Biaryl-based anion receptors bearing thiourea groups: Fluoride anion receptor

Article abstract of DOI:10.1007/s10847-013-0349-3

The synthesis, characterization and binding studies with anions for biaryl-based anion receptors bearing thiourea groups have been described. The results revealed that receptors (1 and 2) showed good selectivity and binding affinity for F-, and among them binaphthyl-based receptor (1a) showed the best binding affinity for F-in comparison to other tested anions (Cl-, Br-, I-, NO-3 ; HSO-4 ; AcO-And H2PO-4 ). This is probably due to the fact that the moderate rigidity of binaphthyl skeleton in 1a is able to provide the better geometry of two thiourea groups for incorporating F-into the binding pocket. The higher basicity of F-Also participated in this selectivity. Springer Science+Business Media Dordrecht 2013.

Full text of DOI:10.1007/s10847-013-0349-3

J Incl Phenom Macrocycl Chem
DOI 10.1007/s10847-013-0349-3
ORIGINAL ARTICLE
Biaryl-based anion receptors bearing thiourea groups: fluoride
anion receptor
•
Yohei Takahashi Masatoshi Endo
•
Kazuaki Ito
Received: 10 June 2013 / Accepted: 27 June 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract The synthesis, characterization and binding
studies with anions for biaryl-based anion receptors bearing
thiourea groups have been described. The results revealed
that receptors (1 and 2) showed good selectivity and
binding affinity for F-, and among them binaphthyl-based
receptor (1a) showed the best binding affinity for F- in
comparison to other tested anions (Cl-, Br-, I-,
NO3ꢀ; HSO4ꢀ; AcO- and H2POꢀ4 ). This is probably due to
the fact that the moderate rigidity of binaphthyl skeleton in
1a is able to provide the better geometry of two thiourea
groups for incorporating F- into the binding pocket. The
higher basicity of F- also participated in this selectivity.
have been extensively studied because hydrogen bonding
exerts directional non-covalent interaction with certain
anions, which can provide one or more hydrogen bonding
sites for selective binding and sensing of certain anions.
Considering that receptors with higher structural
dimension tend to exhibit larger binding ability and
selectivity toward guest species, one of the strategies used
to design receptors which bind a guest anion strongly and
selectively is to increase dimensions of their structures in
order to arrange the binding sites in an appropriate position
for the complexation with a guest anion [17, 18]. There-
fore, we conceived on an idea to be used biaryl unit as a
backbone of an anion receptor because biaryl skeleton
combines moderate rigidity and flexibility [19–21]. This
structural property of biaryl unit will be expected to min-
imize the energy loss by the conformational rearrangement
during the complexation process and also provide the
suitable binding site toward a guest anion. In this context,
we describe here the synthesis and anion binding properties
of the receptors based on biaryl unit bearing two thiourea
groups as the hydrogen bonding donors (Fig. 1).
Keywords Anion receptor ꢁ Biaryl ꢁ Thiourea ꢁ Fluoride
anion
Introduction
Anion sensing and recognition have received increasing
recent attention in supramolecular, organic and inorganic
chemistry [1–11]. A number of anion receptors have been
reported so far which have various functional groups as
anion binding sites, including neutral hydrogen bonding
donors (for example amide, urea and thiourea) or positively
charged functional groups (for example ammonium, gua-
nidium, pyridinium and imidazolium) [12–16]. Neutral
anion receptors capable of hydrogen bonding to anions
Experimental
Melting points were measured by Stuart SMP3 melting
1
point apparatus and were not corrected. H and 13C NMR
spectra were measured by Varian INOVA 500 (500 MHz
for 1H, 125 MHz for 13C) and/or Varian Mercury 200
1
(200 MHz for H, 50 MHz for 13C) spectrophotometers.
Electronic supplementary material The online version of this
article (doi:10.1007/s10847-013-0349-3) contains supplementary
material, which is available to authorized users.
