Synthesis of a crescent aromatic oligothioamide and its high selectivity in recognizing copper(II) ions

Article abstract of DOI:10.1016/j.cclet.2013.05.025

Functionalization of shape-persistent aromatic oligoamides still represents a difficult task nowadays. A crescent aromatic oligothioamide was synthesized by simple thionation of the corresponding oligoamide with the Lawesson's reagent. The results from UV

Full text of DOI:10.1016/j.cclet.2013.05.025

Chinese Chemical Letters 24 (2013) 881–884
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Chinese Chemical Letters
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Original article
Synthesis of a crescent aromatic oligothioamide and its high selectivity in
recognizing copper(II) ions
a
Qian Jiang a, Lu-Tao He a, Shun-Zhong Luo b, Yan-Qiu Yang b, Liang Yang b, Wen Feng a, , Li-Hua Yuan
*
a Key Laboratory for Radiation Physics and Technology of Ministry of Education, College of Chemistry, Institute of Nuclear Science and Technology, Sichuan University, Chengdu
610064, China
b Institute of Nuclear Physics and Chemistry, CAEP, Mianyang 621900, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Functionalization of shape-persistent aromatic oligoamides still represents a difficult task nowadays. A
crescent aromatic oligothioamide was synthesized by simple thionation of the corresponding
oligoamide with the Lawesson’s reagent. The results from UV–vis spectra of the molecule upon metal
ion complexation demonstrated its higher selectivity in recognizing Cu2+ ions compared to the
oligoamide precursor. The stoichiometry of the complex formed between the thioamide and Cu2+ was
found to be 1:1 with a binding constant of (4.3 Æ 0.9) Â 104 mol/L.
Received 1 April 2013
Received in revised form 6 May 2013
Accepted 13 May 2013
Keywords:
Oligothioamide
Recognition
ß 2013 Wen Feng. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Copper(II) ion
UV–vis spectra
1. Introduction
selective and efficient detection of biologically and chemically
important cations [16,17] (e.g., Cu2+, Fe3+, Cr3+, Pb2+, Hg2+, etc.).
Shape-persistent aromatic oligoamides are a class of molecules
defined by their uncollapsable structural framework by the aid of
intramolecular hydrogen bonds [1–6]. Among them, those con-
structed by coupling aromatic amines and acids with electron-
donating groups at the ortho-position of the carbonyl group are
especially appealing due to the crescent molecular structures
containing introverted carbonyl groups in the cavity [7]. The
importance of intramolecular hydrogen bonding interactions
present in these compounds has been showcased by the efficient
formation of the corresponding aromatic oligoamide macrocycles
[8–12]. These aromatic oligoamides have displayed many inter-
esting properties. For example, we recently reported the efficient
extraction of some transition metal ions with acyclic species [13].
In addition, they have been demonstrated to serve as a new class of
diverse mesogens of liquid crystals [14]. It was known that the
introduction of soft donor atoms such as phosphorus or sulphur
atoms into receptor substituents improved their complexing
ability towards transition and heavy metal ions [15]. It is reasoned
that the replacement of the amide carbonyl oxygen atoms by sulfur
atoms may endow them with improved complexation properties.
Selective recognition of transition metal ions has attracted an
increasing interest in recent years because of the need for the
Finding selective receptors for the soft transition metal copper ion
is one of the research focuses. Many synthetic receptors have been
reported for recognizing and sensing copper ions [18–20].
However, shape-persistent aromatic oligothioamides containing
hydrophilic lumen have never been synthesized for this purpose.
So far, modifications of crescent or folding aromatic oligoamides
are still a difficult task. Herein, we report the synthesis of aromatic
oligothioamide 1 with a crescent conformation and its selective
recognition of copper(II) ion. To the best of our knowledge, this
represents the first example of a crescent aromatic oligoamide
with carbonyl oxygen atoms being replaced by sulfur atoms for
metal ion recognition.
2. Experimental
Chemical grade reagents were used without further purification
for synthesis unless stated otherwise. Compounds 3 and 4 were
prepared following our previous method in the literature [8,11].
Column chromatography was carried out using silica gel (300–
400 mesh). Thin layer chromatography (TLC) was performed on
glass-backed plates coated with silica gel 60 with F254 indicator.
NMR spectra were recorded at room temperature on a Bruker
Avance-400 NMR spectrometer. High resolution mass data were
collected by Waters Q-TOF Premier. The UV–vis spectra were
measured using a Shimadzu UV-2350 spectrometer. Stock solu-
* Corresponding author.
E-mail address: wfeng9510@scu.edu.cn (W. Feng).
tions of each ligand were prepared (c 1000
mmol/L) in acetonitrile.
1001-8417/$ – see front matter ß 2013 Wen Feng. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.05.025

