Synthesis of phenolic antioxidants with isobornyl and tert-butyl fragments

Article abstract of DOI:10.1134/S1070363213060170

Hybrid antioxidants, phenols with a terpene and tert-butyl substituents, were synthesized by the alkylation of 2-tert-butyl-4-methylphenol with camphene and 2-isobornylphenol with tert-butyl chloride in the presence of acidic heterogeneous catalysts, montmorillonite KSF and FIBAN K-1. Antioxidant activity of the synthesized terpenophenols was evaluated using spectrophotometry.

Full text of DOI:10.1134/S1070363213060170

ISSN 1070-3632, Russian Journal of General Chemistry, 2013, Vol. 83, No. 6, pp. 1103–1110. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © I.V. Fedorova, I.Yu. Chukicheva, O.A. Shumova, A.V. Kutchin, 2013, published in Zhurnal Obshchei Khimii, 2013, Vol. 83, No. 6,
pp. 972–979.
Synthesis of Phenolic Antioxidants
with Isobornyl and tert-Butyl Fragments
I. V. Fedorova, I. Yu. Chukicheva, O. A. Shumova, and A. V. Kutchin
Institute of Chemistry, Komi Scientific Center, Ural Branch, Russian Academy of Sciences,
ul. Pervomaiskaya 48, Syktyvkar, 167982 Russia
e-mail: chukicheva-iy@chemi.komisc.ru
Received May 10, 2012
Abstract―Hybrid antioxidants, phenols with a terpene and tert-butyl substituents, were synthesized by the
alkylation of 2-tert-butyl-4-methylphenol with camphene and 2-isobornylphenol with tert-butyl chloride in the
presence of acidic heterogeneous catalysts, montmorillonite KSF and FIBAN K-1. Antioxidant activity of the
synthesized terpenophenols was evaluated using spectrophotometry.
DOI: 10.1134/S1070363213060170
Terpenophenols exhibit a number of practically
useful properties [1–3]. By their antioxidant activity,
2,6-diisobornyl-4-methylphenol exceeds the widely
4-methylphenol, 2-tert-butylphenol and 2,6-di-tert-
butylphenol with camphene, and alkylation of 2-
isobornylphenol and 2-isobornyl-4-methylphenol with
either tert-butyl alcohol, methyl tert-butyl ether, or
tert-butyl chloride. As the catalysts heterogenous
(KSF, FIBAN K-1) and homogeneous [(PhO)3Al,
(i-PrO)3Al] ones were studied. The optimal reaction
conditions were selected by varying temperature and
the reactant ratio.
used
in
industry
ionol-, 2,6-di-tert-butyl-4-
methylphenol [4]. We have previously shown that
ionol and 2,6-diisobornyl-4-methylphenol correspond
to compounds with different type of mechanism of
antiradical activity, which may be defined by the
structure of substituents in the aromatic ring [5]. In
order to identify the role of terpene fragment in the
antioxidant activity, it was of interest to synthesize a
phenol containing in its structure isobornyl and tert-
butyl fragments. For the synthesis of this compound
we used several approaches: alkylation of 2-tert-butyl-
The direct alkylation of 2-tert-butylphenol (I) with
camphene (III) in the presence of (PhO)3Al or (i-PrO)3Al
failed. We attempted to perform transalkylation of 2,6-
di-tert-butylphenol (II) with camphene (III) in the
Scheme 1.
OH
OH
OH
CH3
C
R
R
KSF
+ CH3
+
Cl
CH3
IV
V
9
VIa, VIb
VIIa, VIIb
7
8
7
10
10
(b).
(a);
R =
1
4
5
6
9
2
6
3
4
1
2
5
3
H
H
8
1103

1104
FEDOROVA et al.
Table 1. tert-Butylphenol alkylation with camphene III: conditions and products
Ratio of reaction products, %
Initial phenol
Catalyst
Reaction conditions
ortho-
ortho-,ortho-
ortho-, para
2-tert-Butylphenol (I)
(PhO)3Al
(i-PrO)3Al
(i-PrO)3Al
KSF
160°С, 32 h
180–200°С, 46 h
180–200°С, 26 h
100°С, 40 h
13
74
13
38
–
5
–
57
–
2,6-Di-tert-butylphenol (II)
43
–
57
presence of the same organoaluminum catalysts at
160°C and 180–200°C, as well as with acidic hetero-
geneous catalyst montmorillonite KSF in boiling
heptane. The performed reactions resulted in the forma-
tion of a mixture of ortho-/para-t-Bu phenols. Under
these conditions, tert-butyl fragment is easily detached
from the original phenol and then, being more stable
carbocation than the secondary carbocation based on
the camphene, it alkylates phenol at ortho- or para-
position affording a mixture of substituted phenols
(Table 1).
