertꢀbutylꢀ
phenol (50 g, 0.24 mol) and NaOH (19.2 g, 0.48 mol) were
dissolved in DMF (200 mL) under an inert gas atmosphere, then
3ꢀchloropropꢀ1ꢀene (78 mL, 0.96 mol) was added dropwise and
this was stirred for 4 h at 50 °C. The reaction mixture was cooled
down and extracted with benzene. The extract was washed with
water, dried with Na2SO4, the solvent was evaporated. The resiꢀ
due was distilled in vacuo to give ether 5i (57.4 g, 96%).
2ꢀAllylꢀ4,6ꢀdiꢀtertꢀbutylphenol (6i). Allyloxybenzene 5i
(57.4 g, 0.23 mol) was kept for 3 h at 220—230 °C under an inert
gas atmosphere, then it was distilled in vacuo to give allylpheꢀ
nol 6i (52.2 g, 91%).
3ꢀ(3,5ꢀDiꢀtertꢀbutylꢀ2ꢀhydroxyphenyl)propanꢀ1ꢀol (3i). Diꢀ
methyl sulfate (6 mL, 62 mmol) was added dropwise to a susꢀ
pension of allylphenol 6i (15.3 g, 62 mmol) and NaBH4 (2.81 g,
74.4 mmol) in THF (85 mL). After stiring for 0.5 h and cooling
down to 3—5 °С, water (24 mL) was added dropwise to this. The
mixture was heated up to 20 °С and 3 М aq. NaOH (22 mL,
66 mmol of NaOH) and 30% aq. Н2О2 (23.5 mL, 0.23 mol
of Н2О2) were added dropwise, this was stirred for 0.5 h at
20 °С, neutralized with hydrochloric acid and extracted with
toluene. The extract was washed with water, dried with Na2SO4,
the solvent was evaporated. The residue was recrystallized from
light petroleum to give alcohol 3i (10.5 g, 64%).
Allyloxybenzenes 5b,c,e,f, allylphenols 6b,c,e,f, and alcohols
3b,c,e,f were obtained similarly.
6ꢀ(3ꢀChloropropꢀ1ꢀyl)ꢀ2,4ꢀdi(tertꢀbutyl)phenol (4i). Thionyl
chloride (3.3 mL, 45.9 mmol) was added dropwise to a mixture
of alcohol 3i (10 g, 37.8 mmol) and DMF (2.93 mL, 37.8 mmol)
at 50—60 °C, this was heated up to 80 °C and stirred at this
temperature for 3 h. After addition of water (20 mL) and benꢀ
zene (50 mL), this was stirred for another 0.5 h at 70—80 °C.
The organic layer was separated, washed with water, dried with
Na2SO4, the solvent was evaporated. The residue was distilled
in vacuo to give the target chloro derivative 4i (7.4 g, 69%).
The structure and composition of the synthesized compounds
were confirmed by elemental analysis and spectral data (Table 2).
4ꢀ(3ꢀBromopropꢀ1ꢀyl)ꢀ2ꢀcyclohexylphenol (4h). Cyclohexene
(12.8 mL, 126 mmol) was added dropwise to a mixture
of 4ꢀ(3ꢀbromopropꢀ1ꢀyl)phenol 4d (53.8 g, 0.25 mol) and
57% aq. perchloric acid (6 mL, 51 mmol of HClO4) at 120 °C
and this was stirred for 15 min. Then water (200 mL), benzene
(100 mL), and 10% aq. NaOH (50 mL) were sequentially added;
after thorough stirring, the organic and water phases were sepaꢀ
rated. The organic extract was washed with 10% aq. NaOH
Table 2. Yields, melting and boiling points, elemental analysis and 1H NMR spectral data of compounds 1b,c,e,f,h,i, 2b,c,e,h,
3b,c,e,f,i, 4b—i, 5e,i, and 6e,i
Comꢀ Yield
pound (%)
M.p.
