A chemodosimetric probe based on a conjugated oxidized bis-indolyl system for selective naked-eye sensing of cyanide ions in water

Article abstract of DOI:10.1002/asia.201200565

A new bis-indolyl-based colorimetric probe has been synthesized. This allows a Michael-type adduct formation for the detection of cyanide ions. The probe shows a remarkable color change from red to colorless upon addition of the cyanide ions in pure water

Full text of DOI:10.1002/asia.201200565

DOI: 10.1002/asia.201200565
A Chemodosimetric Probe Based on a Conjugated Oxidized Bis-Indolyl
System for Selective Naked-Eye Sensing of Cyanide Ions in Water
Namita Kumari,[a] Satadru Jha,[a, c] and Santanu Bhattacharya*[a, b]
Abstract: A new bis-indolyl-based col-
orimetric probe has been synthesized.
This allows a Michael-type adduct for-
mation for the detection of cyanide
ions. The probe shows a remarkable
color change from red to colorless
upon addition of the cyanide ions in
pure water. The cyanide ion reacts with
the probe and removes the conjugation
of the bis-indolyl moiety of the probe
with that of the 4-substituted aromatic
ring. This renders the probe colorless.
The mechanism of the reaction of the
probe with the cyanide ion was estab-
1
lished by using H and 13C NMR spec-
troscopy, mass spectrometry, and kinet-
ic studies.
Keywords: bis-indolyl
·
chemo-
dosimetry · cyanides · sensors ·
water
Introduction
proach, however, is the lack of selectivity. Other anions—for
example, Fꢀ, acetate, and phosphate ions—often interfere
with such assays. Some of the other ways to detect CNꢀ ions
involve chemical reaction of cyanide with metal-coordinated
sensors,[8] especially to copper-ion-complexed sensors, and
also by the reaction of cyanide ion with CdSe quantum
dots[9] or appropriate boronic acid derivatives.[10]
An alternative strategy used by some researchers for the
detection of CNꢀ employs reaction-based indicators.[6a,11]
This generally provides improved selectivity toward CNꢀ de-
tection due to the nucleophilic character of it. Reported re-
action-based indicators of CNꢀ include probes based on oxa-
zines,[12] cationic boranes,[13] acridinium salts,[14] benzil-based
systems,[15] b-turn motifs,[16] a,b-unsaturated systems,[17] cou-
marins,[18] hydrazones,[19] aldehydes, and ketones.[20] But most
of these probes suffer from limitations such as the require-
ments of high temperature, interference with other ions in
the medium, and lack of visible changes in color. Most im-
portantly for many of these, there is a serious lack of solu-
bility in water. This limits the practical use of such probes
for sensing the CNꢀ in water. Thus development of new re-
action-based probes that work in water are absolutely neces-
sary for detecting CNꢀ in water.
An ideal ion sensor or a probe should fulfill some impor-
tant criteria such as 1) adequate sensitivity, 2) high selectivi-
ty towards the analyte, 3) fast response time, and 4) good
signal-to-noise ratio. In addition, the probe must sense the
ion in water, there should be no hysteresis, and it should
have excellent long-term stability. Apart from these, a good
sensor also needs to be robust, economic, simple, and relia-
ble. Thus there is ongoing effort in search of new sensors
that possess most if not all of these qualities.
Due to our continuing interest in the design of various
small molecular sensors for different ions,[21] we have been
involved in the search of new probes based on original
chemistry. Many bis-indolyl-based probes have been report-
ed for the detection of various ions,[22] but only one system
Cyanide is among the most lethal anions.[1] The maximum
permissible limit for cyanide ions in water is 0.2 ppm as
specified by the United States Environmental Protection
Agency (EPA).[2] The cyanide content detected in the blood
of fire victims is found to be 23–26 mm.[3] Despite its extreme
toxicity, cyanide is used in many industries such as gold
mining, electroplating, metallurgy,[4] and so on, which pro-
duce nearly 140000 tons of cyanide per year worldwide.[5]
This makes the selective detection of CNꢀ in water absolute-
ly crucial.
On account of its high toxicity, many research groups
have made efforts to make efficient cyanide-ion sensors.
The main approaches that have been used for the anion de-
tection involve tinkering with hydrogen-bonding motifs,
donor–acceptor or electrostatic interactions, and so forth.[6]
But for the detection of CNꢀ ion, most of the probes based
on supramolecular approaches depend on the hydrogen-
bonding motifs.[7] The main disadvantage of such an ap-
[a] N. Kumari, Dr. S. Jha, Prof. Dr. S. Bhattacharya
Department of Organic Chemistry
Indian Institute of Science
Bangalore 560012 1 (India)
Fax : (+91)080-2360-0529
E-mail: sb@orgchem.iisc.ernet.in
[b] Prof. Dr. S. Bhattacharya
Chemical Biology Unit
Jawaharlal Nehru Centre of Advanced Scientific Research
Bangalore (India)
[c] Dr. S. Jha
Present address:
Department of Chemistry
Sikkim Manipal Institute of Technology
Majitar, East-Sikkim 737136 (India)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201200565.