882
Q. Jiang et al. / Chinese Chemical Letters 24 (2013) 881–884
CH3
O
CH3
O
CH3
O
CH3
O
R
O
R
O
O
X
O
R
R
R
R
Et3N
Lawesson's reagent
toluene, 70 o
HN
NH
HN
NH
O
O
O
O
+
H
N
C
CH2Cl2
X
ClOC
C2H5
O
O
S
S
3a: X = NO2
O
R
R
R
R
Pd / C, H2
O
O
O
O
3b: X = NH2
4
O
NH
CH2CH3
S
NH
CH2CH3
HN
HN
S
O
R=
2
CH2CH3
CH2CH3
1
Scheme 1. Synthetic route of aromatic oligothioamide 1.
All stock solutions of metal ions were prepared from analytical
grade nitrate salts which were dissolved (c 1000 mol/L) in
Compound 2 was prepared using a coupling reaction of a reduced
product 3b from 3a by hydrogenation and acyl chloride 4 bearing
alkoxy groups. The key precursor 4 was obtained following the
literature procedure [9]. All compounds were characterized by
1H NMR, 13C NMR and HRMS (Figs. S1–S8 in Supporting
information).
m
acetonitrile. Eleven metal nitrates including Li+, Na+, K+, Ca2+, Sr2+
,
Cd2+, Ni2+, Co2+, Cu2+, Zn2+, and Pb2+ salts were employed in the
UV–vis experiment.
2.1. Synthesis of compound 2
The patterns and chemical shifts for each amide proton of
compound 2 are the same or similar to those of the previously
reported compounds [9]. The high resolution ESI mass spectra of
the oligothioamide 1 and oligoamide 2 showed highly intense
peaks at m/z 1117.5958 [M+Na]+ (calcd. 1117.5954 [M+Na]+) and
1053.6865 [M+Na]+ (calcd. 1053.6868 [M+Na]+), respectively,
which are in full agreement with the desired structures (Figs. S7
and S8 in Supporting information). Interestingly, the 1H NMR
spectrum of 1 recorded in CDCl3 revealed that the three-centre H-
bonded amide protons and terminal amide protons all exhibited
noticeable downfield shifts compared to those of compound 2. For
example, a shift of 1.0 ppm (from 9.5 ppm to 10.5 ppm) was
observed for NH protons in 1 relative to those in 2 (Fig. S3 in
Supporting information). We attribute the downfield shift to the
difference of oligothioamide and oligoamide in delocalizing the
lone pair electrons on the nitrogen to the double bond system.
The metal ion binding properties including selectivity of
Compound 4 (1.57 g, 3.36 mmol) was dissolved in dry CH2Cl2
(20 mL) and the mixture was added dropwise into a CH2Cl2
solution (30 mL) containing 3b (0.28 g, 1.68 mmol) and Et3N
(0.42 g, 2.52 mmol). After refluxing for 2 h, the reaction mixture
was washed with diluted hydrochloric acid and water, dried over
anhydrous MgSO4 and filtered. Removal of CH2Cl2 and further
purification by column chromatography (CHCl2/CH3OH = 20/1)
provided the product 2 (1.48 g, 86%) as a white solid (Scheme 1).
1H NMR (400 MHz, CDCl3):
d 9.45 (s, 2H, NH), 9.07 (s, 1H, Ar), (s, 2H,
Ar), 7.53 (t, 2H, J = 5.0 Hz, NH), 6.53 (s, 2H, Ar), 6.50 (s, 1H, Ar), 4.08
(m, 8H, OCH2), 3.86 (s, 6H, OCH3),3.50 (m, 4H, CH2), 1.94 (m, 2H,
CH), 1.81 (m, 2H, CH), 1.47 (m, 16H, CH2), 1.35 (m, 16H, CH2), 1.22
(t, 6H, J = 7.2 Hz, NHCH2CH3), 0.94 (m, 24H, CH3). 13C NMR
(100 MHz, CDCl3): d 164.4, 162.1, 160.3, 160.0, 146.8, 137.3, 120.3,
118.2, 115.6, 115.1, 96.4, 94.8, 72.4, 71.6, 55.8, 39.6, 38.9, 34.5,
30.8, 30.2, 29.7, 29.1, 29.0, 24.1, 23.6, 23.0, 23.9, 14.9, 14.0, 11.2,
10.8. ESI-HRMS (m/z): Calcd. for C60H94N4O10 ([M+H]+):
1031.7048; Found 1031.7031.
oligothioamide
examined in CH3CN using the nitrate salts of Li+, Na+, K+, Ca2+
