Antioxidant activity of 2-methyl-1,3-benzoxazol-6-ol

Article abstract of DOI:10.1134/S1070363211010191

Antioxidant effect of 2-methyl-1,3-benzoxazol-6-ol in radical chain oxidation of organic compounds with molecular oxygen was studied. Antiradical activity in the reaction with stable diphenylpicrylhydrazyl radical was examined by photocolorimetry. The kinetic parameters of the reaction of 2-methyl-1,3-benzoxazol-6-ol with peroxy radicals of different natures were determined by volumetric and chemiluminescence methods. A relation was found between the antioxidant activity and electronic structure parameters calculated by quantum-chemical methods. Factors responsible for differences in chemiluminescence in the oxidation of organic substances with different polarities in the presence of the title compound were analyzed.

Full text of DOI:10.1134/S1070363211010191

ISSN 1070-3632, Russian Journal of General Chemistry, 2011, Vol. 81, No. 1, pp. 122–127. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © E.I. Khizhan, A.I. Khizhan, A.N. Nikolaevskii, O.P. Kniga, T.N. Ivleva, G.A. Tikhonova, 2011, published in Zhurnal Obshchei
Khimii, 2011, Vol. 81, No. 1, pp. 125–130.
Antioxidant Activity of 2-Methyl-1,3-benzoxazol-6-ol
E. I. Khizhana, A. I. Khizhanb, A. N. Nikolaevskiia, O. P. Knigaa,
T. N. Ivlevaa, and G. A. Tikhonovaa
a Donetsk National University, ul. Universitetskaya 24, Donetsk, 83001 Ukraine
e-mail: a_khyzhan@telenet.dn.ua
b Litvinenko Institute of Physical Organic and Coal Chemistry, National Academy of Sciences of Ukraine,
ul. R. Lyuksemburg 70, Donetsk, 83114 Ukraine
Received February 9, 2010
Abstract—Antioxidant effect of 2-methyl-1,3-benzoxazol-6-ol in radical chain oxidation of organic com-
pounds with molecular oxygen was studied. Antiradical activity in the reaction with stable diphenyl-
picrylhydrazyl radical was examined by photocolorimetry. The kinetic parameters of the reaction of 2-methyl-
1,3-benzoxazol-6-ol with peroxy radicals of different natures were determined by volumetric and chemi-
luminescence methods. A relation was found between the antioxidant activity and electronic structure param-
eters calculated by quantum-chemical methods. Factors responsible for differences in chemiluminescence in the
oxidation of organic substances with different polarities in the presence of the title compound were analyzed.
DOI: 10.1134/S1070363211010191
Inhibition of radical chain oxidation of organic
substances and materials based thereon via addition of
antioxidant is a quite significant problem from both
practical and theoretical viewpoints [1]. Phenol deriva-
tives occupy an important place among inhibitors of
oxidation of organic compounds. Sterically hindered
monohydric phenols have been studied most thorough-
ly, and they belong to a group of laboratory and
industrial antioxidants. In the recent time, increased
interest is attracted by unhindered phenols which
constitute the base of natural antioxidants. The most
promising but poorly studied as antioxidants are
heterocyclic phenols; they are interesting due to their
pronounced physiological activity and broad synthetic
potential [2].
rate is given by the equation W = k[DPPH][I]. The rate
constants calculated using the above equation were
5.6±0.2 and 1.80±0.07 l mol–1 s–1 in hexane and
benzene, respectively. The antiradical activity of
compound I turned out to be somewhat higher than
that of standard antioxidant Ionol [peroxy radical
acceptor; k = 1.50±0.06 and 0.27±0.01 l mol–1 s–1 in
hexane and benzene, respectively]. In going from
hexane to benzene the reaction rate constant decreases,
presumably due to the known ability of DPPH to form
π-complexes with aromatic hydrocarbons. Insofar as 2-
methyl-1,3-benzoxazole having no hydroxy group does
not react with DPPH, we can state with certainty that
the reaction center in the 2-methyl-1,3-benzoxazol-6-ol
(I) molecule is the hydroxy group.