/°C
B.p./°C
(1—2 Torr)
Found
Calculated
Molecular
formula
1H NMR,
δ (J/Hz)
(%)
С
H
S
Hal
—
1b
82
210
175
—
—
57.98 7.15 14.63
58.04 7.19 14.76
С21H31NaO4S2 1.05 (m, 2 Н, cycloꢀС6Н11); 1.20 (m, 8 Н,
cycloꢀС6Н11); 1.52 (m, 2 Н, cycloꢀС6Н11);
1.63 (m, 8 Н, cycloꢀС6Н11); 1.93 (m, 2 Н,
ArСН2СН2); 2.51 (t, 2 Н, АrСН2, J =
7.5); 2.67 (m, 2 Н, cycloꢀС6Н11); 3.03 (t,
2 Н, СН2S, J = 8); 6.78 (s, 2 Н, Ar)
С11H15NaO4S2 1.92 (m, 2 Н, АrCH2CH2); 2.12 (s, 6 H,
Me); 2.52 (t, 2 H, ArCH2, J = 7.5); 2.98
(t, 2 H, CH2S, J = 7); 6.84 (s, 2 H, Ar)
1c
89
44.10 5.00 21.33
44.28 5.07 21.49
—
(to be continued)

1140
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 6, June, 2007
Oleynik et al.
Table 2 (continued)
Comꢀ Yield
pound (%)
M.p.
/°C
B.p./°C
(1—2 Torr)
Found
Calculated
Molecular
formula
1H NMR,
δ (J/Hz)
(%)
С
H
S
Hal
—
1e
1f
76
89
170
—
—
49.24 6.13 18.73
49.39 6.22 18.84
С14H21NaO4S2 1.31 (s, 9 H, But); 1.94 (m, 2 Н,
АrCH2CH2); 2.17 (s, 3 H, Me); 2.53 (t,
2 H, ArCH2, J = 8); 3.02 (t, 2 H, CH2S,
J = 7); 6.88, 6.98 (both d, 1 H each, Ar,
J = 1.5)
С16H23NaO4S2 1.28 (m, 1 Н, cycloꢀС6Н11); 1.41 (m, 4 Н,
cycloꢀС6Н11); 1.75 (m, 5 Н + 2 H, cycloꢀ
С6Н11, ArСН2СН2); 2.21 (s, 3 Н, Ме);
2.58 (t, 2 Н, АrСН2, J = 8); 2.74 (m, 1 Н,
cycloꢀС6Н11); 3.13 (t, 2 Н, СН2S, J = 7);
6.78 (d, 1 Н, Ar, J = 1.5); 6.84 (d, 1 Н,
Ar, J = 2)
C15H21NaO4S2 1.15 (m, 1 Н, cycloꢀС6Н11); 1.30 (m, 4 Н,
cycloꢀС6Н11); 1.66 (m, 5 Н, cycloꢀС6Н11);
1.92 (m, 2 Н, ArСН2СН2); 2.44 (t, 2 Н,
АrСН2, J = 7.5); 2.73 (m, 1 Н, cycloꢀ
С6Н11); 2.74 (t, 2 Н, СН2S, J = 7); 6.79
(d, 1 H, Ar, J = 8.5); 6.89 (dd, 1 H, Ar,
J = 8, J = 2.5); 7.00 (d, 1 H, Ar, J = 2)
С17H27NaO4S2 1.28, 1.40 (both s, 9 H each, But); 2.09 (m,
2 Н, ArСН2СН2); 2.78 (t, 2 Н, АrСН2,
J = 7.5); 3.21 (t, 2 Н, СН2S, J = 7.5);
7.11, 7.23 (both d, 1 H each, Ar, J = 2)
С21H31NaO4S 1.05 (m, 2 Н, cycloꢀС6Н11); 1.20 (m, 8 Н,
cycloꢀС6Н11); 1.52 (m, 2 Н, cycloꢀС6Н11);
1.58 (m, 8 Н, cycloꢀС6Н11); 1.87 (m, 2 Н,
ArСН2СН2); 2.44 (t, 2 Н, АrСН2, J =
7.5); 2.67 (m, 2 Н, cycloꢀС6Н11); 2.74 (t,
2 Н, СН2S, J = 8); 6.78 (s, 2 Н, Ar)
150
153
52.33 6.25 17.43
52.44 6.33 17.50
—
—
1h
80
—
51.00 5.93 18.08
51.12 6.01 18.20
1i
72
51
245
290
—
—
53.30 7.05 16.59
53.38 7.11 16.77
—
—
2b
62.49 7.60 7.90
62.66 7.76 7.97
2c
2e
80
85
222
—
—
49.50 6.55 11.87
49.62 5.68 12.04
С11H15NaO4S 1.90 (m, 2 Н, АrCH2CH2); 2.10 (s, 6 H,
Me); 2.48 (t, 2 H, ArCH2, J = 7.5); 2.78
(t, 2 H, CH2S, J = 7.5); 6.80 (s, 2 H, Ar)
С14H21NaO4S 1.45 (s, 9 H, But); 2.10 (m, 2 Н,
АrCH2CH2); 2.30 (s, 3 H, Me); 2.72
>300
(decomp.)