The next approach was to introduce tert-butyl
fragment in the molecule of 2-isobornylphenol IV in
the reaction with either methyl tert-butyl ether, or tert-
butyl alcohol, or tert-butyl chloride V (Scheme 1). The
reactions with methyl-tert-butyl ether and tert-butyl
alcohol were attempted in the presence of an
organoaluminum catalyst, (PhO)3Al or (i-PrO)3Al, at
180–200°C, as well as of KSF clay in boiling methyl
tert-butyl ether or tert-butyl alcohol. According to
GLC analysis, the reaction failed under all these
conditions.
Scheme 2.
OH
OH
OH
R
R
R
KSF
+
+
V
VIII
IХa, IXb
Хa
9
7
8
7
10
10
(b).
(a);
R =
1
4
5
6
9
2
6
3
4
1
2
5
3
H
H
8
Reaction of 2-isobornylphenol IV with tert-butyl
chloride V was performed in the presence of
montmorillonite KSF in boiling CH2Cl2 (the ratio of
IV:V = 1:1) or in boiling tert-butyl chloride. Boiling in
CH2Cl2 promotes the formation of disubstituted
phenols VIIa and VIIb with a total yield 59%, mainly
a terpenephenol with isobornyl substituent (VIIa),
yield 48%. The yield of trisubstituted phenol VIa was
32%. As by-products, we isolated phenols I and II (2%
and 7% respectively). Boiling in tert-butyl chloride of
phenol IV resulted in the selective formation of 2-
isobornyl-4,6-di-tert-butyl-phenol VIa in 96% yield,
and 2-isocamphyl-4,6-di-tert-butylphenol (VIb) was
isolated in 4% yield. It should be noted that in these
conditions isomerization of the isobornyl fragment (a)
occurs to isocamphyl (b), with the formation of
phenols VIb and VIIb due to the presence of HCl in
the reaction mixture.
The alkylation of 2-isobornyl-4-methylphenol VIII
with tert-butyl chloride V in the presence of
montmorillonite KSF (Sceme 2) proceeds selectively
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 6 2013

SYNTHESIS OF PHENOLIC ANTIOXIDANTS
1105
with the predominant formation of 2-isobornyl-4-
methyl-6-tert-butylphenol IXa (74%), phenol (IXb)
with isocamphyl structure of the terpene substituent
(11%) also was isolated. The yield of disubstituted
phenol Xa with isobornyl structure of the terpene
substituent was 15%.
Scheme 3.
9
OR
8
7
10
O
O
1
+
+
2
2
6
CH3
3
ХIIa
ХIII
ХIV
OH
OH
OH
OH
OH
R
R
R
R
KSF
+
+
+ III
+
R
ХI
IХa_IXc
ХVIb, XVIc
ХVb
Хb
Cl
C
O
Cl
Cl
ХVII
9
9
7
8
7
7
10
10
10
(c).
(a);
(b);
R =
4
1
4
1
2
2
5
6
6
6
3
9
4
1
5
8
2
5
3
3
H
H
H
8
Alkylation of 2-tert-butyl-4-methylphenol XI with
camphene III in the presence of heterogeneous
catalysts also contributes to the formation of hybrid
phenol (Scheme 3). As the source the phenol was used
substituted in the para-position, to prevent the isomeriza-
tion of 2-tert-butylphenol in 4-tert-butylphenol.
Scheme 4.
H+
2
+
6
+
А
B
III
Cl
C
H
C
Cl
C
Cl
Cl
[O]
HCl
B
O
H
H
O
Cl
O
Cl
C
Cl
H+
Cl
Cl
Cl
ХVII
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 6 2013

1106
FEDOROVA et al.
