Synthesis and antioxidant activity of 3,5-di-tert-butyl-4-hydroxyphenylthiomethyltetraalkylcalix[4]resorcinarenes

Article abstract of DOI:10.1134/S107036321509011X

Deamination of dimethyl- and diethylaminomethylated tetraalkylcalix[4]resorcinarenes with 3,5-di-tert-butyl-4-hydroxyphenylmercaptan afforded new 3,5-di-tert-butyl-4-hydroxyphenylthiomethyltetraalkylcalix-[4]resorcinarenes. High antioxidant activity of th

Full text of DOI:10.1134/S107036321509011X

ISSN 1070-3632, Russian Journal of General Chemistry, 2015, Vol. 85, No. 9, pp. 2087–2090. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © G.N. Nugumanova, T.A. Barsukov, S.V. Bukharov, V.V. Syakaev, R.Ya. Deberdeev, 2015, published in Zhurnal Obshchei Khimii,
2015, Vol. 85, No. 9, pp. 1506–1510.
To the 85th Anniversary of birthday of late Yu.G. Gololobov
Synthesis and Antioxidant Activity of 3,5-Di-tert-butyl-
4-hydroxyphenylthiomethyltetraalkylcalix[4]resorcinarenes
G. N. Nugumanovaa, T. A. Barsukovb, S. V. Bukharova, V. V. Syakaevb, and R. Ya. Deberdeeva
a Kazan National Research Technological University, ul. Karla Marksa 68, Kazan, Tatarstan, 420015 Russia
e-mail: gulia_nn@yahoo.com
b Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center,
Russian Academy of Sciences, Kazan, Tatarstan, Russia
Received August 3, 2015
Abstract—Deamination of dimethyl- and diethylaminomethylated tetraalkylcalix[4]resorcinarenes with 3,5-di-
tert-butyl-4-hydroxyphenylmercaptan afforded new 3,5-di-tert-butyl-4-hydroxyphenylthiomethyltetraalkylcalix-
[4]resorcinarenes. High antioxidant activity of the synthesized alkylcalix[4]resorcinarenes was established in
the model reaction of initiated oxidation of styrene.
Keywords: calix[4]resorcinarenes, 3,5-di-tert-butyl-4-hydroxyphenylmercaptan, antioxidant activity
DOI: 10.1134/S107036321509011X
Sulfides of hindered phenols are of particular interest
as multifunctional antioxidants because of their pos-
sibility to show antioxidative intramolecular synergism
[1, 2]. Calixarene platform can further enhance the
antioxidant activity due to the effect of pre-organiza-
tion of functional groups attached thereto [3], and wide
possibilities for adjusting hydrophilic-lipophilic balance.
then with water. According to X-ray diffraction data,
compound 2b forms no dimers in the crystal [5] and its
reactivity during storage is not reduced [4].
In this work we performed synthesis of 3,5-di-tert-
butyl-4-hydroxyphenylthiomethyltetraalkylcalix[4]-
resorcinarenes 4a–4c differing by the length of
hydrocarbon substituent at the lower rim of the calix[4]-
resorcinarene platform.
We have previously reported the synthesis of 3,5-
di-tert-butyl-4-hydroxyphenylthiomethylated tetramethyl-
calix[4]resorcinarene 1 by reacting dimethyl- and
diethylaminomethylated tetramethylcalix[4]resorcina-
renes 2a and 2b with 3,5-di-tert-butyl-4-hydroxy-
phenylmercaptan 3 [4] (Scheme 1).
In contrast to compound 1 [4], in the case of calix
[4]resorcinarenes 4a–4c supramolecular organization
of the corresponding macrocyclic Mannich bases had
no effect on the synthesis process. The reactions
proceeded smoothly involving both dimethylamino-
methyl and diethylaminomethyl derivatives. Note that
reactions of tetraalkylcalix[4]resorcinarenes with 3,5-
di-tert-butyl-4-hydroxybenzylacetate, when heptyl and
nonyl moieties were present at the lower rim of the
calix[4]resorcinarene, resulted in the formation of
macrocycles containing only two 3,5-di-tert-butyl-4-
hydroxybenzyl fragments [6]. In the present work we
managed to obtain the tetrasubstituted derivatives with
a satisfactory yield.
It has been found that the reaction is greatly influ-
enced by supramolecular organization of the starting
dialkylaminomethylated calix[4]resorcinarenes. The
molecules of calix[4]resorcinarene 2a form dimers in
the crystal, in which dimethylaminomethyl group of
adjacent molecules are included into the macrocycle
cavities to each other. These steric hindrances prevent
the nucleophilic attack [5]. This leads to a loss of
reactivity of calix[4]resorcinarene 2a when removing
residual solvent molecules during storage accompanied
by the formation of these dimers, and its restoration by
washing the dried sample with dimethylsulfoxide and
Antioxidant activity of calix[4]resorcinarenes 1, 4b,
and 4c was studied in a model reaction of styrene
2087