54.38 6.68 10.27
54.53 6.86 10.40
—
—
(t, 2 H, ArCH2, J = 7.5); 2.97 (t, 2 H,
CH2S, J = 8); 7.06, 7.17 (both d, 1 H each,
Ar, J = 1.5)
2h
3b
82
86
231
—
56.17 6.56 9.94
56.23 6.61 10.01
C15H21NaO4S 1.11 (m, 1 Н, cycloꢀС6Н11); 1.28 (m, 4 Н,
cycloꢀС6Н11); 1.66 (m, 5 Н, cycloꢀС6Н11);
1.91 (m, 2 Н, ArСН2СН2); 2.44 (t, 2 Н,
АrСН2, J = 7.5); 2.73 (m, 1 Н, cycloꢀ
С6Н11); 2.74 (t, 2 Н, СН2S, J = 8); 6.79
(d, 1 H, Ar, J = 8); 6.89 (dd, 1 H, Ar,
J = 8, J = 2); 7.00 (d, 1 H, Ar, J = 2)
99—101 215—235 79.55 10.00
79.70 10.19
—
—
C21H32O2
1.30 (m, 2 Н, cycloꢀС6Н11); 1.45 (m,
8 Н + 1 H, cycloꢀС6Н11, СН2OH); 1.81
(m, 10 Н + 2 H, cycloꢀС6Н11, ArСН2СН2);
2.57 (t, 2 Н, АrСН2, J = 7.5); 2.69 (m,
2 Н, cycloꢀС6Н11); 3.62 (t, 2 Н, СН2ОН,
J = 8); 4.66 (s, 1 Н, ОН); 6.75 (s, 2 Н, Ar)
(to be continued)

Sulfurꢀcontaining phenols as antioxidants
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 6, June, 2007
1141
Table 2 (continued)
Comꢀ Yield
pound (%)
M.p.
/°C
B.p./°C
(1—2 Torr)
Found
Calculated
Molecular
formula
1H NMR,
δ (J/Hz)
(%)
С
H
S
Hal
—
3c
3e
57
75
66—67
—
73.15 8.88
73.30 8.95
—
C11H16O2
1.50 (br.s, 1 H, CH2OH); 1.83 (m, 2 Н,
АrCH2CH2); 2.20 (s, 6 H, Me); 2.56
(t, 2 H, ArCH2, J = 7.5); 3.65 (t, 2 H,
CH2OH, J = 7); 4.47 (br.s, 1 Н, ОН);
6.79 (s, 2 H, Ar)
1.39 (s, 9 H, But); 1.43 (br.s, 1 H,
CH2OH); 1.85 (m, 2 Н, АrCH2CH2);
2.21 (s, 3 H, Me); 2.60 (t, 2 H, ArCH2,
J = 8); 3.66 (t, 2 H, CH2OH, J = 6.5);
4.67 (s, 1 Н, ОН); 6.79 (d, 1 H, Ar,
J = 2); 6.92 (d, 1 H, Ar, J = 2.5)
61—63 148—150 75.57 10.04
75.63 9.97
—
—
—
—
C14H22O2
3f
83
71—72 130—140 77.29 9.65
77.38 9.74
C16Н24O2
1.28 (m, 1 Н + 1 H, cycloꢀС6Н11,
CH2OH); 1.41 (m, 4 Н, cycloꢀС6Н11);
1.75 (m, 1 Н, cycloꢀС6Н11); 1.84 (m, 4 Н,
cycloꢀС6Н11); 2.11 (m, 2 Н, ArСН2СН2);
2.21 (s, 3 Н, Me); 2.59 (t, 2 Н, АrСН2,
J = 7.5); 2.74 (m, 1 Н, cycloꢀС6Н11);
3.65 (t, 2 Н, СН2ОН, J = 6.5); 4.52 (s,