Sr2+ Zn2+ Cd2+ Ni2+ Co2+ Pb2+ and Cu2+ ions by UV–vis
1 and oligoamide 2 (each 20 mmol/L) were
,
,
,
,
,
,
,
spectrometry. Among the metal ions tested, compound 1 only
showed selective recognition of Cu2+. As shown in Fig. 1(a), upon
addition of 25 equiv. of Cu2+ to the solution of 1, the maximum
absorption band at 261 nm disappeared completely along with a
concomitant change of two shoulder bands at 292 nm and 340 nm,
while a new absorption band centred at 234 nm with high intensity
appeared. A large blue shift of 27 nm and the absence of changes for
other metal ions strongly suggest the occurrence of metal
complexation and selectivity towards Cu2+. As a control, compound
2 was also investigated for its selectivity towards these metal ions
under the same conditions. Compound 2 displayed an absorption
band centred around 229 nm as shown in Fig. 1(b). This band
remains almost unchanged upon addition of 25 equivalents of Li+,
Na+, K+, Sr2+, Zn2+, Cd2+, or Pb2+ ions. Upon addition of 25 equivalents
of Ca2+, Ni2+, Co2+, or Cu2+, the absorption maximum was slightly
red-shifted to various extents. Particularly, only a small red shift of
ca. 6 nm was observed for Cu2+. The significant change of compound
1 compared to compound 2 in its absorption maxima and intensity
upon addition of Cu2+ should be ascribed to the efficient interaction
of Cu2+ with the lone pair electron of the S atoms in the thiocarbonyl
group. Thus, a high Cu2+ selectivity was achieved in 1 only when the
oxygen atoms in oligoamide 2 were replaced by the sulfur atoms,
indicating the importance of the softer sulfur atoms in the
oligothioamides for selective recognition of copper(II) ion.
2.2. Synthesis of compound 1
To a solution of 2 (0.80 g, 0.78 mmol) in dry toluene (20 mL)
was added the Lawesson’s reagent (0.75 g, 1.86 mmol). The
mixture was heated for 3 h at 70 8C. Solvent was removed in
vacuo, and the residue was extracted with CH2Cl2. The combined
CH2Cl2 extracts were washed with diluted hydrochloric acid and
water, dried over MgSO4 and filtered. Removal of CH2Cl2 and
further purification by column chromatography (CHCl2/
CH3OH = 50/1) provided product 1 (0.72 g, 86%) as a pale yellow
solid (Scheme 1). 1H NMR (400 MHz, CDCl3):
d 10.17 (s, 2H, NH),
9.43 (S, 2H, ArH), 9.27 (s, 1H, ArH), 8.87 (t, 2H, J = 2.4 Hz, NH), 6.57
(s, 1H, ArH), 6.44 (S, 2H, ArH), 4.08–4.03 (m, 8H, CH2), 3.88–3.80
(m, 10H, CH2CH3),1.84–1.76 (m, 4H, CH), 1.43–1.33 (m, 32H,
CH2),0.98 (t, 12H, J = 7.6 Hz,CH3), 0.90–0.89 (m, 6H, NHCH2CH3),
0.86 (t, 12H, J = 6.4 Hz, CH3). 13C NMR (100 MHz, CDCl3):
d 193.9,
192.2, 157.7, 157.5, 150.6, 141.8, 122.7, 121.2, 121.0, 120.5, 96.1,
95.2, 72.4, 72.0, 56.1, 41.7, 39.5, 39.0, 30.6, 30.2, 29.1, 29.0, 24.0,
23.7, 23.0, 14.1, 13.3, 11.1, 11.0. ESI-HRMS (m/z): Calcd. for
C
60H94N4O6S4 ([M+H]+): 1095.6134; Found 1095.6128.
3. Results and discussion
As shown in Scheme 1, the aromatic oligothioamide 1 was
synthesized by simple thionation of the corresponding oligoamide
2 with the aid of the Lawesson’s reagent [20] in 86% yield.
To elucidate the complexation between 1 and Cu2+, UV–vis
absorption spectral variations of 1 (2.0 Â 10À5 mol/L) in CH3CN
solution were studied by titrating with Cu2+ from
0 to

