A facile electrochemical method for the synthesis of 5-phenyl-1,3,4- oxadiazol-2-ylthio-benzene-1,2-diol derivatives

Article abstract of DOI:10.1002/jhet.86

(Chemical Equation Presented) Electrochemical oxidation of catechols to corresponding o-quinones was successfully performed in aqueous solution by electrolysis at the controlled potentials. Quinones derived from catechols, participate in Michael addition

Full text of DOI:10.1002/jhet.86

May 2009
A Facile Electrochemical Method for the Synthesis of 5-Phenyl-
1,3,4-oxadiazol-2-ylthio-benzene-1,2-diol Derivatives
443
Ali Reza Fakhari,* Saied Saeed Hosseiny Davarani, Hamid Ahmar,
Kobra Hasheminasab, and Hamid Reza Khavasi
Department of Chemistry, Faculty of Sciences, Shahid Beheshti University, G. C., Tehran,
Islamic Republic of Iran
*E-mail: a-zavareh@sbu.ac.ir
Received March 11, 2008
DOI 10.1002/jhet.86
Published online 26 May 2009 in Wiley InterScience (www.interscience.wiley.com).
Electrochemical oxidation of catechols to corresponding o-quinones was successfully performed in
aqueous solution by electrolysis at the controlled potentials. Quinones derived from catechols, partici-
pate in Michael addition reactions with 5-phenyl-1,3,4-oxadiazole-2-thiol and via EC mechanism,
converted to corresponding 5-phenyl-1,3,4-oxadiazol-2-ylthio-benzene-1,2-diol derivatives (4 and 40).
1
The products have been characterized using IR, H NMR, 13C NMR, X-ray, and mass spectral data.
J. Heterocyclic Chem., 46, 443 (2009).
INTRODUCTION
0.15M phosphate buffer (pH 7.2) shows one anodic (A1)
and corresponding cathodic peak (C1), which is related
to the transformation of 4-methylcatechol (1a) to o-ben-
zoquinone (2a) and vice versa through a quasi-reversible
two-electron process (Fig. 1, curve I).
Derivatives of 1,3,4-oxadiazole constitute an impor-
tant family of heterocyclic compounds. Some material
applications of 1,3,4-oxadiazole derivatives lie in the
field of liquid crystals [1]. 1,3,4-Oxadiazole derivatives
are also among the most widely used electron-conduct-
ing and hole-blocking materials in organic light-emitting
diodes [2]. Substituted 1,3,4-oxadiazoles are associated
with many types of biological properties [3–5]. The 2-
aryl-5-(substituted)-1,3,4-oxadiazoles have been reported
to show antibacterial [6,7], antifungal [8], anti-inflam-
matory [9,10], and hypoglycemic [7] activity. Catechols
can be oxidized electrochemically to o-quinones. O-qui-
nones derived from catechols are quite reactive and can
be attacked by nucleophiles [11–15]. Regarding the im-
portance of 1,3,4-oxadiazole derivatives in biological
systems and following our previous works [16–19], we
have reported the simple electrochemical method for the
synthesis of some novel 1,3,4-oxadiazole derivatives
from catechols and 5-phenyl-1,3,4-oxadiazole-2-thiol in
this work.
A peak current ratio (ICP1/IAP 1) of nearly one, particu-
larly during the repetitive recycling of potential, can be
considered as a criterion for the stability of o-benzoqui-
none produced at the surface of electrode under the ex-
perimental conditions. In other words, any hydroxylation
[20] or dimerization [21] reactions are too slow to be
observed on the time scale of the CV. Then, the electro-
chemical oxidation of catechols (1) was studied in the
presence of 5-phenyl-1,3,4-oxadiazole-2-thiol (3) as a
nucleophile. Figure 1 (curve II) shows the cyclic vol-
tammogram obtained for a 1 mM 4-methylcatechol (1a)
in the presence of 1 mM 5-phenyl-1,3,4-oxadiazole-2-
thiol (3). The cyclic voltammogram of 1 mM 5-phenyl-
1,3,4-oxadiazole-2-thiol (3) is shown in Figure 1, curve
III, for comparison.
The multicyclic voltammograms of 1a in the presence
of 3 are shown in Figure 2. The voltammograms exhibit
a relatively intense decrease in anodic peak (A1) to-
gether with some potential shift in a positive direction.
