Dual signaling of m-chloroperbenzoic acid by desulfurization of thiocoumarin

Article abstract of DOI:10.1016/j.tetlet.2010.10.066

The chemosignaling of widely used peracid oxidant of m-chloroperbenzoic acid (mCPBA) by the selective desulfurization of thiocoumarin was investigated. Thiocoumarin was efficiently converted into its corresponding coumarin by the reaction with mCPBA, and resulted in a pronounced fluorescent turn-on type signaling. The conversion also provided a significant change in absorption behavior which allowed a ratiometric analysis. The effective signaling could be used as a convenient determination method for mCPBA in aqueous environment.

Full text of DOI:10.1016/j.tetlet.2010.10.066

Tetrahedron Letters 51 (2010) 6663–6665
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Tetrahedron Letters
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Dual signaling of m-chloroperbenzoic acid by desulfurization of thiocoumarin
⇑
Sunyoung Cha, Jiyoung Hwang, Myung Gil Choi, Suk-Kyu Chang
Department of Chemistry, Chung-Ang University, Seoul 156-756, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
The chemosignaling of widely used peracid oxidant of m-chloroperbenzoic acid (mCPBA) by the selective
desulfurization of thiocoumarin was investigated. Thiocoumarin was efficiently converted into its corre-
sponding coumarin by the reaction with mCPBA, and resulted in a pronounced fluorescent turn-on type
signaling. The conversion also provided a significant change in absorption behavior which allowed a
ratiometric analysis. The effective signaling could be used as a convenient determination method for
mCPBA in aqueous environment.
Received 30 August 2010
Revised 8 October 2010
Accepted 13 October 2010
Available online 20 October 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Selective detection or signaling of various oxidant species is
important in chemical, biological, and industrial processes.1 Re-
cently, considerable research effort has been devoted to the signal-
ing and visualization of biologically important reactive oxygen
species, such as hydrogen peroxide,2 hypochlorous acid,3 peroxyni-
trite,4 and nitric oxide.5 However, convenient signaling systems for
peracid oxidants are scarce, though they are used widely in syn-
thetic organic chemistry.
Treatment of 7-ethoxycoumarin 2 with Lawesson’s reagent
yielded desired thiocoumarin 1 (Scheme 1). A more chromogenic
thiocoumarin derivative 4 was also prepared from coumarin 6
3.15 In 90% aqueous acetonitrile, compounds 1 and 4 appeared yel-
low and red, respectively, with relatively weak emissions due to
the thiocarbonyl function of thiocoumarins.
First, we assayed the chemical resistivity of 7-ethoxycoumarin
2, which is the expected product of mCPBA signaling by the desul-
furization of thiocoumarin 1, toward the mCPBA oxidant. Upon
treatment of ethoxycoumarin 2 with 100 equiv of mCPBA in aque-
ous acetonitrile, the absorption and fluorescence characteristics
were not affected (Figs. S1 and S2, Supplementary data). The 1H
NMR spectrum of 2 in the presence of 2 equiv of mCPBA in deuter-
ated acetonitrile did not change either (Fig. S3, Supplementary
data). These observations suggest that 7-ethoxycoumarin has
chemical resistance to oxidative stress from mCPBA. An attempt
to design more chromogenic system 4, based on coumarin 6 with
a 3-benzothiazolyl substituent, was unsuccessful due to the insuf-
ficient stability of 3 itself toward mCPBA.
Thiocoumarin 1 exhibited a very weak emission around 394 nm
in 90% aqueous acetonitrile solution. Upon treatment with increas-
ing amount of mCPBA, a steady fluorescence enhancement at
394 nm was observed (Fig. 1). The enhancement was over 120-fold
and the solution changed from dark to blue under UV-illumination.
The fluorescence behavior of 1 did not vary significantly in acetate,
phosphate, or tris buffered solutions at pH 4.8, 7.0, and 8.1, respec-
tively (Fig. S4, Supplementary data). To prevent mCPBA from pos-
sible reaction with amines in the buffer,16 signaling experiments
were carried out in phosphate buffered 90% aqueous acetonitrile
(H2O/CH3CN = 90:10, v/v) at pH 7.0. Using a 90% aqueous acetoni-
trile solution for the signaling of mCPBA is because the signaling is
more efficient in aqueous solutions having higher water content
(Fig. S5, Supplementary data).
