1. Study of the Oxidation of
Some Catechols in the
Presence of 4-Amino-3-thio-
1,2,4-triazole by Digital
Simulation of Cyclic
Voltammograms
LIDA FOTOUHI,1 SOLMAZ TAGHAVI KIANI,1 DAVOOD NEMATOLLAHI,2 MAJID M. HERAVI1
1
Department of Chemistry, Faculty of Science, Alzahra University, Vanak, P.O. Box 1993891176, Tehran, Iran
2
Department of Chemistry, Faculty of Science, Bu-Ali-Sina University, Hamadan, Iran
Received 27 September 2006; revised 11 December 2006; accepted 30 December 2006
DOI 10.1002/kin.20246
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: Electrochemical oxidation of catechol and its derivatives (1a–d) has been studied
in the presence of 4-amino-3-thio-1,2,4-triazole (3) at various pHs. Some electrochemical tech-
niques such as cyclic voltammetry using the diagnostic criteria derived by Nicholson and Shain
for various electrode mechanisms and controlled-potential coulometry were used. Results in-
dicate the participation of catechols (1a–d) with 3 in an intramolecular cyclization reaction
to form the corresponding 1,2,4-triazino[5,4-b]-1,3,4-thiadiazine derivatives. In various scan
rates, based on an electron transfer–chemical reaction–electron transfer–chemical reaction
mechanism, the observed homogeneous rate constants (kobs) for Michael addition reaction
were estimated by comparing the experimental cyclic voltammetric responses with the digital
simulated results. The oxidation reaction mechanism of catechols (1a–d) in the presence of
4-amino-3-thio-1,2,4-triazole (3) was also studied. C 2007 Wiley Periodicals, Inc. Int J Chem
Kinet 39: 340–345, 2007
INTRODUCTION
Various 1,2,4-triazole derivatives have been reported to
possess diverse types of biological properties such as
antibacterial [1], antifungal [2], anti-inflammatory [3],
antihypertensive [4], antiviral [5], antieishmanial [6],
Correspondence to: Lida Fotouhi; e-mail: lfotouhi@alzahra.
ac.ir.
c 2007 Wiley Periodicals, Inc.
and antimigraine activities [7]. Substitutions including
thio [8] and alkylthio [9] derivatives have been car-
ried out primarily at the 3-position of the 1,2,4-triazole
ring. As potential antimicrobial agents, 1,2,4-triazole
derivatives will overcome the problems encountered
by today’s infectious disease clinicians [10,11]. An
interesting heterocyclic compound of this group is 4-
amino-3-thio-1,2,4-triazole (3), by virtue of its vicinal
nucleophile mercapto and amine group constitutes. It
is well known that the N-bridged heterocycles derived

2. CATECHOL OXIDATION IN THE PRESENCE OF 4-AMINO-3-THIO-1,2,4-TRIAZOLE 341
from 1,2,4-triazoles find application in the fields of
medicine, agriculture, and industry. A large number of
triazolothiadiazoles and triazolothiadiazines have been
reported to possess central nervous system depressant,
antibacterial, antifungal, antitumor, anti-inflammatory,
pesticidal, and insecticidal properties [12,13].
On the other hand, the presence of an ortho- or para-
quinone ring as a reaction center of electron transfer in
the structure of many natural compounds [14] and bi-
ological material [15] indicates the importance of the
electrochemical properties of these compounds. Al-
though the chemical or electrochemical oxidation path-
way of catechols has been known [16–19] to the best of
our knowledge, there are few reports of the kinetics of
their cyclization reactions [20,21]. The electrochem-
ical oxidation of some catecholamines based on an
electron transfer–chemical reaction–electron transfer
(ECE) mechanism at various pHs has been investi-
gated and the observed homogeneous rate constants
(kobs) were reported [22,23].
In this work, the electrochemical oxidation of some
catechols in the presence of 4-amino-3-thio-1,2,4-
triazole (3) at various pHs have been investigated.
The main goal of the investigation was to carry out
a qualitative detailed study of the electrochemical oxi-
dation of catechols in aqueous solutions. Electrochem-
ical techniques such as cyclic voltammetry, using the
diagnostic criteria derived by Nicholson and Shain for
various electrode mechanisms [24,25], and controlled-
potential coulometry were used. In addition, the kobs
values of intramolecular reaction of o-benzoquinone
derived by the oxidation of catechols with a side-chain
amino group have been estimated by digital simulation
of cyclic voltammograms.
