Electrochemical oxidation of catechols in the presence of pyrimidine-2-thiol: Application to electrosynthesis

Article abstract of DOI:10.1080/10426500802591614

The electrooxidation of catechols (1a-d) in the presence of pyrimidine-2-thiol (3) as a nucleophile in aqueous solution is described. The mechanistic investigations using cyclic voltammetry and controlled potential coulometry indicate that the quinone der

Full text of DOI:10.1080/10426500802591614

This article was downloaded by: [University of Connecticut]
On: 14 August 2013, At: 12:37
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Electrochemical Oxidation of
Catechols in the Presence of
Pyrimidine-2-thiol: Application
to Electrosynthesis
Lida Fotouhi a , Ladan Behrozi a , Majid M. Heravi a
& Davood Nematollahi b
a Department of Chemistry, School of Science,
Alzahra University, Tehran, Iran
b Department of Chemistry, Faculty of Science, Bu-
Ali-Sina University, Hamadan, Iran
Published online: 21 Sep 2009.
To cite this article: Lida Fotouhi , Ladan Behrozi , Majid M. Heravi & Davood
Nematollahi (2009) Electrochemical Oxidation of Catechols in the Presence of
Pyrimidine-2-thiol: Application to Electrosynthesis, Phosphorus, Sulfur, and Silicon and
the Related Elements, 184:10, 2749-2757, DOI: 10.1080/10426500802591614
To link to this article: http://dx.doi.org/10.1080/10426500802591614
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with

primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 184:2749–2757, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802591614
Electrochemical Oxidation of Catechols in the Presence
of Pyrimidine-2-thiol: Application to Electrosynthesis
Lida Fotouhi,1 Ladan Behrozi,1 Majid M. Heravi,1 and
Davood Nematollahi2
1Department of Chemistry, School of Science, Alzahra University,
Tehran, Iran
2Department of Chemistry, Faculty of Science, Bu-Ali-Sina University,
Hamadan, Iran
The electrooxidation of catechols (1a–d) in the presence of pyrimidine-2-thiol (3)
as a nucleophile in aqueous solution is described. The mechanistic investigations
using cyclic voltammetry and controlled potential coulometry indicate that the
quinone derived from catechols participates in a Michael addition reaction with
pyrimidine-2-thiol to form corresponding catechol derivatives of 6a–d (ECEC). The
efficient electrosynthesis of 6a–d has been performed at carbon rod electrodes in an
undivided cell in good yield and purity.
Keywords Catechol; cyclic voltammetry; electrosynthesis; Michael addition; oxidation
INTRODUCTION
The importance of catechols due to the presence of an ortho- or para-
quinone ring as a reactive center of electron transfer in the structure
of many natural compounds1 and biological materials2 caused many
researchers to synthesize a number of catechol derivatives.3–6 Many
researchers have shown that ortho- and para-diphenols can be oxi-
dized electrochemically to o- and p-quinones, which are quite reactive
and can be attacked by a variety of nucleophiles.7–11 In this direction,
the electrosynthesis of various catechol derivatives such as coumes-
tan,12 benzofuran,13 arylsulfonylbenzenediol,14 pyrimidine,15 and thio
derivatives16–19 have been reported. Indeed, in all of these investiga-
tions, attention was focused on both elucidation of the electron transfer
Received 25 August 2008; accepted 22 October 2008.
The authors gratefully acknowledge partial financial support from the Research Coun-
cil of Al-Zahra University.
Address correspondence to Lida Fotouhi, Department of Chemistry, School of Science,
Alzahra University, P.O. Box 1993891176, Tehran, Iran. E-mail: lfotouhi@alzahra.ac.ir
2749

