Reactivity of substituted 4-oxothiazolidine derivatives in electron transfer reactions: A spectroelectrochemical study and mechanistic aspects

Article abstract of DOI:10.1016/j.electacta.2011.03.007

The electrochemical reduction of (5-ethoxycarbonylmethylidene-4- oxothiazolidin-2-ylidene)-N-phenylethanamide (designated as compound 2) as a mixture of the (2E,5Z) and (2Z,5Z) isomers in DMSO to (Z)-(5- ethoxycarbonylmethyl-4-oxothiazolidin-2-ylidene)-N-phenylethanamide (compound 1) was investigated by electrochemical (cyclic voltammetry with a stationary and rotating disc electrode) and spectroelectrochemical (electron paramagnetic resonance and UV-vis absorption) in situ techniques. A reduction mechanism, which consisted of an ECE-Disp sequence and was followed by the protonation of the strong electrogenerated base dianion, was proposed. The results indicate the presence of the same intermediate species, the dianion, when starting from either compound 2 by electrochemical reduction, or from compound 1 in presence of TBOH in DMSO. The suggested mechanism, which is based on the experimental results, corroborated with the gas phase and the solvent-dependent semiempirical PM3-MO calculations, was rationalized in terms of the electronic structure and the reactivity of the intermediate species involved.

Full text of DOI:10.1016/j.electacta.2011.03.007

Electrochimica Acta 56 (2011) 5257–5265
Contents lists available at ScienceDirect
Electrochimica Acta
journal homepage: www.elsevier.com/locate/electacta
Reactivity of substituted 4–oxothiazolidine derivatives in electron transfer
reactions: A spectroelectrochemical study and mechanistic aspects
a,∗
b
a
c,∗∗,1
Isidora Ceki c´ -Laskovi c´ , Rade Markovi c´ , Dragica M. Mini c´ , Elena Volanschi
a
Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12, Belgrade, Serbia
Faculty of Chemistry, University of Belgrade, Studentski trg 16, 11001 Belgrade, Serbia
Department of Physical Chemistry, University of Bucharest, Blvd Elisabeta 4-12, RO-030018, Bucharest, Romania
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
The electrochemical reduction of (5–ethoxycarbonylmethylidene–4–oxothiazolidin–2–ylidene)–
N–phenylethanamide (designated as compound 2) as a mixture of the (2E,5Z) and (2Z,5Z) isomers
in DMSO to (Z)–(5–ethoxycarbonylmethyl–4–oxothiazolidin–2–ylidene)–N–phenylethanamide (com-
pound 1) was investigated by electrochemical (cyclic voltammetry with a stationary and rotating disc
electrode) and spectroelectrochemical (electron paramagnetic resonance and UV–vis absorption) in situ
techniques. A reduction mechanism, which consisted of an ECE–Disp sequence and was followed by the
protonation of the strong electrogenerated base dianion, was proposed. The results indicate the presence
of the same intermediate species, the dianion, when starting from either compound 2 by electrochemical
reduction, or from compound 1 in presence of TBOH in DMSO. The suggested mechanism, which is based
on the experimental results, corroborated with the gas phase and the solvent–dependent semiempirical
PM3–MO calculations, was rationalized in terms of the electronic structure and the reactivity of the
intermediate species involved.
Received 1 December 2010
Received in revised form 1 March 2011
Accepted 2 March 2011
Available online 6 April 2011
Keywords:
Heterocyclic push–pull alkenes
Cyclic voltammetry
UV–vis spectroelectrochemistry
Electron paramagnetic resonance (EPR)
spectroelectrochemistry
Solvent–dependent PM3 modeling
©
2011 Elsevier Ltd. All rights reserved.
1
. Introduction
at the C(2) position, is the Z/E isomerization that may occur
under controlled conditions [2,3]. The equilibrated mixtures of the
structurally related 4–oxothiazolidines consist of the intramolec-
ular H–bonded (2E,5Z)–isomer and the intermolecular H–bonded
(2Z,5Z)–isomer in varying proportions depending on polarity of the
solvent [4,5].
Push–pull alkenesare substitutedolefins that contain one ortwo
electron–donating groups (D) on one end of a C C bond and one or
two electron–accepting groups (A) on the other end. The electronic
D–A interactions via the C C bond result in a polarization of the
“
push–pull” system (Scheme 1) [1].
Consequently, an increase of the push–pull character is asso-
There is considerable interest in oxothiazolidine derivatives,
such as compounds 1 and 2 (Fig. 1), due to their broad range of bio-
logical activity [6] and diverse physicochemical properties, which
include increasing the enaminic reactivity towards electrophiles
and which can be exploited in the preparation of the precursors
that lead to push–pull polyenes [7,8].
The redox properties of the heterocyclic compounds that con-
tain structural fragments with different donor–acceptor properties
are determined by the character of the constituting moieties and
the interactions between them. Therefore, a better knowledge of
the redox behavior of these compounds, as well as of the identi-
fication and reactivity of the intermediate species involved, is of
major importance.
ciated with a decrease of the ␲–bond character of the polarized
C bond. Therefore, the corresponding ␲–bond order of the C–D
C
and C–A bonds is increased. The push–pull effect has a decisive
influence on both the dynamic behavior and the chemical reactivity
of these compounds. The 5–substituted 4–oxothiazolidines (com-
pounds 1 and 2) with one or two exocyclic double bonds attached
to the thiazolidinone ring (Fig. 1) are typical examples of push–pull
compounds that can exist in different configurational and confor-
mational forms.
