9-Benzylidene-9H-fluorene derivatives linked to Monoaza-15-crown-5: Synthesis and metal ion sensing

Article abstract of DOI:10.1002/cjoc.201200047

Two kinds of novel styryl chemosensory 2-FMNC and 3-FMNC, were designed and synthesized by an apporiate introduction of 9-benzylidene-9H-fluorene group as fluorophore with the aim at avoiding photoisomerisation. These 9-benzylidene-9H-fluorene derivatives showed the similar selectivity and sensitivity upon addition of metal ions. The sensitivity of FMNC to alkaline earth metal ions was Ba²⁺>Sr²⁺>Ca ²⁺≈Mg²⁺. Copyright

Full text of DOI:10.1002/cjoc.201200047

FULL PAPER
DOI: 10.1002/cjoc.201200047
9-Benzylidene-9H-fluorene Derivatives Linked to Monoaza-
15-crown-5: Synthesis and Metal Ion Sensing
Cao, Jing*,a,b(曹靖)
Li, Yanga(李阳)
Feng, Junxianga(冯俊香)
a College of Chemistry, Xiangtan University, Xiangtan, Hunan 411105, China
b Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of
Chemistry, Xiangtan University, Xiangtan, Hunan 411105, China
Two kinds of novel styryl chemosensory 2-FMNC and 3-FMNC, were designed and synthesized by an
apporiate introduction of 9-benzylidene-9H-fluorene group as fluorophore with the aim at avoiding photoisomerisa-
tion. These 9-benzylidene-9H-fluorene derivatives showed the similar selectivity and sensitivity upon addition of
＋
＋
＋
＋
metal ions. The sensitivity of FMNC to alkaline earth metal ions was Ba2 ＞Sr2 ＞Ca2 ≈Mg2
.
Keywords 15-aza-5-crown ether, 9-benzylidene-9H-fluorene, alkaline earth metal ion
Introduction
pany and used without further purification.
A lot of direct sensing schemes have been described
using fluorescent chemosensory molecules (fluoro-
ionophores) whose optical properties changed upon di-
rect binding of the cation. The photophysics and photo-
chemistry of fluorophore linked to crown ether is an
area of growing interest.[1-4] A number of these styryl
derivatives linked to crown ether were reported to have
high fluorescence quantum efficiency and selectivity for
the metal ions.[5-10] However, photophysical properties
of these styryl compounds will be worst affected due to
conversion of the trans isomer into the cis isomer
during the radiation of light.[11]
In the search for stable and efficient styryl chemo-
sensory, we found 9-benzylidene-9H-fluorene, a kind of
styryl derivative, was a suitable candidate for fluoro-
phore because it would not occur isomerization during
the radiation of light due to the symmetry property of
double bond in molecular structure. This led us to syn-
thesize a new styryl molecule 13-(2-(9H-fluoren-9-
ylidene)methyl)-4-nitrophenyl)-1,4,7,10-tetraoxa-3-aza-
cyclopentadecane (2-FMNC). For comparison, 13-(2-
(9H-fluoren-9-ylidene)methyl)-4-nitrophenyl)-1,4,7,10-
tetraoxa-3-azacyclopentadecane (3-FMNC) was also
targeted.
Synthesis of 2-FMNC
Process for preparation of 5-nitro-2-(1,4,7,10-
tetraoxa-13-azacyclopentadecan-13-yl) benzaldehyde
(3a) Under N2 protection, Pd(CH3COO)2 (10 mg),
o-phenanthroline (11 mg) and aza-15-crown-5 (0.24 g,
1.10 mmol) were added to a stirred hexamethylphos-
phamide solution of 2-chloro-5-nitrobenzaldehyde (0.2
g, 1.10 mmol). The reaction mixture was immersed in
80 ℃ oil bath and stirred at this temperature for 24 h.
After cooling to room temperature, the reaction mixture
was diluted with 20 mL CH2Cl2, washed with water,
dried over Na2SO4, and the solvent was removed on
vacuum. The residue was purified by chromatography
on silica gel, eluting with EtOAc-petroleum ether (1∶1,
volume ratio), to afford yellow oil.[12] Yield 52%. H
1
NMR (CDCl3, 400 MHz) δ: 10.06 (s, 1 H), 8.59 (s, 1H),
8.22 (d, J＝9.2 Hz, 1H), 7.25—7.27 (m, 1H), 3.77—
3.79 (m, 4H), 3.63—3.71 (m, 16H); 13C NMR (CDCl3,
100 MHz) δ: 188.8, 157.0, 139.7, 129.0, 128.6, 125,
118.9, 77.3, 77.0, 76.7, 71.2, 70.7, 70.4, 69.2, 55.1; MS
m/z: 368.2. Anal. calcd for C17H24N2O7: C 55.43, H 6.57,
N 7.60; found C 55.48, H 6.72, N 7.67.
