Synthesis of coumarin derivatives containing 2-aminothiazole moiety and their recognition of metal ions

Article abstract of DOI:10.1007/s11164-013-1528-y

Two new coumarin derivatives bearing 2-aminothiazole moiety were synthesized and the molecular structures were confirmed by NMR and HRMS. In acetonitrile, C1 exhibited a selective fluorescence enhancement effect to Mg²⁺ among the metal ions examined. C2 showed a selective fluorescence quenching effect to Co²⁺.

Full text of DOI:10.1007/s11164-013-1528-y

Res Chem Intermed
DOI 10.1007/s11164-013-1528-y
Synthesis of coumarin derivatives containing
2-aminothiazole moiety and their recognition of metal
ions
•
•
•
Guo Feng Chen Li Yan Zhang Hong Yang Li
Bao Hua Chen
Received: 1 August 2013 / Accepted: 30 December 2013
Ó Springer Science+Business Media Dordrecht 2014
Abstract Two new coumarin derivatives bearing 2-aminothiazole moiety were
synthesized and the molecular structures were confirmed by NMR and HRMS. In
acetonitrile, C1 exhibited a selective fluorescence enhancement effect to Mg2?
among the metal ions examined. C2 showed a selective fluorescence quenching
effect to Co2?
.
Keywords Fluorescent probe Á Coumarins Á 2-Aminothiazole Á
Metal ions
Introduction
Metal ions recognition is one of the fast growing fields in supramolecular chemistry due
to their fundamental importance to chemistry, biomedicine, and environmental
applications. Fluorescent probes for metal ions as a detection method with advantages
of simplicity, excellent selectivity, high sensitivity, and fast response time (within
minutes) have been widely used, and their design, synthesis, and action mechanisms
have received extensive attention and research [1–5]. Currently, the development of
fluorescent small molecules for metal ion recognition with excellent selectivity and
sensitivity is still a challenging work for many scientists, including chemists, biologists,
and clinical biochemists. Fluorescent probes for metal ions generally contain binding
sites and a signaling subunit that can respond quickly to the changes in absorption
G. F. Chen (&) Á L. Y. Zhang Á H. Y. Li
Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental
Science, Hebei University, Wusi East Road No. 180, Baoding 071002, People’s Republic of China
e-mail: chenguofeng@hbu.edu.cn; chenguofeng@hbu.cn
B. H. Chen
College of Pharmaceutical Sciences, Hebei University, Baoding 071002, People’s Republic of
China
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G. F. Chen et al.
(emission) spectra when binding metal ions. Coumarin derivatives are commonly used
as fluorescent chemical probes for the metal ions because they possess many distinctive
and desirable properties such as high fluorescence quantum yields, strong absorption (a
high molar extinction coefficient), and a large Stokes shifts (up to 160 nm) [6, 7]. These
properties have made them desirable components in many fields, including sensors for
metal cations [8–17], OLEDs [18–21], laser dyes [22–24], and fluorescent intracellular
tags [25, 26]. With these concerns in mind, and in continuation of our ongoing research
work on the use of coumarin derivatives as environmentally sensitive fluorescent
probes [27], we have recently constructed two fluorescent probes, C1 and C2, by
combining a coumarin fragment with 2-aminothiazole (Scheme 1), and studied the
properties of their UV–Vis absorption and fluorescence emission spectra in acetonitrile.
Compound C1 displayed a selective fluorescence enhancement effect with Mg2?, on
the other hand, compound C2 displayed a selective fluorescence quenching effect with
Co2? among the metal ions examined.
Experimental
Materials and measurements
Unless otherwise stated, all reagents were obtained from commercial suppliers and
used without further purification. Solvents employed in this study were of the
highest grade and were used as received. Ethyl 2-oxo-2H-chromene-3-carboxylate
(1) and Ethyl 7-diethylamino-2-oxo-2H-chromene-3-carboxylate (2) were prepared
according to literature procedures [27, 29]. Melting points were determined with by
a TECH X-4 apparatus and the quoted temperatures were uncorrected. TLC analysis
was performed on silica gel plates and column chromatography was carried out on
silica gel (mesh 200–300), both of which were purchased from Qingdao Ocean
Chemicals. The 1H NMR (600 MHz) and 13C NMR (150 MHz) spectra were
recorded on a Bruker AVANCE III 600 spectrometer using DMSO-d6 as the solvent
with tetramethylsilane (TMS) as an internal standard. MS were determined on a
Bruker apex ultra 7.0 T spectrometer (the accuracy is 1 ppm). UV spectra were
measured on a Purkinje TU-1901 UV–Visible spectrophotometer. Fluorescent
spectra were recorded on a HITACHI F-7000 fluorescence spectrophotometer.
