Highly selective fluorescent sensing of Cu2+ ion by an arylisoxazole modified calix[4]arene

Article abstract of DOI:10.1016/j.tetlet.2008.06.060

A novel fluorescent chemosensor 1 with two anthraceneisoxazolymethyl groups at the lower rim of calix[4]arene has been synthesized, which revealed a dual emission (monomer and excimer) when excited at 375 nm. This chemosensor displayed a selective fluorescence quenching only with Cu²⁺ ion over all other metal ions examined. When Cu²⁺ ion was bound to 1, the fluorescence intensities of both monomer and excimer were quenched. Furthermore, the association constant for the 1:1 complex of 1·Cu²⁺ was determined to be (1.58 ± 0.03) × 10⁴ M^-1.

Full text of DOI:10.1016/j.tetlet.2008.06.060

Tetrahedron Letters 49 (2008) 5013–5016
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Highly selective fluorescent sensing of Cu2+ ion by an arylisoxazole
modified calix[4]arene
*
Kai-Chi Chang, Li-Yang Luo, Eric Wei-Guang Diau, Wen-Sheng Chung
Department of Applied Chemistry, National Chiao-Tung University, Hsinchu 30050, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel fluorescent chemosensor 1 with two anthraceneisoxazolymethyl groups at the lower rim of
calix[4]arene has been synthesized, which revealed a dual emission (monomer and excimer) when
excited at 375 nm. This chemosensor displayed a selective fluorescence quenching only with Cu2+ ion
over all other metal ions examined. When Cu2+ ion was bound to 1, the fluorescence intensities of both
monomer and excimer were quenched. Furthermore, the association constant for the 1:1 complex of
Received 25 February 2008
Revised 10 June 2008
Accepted 13 June 2008
Available online 18 June 2008
1ÁCu2+ was determined to be (1.58 0.03) Â 104 MÀ1
.
Ó 2008 Elsevier Ltd. All rights reserved.
The development of specific fluorescent chemosensors for the
efficient detection of metal ion analytes is one of the most impor-
tant areas in supramolecular chemistry due to their fundamental
role in biological, environmental, and chemical processes.1 In par-
ticular, chemosensors for the detection and measurements of Cu2+
ions are actively investigated as this metal ion is a significant envi-
ronmental pollutant and an essential trace element in human
body.2,3
O
OH
O
O
OH
4
3
Calix[4]arenes have been shown to be useful molecular scaffold
in the development of fluorescent chemosensors especially for
metal ion recognition.4 Most calix[4]arene-based fluorescent
sensors have been designed based on photophysical changes upon
metal ion binding and their mechanisms include photoinduced
electron transfer (PET),5 photoinduced charge transfer (PCT),6
formation of monomer/excimer,7 and energy transfer.8
i
45%
i
67%
b
a
In continuation of our interests in the design and synthesis of
chromogenic9 and fluorogenic10 chemosensors, we report here
the synthesis of a novel fluorogenic calix[4]arene using the 1,3-
dipolar cycloaddition of an alkyne and a nitrile oxide to form an
isoxazole cationic binding site.
c
O
OH
O
O
O
OH
d
e
f
O
O
N
N
N
The synthetic routes of host 1 and control compound 2 are
depicted in Scheme 1. The 25,27-bisfluoroionphores 111 was
synthesized in 45% yield starting from 25, 27-bis(O-propargyl)-p-
tert-butylcalix[4]arene 312 using a 1,3-dipolar cycloaddition reac-
tion methodology recently reported by us in capping the lower
and upper rims of calix[4]arenas.13 In this work, 10-chloroanthra-
cene (CA) instead of anthracene was chosen as the fluorophore be-
cause the preparation of parent anthracene hydroximoyl chloride
requires an extremely careful control of the chlorination process,
otherwise mixture of products is usually obtained. Therefore,
excess chlorination reagents were used which produced pure CA
g
Cl
h
Cl
j
Cl
i
2
1
Scheme 1. Synthesis of fluorogenic calix[4]arene 1. Reagents and conditions: (i)
10-chloroanthracene-9-hydroximoyl chloride, Et3N, toluene, reflux, 24 h.
related products in high yield. Similar procedure was employed
in the synthesis of control compound 214 from precursor 4.15 Fluo-
rogenic calix[4]-arene 1 was found to be in cone conformation
based on the information obtained from 1H and 13C NMR spectra
data.