Tetramethylsilane was used as an internal standard refer-
ence. Fab-mass spectra (MS) were collected by JEOL AX-
505HA spectrometer using m-nitrobenzyl alcohol as a
matrix. IR spectra were recorded on FORIBA FT-720
spectrophotometer. UV–vis spectra were recorded on
Y. Takahashi ꢁ M. Endo ꢁ K. Ito (&)
Yamagata University, Yonezawa, Yamagata, Japan
e-mail: itokazu@yz.yamagata-u.ac.jp
123

J Incl Phenom Macrocycl Chem
sulfate. Removal of solvent gave the amorphous reside,
which was subjected to column chromatography on silica
gel using hexane/ethyl acetate, 8/1 as an eluent to give 12
(291 mg, 29 %) as colorless crystals accompanying with
recovery of 7 (585 mg, 65 %).
12
Mp 162–163 °C. 1H NMR (CDCl3) d: 4.57 (d, –OCHHCN,
1H, J = 16.0 Hz), 4.61 (d, –OCHHCN, 1H, J = 16.0 Hz),
4.84 (s, OH, 1H), 7.03 (d, Ar–H, 1H, J = 8.5 Hz),
7.25–7.40 (m, Ar–H, 5H), 7.48 (dd, Ar–H, 1H, J = 6.5,
8.0 Hz), 7.56 (d, Ar–H, 1H, J = 9.0 Hz), 7.88 (d, Ar–H,
1H, J = 8.0 Hz), 7.94 (d, Ar–H, 1H, J = 6.5 Hz), 7.96 (d,
Ar–H, 1H, J = 8.0 Hz), 8.12 (d, Ar–H, 1H, J = 9.0 Hz).
13C NMR (CDCl3) d: 55.3, 113.7, 115.2, 117.7, 119.1,
123.8, 124.5, 125.7, 127.0, 127.9, 128.3, 128.5, 129.2,
130.5, 131.0, 131.6, 133.6, 133.9, 151.3, 153.0. Fab-MS
236 (M?H)?. Anal. calcd for C22H15NO2: C, 81.21 %; H,
4.65 %; N, 4.30 %. Found: C, 81.15 %; H, 4.78 %; N,
4.23 %.
Synthesis of thiourea derivative (1a)
A solution of 8 (364 mg, 1.0 mmol) in dry ether (50 ml)
was added lithium aluminum hydride (152 mg, 4.0 mmol)
at room temperature. After the addition was completed, the
mixture was refluxed for 4 h. The reaction mixture was
cooled in an ice-bath and wet-benzene was added. The
precipitate was removed by filtration. The filtrate was
washed with water and the organic layer was dried over
anhydrous sodium sulfate. Removal of solvent gave oily
residue, which was dissolved with dry chloroform (30 ml).
To the solution was added p-nitrophenyl isothiocyanate
(360 mg, 2.0 mmol) and the mixture was stirred at room
temperature for 16 h. Removal of solvent gave oily resi-
due, which was subjected to column chromatography on
silica gel using hexane/ethyl acetate, 2/3 as an eluent to
give 1a (586 mg, 80 % yield) as pale yellow crystals. The
similar procedure as described above was applied to pre-
pare 1b, 2–4.
Fig. 1 Thiourea derivatives (1–4) and quaternary ammonium
salts (5)
Hitachi U-2020 spectrophotometer. All chemicals were
reagent grade and were used without further purification.
Chloroacetonitrile, sodium iodide, potassium carbonate,
lithium aluminum hydride, p-nitrophenyl isothiocyanate,
phenyl isothiocyanate, tetra-n-butyl ammonium salts (5a–
h) and 2-naphthol (6) were purchased from Kanto Chem-
ical Co., Tokyo Kasei Industry and Aldrich. 1,10-Binaph-
thyl-2,20-diol (7) [22], 2,20-cyanomethoxy-1,10-binaphthyl
(8) [23], 5,50-di-t-butyl biphenyl-2,20-diol (9) [24], 5,50-di-
t-butyl-2,20-cyanomethoxy-1,10-biphenyl (10) [25] and
2-cyanomethoxy naphthalene (11) [26] were prepared
according to the literature.
