Redox properties and radical anions of 2-substituted thioxanthen-9-ones and their 2-methyl S-oxide derivatives

Article abstract of DOI:10.1016/j.mencom.2013.11.010

The electrochemical reduction of 2-substituted thioxanthen-9-ones in MeCN is a one-electron process with the formation of long-lived radical anions, in which the thioxanthen-9-one fragment is planar according to EPR measurements and UB3LYP/6-31+G* calculations. The electrochemical reduction of 2-methylthioxanthen-9-one sulfoxide and sulfone are EEC and EE processes, respectively, their radical anions are not planar, and the electrochemical oxidation of the title compounds is irreversible with consecutive oxidation of the sulfur atom, except for the sulfone, whose oxidation was not observed at the limit of the anodic potential (2.5 V vs. s.c.e.).

Full text of DOI:10.1016/j.mencom.2013.11.010

Mendeleev
Communications
Mendeleev Commun., 2013, 23, 334–336
Redox properties and radical anions of 2-substituted
thioxanthen-9-ones and their 2-methyl S-oxide derivatives
Nadezhda V. Vasilieva, Irina G. Irtegova, Vladimir A. Loskutov and Leonid A. Shundrin*
N. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences,
630090 Novosibirsk, Russian Federation. Fax: +7 383 330 9752; e-mail: shundrin@nioch.nsc.ru
DOI: 10.1016/j.mencom.2013.11.010
The electrochemical reduction of 2-substituted thioxanthen-9-ones in MeCN is a one-electron process with the formation of long-lived
radical anions, in which the thioxanthen-9-one fragment is planar according to EPR measurements and UB3LYP/6-31+G* calculations.
The electrochemical reduction of 2-methylthioxanthen-9-one sulfoxide and sulfone are EEC and EE processes, respectively, their
radical anions are not planar, and the electrochemical oxidation of the title compounds is irreversible with consecutive oxidation of the
sulfur atom, except for the sulfone, whose oxidation was not observed at the limit of the anodic potential (2.5 V vs. s.c.e.).
The derivatives of thioxanthen-9-ones (thioxanthones) are used
as efficient photoinitiators for free radical polymerization1 and as
photogenerators for detrilation in oligonucleotide microarray
synthesis.2,3 Thioxanthone derivatives possess a biological activity
inhibiting the multidrug efflux pump activity in Staphylococcus,4
and they are used for the treatment of infectious diseases.5 On
the other hand, thioxanthones and their S-oxides can be reduced
by a one-electron transfer mechanism to form long-lived radical
anions (RAs),6,7 i.e., these compounds can be considered as
substances with the active electron transport function in living
organisms. The potentials of electrochemical reduction (ECR)
and electrochemical oxidation (ECO) of thioxantone and related
compounds in MeCN and other solvents have been described,8–10
and a good correspondence between experimental potentials and
LUMO/HOMO energies of thioxanthones calculated by semi-
empirical,9 ab initio Hartree–Fock and DFT methods12,13 has
been demonstrated. The EPR spectra of the RAs of unsubstituted
thioxanthone and corresponding sulfoxide and sulfone have been
obtained.6,7 Nevertheless, the RAs of substituted thioxanthone
and its S-oxides have not been described correctly, and the
mechanisms of ECR and ECO of thioxanthone sulfoxide and
its derivatives in aprotic solvents have not been studied. In the
proposed earlier scheme of two-electron ECO of thioxanthone
the first oxidative peak only for potential scan limit up +2.0 V
was described,9 whereas the subsequent steps of ECO at more
positive potentials were not considered. To make up this defi-
ciency we studied redox properties and RAs of 2-substituted
thioxanthones, 2-methylthioxanthone sulfoxide and 2-methylthio-
xanthone sulfone in MeCN† by cyclic voltammetry and EPR
spectroscopy.
