4,4′-Substituted biphenyl coronands. Preparation of a new selective fluorescent sensor for mercury salts

Article abstract of DOI:10.1016/j.tet.2006.09.084

Six new 4,4′-substituted biphenyl coronands have been prepared. The ligands containing dimethylamino groups in the biphenyl moiety have been used in transition metal cations' complexation and one of them (3) has demonstrated to be a selective fluorescent

Full text of DOI:10.1016/j.tet.2006.09.084

Tetrahedron 62 (2006) 11972–11978
4,40-Substituted biphenyl coronands. Preparation of a new
selective fluorescent sensor for mercury salts
a
a
b
Ana M. Costero,a, M. Jose Banuls, M. Jose Aurell and Antonio Domenech
*
ꢀ
ꢀ
ꢀ
˜
a
´
ꢀ
ꢁ
Departamento de Quımica Organica, Universitat de Valencia, Dr. Moliner 50, 46100 Burjassot, Valencia, Spain
b
´
Departamento de Quımica Analıtica, Universitat de Valeꢁncia, Valencia, Spain
´
Received 28 July 2006; revised 19 September 2006; accepted 21 September 2006
Available online 20 October 2006
Abstract—Six new 4,40-substituted biphenyl coronands have been prepared. The ligands containing dimethylamino groups in the biphenyl
moiety have been used in transition metal cations’ complexation and one of them (3) has demonstrated to be a selective fluorescent sensor for
mercury. Stoichiometries of the formed complexes and complexation constants have been determined by titration experiments. In addition, the
extractant ability of some ligands has also been studied. Finally, the electrochemical properties of some of these ligands are also described.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
fluorescent and red-ox chemosensors. Among all the pos-
sible target cations our interest has been mainly directed
toward Cd2+, Hg2+ and Pb2+ because they are highly toxic
environmental pollutants and they are generated from both
natural and industrial sources. In addition Zn2+ has been
also studied due to its electronic configuration that makes
it similar to Cd2+ and Hg2+.
Molecular systems that combine binding ability and photo-
chemical or photophysical properties are of great interest
for designing chemosensors.1 Recently it has been estab-
lished that conformational restriction is a viable mechanism
for transducing ion binding into enhanced fluorescence
emission in organic fluorophores.2 Among the systems stud-
ied it is possible to find biphenyl and bipyridyl derivatives
that experiment fluorescence enhancement after complexa-
tion. It is well established that more rigid fluorophores are
more fluorescent3 even though this restriction is due to com-
plex formation.4 On the other hand, it is also known that sub-
stituents in the biphenyl systems have strong influence on
its fluorescent properties.5 For all these reasons, we have
been interested in using the 4,40-bis(N,N-dimethylamino)-
biphenyl (TMB, tetramethylbenzidine) subunit in the design
and synthesis of red-ox and fluorescent sensors.6 In particu-
lar our interest has been directed toward the preparation
of crown ether and azacrown ether derivatives covalently
attached to the 2,20 position of TMB7 and their use as
The studied ligands are shown in Chart 1 and in addition
to the TMB moiety they contend an ortho-disubstituted
benzene system. The presence of this additional aromatic
ring has the goal of increasing the rigidity of the cavity to
improve cation selectivity. In addition, several heteroatoms
and functional groups are present in these ligands to study
the influence of the donor atom nature.
On the other hand, solvent extraction belongs to one of
the most important processes in water treatment and the
use of complexing agents plays an important role in such
processes. In solvent extraction of metallic ions it is possible
to use a variety of ligands as extracting agents and among
NMe2
NMe2
NMe2
NMe2
O
O
N
N
COO
COO
O
O
COO
COO
O
O
O
O
N
N
O
O
O
O
O
O
O
O
2
1
3
4
NMe2
NMe2
NMe2
NMe2
Chart 1.
* Corresponding author. Tel.: +34 963544410; fax: +34 963543152; e-mail: ana.costero@uv.es
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.09.084