* Corresponding author. Tel.: +886 3 513 1517; fax: +886 3 572 3764.
E-mail address: wschung@cc.nctu.edu.tw (W.-S. Chung).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.06.060

5014
K.-C. Chang et al. / Tetrahedron Letters 49 (2008) 5013–5016
7
6
430 nm
[Cu2+] equiv
0.0
1.0
0.8
0.6
0.4
0.2
0.0
raw data
fitting curve
reconstructed for monomer
reconstructed for excimer
0.6
0.8
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
11.0
12.0
13.0
14.0
15.0
5
4
3
2
1
0
511 nm
400
450
500
550
600
650
400
450
500
550
600
650
Wavelength (nm)
Wavelength (nm)
Figure 1. Normalize fluorescence spectra of 1 (solid line). The solid line is fitted by
multi-Gaussian functions and deconvoluted into two components (short-dash
curve: monomer band; dash curve: excimer band). Excitation wavelength was at
375 nm.
Figure 3. Fluorescence emission spectra of 1 (20 lM) upon addition of various
equivalents of Cu(ClO4)2 in CH3CN/CHCl3 (v/v = 1000:4).
carried out fluorescence quenching experiments on 1 using more
polar solvents such as DMSO and MeOH/CHCl3 (v/v = 1000:4)
instead of CH3CN/CHCl3 (v/v = 1000:4) (see Figs. S10 and S11)
and found that CH3CN/CHCl3 is by far the most efficient solvent
system in sensing Cu2+ ion.
The two isoxazole moieties of 1 are proven to form an efficient
metal ion binding site, whereas compound 2 is lack of such an effi-
cient metal ion binding site. Furthermore, the geometry of the
binding site of the host 1, comprising the two oxygen atoms of
isoxazole units and two hydroxyls of the phenol units, seems to
be ideal in terms of size and arrangement for recognition of Cu2+
ion. The fluorescence quenching of 1 may be explained by either
a reverse PET17 or a heavy atom effect.18 In the former case, when
the Cu2+ ion is bound by two isoxazole oxygen atoms and two phe-
nol moieties, the CA units probably behave as PET donors whereas
the metal ion bound isoxazole groups behave as electron acceptors.
The UV/vis spectra of the anthracene group(s) 1 and 2 showed
four absorption bands at 338, 357, 375, and 396 nm in CH3CN/
CHCl3 (v/v = 1000:4) (see Fig. S7). The fluorescence spectrum of 1
(20 lM) in CH3CN/CHCl3 (v/v = 1000:4) exhibits a dual emission
(i.e., monomer and excimer) when excited at 375 nm (Fig. 1). The
emission spectrum of 1 is composed of a structured feature, culmi-
nating at 430 nm and assigned to the locally excited CA referred to
as monomer (similar in shape to the emission spectrum of mono-
fluorophore 2) and a red-shifted, broad and structureless band
with kmax at 511 nm, ascribable to the emission from an intramo-
lecular excimer (CAÁCA)*.16 The excimer formation comes from
the interaction of one CA unit in the singlet excited state with
the other CA in the ground state.