Table 2. 2-tert-Butyl-4-methylphenol alkylation with camphene III: conditions and products
Ratio of reaction products, %
Molar ratio
Reaction
Conversion,
%
IX
b
ХVI
Mixtureа
XI:III
conditions
X
XIIa XIII XIV
XVb
XVII
а
c
b
c
FIBAN K-1
1:1
1:1
10 h, СН2Сl2,
boiling
40
81
8
9
18
30
–
–
–
–
10
–
26
–
–
2
–
7
–
5
38
–
–
6 h, С7Н16,
boiling
19
–
28
Montmorillonite KSF
10 h, СН2Сl2,
boiling
72
85
84
71
98
50
30
24
20
31
9
50
43
15
19
2
–
–
9
–
–
–
9
–
–
13
–
–
–
–
1
7
7
–
–
–
–
7
–
–
–
–
–
–
–
6
–
–
3
9
19
6
4.5 h, С6Н14,
boiling
7
2 h, С7Н16,
boiling
–
–
–
10
–
1:2
2:1
4.5 h, СН2Сl2,
boiling
8
11
–
34
25
4.5 h, СН2Сl2,
boiling
16
–
a Complex mixture of products of alkylation and oxidation.
The results listed in Table 2 show that regardless of
the catalyst (montmorillonite KSF, FIBAN K-1) a
mixture of the products of O- and C-alkylation is
formed. However, based on the conversion and the
amount of target products IXa–IXc, we conclude that
the optimal procedure consists in the use of the
montmorillonite KSF: at boiling in CH2Cl2 and
equimolar ratio of the initial reactants the products
XIIa–XIIc are formed with a total yield 61%, at 70°C,
80%, and at 100°C, 67%.
We found that in the presence of sulfonic acid
cation exchanger FIBAN K-1 (boiling in CH2Cl2)
trichloromethoxy derivative XVII is formed in a
significant amount (38%), which has not previously
been observed in the alkylation of other phenols in
similar conditions [6]. The formation of product XVII
can be represented by Scheme 4.
The nature of the oxidant is currently unknown.
Under the same conditions products XIII and XIV
were obtained.
Table 3. Antioxidant activity of compounds IXa, IXb, and
XVb
Quantity of compound (µg)
DPPH-binding
The reaction in heptane (100°C) using a sulfonic
acid cation exchanger resulted in the conversion
increase up to 81% and the overall yield of monoalkyl
phenols IXa–IXc, mainly IXb (30%), to 58%.
However, in this case up to 28% of the oxidation
products is formed.
Compound
50% discolorizing
activity, %
in 30 min 37.2 µg of DPPH
Trolox
IXb
0.014659
0.028431
0.029744
5.863587
11.37231
11.89772
Thus, the optimal method of synthesis of the
phenols containing in one molecule both isobornyl and
tert-butyl substituents is alkylation of ortho-
isobornylphenols with tert-butyl chloride in the
presence of clay KSF.
IXa
Ionol
XVb
0.044662
0.09481
17.86479
37.9239
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 6 2013

SYNTHESIS OF PHENOLIC ANTIOXIDANTS
1107
The evaluation of antioxidant activity of the
synthesized hybrid terpenophenols by measuring their
ability to bind the stable radical diphenylpicryl-
hydrazyl (DPPH) using a spectrophotometric method
showed that 2-isocamphyl-4-methyl-6-tert-butylphenol
IXb and 2-isobornyl-4-methyl-6-tert-butylphenol IXa
exhibit a higher antioxidant activity than ionol, but
inferior to trolox (6-hydroxy-2,5,7,8-tetramethyl-
chroman-2-carboxylic acid) (Table 3). For comparison,
the level of antioxidant activity of 2-tert-butyl-4-
methyl-5-isocamphylphenol XVb is significantly
lower.
Alkylation of tert-butylphenols with camphene in
the presence of aluminum-containing catalysts (by
an example of 2-tert-butylphenol). To 0.1 g of a
phenol heated to 160°C was added 0.01 g of aluminum
shavings in small portions. After complete dissolution
of aluminum in the phenol, the solution was cooled to
40°C and then 1 g (0.6 mmol) of 2-tert-butylphenol I
and 1.82 g (13 mmol) of camphene III was added. The
reaction was performed while maintaining the
temperature at 160°C for 32 h (GLC monitoring). The
reaction mixture was cooled, diluted with diethyl ether,
treated with dilute hydrochloric acid to decompose the
catalyst, and washed with water until neutral. The
organic extract was dried over anhydrous Na2SO4, the
solvent was evaporated. The reaction products were
separated by column chromatography (Table 1).
EXPERIMENTAL
1
The H and 13C NMR spectra of the obtained
compounds were recorded on a Bruker Avance II 300
spectrometer (300 MHz and 75 MHz respectively),
solvent CDCl3, at room temperature. As the internal
reference the signal of chloroform (δH 7.26 ppm, δC
76.90 ppm) was used. The assignment of signals was
performed using 13C NMR spectra recorded in JMOD
mode and two-dimensional NMR spectroscopy (HSQC,
COSY, NOESY). The IR spectra were recorded on a
Shimadzu FT-IR spectrometer IR Prestige 21.