One of the characteristic processes of push–pull alkenes, which
is based on a lowering of the rotational barrier of the C C bond
Previous studies on the redox processes of these compounds
have detailed the oxidative bromine–mediated rearrangement of
1
that leads to 2. In addition, the regioselective reduction of 1 in
∗
∗
Corresponding author. Tel.: +381 11 333 66 25; fax: +381 11 218 71 33.
Corresponding author. Tel.: +40 21 410 34 31; fax: +40 21 315 92 49.
E-mail addresses: isidora@ffh.bg.ac.rs (I. Ceki c´ -Laskovi c´ ),
strong alkaline media (using a tenfold excess of NaBH4 in EtOH)
was investigated [9].
Heterogeneous electron transfer (HET) reactions that involve an
organic species in solution usually generate a radical ion, which
∗
elenavolanschi@gmail.com (E. Volanschi).
1
ISE member.
0
013-4686/$ – see front matter © 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.electacta.2011.03.007

5
258
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Fig. 1. Structures of the selected 5–substituted 4–oxothiazolidines 1 and 2.
formed in the presence of the added base, tetrabutyl ammonium
hydroxide (TBOH).
Taking into account the previously reported regioselective
reduction of
1 to (Z)–(5–(2–hydroxyethyl)–4–oxothiazolidin–
2
–ylidene)–N–(2–phenylethylethanamide) [9] in strong alkaline
media, we investigated the electrochemical behavior of this com-
pound in DMSO in the absence and presence of TBOH. Furthermore,
the possibility of the reverse pathway that leads from 1 to 2 was
also considered.
The identification and the investigation of the reactivity of the
intermediate species were performed, and a reduction mechanism
of 2 to 1 in polar aprotic solvents (DMSO) is proposed. Semiem-
pirical gas phase and solvent dependent PM3–MO calculations
reasonably account for the proposed reaction mechanism.
Scheme 1. Polarization of the push–pull system.
may react in subsequent reactions with the various components
of the solution (solvent, electrophiles, nucleophiles, or non–electro
active species). Electrochemical methods accompanied by digital
simulations can provide the thermodynamic and kinetic character-
ization of the electron transfer (ET) step. However, to understand
the complex reaction mechanisms that were determined by the
HET step at a molecular level and the reactivity of the intermediate
species involved, the use of electrochemical and spectral in situ
techniques, in conjunction with theoretical modeling based on
quantum mechanical calculations, is required [11–15].
2. Experimental
The aim of the present paper is to investigate
Cyclic voltammetry (CV) experiments were performed using
a VOLTALAB–40 electrochemical device with a thermostated
one–compartment electrolytic cell that included a stationary and
rotating Pt–EDI 101 disc working electrode with a diameter of
2 mm, a Pt counter electrode and a Ag/Ag+ quasi reference elec-
trode, calibrated in respect with the ferrocene/ferrocenium couple
the
behavior
of
the
electrochemical
reduction
of
–
two typical push–pull compounds in the series
(
–
5–ethoxycarbonylmethylidene–4–oxothiazolidin–2–ylidene)
N–phenylethanamide, which is termed compound 2 in this paper,
and (Z) – (5–ethoxycarbonylmethyl–4–oxothiazolidin–2–ylidene)
N–phenylethanamide, which is termed compound 1, as well as
ꢀ
◦
–
(E Fc/Fc+ = 0.460 V vs. SCE). All measurements were performed at
the reaction sequence that is responsible for the electrochemical
reduction of 2 in the aprotic solvent, dimethyl sulfoxide (DMSO),
while in the presence of protic impurities (impurities that are
always present in commercially available solvents that are used
without further purification) and which is reflected by the overall
room temperature in DMSO with 0.1 M tetra–n–butyl ammonium
hexafluorophosphate (TBAHFP) as the supporting electrolyte. Prior
to each experiment, the solutions in the electrochemical cell were
degassed with high purity Ar. The Ar atmosphere was maintained
over the solution in the cell during the measurements. Experi-
mental results correlated with the results that were obtained by
numerical simulations, which were accomplished by the software
DigiSim 3.03 Bioanalytical Systems Inc. using the default settings
with the assumption of planar diffusion and the Butler–Volmer
law for electron transfer. Optical spectra were recorded during
the chemical and electrochemical reduction on a Unicam Helios–␣
UV–visspectrophotometer andaRadelkis potentiostat. Thecell was
equipped with an optically transparent electrode (OTE), Pt counter
electrode and Ag/Ag+ reference electrode. The radical species for
the EPR studies were generated in situ by the electrochemical
reduction at the potential of the redox couple on the cyclo-
voltammogram [16,17], using the same solvent and supporting
electrolyte as in the electrochemical experiments. The spectra were
recorded on a JEOL FA 100 spectrometer in the X–band frequency
using peroxylamine disulfonate (aN = 1.3 mT, g = 2.0055) as an inter-
nal standard. The simulation of the EPR spectra was performed
using the computer software, WinSim [18]. Solvent–dependent
semiempirical MO calculations were determined using the PM3
hamiltonian AMPAC program package and the HyperChem release
−
+
reaction: 2 + 2e + 2H = 1.
Compound 2 (Fig. 2) was synthesized as a mixture of the
(
2E,5Z)–2a and (2Z,5Z)–2b isomers at a 63:37 ratio according to
previously published methods [7,15].