The present study was aimed at elucidating
specificity of the antioxidant effect of 2-methyl-1,3-
benzoxazol-6-ol (I) in liquid-phase oxidation of
ethylbenzene, isopropylbenzene, and methyl ethyl
ketone. The activity of compound I in the reaction with
stable colored 2,2-diphenyl-1-picrylhydrazyl (DPPH)
radical was examined by photocolorimetry. Compound
I was found to react with DPPH in nonpolar organic
solvents, benzene and hexane. Regardless of the
solvent nature, the reaction was of first order with
respect to the substrate and DPPH, and the reaction
The reactivity of 2-methyl-1,3-benzoxazol-6-ol (I)
toward radicals determines its antioxidant properties in
the radical-initiated oxidation of ethylbenzene. Addi-
tion of compound I to the reaction mixture in the
oxidation of ethylbenzene inhibits the process. The
kinetic curves for oxygen absorption in the presence of
I (Fig. 1) clearly displayed an induction period (τ)
whose duration is directly proportional to the
concentration of compound I; this indicates oxidation
chain termination as a result of reaction with peroxy
radicals derived from ethylbenzene.
122

123
ANTIOXIDANT ACTIVITY OF 2-METHYL-1,3-BENZOXAZOL-6-OL
(b)
[O2]×103,
M
(a)
τ, min
[InH]×104,
M
t, min
Fig. 1. (a) Kinetic curves for oxygen absorption in the radical-initiated oxidation of ethylbenzene (1) in the absence of inhibitor and
(2–4) in the presence of 2-methyl-1,3-benzoxazol-6-ol (I); [InH]×104, M: (2) 0.1, (3) 0.5, (4) 2.0; (b) dependence of the induction
period on the concentration of 2-methyl-1,3-benzoxazol-6-ol (I); Wi = 2×10–7 mol l–1 s–1, 343 K.
2-Methyl-1,3-benzoxazol-6-ol (I) also showed
antioxidant activity in high-temperature autooxidation
of ethylbenzene (Fig. 2); however, in this case the
inhibition efficiency was lower than in the presence of
Ionol; this may be related to unproductive
consumption of compound I.
The rate constants determined by different methods
differed from each other. The chemiluminescence data
should be considered to be more accurate, for the
corresponding procedure is less complicated by pos-
sible side processes with participation of antioxidant.
The obtained data indicate that the reaction center in
molecule I in the reaction with peroxy radicals, as with
DPPH, is the hydroxy group in the benzene ring.
A direct proof for the fact that 2-methyl-1,3-
benzoxazol-6-ol (I) does react with peroxy radicals
derived from ethylbenzene was obtained by the
chemiluminescence method. Chemiluminescence (I0)
appears due to recombination of peroxy radicals during
[ROOH]×102,
M
oxidation of organic substances.
k6
·
·
(1)
R=O + hν.
RO2 + RO2
[ROOOOR]
R=O*
Addition of compound I to the reaction mixture in
the oxidation of ethylbenzene leads to sharp reduction
in the chemiluminescence intensity, i.e., inhibitor I
reacts with substrate peroxy radicals. This effect
becomes stronger as the inhibitor concentration
increases (Fig. 3). The kinetic parameters for the
reaction of hydroxybenzoxazole I with peroxy radicals
were calculated using Eq. (2) [3] and were compared
with the corresponding values obtained by volumetric
analysis (Table 1).
t, h
Fig. 2. Kinetic curves for accumulation of hydroperoxide in
the oxidation of ethylbenzene (1) in the absence of inhibitor
and in the presence of (2) 2-methyl-1,3-benzoxazol-6-ol (I)
and (3) Ionol; [InH] = 1.25×10–4 M, 393 K.