Process for preparation of 13-(2-(9H-fluoren-9-
ylidene)methyl)-4-nitrophenyl)-1,4,7,10-tetraoxa-3-
azacyclopentadecane (2-FMNC)
Compound 3a
(0.160 g, 0.43 mmol) was added to a solution of
triphenylphosponiumfluorenylide (0.188 g, 0.43 mmol)
in 5 mL of chloroform. After heating the orange solu-
tion under reflux for 3 h, the solvent was evaporated on
the steam bath. The residual oil was purified by chro-
matography on silica gel, eluting with EtOAc-petroleum
Experimental
Materials
Solvents and reagents used in the synthesis of
chemosensors 2-FMNC and 3-FMNC were purchased
from Aladdin Reagent Company or Alfa Aesar Com-
*
E-mail: caojing8088@xtu.edu.cn; Tel.: 0086-0731-58292251; Fax: 0086-0731-58292251
Received January 18, 2012; accepted March 29, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200047 or from the author.
Chin. J. Chem. 2012, 30, 1571—1574
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Cao, Li & Feng
FULL PAPER
ether (1∶1, volume ratio), to afford orange product,
m.p. 170 ℃, yield 45%; 1H NMR (CDCl3, 400 MHz) δ:
8.48 (s, 1H), 8.20 (d, J＝8.9 Hz, 1H), 7.81—7.56 (m,
3H), 7.55 (d, J＝7.7 Hz, 1H), 7.44—7.10 (m, 6H), 3.57
—3.67 (m, 20H); 13C NMR (CDCl3, 100 MHz) δ: 155.6,
141.7, 139.9, 139.3, 139.1, 136.7, 136.2, 135.9, 129.0,
128.5, 128.3, 127.1 (2C), 126.8, 126.8, 125.0, 124.6,
124.1, 120.4, 120, 119.7, 117.3, 77.3, 77.0, 76.7, 71.1,
54.0; MS m/z: 516.4. Anal. calcd for C30H32N2O6: C
69.75, H 6.24, N 5.42; found C 69.14, H 6.31, N 5.36.
immersed in 80 ℃ oil bath and stirred at this tempera-
ture for 24 h. After cooling to room temperature, the
reaction mixture was diluted with 100 mL CH2Cl2,
washed with water, dried over Na2SO4, and solvent was
removed on vacuum. The residue was purified by
chromatography on silica gel, eluting with EtOAc-
petroleum ether (1∶1, volume ratio), to afford yellow
solid power (0.56 g), m.p. 120 ℃, yield 34 %; 1H NMR
(CDCl3, 400 MHz) δ: 8.31 (d, J＝9.4 Hz, 1H), 7.97 (s,
1H), 7.89 (d, J＝6.6 Hz, 1H), 7.71—7.72 (m, 2H), 7.18
—7.41 (m, 4H), 6.99—7.05 (m, 1H), 6.78 (d, J＝6.9 Hz,
2H), 3.58—3.73 (m, 20H); 13C NMR (CDCl3, 100 MHz)
δ: 151.5, 141.5, 139.3, 139.2, 136.5, 135.8, 135.3, 128.4,
128.1, 127.1, 126.5, 126.2, 124.5, 120.7, 119.8, 119.5,
113.5, 110.9, 77.28, 76.97, 76.65, 71.21, 70.29, 70.06,
68.25, 53.00. MS m/z: 516.4. Anal. calcd for
C30H32N2O6: C 69.75, H 6.24, N 5.42; found C 69.88, H
6.51, N 5.47.
Synthesis of 3-FMNC
Process for preparation of 9-(5-chloro-2-nitro-
benzylidene)-9H-fluorene (3b) 3-Chloro-6-nitro-
benzaldehyde (0.418 g, 2.26 mmol) was added into a
solution of triphenylphosponium fluorenylide (1.006 g,
2.36 mmol) in 12 mL of chloroform. After heating the
orange solution under reflux for 3 h, the solvent was
evaporated on the steam bath. The residual oil was puri-
fied by chromatography on silica gel, eluting with
EtOAc-petroleum ether (1∶1, volume ratio) to afford
Method
Absorption spectra were recorded on a Lambda 25
spectrophotometer under the control of a Pentium PC
running the manufacturer-supplied software package.
