Synthesis, characterization, and redox property of 3-(2-phenyl-4H- thiochromen-4-ylidene)-3H-chromene-2,4-diones

Article abstract of DOI:10.1055/s-2008-1078497

Two 3-(2-phenyl-4H-thiochromen-4-ylidene)-3H-chromene-2,4-dione derivatives were synthesized and evaluated as reversible redox switches. The prepared purple compound 7 and blue compound 13 instantly changed to colorless when treated with sodium borohydrid

Full text of DOI:10.1055/s-2008-1078497

LETTER
1825
Synthesis, Characterization, and Redox Property of 3-(2-Phenyl-4H-thio-
chromen-4-ylidene)-3H-chromene-2,4-diones
S
ynthesis of 3-(2-
h
Phenyl-4
H
-
t
i
hiochro
n
men-4-yilde
-
ne)-
3
H
-
N
chromene-2,4-dio
enes ng Huang, Rong-Ren Chuang, Pei-Yu Kuo, Ding-Yah Yang*
Department of Chemistry and Center for Nanoscience and Technology, Tunghai University, 181, Taichung-Kang Rd. Sec.3, Taichung
40704, Taiwan
Fax +886(4)23590426; E-mail: yang@thu.edu.tw
Received 28 January 2008
Ph
Abstract: Two 3-(2-phenyl-4H-thiochromen-4-ylidene)-3H-chro-
mene-2,4-dione derivatives were synthesized and evaluated as re-
versible redox switches. The prepared purple compound 7 and blue
compound 13 instantly changed to colorless when treated with so-
dium borohydride in methanol. The corresponding reduced 9 and 14
can be reverted to their original colors via DDQ oxidation or by air.
While no fluorescence of the N,N-dimethylamino-substituted 13
was detected prior to reduction, the reduced 14 emitted blue
fluorescence in methanol with a quantum yield value of 0.19.
O
O
O
O
2
Et3SiH, TFA,
r.t., 16 h
68%
Key words: heterocycles, oxidation, reduction, sulfur, conjugation
compounds
Ph
OH
O
O
O
O
flavone, Ac2O
The field of molecular switches has attracted great interest
in the past decade because of its relevance in the develop-
ment of molecular electronics and photonics,1 especially
for fluorescence redox switches since fluorescence emis-
sion is considered to be one of the most attractive signal
outputs of switching materials owing to its high sensitivi-
ty, easy detection, and low-cost procedure. On the other
hand, 4-hydroxycoumarin and its derivatives represent an
important class of naturally occurring compounds with a
wide spectrum of biological activities, which made them
attractive synthetic targets for organic chemists.2 In our
continuous efforts to develop novel heterobicyclic-based
photochromic colorants, we have synthesized various 4-
hydroxycoumarin derivatives.3 For instance, Scheme 1
shows the preparation of the dioxabicycle 2 by ionic hy-
drogenation of (Z)-2¢-phenyl-[3,4¢]bichromenylidene-
2,4-dione (1), which was prepared by the condensation of
4-hydroxycoumarin and flavone. Reduction of 1 with so-
dium borohydride in methanol gave compound 3, which
subsequently dissociated to the red ion pair 4. Interesting-
ly, compound 4 slowly returned to the starting material 1
via 3 when stood at room temperature for several hours.
This result suggested that compound 1 may have the po-
tential to function as a reversible redox switch if the for-
mation of 4 can be prohibited. Here we report the
preparation of two derivatives of compound 1 by replac-
ing the right-hand side-ring oxygen with sulfur, and the
subsequent evaluation of their potentials to function as ac-
tive fluorescence redox switches.
EtOAc, 70 °C,
48 h
O
O
51%
1
NaBH4, MeOH,
r.t., 0.5 h
Ph
Ph
O
O
OH
O
O
O
O
O
3
red
4
Scheme 1
O
O
O
thiophenol, P2O5
H3PO4, 90–100 °C,
OEt
Ph
1.5 h
87%
S
Ph
5
6
OH
O
Ac2O, EtOAc,
60 °C, 12 h
43%
O
Ph
Ph
S
1. NaBH4,
MeOH, r.t.
OMe
S
O
O
2. CH2N2,
CH2Cl2,
0 °C, 1 h
60%
O
O
O
8
7
Scheme 2
Scheme 2 shows the preparation of the target compound
7. It started with the condensation of thiophenol with ethyl
benzoylacetate in heated (90–100 °C) polyphosphoric
SYNLETT 2008, No. 12, pp 1825–1828
Advanced online publication: 02.07.2008
DOI: 10.1055/s-2008-1078497; Art ID: W01708ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
0
8