д(I/I0)
дt
k7
= 0.22
√Wi .
(2)
√k6
max
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KHIZHAN et al.
We also examined antioxidant properties of com-
I/I0
pound I toward different peroxy radicals and
determined specificity of chemiluminescence in dif-
ferent substrates. The kinetic curves for chemi-
uminescence in the oxidation of both ethylbenzene and
isopropylbenzene in the presence of 2-methyl-1,3-
benzoxazol-6-ol (I) conform to a classical shape (Figs.
3, 4a). The oxidation of methyl ethyl ketone in the
presence of compound I was characterized by
deviation
from
the
classical
pattern:
the
chemiluminescence intensity increased in the initial
part of the induction period (Fig. 4b). These findings
may be rationalized assuming that the process is
accompanied by one more reaction involving
compound I or the corresponding radical, which also
gives rise to chemiluminescence. Most probably, such
reaction is combination of peroxy radicals derived
from methyl ethyl ketone and radicals derived from the
inhibitor.
t, s
Fig. 3. Variation of the relative chemiluminescence intensity
in the initiated oxidation of ethylbenzene in the presence of
2-methyl-1,3-benzoxazol-6-ol (I); cІ, M: (1) 1× 10–5, (2) 2×
10–5, (3) 3×10–5; Wi = 5.4×10–7 mol l–1 s–1, 343 K.
k8
RO2⋅ + PhO⋅
(4)
Reaction products.
N
To identify the source of additional chemilumine-
scence in the oxidation of methyl ethyl ketone in the
presence of 2-methyl-1,3-benzoxazol-6-ol (I) as
inhibitor, we examined the effects of different factors:
nature of the emission activator, nature and concentra-
tion of initiator, and the presence of oxygen. No in-
crease in chemiluminescence intensity was observed in
the absence of initiator or oxygen, and the chemi-
luminescence intensity did not depend on the nature of
initiator. Increase in the initiator concentration was
accompanied by rise in chemiluminescence intensity.
The above data suggest that a new chemiluminescence
emitter appears with participation of peroxy radicals.
CH3
RO2
+
O
N
HO
O
k7
(3)
CH3
+
ROOH
O
On the basis of the k7 values for 2-methyl-1,3-
benzoxazol-6-ol at different temperatures (333–353 K)
we calculated the Arrhenius activation parameters and
obtained the general equation for the rate constant:
k7 = (9.6 ± 0.5) × 108 exp – [(27400 ± 800)/RT] l mol–1 s–1.
The resulting values were consistent with those
typical of phenol type inhibitors, which confirms the
proposed mechanism of antioxidant action of com-
pound I.
The dependence shown in Fig. 5 supports the
assumption that reaction (4) is responsible for ad-
ditional chemiluminescence in the examined system.
At an inhibitor concentration exceeding 7.5× 10–5
M
Table 1. Parametersa of antioxidant effect of 2-methyl-1,3-
benzoxazol-6-ol (I), Ionol, and phenol in the radical-initiated
oxidation of ethylbenzene; Wi = 5.4× 10–7 mol l–1 s–1,
temperature 343 K
the ΔI value approaches a constant value (Fig. 5, curve
1); this means that at an antioxidant concentration
higher than a certain value decay of all peroxy radicals
follows reaction (3), so that chemiluminescence may
result only from reaction (4). At a lower antioxidant
concentration both recombination of peroxy radicals
[reaction (1)] and reaction (4) contribute to the overall
chemiluminescence. In this case, proceeding from the
kinetic scheme of inhibited oxidation and stationary
state, we arrived at:
Stoichiometric
inhibition
coefficient
Compound
k7 × 10–4, l mol–1 s–1
2-Methyl-1,3-
benzoxazol-6-ol
2.0 (2.1)
3.40±0.03 (6.50±0.07)
Ionol
2.0 (2.0)
0.3 (0.3)
5.0±0.4 (5.00±0.25)
Phenol
0.60±0.02 (0.60±0.01)
a
(d[RO2·])/dt = Wi – k6[RO2·]2 – k7[RO2·][PhOH]
According to volumetric data. The data obtained by the chemi-
luminescence method are given in parentheses.