Chem. Asian J. 2012, 7, 2805 – 2812
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FULL PAPER
so far is known that reports the detection of cyanide ions in
a 7:1 water/acetonitrile medium.[23] We report herein the
synthesis of a new water-soluble oxidized bis-indolyl-based
ꢀ
probe, 1, which possesses two COOH groups. This probe
specifically reacts with the CNꢀ ion in pure water at ambient
temperature and produces a remarkable change in color
from red to colorless. The detection limit of the probe for
the cyanide ion is below the ppm level, which is higher than
the permitted limit of cyanide ions in water. The probe
shows an immediate visible change in color from red to
orange with the addition of cyanide, which becomes color-
less with time. The presence of a through conjugation in
1 by means of its oxidized bis-indolyl moiety renders it
highly colored. The added CNꢀ reacts with 1 in such a way
that it cuts off the conjugation of the molecule, thereby re-
sulting in the disappearance of its color. The mechanism of
this process has been investigated by both NMR spectrosco-
py and mass spectrometry, and also by using kinetic studies.
Results and Discussion
Probe 1 was synthesized in good overall yield (ꢁ69%) by
the synthetic route presented in Scheme 1 and was charac-
terized by both NMR (1H and 13C) spectroscopy and mass
spectrometry.
Figure 1. UV/Vis and colorimetric changes in 1 (50 mm) after immediate
addition of CNꢀ (50 equiv) in water and after 2 h of addition.
The UV/Vis spectra showed a change in the absorption
maximum (lmax) from 530 to 488 nm immediately after the
addition of cyanide ions (Figure 1). Then the band with
lmax =488 nm started decreasing progressively, and it com-
pletely vanished after approximately 2 h with a concomitant
increase in the absorbance at 265 nm. The process main-
tained an isosbestic point at 291 nm, which suggests that
there is equilibrium between the species involved. The selec-
tivity of the probe was checked by the addition of a 50-fold
excess amount of each of the various anions such as Fꢀ, Clꢀ,
Brꢀ, Iꢀ, AcOꢀ, SCNꢀ, H2PO4 , N3 , and NO3 (all as potassi-
um salts). None of the above anions showed any color
change (Figure 2). The UV/Vis spectra did not show any
change upon addition of any of these anions (Figure 2a).
The immediate changes were observed both visibly and in
the UV/Vis spectra upon the cyanide ion addition only.
The plot of changes in the absorbance at 413 nm upon the
immediate addition of various anions clearly showed excel-
lent selectivity of probe 1 towards the cyanide ion (Fig-
ure 2b).
ꢀ
ꢀ
ꢀ
Probe 1 showed an emission maximum at 590 nm upon
excitation at 465 nm (lex =465 nm). We checked the fluores-
cence responses of the emission band with the addition of
various anions. Upon excitation of the probe at 465 nm, it
could detect selective changes after the addition of the cya-
nide ion only. It showed a blueshift of approximately 20 nm
immediately and selectively upon the addition of CNꢀ
(Figure 3). None of the other added anions showed any shift
in the emission maximum band under these conditions.
Scheme 1. Synthetic route to 1.
The addition of CNꢀ to 1 in water resulted in an immedi-
ate change in color from red to orange, which progressively
became colorless within approximately 2 h (Figure 1). This
suggests that some reaction probably takes place between
CNꢀ and 1, which removes the conjugation of the molecule
and renders it colorless.
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Chemodosimetric Probe
Figure 3. a) Fluorescence spectra of 1 (10 mm) (lex =465 nm) after imme-
diate addition of various anions (10 equiv). b) Normalized change in fluo-
rescence intensity at 516 nm of 1 (lex =465 nm) after addition of various
anions (10 equiv).
Figure 2. Top: Changes in color after addition of 50 equiv of various
anions to 1 (50 mm) in water observed after 2 h. Bottom: a) Changes in
the UV/Vis spectra of 10 mm of 1 after immediate addition of anions
(50 equiv); b) normalized changes in the absorbance at 413 nm after im-
mediate addition of each anion.
