Electrochemical generation of a Michael acceptor: A green method for the synthesis of 4-amino-3-(phenylsulfonyl)diphenylamine derivatives

Article abstract of DOI:10.1039/c5nj00087d

Electrochemical oxidation of 4-aminodiphenylamine in aqueous solution and in the presence of some arylsulfinic acids as nucleophiles was studied and its reaction mechanism was discussed. Using the voltammetric data, a one-pot and environmentally friendly

Full text of DOI:10.1039/c5nj00087d

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PAPER
Electrochemical generation of Michael acceptor:
A green method for the synthesis of 4-amino-3-
Cite this: DOI: 10.1039/x0xx00000x
(
phenylsulfonyl)diphenylamine derivatives†
Eslam Salahifar and Davood Nematollahi*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
Electrochemical oxidation of 4-aminodiphenylamine in aqueous electrochemical oxidation of 4-aminodiphenylamine (4-APA
)
solution and in the presence of some aryl sulfinic acids as in the presence of sulfinic acid sodium salts as nucleophiles and
nucleophiles was studied and its reaction mechanism was showed that the anodically generated N-phenylquinonediimine
discussed. Using the voltammetric data,
environmentally friendly electrochemical approach for the we have discovered an easy and one-pot electrochemical
synthesis of 4-amino-3-(phenyl sulfonyl)diphenylamine method for the synthesis of new 4-amino-3-(phenylsulfonyl)
a one-pot and as a Michael acceptor reacts with sulfinic acids. In this work,
derivatives via the Michael type addition reaction of anodically diphenylamine derivatives in the high yield and purity, using an
generated N-phenylquinone diimine with aryl sulfinic acids, at a environmentally friendly method with high atom economy.
carbon electrode, without toxic reagents and solvents is reported.
Atom economy is defined as the percentage of reactants that go
into final products. From green chemistry and waste
management viewpoints, this method also minimizes metallic
catalyst consumption as a great pollutant and on the other hand,
catalyst recycling cost decreases particularly.17
Introduction
Arylsulfone compounds are widely used as building blocks for
some drugs, such as Laropiprant and Vioxx. They have also
been shown to have antibacterial, antifungal and antitumor
properties.1,2 On the other hand, diphenylsulfone compounds
3
were found to exhibit anti-bacterial activity. The incorporation
of a diphenylsulfone moiety into some heterocyclic compounds
4
was found to increase their biological activity. For example,
diphenylsulfone is used for the synthesis of dapsone (4,4- Fig. 1. The structure of dapsone (A) and compounds reported here (B).
diaminodiphenylsulfone) (Figure 1) which is a bacteriostatic
drug that inhibits dihydrofolic acid synthesis by competition
with para-aminobenzoic acid. It was also shown that, dapsone
Results and discussion
5
has anti-inflammatory and bacteriostatic properties comparable
with those of nonsteroidal anti-inflammatory drugs.6,7 In
pH studies
Cyclic voltammetry of 4-APA in aqueous perchloric acid
solution (pH = 1.0, c = 0.2 M) is shown in Figure 2, curve d.
addition, it can inhibit cellular adhesion, chemotaxis, and the
expression of prostaglandin, leukotrienes, IL-8, TNF8
The voltammogram showed one anodic peak (A
to the oxidation of 4-APA to N-phenylquinonediimine (
PQD) and one cathodic peak (C ) at 0.38 V during the revers
scan due to the reduction of -PQD to 4-APA (Scheme 1).
1
) at 0.42 V due
The most common methods for the synthesis of sulfone
derivatives are the sulfonylation of arenes using aryl sulfonyl
halides, the oxidation of sulfides or aryl sulfonic acids in the
presence of a strong acid catalyst.9-11 Major disadvantage of
these methods is an incompatibility with numerous functional
groups.12 Our interest in the design and electrochemical
synthesis of new compounds with medicinal activity13-16
N
-
1
N
Under these conditions, the peak current ratio (IpC1/IpA1) is
independent of scan rate and equal to unity which can be
considered as a criterion for the stability of electrogenerated N-
PQD under the experimental conditions. In other words, any
side reactions, such as hydroxylation,18 dimerization,19,20
prompted us to synthesize new molecules similar to dapsone
under mild and ambient condition. Herein we investigated the
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oxidative ring cleavage21 or hydrolysis22,23 on electrochemically cyclic voltammograms {(EpA1 + EpC1)/2}. The values of E1/2 as
generated -PQD are too slow to be observed at the time scale a function of solution’s pH are plotted in Fig. 3. As can be seen,
N
of cyclic voltammetry.
