From catechol-tocopherol to catechol-hydroquinone polyphenolic antioxidant hybrids

Article abstract of DOI:10.1002/hc.21466

Multidefence antioxidants represent a valuable solution for the protection against oxidative stress. From the planned synthesis of a catechol-tocopherol hybrid, we isolated a catechol-hydroquinone hybrid through a BBr₃-mediated benzochromene-fluoren-1-ol transposition. The compound prepared showed a remarkable chain-breaking antioxidant in the catechol portion, while the very sensitive hydroquinone moiety revealed to be an efficient generator of hydroperoxyl radicals.

Full text of DOI:10.1002/hc.21466

Received: 29 September 2018
DOI: 10.1002/hc.21466
Revised: 15 November 2018
Accepted: 16 November 2018
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S P E C I A L I S S U E A R T I C L E
From catechol-tocopherol to catechol-hydroquinone polyphenolic
antioxidant hybrids
Caterina Viglianisi1
Andrea Baschieri2
Stefano Menichetti1
Riccardo Amorati2
Paola Morelli1
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1Department of Chemistry “Ugo
Schiff”, University of Florence, Sesto
Fiorentino, Italy
2Department of Chemistry “G.
Ciamician”, University of Bologna,
Bologna, Italy
Abstract
Multidefence antioxidants represent a valuable solution for the protection against
oxidative stress. From the planned synthesis of a catechol-tocopherol hybrid, we
isolated a catechol-hydroquinone hybrid through a BBr3-mediated benzochromene-
fluoren-1-ol transposition. The compound prepared showed a remarkable chain-
breaking antioxidant in the catechol portion, while the very sensitive hydroquinone
moiety revealed to be an efficient generator of hydroperoxyl radicals.
Correspondence
Stefano Menichetti, Department of
Chemistry “Ugo Schiff”, University of
Florence, Sesto Fiorentino, Italy.
Email: stefano.menichetti@unifi.it
catechin-like structure, with an enhanced planarity due to the
fused dialkyl substituted chromane ring,[8] and the right-side
1
INTRODUCTION
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Polyphenols are probably the most important family of natural
and synthetic chain-breaking antioxidants.[1] Flavonoids,[2] as
quercetin or catechin and tocopherols,[3] are diffuse in vascular
plants where they exert a crucial role in protection against tis-
sue oxidation. At the same time, synthetic phenolic derivatives
based on the structure of butyl hydroxy toluene, BHT, or butyl
hydroxy anisole, BHA, are typically used for protecting foods,
drugs, and polyolefinic polymeric packages from autoxida-
tion.[4] It is well known that either at biological or technological
level, the synergistic action of different antioxidants is manda-
tory in order to achieve an actual protection against oxidative
phenomena. Thus, the preparation of molecules able to exert
a multidefense action is a valuable field of research.[5] In our
group, such goal was accomplished with the synthesis of chalco-
gen containing catechin-like and tocopherol-like polyphenolic
derivatives which showed remarkable antioxidant activities.[6]
Despite the introduction of chalcogen atoms in a polypheno-
lic skeleton could bring interesting additional activities[7] (ie,
peroxides quenching and metal chelation), we decided to study
the possibility of build-up the compacted catechol-tocopherol
hybrid 1 (Figure 1).
chromene skeleton of alpha-tocopherol, the most potent lipo-
philic phenolic antioxidant known in nature.[3]
Our initial approach to the synthesis of 1 was exploit-
ing the radical arylation of p-quinones[9] followed by an
oxa-Pictet–Spengler cyclization as depicted in Scheme 1.
However, neither by generating the aryl radical under clas-
sical method[9] nor by carrying on the reaction using Pd(0)
catalysis, as recently reported by Baran,[10] the arylation of
2,3,5-trimethylhydroquinone was observed.
Thus, we decided to follow a different approach for the
construction of biphenyl units based on a Pd/norbornene dual
catalysis process.[11] As starting materials for this procedure,
we prepared bromo derivative 2, obtained from commercially
available 6-bromo-veratraldehyde by addition of MeMgBr,
oxidation to the corresponding methyl ketone and a further
addition of MeMgBr, and iodo derivatives 3 and 4 as the
result of the iodination with I2/HIO3 of 2,3-dimethyl- and
2,3,5-trimethyl anisole, respectively (Scheme 2).
