Calix[4]arene with lower-rim β-amino α,β-unsaturated ketones containing bis-chelating sites as a highly selective fluorescence turn-on chemosensor for two copper(II) ions

Article abstract of DOI:10.1002/ejoc.201001169

We report herein the synthesis of a fluorescence turn-on chemosensor, 25,27-bis{N-[1-(4-{[4-amino-4-(1-naphthyl)-2-oxo-3-butenyl]oxy}phenyl) aminocarbonyl]methoxy}-26,28-dihydroxycalix[4]arene (3b), which is highly selective toward Cu²⁺. The fluorescence intensity of 3b was enhanced upon adding [Cu(ClO₄)₂], which reached a maximum with approximately 4 equiv. of Cu²⁺ but then started to decrease in intensity at higher Cu²⁺ concentrations. Job plot experiments revealed a 1:2 binding stoichiometry of 3b with Cu²⁺. Based on ¹H NMR titration results, we infer that there are two possible binding sites for Cu²⁺ in 3b: one at the lower-rim phenolic-OH and amide groups, and the second at the β-amino α,β-unsaturated ketone groups. It is important to note that during the complexation of 3b with [Cu(ClO₄)₂], the Cu²⁺ ions were reduced to Cu⁺ by both the phenolic OH and the amines of the β-amino α,β-unsaturated ketones. Furthermore, control compounds 6 and 9b were synthesized to clarify the possible binding sites of Cu²⁺ in 3b. By comparing the binding constants of 3b, 6, and 9b with Cu²⁺, we found that 3b exhibited a positive allosteric behavior toward the coordination of two Cu²⁺ ions. Calix[4]arene 3b shows high binding selectivity toward Cu²⁺ ions, which causes a dramatic enhancement of the fluorescence intensities at 341 and 452 nm by 4- and 40-fold, respectively. Chemosensor 3b can recognized two Cu²⁺ ions; both ions are reduced to Cu⁺ by both the phenolic-OH and the amines of the β-amino α,β- unsaturated ketones. Copyright

Full text of DOI:10.1002/ejoc.201001169

FULL PAPER
DOI: 10.1002/ejoc.201001169
Calix[4]arene with Lower-Rim β-Amino α,β-Unsaturated Ketones Containing
Bis-Chelating Sites as a Highly Selective Fluorescence Turn-On Chemosensor
for Two Copper(II) Ions
I-Ting Ho,[a][‡] Jean-Ho Chu,[a][‡] and Wen-Sheng Chung*[a]
Keywords: Fluorescence / Ionophores / Sensors / Supramolecular chemistry / Copper / UV/Vis spectroscopy
We report herein the synthesis of a fluorescence turn-on
OH and amide groups, and the second at the β-amino α,β-
chemosensor, 25,27-bis{N-[1-(4-{[4-amino-4-(1-naphthyl)-2-
unsaturated ketone groups. It is important to note that during
oxo-3-butenyl]oxy}phenyl)aminocarbonyl]methoxy}-26,28-di- the complexation of 3b with [Cu(ClO4)2], the Cu2+ ions were
hydroxycalix[4]arene (3b), which is highly selective toward
Cu2+. The fluorescence intensity of 3b was enhanced upon
adding [Cu(ClO4)2], which reached a maximum with approx-
imately 4 equiv. of Cu2+ but then started to decrease in inten-
sity at higher Cu2+ concentrations. Job plot experiments re-
vealed a 1:2 binding stoichiometry of 3b with Cu2+. Based on
1H NMR titration results, we infer that there are two possible
binding sites for Cu2+ in 3b: one at the lower-rim phenolic-
reduced to Cu+ by both the phenolic OH and the amines of
the β-amino α,β-unsaturated ketones. Furthermore, control
compounds 6 and 9b were synthesized to clarify the possible
binding sites of Cu2+ in 3b. By comparing the binding con-
stants of 3b, 6, and 9b with Cu2+, we found that 3b exhibited
a positive allosteric behavior toward the coordination of two
Cu2+ ions.
The design of most fluorescent chemosensors for metal
ions are based on photophysical changes that involve, for
example, photoinduced electron transfer (PET),[6] metal–li-
gand charge transfer (MLCT),[7] or excimer/exciplex forma-
tion.[8] Although excimer emission has been frequently ob-
served in bis-fluorophore-substituted chemosensors that
change conformation upon adding metal ions, exciplex for-
mation, in contrast, has rarely been reported as a signaling
mechanism in ion-sensing systems.[8a,8b]
We have been using a strategy to construct a variety of
functionalized isoxazole units on calix[4]arene skeletons
through 1,3-dipolar cycloaddition of alkynes and various
aryl nitrile oxides.[9] Subsequent N–O bond cleavage of the
isoxazole units by [Mo(CO)6]-mediated ring opening reac-
tion leads to the formation of enaminone derivatives ef-
ficiently.[10] Enaminones, also named β-amino α,β-unsatu-
rated ketones, as one kind of 1,3-bifunctional compound,
have been frequently used as metal ion chelating ligands.[11]
For example, they have been used in the synthesis of metallo-
mesogens by coordination with Ni2+ and Cu2+ in liquid
crystal research.[12] Despite the useful properties of enamin-
one groups, to date, there have been few reports[13] on their
use as metal ion binding ligands in calix[4]arene related ion-
ophores. Our recent work showed that calix[4]arene with
lower-rim distal bis-β-amino α,β-unsaturated ketones can
function as a ditopic receptor for the simultaneous com-
plexation of copper and acetate ions.[14] The redox proper-
ties of Cu2+/Cu+ with phenol seems to be a ubiquitous phe-
nomenon, thus, the question arises: Can calix[4]arenes
Introduction
Calix[4]arenes, which are obtained from the oligomeriza-
tion of phenol and formaldehyde, offer a very useful molec-
ular scaffold for the construction of multivalent binding
sites.[1] Over the past few decades, much effort has been de-
voted to the development of appropriate calix[4]arene
chemosensors for the selective and sensitive detection of
heavy metal ions because of their essential or deleterious
roles.[2,3] For instance, although Cu2+ is biologically impor-
tant, its accumulation in the human body may induce he-
patic cirrhosis or neurodegenerative diseases.[4] Accordingly,
many fluorescent sensors for Cu2+ have been designed,[3,5]
however, most of them undergo fluorescence quenching
upon binding with Cu2+ [3a–3c,5a–5d]
Sensors that give fluo-
.
rescence enhancement upon binding with metal ions are
preferred for biological imaging over those that respond to
metal ions with a fluorescence quenching. Nevertheless,
sensors that “turn on” its fluorescence when complexed
with Cu2+ are still rare;[3d,3e,5e,5f] thus, it is still a demanding
task to develop new Cu2+ selective fluorescence turn-on
sensors.