·
– k8[RO2 ][PhO˙] = 0;
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ANTIOXIDANT ACTIVITY OF 2-METHYL-1,3-BENZOXAZOL-6-OL
(b)
(a)
I/I0
I/I0
t, s
t, s
Fig. 4. Variation of the relative chemiluminescence intensity in the AIBN-initiated oxidation of (a) isopropylbenzene and (b) methyl
ethyl ketone in the presence of 3×10–5 mol l–1 of 2-methyl-1,3-benzoxazol-6-ol (I); Wi = 5.4×10–7 mol l–1 s–1, 333 K, [DBA] = 3×10–4
·
·
(d[PhO·])/dt = k7[RO2 ][PhOH] – k8[RO2 ][PhO˙] = 0.
and is thus converted into the excited triplet state [4],
and the excitation energy is transferred to the activator.
Taking into account that I = η6k6[RO2·]2
+
η8k8[RO2·][PhO˙], the relative chemiluminescence
intensity in the oxidation of hydrocarbons is given by
Eq. (5):
Polar molecule
RO2· + PhO· → Ps*
Pt* → P + A* → A + hν.
In the oxidation of ethylbenzene and isopropyl-
benzene, iminoquinone II molecule in the excited
singlet state is deactivated very rapidly; therefore, no
chemiluminescence is observed in the induction period.
η8 – 2η6
k6
2(η8 – 2η6)k72 [InH]2
ΔI2
.
ΔI =
Wi –
(5)
2
[InH]×105, M
Here, ΔI = I – I0; I and I0 are, respectively, the
chemiluminescence intensities in the presence and in
the absence of inhibitor; η6 and η8 are the chemi-
luminescence quantum yields of reactions (1) and (4),
respectively; k6 and k7 are the rate constants of
reactions (1) and (3), respectively; and Wi is the rate of
formation of free radicals. Insofar as the experimental
data fit a linear relation in the coordinates ΔI =
f(ΔI2/[InH]2) (Fig. 5, plot 2), the proposed mechanism
of chemiluminescence in the oxidation of methyl ethyl
ketone in the presence of 2-methyl-1,3-benzoxazol-6-
ol seems to be valid. Thus a new emitter is formed as a
result of reaction (4). Most probably, such an emitter is
iminoquinone II with the following structure.
ΔI
N
CH3
O
O
ΔI2/[InH]2×10–11 (M)–2
II
This compound is formed in the singlet excited
state. It is involved in hydrogen bonding with polar
methyl ethyl ketone molecules present in the system
Fig. 5. Plots of ΔІ vs. (1) concentration of 2-methyl-1,3-
benzoxazol-6-ol (I) and (2) ΔІ2/[InH]2 for the oxidation of
methyl ethyl ketone; Wi = 5.4×10–7 mol l–1 s–1, 333 K.
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KHIZHAN et al.
determined one of the most important electronic
ln k
structure parameters of molecule I and phenol
molecule, the energy of the O–H bond (DO–H). The OH
bond in 2-methyl-1,3-benzoxazol-6-ol turned out to be
much weaker than in phenol (DO–H 321.67 and
363.83 kJ mol–1, respectively); just this factor is most
likely to be responsible for the higher reactivity of
compound I compared to phenol. The O–H bond in
molecule I is weakened due to donor effect of the five-
membered heterocycle fused to the benzene ring.
The calculated O–H bond energies were verified by
plotting a correlation between ln k7 and DO–H values
known for sterically unhindered phenols [5]. The
correlation included the kinetic data for phenols
studied experimentally by other authors [6]. As follows
from Fig. 6, the point for 2-methyl-1,3-benzoxazol-6-
ol fits that correlation, indicating applicability of the
latter for a wide series of phenolic compounds,
including heterocyclic ones.