The positive shift of the A1 peak in the presence of 3 is
due to the formation of thin film of product at the sur-
face of the electrode in the experimental condition [22].
Characteristics of the products are shown in Table 1.
It can be observed that when methyl and methoxy
groups are presented in C-3 position, two products are
formed. This could be due to nucleophilic attack at
either the C-4 or C-5 position. Further investigations
RESULTS AND DISCUSSION
The electrochemical oxidation of catechols (1a–d) in
the presence of 5-phenyl-1,3,4-oxadiazole-2-thiol (3)
undergoes a smooth 1:1 addition reaction in water me-
dium at an ambient temperature to produce 5-phenyl-
1,3,4-oxadiazol-2-ylthio-benzene-1,2-diol (4 and 40).
Cyclic voltammetry (CV) of 1 mM 4-methylcatechol
(1a) in water/acetonitrile (95/5) solution containing
C
V
2009 HeteroCorporation

444
A. R. Fakhari, S. S. Hosseiny Davarani, H. Ahmar, K. Hasheminasab, and H. R. Khavasi
Vol 46
Table 1
The electrochemical synthesis of products (4 and 40).
Entry
R1
R2
%Product yielda(4:40)
a
b
c
H
H
Me
H
94
82
Figure 1. Cyclic voltammograms of 1 mM 4-methylcatechol (1a) in
the absence (I) and in the presence (II) of 1 mM 5-phenyl-1,3,4-oxa-
diazole-2-thiol (3) and 1 mM 5-phenyl-1,3,4-oxadiazole-2-thiol (3) in
the absence of 4-methylcatechol (III) at a glassy carbon electrode (1.8
mm diameter), in phosphate buffer (pH 7.2, C ¼ 0.15M); scan rate:
100 mV sꢁ1; room temperature. [Color figure can be viewed in the
online issue, which is available at www.interscience.wiley.com.]
OCH3
CH3
H
H
91 (75:25)
93 (32:68)
d
a Isolated yield.
EXPERIMENTAL
Apparatus and reagents. Cyclic voltammetry was per-
formed using lAutolab potentiostat/galvanostat type III. Prepa-
rative analysis was carried out using an EG&G PAR A Model
174 A potentiostat/galvanostat. The working electrode (WE)
used in the voltammetry experiment was a glassy carbon disc
(1.8 mm diameter), and the platinum wire was used as the
counter electrode (CE). The WE used in macroscale electroly-
sis was an assembly of three carbon rods (8 mm diameter and
4 cm length) and a large platinum gauze (3 ꢀ 3 cm2) consti-
tuted the CE. The WE potentials were measured versus the
Ag|AgCl|KCl (3M) as a reference electrode (all electrodes
were obtained from Azar electrode, Urmia, I. R. Iran). NMR
spectra were recorded on a Bruker DRx-300 Avance Instru-
ments. IR spectra were recorded on a Bruker IFS-66 FTIR
Spectrophotometer. Mass spectra were obtained using a QP-
1100EX Shimadzu GC-MS (EI at 70 eV). Melting points of
the products were obtained using an electrothermal melting
point model 9200.
1
confirmed the suggestion using H NMR results and sin-
gle crystal X-ray diffraction analysis (Fig. 3).
The percentage of each isomer was calculated from the
1H NMR spectrum according to the intensity of peaks
that are observed in both aliphatic and aromatic regions.
These voltammetry and spectral results allowed us to
propose an EC mechanism [23] for the electrooxidation
of catechols in the presence of 5-phenyl-1,3,4-oxadia-
zole-2-thiol (Scheme 1).
Chemicals (catechol, 3-methoxycatechol, 4-methylcatechol,
and 5-phenyl-1,3,4-oxadiazole-2-thiol) were reagent-grade, and
phosphate salts were of pro-analysis grade from E. Merck and
Figure 2. Multicycle voltammograms of 1 mM 4-methylcatechol (1a)
in the presence of 5-phenyl-1,3,4-oxadiazole-2-thiol (3), at glassy car-
bon electrode (1.8 mm diameter) in water/acetonitrile (95/5) containing
of phosphates (KH2PO4/K2HPO4) as the buffer and supporting electro-
lyte (pH 7.2, C ¼ 0.15M), scan rate: 100 mV sꢁ1; room temperature.
