Estimation of heterogeneous rate constants of reaction of electrochemically generated o-benzoquinones with various nucleophiles containing thiol group

Article abstract of DOI:10.1002/kin.20402

The reaction of o-benzoquinone derived by the oxidation of catechols (1a-c) with some nucleophiles containing thiol group (2a-f) has been studied in various conditions, such as pH, nucleophile concentration, and scan rate, using cyclic voltammetry. In var

Full text of DOI:10.1002/kin.20402

Estimation of
Heterogeneous Rate
Constants of Reaction
of Electrochemically
Generated
o-Benzoquinones with
Various Nucleophiles
Containing Thiol Group
LIDA FOTOUHI,1 ESMAIL TAMMARI,2 SAMANEH ASADI,1 MAJID M. HERAVI,1
DAVOOD NEMATOLLAHI3
1Department of Chemistry, School of Science, Alzahra University, Tehran, Iran
2Payame Noor University (PNU), Iran
3Faculty of Chemistry, Bu-Ali-Sina University, Hamadan, Iran
Received 10 June 2008; revised 28 September 2008; accepted 2 November 2008
DOI 10.1002/kin.20402
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: The reaction of o-benzoquinone derived by the oxidation of catechols (1a–c) with
some nucleophiles containing thiol group (2a–f) has been studied in various conditions,
such as pH, nucleophile concentration, and scan rate, using cyclic voltammetry. In various
conditions, based on an EC electrochemical mechanism (“E” represents an electron transfer
at the electrode surface and “C” represents a homogeneous chemical reaction), the observed
homogeneous rate constants (kobs ) were estimated by comparison of the experimental cyclic
voltammetric responses with the digital simulated results for each of the nucleophile. The
results show that the magnitude of kobs is dependent on the nature of the substituted group on
the catechol ring and nucleophilicity of nucleophile. ꢀ 2009 Wiley Periodicals, Inc. Int J Chem
C
Kinet 41: 426–431, 2009
INTRODUCTION
Correspondence to: Lida Fotouhi; e-mail: lida fotouhi@yahoo.
com, lfotouhi@alzahra.ac.ir.
Contract grant sponsor: Research Council of Al-Zahra
University.
Catechol derivatives are a promising group of com-
pounds worthwhile for further investigation, which
may lead to the discovery of selective acting,
biodegradable agrochemicals having high human,
c
ꢀ
2009 Wiley Periodicals, Inc.