We tried then to apply the mentioned procedure,[11]
reacting derivative 2 with 3, or 4, in the presence of cata-
lytic amounts of Pd(OAc)2, 1.0 equiv of norbornene and
dry K2CO3 in dry DMF at 105°C. Under this condition,
after 24 hours, we were able indeed to isolate derivative 5
(R=H) in 64% yield. On the other hand, compound 6 with
R=Me was not detected in the crude mixture, even forcing
In fact, 1 should possess the structural features ensuring a
remarkable chain-breaking antioxidant action by the left-side
Dedicated to 82nd birthday of Professor Furukawa.
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Heteroatom Chemistry. 2018;e21466.
https://doi.org/10.1002/hc.21466
wileyonlinelibrary.com/journal/hc
© 2018 Wiley Periodicals, Inc.
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VIGLIANISI et AL.
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FIGURE 1 Structure of envisaged compact catechol-tocopherol
hybrid 1
SCHEME 3 Proposed mechanism for benzochromene 5
formation
of a certain steric hindrance when R≠H at the palladacycle
intermediate level, preventing the formation of the benzo-
chromene system.
When we imagined the synthesis of a compact polyphe-
nolic antioxidant like 1, formally deriving from demeth-
ylation of methoxy groups in 6, we selected the skeleton
of alpha-tocopherol with three methyl groups on the
chromene moiety that ensure an optimal chain-breaking
antioxidant activity. However, demethylation of methoxy
groups of compound 5 should allow the preparation of
derivative 7, bearing the skeleton of beta-tocopherol that
ensure a good antioxidant activity as well. Thus, we stud-
ied the demethylation of methoxy groups of 5 using BBr3
in DCM at −78°C as depicted in Scheme 4. The analysis
of the deep purple crude reaction mixture, obtained after
a work-up at low temperature, pointed out the presence of
two derivatives, 8 and 9, with a very similar Rf on TLC,
none corresponding to the expected phenolic species 7.
In fact, the 13C NMR spectrum (d6 acetone) of the crude
mixture indicated two signals at 183.6 and 186.5 support-
ive of the conjugated carbonyls of quinone 8. The analy-
SCHEME 1 Retrosynthetic analysis for catechol-tocopherol
hybrid 1
1
sis of the H NMR spectrum (d6 acetone) of the mixture
was less supportive yet indicating the presence of two dif-
ferent compounds in roughly 1:3 ratio (8:9) with a total
amount of phenolic OH not compatible with the triphe-
nolic compound 7. Thus, we imagined that the reaction of
5 with BBr3, despite carried out at −78°C, caused the de-
methylation of the methoxy groups and the contemporary
opening of the chromene ring. This causes the formation
of tertiary carbocation able to undergo an intramolecular
electrophilic alkylation with formation of the dimethyl-
fluorene skeleton. Additionally, p-hydroquinone portion
of 9 undergoes a facile oxidation, even under the reac-
tion condition used for demethylation, to quinone 8. As a
SCHEME 2 Synthesis of benzochromene derivative 5
the reaction condition in terms of stoichiometry (up to 0.2
equiv Pd(OAc)2, temperature (up to 150°C), and times (up
to 100 h).
Taking in consideration the mechanism proposed for
such transformation (Scheme 3), it is reasonable to consider
that a penta substituted iodo derivative, like 4, could suffer

VIGLIANISI et AL.
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The chain-breaking antioxidant activity of 9 was deter-
mined by studying the inhibition of the thermally initiated
autoxidation of styrene, used as reference hydrocarbon, under
controlled conditions. Autoxidation of styrene is a radical
chain reaction (see Equations 1-6) carried on mainly by al-
kylperoxyl radicals (ROO˙) which are representative of the
reactive oxygen species responsible for the oxidation of natu-
ral lipids and man-made materials under air.[14] The initiator
is represented by azobis(isobutyronitrile) (AIBN), whose de-
composition at 30°C originates a constant flux of free radi-
cals (initiation rate, Ri).
In→R∙
(1)
R∙ +O2 →ROO∙
(2)
ROO∙ +PhCHCH2 →PhC∙HCH2OOR(=ROO∙)
SCHEME 4 BBr3 methoxy groups demethylation and access to
fluoren -1-ol 9
(3)
2ROO∙ →nonradical products
(4)
matter of fact, refluxing the crude mixture obtained after
work-up with an excess of Na2S2O4 in a 1:2 Et2O/H2O
mixture, we observed the complete reduction of 8 to 9 that
was isolated in 74% after a fast column chromatography
(Scheme 4).