[a] Department of Applied Chemistry, National Chiao-Tung
University,
Hsinchu 30050, Taiwan, ROC
Fax: +886-3-572-3764
E-mail: wschung@cc.nctu.edu.tw
[‡] Coauthors contributed equally to this work.
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001169.
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A Fluorescence Chemosensor for Copper(II) Ions
(which contain phenols) be used with fluorophores to gen- obtained through ring-opening reaction of the correspond-
erate useful Cu2+ sensors?
ing bis-isoxazoles 2a and 2b using [Mo(CO)6] as a rea-
Herein, we report a copper(II)-induced fluorescence gent.[10d] Previously, the [Mo(CO)6]-mediated ring-opening
turn-on chemosensor, 25,27-bis{N-[1-(4-{[4-amino-4-(1- reactions were reported[10c] to have 70–85% yields in molec-
naphthyl)-2-oxo-3-butenyl]oxy}phenyl)aminocarbonyl]- ular systems without calix[4]arenes, however, in calix[4]ar-
methoxy}-26,28-dihydroxycalix[4]arene (3b), which con- ene systems the isolated yields were in the range of 40–65%,
tains amide-linked β-amino α,β-unsaturated ketones as the despite the fact that the reactions were usually run to com-
Cu2+ recognition sites and naphthalene pendants as the pletion.[10b] This result might be due to strong coordination
fluorophore units. On the lower rim of the conical calix- of the β-amino ketone products with the pentacarbonylmo-
[4]arene framework, host 3b possesses two potential re- lybdenum, thus, hampering its isolation. Gratifyingly, by ex-
cognition sites for Cu2+ ions: one is near the β-amino α,β- tracting the reaction mixture successively with aqueous
unsaturated ketone groups and the second is situated near NH4OH and ethylenediaminetetraacetic acid (EDTA), fol-
the cavity formed by the phenolic-OH and amide groups. lowed by column chromatography, we were able to improve
The binding ability of 3b and control compounds 6, 9a, and the reaction yields to 60–80%. Control compounds 6, 9a
9b toward Cu2+ has been studied by UV/Vis, fluorescence, and 9b were also obtained using the same methodology.
1
and H NMR titrations.
The control compound 6 was synthesized to test the metal
ion binding ability of the calix[4]arene with two pendant N-
arylamidomethyl groups (the upper component of com-
pound 3b). Compounds 9a and 9b were synthesized to ver-
Results and Discussion
The syntheses of target molecules 3a and 3b and control ify the requirement for a calix[4]arene scaffold for the re-
compounds 6, 9a, and 9b are depicted in Scheme 1. 25,27- cognition of two Cu2+ ions. The structures of all products
1
Bis(carboxymethoxy)calix[4]arene (1) was prepared accord- were confirmed by H and 13C NMR spectroscopy, mass
ing to literature procedures.[15] Compounds 2a and 2b were spectrometry, and HRMS analyses (see Exp. Sect.).
synthesized in 75–80% yields by treatment of compound 1
Using UV/Vis spectroscopy and fluorescence spectrome-
with oxalyl chloride in anhydrous dichloromethane fol- try, the binding properties of 3b toward 15 different per-
lowed by coupling with phenylamines 4a and 4b (see the chlorate salts of metal ions (Li+, Na+, K+, Mg2+, Ca2+
,
Supporting Information). Compounds 3a and 3b were then Ba2+, Cr3+, Mn2+, Ni+, Cu2+, Zn2+, Hg2+, Ag+, Cd2+, and
Scheme 1. Syntheses of target compounds 3a and 3b, control compounds 6, 9a, and 9b. Reagents and conditions: (a) (i) oxalyl chloride,
CH2Cl2, 40 °C, 3 h, (ii) 4-{3-[4-(tert-butyl)phenyl]isoxazol-5-ylmethoxy}phenylamine (4a), 4-{[3-(naphthalen-1-yl)isoxazol-5-yl]-
methoxy}phenylamine (4b), or 4-propoxyaniline (5), Et3N, CH2Cl2, room temp., 24 h; (b) [Mo(CO)6], CH3CN/H2O, reflux, 2 h.
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Figure 1. (a) UV/Vis and (b) fluorescence spectra of 3b (20 μm) upon adding 5 equiv. of metal perchlorates (Li+, Na+, K+, Mg2+, Ca2+
Ba2+, Cr3+, Mn2+, Ni+, Cu2+, Zn2+, Hg2+, Ag+, Cd2+, and Pb2+) in acetonitrile. The excitation wavelength was 308 nm.
,
Pb2+) were screened in CH3CN, and the results are shown
To gain further insight into the binding of Cu2+ to 3b,
1
in Figure 1. In the absence of cations, calix[4]arene 3b ex- UV/Vis, fluorescence, and H NMR titration experiments
hibited an absorption band with λmax = 308 nm (Figure 1, were carried out. Upon titration of 3b with Cu2+, the ab-
a) and a very weak emission in the 300–600 nm region when sorption maximum at 308 nm gradually decreased in inten-
excited at 308 nm (Figure 1, b). Among the 15 metal ions sity with concurrent formation of a new absorption band
screened, only Cu2+ and Hg2+ led to some hypochromic near 438 nm (Figure 2, a). Two isosbestic points at 263 and
and bathochromic shifts in the UV/Vis spectra of 3b; 345 nm were observed, indicating the formation of a well-
furthermore, a small hyperchromic and bathochromic shift defined metal complex. The fluorescence intensity of the
was observed in the presence of Pb2+. In addition, only naphthyl monomer emission (341 nm) was enhanced and a
Cu2+ caused a dramatic enhancement of the fluorescence new broad emission band at 452 nm emerged, which may
intensities of 3b at 341 and 452 nm by 4- and 40-fold, be attributed to the emission of an excimer[17] or an exci-
respectively (Figure 1, b). These observations indicated that plex[8] of the β-amino β-naphthyl groups of 3b. When more
calix[4]arene 3b has a high selectivity and sensitivity toward than 4 equiv. of Cu2+ was added, the emission band at
Cu2+ [16]
.