E1/2 was shifted to negative potentials with the slope of about
′
50 mV/pH (
퐸
= -0.050pH + 0.45) which is in agreement with
/2
1
the theoretical slope (2.303mRT/2F) of 59 mV/pH with m about
. This shows that the same numbers of electrons and
protons23,24 are involved in the redox processes, at pH value
between 0-11. On the basis of the reported pK values of
primary and secondary amine moieties of 4-APA (5.15 and ≈
.8, respectively) (Scheme 2),24 we can conclude Scheme 1 for
the electrochemical oxidation of 4-APA in the pH range 0-11.
2
a
0
Figure 2. Cyclic voltammograms of 4-APA (0.5 mM) in aqueous
buffer solutions with different pH values and same ionic strength, at a
glassy carbon electrode. The pH values from (a) to (n) are: 0.0, 0.2, 0.5,
1
.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0 and 11.0, respectively.
−
1
o
Scan rate; 50 mV s . Temperature = 25 ± 1 C.
Figure 3. The potential-pH diagram of 4-APA
.
The presence of the same numbers of electrons and protons
in the redox processes in pHs less than 5.15 (Scheme 1), shows
that the oxidation products are in protonated forms.24 In pH
values less than 0.8, the high acidity of solution may be
responsible for the generation of diprotonated quinoid form (N-
DPQH
2
) during the oxidation of 4-APA. Bergamini et al
reported that pK
a
of N-DPQH is about 5.6 (very close to the
pKa2 for 4-APA).24 So, we can assert therefore that the
similarity of the basicity of 4-APA and N-PQD can be
responsible for the two-electron/two-proton process in 0.8 <
pHs < 5.15.
Scheme 1. Electrochemical oxidation of 4-APA in the pH range 0-11.
It is well known that in the majority of electro-oxidations of
organic compounds, the transfer of electron(s) is accompanied
by a proton transfer. Therefore, the effects of pH on the
electrochemical oxidation of 4-APA has been studied. Figure 2
also, shows the cyclic voltammograms of 4-APA in various
pHs in the range of 0-11. It was found that the change of pH
does not significantly affect the peak current ratio (IpC1/IpA1),
while, the half wave potential (E1/2) shifted to the negative
potentials by increasing pH. The latter is expected because of
Scheme 2. Acid/base equilibrium of 4-APA
.
the participation of proton(s) in the oxidation of 4-APA to
PQD. The half wave potential (E1/2), is given by:
N-
Mechanistic studies
'
1
E
= E1/2 − (2.303 mRT/2F) pH
The electrochemical oxidation of 4-APA in the presence of 4-
toluenesulfinic acid (1a) was also studied in the pH range 2-9
/2
(
Figure 4, curves b). A comparison of voltammogram of 4-
APA in the absence of 1a with that in the absence of 1a at pH,
.0 shows that: (a) a new redox couple (A /C ) appears at more
positive potentials; (b) the anodic peak A current (IpA1
where m is the number of protons involved in the reaction and
1/2 is the half wave potential at pH = 0.0, R, T and F have their
usual meanings. The half-wave potentials (E1/2) were calculated
E
2
2
2
1
)
as the average of anodic and cathodic peak potentials of the
2
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increases slightly and its potential shifts to less positive values voltammetry, the peak current ratio is
and (c) in the reverse scan, the cathodic peak C nearly homogeneous reaction rate or reactivity of
disappears. These observations indicate that a chemical reaction the surface of the electrode with 1a,25 in this study, a solution
follows the electron transfer process: -PQD formed at the with pH 2.0 has been selected as a suitable medium for the
surface of the electrode by the two-electron oxidation of 4-APA electrochemical synthesis.
is consumed in a reaction with 1a. In this Fig. curve c, is cyclic Controlled-potential coulometry was performed in an
voltammogram of 1a aqueous phosphate buffer (pH = 2.0, c = 0.2 M) solution
a
measure of
1
N-PQD formed at
N
.