ROO∙ +AH2 →ROOH+AH∙
(5)
AH∙ +ROO∙ →ROOH+A
In fact, despite 9 could be completely characterized and its
antioxidant activity measured (vide infra), it spontaneously
reacted with atmospheric oxygen with partial formation of
8. On the other hand, the possibility of completely convert
hydroquinone 9 into quinone 8 failed since any attempt led to
extensive decomposition, probably due to the contemporary
oxidation of the catecholic moiety. The chromane-indene
acid catalyzed transposition is a well-known procedure;[12]
however, very rare are the examples of its use for the syn-
thesis of polyphenolic fluorene derivatives[13] such as the
catechol-hydroquinone hybrid prepared in this study. Several
attempts to obtain 7 under basic conditions using EtSNa,
avoiding the chromane-fluorene transposition, gave only ran-
dom monodemethylation of the methoxy groups.
(6)
The reaction was followed by measuring the oxygen con-
sumption by an automatic oxygen uptake recording appara-
tus, build in our laboratory, based on a differential pressure
transducer.[15] In the absence of antioxidants, the O2 con-
sumption is linear (see Figure 2A, trace a), whereas in the
presence of an antioxidant, the O2 consumption is retarded or
completely inhibited for a period that depends on its concen-
tration (Figure 2A, trace b).
The number of radicals trapped by each antioxidant mol-
ecule (n) is related to the length of the inhibited period τ
through Equation (7), in which the initiation rate Ri can be
determined by using a reference antioxidant.[14] The rate
1.0
(A)
(B)
0.0
0.8
-0.5
a
b
-1.0
-1.5
-2.0
-2.5
0.6
FIGURE 2 (A) Oxygen consumption
observed during the autoxidation of styrene
(4.3 mol L−1) in chlorobenzene initiated
by AIBN (0.05 mol L−1) at 30°C without
antioxidants (a) or in the presence of 9
(10 μmol L−1). (B) Analysis of trace (b) by
Equation 8
0.4
0.2
0
1
2
3
4
0
1000
2000
3000
4000
time / s
-ln(1-t/τ)

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VIGLIANISI et AL.
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constant of the reaction of the antioxidant with ROO˙ radicals
(kinh, see Equation 5) was calculated by using Equation (8):
A plot of Δ[O2]t vs ln(1-t/τ) gives a straight line of slope kp
[styrene]/kinh from which kinh is obtained by using the known
kp value at 30°C of styrene, that is, 41 M−1 s−1.[14,15]
reaction with peroxyl radicals ROO˙ (kinh ≈ 1x106 M−1 s−1)
due to the catechol moiety, but a very short inhibition time
and consumption of radical units (n ≈ 1.5) caused by the
concomitant generation of hydroxyl radical HOO˙ due to the
hydroquinone portion. Further insight on the synthesis and
activity of multipotent hybrid polyphenolic antioxidants are
in due course in our laboratories.
Ri =n[ArOH]∕τ
(7)
Δ[O2]=(kpkinh)[styrene] ln (1−t∕τ)
(8)
2
EXPERIMENTAL
|
1H and 13C NMR spectra were recorded with Varian Mercury
Plus 400, using CDCl3 as solvent when not differently indi-
cated. Residual CHCl3 at 7.26 ppm and central line of CDCl3
The results reported in Table 1 show that the kinh of 9 is
relevant, being only three times lower than that of the best
lipophilic natural antioxidant α-tocopherol, and higher than
that of related catechols and polyphenols. On the other hand,
the number of radical trapped by 9 is unexpectedly small.
The presence of both hydroquinone and catechol moieties
would imply a n factor of 4, whereas experimentally n is 1.5.
The reason for this result can be understood by considering
the magnitudes of n factors of substituted hydroquinones re-
ported in Table 1. While hydroquinone can trap two ROO˙
radicals, the addition of two or three methyl groups lowers
the n factor to 0.6 and 0.1, respectively. This decrease in the
efficiency of radical trapping is due to the reversible reaction
of the semiquinone with O2, which causes the production of
HOO˙ which propagates the oxidative chain (Scheme 5).[18,
1
at 77.00 ppm were used as the reference of H-NMR and
13C-NMR spectra, respectively. FT-IR spectra were recorded
with Spectrum Two FT-IR Spectrometer. GC-MS spectra
were recorded with a QMD 100 Carlo Erba. ESI-MS spec-
tra were recorded with a JEOL MStation JMS700. Melting
points were measured with Stuart SMP50 Automatic Melting
Point Apparatus. All the reactions were monitored by TLC
on commercially available precoated plates (silica gel 60 F
254), and the products were visualized with acidic vanillin
solution. Silica gel 60 (230–400 mesh) was used for col-
umn chromatography. Dry solvents were obtained by The
PureSolv Micro Solvent Purification System.