452 nm started to decrease (Figure 2, b), which might be
Figure 2. (a) UV/Vis and (b) fluorescence emission spectra of 3b (20 μm) with various concentrations of [Cu(ClO4)2] in CH3CN. The
excitation wavelength was 308 nm. The inset shows the variation of fluorescence intensity at 341 and 452 nm of 3b by adding different
amounts of [Cu(ClO4)2]. (c) The Job plot of the 1:2 complex of 3b and Cu2+, where the difference in fluorescence intensity at 341 nm
(ΔI341 nm) was plotted against the mole fraction of 3b at an invariant total concentration of 20 μm in CH3CN. (d) Benesi–Hildebrand
plot of 3b (20 μm) with [Cu(ClO4)2] in CH3CN.[19]
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A Fluorescence Chemosensor for Copper(II) Ions
due to an “inner filter effect”[18] of the absorption band at
438 nm. Alternatively, the increased metal complex concen-
tration may contribute to the static quenching of the emis-
sion at 452 nm. Interestingly, a Job plot experiment, using
the fluorescence spectra of 3b and Cu2+ with a total concen-
tration of 20 μm, revealed that the complexation between 3b
and Cu2+ adopted a 1:2 binding ratio (Figure 2, c). The
association constant (Ka) of the 1:2 complex 3b·(Cu2+)2 was
calculated to be 2.02ϫ109 m–2 by a Banesi–Hildebrand
plot.[19b]
In contrast to the 1:2 binding ratio of 3b with Cu2+, its
binding ratios with Hg2+ and Pb2+ were both determined
to be 1:1 by Job plot experiments (see Figures S-35 and S-
36, see the Supporting Information). Moreover, using Be-
nesi–Hildebrand plots, the association constants (Ka) of 3b
with Hg2+ and Pb2+ ions in CH3CN were calculated to be
6.66ϫ103 and 1.47ϫ104 m–1, respectively (see Table 1).[19]
Figure 3. Excitation spectrum (normalized) of 3b (20 μm) in the
presence of 5 equiv. of [Cu(ClO4)2] in CH3CN monitored at 341 nm
for the monomer (solid line) and at 452 nm for the excimer (dashed
line).
As described above, the lower rim cavity around the
phenolic-OH and amide groups of 3b may constitute the
second possible binding site for Cu2+. The new absorption
band of the complex at 438 nm is characteristic of an
MLCT band between Cu+ and the lower rim phenolic-
OH.[12b,13] This means that Cu2+ was reduced to Cu+ by
the phenolic OH groups of calix[4]arene 3b, and that the
oxidized phenols help to trap the reduced Cu+.[20] The auto-
reduction of Cu2+ by phenol is well-documented,[21] and the
reduction of Cu2+ by 3b was verified by EPR experiments
(Figure 4). The EPR signals of the paramagnetic Cu2+ in
CH3CN at 77 K were diminished by adding different
amounts of 3b. The results are consistent with our previous
observations in other calix[4]arene systems containing pen-
dant β-amino α,β-unsaturated ketones.[14] The addition of
0.5 equiv. of 3b reduced the EPR intensity of Cu2+ to about
12%, which implied that both of the Cu2+ binding sites of
3b have the potential to reduce Cu2+. However, the two
binding sites cannot effectively convert Cu2+ into Cu+ at
once, therefore, 12% of EPR signal remained. To clarify
whether 3b can bind Cu+ directly, we also studied its bind-
ing ability toward [Cu(CH3CN)4]PF6 by using UV/Vis spec-
troscopy; however, no change was observed (see Figure S-
38 in the Supporting Information).
Table 1. Fluorescence intensity changes [(I – Io)/Io], binding ratio,
and association constants (Ka) of 3b, 6, and 9b (20 μm) toward
Cu2+, Hg2+, and Pb2+
.
[a]
Host Metal (I – Io)/Io
Binding ratio Ka
ion
λ341nm λ452 nm
(host/MII)
3b
3b
3b
6
Cu2+
Hg2+
Pb2+
Cu2+
Cu2+
4.4
0.9
–0.2
–
41.8
1.6
1.3
1:2
1:1
1:1
1:1
1:1
2.02 (Ϯ0.11)ϫ109 m–2
6.66 (Ϯ4.01)ϫ103 m–1
1.47 (Ϯ0.17)ϫ104 m–1
6.82 (Ϯ2.81)ϫ103 m–1
2.52 (Ϯ0.30)ϫ104 m–1
–
9b
16.2
221[b]
[a] Fluorescence intensity changes of 3b, 6, and 9b after adding
5 equiv. of metal ions. [b] The emission maximum was at 446 nm.
To explain the observed 1:2 binding ratio of 3b with
Cu2+, we looked for possible binding sites in the host. Un-
doubtedly, the β-amino α,β-unsaturated ketone groups of
3b must constitute one of the possible binding sites for
Cu2+, whereas the lower rim cavity around the phenolic-
OH and amide groups of 3b might constitute the second.
The UV/Vis and fluorescence spectra of 3b with Cu2+ pro-
vided some clues to the possible binding sites. On the one
hand, the absorption band at 308 nm, attributed to the ab-
sorption of β-amino α,β-unsaturated ketone conjugated
naphthalene, gradually decreased in intensity during the ad-
dition of Cu2+. On the other hand, the fluorescence of 3b
was enhanced by the addition of Cu2+, which supports the
notion that β-amino α,β-unsaturated ketones form a strong
complex with Cu2+. Such a chelation-enhanced fluores-
cence (CHEF) of 3b was presumably mainly due to the con-
formational restriction of the two β-amino α,β-unsaturated
ketone groups when chelated with Cu2+, which inhibited
intramolecular charge transfer. Furthermore, the excitation
spectrum of 3b in the presence of 5 equiv. of Cu2+ moni-
tored at 452 nm was broadened and red-shifted (Δλ = 4 nm)
compared to that monitored at 341 nm for the monomer
(Figure 3). The results implied that the two emission bands
observed in Figure 2 (b) should be generated from different
species, which might be a static excimer[17] or an exciplex[8b]
Figure 4. EPR spectra of [Cu(ClO4)2] (5 mm) after adding different
amounts (a) 0, (b) 0.2, (c) 0.5, and (d) 1.0 equiv. of 3b at 77 K,
recorded at X-band with microwave power of 20 mW and micro-
wave frequency of 9.5 GHz.
To further confirm the proposed double binding sites for
when 3b is complexed with Cu2+
.
Cu2+ in 3b, we carried out H NMR titration experiments
1
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with tert-butylphenyl-substituted calix[4]arene 3a by adding servations, we believe that the lower rim phenol hydroxyl
[Cu(ClO4)2]. We used 3a (R = tert-butylphenyl) instead of groups and the amide groups might assist each other in the
3b (R = 1-naphthyl) to investigate the effect of added [Cu- coordination of Cu+.