Cyclic and linear voltammetry with stationary and rotating
disc electrode (RDE) in DMSO were coupled with in situ UV–vis
absorption and electron paramagnetic resonance (EPR) spectral
techniques. To outline the influence of the electrogenerated bases
(
EGB) on the reduction mechanism, the experiments were per-
7
software (Hypercube Inc., Gainesville, Florida), RHF was used for
the closed shell structures and both ROHF and UHF were used for
the open shell structures. The solvent effect was considered under
the framework of the COSMO solvation model [19], implemented
Fig. 2. Configurational isomers of (5–ethoxycarbonylmethylidene–4–oxothiazolidin
2–ylidene)–N–phenylethanamide: a) (2E,5Z)–2a and b) (2Z,5Z)–2b.
–

I. Ceki ´c -Laskovi ´c et al. / Electrochimica Acta 56 (2011) 5257–5265
5259
into AMPAC, based on the dielectric continuum model, with the
parameters and settings for DMSO; a dielectric constant of 48.9, a
refractive index of 1.48 and a sphere of solvation radius of 0.3 nm.
3
. Results and discussions
Preliminary studies on the electrochemical reduction of 2 have
pointed to the ECECE reaction sequence and were verified by the
DigiSim simulations [20]. The previously proposed mechanism,
which consisted mainly of an ECE–Disp sequence in which the
chemical step between the first and the second ET was assigned
to the possible 2E,5Z/2Z,5Z configurational isomerization. It may
be summarized as follows:
◦
2
2
2
2
a + e− = 2a− E1 = −0.8 V
−
•
↔ 2b−•
a
b + e− = 2b− E2 = −0.6 V
◦
−
•
+ 2b−• = 2a + 2b2− or 2b + 2a2−
a
Dianions are strong electrogenerated bases and can undergo
protonation by protic impurities in the solution and they can evolve
to the final reduction product, compound 1 according to the over-
−
+
all reaction: 2 + 2e + 2H = 1. A detailed mechanistic scheme in
which the intermediate species that are involved in the over-
all reaction sequence are identified as chemically defined species
is presented in Scheme 2. The proposed mechanism is based on
our previous IR and NMR spectral studies on related compounds
in which both of the configurational isomers of 2 were charac-
terized by IR and NMR spectra [7]. It was determined that the
−
3
−3
Fig. 3. a) CV of freshly dissolved compound 2 (c = 4 × 10 mol dm ) in 0.1 M
(
2E,5Z)–isomer, which was characterized by an intramolecular
−
1
TBAHFP/DMSO, v= 0.1 V s –curve 1, curve 2 – after about 45 min, and curve 3 –
CV recorded at 40 C, b) RDE curves of the cathodic waves of 2 at rotating rates
100–4000 rpm, insert: plot of the limit current density ratio jl,Ic/jl,IIc in function of
the square root of the rotation rate at E = −0.75 V, i.e. potential in between EIc and
hydrogen bond [IR/KBr spectra, ꢀmax: 3462 (N–H), 1653 (C O) exo,
◦
ꢀ
1
599 (C2 C2 )], is dominant in nonpolar solvents such as CHCl .
3
◦
However, in polar solvents (DMSO), the predominant (2Z,5Z)–form
◦
ꢀ
EIIc
.
[
IR/KBr spectra, ꢀmax: 3323 (N–H), 1674 (C O) exo, 1600 (C2 C2 )]
is stabilized by intermolecular resonance–assisted hydrogen bond-
ing and strong 1,5–type S–O interactions within the S–C C–C
O
The second step in Scheme 2 involves the homogeneous dispro-
portionation between the anion radicals of both isomers, which
moiety. Thermal E/Z isomerization was studied in the solid state by
temperature–dependent IR spectra [21] and in solvents of different
polarity (CDCl3 and DMSO) by dynamic NMR spectroscopy [2–4].
The analysis of the IR spectra recorded in solid state revealed the
temperature–dependent equilibrated mixtures of both isomers in
varying proportions and stability.
The present study brings new experimental evidence for
the characterization of the different intermediates and reaction
sequences, which are presented in Scheme 2, by using cyclic and lin-
ear voltammetry with stationary and rotating disc electrode, as well
as in situ EPR and UV–vis spectroelectrochemistry. In this Scheme,
starting compound 2 indicates a mixture of the (2E,5Z)–2a and
leads to the starting compound (dominant isomer 2a) and the
2−
2−
2− 2−
and 2b , are
2b
dianions (or 2b + 2a ). The dianions, 2a
strong EGB and they can abstract protons either from the pro-
tic impurities present in the solvent or from the substrate itself
(self–protonation). Protonation of the dianion (step 3) leads to the
final reduction product of 1b via the typical keto–enol equilibrium
(step 4).
This reaction sequence and all intermediate species involved
are characterized and supported by experimental and theoretical
results.
(
2Z,5Z)–2b configurational isomers.
3.1. Electrochemical results
The first step in Scheme 2 corresponds to the monoelectronic
reduction of the starting compound (consisting of both configu-
Cyclic voltammetry of compound 2 dissolved in a solution of
−
•
rational isomers) to the corresponding anion radicals, 2b at the
0.1 M TBAHFP/DMSO, presented in the potential range of −1.5 to
−
•
potential of −0.6 V and 2a at the potential of –0.8 V, according to
the simulated DigiSim mechanism. Isomer 2a is reduced at a more
negative potential than 2b due to intramolecular H–bond stabiliza-
tion, as previously reported. This observation is based on solvent
and temperature–dependent IR spectra [21]. As reduction is accom-
0.1 V (Fig. 3a), two irreversible waves that were characterized by
ꢀ
◦
◦ꢀ
E
= −0.6 V (Ic) and E = –0.8 V (IIc). The current density ratio jIc/jIIc
−
1
is about 0.2 at small scan rates (up to 0.1 V s ) (Fig. 3a, curve 1).