The interference was also checked in the presence of
other anions, which showed that none of the other anions in-
terfered with the CNꢀ ion detection (Figure 4). Further-
more, the titration studies with CNꢀ ions were performed
upon excitation at 465 nm. The fluorescence intensity at
516 nm showed an incremental increase upon addition of cy-
anide (see the Supporting Information). The detection limit
that was calculated from this titration showed a detection
limit of approximately 0.38 ppm for the cyanide ion in
water.[24] A gradual and complete change in color of 1 upon
addition of the cyanide ion indicated a reaction-based
change. To check this, we examined the time course of the
reaction of 1 in the presence of an excess amount of cyanide
ions (50-fold over 1). The reaction followed a pseudo-first-
order kinetic behavior in the presence of 50-fold excess
amount of CNꢀ over 1 (Figure 5). The rate constant of the
Figure 4. Normalized change in the emission intensity of 1 after addition
of the CNꢀ ions (10 equiv) in the presence of an excess amount of other
anions (25 equiv).
reaction was found to be (1.658ꢂ0.003)ꢁ10ꢀ2 minꢀ1 (r2 =
0.99994) at 258C. This indicates that in approximately
40 min the absorption intensity at 480 nm almost halved
upon the addition of CNꢀ ions.
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Santanu Bhattacharya et al.
FULL PAPER
Figure 6. a) Arrhenius plot of the rate constants for cyanide complexation
with 1. b) Plot of ln(k/T) against 1/T (Eyring–Polanyi equation for calcu-
lating the activation free energy (DG#), enthalpy (DH#), and entropy
(DS#)) for the reaction of CNꢀ with 1.
Figure 5. a) Changes in the UV/Vis spectra of 1 (50 mm) with time upon
addition of CNꢀ ions (50 equiv). b) Changes in the A480 nm were plotted
against time. Inset: plot showing the first-order reaction.
We further checked the changes in the rates of
Table 2. Activation parameters calculated by using the Eyring–Polanyi equation.[a]
this reaction under pseudo-first-order kinetic con-
ditions at various temperatures (see the Supporting
Information). As expected, the rates increased as
the temperature increased (Table 1), and at 558C,
the absorbance halved in just approximately
Ea
A
A
DH#
DS#
DG#
[a]
[kcalmolꢀ1
]
G
(ꢁ1022)]
[kcalmolꢀ1
]
[calmolꢀ1 Kꢀ1
]
[kcalmolꢀ1
]
8.33
7.70
ꢀ40.76
21.08
[a] For the reaction carried out at 328 K.
ln k ¼ ðꢀEa=RÞð1=TÞ þ ln A
ln ðk=TÞ ¼ ðꢀDH#=RÞð1=TÞ þ ln ðkB=hÞ þ DS#=R
ð1Þ
ð2Þ
Table 1. Rates of reaction of cyanide ions with 1 in water at different
temperatures.
T [8C]
Rateꢁ10ꢀ2 [minꢀ1
]
r2
25
35
45
55
1.658ꢂ0.003
2.682ꢂ0.008
4.049ꢂ0.018
6.032ꢂ0.020
0.9999
0.9998
0.9997
0.9994
in which k=rate constant, Ea =activation energy, R=univer-
sal gas constant, T=absolute temperature, A=pre-exponen-
tial factor, kB =Boltzmann constant, and h=Planckꢂs con-
stant.
The reaction was also monitored by following the changes
in the fluorescence emission spectra as a function of time
upon the addition of an excess amount of cyanide. The fluo-
rescence emission intensity increased at 500 nm with a con-
comitant decrease at 590 nm (Figure 7a). The changes in the
fluorescence emission intensity were compared for each
anion after 2 h of addition, and it showed an enhancement
in the fluorescence intensity at 500 nm of approximately 10
times with CNꢀ specifically (Figure 7b).
11 min.
From the rate constants measured at different tempera-
tures, we determined the activation energy and frequency
factor values on the basis of the Arrhenius rate equation
[Eq. (1)] (Figure 6a). By using the Eyring–Polanyi equation
[Eq. (2)], the activation parameters—for example, free
energy (DG#), enthalpy (DH#), and entropy (DS#)—of the
reaction were calculated (Figure 6b, Table 2). A negative
value of the activation entropy suggested the associative
nature of the reaction.
The pH dependence of the probe in aqueous media was
also checked by both UV/Vis and fluorescence emission
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Chemodosimetric Probe
Figure 7. a) Changes in the fluorescence intensity (lex =465 nm) of
1 (10 mm) with time upon addition of CNꢀ (50 equiv). b) Normalized fluo-
rescence intensity of 1 at 500 nm after 2 h addition of various anions.
Figure 8. a) Plot of absorbance of 1 (50 mm) at 530 nm (observed after
4 h) after adding CNꢀ ions (50 equiv) at different pH. b) Plot of fluores-
cence intensity of 1 (10 mm) (lex =465 nm) at 500 nm (observed after 4 h)
after adding CNꢀ ions (50 equiv) at different pH.
spectroscopy. Cyanide ion was added to the buffered solu-
tion of the probe at different pH values. The results indicat-
ed that the binding of 1 with the CNꢀ only occurred effec-
tively above pH 6 (Figure 8). Below pH 6, no change due to
the addition of CNꢀ ion was observed in either the absorp-
tion or emission spectra.