1
(ClO4)2] on the H NMR chemical shift changes because
The infrared spectra of 3b and 3b·(Cu+)2 provided fur-
the former has a simpler proton splitting pattern than the ther structural information on the complex (see Figure S-
1
latter. Detailed assignment of the H NMR signals of 3a 39 in the Supporting Information). For compound 3b, the
was based on HMQC, HMBC, and 2D H,H-COSY experi- 1604 cm–1 band is characteristic of the conjugated C=O
ments (Figures S-19 to S-22 in the Supporting Infor- group of an enaminone, in which intramolecular hydrogen
1
mation). The H NMR spectra of ligand 3a in CD3CN in bonding substantially lowers the C=O stretching fre-
the presence of different amounts of Cu2+ are depicted in quency.[12b,23] Compound 3b also shows a typical C=O
Figure 5 (for proton labeling of 3a, see Scheme 1). The band of an amide group at 1684 cm–1. The infrared spec-
methylene protons (He) near the α,β-unsaturated ketones trum of the complex 3b·(Cu+)2 showed a significant shift of
were downfield shifted from δ = 5.26 ppm to δ = 5.64 ppm the amide C=O frequency from 1684 to 1664 cm–1, which
(Δδ = +0.38 ppm) in the presence of 2 equiv. of Cu2+. Such might be due to the binding of Cu+ with the nitrogen of
a downfield shift of He is expected when metal ions form a the amide group.[24] A literature survey also supported the
complex with the carbonyl groups of the α,β-unsaturated idea that Cu2+/Cu+ ions preferentially coordinate with the
ketones. In addition, the signals of the amino protons (Hg nitrogen atoms of amide groups.[19b,25] Furthermore, the IR
and Hh) disappeared and this was accompanied by the ap- signals of enaminones (C=O at 1604 cm–1 and C=C at
pearance of a new 1:1:1 triplet signal at δ = 6.82 (J = 1531 cm–1) were found to be broadened and slightly shifted
53 Hz); the unique triplet pattern was probably due to the to higher frequency when 3b complexed with Cu+. The for-
splitting of a metal-bound amino group by the nitrogen nu- mation of complex 3b·(Cu+)2 was also confirmed by the
cleus (I = 1).[14,22] Furthermore, the signals in the aromatic FAB mass spectrum (see Figure S-40 in the Supporting In-
region (δ = 7.5 to 8.8 ppm) became more complicated and formation), which showed a peak at m/z 633.
was accompanied by the appearance of some new signals.
Based on the information obtained from UV/Vis, fluores-
1
Signals of the phenolic-OH and amide-Hb were first broad- cence, IR, H NMR, and EPR spectroscopic studies upon
ened and then disappeared during the addition of 0– adding Cu2+ to 3b, we propose a possible binding mode for
3.0 equiv. of Cu2+ ions (Figure 5, a–e). Based on these ob- the 1:2 complex of 3b with two Cu+ as shown in Scheme 2.
1
Figure 5. H NMR spectra of 3a (5 mm) in CD3CN in the presence of different amounts of Cu[(ClO4)2]: (a) 0, (b) 0.2, (c) 0.4, (d) 0.6,
(e) 0.8, (f) 1.0, (g) 1.5, (h) 2.0 and (i) 3.0 equiv. Where * denotes external standard CHCl3. The intensity of spectra f–i was doubled for
observing the weak new signals. For proton labeling of 3a, see Scheme 1.
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A Fluorescence Chemosensor for Copper(II) Ions
In the lower part of the complex 3b·(Cu+)2, two β-amino Figure S-45 in the Supporting Information) and its absorp-
α,β-unsaturated ketone moieties collaborate to coordinate tion spectra showed a hypochromic effect and a small ba-
to Cu+ with a tetrahedral geometry.[26] Concurrently, the thochromic shift with isosbestic points at 243 and 349 nm
phenolic hydroxyl group on the lower rim of calix[4]arene (Figure 6, a). It should be noted that there is a major differ-
3b also chelates with a Cu+ ion, and the amide groups ence between the absorption spectra of 9b and 3b when
nearby should assist in this coordination.
these compounds were titrated with Cu2+; the former did
not show an MLCT band around 438 nm (cf. Figure 2, a).
Despite this difference in absorption spectra, the emission
phenomena of both compounds were quite similar: both
the monomer emission (λem = 341 nm) and the longer emis-
sion bands (λem = 446 nm) of 9b were gradually enhanced
upon adding Cu2+ (Figure 6, b). The new, broad emission
band at 446 nm is unlikely to arise from the emission from
a naphthyl excimer because the possibility of forming an
intermolecular complex at such a low concentration (20 μm)
is slim.[28] Thus, the new emission band may be attributed
to exciplex formation between Cu+ and the β-amino β-
naphthyl α,β-unsaturated ketone of 9b. Exciplex formation
between Ag+ and several aromatic moieties has been report-
ed,[8a,27] however, to the best of our knowledge, there has
been no report of such an exciplex formation between a β-
amino β-naphthyl α,β-unsaturated ketone and Cu2+. To
fully understand the mechanism of exciplex formation, ad-
ditional photophysical measurements, such as time-resolved
Scheme 2. Possible binding mode of 3b with two Cu+ ions.[27]
Control compounds 6, 9a, and 9b were also synthesized fluorescence or laser flash photolysis experiments, would be
to provide further evidence for the proposed binding modes. needed in the future. We also found that Cu2+ was reduced
The recognition of Cu2+ by calix[4]arene 6, which possessed by 9b, as evidenced by the silent EPR signal of Cu2+ by
only the pendant N-arylamidomethyl groups (the upper added 9b (see Figure S-42c in the Supporting Information).
component of compound 3b) without the β-amino α,β-un- In our previous work,[14] we found that the β-amino α,β-
saturated ketones, was investigated by UV/Vis spectroscopy, unsaturated ketone could participate in the reduction of
1H NMR, ESI-MS, and EPR analyses. The UV/Vis spec- Cu2+ in a lower-rim propyl ether protected calixarene. Here,
trum of calix[4]arene 6 with Cu2+ in CH3CN was similar to
that observed in 3b, where a new broad absorption band at
438 nm appeared (see Figure S-41 in the Supporting Infor-
mation). The association constants (Ka) of 6 with Cu2+ was
calculated to be 6.82ϫ103 m–1 from a Benesi–Hildebrand
plot.[19a] The EPR signal of Cu2+ disappeared after adding
1 equiv. of calix[4]arene 6 (Figure S-42), which supported
the proposal that the autoreduction of Cu2+ to Cu+ oc-
1
curred in the presence of 6. In addition, H NMR signals
of the hydroxyl protons of 6 disappeared after adding
1 equiv. of Cu2+, implying the participation of phenol hy-
droxyl groups in the complexation (see Figure S-43 in the
Supporting Information). It is worth noting that all the pro-
ton signals, except the hydroxyl protons, were little shifted,
which implied that the binding interaction of 6 with Cu+
was weak. Furthermore, the ESI mass spectrum (see Fig-
ure S-44 in the Supporting Information) showed two peaks
at m/z 869.4 and 871.4, which corresponded to the calcu-
lated mass of 6·63Cu+and 6·65Cu+, respectively. These re-
sults support the proposal that the lower rim of 6 alone can
recognize Cu2+ and create a UV/Vis band at 438 nm, which
is similar to the spectra observed in the complexation of 3b
with Cu2+ (see above).