A. M. Costero et al. / Tetrahedron 62 (2006) 11972–11978
11973
ClOC
NO2
O2N
NO2
7
H2, Pd(C) 10%
EtOH, CH2O 30%
X
X
1 X = O
COO
COO
O
O
COCl
2 X=N-CH3
K2CO3, CH2Cl2, TBAI
8 X = O
9 X=N-CH3
X
X
OH
OH
O
O
NO2
1) HNa/THF
2) THF, NaI
3 X = O
5 X = O
4 X=N-CH3
6 X=N-CH3
ClH2C
Me2N
NMe2
10
CH2Cl
Scheme 1.
these complexing agents, macrocyclic polyethers have been
widely used and the strong influence of the ligand topology
on the extraction efficiency has been well established.8 For
this reason, we have been also interested in evaluating the
ability of the prepared ligands in cation extraction.
Complexation experiments were carried out in CH3CN with
solutions of Zn2+, Cd2+, Pb2+, Ni2+, Hg2+ as triflate salts. The
results obtained with ligands 1, 2 and 4 and all the studied
cations were very similar, since a quenching of the fluores-
cence was observed after the salt addition (results obtained
for ligand 4 are reflected in Fig. 1, as an example; for the
other ligands, refer to Supplementary data). This behaviour
could be due not only to the presence of the transition metal
cation in the solution,13 but also to the modifications in the
dihedral angle between both aromatic rings or the conforma-
tional restriction induced by the complexation event.14
2. Results and discussion
2.1. Synthesis
Ligands 1 and 2 were easily prepared as described in
Scheme 1 starting, respectively, from 2,20-bis(chloro-
carbonyl)-4,40-dinitrobiphenyl (7)9 and the corresponding
phenyl derivative compounds 8 and 9 could be isolated.
Reductive amination of the nitro groups gave rise to the cor-
responding dimethylamino ligands 1 and 2, respectively,
almost with quantitative yields. On the other hand, direct
reaction between 4,40-bis(dimethylamino)-2,20-bis(chloro-
methyl)biphenyl (10)7 and the corresponding chains gave
rise to 3 and 4.
By contrast ligand 3 showed a more interesting behaviour
when complexation experiments were carried out with the
studied salts. Thus, even though all the cations are com-
plexed by the ligand the fluorescent properties in each case
were different. Three types of fluorescent behaviours were
observed with this ligand (Fig. 2 for Zn2+, Cd2+ and Hg2+
and Supplementary data for Ni2+ and Pb2+) the most interest-
ing result being those obtained with Hg2+. In the presence of
this cation a new band at l¼464 nm that could be attributed
to the formation of intermolecular excimers15,12 appears.
Oppositely, Cd2+ and Ni2+ did not give rise to any modifica-
tion of the fluorescence and the intensity of the new band
was very small in the presence of Zn2+ and Pb2+.
To carry out the syntheses described above, compound 5 was
prepared from catechol as is described in the literature.10
The synthesis of 6 was accomplished from o-N,N0-dimethyl-
phenylenediamine11 by alkylation with 2-[2-chloroethoxy]-
ethanol (Scheme 2).
The different behaviour observed in the presence of Hg2+
makes compound 3 able to act as a selective fluorescent sen-
sor for this cation. As Zn2+, Cd2+ and Hg2+ have the same
electronic configuration, selectivity experiments were
Me
N
OH
OH
NHMe
NHMe
K2CO3/DMF, NaI
OH
O
O
Cl
N
Me
O
700
6
600
4
4+Ni2+
Scheme 2.
500
4+Hg2+
400
4+Zn2+
4+Cd2+
2.2. Complexation studies
300
4+Pb2+
200
Due to the presence of the TMB moiety in the prepared li-
gands, they present fluorescent properties. The influence of
the cyclic systems directly bound to the 2,20 positions of
the TMB gives rise to the expected changes in the emission
bands.12 Thus, 1 and 2 present the emission band at
lmax¼487 and 481 nm, respectively, whereas both 3 and 4
show values of 372 nm.
100
0
300
350
400
wavelength (nm)
450
500
Figure 1. Fluorescent response of ligand 4 in CH3CN in the presence of
1 equiv of Ni2+, Hg2+, Zn2+, Cd2+ and Pb2+ as triflate salts.