2088
NUGUMANOVA et al.
Scheme 1.
R1
N
R1
HO
OH
R1
OH
HO
HO
OH
R1
Me
Me
Me
N
t-Bu
Bu-t
+ 4
R1
N
Me
OH
SH
R1
3
HO
OH
R1
N
R1
OH
2а, 2b
t-Bu
Bu-t
S
HO
OH
t-Bu
HO
t-Bu
HO
OH
OH
Me
Me
Me
S
Bu-t
OH
Bu-t
−4HN(R1)2
S
Me
HO
HO
OH
S
t-Bu
Bu-t
OH
1
R1 = Me (a), Et (b).
oxidation initiated by 2,2'-azobisisobutyronitrile (AIBN).
Quantitative characteristics of antioxidant activity were
the values of the oxidation rate wO, the induction period
of oxidation τ, and effective inhibition constant f × k7,
where f is an inhibitor capacity, which is equal to the
number of radical intermediates destruction in one inhi-
bitor molecule in acts of chain termination, k7 is a rate
constant of chain termination of oxidation (see table).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 9 2015

SYNTHESIS AND ANTIOXIDANT ACTIVITY
2089
Scheme 2.
R1
N
R3
R1
HO
OHc
HO
OH
R1
HO
HO
OH
OH
HO
HO
OH
OH
R2
R2
R2
R2
R2
R1
Hb
R3
N
4 (2)
−4HN(R1)2
R3
R1
R2
R2
R2
N
R1
HO
OH
HO
OH
R1
R3
N
R1
5a−5d
4a−4c
Ha
Bu-t
OH
R1 = Me (5а, 5c, 5d), Et (5b); R2 = Et (4а), C7H15 (4b), C9H19 (4c);R3 =
S
.
Bu-t
As seen from the data given in the table, the syn-
thesized calix[4]resorcinarenes 1, 4b, and 4c inhibited
significantly styrene oxidation, and the antioxidant
activity of calix[4]resorcinarenes decreased with
increasing length of the hydrocarbon chain at the lower
rim. Apparently, the reason for this may be self-
assembly of the molecules similar to those detected
previously among 3,5-di-tert-butyl-4-hydroxybenz-
ylated calix[4]resorcinarenes [3], which can lead to
spatial shielding of the antioxidant phenol moieties. It
should be noted that even with such negative effect
calix[4]resorcinarenes 4b and 4c outperformed
industrial antioxidant (3,5-di-tert-butyl-4-hydroxy-
benzyl)sulfide 6. This fact shows the availability of
calix[4]resorcinarene platform for efficient synthesis
of multifunctional antioxidants.
IR spectra were registered on a Bruker Vector-22 FT-
IR spectrometer.
The kinetics of initiated styrene oxidation in
chlorobenzene medium at 60°C was studied on a
gasometric apparatus [7] by registering in time the
amount of absorbed oxygen. Styrene concentration
was 1 mol/L, AIBN, 0.122 mol/L, inhibitors 1, 4b and
4c, 0.002 mol/L. The initiating rate [wi 1.38 ×
10–6 mol L–1 s–1)] and f × k7 value were calculated
according to [8, 9]. The value of the induction period
Kinetic parameters of initiated oxidation of styrene in the
presence of inhibitors
wO × 106,
f × k7,
Inhibitor
τ, s
mol L–1 s–1
L mol–1 s–1
EXPERIMENTAL
Without inhibitor
24.31
2.52
3.18
4.06
5.80
–
–
1H NMR spectra were recorded on a Bruker
AVANCE-600 spectrometer (600.13 MHz) using
residual proton signals of the deuterated solvents as
internal reference. Elemental analysis was performed
on a Perkin Elmer PE 2400 series 2 CHNS/O-analyzer.
1
1350
918
783
702
11040
8764
6864
4805
4b
4c
6
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 9 2015