m-Chloroperbenzoic acid (mCPBA) is a peroxycarboxylic acid
used widely as an oxidant in organic synthesis due to its versatile
oxidizing power and relative ease of handling. Its main areas of
use are the conversion of ketones to esters (Baeyer–Villiger oxida-
tion),6 the epoxidation of alkenes,7 the oxidation of sulfides to sulf-
oxides and sulfones,8 and the oxidation of amines to amine oxides.9
In many reactions, mCPBA is highly reactive and more selective than
hydrogen peroxide or other peracids. In some applications, exact
amount of oxidant should be used to avoid side reactions; for exam-
ple, oxidation of sulfide with mCPBA resulted in sulfoxide and sul-
fone depending upon the amounts of mCPBA used.7 mCPBA could
be determined using iodometric titration with iodide10 and via GC
using the conversion of methyl phenyl sulfoxide into its sulfone.11
mCPBA can also be determined by spectroscopic methods, such as
oxidation of azo dye12 and enhanced chemiluminescence for the
oxidation of luminol.13 However, simple and convenient spectro-
scopic methods to determine mCPBA concentrations are rare.
Thioamides are readily transformed to their corresponding
amides via reaction with mCPBA under mild conditions.14 We
developed a new chromogenic and fluorogenic signaling system
for mCPBA based on the desulfurization of thiocoumarin. In the
presence of mCPBA, the sulfur atom of thiocoumarin was expelled
by converting into its oxo analog. This change resulted in a large
fluorescence enhancement and ratiometrically analyzable absorp-
tion changes.
To check the possibility of chromogenic signaling of 1, UV–vis
titration with mCPBA was carried out in 90% aqueous acetonitrile.
Upon titration with mCPBA, the strong absorption band of 1 at
⇑
Corresponding author. Tel.: +82 2 820 5199; fax: +82 2 825 4736.
E-mail addresses: skchang@cau.ac.kr, skchangg@yahoo.co.kr (S.-K. Chang).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.066

6664
S. Cha et al. / Tetrahedron Letters 51 (2010) 6663–6665
0.6
Lawesson's reagent
Toluene
0.6
0.4
0.2
0
406 nm
324 nm
Et
Et
O
O
O
O
O
S
2
1
0.4
0.2
0
N
S
0
5
10
[mCPBA] / [1]
3 : X = O
+
1
only
1
N
O
X
mCPBA
4
: X = S
Scheme 1. Preparation of thiocoumarins.
300
350
400
450
Wavelength (nm)
500
550
600
406 nm steadily decreased, and a new band at 324 nm increased
(Fig. 2). Concomitantly, solution color changed from yellow to col-
orless. Isosbestic point was not so well-defined early in the titra-
tion, which might be due to the formation of thermally unstable
sulfine intermediate.17 However, plotting the absorbance changes
as a function of mCPBA at 406 and 324 nm showed well-defined
profiles (inset of Fig. 2). Particularly, absorbance changes in re-
sponse to the variation of mCPBA could also be analyzed by ratiom-
etry using the ratio of the absorbances at 324 and 406 nm (Fig. S6,
Supplementary data).
Figure 2. UV–vis titration of 1 with mCPBA. In 90% aqueous acetonitrile at pH 7.0
(10 mM phosphate buffer). [1] = 2.0 Â 10À5 M.
mCPBA
Et
Et
O
O
O
O
O
S
CH3CN/H2O = 1:9
at pH 7.0
Weak Fluorescence
Yellow colored
Strong Fluorescence
Colorless
Effective chromogenic and fluorogenic signaling behavior of 1 is
due to mCPBA promoted desulfurization of thiocoumarin to cou-
marin (Scheme 2). The conversion from 1 to 2 was confirmed by
NMR, UV–vis, and fluorescence measurements. The 1H NMR spec-
trum of 1 in the presence of 2 equiv of mCPBA in CD3CN/D2O (1:1,
v/v) was almost identical to that of 2 (Fig. 3). The UV–vis and fluo-
rescence spectra of 1 in the presence of 100 equiv of mCPBA were
also identical to both of 2 in the absence and presence of same
amount of mCPBA.18 Conversion was also confirmed by measure-
ment of 1H NMR spectrum of the purified reaction product of 1
with mCPBA, which is identical to that of 2, in acetonitrile.
mCPBA signaling by 1 was completed within 5 min (Fig. S7,
Supplementary data). Under the same conditions, thiocoumarin 1
was stable and did not hydrolyze appreciably even after 24 h of
sample preparation. The detection limit19 of 1 for mCPBA was
1
2
Scheme 2. Signaling of mCPBA by thiocoumarin 1.