Figure 6. (a) UV/Vis and (b) fluorescence emission spectra of 9b
In a similar way, the binding ability of control compound
(20 μm) with various amounts of [Cu(ClO4)2] in CH3CN. Excitation
9b toward Cu2+ was also investigated. Compound 9b, which
wavelength was 308 nm. The inset shows the variation of fluores-
cence intensity of 9b at 341 and 446 nm with different amounts of
resembles the structure of 3b but without a calix[4]arene
scaffold, also showed selective binding toward Cu2+ (see [Cu(ClO4)2].
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the autoreduction of Cu2+ to Cu+ by a β-amino α,β-unsatu-
rated ketone was again proven to be efficient in the control
compound 9b, therefore, the need for a calixarene scaffold
can be excluded for the autoreduction of Cu2+ to Cu+.
From the titration experiment, the association constant[19a]
of 9b with Cu2+ was calculated to be 2.52ϫ104 m–1, and
the binding ratio determined by the Job plot was 1:1 (see
Figure S-47 in the Supporting Information). The binding
25,27-Bis(N-{1-[4-({3-[4-(tert-butyl)phenyl]-5-isoxazolyl}methoxy)-
phenyl]aminocarbonyl}methoxy)-26,28-dihydroxycalix[4]arene (2a):
Yield 80% (175 mg); white solid; m.p. Ͼ270 °C (decomp.); Rf =
1
0.35 (n-hexane/ethyl acetate, 1:1). H NMR (300 MHz, CDCl3): δ
= 1.32 (s, 18 H, tBu), 3.58 (d, J = 13.5 Hz, 4 H, ArCH2Ar), 4.22
(d, J = 13.5 Hz, 4 H, ArCH2Ar), 4.62 (s, 4 H, Ha), 5.16 (s, 4 H,
He), 6.70 (s, 2 H, Hf), 6.76–6.82 (m, 6 H, Ar-H), 6.90 (t, J = 7.5 Hz,
2 H, Ar-H), 7.03 (d, J = 7.5 Hz, 4 H, Ar-H), 7.15 (d, J = 7.4 Hz,
4 H, Ar-H), 7.34 (d, J = 9.0 Hz, 4 H, Ar-H), 7.45 (d, J = 8.4 Hz,
4 H, tBu-Ph), 7.78 (d, J = 8.4 Hz, 4 H, tBu-Ph), 8.36 (s, 2 H, OH),
1
of Cu+ with 9a was also supported by H NMR titration
experiments (see Figure S-48 in the Supporting Infor- 10.19 (s, 2 H, Hb) ppm. 13C NMR (75 MHz, CDCl3): δ = 31.2
(CH3), 31.8 (CH2), 34.8 (Cq), 61.9 (CH2), 74.8 (CH2), 101.4 (CH),
115.1 (CH), 120.4 (CH), 121.1 (CH), 125.8 (CH), 125.9 (Cq), 126.6
(CH), 127.1 (CH), 127.5 (Cq), 129.2 (CH), 129.9 (CH), 131.6 (Cq),
132.6 (Cq), 150.3 (Cq), 151.7 (Cq), 153.3 (Cq), 154.4 (Cq), 162.4
(Cq), 164.7 (Cq), 168.4 (Cq) ppm. MS (FAB): m/z = 1149 [M +
H+]. HRMS: calcd. for C72H69N4O10 1149.5013; found 1149.5032.
mation). By comparing the binding constants of 3b, 6, and
9b with Cu2+ (see Table 1), we found that 3b exhibited posi-
tive allosteric[29] behavior toward the coordination of two
Cu2+ ions. In other words, when one of the two binding
sites of 3b chelates the first Cu2+, the conformation of the
second binding site changes and helps the complexation of
the second Cu2+ ion.
25,27-Bis{N-[1-(4-{[3-(1-naphthyl)-5-isoxazolyl]methoxy}phenyl)-
aminocarbonyl]methoxy}-26,28-dihydroxycalix[4]arene (2b): Yield
75% (162 mg); yellowish-brown solid; m.p. 150–151 °C; Rf = 0.41
(n-hexane/ethyl acetate, 1:1). 1H NMR (300 MHz, CDCl3): δ = 3.59
(d, J = 13.5 Hz, 4 H, ArCH2Ar), 4.23 (d, J = 13.5 Hz, 4 H, Ar-
CH2Ar), 4.64 (s, 4 H, Ha), 5.22 (s, 4 H, He), 6.71 (s, 2 H, Hf), 6.77–
6.94 (m, 8 H, Ar-H), 7.05 (d, J = 7.5 Hz, 4 H, Ar-H), 7.16 (d, J =
Conclusions
We have reported the syntheses of a novel fluorescence
turn-on chemosensor 3b, which showed high selectivity and
sensitivity toward Cu2+ among 15 different metal ions 7.5 Hz, 4 H, Ar-H), 7.38 (d, J = 9.1 Hz, 4 H, Ar-H), 7.49–7.57 (m,
6 H, naphthyl-H), 7.74 (dd, J = 7.2, 1.2 Hz, 2 H, naphthyl-H),
7.87–7.95 (m, 4 H, naphthyl-H), 8.35 (s, 2 H, OH), 8.41–8.45 (m,
2 H, naphthyl-H), 10.20 (s, 2 H, Hb) ppm. 13C NMR (75 MHz,
CDCl3): δ = 31.8 (CH2), 61.9 (CH2), 74.8 (CH2), 104.8 (CH), 115.2
(CH), 120.5 (CH), 121.1 (CH), 125.2 (CH), 125.7 (CH), 126.3
(CH), 126.5 (Cq), 127.1 (CH), 127.1 (CH), 127.5 (Cq), 128.0 (CH),
128.4 (CH), 129.2 (CH), 129.9 (CH), 130.3 (CH), 130.9 (Cq), 131.7
(Cq), 132.6 (Cq), 133.8 (Cq), 150.3 (Cq), 151.7 (Cq), 154.5 (Cq),
162.7 (Cq), 164.7 (Cq), 167.9 (Cq) ppm. MS (FAB): m/z = 1137 [M
+ H+]. HRMS: calcd. for C72H56N4O10 1136.3999; found
screened. Calix[4]arene 3b was found to coordinate with
two equivalents of [Cu(ClO4)2] through two binding sites:
(1) the lower-rim phenolic-OH and amide groups, and (2)
the pendant β-amino α,β-unsaturated ketones. It should be
noted that the autoreduction of Cu2+ to Cu+ was observed
during complexation of 3b. The association constant (Ka)
of the 1:2 complex 3b·(Cu+)2 was calculated to be
2.02ϫ109 m–2 by the Benesi–Hildebrand plot. Finally, an
exciplex emission from the complexation of 9b with Cu2+ is
unprecedented, and the system deserves further study with 1136.3983.
time-resolved fluorescence lifetime measurements to under-
stand the dynamics of such novel exciplex formation.