2750
L. Fotouhi et al.
mechanism and proposal of an electrochemical route to led to the syn-
thesis of compounds containing ortho- or para-quinone rings in their
framework.20
The purpose of the work, in continuation of our interest in the
electrochemistry of organic compounds,21 is to investigate the electro-
oxidation of catechols in the presence of pyrimidine-2-thiol as a nucle-
ophile. The study is based mainly on the cyclic voltammogram patterns
of catechol in water on a glassy carbon electrode. We have also de-
scribed a facile and efficient electrochemical method for the synthesis
of some new pyrimidin-2-ylthio derivatives. A mechanism also proposed
for electrode reactions and the effect of various parameters on the ad-
vancement of the electrode process is described.
EXPERIMENTAL
Apparatus
Cyclic voltammetry (CV) was performed using a Metrohm Comput-
erized Voltammetric analyzer model 746 VA connected to a 747 VA
stand. Controlled-potential coulometry and preparative analysis were
performed using a potentiostat/galvanostat system model BHP 2061-C.
The working electrode (WE) used in the voltammetry experiment was
a glassy carbon disc (1.8 mm diameter), and platinum wire was used as
the counter electrode (CE). The WE used in controlled-potential coulom-
etry and macroscale electrolysis was an assembly of three graphite rods
(8 mm diameter and 4 cm length) and a large platinum gauze consti-
tuted the CE. The WE potentials were measured versus the 3M Ag/AgCl
reference electrode (all electrodes were obtained from Metrohm). All ex-
periments were carried out at room temperature.
1H NMR and 13C NMR spectra were recorded on a Bruker Avance
DRX500 (500 MHz) spectrometer. TLC was carried out on alumina
sheets precoated with silica gel 60 F 254 (Merck), and spots were visu-

Electrochemical Oxidation of Catechols
2751
alized with UV light. IR spectra were recorded on a Tensor 27 model
HIO23502 FT IR spectrometer. Mass spectra were obtained using Agi-
lent Technologies 6890 N Network GC system.
Chemicals
All chemical reagents were of pro-analysis grade from Merck and
Flucka. These materials were used without further purification.
RESULTS AND DISCUSSIONS
The cyclic voltammogram of a 1 mM solution of catechol (1a) in phos-
phate buffer solution (c = 0.2 M, pH = 7.2) shows one anodic (A1) and a
corresponding cathodic (C1) due to the transformation of catechol (1a)
to o-benzoquinone (2a) and vice-versa within a quasi-reversible, two-
A1
electrons process (Figure 1, curve a). The peak current ratio (IpC1/Ip
)
of near unity, particularly in the repetitive recycling of potential, is a
good indication of the stability of o-quinone to participitating in hy-
droxylation or dimerization side reactions.22,23 As is shown in Figure 1
(curve b), the presence of 3 as a nucleophile causes an anodic potential
shift with increasing the anodic current of peak A1, while the cathodic
counterpart (C1) of the anodic peak A1 disappears. The positive shift of
the A1 peak in the presence of 3, which is enhanced during the repet-
itive recycling of potential, is probably due to the formation of a thin
film of product at the surface of the electrode inhibiting to a certain
extent the performance of the electrode process.7–11 In Figure 1, curve
c is the voltammogram of 3, which is inactive in this potential range.
The cyclic voltammograms of catechol 1a in the presence of 3 at vari-
ous scan rates are shown in Figure 2. It is seen that, proportional to the
augmentation of potential sweep rate, the height of the cathodic (C1)
peak of 1a increases. A similar situation is also observed when the 3 to
1a concentration ratio is decreased. On the other hand, the decreasing
current function and increasing current ratio IpC1/IpA1 are a good indi-
cation of the reactivity of 3 toward 1a in a following coupled chemical
reaction (ECE). The appearance of an additional cathodic peak C0 at
high scan rate can be related to the formation of some polymeric species
as final products.24 For further mechanistic studies, the controlled po-
tential coulometry was performed in phosphate buffer solution includ-
ing 0.1 mmol 1a and 0.2 mmol 3 at 0.22 V versus Ag/AgCl electrode.
The coulometric results show the charge consumption of about 4e per
molecule of 1a. These observations allow us to propose the pathway in
Scheme 1 for electro-oxidation of 1a in the presence of 3.

2752
L. Fotouhi et al.
FIGURE 1 Cyclic voltammograms of 1 mM aqueous catechol 1a: (a) in the
absence, (b) in the presence of 1 mM pyrimidine-2-thiol 3, (c) 1 mM pyrimidine-
2-thiol 3 in the absence of catechol 1a at the glassy carbon electrode in aqueous
phosphate buffer (c = 0.2 M, pH = 7.2), scan rate: 100 mVs−1
.
According to the obtained results, it seems that 3 participates in a
1,4-Michael addition reaction with o-quinone (2a) (reaction 2) resulting
intermediate 4a. The oxidation of this compound (4a) is easier than
the oxidation of the parent starting molecule by virtue of the presence
of electro-donating group. Like o-quinone 1a, o-quinone 5a can also be
attacked from the C-5 position by 3 to form the final production 6a. The
overoxidation of 6a was circumvented during the preparative reaction
FIGURE 2 Typical voltammograms of 1 mM aqueous catechol 1a in the pres-
ence of pyrimidine-2-thiol 3 at the glassy carbon electrode, in phosphate buffer
(c = 0.2 M, pH = 7.2), scan rates: 20, 40, 60, 80, 100, 200, 300, 400, 500, 600
mVs−1. Inset: variation of peak current ratio (IpC1/IpA1) versus scan rate.