5.1 l
M in 90% aqueous acetonitrile solution.20 To check the practi-
cal applicability of 1, possible interferences from common metal
ions were measured ([1] = 5.0 Â 10À6 M, [mCPBA] = 2.5 Â 10À4 M,
[Mn+] = 5.0 Â 10À4 M). In fact, thiocoumarin derivative was used
as a signaling tool for Hg2+ ions by a similar desulfurization pro-
21
cess.
Although, Co2+ and Hg2+ caused significant interference,
Figure 3. Partial 1H NMR spectra of 1, 1 + mCPBA, and 2. In CD3CN/D2O (1:1, v/v).
[1] = [2] = 5.0 Â 10À3 M. [mCPBA] = 1.0 Â 10À2 M. Red starred peaks are residual
mCPBA resonances.
8
7
6
5
4
3
2
1
0
8
6
4
2
0
common coexisting metal ions of alkali (Na+, K+), alkaline earth
(Mg2+, Ca2+), and transition metal ions (Fe3+, Ni2+, Cu2+, Zn2+ and
Cd2+) did not affect the signaling of mCPBA. The reason for these
substantial interferences from Co2+ (ImCPBA+Co(II)/ImCPBA = 0.65) and
Hg2+ (ImCPBA+Hg(II)/ImCPBA = 0.22) might be due to the undesirable
reaction of mCPBA itself with these transition metal ions, as has
been reported for Co2+ ions.22
Finally, the ability to discriminate mCPBA from other widely
used oxidants, hydrogen peroxide, tert-butyl hydroperoxide
(TBHP), and peracetic acid (PAA), was tested (Fig. 4).10,11 Com-
pound 1 exhibited a much larger response (ꢀ80-fold) toward
mCPBA than hydrogen peroxide, as reported for the reaction with
azo dyes12 and TBHP. On the other hand, another important per-
acid, PAA, responded considerably with an 11-fold increase in fluo-
rescence intensity. This observation suggests that thiocoumarin 1
can selectively signal mCPBA in the presence of a large excess of
hydrogen peroxide or TBHP.
0
20
40
60
[mCPBA] / [ ]
1
1 +
mCPBA
1 only
350
400
450
Wavelength (nm)
500
550
Figure 1. Fluorescence titration of 1 with mCPBA. In 90% aqueous acetonitrile at pH
7.0 (10 mM phosphate buffer). [1] = 5.0 Â 10À6 M. kex = 340 nm.

S. Cha et al. / Tetrahedron Letters 51 (2010) 6663–6665
6665
8
7
6
5
4
3
2
1
0
References and notes
10
8
mCPBA
1. (a) Gomes, A.; Fernandes, E.; Lima, J. L. F. C. J. Biochem. Biophys. Methods 2005,
65, 45; (b) Dickinson, B. C.; Srikun, D.; Chang, C. J. Curr. Opin. Chem. Biol. 2010,
14, 50; (c) Oushiki, D.; Kojima, H.; Terai, T.; Arita, M.; Hanaoka, K.; Urano, Y.;
Nagano, T. J. Am. Chem. Soc. 2010, 132, 2795.
2. (a) Chang, M. C. Y.; Pralle, A.; Isacoff, E. Y.; Chang, C. J. J. Am. Chem. Soc. 2004,
126, 15392; (b) Dickinson, B. C.; Chang, C. J. J. Am. Chem. Soc. 2008, 130, 9638.
3. (a) Kenmoku, S.; Urano, Y.; Kojima, H.; Nagano, T. J. Am. Chem. Soc. 2007, 129,
7313; (b) Sun, Z.-N.; Liu, F.-Q.; Chen, Y.; Tam, P. K. H.; Yang, D. Org. Lett. 2008,
10, 2171; (c) Yang, Y.-K.; Cho, H. J.; Lee, J.; Shin, I.; Tae, J. Org. Lett. 2009, 11, 859.
4. (a) Yang, D.; Wang, H.-L.; Sun, Z.-N.; Chung, N.-W.; Shen, J.-G. J. Am. Chem. Soc.
2006, 128, 6004; (b) Sun, Z.-N.; Wang, H.-L.; Liu, F.-Q.; Chen, Y.; Tam, P. K. H.;
Yang, D. Org. Lett. 2009, 11, 1887.