After several polarization cycles, or by increasing the temperature,
the current ratio increases and the peak Ic becomes dominant at
ꢀ
◦
panied by a reduced double bond character of the C(2) C(2 ) bond,
40 C [20]. Taking into account that in non–polar solvents, such as
E/Z isomerization is thermodynamically favored and is supported
by solvent and temperature–dependent CV [20], as well as by the
RDE results shown below. The anion radicals are sufficiently stable
and can be characterized by the EPR spectra.
CDCl , isomer 2a is the highly dominant isomer [7], peaks Ic and
3
IIc were assigned to the monoelectronic reduction of isomers 2b
and 2a, respectively. The CV results, which were supported by the
DigiSim simulations, point to an ECE–Disp mechanism.

5
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Scheme 2. Overall reaction (I) and proposed mechanism (II) for the electrochemical reduction of compound 2 to compound 1 in DMSO, in presence of protic impurities.
The ECE–Disp sequence that is proposed is further supported
by the RDE curves recorded at rotating rates in the range of
rent density ratio, jl,Ic/jl,IIc as function of the rotating rate (Fig. 3b
insert) supports this evolution.
1
00–4000 rpm (Fig. 3b). At low rotating rates, up to 500 rpm, only
The value of the slope dE1/2/d(log ω) = 23 mV, along with the
prior analysis of the CV data in Fig. 3a, confirmed the hypothesis of
an ECE–Disp 2 mechanism with the kinetic control by the homoge-
neous ET reaction [22] and a significant effect of disproportionation
for the potential values between Ic and IIc [23].
the second reduction wave is observed. However, increasing of the
rotating rate favors the appearance and the increase of the first
reduction wave, and at a rotating rate of 4000 rpm, only the Ic wave
assigned to the 2b isomer is observed. The plot of the limiting cur-

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5261
Fig. 4. EPR spectra obtained by in situ electrochemical reduction of compound 2 in
DMSO, at a potential between the Ic and IIc waves: a) experimental and b) simulated.
These results are consistent with an E/Z isomerization that
occurs in polar solvents [10,20] during electrochemical reduction
and are in agreement with the previous dynamic 1H NMR stud-
ies, which have outlined this type of isomerization as one of the
characteristic processes of the push–pull alkenes [3,24].
Fig. 5. Absorption spectra recorded on electrolysis of compound
2
−5
−3
(
c = 4 × 10 mol dm ) in DMSO a) at a potential between the Ic and IIc waves,
−5 −3
after 0, 5, 10, 15 min; b) absorption spectra of compound 2 (c = 5 × 10 mol dm
)
in DMSO at high cTBOH/c2 molar ratios (from 16 to 48).
2
–alkylidene–4–oxothiazolidines [10] with the calculated MO spin
distributions, as discussed below.
3.2. EPR results
The highest hfs was assigned to the vinyl proton of the double
bond at the C(5) position, and is in agreement with the structure
of both radical species that are presented in Scheme 2. Next split-
tings are due to the double bond vinyl proton at the C(2) position
and the NH proton of the heterocyclic ring. The distribution of the
hfs constants attests for the delocalization of the unpaired electron
within the planar moiety of the molecule that comprises the con-
jugated thiazolidinone ring with the double bonds at the C(2) and
C(5) positions.
To identify the paramagnetic species in the reduction process
of 2, EPR spectra were obtained during the in situ electrochemical
reduction at a potential between the Ic and IIc waves.
The experimental EPR spectrum is well resolved (Fig. 4a) and
confirmed the presence of a relatively stable paramagnetic species.
The paramagnetic species was assigned to the electrogenerated
anion radical of the dominant 2a isomer from the starting com-
pound. The EPR spectrum becomes asymmetric over time and is
likely due to a mixture with the anion radical of the isomer 2b,
which has a similar g–value, but slightly different hyperfine split-
ting (hfs). The larger value of the g–factor (2.0062) is in the range of
the reported values for other sulfur containing anion radicals, and
this points to a radical center that is close to the sulfur atom, as
opposed to a carbonyl centered species [25]. A significant spin den-
sity on the sulfur atom, which is ascribed to the higher spin–orbit
3.3. UV–vis spectroelectrochemistry
Aside from the primary anion radicals generated by HET,
to detect the diamagnetic transient species, such as the anions
and dianions, UV–vis spectra were recorded during the in situ
electrochemical reductionof 2. Thecurves obtainedduringtheelec-
trochemical reduction at a potential in between waves Ic and IIc, as
well as with the gradual addition of TBOH in DMSO, are presented
in Fig. 5.
The starting compound, a mixture of the configurational isomers
2a and 2b in a 63:37 ratio [27], presents a band at 372 nm (Fig. 5a).
This band decreases in time and a new broad absorption band cen-
tered at 400 nm is formed, which indicates the presence of new
species. In time, this band becomes asymmetric towards 440 nm
and decreases. The absorption band at 440 nm was assigned to the
−
1
coupling constant of sulfur (ꢁ = −382 cm , compared to that of
−1
oxygen, ꢁ = −152 cm ), is indicated by the g–value shift against
the value of the free electron (2.0023) [26]. The spectrum was sim-
ulated (Fig. 4b) with the EPR parameters presented in Table 1.
The hfs pattern attests for a ␲–type radical and is due to
the interaction of the unpaired electron with three protons and
one nitrogen atom. The assignment of the hfs constants due
to the different positions within the molecule was performed
by comparing the anion radicals of the related 5–substituted

5
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Table 1
EPR parameters of the radical species formed in electrochemical reduction of 2.