1a
1
Synthesis of 2-cyanomethoxy-20-hydroxy-1,10-
Mp 164–165 °C. H NMR (CDCl3) d: 3.62 (m, –CHHN–,
binaphthyl (12)
2H), 3.78 (m, –CHHN–, 2H), 4.09 (m, –OCHH–, 2H), 4.31
(m, –OCHH–, 2H), 6.18 (bs, NH, 2H), 7.10 (d, Ar–H, 2H,
J = 9.0 Hz), 7.27 (dd, Ar–H, 2H, J = 8.0, 8.5 Hz), 7.33
(d, Ar–H, 4H, J = 9.0 Hz), 7.36 (dd, Ar–H, 2H, J = Hz),
7.40 (d, Ar–H, 2H, J = 9.0 Hz), 7.50 (bs, NH, 2H), 7.83
(d, Ar–H, 2H, J = 8.0 Hz), 7.91 (d, Ar–H, 2H,
J = 9.0 Hz), 8.06 (d, Ar–H, 4H, J = 8.5 Hz). 13C NMR
(CDCl3) d: 44.6, 68.8, 116.2, 120.6, 121.6, 124.5, 124.8,
A mixture of 7 (0.90 g, 3.15 mmol), chloroacetonitrile
(0.20 ml, 3.15 mmol), sodium iodide (0.20 g, 9.24 mmol),
potassium carbonate (0.522 g, 3.78 mmol) in dry acetone
(100 ml) was refluxed for 3 h. After removal of solvent, the
residue was dissolved with chloroform. The solution was
washed with water twice and dried over anhydrous sodium
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J Incl Phenom Macrocycl Chem
125.1, 127.0, 128.2, 129.7, 130.1, 133.6, 143.7, 153.4,
180.0. Fab-MS 733 (M?H)?. Anal. calcd for C38
H32N6O6S2: C, 62.28 %; H, 4.40 %; N, 11.47 %, S,
8.75 %. Found: C, 62.09 %; H, 4.65 %; N, 11.25 %; S,
8.55 %.
NH, 1H), 8.23 (m, Ar–H, 2H). 13C NMR (CDCl3) d: 43.7,
66.3, 106.9, 118.5, 120.7, 123.9, 124.4, 126.6, 126.8,
127.6, 129.0, 129.5, 134.4, 142.6, 146.1, 156.3, 180.9. Fab-
MS 368 (M?H)?. Anal. calcd for C19H17N3O3S: C,
62.11 %; H, 4.66 %; N, 11.44 %, S, 8.73 %. Found: C,
61.88 %; H, 4.92 %; N, 11.25 %; S, 8.50 %.
1b
3b
1
Mp 146–147 °C. H NMR (CDCl3) d: 3.55 (m, –CHHN–,
1
2H), 3.70 (m, –CHHN–, 2H), 4.05 (m, –OCHH–, 2H), 4.14
(m, –OCHH–, 2H), 5.97 (bs, NH, 2H), 6.93 (m, Ar–H, 2H),
7.01 (d, Ar–H, 2H, J = 8.5 Hz), 7.17–7.22 (m, Ar–H, 4H),
7.29–7.37 (m, Ar–H, 3H), 7.85 (d, Ar–H, 2H, J = 8.0 Hz),
7.89 (d, Ar–H, 2H, J = 8.5 Hz). 13C NMR (CDCl3) d:
45.2, 68.5, 116.2, 120.5, 124.2, 124.4, 125.1, 126.6, 126.7,
128.1, 129.6, 129.8, 133.7, 136.4, 153.7, 180.6. Fab-MS
642 (M?H)?. Anal. calcd for C38H34N4O2S2: C, 71.00 %;
H, 5.33 %; N, 8.72 %, S, 9.98 %. Found: C, 70.82 %; H,
5.47 %; N, 8.60 %; S, 9.77 %.