O
Me
O
R
9
1
4
8
5
O
7
6
2
3
S
10
S
Me
O
2
1a R = H
1b R = Cl
1c R = C(O)Pri
1d R = Me
S
O
O
3
Ip1A/Ip1C ≈ 0.8–0.9 (1a–c), n = 0.1 V s–1]§ within the potential
sweep range 0 > E > –2.0 V. Corresponding peak potentials are
listed in Table S1 (see Online Supplementary Materials). Cyclic
voltammogram (CV) of 2 is characterized by two reduction peaks
(1C, 2C) in the same potential sweep range [Figure 1(b)], the
peak current ratio Ip1A/Ip1C = 0.23 at n = 0.1 V s–1 within the above
potential sweep. CV wave 1C–1A becomes completely reversible
(Ep1A–Ep1C = 0.06 V, Ip1A/Ip1C = 1.0), if the potential sweep range
does not reach Ep2C (0.0 > E > –1.6 V) [Figure 1(b)]. The first
one-electron peak (1C) corresponds to the formation of RA 2 in
accordance with EPR data¶ [Figure 2(b)]. CVs of 2 measured at
different potential scan rates§ demonstrated that peak 2C corre-
sponds to the formation of dianion (DA) 2 with the subsequent
protonation and the formation of 1d as a result. The latter was
proved by CV of 2 in the range of potential sweep involving both
reduction and oxidation processes because a minor irreversible
oxidative peak [1A'(Ox), Ep1A'(Ox) = 1.62 V] corresponding to the
ECO of 1d was observed in the anodic branch of CV. This peak
was not observed if the potential sweep did not cover second
reduction peak 2C [Figure 1(c)]. The EPR measurements¶ of
paramagnetic species obtained under ECR of 2 at the potential of
The ECR‡ of 1a–d is characterized by one electron reversible
[Figure 1(a), 1d] or quasi-reversible peak [Ep1A – Ep1C = 0.06 V,
†
Compounds 1a,c,d, 2, 3 were prepared as described elsewhere,13,14
not been taken into account for the peak potentials presented in Table S1.
Reduction peaks are diffusion controlled for 1–3, i.e., Ip1Cn–0.5 = const,
where Ip1C is the peak current. Digital simulation of the CV of 1d in
oxidative potentials area was done using electrochemical simulation Package
(ESP, v.2.4) designed by Carlo Nervi, Università di Torino, Italy. Simplex
algorithm was used for multiparametric optimization implemented in the
package. Digital simulation of the CV of 1d [Figure 1(b)] is shifted for
–50 mA for better clearness.
commercial 1b from Aldrich was used.
‡
The CV measurements of 1–3 (2.0 mm solutions) were performed at
298 K in an argon atmosphere in MeCN purified by a standard procedure
(MeCN was distilled from KMnO4 and twice from P2O5, the residual
water content was 5 mm) at a stationary Pt disk electrode (S = 0.08 cm2)
with 0.1 m Et4NClO4 as a supporting electrolyte with potential sweep
rates of 0.1 < n < 1.2V s–1.A PG 310 USB potentiostat (HEKA Elektronik
GmbH, Germany) was used for CV measurements. A standard electro-
chemical cell (solution volume of 5 ml) connected to the potentiostat
with a three-electrode scheme was used. Peak potentials are quoted with
reference to a saturated calomel electrode (s.c.e). iR compensation has
§
For CV of 1a–c, CV of 2 at various n, the EPR spectra of RAs 1a–c,
digital simulation details for CV of 1d in oxidative potentials area, dis-
cussion about disproportionation mechanism of the ECO of 2, see Online
Supplementary Materials.
© 2013 Mendeleev Communications. All rights reserved.