Excess perchlorate salts (10 equiv) of Li+, Na+, K+, Mg2+, Ca2+
,
Ba2+, Cr3+, Pb2+, Cu2+, Hg2+, Cd2+, Ag+, Ni2+, Mn2+, and Zn2+ (total
15 metal ions) were tested to evaluate the metal ion binding prop-
erties of 1 and 2. The results are shown in Figures 2 and S8. Ligand
The fluorescence spectra of 1 (20 lM) at various concentrations
of Cu(ClO4)2 are depicted in Figure 3, as can be seen, no shift in the
fluorescence emission maximum was observed. However, the fluo-
rescence intensities of both the monomer and excimer emission of
1 gradually decreased as the Cu(ClO4)2 concentration increased
concentration in all titration experiments was fixed at 20 lM in
CH3CN/CHCl3 (v/v = 1000:4). The fluorogenic chemosensor 1, hav-
ing two isoxazoles as the metal ligating groups, is found to exhibit
remarkable selectivity toward Cu2+ ion over all other metal ions.
from 12 lM to 300 lM. Based on the fluorescence intensity of 1
as a function of [Cu2+], the association constant for complex
1ÁCu2+ in CH3CN/CHCl3 (v/v = 1000:4) was calculated to be
(1.58 0.03) Â 104 MÀ1 by Stern–Volmer plot.19 (Fig. S12) In the
Job plot,20 the maximum fluorescence change was observed when
the molar fraction of ionophore 1 versus Cu2+ was 0.5, indicative of
a 1:1 complex (Fig. 4).
The fluorescence of 1 (20 l
M) was strongly quenched by Cu2+
ion; however, no such quenching effect was found for the control
compound 2 by any of the fifteen metal perchlorates used above.
Moreover, the UV/vis spectra of 1 did not show any new absorption
band after adding 10 equiv of Cu2+ ion (see Fig. S9). We have also
7
6
5
4
3
2
1
0
430
1.5
1.0
0.5
0.0
1 and 1 + the other metal ions
1 + Cu2+
0.0
0.2
0.4
0.6
0.8
1.0
400
450
500
550
600
650
Wavelength (nm)
X = [1] /([1] + [Cu2+])
Figure 2. Changes in fluorescence emission spectra of 1 (20
adding 200
(v/v = 1000:4).
l
M) before and after
Figure 4. Job plot of a 1:1 complex of 1 and Cu2+ ion, where the emission at 430 nm
was plotted against the mole fraction of 1 at an invariant total concentration of
20 lM in MeCN/CHCl3 (1000:4, v/v).
l
M concentration of various metal perchlorates in CH3CN/CHCl3

K.-C. Chang et al. / Tetrahedron Letters 49 (2008) 5013–5016
5015
•
b
a
b
f
i
j
*
c
e
c
h
g
d
d
• ab
a
e
f
g
j
c
c
i
h
*
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
ppm
Figure 5. 1H NMR spectra of 1 (5.0 mM) in CDCl3/CD3CN (3:1) (a) and in the presence of 25 mM (5.0 equiv) of Cu(ClO4)2 (b), where à denotes an external standard CHCl3 and
the descriptors are shown in Scheme 1.