The rates of change in both absorption as well as emission
spectra upon the addition of 50 equivalents of CNꢀ were
found to be faster at higher pH. But the rate of change in
water was found to be much higher than in the buffered so-
lution of pH 7. To investigate this, we checked the pH of the
probe solution in water after adding 50 equivalents of KCN.
The addition of an excess amount of KCN made the water
basic (the pH changed from 6.8 to 8.5). This observation is
consistent with literature.[25] This explains why a faster rate
of reaction in water was observed. To ensure that the
change in color was not due to a change in pH, we have
checked the UV/Vis spectra of 1 in basic solution. In
a medium of pH>9 it showed only an initial blueshift of the
absorption maximum but did not show any further change
with time. Thus further change in the absorption spectrum
appeared due to the cyanide ion addition, which indicated
the reaction of CNꢀ ions with the probe.
Figure 9. Partial 1H NMR (400 MHz) spectra of 1 in [D6]DMSO in the
absence and presence of 0.5, 1, 5, and 10 equiv of KCN.
1
To further investigate the reaction, H NMR spectroscopic
titration of 1 was performed by adding KCN in [D6]DMSO
(Figure 9 and the Supporting Information).
To ensure that the change in color was not due to hydrol-
ysis, we also checked the stability of compound in water by
allowing the same solution to stand for 48 h. No change was
observed in the solution of 1 after allowing it to stand for
a longer time (see the Supporting Information).
All the protons of 1 shifted upfield upon addition of CNꢀ.
After the addition of 1 equivalent of cyanide, new peaks
started appearing, which indicated the formation of new
species (see the Supporting Information). After the titration,
1
when the H NMR spectra were recorded after keeping the
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Santanu Bhattacharya et al.
FULL PAPER
same solution for approximately 4 h, a completely new set
of peaks emerged, which again supported the formation of
new species.
tigated by various means. The time-course studies in the
presence of an excess amount of CNꢀ showed that the reac-
tion follows an apparent first-order kinetic pathway. The ac-
tivation entropy calculated by using the Eyring–Polanyi
equation suggested the associative nature of the reaction.
1
A comparison between the H NMR spectra of the unoxi-
dized diester precursor of 1, that is, 3, and that of the oxi-
dized diester 2 (Scheme 1) revealed that CNꢀ ion formed an
adduct with 1 under these conditions. Each proton of 3
showed 1H NMR spectroscopic signals upfield relative to
that of the oxidized 2. It further indicates that the added cy-
anide ion attacks the C=C bond that maintains the conjuga-
tion of the 4-substituted aromatic ring with the bis-indolyl
moiety (Scheme 2). Thus when the reaction is over, it com-
pletely cuts off the conjugation, which causes a pronounced
change in color from red to colorless.
1
Furthermore, H NMR spectroscopic titration and 13C NMR
spectroscopic studies confirmed the mode of reaction be-
tween probe 1 and CNꢀ ion. This is further supported by the
DEPT-135 spectrum and mass spectral analysis. Taken to-
gether, a plausible mechanism of the reaction is presented
that is shown to operate by means of a Michael-type adduct
formation under ambient conditions of pH and temperature
in water.
Experimental Section
General
All solvents and reagents were purified and dried by means of the usual
methods. All starting materials were obtained from the best known com-
mercial suppliers and used as received. IR spectra were recorded using
1
a Perkin–Elmer FTIR spectrum BX. H and 13C NMR spectra were mea-
sured using either a 300/75 MHz or a 400/100 MHz spectrometer. HRMS
analyses were performed using an electron spray ionization (ESI) mass
spectrometer (Q-TOF YA263 high-resolution instrument). UV/Vis ab-
sorption spectra were obtained using a Shimadzu UV-2100 spectropho-
tometer. Fluorescence spectra were recorded using a Fluorolog Horiba
Jobin Yvon spectrofluorometer. The stock solution of the compound
1 was made in DMSO and the final concentration of DMSO in all the
studies were less than 0.5%
Scheme 2. Plausible mechanism of the cyanide adduct formation with 1.
The actual mechanism of the reaction was probed by
13C NMR spectroscopy, DEPT-135 (DEPT=distortionless
enhancement by polarization transfer), and mass spectrome-
try. After recording the 13C NMR spectra following the CNꢀ
addition reaction, the peak that corresponded to the forma-
tion of a tetrahedral carbon appeared at d=43.8 ppm (see
the Supporting Information). The peak at d=43.8 ppm was
also not observed in the DEPT spectrum, thereby confirm-
ing the reaction of cyanide to that of the a,b-unsaturated
double bond (see the Supporting Information).