When (i-PrO)3Al was used as the catalyst, the
reagents and catalyst were loaded simultaneously. The
reaction was carried out for 46 h, maintaining the
temperature at 180–200°C (Table 1).
Spectral characteristics of compounds obtained
correspond to published data [8, 9].
Reaction of 2-isobornylphenol with tert-butyl
chloride. A two-neck flask was charged with 2 g
(0.87 mol) of 2-isobornylphenol IV and 0.8 g
(0.87 mol) of tert-butyl chloride V. Montmorillonite
KSF was taken in a weight ratio of 1:1 to the original
2-isobornylphenol IV. The reaction was carried out in
CH2Cl2 for 5 h or in tert-butyl chloride for 1 h, at
reflux.
Purity of starting materials was checked and the
analysis of reaction products was performed by GLC
on a Shimadzu GC-2010AF instrument with the flame
ionization detector (carrier gas helium), capillary
column HP-1 (Agilent, 60 m × 0.25 mm × 0.25 µm,
ramp 100–240°C, heating rate 6 deg min–1). Melting
points were determined on a Koeffler heating block.
The reactions course was monitored by TLC on
Sorbfil plates, using the solvent system petroleum
ether–diethyl ether with an increase in the proportion
of the latter. The development was performed by
treating the plate with a solution of KMnO4 (25 g of
KMnO4, 300 ml of H2O, and 0.5 ml of concn. H2SO4),
and with a solution of vanillin (1 g of vanillin of 5 ml
of conc. H2SO4 in 100 ml of 95% ethanol) followed by
heating to 100–150°C. The separation of reaction
products was performed by column chromato-graphy
on a 70/230μ silica gel (from Alfa Aesar).
After the reaction completing, the reaction mixture
was dissolved in diethyl ether, filtered from the
catalyst, and the separation of reaction products was
performed by column chromatography.
2,4-Di-tert-butyl-6-(1,7,7-trimethylbicyclo[2.2.1]-
hept-2-yl)phenol (VIa). Colorless powder, mp 119°C.
IR spectrum (KBr, ν, cm–1): 3641, 3604 (OH), 2953,
2874, 1462, 1388, 1363 (CH3, CH2), 1600 (C=C), 1186
(=C–O), 881 , 727 (=C–H). 1H NMR spectrum, δ, ppm
9
(J, Hz): 0.82 s (3H, CH310), 0.88 s (3H, CH3 ), 0.92 s
8
(3H, CH3 ), 1.44 s (9H, CH318, CH319, CH320), 1.47 s
Camphene (racemate) used contained 5% of
tricyclene. (i-PrO)3Al (Alfa Aesar), (PhO)3Al (syn-
thesized in situ), montmorillonite KSF (Acros
Organics), and cationite FIBAN K-1 provided by the
Institute of Physical Organic Chemistry, National
Academy of Sciences of Belarus' were used as
catalysts.
(9H, CH322, CH323, CH324), 1.69–1.73 m (2H, H5, H6),
1.89–1.91 m (1H, H3, H4, H5, H6), 2.58–2.32 m (1H,
H3 ), 2.92 m (1H, H2, J 8.4 Hz), 4.80 s (1H, OH), 7.17
s (1H, H16), 7.23 s (1H, H14). 13C NMR spectrum, δC,
ppm: 12.48 (C10), 20.17 (C9), 21.47 (C8), 27.67 (C5),
29.96 (C18, C19, C20), 30.43 (C21), 31.67 (C22, C23, C24),
34.62 (C6), 40.57 (C3), 45.52 (C2), 46.53 (C4), 48.27
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 6 2013

1108
FEDOROVA et al.
(C1), 49.41 (C7), 121.15 (C14), 127.73 (C16), 127.85
(C11), 134.51 ( C13), 140.98 (C15), 150.95 (C12).
ethyl ether, filtered from the catalyst, and the reaction
products were separated by column chromatography.