General Procedure for the Synthesis of 3a and 3b: To a well-stirred
solution of compound 2a–b (2a: 60.0 mg, 0.05 mmol; 2b: 100 mg,
0.09 mmol) and [Mo(CO)6] (4 equiv.) in CH3CN, was added 2–3
drops of water, then the reaction mixture was heated to reflux tem-
perature for 2 h. Subsequently, solvent was removed and the residue
was dissolved in CH2Cl2 (10 mL). The solution was treated with
aq. NH4OH (10 mL) and the organic layer was washed with water
(100 mL) and aq. 1 m EDTA (50 mL), dried with MgSO4, filtered,
and concentrated under reduced pressure. The residue was purified
by column chromatography to afford pure 3a–b in 60–80% yields.
Experimental Section
General: 1H NMR spectra were measured with either a 300 or
500 MHz spectrometer. Natural abundance 13C NMR spectra were
measured using pulse Fourier transform techniques, with a 300 or
500 MHz NMR spectrometer operating at 75.4 and 125.7 MHz,
respectively. Broad-band decoupling, DEPT, H,H-COSY, H,C-
COSY, HMQC, and HMBC were carried out to simplify spectra
and aid peak identification. All reported yields are quoted as an
average of three runs and are based on recovered starting materials.
25,27-Bis(N-{1-[4-({4-amino-4-[4-(tert-butyl)phenyl]-2-oxo-3-
butenyl}oxy)phenyl]aminocarbonyl}methoxy)-26,28-dihydroxy-
calix[4]arene (3a): Yield 80% (48.0 mg, 0.04 mmol); pale-yellow so-
lid; m.p. 196–198 °C; Rf = 0.44 (n-hexane/ethyl acetate, 1:3). 1H
NMR (300 MHz, CD3CN): δ = 1.28 (s, 18 H, tBu), 3.59 (d, J =
13.5 Hz, 4 H, ArCH2Ar), 4.28 (d, J = 13.5 Hz, 4 H, ArCH2Ar),
4.50 (s, 4 H, Ha), 4.63 (s, 4 H, He), 5.73 (s, 2 H, Hf), 6.51 (s, 2 H,
Hh), 6.71–6.83 (m, 6 H, Hd and Ho), 6.92 (t, J = 7.5 Hz, 2 H, Hk),
7.09 (d, J = 7.5 Hz, 4 H, Hl), 7.22 (d, J = 7.5 Hz, 4 H, Hp), 7.32
(d, J = 8.8 Hz, 4 H, Hc), 7.47 (d, J = 8.3 Hz, 4 H, Hj), 7.58 (d, J
= 8.3 Hz, 4 H, Hi), 8.33 (s, 2 H, OH), 9.89 (s, 2 H, Hb), 10.07 (br.
s, 2 H, Hg) ppm. 13C NMR (75 MHz, CDCl3): δ = 32.0 (CH3), 32.7
(CH2), 36.1 (Cq), 73.5 (CH2), 76.1 (CH2), 91.1 (CH), 116.3 (CH),
122.2 (CH), 122.6 (CH), 127.5 (CH), 128.0 (CH), 128.3 (CH), 129.3
(Cq), 130.8 (CH), 131.2 (CH), 133.0 (Cq), 135.0 (Cq), 135.3 (Cq),
152.5 (Cq), 153.3 (Cq), 156.1 (Cq), 156.5 (Cq), 164.5 (Cq), 166.6
General Procedure for the Synthesis of 2a and 2b: To a well-stirred
solution of 1 (100 mg, 0.19 mmol) and 2–3 drops of N,N-dimethyl-
formamide (DMF) in anhydrous CH2Cl2 (10 mL), was added ox-
alyl chloride (0.18 mL, 2.05 mmol) under nitrogen at room tem-
perature. The reaction mixture was heated at reflux temperature for
3 h. Solvent and excess oxalyl chloride were removed under reduced
pressure and the residue was further dried in vacuo. The residue
was dissolved in anhydrous CH2Cl2 (10 mL) followed by addition
of a solution of amines 4a–b (4a: 123 mg, 0.38 mmol; 4b: 120 mg,
0.38 mmol) and triethylamine (8–10 drops) in anhydrous CH2Cl2
(10 mL). The reaction mixture was heated to 40 °C for 24 h. After
evaporation of solvent, the crude product was purified by column
chromatography to afford 2a–b.
1478
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 1472–1481

A Fluorescence Chemosensor for Copper(II) Ions
(Cq), 195.2 (Cq) ppm. MS (FAB): m/z = 1153 [M + H+]. HRMS:
then, after evaporation of solvent, the crude product was purified
calcd. for C72H73N4O10 1153.5327; found 1153.5350.
by column chromatography to afford 8a–b.
25,27-Bis{N-[1-(4-{[4-amino-4-(1-naphthyl)-2-oxo-3-butenyl]oxy}- N-(4-{[3-(4-tert-Butylphenyl)isoxazol-5-yl]methoxy}phenyl)-2-(2,6-
phenyl)aminocarbonyl]methoxy}-26,28-dihydroxycalix[4]arene (3b): dimethylphenoxy)acetamide (8a): Yield 82% (218 mg); grayish white
Yield 60 % (60.0 mg, 0.05 mmol); pale-yellow solid; m.p. 170–
solid; m.p. 142–144 °C; Rf = 0.5 (n-hexane/ethyl acetate, 2:1). 1H
NMR (300 MHz, CDCl3): δ = 1.34 (s, 9 H, tBu), 2.28 (s, 6 H, Ar-
172 °C; Rf = 0.23 (n-hexane/ethyl acetate, 1:2). 1H NMR
(300 MHz, CDCl3): δ = 3.55 (d, J = 13.4 Hz, 4 H, ArCH2Ar), 4.20 CH3), 4.38 (s, 2 H, Ha), 5.16 (s, 2 H, Hc), 6.62 (s, 1 H, Hd), 6.97–
(d, J = 13.4 Hz, 4 H, ArCH2Ar), 4.54 (s, 4 H, Ha), 4.56 (s, 4 H,
7.05 (m, 5 H, Ar-H), 7.46 (d, J = 8.3 Hz, 2 H, Ar-H), 7.60 (d, J =
8.9 Hz, 2 H, Ar-H), 7.73 (d, J = 8.3 Hz, 2 H, Ar-H), 8.64 (s, 1 H,
He), 5.60 (br. s, 2 H, Hh), 5.74 (s, 2 H, Hf), 6.67–6.87 (m, 8 H, Ar-
H), 6.99 (d, J = 7.5 Hz, 4 H, Ar-H), 7.14 (d, J = 7.5 Hz, 4 H, Ar- Hb) ppm. 13C NMR (75 MHz, CDCl3): δ = 16.2 (CH3), 31.1 (CH3),
H), 7.28 (d, J = 8.9 Hz, 4 H, Ar-H), 7.39–7.53 (m, 8 H, naphthyl-
H), 7.79–7.85 (m, 4 H, naphthyl-H), 8.08–8.12 (m, 2 H, naphthyl-
H), 8.31 (s, 2 H, OH), 10.09 (s, 2 H, Hb), 10.23 (br. s, 2 H, Hg) ppm.