ESTIMATION OF HETEROGENEOUS RATE CONSTANTS OF REACTION OF o-BENZOQUINONES
427
R1
OH
R2
OH
R1=H
R2=H
1a, catechol
1b, 3-methylcatechol
1c, 3,4-dihydroxybenzoic acid
R1=CH3
R1=H
R2=H
R2=COOH
R
R
N
N
SH
S
H
O
H3C
SH
N
N
N
N
CH3
H3C
R
N
SH
2c
N
CH3
R=H
2a
R=H
2e
2f
R=NH 2 2b
R=CH3 2d
Scheme 1
animal, and plant compatibility [1]. On the other hand,
quinones are of considerable interest because many
drugs such as doxorubicin, daunorubicin, and mito-
mycin C in cancer chemotherapy contain quinones [2],
whereas various quinones have been found useful in
industry [3]. Some of them also exhibit antitumor and
antimalarial activities [4], and many of them are also
involved in enzyme inhibition and DNA cross-linking
[5].
chol derivatives (1a–c) in the presence of some side-
chain thiol group nucleophiles (2a–f) in detail. In this
work, the kobs values of the reaction of o-benzoquinone
derived from 1a–c with 2a–f (Scheme 1) have been
estimated by digital simulation of CV at various exper-
imental conditions, such as pH, scan rate, and nucle-
ophile concentration.
Application of biological thiols as nucleophilic
species in 1,4-Michael additions to electrogenerated
o-quinones as protocols for the detection of these com-
pounds is also reported [6,7]. Substitutions including
thiol [8] and alkylthiol [9] derivatives have been carried
out primarily at the 3-position of the 1,2,4-triazole ring.
A large number of 1,2,4-triazole derivatives have been
reported to possess central nervous system–depressant
antibacterial [10], antifungal [11], antitumor [12], and
insecticidal properties [13].
Some electrochemical techniques such as cyclic
voltammetry (CV), using diagnostic criteria derived
by Nicholson and Shain for various electrode mecha-
nisms, have been used as a powerful independent route
for quantitative characterization of complex electrode
processes [14–16]. In addition, general treatment of
the reaction mechanism is probably best carried out
through digital simulation [17].
EXPERIMENTAL
Apparatus
Cyclic voltammetry was performed using an Autolab
PGSTATE12 (Eco Chemie, Utrecht, Netherlands). The
working electrode (WE) used in the voltammetry ex-
periment was a glassy carbon disc (1.8-mm diameter)
and platinum wire was used as the counter electrode
(CE). The WE potentials were measured versus the
3 M KCl Ag/AgCl reference electrode (all electrodes
were obtained from Metrohm, Herisau, Switzerland).
The homogeneous rate constants were estimated
by analyzing the cyclic voltammetric responses using
the simulation CVSIM software [26]. All experiments
were carried out at room temperature.
Chemicals
With due attention to our experiences [18–20], we
thought that the kinetic study of reaction of electrogen-
erated o-benzoquinone with thionucleophiles would
be of interest from the point of view of pharmaceu-
tical properties. In our previous works [21–25], we
have investigated the electrooxidation of some cate-
Catechols were reagent-grade materials from Aldrich.
All chemical reagents were of pro-analysis grade from
Merck (Darmstadt, Germany) and Fluka (Milwaukee,
WI, USA). These materials were used without further
purification.
International Journal of Chemical Kinetics DOI 10.1002/kin

428
FOTOUHI ET AL.
ECEC mechanism via consumption of 4-electrons per
catechol molecule without any cyclization. Finally in
nucleophiles 2e and 2f when o-quinone is formed, it
will be attacked by nucleophile to furnish catecholth-
ioether via 2- or 4-electrons per catechol molecules
(Scheme 2). However, all nucleophiles show similar
1,4-Michael addition EC mechanism at the first step
in which the electrogenerated o-quinone as a Michael
acceptor is attacked by the SH group. Herein, we wish
to investigate a quantitative detailed study of the elec-
trochemical oxidation of catechols in the presence of
various thionucleophiles for finding any relationship
between them. CV using diagnostic criteria derived
by Nicholson and Shain [14–16] for various electrode
mechanisms were used. To study the effect of the pres-
ence of an electron-donating and electron-withdrawing
group in a reactive catechol ring site, electrochemical
oxidation (1a–c) has been studied in the presence of
some thionucleophiles (2a–f).
RESULTS AND DISCUSSION
Voltammetric Studies
Cyclic voltammogram of catechol (1a) in aqueous so-
lution containing 0.2 M phosphate buffer (pH = 7.0)
shows one anodic and the corresponding cathodic peak,
which belongs to the transformation of catechol to o-
benzoquinone and vice versa within a quasi-reversible
two-electron process. In the presence of a nucleophile,
the height of cathodic counterpart decreased, while the
potential of anodic peak slightly shifted toward the less
positive potential. Recording cyclic voltammogram of
catechol in the presence of nucleophile at different scan
rates shows a decreasing both peak current ratio (Ia/Ic)
and current function (Ia/υ1/2) with an increasing scan
rate, which is a clear indication of coupled chemical
reaction via EC or ECEC mechanism. In our previous
works [21–25], we have studied the electrooxidation
of catechols in aqueous solutions in the presence of
some nucleophiles containing thiol group and have
shown that catechols undergo Michael addition with
consumption 2- or 4-electrons per molecule of catechol
(Scheme 2). As it is shown in Scheme 2, in the case of
nucleophiles 2a and 2b generation of o-benzoquinone
is followed by a 1,4-Michael addition of nucleophile to
the quinone producing the adduct, which undergoes the
abstraction of a second pair of electrons and cycliza-
tion via attack by the NH2 group (ECEC mechanism).
On the other hand, nucleophiles 2c and 2d show an
Kinetic Considerations
The simulation was carried out assuming semi-infinite
one-dimensional diffusion and planar electrode geom-
etry. The experimental parameters entered for digital
simulation consisted of the following: Estart = −0.3 V
(or −0.2 V), Eswitch = 0.6 V (or 0.75 V), t = 25◦C,
and analytical concentration of catechol 1.0 mM. The
transfer coefficients (α) were assumed to be 0.5 and
O
H
OH
OH
S
N
H3C
N
OH
OH
N
N
O
N
N
N
S
2b 4e, 4H+
e, 4H+
2a
CH3
N
N
R1
N
N
OH
S
S
OH
OH
N
S
OH
OH
e, 2H+
2f
e, 4H+
2e
R2
OH
CH3
1a-c
e, H+
N
CH3
2c
2d
4e, H+
N
H3C
H3C
N
N
S
OH
OH
N
S
OH
OH
S
N
S
N
N
CH3
Scheme 2
International Journal of Chemical Kinetics DOI 10.1002/kin

ESTIMATION OF HETEROGENEOUS RATE CONSTANTS OF REACTION OF o-BENZOQUINONES
429
30
15
0
25
15
5
10
5
pH = 4
pH =
8
pH =7
a
a
b
b
0
b
a
5
5
15
15
10
0.5
0.1
0.3
0.7
0.6
0.2
0.2
0.6
0.4
0
0.4
0.8
E/V vs. Ag/AgCl
E/V vs. Ag/AgCl
E/V vs. Ag/AgCl
Figure 1 Typical cyclic voltammograms of 1 mM 3-methylcatechol (1b) and 1 mM 2b at various pHs. (a) Experimental
(dashed line); (b) simulated (solid line). Scan rates: 200 mV s−1. WE: glassy carbon electrode.
the formal potentials were obtained experimentally as
the midpoint potential between the anodic and cathodic
peaks (Emid). The heterogeneous rate constants (0.01
cm s−1) for oxidation of catechols were estimated by
use of an experimental working cure [27]. All param-
eters were kept constant throughout the fitting of the
digitally simulated voltammogram to the experimen-
tal data. The parameter kobs was allowed to change
through the fitting processes. The observed homoge-
neous rate constants (kobs/s−1) of the reaction of o-
benzoquinone with 2a–f were estimated by compari-
son of the simulation results with experimental cyclic
voltammograms at various pH, nucleophile concentra-
tion, and scan rates.
The anodic peak potential of catechol shifted to the
negative potential by increasing pH. The formal poten-
tial for this reaction scheme is given by the following
equation:
ꢁ
E0 =E0(pH0) − (2.303 RT/nF) pH
where E0 (pH0) is the formal potential of pH0, R the
gas constant, T the absolute temperature, and F the
Faraday constant [17]. The plot of formal potential
(E0ꢁ) of catechol as a function of pH shows the slope
of 0.061 mV pH−1, which is in good agreement with
the theoretical slope (2.303 RT/nF) of 59 mV pH−1
with m = 2.
The Effect of Nucleophile Concentration
and Scan Rate
The Effect of pH
The schemes for the electrochemical oxidation of cate-
chols (1a–c) in the presence of 2a–f were proposed and
tested by digital simulation for calculation of kobs val-
ues. Typical experimental and simulated cyclic voltam-
mograms of 3-methylcatechol (1c) in the presence of
2b at various pHs are shown in Fig. 1. From the fitting
of the digitally simulated voltammogram to the exper-
imental data, the kobs values were calculated. A typical
Fig. 2 shows the calculated kobs as a function of pH
and constant scan rate and nucleophile concentration.
As is shown in Fig. 2 by increasing pH, the kobs values
increased. Because at high pHs, the nucleophiles are
in the deprotonated form, their nucleophilicity charac-
ter is increased in the Michael addition of o-quinone
derivatives. The other reason of increasing kobs with pH
is due to easier oxidation of catechol at basic pHs due
to the participation of proton in the oxidation reaction
of catechol to o-quinone.
The simulation was also performed on the basis of EC
mechanism at both various nucleophiles concentration
and scan rates. It was found that the magnitude of kobs is
0
c
b
a
2
4
6
8
10
pH
Figure 2 Plot of log kobs for Michael addition of catechols
(1a–c) as a function of pH for 2b in the presence of (a) 1c,
(b) 1a, (c) 1b.
R ↔ O + mH+ + 2e
International Journal of Chemical Kinetics DOI 10.1002/kin