Synthesis of 5
Ethyl bromoacetate (4.67 g, 28.0 mmol) was added slowly to a mixture of
aniline (0.931 g, 10.0 mmol) and K2HPO4 (5.22 g, 30.0 mmol) in CH3CN
(10 mL) at 08C and then allowed to stir at RT for 30 min. The reaction
mixture was then heated to reflux for 24 h.[26] After evaporation of the
excess amount of solvent under vacuum, water (5 mL) was added to it. A
crude material was obtained after separation and extraction with EtOAc
followed by evaporation of the organic solvent. The compound 5 was ob-
tained after purification of the crude oil by column chromatography over
silica gel (eluted at 5% EtOAc/n-hexane). Yield 99%, 2.62 g (pale
The formation of the 1-CNꢀ adduct was also evident from
the detection of a mass spectral peak at 477.155 (m/z calcd
477.156), which might be assigned due to the formation of
the cyanide addition product of 1 (see the Supporting Infor-
mation).
1
yellow oil). H NMR (300 MHz, CDCl3): d=1.29 (t, J=5.4 Hz, 6H), 4.18
(s, 4H), 4.19–4.24 (q, 4H), 6.63 (d, J=8.1 Hz, 2H), 6.80 (t, J=7.35 Hz,
1H), 7.21–7.26 ppm (m, 2H); IR (neat): n˜2981.2, 1745.2, 1733.6, 1600.6,
1508.0, 1386.5, 1172.5, 1024.0, 748.2 cmꢀ1; MS (ESI): m/z: 266 [M+H]+,
288 [M+Na]+; HRMS: m/z: calcd for C14H19NO4Na [M+Na]+: 288.1212;
found: 288.1213.
Synthesis of 4
Conclusion
POCl3 (3.54 g, 23.0 mmol) was added dropwise over a period of 10 min to
cold N,N-dimethylformamide (DMF; 5.6 mL, 72.4 mmol), and then the
mixture was allowed to mix under stirring for 30 min.[27] Compound 5
(5.52 g, 20.8 mmol) was added to this slowly under cold conditions and
the solution was heated at 908C for 2 h. After completion of the reaction,
the reaction mixture was cooled and poured over ice-cold water. This
mixture was then neutralized to pH 7 by addition of solid sodium acetate.
It was then extracted with EtOAc, washed successively with water and
brine, and dried over anhydrous Na2SO4. Crude oily material was ob-
tained after evaporation of the solvent. Compound 4 was obtained from
this after purification by silica gel column (eluent: 20% EtOAc/n-
hexane) as a white solid. Yield 92%, 5.6 g. M.p. 57–598C; 1H NMR
(300 MHz, CDCl3): d=1.26 (t, J=7.0 Hz, 6H), 4.17–4.25 (m, 8H), 6.63
(d, J=8.4 Hz, 2H), 7.72 (d, J=8.4 Hz, 2H), 9.76 ppm (s, 1H); 13C NMR
(75 MHz, CDCl3): d=14.1, 53.3, 61.5, 111.7, 127.3, 131.9, 152.5, 169.6,
190.4 ppm; IR (neat): n˜ =3478.9, 2919.2, 2829.0, 2749.7, 1742.3, 1672.0,
In conclusion, we have synthesized a new colorimetric probe
for the effective detection of cyanide ions in water. The de-
tection of CNꢀ by using probe 1 was found to be totally free
of interference from any other anions. The probe gives an
immediate response to the cyanide ion both by visible color
change as well as by spectroscopic means (UV/Vis and emis-
sion spectra). The cyanide ion can be detected below ppm
level by using fluorescence emission spectroscopy. In con-
trast to other reported reaction-based probes for cyanide,
the present system does not require any preoptimized condi-
tions such as mixing of solvents, phase-transfer reagents, or
high temperature. The mechanism of the reaction was inves-
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Chemodosimetric Probe
1596.1, 1525.5, 1385.9, 1320.5, 1167.0, 1020.5, 961.1, 812.6 cmꢀ1; MS (ESI):
m/z: 294 [M+H]+, 316 [M+Na]+; HRMS: m/z: calcd for C15H19NO5Na
[M+Na]+: 316.1161; found: 316.1162.
[1] R. Koenig, Science 2000, 287, 1737–1738..
[2] www.epa.gov/safewater/mcl.html#mcls web page (20 July 2006).
[3] A. Ishii, H. Seno, K. Watanabe-Suzuki, O. Suzuki, T. Kumazawa,
Anal. Chem. 1998, 70, 4873–4876.
[4] C. Young, L. Tidwell, C. Anderson, Cyanide: Social, Industrial, and
Economic Aspects, Minerals, Metals, and Materials Society, Warren-
dale, 2001.
[5] H. Sun, Y. Y. Zhang, S. H. Si, D. R. Zhu, Y. S. Fung, Sens. Actuators
B 2005, 108, 925–932.
[6] Z. Xu, X. Chen, H. N. Kim, J. Yoon, Chem. Soc. Rev. 2010, 39, 127–
137.
[7] a) H. Miyaji, J. L. Sessler, Angew. Chem. 2001, 113, 158–161;
Angew. Chem. Int. Ed. 2001, 40, 154–157; b) N. Gimeno, X. Li, J. R.