Metal ion-induced chemical shift changes in the 1H NMR spec-
Supplementary data
tra support that Cu2+ is bound to the two oxygen atoms of the isox-
azole units and the two hydroxyl phenol groups of 1 (see Fig. 5). In
the presence of 5.0 equiv of Cu2+, the peaks of Ha–Hc were down-
field shifted by 0.23, 0.22, 0.21, and 0.22 ppm, respectively, and
the peak of Hd in the hydroxyls of the phenol units was also down-
field shifted by 0.22 nm with a reduced intensity. Furthermore, the
peak of He on the OCH2-isoxazole unit was downfield shifted by
0.24 ppm; however, the peak of Hf on the isoxazole group was sig-
nificantly downfield shifted by 1.30 ppm, suggesting that the two
isoxazole groups were involved in the complexation of Cu2+. In
contrast, the chemical shifts of protons Hg–Hj on the anthracene
groups were modestly downfield shifted and the peak shapes were
slightly broadened. However, upon adding 5.0 equiv of Cu2+ to the
solution of 2, the peak of Hf on the isoxazole group was downfield
shifted by only 0.26 ppm (Fig. S13). Its downfield shift is much
smaller than that for 1 (Fig. 5), suggesting that the complexation
of Cu2+ with the mono-isoxazole group of 2 is weaker than its com-
plexation with the two isoxazole groups of 1. In principle, the 1H
NMR spectrum of 1 should become broadened in the presence of
Cu2+; however, it appeared to be quite sharp, implying that the
Cu2+ might have been reduced to Cu+. The auto-reduction of Cu2+
by a phenol is well documented,21 which is probably the source
for the redox observed in the addition of Cu2+ to 1. We have also
carried out experiments using [(CH3CN)4Cu]PF6 to affect the fluo-
rescence of 1; however, no change in fluorescence emission spectra
of 1 was observed in the presence of excess Cu+ ion (Fig. S14). The
above results suggest that Cu2+ might be reduced by the phenols of
the host 1 and the oxidized phenols then help to trap the reduced
Cu+ ions (Fig. S15).22 Thus, the compound 1 is a highly selective
fluorogenic chemodosimeter for Cu2+ ion.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2008.06.060.
References and notes
1. (a) Czarnik, A. W. Chem. Biol. 1995, 2, 423; (b) de Silva, A. P.; Gunaratne, H. Q.
N.; Gunnlaugsson, T.; Huxley, A. J. M.; McCoy, C. P.; Rademacher, J. T.; Rice, T. E.
Chem. Rev. 1997, 97, 1515; (c) de Silva, A. P.; Fox, D. B.; Huxley, A. J. M.; Moody,
T. S. Coord. Chem. Rev. 2000, 205, 41; (d) Molecular Fluorescence; Valeur, B., Ed.;
Wiley-VCH: Weinheim, Germany, 2001.
2. Kramer, R. Angew. Chem., Int. Ed. 1998, 37, 772.
3. (a) Jang, Y. J.; Moon, B.-S.; Park, M. S.; Kang, B.-G.; Kwon, J. Y.; Hong, J. S. J.;
Yoon, Y. J.; Lee, K. D.; Yoon, J. Tetrahedron Lett. 2006, 47, 2702; (b) Yang, H.; Liu,
Z.-Q.; Zhou, Z.-G.; Shi, E.-X.; Li, F.-Y.; Du, Y.-K.; Yi, T.; Huang, C.-H. Tetrahedron
Lett. 2006, 47, 2911; (c) Jun, J. E.; Won, H. N.; Kim, J. S.; Lee, K.-H.; Yoon, J.
Tetrahedron Lett. 2006, 47, 4577; (d) Qi, X.; Jun, E. J.; Xu, L.; Kim, S.-J.; Hong, J. S.
J.; Yoon, Y. J.; Yoon, J. J. Org. Chem. 2006, 71, 2881; (e) Kim, S. H.; Kim, J. S.; Park,
S. M.; Chang, S.-K. Org. Lett. 2006, 8, 371; (f) Xiang, Y.; Tong, A.; Jin, P.; Ju, Y. Org.
Lett. 2006, 8, 2863; (g) Zeng, L.; Miller, E. W.; Pralle, A.; Isacoff, E. Y.; Chang, C. J.
J. Am. Chem. Soc. 2006, 128, 10; (h) Kamila, S.; Callan, J. F.; Mulrooney, R. C.;
Middleton, M. Tetrahedron Lett. 2007, 48, 7756; (i) Liu, J.; Lu, Y. J. Am. Chem. Soc.
2007, 129, 9838.
4. (a) Ikeda, A.; Shinkai, S. Chem. Rev. 1997, 97, 1713; (b) Kim, J. S.; Quang, D. T.