DO–H, kJ mol–1
Fig. 6. Correlation between lnk7 and O–H bond energy
(DO–H) in molecules of sterically unhindered phenols; the
point corresponding to 2-methyl-1,3-benzoxazol-6-ol (I) is
marked with an asterisk.
Table 2 contains the rate constants for the reactions
of 2-methyl-1,3-benzoxazol-6-ol with different peroxy
radicals, which were determined using classical
equation (2) and Eq. (5). It is seen that k7 decreases by
more than an order of magnitude in going from
ethylbenzene to isopropylbenzene. This may be
attributed to the higher reactivity of sec-alkylperoxy
radicals as compared to tert-alkylperoxy radicals.
To conclude, 2-methyl-1,3-benzoxazol-6-ol (I) is an
effective inhibitor of oxidation of organic compounds.
Its antioxidant effect involves termination of radical
chains via reaction with peroxy radicals derived from
substrate, and it follows general relations intrinsic to
inhibitory effect sterically unhindered phenols. Spe-
cificity of chemiluminescence in the oxidation of or-
ganic compounds with different polarities in the pres-
ence of 2-methyl-1,3-benzoxazol-6-ol (I) was determined.
Comparison of the kinetic parameters for the
oxidation of ethylbenzene and methyl ethyl ketone
shows that antioxidant I in nonpolar medium is
slightly more efficient than in polar medium (Table 2).
This may be related to the formation of hydrogen
bonds between antioxidant and methyl ethyl ketone
molecules.
EXPERIMENTAL
Compounds necessary for our study were
synthesized and identified at the Chemistry of
Biologically Active Substances Department, Litvinenko
Institute of Physical Organic and Coal Chemistry,
National Academy of Sciences of Ukraine.
We also tried to rationalize high reactivity of the
examined antioxidant toward peroxy radicals RO2· in
terms of the restricted and unrestricted Hartree–Fock
approximations. Using AM1 semiempirical method we
The reaction kinetics were studied by volumetric
(following oxygen absorption, chemiluminescence
(following luminescence intensity; FEU-38 multiplier),
photocolorimetric (KFK-3 photometer), and iodo-
metric methods (autooxidation). Azobis(isobutyro-
nitrile) (AIBN) was used as radical initiator. The rate
of initiation Wi was calculated with account taken of
the thermal decomposition constant of AIBN [1].
Dibromoanthracene was used s activator in chemi-
luminescence studies. The reagents used were purified
according to known procedures [5, 7].
Table 2. Rate constants for reactions of 2-methyl-1,3-
benzoxazol-6-ol with peroxy radicals derived from different
substrates, Wi = 5.4×10–7 mol l–1 s–1, [DBA] = 3×10–4
M
Substrate
Temperature, K
343
k7, l mol–1 s–1
(6.50 ± 0.07) × 104
Ethylbenzene
Ethylbenzene
333
343
333
(4.8 ± 0.2) × 104
(4.4 ± 0.2) × 103
(1.70 ± 0.09) × 104
Isopropylbenzene
Methyl ethyl ketone
The antioxidant activity of inhibitors (InH) was
quantitatively characterized by induction period τ,
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ANTIOXIDANT ACTIVITY OF 2-METHYL-1,3-BENZOXAZOL-6-OL
issledovaniya medlennykh khimicheskikh protsessov
(Chemiluminescence Methods for Studying Slow
Chemical Processes), Moscow: Nauka, 1966.
stoichiometric inhibition coefficient, and rate constant
k7 for its reaction with peroxy radicals RO2· derived
from the substrate.
4. Vardanyan, R.L., Kharitonov, V.V., and Denisov, E.T.,
Kinet. Katal., 1971, vol. 12, no. 4, p. 903.
5. Belaya, N.I., Ovcharova, O.Yu., and Nikolaevskii, A.N.,
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