Radical species
Hyperfine splitting constants (mT)
Line width (mT)
0.028
aN (3)a
aH (8)
aH (10)
aH (6)
−
•
Anion radical 2a
0.070
0.425
0.253
0.080
a
Numbers correspond to atom numbering presented in Fig. 2.
anion radical that was identified and characterized under similar
conditions by EPR spectroscopy.
The normalized absorbance at 372 nm decreases to a minimum,
whereas the band at 440 nm initially increases due to the accu-
mulation of the anion radical, and the minimum on the 372 nm
curve corresponds to the maximum on the curve at 440 nm.
The further decrease of the absorbance at 440 nm, parallel to
the increase in absorbances at 350 nm, (dianion), and at 372 nm
(starting compound 2) may be considered as support for the sub-
sequent homogeneous disproportionation reaction (Scheme 2, step
2). The time evolution of the absorbance at 316 nm, which increases
simultaneously with the absorbance at 350 nm, that is after the
appearance of the dianion in the system, gives further evidence for
its assignment to the reaction product of the dianion protonation,
1b, presumably in the enolic form (Scheme 2, step 3).
Based on the similarity with the spectra that were recorded
in the presence of TBOH added in DMSO (data not presented),
the band at 400 nm was assigned to the anion that was formed
by the ionization of the NH–lactam group due to the action of
the electrogenerated base anion radical on the substrate. Up to
a cTBOH:c = 1:1 molar ratio, this process is reversible and the
2
addition of water recovers the starting compound. The acid char-
acter of the thiazolidinone ring is reflected by the reported pKa
value (18.5) for 4–oxothiazolidine in DMSO [28] and is ascribed
to the sulfur substitution in the 5–membered ring. A similar
behavior was noted for the electrochemical reduction of the
related 5–substituted–N–phenylethanone derivative in DMSO [10].
A highly stabilized anion has been postulated as an intermediate in
the reduction process of 2 with NaBH4 [9].
The spectra were recorded by in situ spectroelectrochem-
istry after prolonged electrolysis or at high TBOH/substrate molar
ratios, as shown in Fig. 5b; this figure also shows the decrease of
the absorption band at 400–440 nm, along with the progressive
increase of the absorption bands at 350–370 nm and 316 nm. This
behavior is consistent with the disproportionation reaction of the
The evolution of the bands, presented in Fig. 6, is consistent with
a reaction sequence [29]:
A + e → B
2
B → A + C
C → D
where A stands for starting compound 2, B for the anion radical, C
for the dianion and D for reaction product 1b. This is supported by
the spectral behavior of compound 1 that was obtained as a pure
anion radical, resulting in the partial recovery of the starting com-
pound (372 nm) and the 2b2− dianion (350 nm), which was further
protonated to the final reduction product, compound 1b (316 nm),
via the typical keto–enol equilibrium (Scheme 2, steps 2–4). Further
support for this assignment is substantiated by the time evolution
of the absorbance at these wavelengths, A = f(log t), where A was
recorded at a potential value between waves Ic and IIc, (Fig. 6).
(Z)–isomer by synthesis [8,24] and was recorded on the gradual
addition of TBOH in DMSO.
The family of spectra in Fig. 7 shows a typical keto–enol tau-
tomeric equilibrium, (step 4 in Scheme 2) which is highlighted by
a decrease of the absorption band at 307 nm that corresponds to
the keto form of 1b [9], along with the increase of the bands at 322
and 340 nm and an isobestic point at 316 nm. In basic media, the
tautomeric equilibrium of compound 1b is shifted towards the less
stable enolic form and these bands were assigned to the enolate
A
convenient method to present data in a transmission
chronoabsorptometry experiment is to plot the normalized
absorbance (ratio of the absorbance at time t to the absorbance
in the absence of the chemical reaction) as a function of time
(
log t). Comparison of these plots with the theoretically calculated
−
2−
anion 1b (322 nm) and the dianion 1b (340 nm), respectively.
For cTBOH/c1b molar ratios of up to 6.4:1, a reversible behavior is
observed, and the substrate 1b can be entirely recovered by acidi-
fying the solution with 7.01 mM trichloroacetic acid.
curves for different mechanisms offers further diagnostic criteria
for a complex reaction mechanisms that involve coupled chemical
reactions to electron transfer steps [29].
Fig. 6. Normalized absorbance A = f(log t) for the bands at 372 (starting compound),
Fig. 7. Keto–enol equilibrium of compound 1: absorption spectra of 1
(c = 4 × 10 mol dm ) in DMSO, at different cTBOH/c2 molar ratios (from 0 to 10).
−
5
−3
3
50 (dianion), 316 (reaction product) and 440 nm (anion radical).

I. Ceki ´c -Laskovi ´c et al. / Electrochimica Acta 56 (2011) 5257–5265
5263
Fig. 8. Shape of the PM3 calculated single occupied molecular orbital (SOMO) of
−
•
anion radical 2a in DMSO.
By comparing the spectra that were recorded after the pro-
longed electrolysis of compound 2 and/or at high cTBOH/c2 molar
ratios (Fig. 5b) with those of 1 in presence of TBOH (Fig. 7), it was
inferred that the same intermediate species was identified, which
was characterized by the absorption band at 340–350 nm. This
2
−
2−
species, the dianion 2b or 1b (resonance formulae A and B of
the same species, Scheme 2, step 3), may be obtained either by start-
ing from compound 2 by electrochemical reduction at potentials
higher than wave IIc and/or disproportionation of the anion radi-
cals (step 2, Scheme 2), or from 1 in the presence of TBOH in DMSO
and it represents experimental evidence for the proposed reaction
mechanism. These results were validated by the semiempirical MO
calculations that are discussed below.