Mp 137–138 °C. H NMR (CDCl3) d: 4.15 (dt, –CH2N–,
2H, J = 5.0, 5.5 Hz), 4.30 (t, –OCH2–, 2H, J = 5.0 Hz),
6.57 (bs, NH, 1H), 7.02 (dd, Ar–H, 1H, J = 2.0, 9.0 Hz),
7.13 (d, Ar–H, 1H, J = 2.0 Hz), 7.18 (d, Ar–H, 2H,
J = 8.0 Hz), 7.31 (t, Ar–H, 1H, J = 8.0 Hz), 7.36 (dd, Ar–
H, 1H, J = 7.5, 8.0 Hz), 7.41 (t, Ar–H, 2H, J = 8.0 Hz),
7.45 (dd, Ar–H, 1H, J = 6.5, 8.0 Hz), 7.65 (bs, NH, 1H),
7.72 (d, Ar–H, 1H, J = 6.5 Hz), 7.74 (d, Ar–H, 1H,
J = 9.0 Hz), 7.77 (d, Ar–H, 1H, J = 7.5 Hz). 13C NMR
(CDCl3) d: 46.9, 66.4, 107.1, 118.4, 124.1, 125.3, 126.7,
126.9, 127.6, 127.7, 129.2, 129.7, 130.4, 134.5, 135.9,
156.2, 180.8. Fab-MS 322 (M?H)?. Anal. calcd for
C19H18N2OS: C, 70.78 %; H, 5.63 %; N, 8.69 %; S,
9.94 %. Found: C, 70.58 %; H, 5.80 %; N, 8.45 %; S,
9.87 %.
2a
Mp 140–141 °C. 1H NMR (CDCl3) d:0.1.32 (e, t-Bu, 18H),
3.82 (bs, –CH2N–, 4H), 4.13 (bs, –OCH2–, 4H), 6.87 (bs,
NH 2H), 7.20–7.40 (m, Ar–H, 12H), 8.03 (bs, Ar–H, 2H),
9.00 (bs, NH, 2H). 13C NMR (CDCl3) d: 31.7, 34.6, 45.0,
67.3, 113.4, 121.9, 125.3, 125.9, 127.7, 129.4, 143.6,
143.9, 145.2, 153.1, 180.3. Fab-MS 745 (M?H)?. Anal.
calcd for C38H44N6O6S2: C, 61.27 %; H, 5.95 %; N,
11.28 %, S, 8.61 %. Found: C, 61.02 %; H, 6.02 %; N,
11.05 %; S, 8.40 %.
4a
1
Mp 157–158 °C. H NMR (CDCl3) d: 3.75 (bs, –CHHN–,
1H), 3.88 (bs, –CHHN–, 1H), 4.22 (bs, –OCHH–, 1H), 4.33
(bs, –OCHH–, 1H), 5.03 (s, OH, 1H), 5.83 (bs, NH, 1H),
7.05 (bs, NH, 1H), 7.09 (d, Ar–H, 1H, J = 9.0 Hz), 7.19
(d, Ar–H, 1H, J = 8.5 Hz), 7.26 (dd, Ar–H, 1H, J = 8.0,
9.0 Hz), 7.28 (d, Ar–H, 1H, J = 8.0 Hz), 7.32 (dd, Ar–H,
1H, J = 8.0, 8.5 Hz), 7.34 (dd, Ar–H, 1H, J = 8.0,
8.5 Hz), 7.37 (m, Ar–H, 2H), 7.43 (dd, Ar–H, 1H, J = 5.5,
8.0 Hz), 7.46 (d, Ar–H, 1H, J = 9.0 Hz), 7.86 (d, Ar–H,
1H, J = 8.0 Hz), 7.88 (d, Ar–H, 1H, J = 8.5 Hz), 7.94 (d,
Ar–H, 1H, J = 8.5 Hz), 8.09 (d, Ar–H, 1H, J = 9.0 Hz),
8.15 (m, Ar–H, 2H). 13C NMR (CDCl3) d: 44.6, 67.9,
115.1, 115.3, 117.6, 122.1, 123.8, 124.8, 124.9, 125.0,
125.1, 125.2, 127.0, 127.8, 128.5, 129.6, 129.7, 128.0,
130.2, 131.6, 133.6, 133.8, 143.7, 144.1, 150.9, 154.5,
180.3. Fab-MS 510 (M?H)?. Anal. calcd for C29
H23N3O4S: C, 68.35 %; H, 4.55 %; N, 8.25 %, S, 6.29 %.
Found: C, 68.15 %; H, 4.78 %; N, 8.10 %; S, 6.22 %.