Durrant, R. Vilar, Chem. Eur. J. 2008, 14, 3006–3012; c) S.-S. Sun,
A. J. Lees, Chem. Commun. 2000, 1687–1688; d) P. Anzenbacher Jr.,
D. S. Tyson, K. Jursꢃkovꢄ, F. N. Castellano, J. Am. Chem. Soc. 2002,
124, 6232–6233; e) I. S. Park, E.-J. Heo, J.-M. Kim, Tetrahedron
Lett. 2011, 52, 2454–2457.
[8] a) Y. H. Kim, J. I. Hong, Chem. Commun. 2002, 512–513; b) X.
Chen, S.-W. Nam, G.-H. Kim, N. Song, Y. Jeong, I. Shin, S. K. Kim,
J. Kim, S. Park, J. Yoon, Chem. Commun. 2010, 46, 8953–8955;
c) C.-F. Chow, M. H. W. Lam, W.-Y. Wong, Inorg. Chem. 2004, 43,
8387–8393; d) J. H. Lee, A. R. Jeong, I.-S. Shin, H.-J. Kim, J.-I.
Synthesis of 3
A mixture of 4 (293 mg, 1.0 mmol), indole (234 mg, 2.0 mmol), and a cata-
lytic amount of iodine (approximately 13 mg, 0.2 mmol) in acetonitrile
(10 mL) was stirred at room temperature for approximately 1 h. After
completion of the reaction, the mixture was quenched with aqueous
Na2S2O3 solution (5%, 10 mL) and the aqueous phase was extracted with
ethyl acetate (3ꢁ5 mL). The organic phase was dried over anhydrous
Na2SO4, and the solvent was removed under vacuum. The residue was
purified by column chromatography over silica gel to afford 3 (eluent:
ꢁ20% EtOAc in n-hexane). Yield 94%, 478 mg (white solid). M.p. 146–
1478C; TLC: Rf =0.2 (30% EtOAc/petroleum ether); 1H NMR
(300 MHz, CDCl3): d=1.23 (t, J=6.9 Hz, 6H), 4.08 (s, 4H), 4.17 (q, J=
7.1 Hz, 4H), 5.75 (s, 1H), 6.47–6.57 (m, 4H), 6.96 (t, J=7.3 Hz, 2H),
7.10–7.14 (m, 4H), 7.29–7.37 (m, 4H), 7.87 ppm (s, 2H); 13C NMR
(100 MHz, CDCl3): d=14.1, 38.9, 53.4, 61.0, 110.9, 112.3, 118.9, 119.9,
121.6, 123.6, 127.0, 129.3, 133.8, 136.6, 146.0, 171.2 ppm; IR (KBr): n˜ =
3451.9, 3353.6, 2981.4, 1725.9, 1610.2, 1517.7, 1455.9, 1415.4, 1336.4,
1193.7, 1095.3, 1025.9, 736.7 cmꢀ1; MS (ESI): m/z: 508 [M+H]+, 510
[M+H]+, 532 [M+Na]+; HRMS: m/z: calcd. for C31H31N3O4Na [M+Na]+
: 532.2212; found: 532.2212.
¨
Hong, Org. Lett. 2010, 12, 764–767; e) C. R. Wade, F. P. Gabbai,
Inorg. Chem. 2010, 49, 714–720; g) K. P. Divya, S. Sreejith, B. Ba-
lakrishna, P. Jayamurthy, P. Aneesa, A. Ajayaghosh, Chem.
Commun. 2010, 46, 6069–6071; f) H. S. Jung, J. H. Han, Z. H. Kim,
C. Kang, J. S. Kim, Org. Lett. 2011, 13, 5056–5059.
Synthesis of 2
A solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ; 227 mg,
1.0 mmol) in acetonitrile was added dropwise to a solution of 3 (510 mg,
1.0 mmol) in acetonitrile at room temperature. Upon addition of the first
few drops of DDQ solution, the initial color turned to dark red immedi-
ately. After stirring at room temperature for 2 h, a dark red solid precipi-
tated, which was filtered, washed thoroughly with CH3CN, and dried
under vacuum. Yield 90%, 457 mg (green solid). M.p. 204–2058C;
1H NMR (400 MHz, [D6]DMSO): d=1.22 (t, J=6.8 Hz, 6H), 4.16 (q, J=
6.8 Hz, 4H), 4.48 (s, 4H), 6.90 (d, J=7.6 Hz, 4H), 7.11 (s, 2H), 7.35 (t,
J=7.2 Hz, 2H), 7.58 (s, 2H), 7.66 (d, J=8.0 Hz, 2H), 8.34 (s, 2H),
13.4 ppm (s, 1H); 13C NMR (100 MHz, [D6]DMSO): d=14.0, 52.5, 60.8,
112.6, 113.9, 120.0, 120.6, 123.4, 125.0, 139.0, 144.6, 154.2, 169.1 ppm; IR
(KBr): n˜ =3149.8, 2987.5, 2217.9, 1741.2, 1598.7, 1512.0, 1477.9, 1411.9,
1186.7, 1123.8, 747.6 cmꢀ1; MS (ESI): m/z: 508 [M[+H]+; HRMS: m/z:
calcd for C31H30N3O4 [M+H]+: 508.2236; found: 508.2257.