13C NMR (75 MHz, CDCl3): δc = 31.7 (CH2), 72.1 (CH2), 74.7
34.7 (Cq), 61.6 (CH2), 70.3 (CH2), 101.3 (CH), 115.2 (CH), 121.6
(CH), 124.8 (CH), 125.8 (CH), 126.5 (CH), 129.1 (CH), 130.2 (Cq),
131.2 (Cq), 153.3 (Cq), 154.0 (Cq), 154.7 (Cq), 162.3 (Cq), 166.4
(Cq), 168.0 (Cq) ppm. MS (FAB): m/z = 485 [M + H+]. HRMS:
(CH2), 94.0 (CH), 114.8 (CH), 120.6 (CH), 120.9 (CH), 125.0 (CH), calcd. for C30H32N2O4 484.2362; found 484.2367.
125.1 (CH), 125.7 (CH), 126.3 (CH), 126.9 (CH), 127.0 (CH), 127.5
2-(2,6-Dimethylphenoxy)-N-(4-{[3-(naphthalen-1-yl)isoxazol-5-
(CH), 128.3 (CH), 129.1 (CH), 129.8 (CH), 129.9 (Cq), 130.0 (CH),
130.8 (Cq), 132.6 (Cq), 133.5 (Cq), 135.1 (Cq), 150.4 (Cq), 151.7
(Cq), 155.0 (Cq), 163.3 (Cq), 164.6 (Cq), 194.7 (Cq) ppm. MS
(FAB): m/z = 1141 [M + H+]. HRMS: calcd. for C72H60N4O10
1140.4309; found 1140.4326.
yl]methoxy}phenyl)acetamide (8b): Yield 77% (203 mg); pale-yellow
1
solid; m.p. 129–130 °C; Rf = 0.65 (n-hexane/ethyl acetate, 1:1). H
NMR (300 MHz, CDCl3): δ = 2.26 (s, 6 H, Ar-CH3), 4.36 (s, 2 H,
Ha), 5.17 (s, 2 H, Hc), 6.63 (s, 1 H, Hd), 6.96–7.03 (m, 5 H, Ar-H),
7.45–7.53 (m, 3 H, naphthyl-H),7.59 (d, J = 8.9 Hz, 2 H, Ar-H),
General Procedure for the Synthesis of 25,27-Bis[N-(1-propoxy- 7.66 (d, J = 6.6 Hz, 1 H, naphthyl-H), 7.85–7.91 (m, 2 H, naphthyl-
phenyl)aminocarbonyl]methoxy-26,28-dihydroxycalix[4]arene (6): H), 8.34–8.39 (m, 1 H, naphthyl-H), 8.64 (s, 1 H, Hb) ppm. 13C
The synthetic procedure was adapted from that used for com-
pounds 2a–b. Compounds 1 (100 mg, 0.19 mmol) and 5 (58.0 mg,
0.38 mmol) were used. Yield 80% (123 mg, 0.15 mmol); white solid;
NMR (75 MHz, CDCl3): δ = 16.2 (CH3), 61.5 (CH2), 70.3 (CH2),
104.7 (CH), 115.2 (CH), 121.5 (CH), 124.8 (CH), 125.0 (CH), 125.4
(CH), 126.1 (CH), 126.3 (Cq), 127.0 (CH), 127.7 (CH), 128.3 (CH),
m.p. 286–287 °C. 1H NMR (300 MHz, CDCl3): δ = 1.05 (t, J = 129.1 (CH), 130.2 (CH), 130.7 (Cq), 131.2 (Cq), 133.6 (Cq), 154.0
7.5 Hz, 6 H, CH3), 1.78–1.85 (m, 4 H, CH3CH2CH2), 3.58 (d, J = (Cq), 154.6 (Cq), 162.5 (Cq), 166.4 (Cq), 167.5 (Cq) ppm. MS (EI):
13.5 Hz, 4 H, Ar-CH2-Ar), 3.91 (t, J = 6.6 Hz, 4 H, CH3CH2CH2),
m/z = 478 [M]+. HRMS: calcd. for C30H26N2O4 478.1894; found
4.24 (d, J = 13.5 Hz, 4 H, Ar-CH2-Ar), 4.63 (s, 4 H, COCH2), 478.1884.
6.74–6.82 (m, 6 H, Ar-H), 6.88–6.93 (m, 2 H, Ar-H), 7.03 (d, J =
General Procedure for the Synthesis of 9a and 9b: To a well-stirred
7.5 Hz, 4 H, Ar-H), 7.16 (d, J = 7.5 Hz, 4 H, Ar-H), 7.29–7.32 (m,
4 H, Ar-H), 8.29 (s, 2 H, OH), 10.10 (s, 2 H, -NHCO) ppm. 13C
NMR (75 MHz, CDCl3): δ = 10.5 (CH3), 22.6 (CH2), 31.7 (CH2),
69.8 (CH2), 74.8 (CH2), 114.6 (CH), 120.7 (CH), 120.9 (CH), 126.9
(CH), 127.5 (Cq), 129.1 (CH), 129.8 (CH), 130.3 (Cq), 132.6 (Cq),
150.5 (Cq), 151.8 (Cq), 156.0 (Cq), 164.7 (Cq) ppm. MS (FAB):
m/z = 807 [M + H+]. HRMS: calcd. for C50H51N2O8 807.3647;
found 807.3628.
solution of compound 8a–b (8a: 100 mg, 0.21 mmol; 8b: 200 mg,
0.42 mmol) and [Mo(CO)6] (1.3 equiv.) in CH3CN (10 mL), was
added 2–3 drops of water, then the reaction mixture was heated to
reflux temperature for 2 h. The solvent was removed and the resi-
due was dissolved in CH2Cl2 (10 mL). The solution was treated
with aq NH4OH (10 mL) and the organic layer was washed with
water (100 mL) and aq. 1 m EDTA (50 mL), dried with MgSO4,
filtered, and concentrated under reduced pressure. The residue was
X-ray Crystal Data for Compound 6: C53H48N3.50O8; M = 861.95; purified by column chromatography to afford pure 9a–b in 65–80%
monoclinic; a = 9.9577(5) Å, b = 16.1397(8) Å, c = 28.3971(14) Å,
α = 90°, β = 92.523(1)°, γ = 90°; V = 4559.4(4) Å3; space group
P21/n; Z = 4; calculated density 1.256 Mgm–3; crystal dimensions
(mm3): 0.45ϫ0.28ϫ0.25; T = 150(2) K; λ (Mo-Kα) = 0.71073 Å;
μ = 0.085 mm–1; 29335 reflections collected, 10455 independent
(Rint = 0.0450), 607 parameter refined on F2; R1 = 0.0717; wR2[F2]
= 0.1696 (all data); GOF on F2 1.096; Δρmax = 0.508 eÅ–3.
yields.