Scheme 1 Chemical structure of sensors C1 and C2
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Metal ion recognition based on coumarin derivatives
Synthesis
Preparation of 2-Oxo-2H-chromene-3-carboxylic acid (3)
To a solution of ethyl 2-oxo-2H-chromene-3-carboxylate (1) (2.000 g, 9.2 mmol) in
EtOH/H2O 2:1 (v/v, 15 mL) was added 1.5 g NaOH and heated under reflux for
18 min. After cooling to room temperature, the solution was slowly poured into
hydrochloric acid solution 20 % (v/v, 30 mL) and cooling to 0 °C gave a white
crystalline deposit. The solid was collected by filtration and washed with cold water
to afford 3 as white crystals, and finally dried in vacuo. (1.479 g, 84.8 %): m.p.
187–188 °C (lit. value 191–192 °C) [30]. An analogous procedure starting with 2
gave 7-diethylamino-2-oxo-2H-chromene-3-carboxylic acid (4) (78.6 %); m.p.
236–238 °C (lit. value 228 °C) [31].
Preparation of 2-oxo-N-(thiazol-2-yl)-2H-chromene-3-carboxamide (C1)
2-Oxo-2H-chromene-3-carboxylic acid (3) (0.190 g, 1.0 mmol) and 8 mL SOCl2
were added into a 25-mL single-necked flask equipped with a water-cooled
condenser and tail gas absorption device and heated under reflux for 4 h. After
cooling to room temperature, the SOCl2 was evaporated under reduced pressure.
2-Aminothiazole (0.095 g, 0.95 mmol) in 2 mL of CH2Cl2 was added dropwise to
the above 2-oxo-2H-chromene-3-carbonyl chloride in 10 mL CH2Cl2 cooled at
0 °C. The mixture was stirred for 1 h at 0 °C, then for 8 h at r.t. The solvent was
evaporated under reduced pressure. The crude product was subjected to chroma-
tography on silica gel (200–300 mesh) and eluted with a mixture of petroleum ether
and ethyl acetate to afford C1 as light yellow crystals (0.099 g, 38.3 % yield). m.p.
278–280 °C. 1H NMR (DMSO-d6, 600 MHz), d: 12.05 (s, 1H), 9.04 (s, 1H),
8.05–8.06 (m, 1H), 7.81–7.85 (m, 1H), 7.58–7.59 (m, 2H), 7.50–7.52 (m, 1H), 7.38
(d, J = 3.5 Hz, 1H). 13C NMR (DMSO-d6, 150 MHz), d: 160.9, 154.5, 149.0,
138.7, 135.4, 131.1, 126.0, 118.8, 116.9, 115.4. HRMS m/z (ESI): calcd for
C13H9N2O3S [M?H]? 273.0328, found 273.0332.
Preparation of 7-(diethylamino)-2-oxo-N-(thiazol-2-yl)-2H-chromene-3-
carboxamide (C2)
To
a solution of 7-diethylamino-2-oxo-2H-chromene-3-carboxylic acid (4)
(0.261 g, 1.0 mmol) in 5 mL CH2Cl2, was added EDCI (0.230 g, 1.2 mmol). After
stirring for 0.5 h at r.t., the HOBt (0.162, 1.2 mmol) was added and the mixture was
stirred for 1.0 h at r.t. 2-Aminothiazole (0.105 g, 1.05 mmol) was added to the
above reacting system and stirred for 25 h at r.t. After removal of the solvent by
rotary evaporation, the residue was mixed with water (100 mL). The solid was
collected by filtration and washed with a small amount of ethyl acetate, then
recrystallized from DMF/CH3OH (5/1, V/V) to afford 7-(diethylamino)-2-oxo-N-
(thiazol-2-yl)-2H-chromene-3-carboxamide (C2) as light yellow crystals (0.105 g,
30.6 % yield). m.p. 212–213 °C. 1H NMR (DMSO-d6, 600 MHz), d: 11.93 (s, 1H),
8.81 (s, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.53 (d, J = 2.7 Hz, 1H), 7.30 (d,
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G. F. Chen et al.