[9] W. J. Jin, M. T. Fernꢄndez-Argꢅelles, J. M. Costa-Fernꢄndez, R. Per-
eiro, A. Sanz-Medel, Chem. Commun. 2005, 883–885.
[10] a) R. Badugu, J. R. Lakowicz, C. D. Geddes, J. Am. Chem. Soc.
2005, 127, 3635–3641; b) J. V. Ros-Lis, R. Martꢃnez-Mꢄnꢂez, J. Soto,
Chem. Commun. 2005, 5260–5262; c) R. Badugu, J. R. Lakowicz,
C. D. Geddes, Dyes Pigm. 2005, 64, 49–55; d) Y. Kim, H. Zhao, F. P.
Gabbaꢆ, Angew. Chem. 2009, 121, 5057–5060; Angew. Chem. Int.
Ed. 2009, 48, 4957–4960.
[11] D.-G. Choa, J. L. Sessler, Chem. Soc. Rev. 2009, 38, 1647–1662.
[12] a) M. Tomasulo, S. Sortino, A. J. P. White, F. M. Raymo, J. Org.
Chem. 2006, 71, 744–753; b) M. Tomasulo, S. Sortino, A. J. P. White,
F. M. Raymo, J. Org. Chem. 2005, 70, 8180–8189.
[13] a) Y. Kim, H.-S. Huh, M. H. Lee, I. L. Lenov, H. Zhao, F. P. Gabbaı,
Chem. Eur. J. 2011, 17, 2057–2062; b) T. W. Hudnall, F. P. Gabbaı, J.
Am. Chem. Soc. 2007, 129, 11978–11986.
Synthesis of 1
Aqueous KOH (39 mg, 0.68 mmol) was added dropwise at RT to a solu-
tion of 2 (86 mg, 0.17 mmol) in MeOH (0.2 mL), and then the mixture
was heated to reflux for 2 h.[27] After cooling to RT, the reaction mixture
was acidified to pH ꢁ2.0 by dropwise addition of diluted HCl. A solid
was precipitated out, which was then filtered. The solid was then washed
with MeOH/H2O (1:1) and dried under vacuum. Yield 90%, 69 mg (red
solid). M.p.>2508C; 1H NMR (400 MHz, [D6]DMSO): d=4.28 (s, 4H),
6.80 (d, J=8.4 Hz, 2H), 6.89 (s, 2H), 7.11 (d, J=6.4 Hz, 2H), 7.34 (t, J=
7.6 Hz, 2H), 7.61 (d, J=8.4 Hz, 2H), 7.66 (d, J=8.0 Hz, 2H), 8.30 (s,
2H), 13.43 ppm (brs, 2H); 13C NMR (100 MHz, [D6]DMSO): d=55.9,
112.3, 113.9, 119.9, 120.8, 123.3, 124.9, 126.7, 138.0, 139.1, 144.2, 154.0,
171.6 ppm; IR (KBr): n˜ =3114.3, 2226.7, 1721.6, 1600.2, 1496.2, 1412.1,
1387.1, 1317.0, 1212.9, 1187.6, 1129.9, 965.6, 749.0 cmꢀ1; MS (ESI): m/z:
452 [M+H]+; HRMS: m/z: calcd for C27H22N3O4 [M+H]+: 452.1601;
found: 452.1610.
[14] Y.-K. Yang, J. Tae, Org. Lett. 2006, 8, 5721–5723.
[15] a) J. L. Sessler, D.-G. Cho, Org. Lett. 2008, 10, 73–75; b) D.-G. Cho,
J. H. Kim, J. L. Sessler, J. Am. Chem. Soc. 2008, 130, 12163–12167.
[16] J. Jo, D. Lee, J. Am. Chem. Soc. 2009, 131, 16283–16291.
[17] a) Z. Liu, X. Wang, Z. Yang, W. He, J. Org. Chem. 2011, 76, 10286–
10290; b) L. Yuan, W. Lin, Y. Yang, J. Song, J. Wang, Org. Lett.
2011, 13, 3730–3733; c) G. J. Kim, H. J. Kim, Tetrahedron Lett. 2010,
51, 185–187; d) X. Wu, B. Xu, H. Tong, L. Wang, Macromolecules
2011, 44, 4241–4248; e) S.-J. Hong, J. Yoon, S.-H. Kim, J. S. Kim, J.
Yoon, C.-H. Lee, Chem. Commun. 2009, 189–191; f) P. Kaur, D.