3.4. MO calculations
The aim of the MO calculations was to provide theoretical
support to the proposed electrochemical reduction mechanism in
−
+
Fig. 9. a) Potential energy surface calculated in DMSO for the 2E,5Z/2Z,5Z isomer-
DMSO in the presence of protic impurities (2a,b + 2e + 2H → 1b,
Scheme 2) and to obtain insight into the electronic structure and
reactivity of the different intermediates that were observed by
the experimental results. Therefore, all steps in Scheme 2 were
analyzed and all of the intermediate species, such as the anion rad-
icals, dianions, and enolate anions, were calculated. The reverse
sequence of 1 → 2 was also examined and the possibility of the
−
•
2−
ization of the anion radical 2a (open circles) and dianion 2a (full symbols), with
ꢀ
respect to the rotation around C(2) C(2 ) bond, dihedral angle (–S–C C–C–). ꢂHrel
represents the formation enthalpy including solvation with respect to the minimum
of the (2E,5Z)–2a isomer (left) of the anion radical and dianion, respectively; b) Evo-
ꢀ
ꢀ
lution of the bond orders P(2–2 ) (open triangles) and P(5–5 ) (full symbols) during
−
•
.
the 2E,5Z/2Z,5Z isomerization of the anion radical 2a
−
•
for (2E,5Z)–2a ) and a lower bond order (1.341–1.351 vs. 1.837)
2
E,5Z/2Z,5Z isomerization of the intermediate reduction species
in the corresponding neutral molecules. Second, the lower bond
was considered.
ꢀ
order for the exocyclic C(2) C(2 ) bond compared to the neutral
molecule attests for a possible isomerization during the reduction
process.
The electronic structure of the anion radicals accounted for
the experimental EPR spectra (Fig. 4a), with the highest splitting
3
.4.1. Radical anions
The anion radicals obtained from the 2a and 2b isomers, as
depicted in Scheme 2, were optimized in the gas phase and in
DMSO. The geometry of the anion radicals was similar to the corre-
sponding neutral molecules, and the increased stability of the anion
radical (2E,5Z)–2a (ꢂH = −828.93 kJ mol ) when compared to
(
0.425 mT) (highest calculated spin density) assigned to the exo-
ꢀ
−
•
−1
cyclic C(5) C(5 ) bond proton, which is in agreement with the
structure of the anion radicals that were presented in Scheme 2.
The next greatest hfs (0.253 mT) was assigned to the proton on
−
•
−1
(
2Z,5Z)–2b (ꢂH = −811.86 kJ mol ) was due to intramolecular
H–bonding and was experimentally supported by solvent and tem-
perature IR spectra [20]. However, the calculated –N–H–O C–
distance of the anion radical was 0.232 nm, which is higher than
that in the neutral molecule (0.187 nm) and denotes a weaker inter-
action compared to the neutral molecule. Therefore this molecule
presents a tendency for E/Z isomerization. The calculated charge
ꢀ
the exocyclic C(2) C(2 ) bond, whereas the smallest splittings
were assigned to the lactam nitrogen and proton. The assign-
ment of the EPR spectra was performed by comparison with the
semiempirical MO calculations and assumed a ␲–type radical and
a McConnell–type formula:
−
•
−•
distribution of the anion radicals 2a and 2b attests for the res-
onance formulae of both isomers that were assigned in Scheme 2.
First, the reduction of the exocyclic C(5) C(5 ) bond is reflected by
H
aK = Q ꢃK
CH
ꢀ
where Q is the spin polarization parameter (a proportionality con-
stant that is expressed in magnetic field units) and ꢃ is the spin
density in the pz MO occupied by the unpaired electron (unpaired
an increased repulsion due to high negative net charges on both C
atoms (−0.324 and −0.279 for (2Z,5Z)–2b− and −0.308 and −0.276
•

5
264
I. Ceki ´c -Laskovi ´c et al. / Electrochimica Acta 56 (2011) 5257–5265
Scheme 3. Tautomeric keto–enol equilibrium of compound 1b, with the numbering used in the calculations (Table 3).
Table 2
solvent–dependent PM3–MO calculations, which began with the
2
−
2−
PM3-calculated electronic parameters for the dianions 2b and 1b in DMSO (for-
mation enthalpy including solvation, ꢂH, and energies of the frontier orbitals, εHOMO,
εLUMO).
−•
2−
.
anion radical 2a , or the dianion 2a
The reaction paths for the possible 2E,5Z/2Z,5Z isomerization
−
•
2−
and the dianion 2a , with respect to
of the anion radical 2a
the dihedral angle–S–C C–C–, as well as the evolution of the bond
ꢂH (kJ mol 1
−
)
εHOMO (eV)
−5.97
εLUMO (eV)
−0.031
Radical species
−
b2 , 1b
2−
ꢀ
ꢀ
ꢀ
ꢀ
2
−1127.93
order of the exocyclic C(2)–C(2 ), P(2–2 ) and the C(5)–C(5 ), P(5–5 )
double bonds are presented in Fig. 9.