2,4-Di-tert-butyl-6-(2,3,3-trimethylbicyclo[2.2.1]-
hept-5-yl)phenol (VIb). Colorless oil. 1H NMR
spectrum, δ, ppm (J, Hz): 0.98 d (3H, CH310, J 3.3 Hz),
2-tert-Butyl-4-methyl-6-(1,7,7-trimethylbicyclo-
[2.2.1]hept-2-yl)phenol (Xa). Colorless powder, mp
112°C. IR spectrum (KBr, ν, cm–1): 3603 (OH), 2954,
2920, 2876, 1442, 1386, 1361 (CH3, CH2), 1607
(C=C), 1166 (=C–O), 860 , 794, 765 (=C–H). 1H NMR
spectrum, δ, ppm (J, Hz): 0.84 s (3H, CH310), 0.90 s
8
9
19
1.12 s (6H, CH3 , CH3 ), 1.44 s (9H, CH318, CH3
,
CH320) 1.47 s (9H, CH322, CH323, CH324), 1.69–1.73 m
(3H, H1, H3, H5), 1.89–1.91 m (1H, H6, H4), 2.76 t (1H,
H5, J 7.2 Hz), 4.80 s (1H, OH), 7.17 s (1H, H16), 7.23 s
(1H, H14). 13C NMR spectrum, δC, ppm: 16.28 (C10),
24.47 (C9), 27.49 (C8), 27.67 (C5), 29.96 (C18, C19,
C20), 30.43 (C21), 31.67 (C22, C23 , C24), 32.72 (C7),
33.58 (C6), 45.52 (C2), 46.53 (C4), 49.57 (C1), 48.27
(C3), 121.15 (C14), 127.73 (C16), 127.85 (C11), 134.51
( C13), 140.98 (C15), 150.95 (C12).
9
8
19
(3H, CH3 ), 0.93 s (3H, CH3 ), 1.47 s (9H, CH3
,
CH320, CH321), 1.68–1.74 m (6H, H3, H4, 2H5, 2H6),
1.93–1.99 m (1H, 3H), 2.33 s (3H, CH317), 2.93 t (1H,
H2, J 8.4 Hz), 4.82 s (1H, OH), 7.01 s (1H, H16), 7.03 s
(1H, H14). 13C NMR spectrum, δC, ppm: 12.25 (C10),
20.23 (C9), 21.46 (C8), 21.35 (C17), 27.65 (C5), 29.90
(C19, C20, C21), 34.28 (C6) 34.40 (C18), 40.35 (C3),
45.44 (C2), 46.29 (C4), 48.39 (C1), 49.47 (C7), 125.07
(C16), 126.14 (C14), 127.93 (C11), 128.46 (C15), 135.34
(C13), 151.26 (C12).
2-tert-Butyl-6-(1,7,7-trimethylbicyclo[2.2.1]hept-
1
2-yl)phenol (VIIa). Colorless oil. H NMR spectrum,
9
δ, ppm (J, Hz): 0.85 s (3H, CH310), 0.90 s (3H, CH3 ),
8
0.97 s (3H, CH3 ), 1.46 s (9H, CH318, CH319, CH320),
2-tert-Butyl-4-methyl-6-(2,3,3-trimethylbicyclo-
1.61–1.69 m (2H, H5, H6), 1.90–1.91 m (4H, H3, H4,
H5, H6), 2.23–2.31 m (1H, 3H), 3.16 m (1H, H2, J 8.4 Hz)
4.56 s (1H, OH), 7.07–7.13 m (1H, H15), 7.33 d (1H,
H14, J 2.1 Hz), 7.39 d (1H, H16, J 2.1 Hz). 13C NMR
spectrum, δC, ppm: 12.57 (C10), 20.26 (C9), 21.49 (C8),
27.58 (C5), 29.58 (C18, C19, C20), 34.12 (C17), 34.24
(C6) 40.22 (C3), 45.67 (C2), 45.74 (C4), 48.39 (C1),
49.47 (C7), 114.31 (C15), 122.94 (C14), 124.10 (C16),
132.46 (C11), 135.34 (C13), 151.26 (C12).
[2.2.1]hept-5-yl)phenol (Xb). Brown oil. H NMR
1
spectrum, δ, ppm (J, Hz): 0.99 d (3H, CH310, J 3.3 Hz),
8
9
20
1.12 s (6H, CH3 , CH3 ), 1.47 s (9H, CH319, CH3
,
CH321) 1.85–2.09 m (7H, H1, H3, H4, 2H6, 2H7), 2.33 s
(3H, CH317), 2.76 t (1H, H5, J 7.2 Hz), 4.81 s (1H,
OH), 6.90 s (1H , H16), 7.00 s (1H, H14). 13C NMR
spectrum, δC, ppm: 16.29 (C10), 21.30 (C17), 24.46
(C9), 27.67 (C8), 29.91 (C19, C20, C21), 32.72 (C7),
33.58 (C6) 34.09 (C18), 40.07 (C2), 40.96 (C1), 49.16
(C3), 49.87 (C4), 50.73 (C5), 123.44 (C16), 123.85
(C14), 128.37 (C11), 132.35 (C15), 135.70 (C13), 150.05
(C12).