J = 2.2 Hz, 1H), 6.88 (d, J = 8.3 Hz, 1H), 6.69 (s, 1H), 3.52–3.53 (m, 4H), 1.16 (t,
J = 6.7 Hz, 6H); 13C NMR (DMSO-d6, 150 MHz), d: 162.6, 160.8, 158.2, 157.5,
153.9, 149.3, 138.5, 132.7, 114.8, 111.3, 108.5, 107.1, 96.6, 45.0, 12.8. HRMS m/
z (ESI): calcd for C17H17N3NaO3S [M?Na]? 366.0883, found 366.0883.
Results and discussion
Aminothiazole-based probes C1 and C2 were synthesized by condensation of
2-aminothiazole with 2-oxo-2H-chromene-3-carboxylic acid or 7-diethylamino-2-
oxo-2H-chromene-3-carboxylic acid, respectively. The target molecules and their
precursors were synthesized according to the procedure shown in Scheme 2. The
synthesis of reaction intermediates 1 and 2 has been reported by us previously [27].
Reaction of 1 or 2 with NaOH in EtOH/H2O resulted in the desired key
intermediates, 3 and 4, respectively. Treatment of compounds 3 with SOCl2 in
CH2Cl2 led to 2-oxo-2H-chromene-3-carbonyl chloride. After the solvent was
evaporated under reduced pressure, 2-aminothiazole was reacted with the above
carbonyl chloride in CH2Cl2 to give compound 2-oxo-N-(thiazol-2-yl)-2H-chro-
mene-3-carboxamide (C1) in 38.3 % yield as yellow crystals after purification by
flash chromatography. 7-(Diethylamino)-2-oxo-N-(thiazol-2-yl)-2H-chromene-3-
carboxamide (C2) was synthesized in 30.6 % yields from compounds 4 and
2-aminothiazole by a one-step reaction in the presence of HOBt/EDCI in CH2Cl2 at
1
r.t. Compounds C1 and C2 were fully characterized by H NMR, 13C NMR, and
HRMS.
To evaluate the photo-physical properties of probes C1 and C2, their UV–Vis
absorption spectra were recorded at 10 mM concentration in acetonitrile (Fig. 1).
Probe C1 displayed a milder strong absorbance band centered at 343 nm and a
milder weak absorbance band on the shorter wavelength side centered at about
307 nm. Probe C2 exhibited a strong band centered at 436 nm and a weaker
absorption band at about 269 nm. The large difference in the absorption between C1
and C2 is attributed to the strongly electron-donating N,N-diethylamino moiety
groups on the side aromatic ring of C2.
Preliminary complexation properties of sensors C1 and C2 were studied toward
metal ions (Na?, K?, Mg2?, Ca2?, Zn2?, Cu2?, Co2?, Ni2?, Fe3?, Mn2?, Cd2?
,
Ag?, Hg2?, and Pb2?) by fluorescence spectra in acetonitrile. As shown in Fig. 2,
the addition of ten equiv. of metal ions, such as Na?, K?, Zn2?, Cu2?, Co2?, Mn2?
,
Cd2?, Hg2?, and Pb2? resulted in negligible changes in the emission spectrum of
C1. When Ni2? was added to C1, the intensity of the emission band at 380 nm
increased by 5.6-fold in acetonitrile. In addition, Fe3?, Ag?, and Ca2? also showed
increased emission bands at 380 nm, but the intensity was lower than that with
Ni2?. On the other hand, a fluorescence enhancement effect at 400 nm was observed
in the case of C1 Mg2?. The inset in Fig. 2 exhibits the fluorescent intensity ratio
(I400/I380) of free C1 and C1 in the presence of 10.0 equiv. of different metal ions.