The highest energy point in Fig. 9a corresponds to a dihedral
−
1
␲
–electron population at the adjacent carbon atom k). Even if the
angle of 83–86 deg and energy barriers of 96 and 63 kJ mol for the
−
•
2−
semiempirical PM3 calculations are not the appropriate methods
for the spin density calculations, the spin density in the pz orbital
and the shape of the molecular orbital occupied by the single
electron (SOMO) in the anion radical (Fig. 8) attests for the delocal-
ization of the unpaired electron onto the thiazolidinone ring, the
exocyclic double bonds and the carbonyl groups, and supports the
assignment of the splitting constants that are presented in Table 1,
as well as the higher g–factor values that were experimentally
observed.
anion radical 2a and the dianion 2a , respectively. These data
indicate a possible, but slow, isomerization process during electro-
chemical reduction. This result is within the range of the values
reported for related compounds from dynamic 1H NMR studies of
thermal E/Z isomerization in DMSO [3], and it is in agreement with
the temperature dependence of the cyclic voltammetry curves,
which showed that isomer 2b is favored at higher temperatures
[20]. Analysis of the calculated bond orders in Fig. 9b indicates
ꢀ
−•
a lower C(2) C(2 ) bond order in the (2E,5Z)–2a (1.585) when
compared to (2Z,5Z)–2b (1.732), which points to an enhanced
conjugation due to the intramolecular H–bond in 2a equal val-
−
•
−
•
3.4.2. Dianions
ꢀ
ues (∼1.35) for the C(5) C(5 ) in both isomers are consistent with
The dianions were calculated starting from either the opti-
the electrochemical reduction that occurrs at this bond and attests
for the structures assigned to the anion radicals in Scheme 2 (step
−
mized geometries of neutral compound 2, [2a,b + 2e ] or from 1
+
[
1b − 2H ]. When starting from 2, the dianions were generated
1
). The evolution of the bond orders during the isomerization of
the anion radicals 2a /2b in Fig. 9b shows a reverse variation,
where the minimum of the C(2) C(2 ) bond order corresponds to
the highest energy point and coincides with a maximum value
of the C(5) C(5 ) bond order. In other words, the weakening of
the C(2) C(2 ) bond is accompanied by a reinforcement of the
C(5) C(5 ) bond, which indicates the transition state of the struc-
either by HET at the electrode at potential values that were greater
than wave IIc, or by homogeneous ET and disproportionation of
the anion radicals (Scheme 2, step 2). The results indicated that the
same structure is obtained by either the two–electron reduction of
−
•
−•
ꢀ
ꢀ
2− 2−
2, (2b ) or by deprotonation of 1b, (1b ), which corresponds to
ꢀ
resonance formulae A and B in Scheme 2 and is characterized by
the electronic parameters in Table 2.
The charge distribution is consistent with equal contributions
from structures A and B in Scheme 2 with the high negative charges
ꢀ
ture in Fig. 9b.
(
−0.798 and −0.767) representing the oxygen atoms of the lac-
3
.4.4. Tautomerization of 1b:
The tautomeric equilibrium (Scheme 3, or step 4 in Scheme 2)
tam and carbonyl groups (form B) and (−0.369 and −0.514) the
exocyclic double bond carbon atoms at the C(5) position (form A),
respectively.
was analyzed, and the relevant results are presented in Table 3.
−1
The keto form is more stable by −141.4 kJ mol and the lower
energy values of the HOMO and the LUMO attest for the increased
−
−
3
.4.3. Reactivity of the intermediate species
e –acceptor (and poorer e –donor) properties of the keto form
when compared to the enol form of 1b. The charge distribution,
shown in Table 3, is in agreement with the structure for both the
keto (high bond order for both carbonyl groups and the intermedi-
ate between the single and double bond order for the ring 12–13
2E,5Z/2Z,5Z isomerization is one of the characteristic reac-
tions of the investigated push–pull oxothiazolidines and was
observed by experimental data during the electrochemical reduc-
tion of 2a,b to 1b. The isomerization was analyzed in terms of the
Table 3
PM3-calculated ꢂH (formation enthalpy including solvation), energies of the frontier orbitals, ␧HOMO, ␧LUMO and selected bond orders for the 1b tautomers.
ꢂH (kJ mol 1
−
)
εHOMO (eV)
εLUMO (eV)
p9–10a
p12–13
p13–17
p15–18
Tautomer
1
1
b keto form
b enol form
−514.59
−373.21
−9.035
−8.038
−0.969
−0.629
1.786
1.716
1.525
1.531
1.721
1.067
1.721
1.039
a
Numbers correspond to atom numbering presented in Scheme 3.

I. Ceki ´c -Laskovi ´c et al. / Electrochimica Acta 56 (2011) 5257–5265
5265
bond) and the enol (low bond orders for the C–O bonds and the
Acknowledgements
intermediate (∼1.5) bond order for the ring 12–13 bond) forms.
The keto form is present mostly in acidic and neutral conditions,
whereas the enol form is favored under basic conditions.
The financial support by the Ministry of Science of the Republic
of Serbia, grant no. 172020 (to R.M.) is acknowledged.
In our experimental conditions, in DMSO, in the presence of
TBOH or electrochemically generated negative species, like anion
radicals or dianions (such as electrogenerated bases), the enolate
anions and the dianions are favored. The similarity of the absorp-
tion spectra recorded in the electrochemical reduction to those
in the presence of TBOH is experimental evidence in this respect.
Consequently, all of these intermediates were calculated, and the
References
[
[
[
[
1] R.G. Giles, N.J. Lewis, J.K. Quick, M.J. Sasse, M.W.J. Urquhart, Tetrahedron 56
(
2000) 4531.
2] Z. D zˇ ambaski, M. Stojanovi c´ , M. Baranac-Stojanovi c´ , D.M. Mini c´ , R. Markovi c´ , J.