Chem. Rev. 2007, 107, 3780; (c) Liang, Z.; Liu, Z.; Jiang, L.; Gao, Y. Tetrahedron
Lett. 2007, 48, 1629; (d) Xu, Z.; Kim, S.; Kim, H. N.; Han, S. J.; Lee, C.; Kim, J. S.;
Qian, X.; Yoon, J. Tetrahedron Lett. 2007, 48, 9151.
5. (a) Kim, J. S.; Noh, K. H.; Lee, S. H.; Kim, S. K.; Kim, S. K.; Yoon, J. J. Org. Chem.
2003, 68, 597; (b) Bu, J.-H.; Zheng, Q.-Y.; Chen, C.-F.; Huang, Z.-T. Org. Lett.
2004, 6, 3301; (c) Li, G.-K.; Xu, Z.-X.; Chen, C.-F.; Huang, Z.-T. Chem. Commun.
2008, 1774.
6. (a) Kim, S. K.; Bok, J. H.; Bartsch, R. A.; Lee, J. Y.; Kim, J. S. Org. Lett. 2005, 7, 4839;
(b) Choi, J. K.; Kim, S. H.; Yoon, J.; Lee, K.-H.; Bartsch, R. A.; Kim, J. S. J. Org. Chem.
2006, 71, 8011.
7. (a) Kim, S. K.; Lee, S. H.; Lee, J. Y.; Lee, J. Y.; Bartsch, R. A.; Kim, J. S. J. Am. Chem.
Soc. 2004, 126, 16499; (b) Schazmann, B.; Alhashimy, N.; Diamond, D. J. Am.
Chem. Soc. 2006, 128, 8607.
8. (a) Lee, M. H.; Quang, D. T.; Jung, H. S.; Yoon, J.; Lee, C.-H.; Kim, J. S. J. Org. Chem.
2007, 72, 4242; (b) Othman, A. B.; Lee, J. W.; Wu, J.-S.; Kim, J. S.; Abidi, R.;
Thuéry, P.; Strub, J. M.; Van Dorsselaer, A.; Vicens, J. J. Org. Chem. 2007, 72,
7634.
9. (a) Kao, T.-L.; Wang, C.-C.; Pan, Y.-T.; Shiao, Y.-J.; Yen, J.-Y.; Shu, C.-M.; Lee,
G.-H.; Peng, S.-M.; Chung, W.-S. J. Org. Chem. 2005, 70, 2912; (b) Ho, I.-T.;
Lee, G.-H.; Chung, W.-S. J. Org. Chem. 2007, 72, 2434; (c) Chang, K.-C.; Su, I.-H.;
Lee, G.-H.; Chung, W.-S. Tetrahedron Lett. 2007, 48, 7274.
In conclusion, we have synthesized a new bisisoxazolyl-meth-
ylcalix[4]arene 1 bearing two anthracene groups, which displayed
a dual fluorescent emission (monomer and excimer) and showed
an extreme selectivity toward Cu2+ ion over all other metal ions
examined.
10. Chang, K.-C.; Su, I.-H.; Senthilvelan, A.; Chung, W.-S. Org. Lett. 2007, 9, 3363.
11. Compound 1: A mixture of 3 (0.200 g, 0.276 mmol) and 10-chloroanthracene-
9-hydroximoyl chloride (10.0 equiv) in toluene (50 mL) was stirred. Then, Et3N
(20.0 equiv) was added dropwise and the mixture was refluxed for 24 h. The
solvent was removed under vacuum, and the residue was dissolved in
chloroform (30 mL), washed with water, and dried over MgSO4. The residue
Acknowledgments
We thank the National Science Council (NSC) and MOE ATU pro-
gram of the Ministry of Education of Taiwan, ROC for financial
support.