2-tert-Butyl-6-(2,3,3-trimethylbicyclo[2.2.1]hept-
1
5-yl)phenol (VIIb). Colorless oil. H NMR spectrum,
δ, ppm (J, Hz): d 0.98 (3H, CH310, J 3.3 Hz), 1.12 s
8
9
20
(6H, CH3 , CH3 ), 1.49 s (9H, CH318, CH319, CH3
)
Alkylation of 2-tert-butyl-4-methylphenol cam-
phene in the presence of acid catalysts. In the case of
sulfonic acid cation exchanger FIBAN K-1 the catalyst
was taken in amount 10% to the initial 2-tert-butyl-4-
methylphenol, montmorillonite KSF was taken in a
weight ratio of 1:1 to the original 2-tert-butyl-4-
methylphenol. A mixture of 2-tert-butyl-4-methyl-
phenol XI, camphene III, and the catalyst taken in the
calculated amount was heated at a predetermined
temperature in a two-neck flask equipped with
thermometer and reflux condenser. The reaction was
carried out in an organic solvent (methylene chloride,
hexane, or heptane). The reaction conditions and
results are listed in Table 2.
1.67–1.75 m (2H, H1, H7), 1.92–1.94 m (3H, H3, H6,
H7), 3.19 t (1H, H5, J 7.2 Hz), 4.70 s (1H, OH), 7.11–
7.16 m (1H, H15), 7.37 d (1H, H14, J 2.1 Hz), 7.43 d
(1H, H16, J 2.1 Hz). 13C NMR spectrum, δC, ppm:
16.35 (C10), 24.80 (C9), 27.73 (C8), 32.51 (C18, C19,
C20), 33.45 (C7), 33.81 (C17), 34.28 (C3) 41.47 (C1),
48.09 (C2), 49.86 (C5), 49.99 (C6), 50.79 (C4), 115.99
(C15), 123.56 (C14), 124.11 (C16), 134.51 (C11), 142.08
(C13), 151.81 (C12).
Reaction of 2-isobornyl-4-methylphenol with tert-
butyl chloride. In a round-bottom flask was placed 0.2 g
of 2-isobornyl-4-methylphenol VIII dissolved in
0.2 ml of tert-butyl chloride V. Montmorillonite KSF
was taken in a weight ratio of 1:1 to the initial ortho-
isobornylphenol. The reaction mixture was heated at
reflux of tert-butyl chloride for 30 min. After the reac-
tion completing, the reaction mixture was dissolved in di-
After the reaction completing, the reaction mixture
was dissolved in diethyl ether, filtered from the
catalyst, and the reaction products were separated by
column chromatography.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 6 2013

SYNTHESIS OF PHENOLIC ANTIOXIDANTS
1109
Spectral characteristics of compounds Xa, Xb, and
XVIb, XVIc correspond to published data [6, 7].
(C3), 47.62 (C7), 50.50 (C1), 124.98 (C16), 126.22
(C14), 128.37 (C11), 130.54 (C15), 135.68 (C13), 150.02
(C12).
2-(2-tert-Butyl-4-methylphenoxy)-1,7,7-trimethyl-
bicyclo[2.2.1]heptane (XIIa). Viscous oil of light
brown color. IR spectrum (thin film, ν, cm–1): 2953,
2874, 1492, 1454, 1388 (CH3, CH2), 1606 (C=C), 1220
2-tert-Butyl-4-methyl-5-(2,3,3-trimethylbicyclo-
1
[2.2.1]hept-5-yl)phenol (XVb). Brown oil. H NMR
spectrum, δ, ppm (J, Hz): 0.94 d (3H, CH310, J 3.2 Hz),
8
9
20
1.12 s (6H, CH3 , CH3 ), 1.47 s (9H, CH319, CH3
,
1
(=C–O), 1189 (C–O), 802, 771 (=C–H). H NMR
CH321) 1.59–1.81 m (7H, H1, H3, H4, 2H6, 2H7), 2.27 s
(3H, CH317), 2.77 m (1H, H5, J 7.5 Hz), 4.58 s (1H,
OH), 6.58 s (1H , H12), 7.04 s (1H, H15). 13C NMR
spectrum, δC, ppm: 16.29 (C10), 21.30 (C17), 24.77
(C9), 27.69 (C8), 29.78 (C19, C20, C21), 33.03 (C7),
33.76 (C6) 34.09 (C18), 43.73 (C1), 44.89 (C2), 49.13
(C3), 49.79 (C4), 51.45 (C5), 113.57 (C12), 126.85
(C16), 128.85 (C15), 129.35 (C14) 132.70 (C11), 150.85
(C13).