1826
C.-N. Huang et al.
LETTER
Figure 2 The redox switch between 7 and 9, and the corresponding
colors in the oxidized (left) and the reduced form (right)
Figure 1 The X-ray crystal structure of compound 8
acid (PPA, generated in situ by mixing phosphorus pent-
oxide with concentrated phosphoric acid) for 1.5 hours to
give 2-phenylthiochromen-4-one (6).4
Coupling of 6 with 4-hydroxycoumarin in acetic anhy-
dride and ethyl acetate yielded the desired compound 7.
Compound 7 instantly changed from purple to colorless
when reduced with sodium borohydride in methanol. The
reduced compound 9 can be reverted to colorless by DDQ
oxidation or by air. The structure of 9 was confirmed by
methylation of the 4-hydroxy group on the coumarin moi-
ety in situ with diazomethane. The resulting 4-hydroxy-
Figure 3 UV/Vis spectra of 7 (3.4·10–5 M in MeOH) prior to and af-
ter NaBH4 reduction
coumarin derivative
8 was isolated and further
characterized. Figure 1 shows the X-ray crystal structure
of 8, which clearly revealing a 4H-thiochromene skele-
ton.5 Figure 2 presents the redox switch between 7 and 9,
and the corresponding colors in the oxidized (purple) and
the reduced (colorless) forms. Figure 3 depicts the UV/
Vis absorption spectra of 7 prior to and after reduction. It
displayed two broad bands at 382 and 549 nm before re-
duction, which are associated with the increased p-delo-
calization of the conjugated chromophore. A rather
different spectrum was obtained when 7 was reduced to 9.
The reduction of 7 to 9 resulted in the complete disappear-
ance of the long-wavelength absorbance due to the disrup-
tion of the conjugation, and the appearance of a broad
band at approximately 288 nm, which resembles the ab-
sorption behavior of 4-hydroxycoumarin.
OH
O
O
O
OH
O
N
O
O
N
11
strong fluorescence in CH2Cl2
10
non fluorescence in MeOH
Figure 4
phenylthiochromen-4-one (6) with 4-hydroxy-7-N,N-
dimethylaminocoumarin7 failed to give a satisfactory
yield.
Thus, an alternative synthesis was carried out, as depicted
in Scheme 3. The 2-phenylthiochromen-4-one was first
reduced by LiAlH4 in THF to obtain 2-phenylthiochro-
man-4-ol (12). The subsequent coupling of alcohol 12
with 4-hydroxy-7-N,N-dimethylaminocoumarin in the
presence of a catalytic amount of p-toluenesulfonic acid at
50 °C afforded the compound 13.7
After the reversible redox switch between 7 and 9 was
successfully established, we then focused our attention to
introduce a fluorophore into the system. Our previous
studies6 on the coumarin-containing triketones have dem-
onstrated that the exocyclic enol form 10 of 3-acetyl-4-hy-
droxy-7-N,N-dimethylaminocoumarin
emits
no
Figure 5 shows the redox switch between 13 and 14, and
the corresponding colors in the oxidized (blue) and the re-
duced (colorless) forms. Figure 6 presents the UV/Vis ab-
sorption spectra of 13 prior to and after reduction.
fluorescence but the corresponding endocyclic enol tau-
tomer 11 is highly fluorescent (Figure 4). This observa-
tion suggested that the incorporation of an N,N-
dimethylamino group at the 7-position of the coumarin
ring on 7 may significantly enhance its fluorescence emis-
sion after reduction. The initial attempt to prepare the pro-
posed compound 13 by a direct coupling of 2-
Similar to compound 7, the reduction of 13 to 14 resulted
in the complete disappearance of the long-wavelength ab-
sorbance. The absorption parameters for compounds 7, 9,
13, and 14 in methanol are listed in Table 1. The cyclic
Synlett 2008, No. 12, 1825–1828 © Thieme Stuttgart · New York