1 Н, ОН); 6.77 (d, 1 Н, Ar, J = 1.5);
6.84 (d, 1 Н, Ar, J = 2)
3i
64
70
98—100
—
77.00 10.55
77.22 10.67
—
—
—
C17H28O2
1.28, 1.41 (both s, 9 H each, But); 1.87 (m,
2 Н, АrCH2CH2); 1.88 (s, 1 H, CH2OH);
2.75 (t, 2 Н, АrСН2, J = 7); 3.66 (t, 2 Н,
СН2ОН, J = 6); 6.70 (s, 1 Н, ОН); 6.96,
7.17 (both d, 1 H each, Ar, J = 2.5)
1.35 (m, 2 Н, cycloꢀС6Н11); 1.45 (m, 8 Н,
cycloꢀС6Н11); 1.81 (m, 2 Н, cycloꢀС6Н11);
1.89 (m, 8 Н, cycloꢀС6Н11); 2.05 (m, 2 Н,
ArСН2СН2); 2.71 (t, 2 Н, АrСН2, J =
7.5); 2.76 (m, 2 Н, cycloꢀС6Н11); 3.37 (t,
2 Н, СН2Br, J = 7); 4.70 (s, 1 Н, ОН);
6.75 (s, 2 Н, Ar)
4b
74—75 205—207 66.43 8.19
66.49 8.24
20.89 C21H31BrO
21.06
4c
4d
4e
89
91
77
53—55 120—130 54.25 6.13
54.34 6.22
—
—
—
32.75 C11H15BrO
32.86
2.19 (m, 2 Н, АrCH2CH2); 2.30 (s, 6 H,
Me); 2.71 (t, 2 H, ArCH2, J = 7.5); 3.46
(t, 2 H, CH2Br, J = 7); 4.68 (s, 1 Н, ОН);
6.87 (s, 2 H, Ar)
38—40 121—124 50.33 5.21
50.26 5.15
36.97 C9H11BrO
37.15
2.11 (m, 2 Н, ArСН2СН2); 2.70 (t, 2 Н,
ArCH2, J = 7.5); 3.37 (t, 2 Н, СН2Br,
J = 7); 5.00 (s, 1 Н, ОН); 6.76, 7.14
(both d, 2 H each, Ar, J = 8)
Tar
122—123 58.84 7.29
58.96 7.42
27.89 C14H21BrO
28.01
1.43 (s, 9 H, But); 2.05 (m, 2 Н,
АrCH2CH2); 2.23 (s, 3 H, Me); 2.68 (t,
2 H, ArCH2, J = 8); 3.40 (t, 2 H, CH2Br,
J = 6.5); 4.66 (s, 1 Н, ОН); 6.84 (d, 1 H,
Ar, J = 1.5); 7.17 (d, 1 H, Ar, J = 2.5)
1.28 (m, 1 Н, cycloꢀС6Н11); 1.41 (m, 4 Н,
cycloꢀС6Н11); 1.75 (m, 1 Н, cycloꢀС6Н11);
1.85 (m, 4 Н, cycloꢀС6Н11); 2.10 (m, 2 Н,
ArСН2СН2); 2.21 (s, 3 Н, Me); 2.64 (t,
2 Н, АrСН2, J = 8); 2.74 (m, 1 Н, cycloꢀ
С6Н11); 3.38 (t, 2 Н, СН2Br, J = 6.5);
4.49 (s, 1 Н, ОН); 6.77, 6.83 (both d,
1 H each, Ar, J = 2)
4f
76
43—44 170—175 61.60 7.31
61.74 7.45
—
25.52 C16H23BrO
25.67
(to be continued)

1142
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 6, June, 2007
Oleynik et al.
Table 2 (continued)
Comꢀ Yield
pound (%)
M.p.