2090
NUGUMANOVA et al.
of oxidation was determined by extrapolating the
straight section of the kinetic oxidation curve on the
time axis.
(1.03 mmol) of mercaptan 3. Yield 0.29 g (63%), mp >
300°C (decomp.). IR spectrum, ν, cm–1: 3635, 3344
(OH), 1610 (C=CAr). 1H NMR spectrum (30°C,
CDCl3), δ, ppm: 0.50–1.60 m (76H, C9H19), 1.27 br.s
(72H, CMe3), 4.00–4.50 br.s (8H, CH2S; 4H, CH),
5.10–5.30 br.s (4H, OH), 6.90–7.30 br.s (8H, Hа; 4H,
Hb; 8H, OHc). Found, %: C 75.12; H 9.35; S 6.00.
C124H184O12S4. Calculated, %: C 74.65; H 9.30; S 6.43.
Calix[4]resorcinarene 1 was synthesized by the
method described in [4]. Chlorobenzene was purified
as described in [10]. 2,2'-Azobisisobutyronitrile was
twice recrystallized from ethanol before use, mp 132°C.
4,6,10,12,16,18,22,24-Octahydroxy-5,11,17,19-
ACKNOWLEDGMENTS
tetrakis(3,5-di-tert-butyl-4-hydroxyphenylthiomethyl)-
2,8,14,20-tetraethylpentacyclo[19.3.1.13,7.19,13.115,19
]
This work was supported by the Ministry of
Education and Science of the Russian Federation in the
frame of the basic part of governmental contract.
octacosa-1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-
dodecaene (4a). a. A mixture of 0.50 g (0.60 mmol) of
calix[4]resorcinarene 5а, 0.63 g (2.66 mmol) of mer-
captan 3, and 18 mL of o-xylene was stirred at 125°C
under argon for 14 h. Then the solvent was removed;
the residue was washed with hexane and dried. Yield
0.66 g (68 %), mp > 180°C (decomp.). IR spectrum, ν,
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cm–1: 3633, 3367 (OH), 1607 (C=CAr). H NMR
spectrum (30°C, CDCl3), δ, ppm: 0.84 t (12H, CH3,
3JHH 7.0 Hz), 1.25 s (72H, CMe3), 2.10–2.25 m (8H,
CH2), 4.12 s (8H, CH2S), 4.15 t (4H, CH, 3JHH 7.3 Hz),
5.18 s (4H, OH), 7.11 s (8H, Ha), 7.12 s (4H, Hb), 7.60
s (8H, OHc). Found, %: C 72.34; H 8.20; S 7.63.
C96H128O12S4. Calculated, %: C 71.96; H 8.05; S 8.00.
b. Similarly from 0.30 g (0.34 mmol) of calix[4]-
resorcinarene 5b and 0.36 g (1.49 mmol) of mercaptan
3 were obtained 0.38 g (70%) of calix[4]resorcinarene 4a.
4,6,10,12,16,18,22,24-Octahydroxy-5,11,17,19-
tetrakis(3,5-di-tert-butyl-4-hydroxyphenylthiomethyl)-
2,8,14,20-tetraheptylpentacyclo-[19.3.1.13,7.19,13.115,19]-
octacosa-1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-
dodecaene (4b) was prepared similarly from 0.3 g
(0.26 mmol) of calix[4]resorcinarene 5c and 0.27 g
(1.13 mmol) of mercaptan 3. Yield 0.32 g (65%), mp >
200°C (decomp.). IR spectrum, ν, cm–1: 3620, 3361
1
(OH), 1603 (C=CAr). H NMR spectrum (CDCl3), δ,
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3
ppm: 0.93 t (12H, CH3, JHH 7.1 Hz), 1.25 s (72H,
CMe3), 1.26–1.49 m (40H, C5H10), 2.08–2.19 m (8H,
CHCH2), 4.13 s (8H, CH2S), 4.26 t (4H, CH, 3JHH 7.6 Hz),
5.19 s (4H, OH), 7.11 s (8H, Hа), 7.16 s (4H, Hb), 7.65
s (8H, OHc). Found, %: C 73.84; H 9.12; S 6.13.
C116H168O12S4. Calculated, %: C 74.00; H 8.99; S 6.81.
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octacosa-1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-
dodecaene (4c) was prepared similarly from 0.30 g
(0.24 mmol) of calix[4]resorcinarene 5d and 0.25 g
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