5016
K.-C. Chang et al. / Tetrahedron Letters 49 (2008) 5013–5016
15. Compound 4: solution of 4-tert-butyl-2,6-dimethylphenol (0.200 g,
obtained after evaporation of the solvent was subjected to a silica gel column
A
chromatography using a gradient polarity (eluent: ethyl acetate/n-hexane,
1:14 to 1:6) to afford 0.153 g (45%) of 1 as a white solid; mp 172–174 °C;
Rf = 0.93 (ethyl acetate/n-hexane = 1:3); 1H NMR (CDCl3, 300 MHz) d 8.49 (d,
J = 8.7 Hz, 4H), 7.83 (d, J = 8.7 Hz, 4H), 7.60–7.49 (m, 4H), 7.47–7.36 (m, 4H),
7.22 (s, 4H), 6.94 (s, 4H), 6.91 (s, 2H), 6.55 (s, 2H), 5.34 (s, 4H), 4.41 (d,
J = 13.2 Hz., 4H), 3.49 (d, J = 13.2 Hz, 4H), 1.43 (s, 18H), 1.07 (s, 18H); 13C NMR
(CDCl3, 75.4 MHz) d 168.0 (Cq), 160.5 (Cq), 150.3 (Cq), 149.5 (Cq), 147.7 (Cq),
141.9 (Cq), 132.4 (Cq), 131.1 (Cq), 130.7 (Cq), 128.1 (Cq), 127.7 (Cq), 126.6
(CH), 126.5 (CH), 125.8 (CH), 125.8 (CH), 125.2 (CH), 124.8 (CH), 122.4 (Cq),
108.0 (CH), 67.6 (CH2), 33.9 (Cq), 33.8 (Cq), 31.8 (CH2), 31.7 (CH3), 30.9 (CH3);
FABMS m/z 1231 (M+); HR FABMS calcd for C80H7635Cl2N2O6, 1230.5080; found,
1230.5098.
1.12 mmol), potassium carbonate (2.00 equiv) and propargyl bromide
(1.50 equiv) in acetonitrile (50 mL) was stirred and heated at reflux for 4 h.
The solvent was removed under vacuum and the residue was purified by
column chromatography with ethyl acetate/n-hexane (v/v = 1:6) to give
0.206 g (85%) of 4 as a colorless oil; Rf = 0.83 (ethyl acetate/n-hexane = 1:3);
1H NMR (CDCl3, 300 MHz) d 7.05 (s, 2H), 4.50 (d, J = 2.1 Hz, 2H), 2.53 (t,
J = 2.1 Hz, 1H), 2.35 (s, 6H), 1.32 (s, 9H); 13C NMR (CDCl3, 75.4 MHz) d 153.1
(Cq), 146.9 (Cq), 130.2 (Cq), 125.7 (CH), 79.3 (Cq), 74.7 (CH), 59.8 (CH2), 34.1
(Cq), 31.4 (CH3), 16.7 (CH3); EIMS m/z 216 (M+, 39), 177 (100), 119 (81); HRMS
calcd for C15H20O, 216.1514; found, 216.1515.
16. (a) Bouas-Laurent, H.; Castellan, A.; Daney, M.; Desvergne, J.-P.; Guinand, G.;
Marsau, P.; Riffaud, M.-H. J. Am. Chem. Soc. 1986, 108, 315; (b) Fages, F.;
Desvergne, J.-P.; Bouas-Laurent, H.; Marsau, P.; Lehn, J.-M.; Kotzyba-Hibert, F.;
Albrecht-Gary, A.-M.; Al Joubbeh, M. J. Am. Chem. Soc. 1989, 111, 8672; (c)
Fages, F.; Desvergne, J.-P.; Bouas-Laurent, H.; Lehn, J.-M.; Konopelski, J.-P.;
Marsau, P.; Barrans, Y. J. Chem. Soc., Chem. Commun. 1990, 655; (d) Fages, F.;
Desvergne, J.-P.; Kampke, K.; Bouas-Laurent, H.; Lehn, J.-M.; Meyer, M.;
Albrecht-Gary, A.-M. J. Am. Chem. Soc. 1993, 115, 3658; (e) Marquis, D.;
Desvergne, J.-P.; Bouas-Laurent, H. J. Org. Chem. 1995, 60, 7984.