This is further confirmed by the effect of the scan rate and containing 4-APA (0.25 mmol) and 1a (0.25 mmol) at 0.30 V
of the concentration of 1a on the cyclic voltammogram of 4- vs. Ag/AgCl. The electrolysis progress was monitored using
APA in the presence of 1a. Our data shows that, IpA1 increases cyclic voltammetry (Figure 6). As shown, the following
with respect of that of peak A
does the current of peak C (IpC1) (Figure 5). Such increase at in the anodic peak current A
faster scan rates is related to a decrease of the experimental after consumption of about 2e per molecule of 4-APA, are
time scale. A faster scan rate results in a lesser amount of observed in cyclic voltammograms during the advancement of
2
upon increasing the scan rate as changes: a) decrease in the anodic peak current A
1
, b) increase
1
2
and c) disappearance of peak A
-
1
N
-
PQD reacting with 1a, hence the observe increase of the peak coulometry.
current ratio (IpC1/IpA1). Figure 5 also shows that EpA1 shifts to
positive potentials with increasing potential scan rate. Because
of the following reaction, EpA1 is less positive than EpA1 in the
absence of 1a (Fig. 4). However, it shifts in a positive direction
(
toward the unperturbed curve) with increasing v (Figure 5).
In addition, upon the increasing of the concentration of 1a
,
I
pA2 and IpC2 increase, and IpC1 decreases. Peak A
2
is due to the
oxidation of adduct formed by the reaction of
N
-PQD with 1a.
The higher the concentration of 1a, the faster is its reaction with
-PQD, the lesser is the amount of -PQD be reduced (peak
).
N
N
C
1
Figure 5. Cyclic voltammograms of 4-APA (1.0 mM) in the presence of 4-
toluenesulfinic acid (1a) (1.0 mM) at various scan rates. Scan rates from a) to g)
-
1
are: 50, 100, 150, 250, 1000, 2500 and 5000 mV s , respectively, at glassy carbon
electrode in aqueous phosphate buffer (pH = 2.0, c = 0.2 M). Temperature = 25
o
±
1 C.
Figure 4. Cyclic voltammograms of 4-APA (1.0 mM) (a) in the absence, (b) in the
presence of 1a (1.0 mM). (c) 1a (1.0 mM) in the absence of 4-APA at glassy
carbon electrode in aqueous buffer solutions with different pH values and same
−
1
o
ionic strength. Scan rate; 100 mV s . Temperature = 25 ± 1 C. Inset: A plot of
peak current ratio (IpA1/IpC1) in the absence (a) and presence of 1a (b) in pH
values. The pH values are shown on horizontal axis.
Contrary to pH 2.0, the cyclic voltammograms of 4-APA in
the presence of 1a (curves b) in pH values 5.0, 7.0 and 9.0, do
not show any sign of reactivity of
N-PQD toward 1a in the time
scale of our experiments. A plot of peak current ratio (IpA1/IpC1
)
in the absence (curves a) and presence of 1a (curves b) in pH
values 2-9 is shown in Fig. 4, inset. It was found that the
change of pH has only a great influence on the peak current
ratio (IpC1/IpA1) in the presence of 1a in pH 2.0. Since, in cyclic
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Figure 6. Cyclic voltammograms of 4-APA (0.25 mmol) in the presence of 4-
toluenesulfinic acid (1a) (0.25 mmol) during controlled potential coulometry at
0
.30 V vs. Ag/AgCl (3 M) in aqueous phosphate buffer (pH = 2.0, c = 0.2 M). Scan
−
1
o
rate: 100 mV s . Temperature =25 ± 1 C.