Fluorescence spectra were obtained on a Perkin-Elmer
LS55 luminescence spectrometer with 10 nm excitation
and emission slit widths, excitation at 378 nm. All solu-
tions of fluorescent chemosensory were prepared in
spectroscopic grade acetonitrile without special efforts
to exclude water or air. Fluorescence titrations were
1
yellow powder, m.p. 173 ℃, yield 46%; H NMR
(CDCl3, 400 MHz) δ: 8.26 (d, J＝8.8 Hz, 1H), 7.83 (d,
J＝7.4 Hz, 1H), 7.78—7.71 (m, 3H), 7.59 (dd, J＝1.8,
8.8 Hz, 1H), 7.43—7.34 (m, 3H), 7.28 (s, 1H), 7.05—
6.97 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ: 146.1,
141.8, 139.8, 138.7, 137.9, 135.7, 134.7, 132.4, 129.3,
129.1, 127.4, 126.9, 126.5, 124.0, 121.1, 120.8, 120.1,
119.7. MS m/z: 333.1. Anal. calcd for C20H12ClNO2: C
71.97, H 3.62, N 4.20; found C 72.03, H 3.68, N 4.35.
Process for preparation of 13-(2-(9H-fluoren-
9-ylidene)methyl)-4-nitrophenyl)-1,4,7,10-tetraoxa-
3-azacyclopentadecane (3-FMNC) To a stirred
hexamethylphosphamide solution of 9-(5-chloro-
2-nitrobenzylidene)-9H-fluorene (1.024 g, 3.10 mmol),
CuI (33.9 mg) and o-phenanthroline (28.8 mg) were
added, aza-15-crown-5 (0.7075 g, 3.23 mmol) was
added in under N2 protection. The reaction mixture was
carried out with metal ion aqueous solutions (2.1×10－
6
－
1
mol•L ) to acetonitrile solution of compound FMNC
－
(2.1×10－6 mol•L ).
1
Results and Discussion
The stability of 2-FMNC and 3-FMNC to the
radaition
As we known, stilbene would occur trans-cis
Scheme 1 Synthetic routes for chemosensory 2-FMNC and 3-FMNC
CHO
NO2
Cl
OHC
O
O
O
PPh3
HNO3
aza-15-crown-5 O2N
CHO
Cl
O
N
O
N
O
O
O
3a
O2N
2-FMNC
Cl
CHO
O2N
aza-15-crown-5
Cl
HNO3
PPh3
O
CHO
N
Cl
NO2
O
O2N
3b
O
O
3-FMNC
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 1571—1574

9-Benzylidene-9H-fluorene Derivatives Linked to Monoaza-15-crown-5
＋
＋
＋
isomerization under the radiation of light since the tor-
sion of double bond became easy in the excited state.[11]
Although the compounds of FMNC we designed
contained a double bond, they did not give isomers since
in the case of a molecule containing a double bond, for
example, WXC＝CYZ (W, X, Y and Z are substituting
groups on the double bond), isomerization would not
exist where W＝X or Y＝Z.
The experiment also demonstrated that FMNC were
very stable in solution that repetitive absorption spectra
showed almost no change under ambient light for
several days. Instead, the literature reported some of the
styryl compounds linked to azacrown showed a partial
conversion of the trans isomer into the cis isomer in a
short period.[13]
Sr2 and Ba2 , especially for Ba2 . The relative fluo-
rescence intensity of 2-FMNC and 3-FMNC reached to
41, and 34.8 respectively, which was about three times
＋
＋
of that of the Sr2 and much more than that of the Ca2 .
As a result of all above, we have come to the conclusion
that the substituting position on benzene nucleus had
slightly effect on selectivity and sensitivity of chemo-
sensory molecules. The experiment results indicated that
alkaline earth metal ions with the larger atomic weight
would cause the stronger fluorescence enhancement of
FMNC.