spectrum, δ, ppm (J, Hz): 0.81 s (3H, CH310), 0.88 s
9
8
(3H, CH3 ), 0.94 s (3H, CH3 ), 1.45 s (9H, H19, H20,
H21 ), 1.69–2.02 m (7H, 2H3, H4, 2H5, 2H6), 2.34 s
(3H, CH317), 4.10–4.13 m (1H, H2), 6.83 d (1H, H16, J
8.1 Hz), 7.01 d (1H, H15, J 8.1 Hz), 7.17 s (1H, H13).
13C NMR spectrum, δC, ppm: 12.83 (C10), 20.35 (C9),
20.67 (C8), 21.3 (C17), 27.41 (C5), 34.68 (C18), 35.05
(C6), 40.91 (C3) , 45.26 (C2), 45.65 (C4), 48.10 (C1),
49.92 (C7), 85.34 (C2), 112.54 (C16), 124.68 (C14),
126.92 (C15), 127.88 (C13), 128.23 (C12) , 154.32 (C11).
1,7,7–Trimethyl-2-(trichloromethoxy)bicyclo-
[2.2.1]heptane (XVII). Colorless oil. IR spectrum
(thin film, ν, cm–1): 2954, 2927, 2870, 1458, 1366
(CH3, CH2), 796 (C–Cl). 1H NMR spectrum, δ, ppm (J,
2-Methoxy-1,7,7-trimethylbicyclo[2.2.1]heptane
(XIII). Light yellow oil. IR spectrum (thin film, ν, cm–1):
2949, 2874, 1452, 1365 (CH3, CH2), 1123, 1080 (C–O).
1H NMR spectrum, δ, ppm (J, Hz) : 0.84 s (3H,
9
8
Hz): 0.86 s (3H, CH3 ), 0.94 s (3H, CH3 ), 1.05 s (3H,
CH310), 1.21–1.46 m (6H, 2H3, 2H5 , 2H6), 1.75–1.77
m (1H, H4), 3.64–3.67 m (1H, H2). 13C NMR
spectrum, δC, ppm: 11.30 (C10), 20.11 (C9), 20.48 (C8),
27.24 (C5), 33.93 (C6), 40.41 (C3), 45.06 (C4), 46.78
(C7) , 48.52 (C1), 79.95 (C2), 115.40 (C11).
9
8
CH310), 0.93 s (3H, CH3 ), 0.99 s (3H, CH3 ), 1.44–
1.49 m (5H, H3, H4, H5, 2H6), 1.52–1.80 m (2H, 3H,
H5'), 3.13–3.17 m (1H, H2), 3.27 s (3H, CH311). 13C
NMR spectrum, δC, ppm: 11.80 (C10), 20.15 (C9),
20.24 (C8), 27.34 (C5), 34.64 (C6), 37.91 (C3), 45.05
(C4), 47.02 (C7) , 49.5 (C1), 56.57 (C11), 89.06 (C2).