According to Scheme 3, the overall reaction mechanism for
The coulometry and voltammetry results, the ( H, 13C) electrochemical synthesis of 3a-3c is shown in Scheme 4:
1
NMR and FTIR data and the molecular mass of 338 of the
1
isolated electrolysis product all point out to N -phenyl-3-
tosylbenzene-1,4-diamine (3a) which would have been formed
according to the pathway shown in Scheme
mechanism). In proposed mechanism, for simplification the
protonation of species are omitted. The first step (E ) is the
generation of -PQD. In the next step, -PQD would serve as
a Michael acceptor in a reaction with 1a to form the final
product 3a (C step). The oxidation of 3a is more difficult than
r i
3 (E C
r
N
N
i
the oxidation of 4-APA due to the presence of the electron-
withdrawing tolylsulfonyl group. Therefore, the oxidation of 3a
did not occur during the electrochemical oxidation at the
potential of 0.30 V. According to the proposed mechanism, the
anodic peak A
quinonediimine 3aox
2
should correspond to the oxidation of 3a to the Figure 7. Variation of anodic peak current (IpA1) versus consumed charge. All data
obtained from Fig. 6.
.
Obviously, the cathodic peak
C
2
corresponds to the reduction of 3aox to 3a
.
Scheme 4. The overall reaction of electrooxidation of 4-APA in the presence of
a-1c.
1
The calculated atom economy for the synthesis 3a-3c are
9.41, 99.39 and 99.45%, respectively. The high atom economy
9
indicates that all atoms (except two hydrogen atoms) from the
two starting materials are incorporated into the product.
N
-PQD can be attacked by 1c from sites A or B to yield two
types of compounds (3c and 4c) (Scheme 5). However, single-
crystal X-ray diffraction analysis of synthesized compound
confirms the structure of 3c (Figure 8).
This regioselectivity may presumably be due to the large
steric hindrance in the molecule 4c in comparison with 3c. The
steric energies have been calculated for 3c and 4c, using MM2
program after minimization of structures (Fig. 9). Results
indicate that structure 3c is energetically more stable than the
Scheme 3. Electrochemical oxidation of 4-APA in the presence of 1a-1c.
4c with about 11 kcal/mol lower energy.
Figure 7 shows the variation of anodic peak current (IpA1
)
versus consumed charge (all data obtained from Fig. 6). As
expected, a linear relationship was found between IpA1 and the
consumed charge. The equation of the line is IpA1 = -0.49Q +
28.8, with a correlation coefficient, R= 0.995. Using these data,
the current efficiency for the electrochemical synthesis of 3a
was calculated based on Faraday's law (deviation between
theoretical and experimental charge). The calculated current
efficiency value is about 82%. The same data were obtained for
the electrochemical synthesis of 3b and 3c
.
To calculate atom economy, equation (1) was used,
according to Eissen and coworkers.26
4
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Scheme 5. The structures of possible compounds.
as hydroxylation,18 dimerization,19,20 oxidative ring cleavage21
and/or hydrolysis.22,23
Figure 8. ORTEP view of X-ray crystal structure of 3c
.
Figure 10. (a) Cyclic voltammogram of 4-APA (1.0 mM) and (b) cyclic
voltammogram of saturated solution of 3c at glassy carbon electrode in aqueous
phosphate buffer (pH = 2.0, c = 0.2 M)/ethanol (90/10 v/v) mixture. Scan rate;
−
1
o
1
00 mV s . Temperature = 25 ± 1 C.
The effect of the potential scan rate on the cyclic
voltammogram of 3c was also studied (Fig. 11). The obtained
data show that with increasing scan rate, the peak current ratio
(IpC2/IpA2) increase. The time scale of a cyclic voltammetry
experiment is determined by the potential scan rate, as
increasing the scan rate decreases the experimental time scale
and removes the effects of the following chemical reaction(s)
appearing as an increase in IpC2/IpA2
.
Figure 9. The results of MM2 calculation for 3c (above) and 4c (below).
In order to investigate the electrochemical properties of the
isolated product (3c), its voltammetric behavior was examined.