Serb. Chem. Soc., doi:10.2298/JSC100607038D.
3] R. Markovi c´ , M. Baranac, N. Jurani c´ , S. Macura, I. Ceki c´ , D. Mini c´ , J. Mol. Struct.
800 (2006) 85.
4] R. Markovi c´ , A. Shirazi, M. Baranac, Z. D zˇ ambaski, D. Mini c´ , J. Phys. Org. Chem.
−
+
energetics of the global reaction, 2a,b + 2e + 2H = 1b, was eval-
uated for both the enol and the keto forms of 1b. The results
indicate that the global reduction of 2a,b to the 1b–enol is slightly
17 (2004) 118.
[5] P.J. Taylor, Spectrochim. Acta 26A (1970) 153.
[6] S. Rajappa, Tetrahedron 55 (1999) 7065.
−1
endothermic (52.72 and 33.14 kJ mol
for 2a and 2b, respec-
[
7] R. Markovi c´ , Z. D zˇ ambaski, M. Baranac, Tetrahedron 57 (2001) 5833.
[
8] R. Markovi c´ , M. Baranac, Z. D zˇ ambaski, M. Stojanovi c´ , P.J. Steel, Tetrahedron 59
(2003) 7803.
tively), whereas the 1b–keto form is largely exothermic (−88.58
−1
and −108.28 kJ mol for 2a and 2b, respectively). Therefore, the
acid–base properties of these species play an important role in the
overall electrochemical reduction of 2 to 1 and must be considered
for the complete understanding of the reaction mechanism.
[
9] R. Markovi c´ , M. Baranac, M. Stojanovi c´ , Synlett 6 (2004) 1034.
[
10] I. Ceki c´ -Laskovi c´ , D.M. Mini c´ , R. Markovi c´ , E. Volanschi, J. Electroanal. Chem.
51 (2011) 50.
[11] M. Enache, I. Anghelache, E. Volanschi, International J. Pharm. 390 (2010) 100.
6
[
[
[
12] L. Preda, E. Volanschi, Cent. Eur. J. Chem. 7 (3) (2009) 486.
13] M. Enache, C. Bendic, E. Volanschi, Bioelectrochemistry 72 (2008) 10.
14] J.F. Bergamini, J. Delaunay, P. Hapiot, M. Hillebrand, C. Lagrost, J. Simonet, E.
Volanschi, J. Electroanal. Chem. 569 (2004) 175.
4
. CONCLUSIONS
[
[
[
15] R. Markovi c´ , M. Baranac, Z. D zˇ ambaski, Heterocycles 63 (2004) 851.
16] M. Ciureanu, M. Hillebrand, E. Volanschi, J. Electroanal. Chem. 291 (1990) 201.
17] M. Ciureanu, M. Hillebrand, E. Volanschi, J. Electroanal. Chem. 322 (1992) 221.
The electrochemical reduction of (5–ethoxycarbonyleth-
ylidene–4–oxothiazolidin–2–ylidene)–N–phenylethanamide (2)
to (Z)–(5–ethoxycarbonylmethyl–4–oxothiazolidin–2–ylidene)–
N–phenylethanamide (1) in DMSO in the presence of protic impu-
rities was investigated by coupled in situ electrochemical (CV with
stationary and RDE) and spectral (EPR, UV–vis absorption) tech-
niques. A reduction mechanism, which consisted of an ECE–Disp
sequence that was followed by the protonation of the strong
EGB, was proposed. The same intermediate species, the dianion
[18] EPR Simulation Program for Windows, http://epr.niehs.nih.gov/pest.html.
[
[
19] A. Klamt, G. Schurmann, J. Chem. Soc, Perkin Trans. 2 (1993) 799.
20] I. Ceki c´ -Laskovi c´ , D. Mini c´ , M. Baranac-Stojanovi c´ , R. Markovi c´ , E. Volanschi,
Russ. J. Phys. Chem. A 83 (9) (2009) 1571.
[21] D.M. Mini c´ , Z. Nedi c´ , R. Markovi c´ , J. Therm. Anal. Calorim. 95 (2009) 167.
[
[
22] C.P. Andrieux, J.M. Saveant, in: C.F. Bernasconi (Ed.), Investigation of rates and
mechanisms of reactions, vol. 4, part 2, Wiley & Sons, New York, 1986.
23] RiegerF P.H. (Ed.), Electrochemistry, Chapman & Hall, New York, 1994, pp.
285–304.
2−
2−
2
b
or 1b (different resonance formulae of the same species,
[24] R. Markovi c´ , M. Baranac, Heterocycles 48 (1998) 893.
[
[
[
25] L.J. Aarons, F.C. Adams, Canad. J. Chem. 50 (1972) 1390.
26] H.C. Heller, J. Amer. Chem. Soc. 89 (1967) 4288.
27] R. Markovi c´ , M. Baranac, Z. D zˇ ambaski, J. Serb. Chem. Soc. 69 (4) (2004) 239.
shown in Scheme 2, step 3), was identified either starting from
compound 2 by electrochemical reduction or from compound 1 in
the presence of TBOH in DMSO. The proposed reaction mechanism
is supported by the experimental results and by the semiempirical
solvent–dependent PM3–MO calculations that were performed.
[28] M.M. Hansen, P.R. Harkness, D.S. Coffey, F.G. Bordwell, Y. Zhao, Tetrahedron
Lett. 49 (1995) 8949.
29] Li Chia-Yu, G.S. Wilson, Anal. Chem. 45 (1973) 2370.
[