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Mendeleev Commun., 2013, 23, 334–336
(a)
(b)
–100
–50
0
2C
1C
–100
–50
0
–50
2C'
3
–100
–50
0
1C'
1C
2
0
2
2C'
3
1A
50
2A
1
50
1
1A
50
100
150
1A(Ox)
50
1A(Ox)
100
2A(Ox)
100
–2
–1
0
1
2
–2
–1
0
1
2
E/V
E/V
1C
–100
–50
0
(c)
(d)
–200
–100
0
2C
2A
1
–100
0
2C'
2C
2A
3C
1C
3
1
2
100
200
2
1A'(Ox)
1A(Ox)
3A
1A
–1
100
200
1A
–1
50
–2
0
1
2
–2
0
1
2
E/V
E/V
Figure 1 (a) CV of 1d (2.0 mm) in MeCN (n = 0.1 V s–1) within potential sweep regions (1) 0.0 > E > –2.0 V, (2) –1.4 < E < 2.5 V and (3) digital simulation
of the CV of 1d in oxidative potentials area. (b) CV of 2 in MeCN (n = 0.1 V s–1) within potential sweep regions (1) 0.0 > E > –1.6 V, (2) 0.0 > E > –1.9 V
and (3) 0.0 < E < 2.3 V. (c) CV of 2 (n = 0.5 V s–1) within wide potential sweep cycle E: (1) 0.0 ® –1.6 ® 2.3 ® 0.0 V, (2) 0.0 ® –1.9 ® 2.3 ® 0.0 V, and
(3) 0.0 ® 2.3 ® –1.6 ® 0.0 V. (d) CV of 3 in MeCN (n = 0.1 V s–1) within potential sweep regions (1) 0.0 > E > –2.0 V and (2) 0.0 < E < 2.5 V.
2C peak verified the formation of 1d at the second step of ECR
because a mixed EPR spectrum from RAs 2 and 1d (10 and 90%
of the total ERP signal intensity, respectively) was observed
[Figure 2(c)]. The total current of peak 2C includes the
dominating contribution from ECR of 2 to DA 2 and a minor
contribution from one-electron ECR of 1d because the latter
process is characterized by a potential close to the potential of
peak 2C [Figure 1(a),(b), Table S1]. As a result, peak current ratio
Ip2C/Ip1C = 1.38 at n = 0.1 V s–1 [Figure 1(b)] and tends to 1 when
n is increased.§ The ECR of 3 is an EE process with two well
separated one-electron and diffusion-controlled peaks correspond-
ing to the formation of RA and DA of 3, respectively [Figure 1(d)].
The RAs of 1–3 were obtained by the one-electron ECR of
neutral precursors in MeCN (Figure 2).§ The corresponding hyper-
group with a smaller contribution from carbon atoms in the 1-, 3-,
6- and 8-positions of RAs 1d, 2, 3 (Figure 3). The largest HFCCs
are related to the protons in the above positions for all of the test
RAs, and the presence of SO and SO2 groups in RA 2, 3 leads to
a decrease in HFCC with 1H nuclei in these positions (Table S2).
(a)
(b)
1
1
2
2
1
fine coupling constants (HFCC) with H nuclei are in a good
agreement with those calculated by the UB3LYP/6-31+G* method
(Table S2, see Online Supplementary Materials).¶ In accordance
with the calculations, the thioxanthone fragment is planar in
optimized conformations of RAs 1a–d [Figure 3(a)] and their
single occupied molecular orbital (SOMO) is of the p-type. The
presence of oxygen atoms in the 10-position of RAs 2 and 3 leads to
a bending of their structure along the axis O–C(9)–S and pyramidal
structure of sulfoxide and sulfone fragments. The dihedral angles
between aromatic rings are 10.2° and 16.6° in RAs 2 and 3,
respectively [Figure 3(b),(c)], and SOMO is of the pseudo p-type.