[Color figure can be viewed in the online issue, which is available at
www.interscience.wiley.com.]
Figure 3. ORTEP structure of 40d. [Color figure can be viewed in the
online issue, which is available at www.interscience.wiley.com.]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2009
A Facile Electrochemical Method for the Synthesis of 5-Phenyl-1,3,4-oxadiazol-
2-ylthio-benzene-1,2-diol Derivatives
445
Scheme 1. Proposed mechanism for the electrooxidation of catechols in the presence of 5-phenyl-1,3,4-oxadiazole-2-thiol (3). [Color figure can be
viewed in the online issue, which is available at www.interscience.wiley.com.]
3
3-methylcatechol was reagent-grade from Acros. These chemi-
cals were used without further purification. All experiments
were carried out at room temperature.
3.74 (s, 3H, OCH3), 3.78 (s, 3H, OCH3), 6.68 (d, JHH ¼ 8.40
Hz, 1H, CH), 6.80 (s, 1H, CH), 6.83 (s, 1H, CH), 6.98 (d,
3JHH ¼ 8.40 Hz, 1H, CH), 7.56 (m, 6H, CH), 7.87 (m, 4H,
CH), 9.34 (broad, 4H, OH). 13C NMR (75 MHz, DMSO-d6) d
(ppm): 56.59, 61.00, 108.67, 110.03, 112.28, 113.76, 115.55,
123.42, 125.69, 126.72, 126.80, 129.91, 132.56, 137.03,
139.92, 146.91, 149.27, 150.32, 163.66, 165.62, 165.91. MS
(70 eV) m/z (relative intensity): 317 (20), 178 (40), 140 (100),
97 (50), 77 (75), 43 (60).
Electroorganic synthesis of products. In a typical proce-
dure, 100 mL mixture of water/acetonitrile (95/5) containing
phosphates (KH2PO4/K2HPO4) as the buffer and supporting
electrolyte (pH 7.2, C ¼ 0.15M) was preelectrolyzed at the
potential mentioned in Table 2 in an undivided cell. Subse-
quently, 2 mmol of catechols (1a–d) and 2 mmol of nucleo-
phile (3) were added to the cell. Finally, the electrolysis was
performed at the same potential.
The electrolysis was terminated when the decay of the current
became more than 95%. The process was interrupted several
times during the electrolysis and the carbon anode was washed
in acetone to reactivate it. At the end of electrolysis, the cell was
placed in a refrigerator overnight. The precipitated solid was col-
lected by filtration and then was washed several times with dis-
tilled water. After purification, products were characterized using
IR, 1H NMR, 13C NMR, X-ray, and Mass spectral data.
5-(5-Phenyl-1,3,4-oxadiazol-2-ylthio)-3-methylbenzene-1,2-
diol (4d). m.p. 180–181ꢂC. IR (KBr) m (cmꢁ1): 3062, 2924,
1591, 1550, 1514, 1471, 1414, 1349, 1266, 1189. 1H NMR
(300 MHz, DMSO-d6) d (ppm): 2.12 (s, 3H, CH3), 6.94 (br s,
2H, CH), 7.59 (m, 3H, CH), 7.88 (m, 2H, CH), 8.91 (broad,
1H, OH), 9.77 (broad, 1H, OH). 13C NMR (75 MHz, DMSO-
d6) d (ppm):16.26, 113.40, 118.94, 123.42, 126.50, 126.84,
127.77, 129.94, 132.59, 146.08, 146.28, 163.88, 165.90. MS
(70 eV) m/z (relative intensity): 300 (30), 178 (32), 145 (75),
124 (36), 77 (100), 51 (48).