The cyclic voltammogram of saturated solution of 3c in
aqueous phosphate buffer (pH = 2.0, c = 0.2 M)/ethanol (90/10
v/v) is shown in Fig. 10. Contrary to 4-APA, in potential scan
Figure 11. Cyclic voltammograms of saturated solution of 3c at glassy carbon
electrode in aqueous phosphate buffer (pH = 2.0, c = 0.2 M)/ethanol (90/10 v/v)
−
1
rate 100 mV s , it shows an irreversible feature with one mixture in different scan rate. Scan rates from a to e are: 100, 250. 500, 750 and
anodic peak (A ) at 0.44 V vs. SCE which corresponds to the
2
-
1
o
1
000 mV s . Temperature = 25 ± 1 C.
transformation of 3c to 3cox (Scheme 3). In addition, in
comparison with 4-APA, EpA2 is more positive than EpA1. The
results were predictable. In general, the attachment of an
electron-withdrawing group (EWG) to a molecule, unstable the
Conclusions
The present method for the synthesis of 4-amino-3-
(
phenylsulfonyl)diphenylamine
derivatives
has
several
oxidized form of molecule and arrives it in the fast following
chemical reaction(s).13,27 In this case, the presence of
arylsulfonyl group with electron withdrawing character in the
structure of 3c unstable the electro-generated quinonediimine
3cox and arrives it in the fast following chemical reactions such
advantages over conventional methods. This process is
practically convenient to carry out and can be performed at
atmospheric pressure and room temperature. Neither catalyst
nor organic/inorganic oxidizing agents are necessary and the
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Cl
reaction can be performed under green and mild condition with
high atom economy (>99%). The in situ formation of N-
phenylquinonediimine is achieved and there is no need to
prepare N-phenylquinonediimine in advance.
O
H
N
S
O
3
b
NH2
-
1
Isolated yield: 70%. IR (KBr, cm ): 3428, 3353, 2923, 2853,
631, 1598, 1516, 1486, 1397, 1314, 1146, 1088, 758, 587,
Experimental section
1
1
Apparatus and reagents
6 2
480. H NMR (400 MHz DMSO-d ): δ 5.86 (s, 2H, NH ,
disappeared by the addition of D
=
=
2
O), 6.72 (t, 1H), 6.79 (d, 2H, J
8.8 Hz), 6.84 (d, 2H, J = 8.0 Hz), 7.17 (m, 3H), 7.44 (d, 1H, J
2.4 Hz), 7.68 (dd, 2H, J = 8.8, 2.0 Hz) 7.89 (s, 1H, NH,
O), 7.94 (dd, 2H, J = 8.8, 2.0
Hz). 13C NMR (100 MHz DMSO-d
): δ 115.1, 118.7, 118.9,
19.3, 119.9, 128.9, 129.1, 129.7, 130.0, 132.9, 138.9, 140.4,
42.5, 145.4. MS (EI) m/z (relative intensity): 358 (21), 324
The working electrode used in macro-scale electrolysis and
controlled-potential coulometry was an assembly of four
ordinary soft carbon rods (6 mm diameter and 4 cm length),
placed as single rods in the edges of a square with a distance of
disappeared by the addition of D
2
cm, and a large stainless steel cylinder (25 cm2 area)
6
3
1
1
constituted the counter electrode. The working electrode used
in the cyclic voltammetry experiments was a glassy carbon disc
(
14), 252 (100), 195 (43), 171 (64), 135 (75), 85 (86).