19]
The rate constant of this reaction appears to be propor-
tional to the number of electron-donating groups on the aro-
matic ring of the hydroquinone portion of compound 9, and
it can be expected that a hydroquinone having four alkyl sub-
stituents has a n factor of 0, that is, every ROO˙ trapped is
converted into HOO˙.
It can be therefore concluded that the low n factor of 9
is due to quantitative HOO˙ production by its hydroquinone
moiety, whereas in the case of the catechol portion of the
molecule, this effect is small (see Scheme 5).
In conclusion, in this paper, we described the serendipitous
synthesis of a catechol-hydroquinone polyphenolic antioxi-
dant hybrid based on a rare benzo[b]chromene fluoren-1-ol
BBr3-mediated transposition. Studying the chain-breaking
antioxidant ability of derivative 9 we pointed out a very fast
2.1
ethanol
1-(2-Bromo-4,5-dimethoxyphenyl)
|
To a cold (-10°C) solution of 6-bromo-veratraldehyde
(500 mg, 2.04 mmol) in dry THF (20 mL), a solution of 3M
MeMgBr in Et2O (1.36 mL, 4.08 mmol) is added. The reac-
tion mixture is stirred under a positive nitrogen atmosphere,
at −10°C for 1 hour and then at rt for 20 hours. It is then
poured into a saturated aqueous NH4Cl solution (20 mL)
and extracted with Et2O (3 × 40 mL). The combined organic
layers are dried over Na2SO4, filtered, and concentrated in
vacuum to yield the desired product as a pale-yellow oil
(555 mg, quantitative yield) used without further purification
1
in the next step. H-NMR, 400 MHz: 7.11 (s, 1H); 6.97 (s,
TABLE 1 Rate constants of reaction
Antioxidant
kinh (M−1 s−1
)
n
Ref.
with ROO˙ radicals and stoichiometric
9
(1.0 0.1) × 106
3.2 × 106
4.2 × 105
6.8 × 105
5.5 × 106
1.2×106
1.5
2
1.9
1.5
2.0
This work
coefficient for 9 and other relevant phenolic
antioxidantsa
[14]
alpha-tocopherol
[16]
[17]
[18]
[19]
[19]
4-methylcatechol
caffeic acid phenethyl ester
hydroquinone
2,5-dimethylhydroquinone
2,3,5-trimethylhydroquinone
≈0.6
≈0.1
2.3 × 106
aIn chlorobenzene at 30°C.

VIGLIANISI et AL.
5 of 7
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concentrated in vacuum. The crude product is purified by col-
umn chromatography (eluent DCM/EtOAc = 3/1) to yield the
desired product as an orange oil (365 mg, 81%) used without
further purification in the next step.[20] 1H-NMR, 400 MHz:
7.27 (s, 1H); 7.02(s, 1H); 3.86 (s, 3H); 3.85 (s, 3H); 1.72 (s,
6H) ppm.
2.4
(3)
1-iodo-4-methoxy-2,3-dimethylbenzene
|
To a solution of 2,3-dimethylanisole (1.326 g, 9.74 mmol) in
acetic acid (31 mL) and water (3.5 mL), H2SO4 (0.39 mL),
I2 (0.989 g, 3.896 mmol), and HIO3 (0.342 g, 1.948 mmol)
were added in sequence. The reaction mixture is heated at
50°C for 4 days. It is then decolorized with aqueous sodium
hydrogen sulfite (10% w/v), diluted with water (200 mL),
and extracted with petroleum ether (3 × 100 mL). The com-
bined organic extracts are washed with water (100 mL), a
saturated aqueous NaHCO3 solution (2 × 100 mL), water
(100 mL), and brine (100 mL). The organic layer is then
dried over Na2SO4, filtered, and concentrated in vacuum.
The crude is purified by column chromatography (eluent:
petroleum ether (EP)] to yield the desired product as a
white solid (1.433 g, 56%).[21] 1H-NMR, 200 MHz, CDCl3:
7.63 (d, J = 4.0 Hz, 1H); 6.48(d, J = 4.0 Hz, 1H); 3.79 (s,
3H); 2.42 (s, 3H); 2.23 (s, 3H) ppm.