The fluorescence emission changes of sensor C2 after addition of the above ions
are depicted in Fig. 3. Compound C2 presents a different extent of fluorescence
quenching upon the addition of Mg2? (41.5 %), Ni2? (60.1 %), and Co2? (81.7 %)
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Metal ion recognition based on coumarin derivatives
Scheme 2 Synthetic approach for sensors C1 and C2
Fig. 1 UV–Vis spectra of sensor C1 and C2 in acetonitrile
among the metal ions examined. Under the same conditions, upon the addition of
metal ions such as Na?, K?, Ca2?, Zn2?, Cu2?, Fe3?, Mn2?, Cd2?, Ag?, Hg2?, and
Pb2? (10 equiv.) to the solutions of C2, no significant fluorescence changes were
observed. The inset in Fig. 3 exhibits the fluorescent intensity ratio (I0/I) of free C2
and C2 in the presence of 10.0 equiv. of different metal ions at 477 nm.
The fluorogenic affinity of C1 with Mg2? ions was evaluated by a fluorescence
titration experiment (Fig. 4). Probe C1 has a milder weak fluorescence emission at
about 400 nm with excitation at 343 nm. Upon addition of Mg2? ion (0–4 N),
relative fluorescence intensity increased significantly at 400 nm. The binding
constant (Ka) for the interaction of C1 with Mg2? estimated from the fluorescence
titration data was found to be 7.9 9 104 M-1 [28]. The inset in Fig. 4 exhibits the
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G. F. Chen et al.
Fig. 2 Fluorescence spectra of free C1 and C1 in the presence of 10 equiv. of various metal ions in
acetonitrile. [C1] = 1.0 9 10-5 M. Excitation wavelength: 343 nm; bandwidth (Ex): 5 nm; bandwidth
(Em): 10 nm. Inset fluorescent intensity ratio (I400/I380) of free C1 and C1 with different metal ions
Fig. 3 Fluorescence spectra of free C2 and C2 in the presence of 10 equiv. of various metal ions in
acetonitrile. [C2] = 1.0 9 10-5 M. Excitation wavelength: 436 nm; bandwidth (Ex): 5 nm; bandwidth
(Em): 5 nm. Inset fluorescent intensity ratio (I0/I) of free C2 and C2 with different metal ions at 477 nm
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Metal ion recognition based on coumarin derivatives
Fig. 4 Fluorescence spectral changes of C1 (1.0 9 10-5 M) upon addition of Mg2? in acetonitrile.
Excitation wavelength: 343 nm; bandwidth (Ex): 5 nm; bandwidth (Em): 10 nm. Inset the plot of ratio
fluorescence intensity of C1 (I400/I380) versus the concentrations of Mg2?
Fig. 5 Absorption spectral changes of C1 (1.0 9 10-5 M) upon addition of Mg2? in acetonitrile
dependence of the intensity ratios of emission at 400 nm to that at 380 nm (I400/
I380) on Mg2?
.
To understand the coordination behavior between C1 and the Mg2? ion, the
UV–Vis absorption spectral titration experiment of C1 (10 mM) with Mg2? ion
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Fig. 6 Fluorescence spectral changes of C2 (1.0 9 10-5 M) upon addition of Co2? in acetonitrile.
Excitation wavelength: 436 nm; bandwidth (Ex): 5 nm; bandwidth (Em): 5 nm
(0–40 mM) in acetonitrile was carried out. With the stepwise addition of Mg2? ion,
the absorbance increased gradually and then remained constant after adding
approximately 40 mM Mg2? (Fig. 5).
Figure 6 displays fluorescence changes of C2 upon addition of increasing
concentrations of Co2? (0–10 N) in acetonitrile. Probe C2 has a very strong
fluorescence emission at about 477 nm with excitation at 436 nm. The fluorescence
intensity gradually decreased at 477 nm upon addition of Co2?. From the
fluorescent titrations (Fig. 6), the associated constant (Ka) for the interaction of
C2 with Co2? was calculated as 1.25 9 105 M-1 [28].
Conclusions
In summary, two new coumarin derivatives (C1, C2) bearing 2-aminothiazole
moiety were synthesized as fluorescent sensors for metal ions. Compound C1
displayed enhanced fluorescent effects upon the addition of Mg2? among the metal
ions examined. On the other hand, sensor C2 with the N,N-diethylamino donor
group showed selective fluorescence quenching effect with Co2?
.
Acknowledgments The project was supported by Natural Science Foundation of Hebei Province
(B2011201072). and Foundation of Hebei University (2009-163).
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