Electrochemical Oxidation of Catechols
2753
SCHEME 1
because of the insolubility of the product in phosphate buffer solution
1
media. The H-NMR spectrum of 6a shows as a symmetric structure.
The two aromatic protons of catechol appeared as a singlet, which
confirms that the product of 6a is 4,5-bis(pyrimidin-2-ylthio)benzene-
1,2-diol rather than another symmetric structure of 3,6-bis(pyrimidin-
2-ylthio)benzene-1,2-diol (Scheme 1).
Electrosynthesis of 6b–d
The first step of electro-oxidation of 1b-d in the presence of 3 as a nucle-
ophile in buffer solution proceeds in a way similar to that of 1a. In the
all cases the presence of methyl or methoxy groups as electron-donating
substituents on the molecular ring causes a diminution in activity of

2754
L. Fotouhi et al.
SCHEME 2
o-quinones 2b–d as Michael acceptors toward the 1,4-addition reac-
tions. However, the plot of peak current ratio versus scan rate confirms
the reaction between o-quinones 2b–d and 3, appearing as an increase
in peak current ratio, IpC1/IpA1 with increasing scan rate.
After formation of o-quinone 5b,c via 1,4-(Michael) addition reac-
tion7–19 and oxidation, it can be attacked by the 3 from C-4 or C-6,
to yield two types of products (6b,c and 7b,c) (Scheme 2). However,
thin-layer chromatographic (TLC) results indicate the formation of one
component in electrooxidation of 1b,c in the presence of 3.
The steric energy has been calculated for 6b,c and 7b,c, using the
MM2 program after minimization of structures (Table I).25 Results in-
dicate that structures 6b, c are energically more stable than the 7b,c.

Electrochemical Oxidation of Catechols
2755
TABLE I Calculated Steric Energy by MM2
Program
Entry
Steric Energy (kcal/mol)
6b
7b
6c
7c
6d
7d
9.31
9.66
9.72
16.83
8.51
9.70
Therefore, because of less steric energy (about 0.35 and 7.11 kcal/mol
for 6b and 6c, respectively) we think that o-quinone 5b,c is attacked
in all probability by the 3 from C-6 (path I, Scheme 2), leading to the
formation of the products 6b,c.
The existence of methyl group at C-4 position of o-quinone ring (1a)
causes 5d to probably be attacked by 3 from C-3 or C-6 positions to
yield two types of products. As it can been seen from Table I, 6d is the
final product (path II, Scheme 2).
Data for 6a (C14H10N4O2S2)
Mp >300◦C, yield 74%. IR (KBr) υ (cm−1): 3416 (-Hstr.), 2925, 1557,
1379, 1290, 1182, 985, 863; 1HNMR (TMS) δppm: 5.97 (s, 2H, catechol),
7.14 (t, 2H, pyrimidine-2-thiol), 8.62 (d, 4H, pyrimidine-2-thiol), 9.01
(b, 2H, hydroxy); MS (EI) m/e (relative intensity): 330 [M+.] (20), 313
(75), 297 (90), 279 (24), 258 (52), 219 (26), 190 (29), 132 (44), 79 (75), 53
(85).
Data for 6b (C15H12N4O2S2)
Mp >300◦C, yield 72%. IR (KBr) υ (cm−1): 3325 (-OHstr.), 3121, 2924,
1587, 1490, 1380, 1283, 1190, 1034, 851; 1HNMR (TMS) δppm: 2.21 (s,
3H, methyl), 7.09 (s, 1H, catechol), 7.15 (t, 2H, pyrimidine-2-thiol), 8.51
(d, 4H, pyrimidine-2-thiol); MS (EI) m/e (relative intensity): 344 [M+.]
(12), 311 (20), 295 (8), 233 (85), 217 (12), 186 (8), 112 (8), 79 (12), 53
(20).
Data for 6c (C15H12N4O3S2)
Mp >300◦C, yield 81%. IR (KBr) υ (cm−1): 3416 (-OHstr.), 3065, 2931,
1602, 1559, 1505, 1378, 1311, 1181, 958; 1HNMR (TMS) δppm: 2.48 (s,
3H, methoxy), 6.65 (s, 1H, catechol), 7.17 (t, 2H, pyrimidine-2-thiol),
8.56 (d, 4H, pyrimidine-2-thiol), 8.56 (b, 2H, hydroxy); MS (EI) m/e