EXPERIMENTAL
Apparatus
Cyclic voltammetry was performed using a Metrohm
model 746VA trace analyzer connected to a 747 VA
stand. A glassy carbon electrode (0.2-mm diameter)
was used as the working electrode, which was polished
sequentially with alumina powder. A platinum wire and
a commercial KCl Ag/AgCl electrode from Metrohm
were used as the auxiliary and reference electrodes,
respectively.
Controlled-potential coulometry was performed
using an Autolab model PGSTAT 20 potentio-
stat/galvanostat. The working electrode used in
controlled-potential coulometry was an assembly of
four carbon rods (6-mm diameter and 4-cm length),
and a large platinum gauze constituted the counter elec-
trode. The homogeneous rate constants were estimated
by analyzing the responses using a cyclic voltammet-
ric simulation software [26]. The solutions were purged
with 99.999% argon for 10 min before the start of the
experiments.
Reagents
4-Amino-3-thio-1,2,4-triazole (3) was prepared by the
procedure reported previously [27]. All other chem-
icals were of proanalysis grade from Merck. These
chemicals were used without further purification.
RESULTS AND DISCUSSION
Voltammetric Studies
Cyclic voltammogram of 1 mM catechol 1a in aque-
ous solution containing 0.2 M phosphate buffer (pH
7.0) at a glassy carbon electrode is shown in Fig. 1
(curve a). The voltammogram shows one anodic (A1)
and a corresponding cathodic (C1) peak at 0.37 V and
0.08 V versus saturated KCl Ag/AgCl, respectively,
which corresponds to the transformation of catechol
1a to o-quinone 2a and vice versa within a quasi-
reversible two-electron process (Scheme 1, Eq. (1)).
A peak current ratio (IC1
p /IA1
p ) of near unity can be
considered as a criterion for the stability of o-quinone
2a produced at the surface of the electrode under the
experimental conditions. In other words, hydroxyla-
tion [28], or dimerization [29], reactions are too slow
to be observed on the time scale of cyclic voltamme-
try. The oxidation of catechol 1a in the presence of
4-amino-3-thio-1,2,4-triazole (3) as a nucleophile was
studied in some detail. Figure 1, curve b, shows the
cyclic voltammogram obtained for a 1 mM solution of
1a in the presence of 1 mM solution of 3. The voltam-
mogram exhibits one anodic peak at 0.45 V versus
Ag/AgCl, and the cathodic counterpart of the anodic
peak A1 at 0.01 V versus saturated KCl Ag/AgCl (C1),
which is seen to be decreasing in comparison to the
cathodic peak of catechol 1a in the absence of nucle-
ophile. In this figure, curve c is the voltammogram of 3
in the same condition and in the absence of catechol 1a.
The multicyclic voltammetry of 1a in the presence of 3
shows that parallel to the shift of A1 in a positive direc-
tion, a new anodic peak (A0) appears at the less positive
potential of 0.11 V, in the second cycle (Fig. 1, curve
d). This new peak is related to the electro-oxidation
of intermediate 4a [19h]. The positive shift of the A1
peak in the presence of 3 is due to the formation of a
thin film of product at the surface of the electrode [30].
International Journal of Chemical Kinetics DOI 10.1002/kin

3. 342 FOTOUHI ET AL.
Figure 1 Cyclic voltammograms of 1 mM catechol (1a): (a) in the absence and (b) in the presence of 1 mM 4-amino-3-thio-
1,2,4-triazole (3), (c) 1 mM 4-amino-3-thio-1,2,4-triazole (3) in the absence of catechols (1a), and (d) multicyclic voltammograms
of 1a in the presence of 3, at glassy carbon electrode in aqueous solution. 0.2 M Phosphate buffer (pH 7.2); scan rate: 50 mV
s−1.
Furthermore, it is seen that proportional to the aug-
mentation of potential sweep rate, the height of the C1
peak of 1a increases (Fig. 2). A similar situation is
observed when the 3-to-1a concentration ratio is de-
creased. A plot of (IC1
p /IA1
p ) versus scan rate, υ, for
Scheme 1
a mixture of 1a and 3 confirms the reactivity of 1a
toward 3, appearing as an increase in the height of the
cathodic peak C1 at higher scan rates (Fig. 2, inset).
On the other hand, current function for the A1 peak
(IA1
P /υ1/2
) decreases on increasing the scan rate, and
International Journal of Chemical Kinetics DOI 10.1002/kin

4. CATECHOL OXIDATION IN THE PRESENCE OF 4-AMINO-3-THIO-1,2,4-TRIAZOLE 343
Figure 2 Cyclic voltammograms of 1 mM catechol (1a)
in the presence of 1 mM 4-amino-3-thio-1,2,4-triazole (3) at
glassy carbon electrode, in 0.2 M phosphate buffer (pH 7.2).
Scan rate: 20, 40, 60, 80, 100, 150, 200, 300, 400, 500, 600,
800, and 1000, 2000, 3000 mV s−1. Inset: variation of peak
current ratio versus scan rate.
such a behavior is indicative of an electron transfer–
chemical reaction–electron transfer–chemical reaction
(ECEC) mechanism [31].
The influence of pH on the electrochemical behav-
ior of catechols both in the absence and presence of 3
was studied through the examination of the electrode
response in solution buffered between pHs 3 and 8. In
the acidic and neutral media, cyclic voltammograms of
catechol 1a show one anodic (A1) and a corresponding
cathodic peak (C1), with IC1
p /IA1
p near unity. However,
in basic solution, IC1
p /IA1
p is less than unity and
decreases with increasing pH (Fig. 3A, curve I) and
decreasing sweep rate. This is related to the coupling
of anionic or dianionic forms of catechols with
o-benzoquinones (dimerization reaction) [32]. The
Figure 3 (A) Curve I, variation of peak current ratio (IC1
p /IA1
p ) of catechol in the absence of 3; curve II, variation of IC1
p /IA1
p
in the presence of 3; and curve III, difference between the peak current ratios in the presence and absence of 3. (B) Variation of
formal potential of catechol 1a as a function of pH.
rate of the coupling reaction is pH dependent and is en-
hanced by an increasing pH. The oxidation of catechol
(1a) in the presence of 3 was studied at various pHs.
The results show that IC1
p /IA1
p increases with decreas-
ing pH (Fig. 3A, curve II). This can be related to the
protonation of thio and amino groups and their subse-
quent inactivation toward Michael addition reaction.
As shown in Fig. 3A, curve III, because of the decrease
in the rate of polymerization at pH 7.0 (in the absence
of 3, IC1
p /IA1
p = 0.88; Fig 3A, curve I) and the increase
in the rate of the coupling reaction between 3 and o-
benzoquinone 2a (in the presence of 3, IC1
p /IA1
p = 0.62;
Fig. 3A, curve II), an aqueous solution of 0.2 M phos-
phate buffer (pH 7.0) was the solvent system most
suitable for the electrochemical study of the catechols.
Figure 3B shows the plot of formal potential (E0
)
of catechols (1a) as a function of pH. As shown, the
peak potentials for peak A1 shifted to the negative
potentials by increasing pH. This is expected because
of the participation of proton in the oxidation reaction
of 1a to 2a.
R O + mH+
+ 2e−
(a)
Where R stands for 1a, O stands for 2a, and m is the
number of protons involved in the reaction. The formal
potential (E0
)—which is approximated by the mid-
point potential (Emid) between the anodic and cathodic
peaks—for this reaction scheme is given by
E0
= E0
pH0
− (2.303RT /2F)pH (b)
where E0
pH0
is the formal potential at pH0, R is the
gas constant, T is the absolute temperature, and F the
Faraday constant. The values of E0
were shifted to
negative potentials with the slope of 58 mV pH−1
. In
International Journal of Chemical Kinetics DOI 10.1002/kin

5. 344 FOTOUHI ET AL.
Figure 4 Cyclic voltammograms of 1.0 mM catechol (1a) in the presence of 1.0 mM 4-amino-3-thio-1,2,4-triazole (3):
(a) experimental; (b) simulated at scan rates 100, 200, and 300 mV s−1. Experimental conditions: 0.2 M phosphate buffer (pH
7.0). Working electrode: glassy carbon electrode.
all cases, 1a–d, the slopes are in good agreement with
the theoretical slope (2.303mRT/2F) of 59 mV pH−1
with m = 2.
Controlled-potential coulometry was performed in
an aqueous solution containing 0.5 mmol of 1a and
0.5 mmol of 3 at 0.40 V versus saturated KCl Ag/AgCl.
All anodic and cathodic charges disappear when the
charge consumption becomes 4e per molecule of 1a.
These observations allow us to propose the pathway in
Scheme 1 for the electro-oxidation of catechols 1a–d
and their derivatives in the presence of 3.
The electrochemical oxidation of 3-methylcatechol
(1b), 3-methoxycatechol (1c), and 3,4-dihydroxy-
catechol (1d) in the presence of 3 as a nucleophile
in 0.2 M phosphate buffer solution (pH 7.2) proceeds
in a similar way to that of 1a.