2b
1
Mp 170–171 °C. H NMR (CDCl3) d: 1.27 (s, t-Bu, 18H),
3.81 (bs, –CH2N–, 4H), 3.99 (bs, –OCH2–, 4H), 6.30 (bs,
NH, 2H), 6.74 (d, Ar–H, 2H, J = 7.0 Hz), 7.04–7.32 (m,
Ar–H, 14H), 7.60 (bs, NH, 2H). 13C NMR (CDCl3) d: 31.4,
34.1, 45.0, 67.6, 113.1, 124.3, 125.3, 126.6, 127.8, 128.8,
129.9, 136.4, 144.1, 153.2, 180.6. Fab-MS 655 (M?H)?.
Anal. calcd for C38H46N4O2S2: C, 69.69 %; H, 7.08 %; N,
8.55 %, S, 9.79 %. Found: C, 69.88 %; H, 6.92 %; N,
8.43 %; S, 9.53 %.
3a
1
Mp 157–158 °C. H NMR (CDCl3) d: 4.19 (bs, –CH2N–,
2H), 4.36 (t, –OCH2–, 2H, J = 5.0 Hz), 6.79 (bs, NH, 1H),
7.08 (dd, Ar–H, 1H, J = 2.0, 8.5 Hz), 7.17 (d, Ar–H, 1H,
J = 2.0 Hz), 7.36 (m, Ar–H, 2H), 7.37 (dd, Ar–H, 1H,
J = 7.5, 8.0 Hz), 7.47 (dd, Ar–H, 1H, J = 7.5, 8.0 Hz),
7.73 (d, Ar–H, 1H, J = 8.5 Hz), 7.78 (d, Ar–H, 1H,
J = 8.0 Hz), 7.79 (d, Ar–H, 1H, J = 8.0 Hz), 7.90 (bs,
4b
1
Mp 139–140 °C. H NMR (CDCl3) d: 3.64 (m, –CHH–N,
1H), 3.89 (m, –CHH–N, 1H), 4.21 (m, O–CHH–, 1H), 4.34
(m, O–CHH–, 1H), 4.80 (bs, OH, 1H), 6.01 (bs, 1H, NH,
1H), 6.97–7.00 (m, Ar–H, 3H), 7.14 (d, Ar–H, 1H,
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J Incl Phenom Macrocycl Chem
Interaction of thioureas with anions
J = 8.0 Hz), 7.15 (d, Ar–H, 1H, J = 8.5 Hz), 7.18 (dd,
Ar–H, 1H, J = 8.0, 8.5 Hz), 7.22–7.30 (m, Ar–H and NH,
6H), 7.40 (dd, Ar–H, 1H, J = 8.0, 8.5 Hz), 7.46 (d, Ar–H,
1H, J = 9.0 Hz), 7.82 (d, Ar–H, 1H, J = 9.0 Hz), 7.83 (d,
Ar–H, 1H, J = 8.5 Hz), 7.92 (d, Ar–H, 1H, J = 8.2 Hz),
8.06 (d, Ar–H, 1H, J = 9.0 Hz). 13C NMR (CDCl3) d:
45.2, 68.0, 115.1, 115.2, 116.4, 117.5, 123.5, 124.6, 124.8,
124.8, 125.1, 126.7, 127.0, 127.5, 128.2, 128.3, 129.1,
129.9, 130.0, 130.0, 131.3, 133.7, 134.0, 136.3, 151.0,
154.8, 180.9. Fab-MS 465 (M?H)?. Anal. calcd for
C29H24N2O2S: C, 74.97 %; H, 5.21 %; N, 6.03 %, S,
6.90 %. Found: C, 74.77 %; H, 5.40 %; N, 5.98 %; S,
6.68 %.