N-{4-[4-Amino-4-(4-tert-butylphenyl)-2-oxobut-3-enyloxy]phenyl}-2-
(2,6-dimethylphenoxy)acetamide (9a): Yield 65 % (65.0 mg,
0.13 mmol); pale-yellow solid; m.p. 70–72 °C; Rf = 0.43 (n-hexane/
ethyl acetate, 1:1). 1H NMR (300 MHz, CD3CN): δ = 1.33 (s, 9 H,
tBu), 2.29 (s, 6 H, Ar-CH3), 4.38 (s, 2 H, Ha), 4.57 (s, 2 H, Hc),
5.63 (br. s, 1 H, Hf), 5.81 (s, 1 H, Hd), 6.93–7.06 (m, 6 H, Ar-H),
7.43–7.57 (m, 6 H, Ar-H), 8.58 (s, 1 H, Hb), 10.15 (br. s, 1 H,
He) ppm. 13C NMR (75 MHz, CDCl3): δ = 16.3 (CH3), 31.1 (CH3),
CCDC-680702 (for 6) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via 34.8 (Cq), 70.38 (CH2), 72.1 (CH2), 90.25 (CH), 115.1 (CH), 121.6
www.ccdc.cam.ac.uk/data_request/cif.
(CH), 124.9 (CH), 125.9 (CH), 126.0 (CH), 129.2 (CH), 130.3 (Cq),
130.5 (Cq), 133.6 (Cq), 154.1 (Cq), 154.5 (Cq), 155.4 (Cq), 163.2
(Cq), 166.4 (Cq) ppm. MS (FAB): m/z = 487 [M + H+]. HRMS:
calcd. for C30H34N2O4 486.2519; found 486.2520.
General Procedure for the Synthesis of Compounds 8a and 8b: To a
well-stirred solution of 7 (100 mg, 0.55 mmol) and 2–3 drops of
dimethylformamide (DMF) in anhydrous CH2Cl2 (10 mL), was
added oxalyl chloride (0.24 mL, 2.77 mmol) under nitrogen at
room temperature. The reaction mixture was heated to reflux tem-
perature for 3 h. Solvent and excess oxalyl chloride were removed
under reduced pressure and the residue was further dried in vacuo.
The residue was dissolved in anhydrous CH2Cl2 (10 mL) followed
by addition of a solution of amines 4a–b (4a: 177 mg, 0.55 mmol;
4b: 174 mg, 0.55 mmol) and triethylamine (8–10 drops) in anhy-
drous CH2Cl2 (10 mL). The reaction was heated to 40 °C for 24 h,
N-{4-[4-Amino-4-(naphthalen-1-yl)-2-oxobut-3-enyloxy]phenyl}-2-
(2,6-dimethylphenoxy)acetamide (9b): Yield 80 % (160 mg,
0.33 mmol); pale-yellow solid; m.p. 79–81 °C; Rf = 0.2 (n-hexane/
1
ethyl acetate, 2:1). H NMR (300 MHz, CDCl3): δ = 2.31 (s, 6 H,
Ar-CH3), 4.35 (s, 2 H, Ha), 4.60 (s, 2 H, Hc), 5.74 (s, 1 H, Hd), 5.84
(br. s, 1 H, Hf), 6.93 (d, J = 8.8 Hz, 2 H, Ar-H), 6.99–7.09 (m, 2
H, Ar-H), 7.46–7.57 (m, 6 H, Ar-H and naphthyl-H), 7.86–7.92 (m,
2 H, naphthyl-H), 8.09–8.12 (m, 1 H, naphthyl-H), 8.61 (s, 1 H,
Eur. J. Org. Chem. 2011, 1472–1481
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1479

W.-S. Chung et al.
FULL PAPER
Hb), 10.25 (br. s, 1 H, He) ppm. 13C NMR (75 MHz, CDCl3): δ =
16.2 (CH3), 70.3 (CH2), 71.8 (CH2), 93.8 (CH), 115.0 (CH), 121.5
(CH), 124.8 (CH), 124.9 (CH), 124.9 (CH), 125.6 (CH), 126.4
(CH), 126.9 (CH), 128.4 (CH), 129.1 (CH), 129.9 (Cq), 130.1 (CH),
130.3 (Cq), 130.5 (Cq), 133.5 (Cq), 135.0 (Cq), 154.0 (Cq), 155.3
(Cq), 163.5 (Cq), 166.4 (Cq), 194.1 (Cq) ppm. MS (FAB): m/z =
481 [M + H+]. HRMS: calcd. for C30H28N2O4 480.2049; found
480.2056.
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General Procedures for the UV/Vis and Fluorescence Spectroscopic
Experiments: UV/Vis spectra were recorded with an HP-8453 spec-
trophotometer equipped with a diode array detector; the resolution
was set at 1 nm. Fluorescence spectra were recorded with an Ami-
noco Bowman Series 2 type spectrofluorimeter. For all measure-
ments of fluorescence spectra, excitation was at 308 nm with the
excitation and emission slit width at 4.0 nm. UV/Vis and fluores-
cence titration experiments were performed with 20 μm solutions
of 3b and 9b in CH3CN and varying concentrations of metal per-
chlorate in CH3CN. During the measurements, the temperature of
the quartz sample cell and chamber was kept at 25 °C.
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General Procedures for the 1H NMR Titration Experiments: 1H
NMR titration spectra were recorded at 300 MHz with tetrameth-
ylsilane (TMS) in a coaxial capillary tube as an external standard.
Experiments were performed with 5 mm solutions of 3b, 6, and 9b
in CH3CN and varying concentrations of [Cu(ClO4)2] in CH3CN
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 1472–1481

A Fluorescence Chemosensor for Copper(II) Ions
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Received: August 19, 2010
Published Online: February 2, 2011
Eur. J. Org. Chem. 2011, 1472–1481
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1481