Determination of antioxidant activity of the
terpenophenols (spectrophotometric method). The
antioxidant activity was determined by the ability of a
terpenophenol to bind in vitro the stable radical DPPH
(2,2-diphenyl-1-picrylhydrazyl) [10]. Each sample was
studied thrice. As a control served a mixture
containing all components except the analyte. To the
50 µl of 1, 0.1, 0.01 and 0.001% alcoholic solution of
the preparation was added 150 µl of 0.6 mM solution
of DPPH in ethanol. In parallel were carried out the
reactions with an alcoholic solution of ionol and trolox
at the same concentrations. The optical density was
measured on a plate spectrophotometer PowerWave
200TM (Bio-Tek Instruments, USA) at λ = 517 nm,
first immediately after adding DPPH and intensive
mixing (t0), then after 30 min of incubation in the dark
under a polyethylene film (t1) The antioxidant activity
was calculated by the formula [11]:
(1S,1'R,2R,4R,4'S,6'R)-2,6'-Oxybis(1,7,7-trimethyl-
1
bicyclo[2.2.1] heptane) (XIV). Light yellow oil. H
9
NMR spectrum, δ, ppm (J, Hz): 0.82 s (6H, CH3 ,
9'
8
8'
10
CH3 ), 0.86 s (6H, CH3 , CH3 ), 1.00 (6H, CH3
,
CH310'), 1.09 –1.23 m (4H, 2H6, 2H6'), 1.50–1.76 m
(10H, 2H3, 2H3', 1H4, 1H4', 2H5, 2H5'), 3.20–3.24 m
(2H, 1H2, 1H2'). 13C NMR spectrum, δC, ppm: 12.45
(C10, C10'), 20.18 (C9, C9'), 20.71 (C8, C8'), 27.39 (C5,
C5'), 34.45 (C6, C6') , 38.46 (C3'), 39.45 (C3), 45.63 (C4,
C4'), 47.08 (C1, C1'), 48.75 (C1, C1'), 84.42 (C2'), 86.78
(C2).
2-tert-Butyl-4-methyl-6-(1,4,7-trimethylbicyclo-
1
[2.2.1]hept-2-yl)phenol (IXc). Brown oil. H NMR
8
spectrum, δ, ppm (J, Hz): 0.71 s (6H, CH3 , CH310),
9
0.76 d (3H, CH3 , J 6.9 Hz), 1.07–1.17 m (2H, H5, H6),
1.46 s (9H, CH319, CH320, CH321), 1.58–1.62 m (2H,
H5, H6), 1.84–1.87 m (2H, H3, H7), 2.08–2.10 m (1H,
3H), 2.33 s (3H , CH317), 2.99–3.01 m (1H, H2), 4.88 s
(1H, OH), 6.90 s (1H, H16), 7.04 m (1H, H14). 13C
NMR spectrum, δC, ppm: 8.30 (C9), 15.61 (C10), 19.3
(C8), 21.34 (C17), 29.91 (C19, C20, C21), 33.59 (C18),
34.71 (C6) 37.78 (C5), 40.94 (C4), 44.19 (C2), 45.15
AOA (%) = (OD517blanc(0) – OD517sample(1))/OD517blanc(0)×100,
where OD517blanc(0) is optical density of the blank
measured immediately after adding DPPH, OD517sample(1)
is optical density of the sample, measured after 30 min
of incubation.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 6 2013

1110
FEDOROVA et al.
3. Plotnikov, M.B., Smolyakova, V.I., Ivanov, I.S., Ku-
Then were drawn the plots of dependence of the
chin, A.V., Chukicheva, I.J., and Krasnov, E.A., Bull.
Experiment. Biol. Med., 2008, vol. 145, no. 3, p. 328.
4. Chukucheva, I.Yu., Buravlev, Е.V., Fedorova, I.V.,
Borisenkov, M.F., and Kuchin, А.V., Izv. Akad. Nauk,
Ser. Khim., 2010, no. 12, p. 2220.
antioxidant activity on the concentration of the analyte
and the concentration of the substance was found
required for the discoloration of DPPH by 50%
(DPPH50).
5. Mazaletskaya, L.I., Sheludchenko, N.I., Shishkina, L.N.,
Kuchin, А.V., Fedorova, I.V., and Chukucheva, I.Yu.,
Petroleum Chem., 2011, vol. 51, no. 5, p. 348.
6. Chukucheva, I.Yu., Fedorova, I.V., and Kuchin, А.V.,
Khim. Rast. Syr’ya, 2009, no. 3, p. 63.
ACKNOWLEDGMENTS
The authors thank M.F. Borisenkova of the Institute
of Physiology, Komi Science Center, for the analysis
of antioxidant activity of the synthesized alkylphenols.
7. Chukucheva, I.Yu., Fedorova, I.V., Shumova, О.А., and
Kuchin, А.V., Russ. J. Bioorg. Chem., 2011, vol. 37,
no. 7, pp. 855–857.
This work was performed under the program of
Presidium of Russian Academy of Sciences no. 8
(project no. 12-P-3-1028).
8. Parton, R.F., Jacobs, J.M., Huybrechts, D.R., and Jacobs, P.A.,
Stud. Surf. Sci. Catal., 1988, no. 46, p. 163.
9. Namba, S., Yahima, T., Itaba, Y., and Hara, N., Stud.
Surf. Sci. Catal., 1980, no. 5, p. 105.
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