The interaction behavior of di-thioureas (1) and anions (5)
1
was investigated by H NMR spectroscopy. A downfield
shift of the di-thiourea NH protons (DdNH = 1.83 (NHa),
3.25 (NHb) ppm) of 1a was observed upon the addition of
tetra-n-butyl ammonium chloride (5a) to the solution of 1a
in CDCl3 ([1a] = [5a] = 3 mM), indicating the formation
of the complex (1a–5a) through the intermolecular
hydrogen bonding between the thiourea NH protons and
Cl- (Fig. 2). A similar tendency was also observed using
other receptors (1b, 2–4) and quaternary ammonium salts
(5a–e). Interestingly, the OH proton of 4 also fairly shifted
downfield (DdOH = 3.70 ppm [4a], 1.85 ppm [4b])
(Fig. 3), indicating the participation of the OH proton in
the formation of the complexes (4, 5a) [28–32]. In contrast,
the NH proton signals of receptors (1–4) became signifi-
cantly broad upon the addition of basic anions (F- [5f],
AcO- [5g] and H2POꢀ4 [5h]).
Results and discussion
Synthesis of receptors
The resonances of the n-butyl groups of quaternary
ammonium salts (5a) shifted upfield in the presence of the
thiourea derivatives (1a). The induced chemical shift chan-
ges (Dd) in the n-butyl groups of 5a increased due to the
protons near the cation moiety (N?) of the quaternary
1,10-Binaphthyl-2,20-diol (7) was prepared by oxidative
coupling reaction of 2-naphthol (6) with FeCl3ꢁ6H2O in the
solid state at 50 °C for 3 h with 90 % yield. The reaction of
7 with chloroacetonitrile in the presence of potassium
carbonate and sodium iodide in dry acetone at reflux for
14 h gave 2,20-bis(cyanomethoxy)-1,10-binaphthyl (8) in
49 % yield. Reduction of 8 was achieved by using lithium
aluminum hydride and the condensation reactions of the
reductant with p-nitrophenyl isothiocyanate gave di-thio-
urea derivative (1a) in 28 % yield. The di-thiourea deriv-
atives (1b and 2) and mono-thiourea derivatives (3 and 4)
was also prepared by the similar procedure as described for
1a in 15 % (1b), 43 % (2a), 20 % (2b), 31 % (3a), 66 %
(3b), 33 % (4a) and 31 % (4b) yields, respectively
ammonium component (Fig. S1). This order ðDd1H [ DdH2
[ Dd3H [ Dd4HÞ is similar to the acidity of the alkyl protons.
Therefore, it is likely that the upfield shift of the n-butyl
groups is the main cause of the cation–p interaction between
the quaternary ammonium part of 5 and the naphthyl moie-
ties of the receptors as the p-component [33, 34].
We also found that the thiourea NH protons of 1–4 (Dd/
DT [ppb/K] = 3.5–10.9) displayed a temperature depen-
dence in the presence of 5a (Fig. S2). Contrary to this,
there was slight change in the thiourea NH protons (Dd/
DT [ppb/K] = 0.8–3.5) in the absence of an anion (Fig.
S3). The OH protons of the mono-thiourea derivatives (4)
were more sensitive to the temperature and showed a sig-
nificant change in the presence of 5a (Dd/DT [ppb/
K] = 18.8 [4a], 19.3 [4b]), while the temperature depen-
dencies (Dd/DT) of 4 were 2.3 (4a) and 0.8 (4b) (ppb/K) in
the absence of an anion (Fig. S4). These temperature
dependencies suggest that the NH and OH protons in the
presence of 5a equilibrate between the hydrogen-bonded
and non-hydrogen-bonded states [35–37], and provide
further support that the NH and OH protons of the recep-
tors are the anion binding sites.
1
(Scheme 1). All products (1–4) were characterized by H
and 13C NMR, Fab-MS and elemental analysis.
Intermolecular hydrogen bonding
The self-association tendency of the di-thiourea derivative
1
(1a) was evaluated using H NMR analysis in CDCl3. The
NH signals of thiourea derivative (1a) were observed at
dNH 5.0–7.8 ppm at a 1 mM concentration. When the
concentration of 1 mM increased to 5 mM, the NH signals
moved slightly downfield (Table S1). A similar tendency
was also observed for the NH protons of other mono- and
di-thiourea derivatives (1b, 2–4). It is postulated that the
intermolecular hydrogen bonding hardly occurs based on
the slight change in the NH proton chemical shifts of the
thiourea derivatives (1–4) in this range of concentrations
[27]. Therefore, we carried out the following NMR
experiments using a solution of the thiourea derivatives (1–
4) under a 3 mM concentration.