Sareen, S. Kaur, K. Singh, Inorg. Chem. Commun. 2009, 12, 272–
275; g) A. Afkhami, N. Sarlak, Sens. Actuators B 2007, 122, 437–
441; h) H.-T. Niu, X. Jiang, J. He, J.-P. Cheng, Tetrahedron Lett.
2009, 50, 6668–6671; i) S.-J. Hong, C.-H. Lee, Tetrahedron Lett.
2012, 53, 3119–3122.
[18] a) H. J. Kim, K. C. Ko, J. H. Lee, J. Y. Lee, J. S. Kim, Chem.
Commun. 2011, 47, 2886–2888; b) Z. Yang, Z. Liu, Y. Chen, X.
Wang, W. He, Y. Lu, Org. Biomol. Chem. 2012, 10, 5073–5076.
[19] X. Lv, J. Liu, Y. Liu, Y. Zhao, M. Chen, P. Wang, W. Guo, Org.
Biomol. Chem. 2011, 9, 4954–4958.
Acknowledgements
[20] a) Y. Ding, T. Li, W. Zhu, Y. Xie, Org. Biomol. Chem. 2012, 10,
4201–4207; b) S. K. Kwona, S. Kou, H. N. Kim, X. Chen, H. Hwang,
S.-W. Nam, S. H. Kim, K. M. K. Swamy, S. Park, J. Yoon, Tetrahe-
dron Lett. 2008, 49, 4102–4105; c) H. Lee, Y. M. Chung, K. H. Ahn,
Tetrahedron Lett. 2008, 49, 5544–5547; d) H.-T. Niu, X. Jiang, J. He,
S.B. thanks DST (J.C. Bose Fellowship) for the financial support of this
work. N.K. thanks the University Grants Commission (UGC) for
a Senior Research Fellowship (SRF).
Chem. Asian J. 2012, 7, 2805 – 2812
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
2811

Santanu Bhattacharya et al.
FULL PAPER
J.-P. Cheng, Tetrahedron Lett. 2008, 49, 6521–6524; e) J. Isaad, A.
Perwuelz, Tetrahedron Lett. 2010, 51, 5810–5814.
Kim, Tetrahedron Lett. 2007, 48, 2541–2546; e) J. L. Sessler, D.-G.
Cho, V. Lynch, J. Am. Chem. Soc. 2006, 128, 16518–16519; f) X. He,
S. Hu, K. Liu, Y. Guo, J. Xu, S. Shao, Org. Lett. 2006, 8, 333–336.
[23] H. J. Kim, H. Lee, J. H. Lee, D. H. Choi, J. H. Jung, J. S. Kim, Chem.
Commun. 2011, 47, 10918–10920.
[24] Method described in E. Ballesteros, D. Moreno, T. Gꢇmez, T. Rodrꢃ-
guez, J. Rojo, M. Garcꢃa-Valverde, T. Torroba, Org. Lett. 2009, 11,
1269.
[21] a) N. Kumari, S. Jha, S. Bhattacharya, J. Org. Chem. 2011, 76, 8215–
8222; b) S. Bhattacharya, A. Gulyani, Chem. Commun. 2003, 1158–
1159; c) Y. Singh, A. Gulyani, S. Bhattacharya, FEBS Lett. 2003,
541, 132–136; d) S. Bhattacharya, V. P. Kumar, J. Org. Chem. 2003,
68, 2741–2747; e) S. Bhattacharya, M. Thomas, Tetrahedron Lett.
2000, 41, 10313–10317; f) S. Bhattacharya, K. Snehalatha, S. K.
George, J. Org. Chem. 1998, 63, 27–35; g) S. Bhattacharya, S. S.
Mandal, Chem. Commun. 1996, 1515–1516.
[25] L. Peng, M. Wang, G. Zhang, D. Zhang, D. Zhu, Org. Lett. 2009, 11,
1943–1946.
[22] a) L. Wang, X. He, Y. Guo, J. Xu, S. Shao, Beilstein J. Org. Chem.
2011, 7, 218–221; b) W. Wei, X. Liang, G. Hua, Y. Guo, S. Shao, Tet-
rahedron Lett. 2011, 52, 1422–1425; c) R. M. F. Batista, E. Oliveira,
C. NuÇez, S. P. G. Costa, C. Lodeiro, M. M. M. Raposo, J. Phys. Org.
Chem. 2009, 22, 362–366; d) J. W. Lee, S. Y. Park, B.-K. Cho, J. S.
[26] T. Gunnlaugsson, C. Lee, R. Parkesh, Org. Lett. 2003, 5, 4065–4068.
[27] K.-J. Moon, H.-K. Shim, Macromolecules 1996, 29, 861–867.
Received: June 24, 2012
Published online: October 5, 2012
2812
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Chem. Asian J. 2012, 7, 2805 – 2812