According to our results, it seems that the 1,4-
(Michael) addition reaction of 3 to o-quinone 2a (Eq.
(2)) is faster than the secondary reaction, leading to
the intermediate 4a. The oxidation of compound 4a is
easier than the oxidation of the parent starting material
(1a) by virtue of the presence of an electron-donating
group and converts to o-quinone 5a (Eq. (3)). The in-
tramolecular cyclization of 5a produces compound 6a
as the final product.
In addition, we have examined to isolate the prod-
ucts of preparative electrolysis. Since the electrodes
were deactivated significantly during bulk electroly-
sis, we think the bulk electrosynthesis of the products
should be difficult. However, for confirmation of the
proposed mechanism, we have isolated one of the prod-
ucts obtained from 3-methylcatechol electrosynthesis
in small yields. In the FT-IR spectrum, the disappear-
ance of the S-H band of 3 in 2848 cm−1
with the
appearance of C-S band at 1078 and 1168 cm−1
is a
good indication of the participation of S-H in ring for-
mation (Eq. (2)). Participation of the NH2 group of 3 in
ring formation was also confirmed by displacement of
NH2 bands of 3 at 3123 and 3171 cm−1
by OH bands
at 3423 cm−1
. The methyl protons of 3-methylcatechol
was observed at 2 ppm in the 1
H NMR spectrum. In
addition, mass spectrometric analysis gives an m/z ra-
tio of 237, which can be assigned for the formation of
6a.
Kinetic Evaluations
The scheme for the oxidation of catechols in the pres-
ence of 3 was proposed and tested by digital simu-
lation. Based on an ECEC mechanism, the observed
homogeneous rate constants (kobs) of the reaction of
o-benzoquinones (2a–d) with 3 have been estimated by
comparison of the simulation results with experimen-
tal cyclic voltamograms in phosphate buffer (pH 7.0,
0.2 M) and at various scan rates (Fig. 4). The transfer
coefficients were assumed to be 0.5, the formal poten-
tials were obtained experimentally as the midpoint po-
tential between the anodic and cathodic peaks (Emid),
and the heterogeneous rate constants, 0.08 cm s−1
, for
oxidation of catechol were estimated by using an ex-
perimental working curve [33].
The observed homogeneous rate constants (kobs)
of the reaction of o-benzoquinone 2a with 3
were estimated by comparison of the simulation
results with experimental cyclic voltammograms
in various scan rates for each of the catechols.
The calculated homogeneous rate constants in the
case of catechol (1a), 3-methylcatechol (1b), 3-
methoxycatechol (1c), and 3,4-dihydroxybenzoic acid
(1d) in pH 7.0 are 0.060 (relative standard devi-
ation, RSDn=3
= 1.6%) M−1
s−1
, 0.050 (RSDn = 3
=
5.2%) M−1
s−1
, 0.029 (RSDn = 3
= 3.45%) M−1
s−1
,
and 0.082 (RSDn = 3
= 2.5%) M−1
s−1
, respectively,
and n is the number of individual homogeneous rate
constants at various scan rates. As is shown, the mag-
nitude of the observed homogeneous rate constant is
dependent on the nature of the substituted group on the
International Journal of Chemical Kinetics DOI 10.1002/kin

6. CATECHOL OXIDATION IN THE PRESENCE OF 4-AMINO-3-THIO-1,2,4-TRIAZOLE 345
catechol ring as the order of 3,4-dihydroxybenzoic acid
> catechol > 3-methoxycatechol > 3-methylcatechol.
The presence of electron-donating groups, such as
methyl (1b) or methoxy (1c), on the catechol ring
causes a decrease in the observed homogeneous rate
constant [19f].
CONCLUSIONS
The results of this work show that catechols (1a–
d) are oxidized in water to their corresponding o-
quinones (2a–d). The quinines are then attached by
the side-chain thio group to form cyclized o-quinone
derivatives. The overall reaction mechanism for an-
odic oxidation of catechols (1a–d) is presented in
Scheme 1. In addition, the kinetics for the reactions
of the electrogenerated two-electron oxidation product
of catechols with the side-chain thio group is studied
by cyclic voltammetric technique. The cyclic voltam-
mograms were digitally simulated under an ECEC
mechanism. There is good agreement between the sim-
ulated voltammograms and those obtained experimen-
tally. The effect of pH on the oxidation pathway of
catechols (1a–d) has been discussed.
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