The observed variations in the FMN-crown emission
spectrum with cations were believed to be due to hin-
dering process of photoinduced electron transfer (PET)
between the aza group and fluorophore, coordination of
the alkali earth ion to the oxygens and nitrogen atom of
the crown raised the one-electron oxidation potential of
the crown, effectively shutting down photoinduced elec-
tron transfer to the excited fluorophore.[14]
The selectivity of 2-FMNC and 3-FMNC to metal
ions
2-FMNC and 3-FMNC displayed very weak fluo-
rescence in solution. The selectivity of the probes
2-FMNC and 3-FMNC towards metal ions were tested
upon addition of metal ions (50 equiv.), as shown in
Figure 1. Nearly no fluorescence intensity changes were
As mentioned above, the largest fluorescence en-
＋
hancement was observed upon addition of Ba2 , next
＋
＋
＋
Sr2 , Ca2 and Mg2 were least. The results were
hardly explained because the cavity size of the crown
＋
＋
observed in emission spectra with Na＋, K＋, Cd2 , Mg2 ,
＋
was more suitable for Ca2 . We assumed that the heavy
＋
＋
Mn2 , Hg2 and Li＋. However, under identical condi-
cations were also difficult for photoejection since
photorelease of cations from a “cage” was possible by
photoinduced irreversible changes in the chemical
structure of a chelator.[15,16] The rate of photorelease of
tions, fluorescence intensities were greatly enhanced in
＋
the presence of alkaline earth metal ions such as Ca2 ,
some cations from complexes of crowned styryl deriva-
＋
tives found to be slower for the Ca2 complex than for
＋
the Li＋ complex, was reported (see Figure 2).[17] Sr2
in acetonitrile was also found to exhibit the same trends
＋
as reported and much slower than that of Ca2 .[18] All
these gave supports for our assumption.
hv
O
M+
NC
O
O
N
O
A
D
Figure 2 Photorelease of cation from a “cage” of styryl deriva-
tives.
＋
The fluorescence titration of FMNC with Ba2 and
＋
Sr2
Figure 3 showed the results of fluorescence titration
＋
of FMNC with Ba2 . When excited at 378 nm, the fluo-
rescence emission intensity around 420 nm was quite
＋
weak in the absence of Ba2
ion in acetonitrile
(Off-state). However, emission intensity created re-
markably enhancement (On-state) on changing the con-
＋
－
1
centration of Ba2 from 0 to 200 μmol•L . Similar
Figure 1 The relative fluorescence enhancement intensity of
(2.1×10－ mol•L－1) in acetonitrile at room temperature upon
6
‘Off-On’ behaviour was also observed in the presence of
＋
Sr2 (Figure S9). The equilibrium constant for the for-
addition of various metal cations; excitation at 392 nm; The con-
－
centration of metal cations (4.2×10－ mol•L 1) was 50 equiv. to
3
mation of [ML] from the interaction of FMNC and
compound. (a) 2-FMNC; (b) 3-FMNC.
metal ion could be calculated from the plot I0/[I－I0] vs.
Chin. J. Chem. 2012, 30, 1571—1574
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1573

Cao, Li & Feng
FULL PAPER
1/[M] using the Benesi-Hildebrand equation.[19] For
designed and synthesized by an apporiate introduction
of 9-benzylidene-9H-fluorene group as fluorophore. The
experiment results showed that 2-FMNC and 3-FMNC
have the similar response to alkaline earth metal ions.
The sensitivity of FMNC to alkaline earth metal ions
＋
example, the Ksv of Ba2 with 2-FMNC was 4.30×105,
＋
but that of Sr2 was 7.17×103.
＋
＋
＋
＋
(Ba2 ＞Sr2 ＞Ca2 ≈Mg2 ) revealed that the larger
size and atomic weight of alkaline earth metal ion led to
a better fit to aza-15-crown-5.
Acknowledgement
We thank for financial support by the open project
program of Key Laboratory of Environmentally
Friendly Chemistry and Applications of Ministry of
Education, China (No. 09HJYH04).
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6
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＋
The UV-vis absorption titration of FMNC with Ba2
＋
and Sr2
The UV-vis absorption spectra of 2-FMNC and its
＋
titration with Ba2 were measured in acetonitrile (Fig-
ure S10 (a)). 2-FMNC exhibited its lowest energy ab-
sorption at 230 and 380 nm, which gradually increased
in intensity and did not shift in wavelength with the se-
＋
quential addition of Ba2 ion. This also proved that the
fluorescence ‘on-off’ of FMNC was due to the PET
＋
process. The 2-FMNC and Sr2 complex had the simi-
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difference (Figure S10 (b)).
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To avoid photoisomerisation of chemosensory, two
new styryl molecules, 2-FMNC and 3-FMNC, were
(Cheng, F.)
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