Calculated spin density distribution is dominated by the C=O
3475
3485
H/10–4
3495
3475
3485
H/10–4
T
3495
T
(c)
1
¶
The EPR spectra were recorded on a Bruker ELEXSYS E-540 X-band
spectrometer (MW power of 20 mW, modulation frequency of 100 KHz
and modulation amplitude of 0.005 mT). RAs of 1–3 were obtained by
ECR in MeCN under argon atmosphere at 298 K with the standard electro-
chemical cell for EPR measurements. Simulations of the experimental EPR
spectra were performed with the Winsim 2002 program15 (the accuracy in
calculating of HFCC is 0.0001 mT). The quantum-chemical calculations
were performed using the GAMESS suite of programs.16 The geometries
of RAs 1–3 were fully optimized at the UB3LYP/6-31+G* level of theory
for gas phase. The symbols «+» and «–» (Figure 3) indicate the signs of
spin density. Lowding charges at carbon, oxygen and sulfur atoms in
RAs 1–3 are presented in Online Supplementary Materials (Table S3).
2
3475
3485
H/10–4
3495
T
Figure 2 EPR spectra of RAs (a) 1d, (b) 2 and (c) a mixed spectrum of
RAs 1d, 2 (90 and 10% of intensity, respectively) obtained under ECR at
the potential of 2C peak: (1) experimental and (2) simulated spectrum.
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Mendeleev Commun., 2013, 23, 334–336
O
(a)
(b)
(c)
O
O
S
O
S
S
O
O
1
2
1
2
1
2
O
S
10.2°
S
S
16.6°
O
O
+
+
+
+
+
–
+
+
+
–
+
+
–
+
+
–
–
–
–
–
–
–
–
+
+
+
+
+
+
+
+
+
+
+
+
–
+
+
3
3
+
3
+
Figure 3 (1) UB3LYP/6-31+G* geometry, (2) view along O–C(9)–S axis and (3) distribution of spin density in RAs (a) 1d, (b) 2 and (c) 3. The bond lengths
are given in Å.
The ECO of 1a–d is characterized by two or, in some cases,
three§ (Table S1) irreversible peaks [Figure 1(a)] within the poten-
tial sweep range 0 < E < 2.5 V. Digital simulation of the CV of
1d in the potential sweep range 1.0 < E < 2.5 V [Figure 1(a)]
demonstrated that the first irreversible peak is two-electron, and
it corresponds to the formation of 2. As the proof of it, the change
in potential sweep range up to –1.4 < E < 1.8 V results in the
appearance of a one-electron reversible peak (1C') in CV of 1d,
which conforms to the ECR of 2 [Figure 1(a)]. The second
oxidative peak of 1d is noticeably wider than the first one.
According to a simulation, the 2A(Ox) peak in CV of 1d, being
two-electron as a whole, includes two one-electron irreversible
peaks with close potentials corresponding to the consecutive ECO
of 2 up to 3. For this reason, two irreversible oxidative peaks are
observed in the second step of the ECO for compounds 1a,b,§ for
which the total process of ECO is three-step and four-electron.
CV of 2 (0.0 < E < 2.5 V) reveals the only irreversible two-
electron oxidative peak [Figure 1(b)], the potential of which is the
same as the potential of 2A(Ox) peak in the CV of 1d (Table S1).
The expansion of potential sweep to the range covering the oxida-
tion and first reduction steps of 2 (–1.6 < E < 2.3 V) leads to the
superimposed reversible reduction CV waves corresponding to the
one-electron reduction of 3 (3C–3A) and 2 (1C–1A) [Figure 1(c),
curve 3]. Thus, the second ECO stage of 1d and the first stage of
2 correspond to the formation of 3 in agreement with the proposed
earlier common scheme of multielectron ECO for unsubstituted
thioxanthene.9 Note that the ECO of 2 can proceed by a dis-
proportionation mechanism, which is not preferable from the
kinetic point of view.§ No peaks were observed in the CV of 3
within the potential sweep range 0 < E < 2.5 V [Figure 1(d)].
The nature of the reductive peak (2C'), which was detected at the
cathodic branch of CV of 1a–d,§ 2 [Figure 1(a),(b)] is not clear.