Anion binding properties of thiourea derivatives (1–4)
We estimated the stoichiometry of the complexes between
the thioureas (1–4) and quaternary ammonium salts (5)
using the Job plot method [38]. The 1:1 stoichiometry of
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J Incl Phenom Macrocycl Chem
Scheme 1 Synthesis of
thiourea derivatives (1–4).
(i) FeCl3, solvent free, 50 , 4 h,
(ii) ClCH2CN, K2CO3, NaI, in
dry acetone, reflux, (iii) LiAlH4,
in dry THF, reflux, (iv)
SCNC6H4(p-NO2) or SCNPh in
dry benzene, rt
the complexes was confirmed by a plot that contains a
maximum at the mole ratio of 0.5 in these cases (Fig. S5).
The association constants (Ka) of the thioureas (1–4)
toward the various anions (5a–e) were determined by a
nonlinear regression method following the chemical shifts
on binaphthyl exhibited a higher selectivity toward Cl-. It
is well known that the phenolic OH exhibits a high affin-
ity for Cl- [28–32]. Therefore, the observed chloride
anion selectivity will be attributed to the cooperative effect
of the hydroxyl group in the formation of the complex
between 4 and Cl-. As mentioned above, this was clearly
established from the 1H NMR titration experiments in
CDCl3 in which a substantial shift in the resonance for the
hydroxyl group was observed concomitant with the
expected thiourea NH chemical shift migration upon the
addition of anions.
1
of the NH protons of the thiourea moiety by H NMR
titration (Figs. S6–S11) [39, 40], and were summarized in
Table 1.
Generally, the p-nitrophenyl thiourea derivatives (1a–4a)
exhibited an enhanced anion binding ability compared to the
corresponding phenyl thiourea derivatives (1b–4b) due to
the increasing acidity of the p-nitrophenyl thiourea NH
protons, although these receptors (1–4) resembled each
other in anion selectivity (Cl- [ Br- & HSO4ꢀ & NO3ꢀ
[ I-). The cooperativity of the two symmetrical halves of
the di-thiourea receptors (1) for anion binding was estab-
lished by comparing the binding of the mono-thiourea
receptors (3), which had an obviously lower anion binding
ability compared to 1 under the same experimental condi-
tions. Interestingly, the mono-thiourea receptors (4) based
As mentioned above, it is difficult to obtain the binding
ability of the thiourea derivatives (1–4) toward strong basic
1
anion species (F-, AcO- and H2POꢀ4 ) by H NMR spec-
troscopy due to the exclusively broadening of the thiourea
NH protons upon the addition of the anions. Therefore, we
studied the interaction between basic anions and thiourea
derivatives (1–4) by using UV–vis spectroscopy. Figure 4
shows the anion-induced UV–vis spectral changes of the
chloroform solution of 1a. Upon addition of F-, the
123

J Incl Phenom Macrocycl Chem
1
Fig. 2 Partial H NMR spectra
of 1a in CDCl3 at 297 K.
(A) 1a ? 5a, (B) 1a
([1a] = [5a] = 3.0 mM)
1
Fig. 3 Partial H NMR spectra
of 4a in CDCl3 at 297 K.
(A) 4a ? 5a, (B) 4a
([4a] = [5a] = 3.0 mM)
intensity of the absorption band of 1a at 333 nm decreased,
while the new red-shifted absorption band at around
365 nm appeared. At this time, the presence of a well-
defined isosbestic points at 341 and 260 nm was observed.