/°C
B.p./°C
(1—2 Torr)
Found
Calculated
Molecular
formula
1H NMR,
δ (J/Hz)
(%)
С
H
S
Hal
4g
60
Tar
128—129 57.49 6.99
57.57 7.06
—
29.39 C13H19BrО
29.46
1.40 (s, 9 Н, But); 2.00—2.06 (m, 2 Н,
АrCH2CH2); 2.68 (t, 2 Н, ArCH2, J =
7.5); 3.35 (t, 2 Н, СН2Br, J = 6.5); 4.85
(s, 1 Н, ОН); 6.56 (d, 1 Н, Ar, J = 8);
6.87 (dd, 1 Н, Ar, J = 8, J = 2); 7.07
(d, 1 Н, Ar, J = 2)
4h
50
Tar
202—207 60.70 7.23
60.61 7.12
—
—
26.75 C15H21BrO
26.88
1.30 (m, 1 Н, cycloꢀС6Н11); 1.44 (m, 4 Н,
cycloꢀС6Н11); 1.78 (m, 1 Н, cycloꢀС6Н11);
1.88 (m, 4 Н, cycloꢀС6Н11); 2.14 (m, 2 Н,
АrCH2CH2); 2.71 (t, 2 Н, АrСН2, J = 7);
2.83 (m, 1 Н, cycloꢀС6Н11); 3.41 (t, 2 Н,
СН2Br, J = 7); 4.97 (s, 1 Н, ОН); 6.69
(d, 1 Н, Ar, J = 8); 6.89 (dd, 1 H, Ar,
J = 8, J = 2); 7.03 (d, 1 Н, Ar, J = 2)
1.27, 1.42 (both s, 9 H each, But); 2.04 (m,
2 Н, АrCH2CH2); 2.69 (t, 2 Н, АrСН2,
J = 7); 2.75 (t, 2 Н, СН2Cl, J = 6); 4.99
(br.s, 1 Н, ОН); 6.98, 7.17 (both d,
1 H each, Ar, J = 2.5)
4i
69
Tar
123—127 72.00 9.49
72.19 9.62
12.45 C17H27СlO
12.53
5e
5i
93
96
Tar
Tar
90—95
82.40 9.93
82.30 9.87
—
—
—
—
C14H20
O
1.45 (s, 9 H, But); 2.25 (s, 3 H, Me); 4.26
(m, 2 H, OCH2); 5.28, 5.49 (both m, 1 H
each, =CH2); 6.15 (m, 1 Н, —CH=); 7.02
(m, 2 Н, Ar); 7.10 (m, 1 Н, Ar)
1.41, 1.52 (both s, 9 H each, But); 4.61 (dt,
2 H, OCH2, J = 5, J = 1.5); 5.33 (dm,
1 Н, =CH2, J = 5.5); 5.52 (dm, 1 Н,
=CH2, J = 17.5); 6.14 (m, 1 Н, —CH=);
6.82 (d, 1 Н, Ar, J = 8.5); 7.19 (dd, 1 Н,
Ar, J = 8.5, J = 2.5); 7.37 (d, 1 Н, Ar,
J = 2.5)
103—107 82.91 10.68
82.87 10.64
C17H26
O
6e
6i
85
91
Tar
Tar
95—98
82.24 9.79
82.30 9.87
—
—
—
—
C14H20
O
1.45 (s, 9 H, But); 2.25 (s, 3 H, Me); 4.27
(m, 2 Н, ArСН2); 4.65 (s, 1 Н, ОН); 5.09
(m, 2 Н, =CH2); 5.99 (m, 1 Н, —CH=);
7.05 (d, 1 Н, Ar, J = 2); 7.13 (d, 1 Н, Ar,
J = 1.5)
1.34, 1.46 (both s, 9 H each, But); 3.45 (dt,
2 Н, АrСН2, J = 6.5, J = 1.5); 5.10 (s,
1 Н, ОН); 5.25—5.32 (m, 2 Н, =СН2);
6.03—6.11 (m, 1 Н, —СН=); 6.99 (d, 1 Н,
Ar, J = 2.5); 7.17 (d, 1 Н, Ar, J = 2)
110—115 82.80 10.57
82.87 10.64
C17H26
O
The synthesis and physical and chemical characteristics of allyl
derivatives 5b,с,f 14 and 6b,с,f 14 and bromopropane 4а 9 were
described earlier.
mathematical treatment were carried out with Origin 6.0
program.
The working concentrations of components in a sample were
In the kinetic studies, a manometric method for the deterꢀ
mination of the rate constant values for the reaction of phenols
with peroxide radicals was used.12 In this work, methyl oleate
(Аcros Organics) was used, oxidation of which was carried out
at 60 °C in aq. SDS, containing dihydrate of tetrasodium salt of
ethylenediaminetetraacetic acid (0.2 mmol L–1); pH 7.37 (phosꢀ
phate buffer, 50 mmol L–1). APH (Acros Organics) was used as
the initiator. The rate of oxidation was monitored using a highꢀ
sensitive capillary. A construction of kinetic curves and their
as follows: methyl oleate, 0.133 mol L–1; АРН, 6.15 mmol L–1
;
SDS, 0.25 mol L–1. Compound 1 and 2 were added in amounts
of 4.5•10–5—2.3•10–4 mol L–1. The rate of initiation Wi (deterꢀ
mined by the method of inhibitors12) was 7•10–8 mol L–1 s–1
the length of oxidation chains was no less than 27 units.
,
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 05ꢀ04ꢀ
48819).

Sulfurꢀcontaining phenols as antioxidants
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 6, June, 2007
1143
ternational Conf. "Bioantioxidant"] (Moscow, April 16—19,
2002), Moscow, 2002, 278.
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