This peak was observed but not interpreted earlier in the CV of
unsubstituted thioxanthone.8 Note that the replacement of a
supporting electrolyte by Bu4NBF4 resulted in the absence of
2C' peak from the CV of 1d.
stage four-electron irreversible process with the formation of cor-
responding thioxanthone sulfoxides and sulfones in the potential
sweep range 0 < E < 2.5 V, sulfoxide 2 is oxidized to 3, and 3 is
not oxidized in the above potential sweep range.
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2013.11.010.
References
1 Q. A. Sun, J. T. Wang, L. M. Zhang and M. P. Yang, Acta Phys. Chim.
Sin., 2010, 26, 2481.
2 A. N. Sinyakov, A. A. Ryabinin, G. A. Maksakova, V. V. Shelkovnikov,
V. A. Loskutov, E. V. Vasil’ev and N. V. Shekleina, Russ. J. Bioorg. Chem.,
2010, 36, 130 (Zh. Bioorg. Khim., 2010, 36, 139).
3 V. V. Shelkovnikov, V. A. Loskutov, E. V. Vasil’ev, N. V. Shekleina, V. A.
Ryabinin and A. N. Sinyakov, Russ. Chem. Bull., Int. Ed., 2011, 60, 561
(Izv. Akad Nauk, Ser. Khim., 2011, 548).
4 G. W. Kaatz, V. V. Moudgal, S. M. Seo and J. E. Kristiansen, Antimicrob.
Agents Chemother., 2003, 47, 719.
5 B. K. Giwercman, US Patent 2012/0122880 A1, 2010 (Chem. Abstr.,
2010, 153, 554920).
6 M. M. Urberg and E. T. Kaiser, J. Am. Chem. Soc., 1967, 89, 5179.
7 T. Aruga, O. Ito and M. Matsuda, J. Am. Chem. Soc., 1979, 101, 7585.
8 P. T. Kissinger, P. T. Holt and C. N. Reilley, J. Electroanal. Chem., 1971,
33, 1.
9 E. W. Tsai, L. Throckmorton, R. McKellar, M. Baar, M. Kluba, D. S.
Marynick, K. Rajeshwar and A. L. Ternay, Jr., J. Electroanal. Chem.,
1986, 210, 45.
10 N. V. Vasilieva, I. G. Irtegova, V. A. Loskutov and L. A. Shundrin,
Mendeleev Commun., 2012, 22, 111.
11 K.-D. Kwak, M. L. Seo, K. S. Ha and U.-H. Paek, Bull. Korean Chem.
Soc., 1998, 19, 527.
12 S. Riahi, P. Norouzi, A.B. Moghaddam, M.R. Ganjali, G.R. Karimipour
and H. Shargi, Chem. Phys., 2007, 337, 33.
13 R. Ran and Ch. U. Pittman, Jr., J. Heterocycl. Chem., 1993, 30, 1673.
14 (a) V. A. Loskutov and V. V. Shelkovnikov, Russ. J. Org. Chem., 2006,
42, 298 (Zh. Org. Khim., 2006, 42, 313); (b) V. A. Loskutov and V. V.
Shelkovnikov, Russ. J. Org. Chem., 2009, 45, 158 (Zh. Org. Khim.,
2009, 45, 160).
15 D. R. Duling, J. Magn. Reson., 1994, 104, 105.
Thus, the ECR of thioxanthones 1a–d is characterized by
reversible or quasi-reversible one-electron transfer in the potential
sweep range 0 > E > –2.0 V, whereas the ECR of 2, 3 is a EEC-
or EE-process, respectively. RAs 1a–d have the planar structure
of the thioxanthone fragment, but RAs 2, 3 are not planar with
SOMO of the pseudo-p type. The ECO of 1a–d is two or three
16 M. W. Schmidt, K. K. Baldridge, J. A. Boatz, S. T. Elbert, M. S. Gordon,
J. H. Jensen, S. Koseki, N. Matsunaga, K. A. Nguyen, S. J. Su, T .L.
Windus, M. Dupuis and J. A. Montgomery, J. Comput. Chem., 1993,
14, 1347.
Received: 6th May 2013; Com. 13/4116
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