430
FOTOUHI ET AL.
Table I The Averaged Values of Observed Homogeneous Rate Constants (kobs(s−1)) for the Studied Catechols (1a–c)
in the Presence of Different Concentrations of 2a–f (0.10, 0.50, and 1.0 mM) and Various Scan Rates (25, 50, 100, 250,
and 500 mV s−1
)
Nucleophile
3-Methylcatechol
Catechol
3,4-Dihydroxybenzoic Acid
2a
2b
2c
2d
2e
2f
0.14 ( 0.02)
0.21 ( 0.03)
0.40 ( 0.02)
0.53 ( 0.02)
0.67 ( 0.02)
0.93 ( 0.02)
0.25 ( 0.02)
0.30 ( 0.01)
0.57 ( 0.01)
0.68 ( 0.03)
0.80 ( 0.01)
1.05 ( 0.05)
0.48 ( 0.02)
0.58 ( 0.01)
0.78 ( 0.06)
0.89 ( 0.05)
0.98 ( 0.02)
1.42 ( 0.04)
independent on both concentration of nucleophile and
scan rate. Because kobs is a thermodynamic parameter,
it is obvious that it should be concentration indepen-
dent. The averaged values of kobs at various scan rates
(25, 50, 100, 250, and 500 mV s−1) and different nu-
cleophile concentrations (0.10, 0.50, and 1.0 mM) are
shown in Table I. On the other hand, kobs values are
dependent on the nature of the substituted group on
the catechol ring. The presence of electron-donating
group of methyl group on catechol ring causes a de-
crease in kobs. In contrast, the presence of carboxylic
group with electron-withdrawing character causes an
increase in kobs. The observed rate constants can be
related with the Hammett ρ–σ parameters, where the
Hammett equation is
stituents. This result is consistent with the attack of
thiolate to the o-benzoquinone. The similar behavior
was observed for other nucleophiles.
The order of observed homogeneous rate constants
may also be explained according to the donating ability
of substituted nucleophile. Nucleophile 2e shows the
higher value of kobs, and then presence of electron-
donating groups such as NH2 or methyl on nucleophile
causes an increase in kobs.The order of kobs for various
nucleophiles is 2f > 2e > 2d > 2c > 2b > 2a.
CONCLUSIONS
The results of this work show the kinetics of the reac-
tions of electrochemically generated o-benzoquinone,
with some thionucleophils by the cyclic voltammet-
ric technique and the simulation of obtained voltam-
mograms performed under EC mechanism. There is
a good agreement between the simulated voltammo-
grams with those obtained experimentally. The effects
of scan rate, nucleophile concentration, and pH on the
oxidation pathway and the observed homogeneous rate
constants have been discussed. In addition, the effects
of the substituted groups on the catechol ring in kobs
log ki = log k0 + ρσ
where ki is the rate constant for substituted catechol,
k0 the rate constant for catechol, σ a constant char-
acteristic of a given subsistent group [28], and ρ the
slope of the log k0 – σ graph. The Hammett plot is
shown in Fig. 3. The positive ρ values (e.g., 1.03, r =
0.97 for 2b) mean that the transition state has a sub-
stantial negative charge because the reaction rate is
increased significantly for electron-withdrawing sub-
(Hammett plot) have been studied.
.
0.4
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