(
1.8 mm diameter) and a glass carbon rod was used as the
counter electrode. The electrosynthesis were performed under
controlled-potential condition in a two compartments cell,
separated by an ordinary porous fritted-glass diaphragm (a tube
with 1.5 cm diameter) and equipped with a magnetic stirrer. 4-
APA, aryl sulfinic acids, phosphate salts and ethanol were
obtained from commercial sources. These chemicals were used
without further purification. The glassy carbon electrode was
polished using alumina slurry (from Iran Alumina Co.). More
details are described in the previous paper.28
1
N -phenyl-3-(phenylsulfonyl)benzene-1,4-diamine (C18
(
H
16
N
2
O
2
S)
3c)
O
H
N
S
O
NH2
3c
-1
Isolated yield: 72%. IR (KBr, cm ): 3451, 3404, 3366, 1634,
1
1
598, 1505, 1312, 1292, 1142, 1095, 751, 588, 537. H NMR
400 MHz DMSO-d ): δ 5.86 (s, 2H, NH , disappeared by the
O), 6.72 (t, 1H), 6.78 (d, 1H, J = 8.8 Hz), 6.83 (d,
1b 2H, J = 7.6 Hz), 7.15 (m, 3H), 7.45 (d, 1H, J = 2.4 Hz), 7.61 (t,
or 1c) (0.25 mmol), was electrolyzed in a divided cell at 0.30 V 2H), 7.69 (t, 1H), 7.88 (s, 1H, NH, disappeared by the addition
vs. Ag/AgCl (3M). The electrolysis was terminated when the of D
O), 7.93 (dd, 2H, J = 8.4, 1.6 Hz). 13C NMR (100 MHz
decay of current became more than 95%. At the end of DMSO-d ): δ 115.0, 118.8, 119.0, 119.1, 120.4, 127.1, 128.7,
Electroorganic synthesis of 3a-3c.
(
6
2
A solution of phosphate bu
ff
er (c = 0.2 M, pH = 2.0)/ethanol addition of D
2
(
50/50 v/v) mixture, containing 4-APA (0.25 mmol) and 1a
(
2
6
electrolysis, the cell was placed in a refrigerator overnight. The 129.7, 129.9, 132.8, 133.9, 141.7, 142.5, 145.5. MS (EI) m/z
precipitated solid was collected by filtration and recrystallized (relative intensity): 324 (39), 252 (55), 223 (17), 195 (38), 149
from acetone/n-hexane mixture (30/70 v/v).
(28), 115 (61), 55(100).
N1-Phenyl-3-tosylbenzene-1,4-diamine (C19
H N O S) (3a)
18 2 2
Acknowledgements
CH3
We acknowledge the Bu-Ali Sina University Research Council
and the Center of Excellence in Development of
Environmentally Friendly Methods for Chemical Synthesis
O
H
N
S
O
3a
NH2
(
CEDEFMCS) for their support of this work.
-
1
Isolated yield: 72%. IR (KBr, cm ): 3429, 3347, 1599, 1514,
Notes and references
1
6
1284, 1142, 751, 586. H NMR (400 MHz DMSO-d ): δ 2.36
(
s, 3H, methyl), 5.83 (s, 2H, NH
2
, disappeared by the addition Faculty of Chemistry, Bu-Ali-Sina University, Hamedan 65178-38683, I.
R. Iran. nemat@basu.ac.ir
2
of D O), 6.71 (t, 1H), 6.76 (d, 2H, J = 8.8 Hz), 6.83 (d, 2H, J =
1
†
Electronic Supplementary Information (ESI) available: FT-IR, H
7
(
.6 Hz), 7.12-7.18 (m, 3H), 7.40 (d, 2H, J = 8.4 Hz), 7.44
d,1H, J = 2.4 Hz), 7.81 (d, 2H, J = 8.4 Hz), 7.86 (s, 1H, NH,
disappeared by the addition of D
O). 13C NMR (100 MHz
DMSO-d ): δ 21.5, 115.0, 118.8, 119.0, 119.1, 120.8, 127.2,
28.6, 129.7, 130.3, 132.7, 133.8, 142.3, 144.4, 145.5. MS (EI)
m/z (relative intensity): 338 (100), 263 (41), 236 (38), 183 (41),
54 (29), 69 (38).
1
3
NMR and C NMR spectra of 3a-3c and crystallographic Information
data of 3c (CIF). See DOI: 10.1039/c000000x/
2
1
Z. Y. Sun, E. Botros, A. D. Su, Y. Kim, E. Wang, N. Z. Baturay and
C. H. Kwon, J. Med. Chem., 2000, 43, 4160-4168.
6
1
2
T. Otzen, E. G. Wempe, B. Kunz, R. Bartels, G. Lehwark-Yvetot, W.
Hänsel, K. J. Schaper and J. K. Seydel, J. Med. Chem., 2003, 47
40-253.