Q. Jiang et al. / Chinese Chemical Letters 24 (2013) 881–884
883
2.0
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
2, Li+, Na+, K+, Sr2+
,
(a)
(b)
Cu2+
1.8
1.6
Zn2+, Cd2+, Pb2+
1, Li+, Na+, K+, Ca2+,
Sr2+, Pb2+, Ni2+, Co2+, Zn2+
Ca2+
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
Ni2+, Co2+, Cu2+
Cd2+
200
225
250
275
300
325
350
375
400
200
225
250
275
300
325
350
375
400
Wavelength /nm
Wavelength /nm
Fig. 1. (a) UV–vis absorption spectra of 1 (20
m
mol/L) upon addition of salts (25 equiv.) of Li+, Na+, K+, Ca2+, Sr2+, Zn2+, Cd2+, Ni2+, Co2+, Pb2+, and Cu2+ in CH3CN; (b) UV–vis
absorption spectra of 2 (20
m
mol/L) upon addition of salts (25 equiv.) of Li+, Na+, K+, Ca2+, Sr2+, Zn2+, Cd2+, Ni2+, Co2+, Pb2+, and Cu2+ in CH3CN.
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
5.0
(b)
(a)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
-0.5
-0.1 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1
[1]/ [1]+
Cu2+
200
225
250
275
300
325
350
375
400
Wavelength/nm
[
]
Fig. 2. (a) Titration curves of compound 1 in CH3CN (2.0 Â 10À5 mol/L) upon addition of Cu2+ at 0, 0.4, 0.8, 1.2, 1.6, 2.0, 2.2, 2.4, 2.8, 3.2, 3.6, 4.0, 4.4, 4.8, 5.2, 5.6, and
6.0 Â 10À5 mol/L; (b) Job’s plot for the determination of stoichiometry of the complex formed by 1 and Cu2+
.
6.0 Â 10À5 mol/L. As shown in Fig. 2(a), the maximum absorbance
at 261 nm gradually decreased, while two new absorbances that
centred at ca. 210 nm and 225 nm appeared. The presence of an
isosbestic point at 250 nm indicated the formation of a new
complex between 1 and Cu2+. The data of Job’s plot from absorption
spectra in Fig. 2(b) afforded a 1:1 stoichiometry for the complex of
1 and Cu2+. The binding constant of the complex between 1 and
Cu2+ was thus estimated to be (4.3 Æ 0.9) Â 104 L/mol (R2 = 0.991)
by using the nonlinear fitting of the titration curve (Fig. S9 in
Supporting information). In addition, the complexation of compound
1 and Cu2+ was also examined in CD3CN by 1H NMR technique. The
signals from both amide protons (c, f) and interior aromatic protons
(b, e) broadened upon the addition of Cu(NO3)2. The exterior aromatic
protons (a, d) experienced the same change in signal broadening (Fig.
S4 in Supporting information). This result indicated that the
complexation of compound 1 with Cu2+ did occur via coordination
of its internal thiocarbonyl sulfurs with the cation, which explains the
0.85
0.80
0.75
0.70
0.65
0.60
0.55
0.50
efficient recognition of Cu2+
.
Detection limit (DL) is usually evaluated according to the
equation DL = K Â Sb1/S, where K = 3, where Sb1 is the standard
deviation of the blank solution and S is the slope of the calibration
curve [21] (see Fig. 3). The detection limit of compound 1 for Cu2+
was determined to be about 6.3 Â 10À7 mol/L.
4. Conclusion
In summary, the aromatic oligothioamide 1 with a crescent
conformation was synthesized by one-pot thionation of the
corresponding oligoamide with the Lawesson’s reagent. The study
of the UV–vis spectra revealed that the compound 1 displayed high
selectivity for Cu2+ due to the presence of highly electron-rich S
atoms. In sharp contrast, the corresponding oligoamide 2 failed to
show any Cu2+ recognition preference over other metal ions.
0
5
10
15
20
25
30
C
(
mol/L)
2+
Cu
Fig. 3. Absorbance of compound 1 at 292 nm as a function of Cu2+ concentration.

884
Q. Jiang et al. / Chinese Chemical Letters 24 (2013) 881–884
[7] J. Zhu, R.D. Parra, H.Q. Zeng, et al., A new class of folding oligomers: crescent
Acknowledgments
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This work was supported by the National Natural Science
Foundation (No. 21172158), NSAF (No. 11076018), Sichuan
Province Science and Technology Support Programme (No.
2011FZ0048), the National Fund of China for Fostering Talents
in Basic Science (No. J1210004) and Open Project of Key Laboratory
for Radiation Physics and Technology of Ministry of Education (No.
2010-08). Analytical & Testing Center of Sichuan University is
acknowledged for NMR analyses.
Appendix A. Supplementary data
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Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.cclet.2013.05.025.
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