5. (a) Gabe, Y.; Urano, Y.; Kikuchi, K.; Kojima, H.; Nagano, T. J. Am. Chem. Soc. 2004,
126, 3357; (b) Zheng, H.; Shang, G.-Q.; Yang, S.-Y.; Gao, X.; Xu, J.-G. Org. Lett.
2008, 10, 2357.
6. Mascal, M.; Warmuth, R.; Naven, R. T.; Edwards, R. A.; Hursthouse, M. B.; Hibbs,
D. E. J. Chem. Soc., Perkin Trans. 1 1999, 3435.
6.95
6
4
2
0.80
0.07
0.09
0.07
0
PAA
only, H O , TBHP
[
1
]
2
2
350
400
450
500
550
Wavelength (nm)
7. Jana, N. K.; Verkade, J. G. Org. Lett. 2003, 5, 3787.
8. Luly, J. R.; Yi, N.; Soderquist, J.; Stein, H.; Cohen, J.; Perun, T. J.; Plattner, J. J. J.
Med. Chem. 1987, 30, 1609.
9. (a) Stappers, F.; Broeckx, R.; Leurs, S.; Van den Bergh, L.; Agten, J.; Lambrechts,
A.; Van den Heuvel, D.; De Smaele, D. Org. Process Res. Dev. 2002, 6, 911; (b) Liu,
S.; Pestano, J. P. C.; Wolf, C. J. Org. Chem. 2008, 73, 4267.
Figure 4. Changes in fluorescence spectra of 1 in the presence of commonly used
oxidants. [1] = 5.0 Â 10À6 M, [mCPBA] = [H2O2] = [TBHP] = [PAA] = 5.0 Â 10À4 M.
kex = 340 nm.
10. Davies, D. M.; Deary, M. E. Analyst 1988, 113, 1477.
11. Furia, F. D.; Prato, M.; Scorrano, G.; Stivanello, M. Analyst 1988, 113, 793.
12. Akerman, D.; Phillips, D. A. S.; Taylor, J. A. Dyes Pigments 2003, 59, 285.
13. Yeh, H.-C.; Lin, W.-Y. Anal. Bioanal. Chem. 2002, 372, 525.
14. Kochhar, K. S.; Cottrell, D. A.; Pinnick, H. W. Tetrahedron Lett. 1983, 24, 1323.
15. Iwanaga, H.; Naito, K.; Sunohara, K.; Okajima, M. Bull. Chem. Soc. Jpn. 1998, 71,
1719.
In summary, a convenient dual signaling system for mCPBA was
devised based on a simple thiocoumarin derivative. Signaling was
due to the efficient desulfurization of thiocoumarin to coumarin by
mCPBA. Thiocoumarin also exhibited mCPBA-selective signaling in
the presence of a large excess of hydrogen peroxide. The reported
system could be used as a convenient spectroscopic signaling tool
to determine mCPBA concentration.
16. Davies, D. M.; Jones, R. M. J. Chem. Soc., Perkin Trans. 2 1989, 1323.
17. Thiocarbonyl groups are known to be desulfurized by the reaction with mCPBA
via unstable intermediate sulfine. With increasing amount of mCPBA, sulfine
formed at early stage of titration was subsequently decomposed to carbonyl
function. Lemarié, M.; Pham, T.-N.; Metzner, P. Tetrahedron Lett. 1991, 32, 7411.
= 2.52 Â 104 MÀ1 cmÀ1
. U = 0.050. Compound 2:
U = 0.0004 in 90% aqueous
Acknowledgment
18. Compound 1: kmax = 406 nm,
e
kmax = 324 nm,
e
= 1.65 Â 104 MÀ1 cmÀ1
.
acetonitrile at pH 7.0. Quantum yields were measured using anthracene as a
This work was supported by a fund from Korea Research Foun-
dation of Korean Government (2010-0008631).
quantum yield standard (U = 0.27 in ethanol).
19. Shortreed, M.; Kopelman, R.; Kuhn, M.; Hoyland, B. Anal. Chem. 1996, 68, 1414.
20. With thiocoumarin probe, the percentage of active oxidizing agent in mCPBA
could be determined by using
iodometrically standardized mCPBA.
a calibration curve obtained with an
Supplementary data
21. Choi, M. G.; Kim, Y. H.; Namgoong, J. E.; Chang, S.-K. Chem. Commun. 2009,
3560.
22. Nam, W.; Ryu, J. Y.; Kim, I.; Kim, C. Tetrahedron Lett. 2002, 43, 5487.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.10.066.