,
1
2
1
3
-((4-Chlorophenyl)sulfonyl)-N -phenylbenzene-1,4-diamine
3
E. F. Elslager, Z. B. Gavrilis, A. A. Phillips and D. F. Worth, J. Med.
Chem., 1969, 12, 357–363.
(
C H15ClN O S) (3b)
18 2 2
6
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4
G. L. Almajan, S. F. Barbuceanu, E. R. Almajan, C. Draghici and G.
Saramet, Eur. J. Med. Chem., 2009, 44, 3083–3089.
M. D. Coleman, Br. J. Dermatol., 1993, 129, 507-513.
S. Repichet, C. Le Roux, P. Hernandez and J. Dubacjean-Roger, J.
Org. Chem., 1999, 64, 6479–6482.
5
6
7
8
9
M. D. Coleman and M. D. Tingle, Drug Dev. Res., 1992, 25, 1–16.
G. Wozel and C. Blasum, Arch. Dermatol. Res., 2014, 306, 103-124.
K. Schank, In The Chemistry of Sulfones and Sulfoxides: S. Patai, Z.
Rappopor and C. J. M. Stirling, Eds.; Wiley: New York, 1988;
Chapter 7.
1
0 W. E. Truce, T. C. Klinger and W. W. Brand, In Organic Chemistry
of Sulfur: S. Oae, Ed.; Plenum Press: New York, 1977.
1 H. Suzuki and H. Abe, Tetrahedron Lett., 1995, 36, 6239-6242.
1
1
1
2 J. M. Baskin and Z. Wang, Org. Lett., 2002, 4, 4423-4425.
3 F. Varmaghani, D. Nematollahi, S. Mallakpour and R. Esmaili,
Green Chem., 2012, 14, 963-967.
1
1
4 D. Nematollahi and M. Rafiee, Green Chem., 2005,
5 H. Salehzadeh, D. Nematollahi and H. Hesari, Green Chem., 2013,
, 2441-2446.
7, 638–644.
1
5
1
1
6 A. Maleki and D. Nematollahi, Org. Lett., 2011, 13, 1928–1931.
7 B. A. Frontana-Uribe, R. D. Little, J. G. Ibanez, A. Palmad and R.
Vasquez-Medrano, Green Chem., 2010, 12, 2099–2119.
1
1
2
2
8 L. Papouchado, G. Petrie, J. H. Sharp amd R. N. Adams, J. Am.
Chem. Soc., 1968, 90, 5620-5621.
9 H. Salehzadeh, D. Nematollahi and M. Rafiee, J. Electroanal. Chem.,
2
011, 650, 226-232.
0 D. Nematollahi, M. Rafiee and A. Samadi-Maybodi, Electrochim.
Acta, 2004, 49, 2495-2502.
1 D. Nematollahi and F. Varmaghani, J. Iran. Chem. Soc., 2011,
03-810.
2 H. Yang and A. J. Bard, J. Electroanal. Chem., 1992, 339, 423-449.
3 R. L. Hand and R. F. Nelson, J. Am. Chem. Soc., 1974, 96, 850-860.
8,
8
2
2
2
4 J. F. Bergamini, M. Belabbas, M. Jouini, S. Aeiyach, J. C. Lacroix,
K. I. Chane-Ching and P. C. Lacaze, J. Electroanal. Chem., 2000,
4
82, 156-67.
2
2
2
2
5 A. J. Bard and L. R. Faulker, Electrochemical Methods, 2nd ed.,
Wiley, New York, 2001.
6 M. Eissen, R. Mazur, H. G. Quebbemann and K. H. Pennemann,
Helv. Chim. Acta, 2004, 87, 524–535.
7 D. Nematollahi, A. Sayadi and F. Varmaghani, J. Electroanal.
Chem., 2012, 671, 44−50.
8 D. Nematollahi, S. Dehdashtian and A. Niazi, J. Electroanal. Chem.,
2
008, 616, 79-86.
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