LETTER
Synthesis of 3-(2-Phenyl-4H-thiochromen-4-ylidene)-3H-chromene-2,4-diones
1827
O
OH
LiAlH4, THF
0 °C, 2 h
81%
S
Ph
S
Ph
12
6
OH
O
PTSA (cat.),
DCE,
50 °C, 6 h
35%
N
O
Figure 6 UV/Vis spectra of 13 (2.6·10–5 M in MeOH) prior to and
after reduction
Ph
S
O
N
O
O
13
Scheme 3
Figure 7 Cyclic voltammogram of 13 in CH2Cl2 using tetra-n-bu-
tylammonium hexafluorophosphate (0.1 M) as the supporting electro-
lyte at a scan rate of 100 mV/s
the former occurs at the fluorophore rather than the fluo-
rescent quencher as in the latter. Therefore, no fluorescent
quencher is required in our system.
In summary, this study synthesized two 3-(2-phenyl-4H-
thiochromen-4-ylidene)-3H-chromene-2,4-dione deriva-
tives in two-to-three steps from thiophenol and 4-
hydroxycoumarins with overall yields of 25–37%. Both
prepared compounds can be instantly reduced by NaBH4
in methanol to afford the conjugation-disrupted product
with a distinct change in color. The reduced 4-hydroxy-
coumarin derivatives can be oxidized back to the original
compound via DDQ oxidation or by oxygen in the air. Fi-
nally, a fluorescence redox switch that can be turned ON
and OFF based on the redox potential of the 4-hydroxy-
coumarin moiety is demonstrated.
Figure 5 The redox switch between 13 and 14, and the correspon-
ding colors in the oxidized (left) and the reduced form (right)
voltammetric studies revealed that compound 7 has a re-
duction potential at –0.57 V vs. Ag/AgCl. The addition of
an N,N-dimethylamino group at the 7-position of the cou-
marin ring increased the reduction potential of 13 to –0.66
V. Figure 7 shows the cyclic voltammogram of 13 in
methylene chloride using tetra-n-butylammonium
hexafluorophosphate (0.1 M) as the supporting electrolyte
at a scan rate of 100 mV/s. While 13 emitted no fluores-
cence at room temperature, the corresponding reduced 14
was blue fluorescent in methanol with a quantum yield of
0.19. Figure 8 shows the excitation (336 nm) and emis-
sion (383 nm) spectra of 14 with the Stoke’s shift of 3,652
cm–1. The redox process was repeated ten times without
significant changes in the UV/Vis absorbance at 598 nm
(see Supporting Information available from the author).
Thus, the reversible redox process between 13 and 14 can
be regarded as a molecular switching system, in which the
absorption and emission properties are controlled by the
redox state of the 4-hydroxycoumarin moiety. This redox
switch system is quite different from the most reported
donor–acceptor systems,8 because the redox reaction of
Table 1 Absorption Parameters of Compounds 7, 9, 13, and 14 in
Methanol
Compd
l
max (nm)
log e (M–1 cm–1)
4.26, 4.17, 4.61, 4.91
4.58, 4.94
7
549, 382, 266, 207
288, 210
9
13
598, 372, 325, 251, 208
4.35, 4.07, 4.39, 4.50,
4.78
14
335, 207
4.52, 5.03
Synlett 2008, No. 12, 1825–1828 © Thieme Stuttgart · New York

1828
C.-N. Huang et al.
LETTER
Moon, J. B.; Lynn, J. C.; Horng, M. M.; Hinshaw, R. R.;
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(5) Crystallographic data (excluding structure factors) of
compound 8 have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication
number CCDC-665160. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif or by
emailing data_request@ccdc.cam.ac.uk or by contacting
The Cambridge Crystallographic Data Centre, 12, Union
Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033.
(6) Chen, Y. S.; Kuo, P. Y.; Shie, T. L.; Yang, D. Y.
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Figure 8 The excitation (336 nm) and emission (383 nm) spectra of
14 in methanol at room temperature
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
(7) Procedure for the Preparation of 13
To a solution of 12 (500 mg, 2.06 mmol) in DCE (10 mL)
was added 4-hydroxy-7-N,N-dimethylaminocoumarin (423
mg, 2.06 mmol) and a catalytic amount of PTSA. After the
mixture was stirred at 50 °C for 6 h, H2O (5 mL) was added
to the mixture and the product was extracted twice with
CH2Cl2. The combined organic extracts were dried over
anhyd MgSO4, filtered, and concentrated. The resulting
crude product was purified by column chromatography
(EtOAc–hexane, 7:15) to give a blue solid with a 35% yield;
mp 258–259 °C. 1H NMR (300 MHz, CDCl3): d = 9.62 (s, 1
H), 8.34 (dd, J = 8.4, 1.2 Hz, 1 H), 7.98 (d, J = 8.7 Hz, 1 H),
7.90 (dd, J = 8.1, 1.2 Hz, 1 H), 7.87–7.84 (m, 2 H), 7.74
(ddd, J = 8.1, 7.2, 1.2 Hz, 1 H), 7.63–7.52 (m, 4 H), 6.60 (dd,
J = 9.0, 2.4 Hz, 1 H), 6.42 (d, J = 2.4 Hz, 1 H), 3.09 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 176.9, 165.1, 164.2,
156.48, 156.47, 155.9, 154.5, 139.1, 136.2, 134.9, 132.2,
131.8, 129.8, 129.7, 128.2, 128.0, 127.8, 126.6, 110.7,
108.4, 108.1, 97.3, 40.2. IR (KBr): n = 1674, 1615, 1488,
1205 cm–1. HRMS (EI): m/z calcd for C26H19NSO3:
425.1086; found: 425.1081 [M+].
Acknowledgment
The authors would like to thank the National Science Council of the
Republic of China, Taiwan, for financially supporting this research
under Contract No. NSC 95-2113-M-029-003.
References and Notes
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