Similar spectral changes were also observed upon addition
of AcO- and H2POꢀ4 (Figs. S12, S13). The observed red-
shifted absorption band indicates the formation of the
complex between 1a and the anions (5e–g) through the
hydrogen bonding. [41, 42]. The association constants (Ka)
between the receptors (1a–3a) and basic anions (F-, AcO-
and H2POꢀ4 ) were obtained by UV–vis titration experi-
ments in CHCl3 (Figs. S14–S19) [39, 40, 43] and the
results were summarized in Table 2. Biaryl-based receptors
(1a, 2a) were shown in higher selectivity and affinity for
F- in comparison with other basic anions (AcO- and
H2POꢀ4 ). This selectivity will be attributed to fit the size
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Table 1 Logarithms of the association constants (log Ka [M-1] in CDCl3 at 297 K) for 1:1 complexes of thiourea derivatives (1–4) and
1
quaternary ammonium salts (5) and free energy (-DG [kJ/mol] in CDCl3 at 297 K), as evaluated by H NMR titration experiments
Log Kaa (free energy (-DG [kJ/mol]))
Receptors
Anionsb
Cl- (5a)
Br- (5b)
I- (5c)
NOꢀ3 (5d)
HSOꢀ4 (5e)
1a
1b
2a
2b
3a
3b
4a
4b
a
4.78 (27.2)
2.06 (11.7)
4.46c (25.5)
1.76 (10.0)
4.32 (24.6)
1.49 (8.5)
3.97c (22.6)
1.40 (8.0)
3.32 (19.0)
1.00 (5.7)
3.27 (18.6)
1.70 (9.7)
3.15 (17.9)
1.17 (6.7)
3.04c (17.4)
\1
4.15 (23.6)
1.45 (8.2)
3.97c (22.6)
1.78 (10.1)
3.43 (19.6)
1.20 (6.8)
3.00 (17.1)
1.43 (8.1)
4.30 (24.5)
1.60 (9.1)
4.18c (23.8)
2.40 (13.6)
3.15 (17.9)
1.97 (13.0)
2.95 (16.8)
1.54 (8.8)
d
–
2.86 (16.3)
1.30 (7.4)
2.30 (13.1)
1.30 (7.4)
1.30 (7.4)
3.90 (22.2)
2.45 (14.0)
Errors were estimated to be 10 %
Anions were used as their n-Bu4N? salts
b
c
d
CDCl3/DMSO (95/5, v/v) was used as a solvent due to the low solubility of 2a in CDCl3
The data does not fit satisfactorily to a 1:1 binding model
Fig. 4 Changes in UV–vis
spectral absorption of 1a
(3.0 9 10-5 mM) upon
addition of n-Bu4N? F- (5f) in
CHCI3 at 297 K. Inset
absorbance at 365 nm versus
number of mole equivalents of
5f added
and shape of F- that is incorporated into the binding
pocket, which was constructed from two thiourea groups.
The higher basicity of fluoride anion is also considered to
participate in this selectivity. Binaphthyl-based receptor
(1a) is more effectively bound to F- compared to biphenyl-
based receptors (2a). This is probably due to the fact that
the moderate rigidity of binaphthyl skeleton in 1a is able to
provide the better geometry of two thiourea groups for
incorporating F- into the binding pocket.
constructed by the two thiourea groups. It is noteworthy that
the two thiourea groups of 1 in the complex are perpendicular
to each other (Fig. 5). The obtained four NHꢁꢁꢁF- distances
(1.63–1.71 A) are reasonable values as hydrogen bonding
distances [48]. We also calculated the structure of the com-
plex between F- and two thioureas by DFT method (B3LYP/
6-31G(d,p) level) and obtained the optimized structure,
which has a great resemblance to the optimized structure of
the complex (1–F-) (Fig. 6). This result suggests that
binaphthyl-based receptor (1) bearing two thiourea groups
through oxyethylene linker (–OCH2CH2–) provide the
excellent binding site for F-.
A density functional theory (DFT) by B3LYP/6-31G(d,p)
level theory has been applied to elucidate the structure of the
complex between F- and binaphthyl-based receptor (1) [44–
47]. In the optimized structure of the complex (1–F-), 1
incorporated F- into a suitable binding site, which was
In summary, we herein described the anion recognition
of bis(p-nitrophenyl thiourea) derivative (1a) based on
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J Incl Phenom Macrocycl Chem
Table 2 Logarithms of the association constants (log Ka [M-1] in
CHCl3 at 297 K) for 1:1 complexes of thiourea derivatives (1–3) and
quaternary ammonium salts (5f–h) and free energy (-DG [kJ/mol] in
CHCl3 at 297 K), as evaluated by UV–vis titration
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