SCHEME 5 Mechanism of the reaction of 9 with ROO˙ radicals
and generation of chain-propagating HOO˙ radicals from hydroquinone
portion
1H); 5.18 (q, J = 6.8 Hz, 1H); 3.90 (s, 3H); 3.86 (s, 3H); 1.45
(d, J = 6.8 Hz, 3H) ppm.
2.5
1-iodo-4-methoxy-2,3,5-
|
2.2
1-(2-bromo-4,5-dimethoxyphenyl)
trimethylbenzene (4)
|
ethanone
To
a
solution of 2,3,5-trimethylanisole (1.683 g,
To a solution of 1-(2-Bromo-4,5-dimethoxyphenyl)etha-
nol (500 mg, 1.91 mmol) in dry DCM (20 mL), a homoge-
neous mixture of PCC (1.235 g, 5.73 mmol) and silica gel
(6 g) is added. The resulted reaction mixture is stirred at rt
for 6 hours. The solvent is then evaporated, and the resulting
crude product is filtered through a short silica gel column and
eluted with DCM and then EtOAc to yield the desired product
as a yellowish solid (421 mg, 81%) used without further puri-
fication in the next step. 1H-NMR, 400 MHz, CDCl3: 7.14 (s,
1H); 7.04 (s, 1H); 3.91 (s, 3H); 3.89 (s, 3H); 2.67 (s, 3H) ppm.
11.21 mmol) in acetic acid (36 mL) and water (4 mL),
H2SO4 (0.45 mL), I2 (1.138 g, 4.484 mmol), and HIO3
(0.394 g, 2.242 mmol) were added in sequence. The reac-
tion mixture is heated at 50°C for 5 days. It is then decol-
orized with aqueous sodium hydrogen sulfite (10% w/v),
diluted with water (200 mL), and extracted with petro-
leum ether (3 × 100 mL). The combined organic extracts
are washed with water (100 mL), a saturated aqueous
NaHCO3 solution (2 × 100 mL), water (100 mL), and brine
(100 mL). The organic layer is then dried over Na2SO4, fil-
tered, and concentrated in vacuum. The crude is purified by
column chromatography (eluent: EP/EtOAc=12/1) to yield
the desired product as a colorless oil (1550 mg, 50%).[22]
1H-NMR, 400 MHz, CDCl3: 7.50 (s, 1H); 3.81 (s, 3H);
2.44 (s, 3H); 2.33 (s, 3H), 2.23 (s, 3H) ppm.
2.3
2-(2-bromo-4,5-dimethoxyphenyl)
|
propan-2-ol (2)
To a cold (−10°C) solution of 1-(2-bromo-4,5-dimethoxyphenyl)
ethanone (421 mg, 1.54 mmol) in dry THF (15 mL), a solu-
tion of 3M MeMgBr in Et2O (1.50 mL, 3.08 mmol) is added.
The reaction mixture is stirred under a nitrogen atmosphere at
−10°C for 1 hour and then at rt for 10 hour. It is then diluted
with DCM (40 mL), poured into a saturated aqueous NH4Cl
solution (20 mL), and extracted with DCM (2 × 40 mL). The
combined organic layers are dried over Na2SO4, filtered, and
2.6
2,8,9-trimethoxy-3,4,6,6-tetramethyl-
|
6H-benzo[c]chromene (5)
To a Schlenk-type flask, containing Pd(OAc)2 (4.27 mg,
0.02 mmol) and K2CO3 (131 mg, 0.95 mmol), a solu-
tion of iodo derivative 3 (100 mg, 0.38 mmol), bromo

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VIGLIANISI et AL.