2756
L. Fotouhi et al.
(relative intensity): 360 [M+.] (8), 329 [M-OCH3] (11), 249 (100), 234
(25), 189 (15), 113 (18), 79 (25), 53 (50).
Data for 6d (C15H12N4O2S2)
Mp>300◦C, yield 76%. IR (KBr) υ (cm−1): 3416 (-OHstr.), 1563, 1409,
1380, 1303, 1186, 1036, 808; 1HNMR (TMS) δppm: 2.35 (s, 3H, methyl),
5.98 (s, 1H, catechol), 7.5 (t, 2H, pyrimidine-2-thiol), 8.45 (d, 4H,
pyrimidine-2-thiol) ; MS (EI) m/e (relative intensity): 344[M+.] (8), 327
(6), 310 (12), 296 (14), 279 (30), 233 (44), 214 (28), 201 (74), 183 (10),
155 (26), 112 (34), 79 (42), 53 (84).
CONCLUSION
The results of this work show that catechols are oxidized to their re-
spective o-quinones. The quinones are then attacked by 3. Final prod-
ucts are obtained via an EC mechanism, after consumption of 4e per
molecule of catechols (1a–d).
REFERENCES
[1] R. H. Thomson, Naturally Occurring Quinones, 3rd ed. (Chapman and Hall, London,
1987).
[2] K. Hostettmann and I. P. Lea, Biologically Active Natural Products (Oxford Univer-
sity Press, Oxford, UK, 1988).
[3] S. M. Golabi and D. Nematollahi, J. Pharm. Biomed. Anal., 10, 1053 (1992).
[4] D. Nematollahi and M. Hesari, J. Electroanal. Chem., 577, 197 (2005).
[5] S. A. Petrova, M. V. Kolodyazhny, and O. S. Ksenzhek, J. Electroanal. Chem., 277,
189 (1990).
[6] A. Desbenemonvernay, P. C. Lacaze, and A. Cherigui, J. Electroanal. Chem., 260,
75 (1989).
[7] D. Nematollahi and S. M. Golabi, J. Electroanal. Chem., 481, 208 (2000).
[8] D. Nematollahi and S. M. Golabi, Electroanalysis, 13, 1008 (2001).
[9] Z. Grujic, I. Tabakovic, and M. Trkovnik, Tetrahedron Lett., 52, 4823 (1976).
[10] D. Nematollahi and Z. Forooghi, Tetrahedron, 58, 4949 (2002).
[11] I. Tabakovic, Z. Grujic, and Z. Bejtovic, J. Heterocyc. Chem., 20, 635 (1983).
[12] D. Nematollahi and M. Rafiee, Green Chem., 7, 638 (2005).
[13] D. Nematollahi and E. Tammari, J. Org. Chem., 67, 5036 (2002).
[14] D. Nematollahi, R. Rahchamani, and M. Malekzadeh, Synth. Commun., 13, 2269
(2003).
[15] D. Nematollahi and E. Tammari, J. Org. Chem., 70, 7769 (2005).
[16] L. Fotouhi, M. Mosavi, M. M. Heravi, and D. Nematollahi, Tetrahedron Lett., 47,
8553 (2006).
[17] L. Fotouhi, D. Nematollahi, M. M. Heravi, and E. Tammari, Tetrahedron Lett., 47,
1713 (2006).
[18] D. Nematollahi, D. Habibi, M. Rahmati, and M. Rafiee, J. Org. Chem., 69, 2637
(2004).

Electrochemical Oxidation of Catechols
2757
[19] L. Fotouhi, S. Taghavi Kiani, M. M. Heravi, and D. Nematollahi, Inter. J. Chem.
Kint., 39, 340 (2007).
[20] J. Y. Becker, and T. A. Koch, Electrochim. Acta, 38, 357 (1993).
[21] L. Fotouhi, M. Zeienali, S. Dehghanpour, and D. Nematollahi, Chin. J. Chem., 25,
1577 (2007).
[22] T. E. Young, J. R. Griswold, and M. H. Hulbert, J. Org. Chem., 39, 1980 (1974).
[23] M. D. Ryan, A. Yueh, and C. Wen-Yu, J. Electrochem. Soc., 127, 1489 (1980).
[24] J. Davis, D. H. Vaughan, and M. F. Cardosi, Electrochim. Acta, 43, 291 (1998).
[25] CS ChemDraw Ultra, Version 8.0, CambridgeSoft Corporation, Cambridge, MA,
USA.