17. (a) de Silva, A. P.; Gunaratne, H. Q. N.; Lynch, P. L. M. J. Chem. Soc., Perkin Trans. 2
1995, 685; (b) Ojida, A.; Mito-oka, Y.; Inoue, M.-A.; Hamachi, I. J. Am. Chem. Soc.
2002, 124, 6256.
18. Chae, M.-Y.; Cherian, X. M.; Czarnik, A. W. J. Org. Chem. 1993, 58, 5797.
19. Stern, O.; Volmer, M. Phys. Z. 1919, 20, 183.
20. (a) Job, P. Ann. Chim. Appl. 1928, 9, 113; (b) Connors, K. A. Binding Constants;
Wiley: New York, 1987.
21. Hay, A. S.; Blanchard, H. S.; Endres, C. F.; Eustance, J. W. J. Am. Chem. Soc. 1959,
81, 6335.
22. It was found that if compound 1 in CH3CN/CHCl3 (v/v = 1000:4) was pretreated
with 3 equiv of Cu2+, then, any added Cu+ (ca. 10–30 equiv) showed significant
quenching of the fluorescence of 1; however, no such quenching effect was
found if compound 1 was directly titrated with 30 equiv of Cu+ (see Fig. S15).
12. Asfari, Z.; Bilyk, A.; Bond, C.; Harrowfied, J. M.; Koutsantonis, G. A.; Lengkeek,
N.; Mocerino, M.; Skelton, B. W.; Sobolev, A. N.; Strano, S.; Vicens, J.; White, A.
H. Org. Biomol. Chem. 2004, 2, 387.
13. (a) Shiao, Y.-J.; Chiang, P.-C.; Senthilvelan, A.; Tsai, M.-T.; Lee, G.-H.; Chung,
W.-S. Tetrahedron Lett. 2006, 47, 8383; (b) Senthilvelan, A.; Tsai, M.-T.;
Chang, K.-C.; Chung, W.-S. Tetrahedron Lett. 2006, 47, 9077.
14. Compound 2: A mixture of 4 (0.200 g, 0.926 mmol) and 10-chloroanthracene-
9-hydroximoyl chloride (2.50 equiv) in toluene (50 mL) was stirred. Then, Et3N
(15.0 equiv) was added dropwise and the mixture was refluxed for 24 h. The
solvent was removed under vacuum, and the residue was dissolved in
chloroform (30 mL), washed with water, and dried over MgSO4. The solid
residue was purified by column chromatography with ethyl acetate/n-hexane
(v/v = 1:10) to give 0.292 g (67%) of 2 as a yellowish green powder; mp 175–
177 °C; Rf = 0.91 (ethyl acetate/n-hexane = 1:3); 1H NMR (CDCl3, 300 MHz) d
8.61 (d, J = 8.8 Hz, 2H), 7.88 (d, J = 8.8 Hz, 2H) 7.70–7.58 (m, 2H), 7.57–7.47 (m,
2H), 7.09 (s, 2H), 6.62 (s, 1H), 5.13 (s, 2H), 2.40 (s, 6H), 1.32 (s, 9H); 13C NMR
(CDCl3, 75.4 MHz) d 169.2 (Cq), 160.7 (Cq), 152.9 (Cq), 147.4 (Cq), 131.3 (Cq),
131.0 (Cq), 130.0 (Cq), 128.4 (Cq), 126.8 (CH), 126.7 (CH), 126.0 (CH), 125.1
(CH), 122.8 (Cq), 107.0 (CH), 64.7 (CH2), 34.2 (Cq), 31.5 (CH3), 16.6 (CH3); EIMS
m/z 469 (M+, 34), 237 (100), 177 (54); HRMS calcd for C30H2835ClNO2,
469.1809; found, 469.1795.