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derivative 2 (100 mg, 0.36 mmol), and norbornene (36 mg,
0.38 mmol) in dry DMF is added. The reaction mixture is
stirred under nitrogen at 105°C for 24 hours. After cool-
ing to rt, the organic layer is diluted with EtOAc (10 mL),
washed with water (2 × 10 mL), and dried over Na2SO4,
filtered, and concentrated in vacuum. The crude is puri-
fied by column chromatography (eluent: EP/EtOAc=8/1)
to yield the desired product as a yellow solid (75 mg,
chain-breaking antioxidant activity of 9 was evaluated by
studying the inhibition of the thermally initiated autoxidation
of styrene (4.3 mol L−1) in chlorobenzene. In a typical ex-
periment, an air-saturated mixture of the oxidizable substrate
and the solvent, 1:1 (v/v), containing AIBN (0.05 mol L−1)
as an initiator was equilibrated with an identical reference
solution containing an excess of 2,2,5,7,8-pentamethyl-6-ch
romanol (PMHC). After equilibration, and when a constant
O2 consumption was reached, a concentrated solution of the
antioxidant (final concentration = 5–10 μmol L−1) was in-
jected in the sample flask. The oxygen consumption in the
sample was measured after the calibration of the apparatus
from the differential pressure recorded with time between
the two channels. Initiation rates, Ri, were determined by the
inhibitor method using PMHC as a reference antioxidant:
Ri = 2[PMHC]/τ], where τ is the length of the induction pe-
1
64%). Mp = 115-116 °C. H-NMR, 400 MHz: 7.14 (s,
1H); 6.96 (s, 1H); 6.74 (s, 1H); 3.98 (s, 3H); 3.92 (s,
1H); 3.88 (s, 3H); 2.20 (s, 3H); 2.19 (s, 3H); 1.60 (s, 6H)
ppm. 13C-NMR, 100 MHz: 152.2; 148.6; 148.4; 144.3;
132.6; 127.0; 126.2; 122.5; 119.5; 106.6; 105.5; 102.1;
77.3; 56.4; 56.1; 56.0; 27.3; 12.1; 11.9 ppm. Elemental
Analysis for C20H24O4, Calcd: C, 73.15; H, 7.37. Found:
C, 73.46; H, 7.38.
riod (Ri = 5-7 × 10−9 M s−1)[14]
.
2.7
2,3,9,9-tetramethyl-9H-fluorene-
|
1,4,6,7-tetraol (9)
ORCID
To a solution of derivative 5 (55 mg, 0.17 mmol) in DCM dry
(3.5 mL) cooled at -78°C, a solution of BBr3, 1M in DCM
(770 μL, 0.77 mmol) is added. The mixture is then warmed to
rt and stirred for 4 hours, then poured slowly into ice, and ex-
tracted with DCM (4 × 30 mL). The combined organic layers
are dried over Na2SO4, filtered and concentrated in vacuum
to give a mixture of derivatives 8 and 9 as a purple solid.
The crude is poured in Et2O (2 mL), H2O (1 mL), phosphate
buffer 0.1 mol L−1 pH = 7.5 (1 mL), and 1.5 mol L−1 aque-
ous Na2S2O4 (1 mL) and refluxed for 1 hour. A discoloration
of the reaction mixture from purple to yellow is observed,
and the mixture is cooled to rt, diluted with Et2O (20 mL),
and washed with 10% HCl (2 × 20 mL). The organic layer is
dried over Na2SO4, filtered, and concentrated in vacuum to
yield the desired product 9 (36 mg, 74%, mp = 162-165°C)
as dark yellow solid turning purple standing over atmos-
pheric oxygen. 1H-NMR, 400 MHz, (CD3)2CO: 7.65 (s,
OH); 7.63 (s, 1H); 7.59 (s, OH); 6.89 (s, OH); 6.88 (s, 1H);
6.59 (s, OH); 2.21 (s, 3H); 2.19 (s, 3H); 1.51 (s, 6H) ppm.
13C-NMR, 100 MHz,(CD3)2CO: 146.1; 145.1; 143.8; 143.5;
137.2; 131.0; 126.4; 122.9; 122.0; 110.5; 108.7; 46.7; 24.7;
12.0; 11.9 ppm. IR, KBr: 3521 (OH stret.); 3435-3262 (OH
Caterina Viglianisi
Stefano Menichetti
Paola Morelli
https://orcid.org/0000-0002-2451-5856
https://orcid.org/0000-0001-6745-7484
https://orcid.org/0000-0002-3284-4000
https://orcid.org/0000-0002-2108-8190
https://orcid.org/0000-0002-6417-9957
Andrea Baschieri
Riccardo Amorati
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−
stretc.) cm−1. ESI-MS m/z negative mode: 285.23 [M-H] ;
570.87 [2M-H]−. Elemental Analysis for C17H18O4, Calcd:
C, 71.31; H, 6.34. Found: C,71.45; H, 6.63.
3
AUTOXIDATION
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How to cite this article: Viglianisi C, Menichetti S,
Morelli P, Baschieri A, Amorati R. From catechol-
tocopherol to catechol-hydroquinone polyphenolic
antioxidant hybrids. Heteroatom Chem. 2018;e21466.
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