Characteristics of the products. 4-(5-Phenyl-1,3,4-oxa-
diazol-2-ylthio)-5-methylbenzene-1,2-diol (4a). m.p. 205–
207ꢂC. IR (KBr) m (cmꢁ1): 3443, 2924, 1709, 1608, 1583,
4-(5-Phenyl-1,3,4-oxadiazol-2-ylthio)-3-methylbenzene-1,2-
diol (40d). m.p.178–180ꢂC. IR (KBr) m (cmꢁ1): 3077, 2660,
1608, 1552, 1479, 1353, 1290, 1213, 1178. 1H NMR (300
1
3
1555, 1472, 1420, 1364, 1292, 1224, 1197. H NMR (300 MHz,
MHz, DMSO-d6) d (ppm): 2.28 (s, 3H, CH3), 6.75 (d, JHH
¼
3
DMSO-d6) d (ppm): 2.29 (s, 3H, CH3), 6.81 (s, 1H, CH), 7.07
(s, 1H, CH), 7.58 (m, 3H, CH), 7.87 (m, 2H, CH), 9.42 (broad,
2H, OH). 13C NMR (75 MHz, DMSO-d6) d (ppm): 20.08,
113.00, 118.55, 123.08, 123.43, 126.76, 129.90, 132.50, 133.80,
144.55, 148.63, 163.71, 165.76. MS (70 eV) m/z (relative inten-
sity): 301 (5), 178 (30), 145 (30), 124 (63), 77 (100), 39 (60).
4-(5-Phenyl-1,3,4-oxadiazol-2-ylthio)benzene-1,2-diol (4b).
m.p. 164–166ꢂC. IR (KBr) m (cmꢁ1): 3447, 2924, 1603, 1550,
1477, 1434, 1358, 1277, 1253, 1187, 1150. 1H NMR (300
8.29 Hz, 1H, CH), 7.07 (d, JHH ¼ 8.29 Hz, 1H, CH), 7.56
(m, 3H, CH), 7.87 (m, 2H, CH), 8.74 (broad, 1H, OH), 9.98
(brod, 1H, OH). 13C NMR (75 MHz, DMSO-d6) d (ppm):
14.52, 113.83, 114.46, 126.82, 127.83, 129.62, 132.47, 132.56,
144.95, 148.22, 165.67, 165.89. MS (70 eV) m/z (relative
intensity): 300 (22), 178 (38), 124 (42), 77 (100), 39 (43).
Crystal data for (40d) C15H12N2O3S1, Mw ¼ 300.34: space
˚
group monoclinic, P21/a, a ¼ 8.3924(6) A, b ¼ 18.4381(15)
ꢁ3
˚
ꢂ
˚
˚
A, c ¼ 9.7245(6) A, b ¼ 111.713(5) , V ¼ 1398.00(17) A
:
3
MHz, DMSO-d6) d (ppm): 6.84 (d, JHH ¼ 8.22 Hz, 1H, CH),
3
7.01 (d, JHH ¼ 8.22 Hz, 1H, CH), 7.07 (s, 1H, CH), 7.57 (m,
3H, CH), 7.88 (m, 2H, CH), 9.62 (broad, 2H, OH). 13C NMR
(75 MHz, DMSO-d6) d (ppm): 114.21, 117.10, 121.64, 123.40,
126.51, 126.81, 129.91, 132.57, 146.76, 148.34, 163.83,
165.88. MS (70 eV) m/z (relative intensity): 287 (10), 178
(55), 145 (30), 110 (70), 77 (100), 51 (55).
Table 2
Applied potentials for the synthesis of products.
Applied potential (V) vs.
Ag|AgCl|KCl (3M)
Conversion
Mixture of 5-(5-phenyl-1,3,4-oxadiazol-2-ylthio)-3-meth-
oxybenzene-1,2-diol (4c) 4-(5-phenyl-1,3,4-oxadiazol-2-yl-
thio)-3-methoxybenzene-1,2-diol (40c). m.p. 175–178ꢂC. IR
(KBr) m (cmꢁ1): 3367, 2937, 1600, 1551, 1503, 1472, 1341,
1293, 1196, 1088. 1H NMR (300 MHz, DMSO-d6) d (ppm):
1a ! 4a
0.15
0.2
1b ! 4b
1c ! (4c:40c)
1d ! (4d:40d)
0.10
0.15
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

446
A. R. Fakhari, S. S. Hosseiny Davarani, H. Ahmar, K. Hasheminasab, and H. R. Khavasi
Vol 46
Z ¼ 4, Dc ¼ 1.427 mg/m3: F(000) ¼ 624, crystal size ¼ 0.20
mm ꢀ 0.16 mm ꢀ 0.12 mm, radiation Mo Ka (k ¼ 0.71073
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ꢂ
ꢂ
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was solved by direct methods [24] and refined an F2 by full-
matrix least squares using the X-STEP32 program package
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Acknowledgment. Financial support from the research affairs of
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet