Anion sensor based on the indoaniline-thiourea system

Article abstract of DOI:10.1016/S0040-4039(02)01455-7

A new chromogenic indoaniline-thiourea-based sensor was designed to recognize anions in an organic solvent through complementary intermolecular hydrogen bonding. Complexed anions cause significant disturbance to the intramolecular hydrogen-bonded structure of the sensor, which then induces color and UV-vis spectral changes. This sensor allows for selective colorimetric detection of tetrahedral oxoanions (HSO₄^- and H₂PO₄^-).

Full text of DOI:10.1016/S0040-4039(02)01455-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7273–7276
Anion sensor based on the indoaniline–thiourea system
Dong Hoon Lee,a Ho Yong Leea and Jong-In Honga,b,
*
aSchool of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742, South Korea
bCenter for Molecular Design and Synthesis, KAIST, Taejon 305-701, South Korea
Received 24 May 2002; revised 15 July 2002; accepted 17 July 2002
Abstract—A new chromogenic indoaniline–thiourea-based sensor was designed to recognize anions in an organic solvent through
complementary intermolecular hydrogen bonding. Complexed anions cause significant disturbance to the intramolecular hydro-
gen-bonded structure of the sensor, which then induces color and UV–vis spectral changes. This sensor allows for selective
−
colorimetric detection of tetrahedral oxoanions (HSO4 and H2PO4−). © 2002 Elsevier Science Ltd. All rights reserved.
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−
The development of chemosensors for biologically
important anions has recently emerged as a key
research area.1 One attractive approach involves the
construction of optical sensors.2–4 Such a system gener-
ally consists of two parts. One is the anion-binding part
employing various combinations of pyrroles, guanidini-
ums, Lewis acids, amides and urea/thioureas.1–5 The
other is the chromophore part which converts binding-
induced changes into optical signals.2–4 These two parts
can be either covalently attached4 or intermolecularly
linked.2a,b,3 According to previous studies,4 F− seems to
interact with a hydrogen bond donor (-NH2, -OH,
-C(O)NHR) of a chromophore more strongly than any
other anions. This allows F− to give rise to the most
intense color change in an organic solvent among all
anions. Therefore, it has been difficult for other anions
to provide a more selective color change than F− using
the chemosensors with H-bond donors within a chro-
mophoric unit. In this paper, we present a new strat-
egy for a chemosensor to render it capable of showing
more selective color and spectral changes for tetra-
hedral oxoanions (HSO4 and H2PO4 ) compared to
F− by using an indoaniline chromophore containing a
quinone-type carbonyl group. This chromophore acts
not only as a color-reporting group, but also as a
binding affinity control group. 1 allows for selective
−
−
colorimetric detection of H2PO4 and HSO4 (Fig. 1).
Indoaniline-based sensors 1 was synthesized from a
known precursor 4.6 Removal of the Boc protecting
group from 4 followed by treatment of the resulting
ammonium salt in THF with 2 equiv. of n-butyl–
isothiocyanate and TEA provided 5 in 70% yield.
Condensing 5 with 4-(diethylamino)-2-methylaniline
hydrochloride under alkaline conditions in the pres-
ence of K3[Fe(CN)6] as an oxidizing agent afforded
the indoaniline-based anion sensor 1 (Scheme 1).7–9
Compound 1 contains four thiourea NH groups as
H-bond donors for anions, and one indoaniline group
for monitoring anion-binding events.
Figure 1. Indoanaline-based chromagenic sensors.
* Corresponding author. Tel.: +82-2-880-6682; fax: +82-2-889-1568; e-mail: jihong@plaza.snu.ac.kr
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01455-7

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D. H. Lee et al. / Tetrahedron Letters 43 (2002) 7273–7276
Scheme 1. Reagents and conditions: (a) i. TFA, anisole, CH2Cl2, ii. n-BuNCS, TEA, DMF, rt, 70%; (b) i. 4-(diethylamino)-2-
methylaniline·hydrochloride, aq. NaOH, MeOH, rt, ii. K3[FeCN)6], 52%.
Sensor 1 showed a bathochromic shift of umax, com-
pared to that of control 3, which indicates that the
indoaniline chromophore appears to be influenced by
intramolecular hydrogen bonding between the carbonyl
oxygen of indoaniline and adjacent thiourea NHs.7
Wavelength maxima (umax), molecular extinction coeffi-
cients, and frequencies (cm−1) of CꢀO of 1 as well as
related compounds are summarized in Table 1.
anions resulted in similar blue shift tendencies. The 1:1
binding ratio was confirmed by clear isosbestic points
and Job’s plots10a (Figs. 2 and 3). As expected from
UV–vis data, a color change occurs through addition of
anions to the solution of 1 (Fig. 2).
Upon the addition of H2PO4− or HSO4, the color of the
solution changed from blue–green to deep blue. How-
ever, addition of AcO− or F− with higher basicity
caused a less intense color change. The color change
terminated after the addition of 40 equiv. of each
anion. However, in the case of Cl−, Br− and I−, no
detectable color changes were observed upon excess
addition of anions to the solution of 1 (Fig. 4). The
qualitative changes described above are reflected in the
quantitative data in the UV–vis absorption experiment
(Table 2).10b The color discrimination is explained by
the difference in umax and absorbance of each complex.
Table 1 shows an insight into the intramolecular hydro-
gen bonded structure of 1 and 2. Sensors with more
acidic NHs display larger bathochromic shifts and
lower frequency of CꢀO (quinone), compared to the
free indoaniline compound 3. In the case of 1, which
has the more acidic NH group than 2, a pronounced
wavelength change (71 nm) was detected. These results,
in turn, enable us to assume that an anion complexed
with a bis-thiourea moiety could cause significant dis-
turbance of an intramolecular hydrogen bonded struc-
ture of free 1 (Scheme 2). This would subsequently
induce spectral absorption change in the complexes. In
−
−
The specific UV–vis absorbance for H2PO4 and HSO4
can be rationalized on the basis of the guest structure.
The structural complementarity is an important factor
for effective hydrogen bonding. Thus, 1 with four NHs
−
fact, complex of 1 and H2PO4 (1:20, v/v) showed large
absorption and IR spectral shifts of CꢀO of 1, indicat-
ing a large degree of breakdown of the intra-molecular
H-bonds in the free 1.
−
−
would preferably binds with H2PO4 and HSO4 of a
tetrahedral geometry but not with spherical (e.g. Br−),
or planar (e.g. AcO−) ions.11 Energy minimized struc-
−
−
Indeed, upon addition of anions, the thiourea NHs are
forced to participate in the hydrogen bonding with
anions, hence the contribution of NHs to the hydrogen
bonding with the indoanilne CꢀO group decreases. This
structural disturbance is reflected in the observed spec-
tral blue shift of the complexes. In the absence of
anions, the UV spectrum of 1 is characterized by the
presence of an absorption band at 678 nm. Addition of
tures for the complexes with H2PO4 and HSO4 show
multitopic hydrogen bonds between four thiourea NHs
and anions as expected.12
In CH3CN, the UV spectrum of 1 is characterized by
the presence of an absorption band at 634 nm, indicat-
ing that intramolecular H-bonds of 1 (Scheme 2, Table
1) were weakened due to the more polar nature of
−
H2PO4 caused hypsochromic band shifts from 678 nm
−
CH3CN. Although an addition of H2PO4 caused hyp-
(umax) down to 632 nm. Complexation with a series of
sochromic band shift from 634 nm (umax) down to 610
nm,13 amount of UV absorption changes was small and
color change was not detectable by ‘naked eye’. How-
ever, selectivity trends for binding affinities of anions in
CH3CN was similar to those in CHCl3 (Table 2). Thus,
Table 1. Absorption and IR spectral data of CꢀO of com-
pounds 1–3 in CHCl3
a
w/cm−1 (CꢀO)
−
−
Compd
umax/nm (mmax
)
H2PO4 and HSO4 of a tetrahedral geometry also
showed stronger affinity to 1 with four thiourea NHs in
CH3CN. This means that the binding and sensing mode
are the same in both CHCl3 and CH3CN.
1
2
3
678 (30,000)
640 (25,000)
607 (18,000)
632 (13,000)
1597
1601
1606
1603
1-hpb
Compound 2, which has an indoanilne and two carba-
mate NH groups, does not show detectable color
changes upon addition of the same amounts of anions.
a The unit: dm3 mol−1 cm−1
b Sensor 1: H2PO4−n-Bu4N+ complex.

D. H. Lee et al. / Tetrahedron Letters 43 (2002) 7273–7276
7275
Scheme 2. Proposed mechanism for complexation of sensor 1 with anion.
This result indicates that the introduction of four
thiourea NH groups as the anion-binding site increases
the binding strength.
In summary, the new chromogenic indoaniline-thiourea
based anion sensor 1 was designed to selectively recog-
−
−
nize tetrahedral oxoanions (H2PO4 , HSO4 ) in an
organic solvent through complementary intermolecular
hydrogen bonding. Complexed anions significantly dis-
Figure 3. Job’s plots between sensor 1 and anions in chloro-
form at 20°C. Rectangle, diamond and triangle represent
AcO−n-Bu4N+, F−n-Bu4N+ and H2PO4−n-Bu4N+, respectively.
[H]+[G]=2.0×10−5 M.
Figure 2. (a) UV–vis titration of 1 with H2PO4−n-Bu4N+ in
chloroform. [1]=2.0×10−5 M, [H2PO4−]=0–40 equiv. of 1; (b)
UV–vis changes of 1 operated in CHCl3 (2.0×10−5 M) after
the addition of 30 equiv. of anions.
Figure 4. Color changes of
1
in CHCl3. [1]=2.0×10−5
,
[anion]=40 equiv.: (a) 1 (b) 1+F− (c) 1+H2PO4 (d) 1+AcO−
−
(e) 1+HSO4 (f) 1+Br− (g) 1+Cl− (h) 1+I−.
−

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D. H. Lee et al. / Tetrahedron Letters 43 (2002) 7273–7276
Table 2. Association constants (M−1) from UV–vis titrations for complexes of 1 with anionic guests in CHCl3 and MeCN
at 20°Ca
−
−
F−
H2PO4
AcO−
HSO4
Cl−
CHCl3
CH3CN
3.0×103
3.3×103
1.1×104
6.3×103
−2.0×103
2.5×104
1.0×104
1.4×103
NDb
NDb
a The anions were added as their tetrabutylammonium salts except for Cl−, which was used as tetraethylammonium salt.
b ND=not determined (spectral change too small to determine).
turb the intramolecular hydrogen-bonded structure of
1, and then induce spectral absorption change in the
complexes. This system allows for selective colorimetric
5. For reviews, see: (a) Supramolecular Chemistry of Anions;
Binachi, A., Bowman-James K., Garcia-Espana, E., Eds.;
Wiley-VCH: New York, 1997; (b) Lehn, J.-M.
Supramolecular Chemistry, Concepts and Perspectives;
Wiley-VCH: Weinheim, 1995.
detection of H2PO4 and HSO4 over F−.
−
−
6. Lee, D. H.; Lee, K. H.; Hong, J.-I. Org. Lett. 2001, 3,
5–8.
Acknowledgements
7. Kubo, Y.; Tokita, S.; Kojima, Y.; Osano, Y. T.; Mat-
suzaki, T. J. Org. Chem. 1996, 61, 3758–3765.
8. Selected spectral data for 1: 1H NMR (300 MHz, ace-
tone-d6, ppm) l 0.86–0.93 (m, 6H), 1.22 (t, 6H, J=7.0
Hz), 1.27–1.43 (m, 4H), 1.53–1.63 (m, 4H), 2.33 (s, 3H),
3.49–3.56 (m, 8H), 4.55 (d, 2H, J=4.3 Hz), 4.62 (d,
J=3.6 Hz), 6.58 (dd, 1H, J=2.8, 8.9 Hz), 6.77 (d, 1H,
J=2.5 Hz), 6.82 (d, J=8.9 Hz), 7.20 (br, 1H), 7.29 (br,
1H); 13C NMR (300 MHz, acetone-d6, ppm) l 12.60,
13.61, 18.73, 20.23, 26.93, 31.56, 43.29, 44.64, 109.65,
113.82, 124.78, 126.28, 138.12, 138.63, 138.88, 149.03,
151.76, 184.18, 186.98; MS (FAB) m/z=557.3110 (M+1+).
9. Selected spectral data for 5; 1H NMR (300 MHz, ace-
tone-d6, ppm) l 0.87–0.92 (t, 6H, CH2CH3), 1.27–1.39
(m, 4H, CH2CH2CH3), 1.50–1.59 (m, 4H, CH2CH2CH2),
3.46 (br, 4H, NHCH2CH3), 4.74 (br, 4H, ArCH2NH),
6.74–6.79 (t, 1H, ArH), 7.15–7.18 (d, 2H, ArHs), 7.19
(br, 2H, CSNHCH2), 7.44 (br, 2H, ArCH2NHCS), 9.34
(s, 1H, ArOH); 13C NMR (300 MHz, acetone-d6, ppm) l
13.72, 20.25, 31.46, 44.37, 119.90, 125.81, 130.28, 153.57,
182.37; MS (FAB) m/z: 383.1946 (M+1+).
Financial support from KRF (Grant No. 99-042-
D00073) is gratefully acknowledged. D.H.L. and
H.Y.L. thank the Ministry of Education for the BK21
fellowship.
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