11974
A. M. Costero et al. / Tetrahedron 62 (2006) 11972–11978
800
700
600
500
400
300
200
100
0
800
700
600
500
400
300
200
100
0
800
700
600
500
400
300
200
100
0
300
35
0
4
00
45
0
500
550
300
35
0
4
00
45
0
wavelength (nm)
500
550
300
35
0
4
wavelength (nm)
00
45
0
5
00
550
wavelength (nm)
Figure 2. (From left to right) Complexation experiments with ligand 3 in CH3CN with Hg2+, Cd2+ and Zn2+, all of them as triflate salts.
carried out with an equimolecular mixture of these three cat-
ions. The results obtained with the mixture were the same
observed in the presence of pure Hg2+ samples (Fig. 3).
containing six oxygen atoms16 and the usual coordination
properties in divalent lead complexes.17
2.3. Extraction experiments
Titration experiments with the different cations using fluo-
rescence showed that the stoichiometries of the formed
complexes were always 1:1 (see Supplementary data). Com-
plexation constants for these complexes were determined as
described in Section 4 and they are reflected in Table 1.
Extraction experiments were carried out with ligands 2, 4, 8
and 9 that were chosen to study the influence of different
functional groups in extraction ability. Thus, comparison be-
tween ligands 2 and 4 results allows knowing the influence
that ester or ether groups have in extraction properties.
The preliminary extraction experiments were carried out
with alkaline cations as their picrate salts. Extraction con-
stants for these ligands determined by using the Cram’s
method are shown in Table 2.18
The values of the complexation constants suggest that substi-
tution of the ester groups for the corresponding ether groups
gives rise to very small changes in Ni2+ and Zn2+ complex-
ation and slightly larger in Cd2+ complexation. On the other
hand, complexation of Hg2+ and Pb2+ was stronger with 3
(log K¼6.8ꢀ0.4 and 6.2ꢀ0.2, respectively) than with 1
(log K¼5.6ꢀ0.2 and 5.3ꢀ0.1, respectively) but shows the
opposite tendency when 2 (log K¼6.3ꢀ0.4 and 6.2ꢀ0.2,
respectively) and 4 (log K¼4.9ꢀ0.2 and 5.9ꢀ0.1, respec-
tively) were compared. When complexation constants with
ligands 3 and 4 were compared it was observed that substi-
tution of oxygen by nitrogen atoms gives rise to stronger
complexes with Ni2+ and Cd2+ and keeping similar strength
with Zn2+. The opposite behaviour was observed with Pb2+
and even more with Hg2+. This behaviour agrees with both
the preference of Hg2+ for being complexated by crown ether
As can be seen in Figure 4 substitution of ester by ether
groups gives rise to a big increase of the extraction proper-
ties. This behaviour could be related to two factors: (a) the
higher flexibility and size showed by the cavity and (b) the
much more donor character of the ether oxygen atom. Com-
parison between ligands 2 and 9 demonstrates that the type
of substitution in the biphenyl moiety has a very small influ-
ence on extraction of Li+ and Na+. However, larger effects
were observed with Cs+ and even more with K+. Thus the
extraction constants for these cations were around 20 and
10 times higher, respectively, when ligand 9 was used.
One explanation to this fact can be found in the higher
300
Table 2. ꢂlog Ke (water/chloroform) determined by using Cram’s method
Hg(II)
250
200
150
100
50
2
4
8
9
Cd(II)
Zn(II)
Pb(II)
Ni(II)
Li+
Na+
K+
2.46
2.38
2.77
2.13
4.77
4.75
5.19
3.79
4.76
4.66
4.52
4.13
2.83
2.75
4.05
3.22
Cs+
All the salts were picrates.
160000
140000
120000
100000
80000
Li
0
0
0.5
1
1.5
2
Na
K
Figure 3. Effect of 1 equiv of metal ions on the emission at 470 nm
for solutions of 3 (3.0ꢁ10ꢂ5 M) in acetonitrile.
Cs
60000
Table 1. Complexation constants (log K) for ligands 1–4 in acetonitrile
determined by fluorescence titrations
40000
20000
Ni2+
Zn2+
Cd2+
Hg2+
Pb2+
0
2
4
8
9
1
2
3
4
5.1ꢀ0.5
6.1ꢀ0.4
5.7ꢀ0.5
6.9ꢀ0.3
5.9ꢀ0.3
5.8ꢀ0.3
5.9ꢀ0.2
5.6ꢀ0.2
5.8ꢀ0.2
5.4ꢀ0.3
5.7ꢀ0.2
7.0ꢀ0.5
5.6ꢀ0.2
6.3ꢀ0.4
6.8ꢀ0.4
4.9ꢀ0.2
5.3ꢀ0.1
6.2ꢀ0.2
6.2ꢀ0.2
5.9ꢀ0.1
Ligand
Figure 4. Comparison of alkaline cation extraction (water/chloroform) with
ligands 2, 4, 8 and 9.

A. M. Costero et al. / Tetrahedron 62 (2006) 11972–11978
11975
lipophilic character of the nitro group, which is an important
point for the extraction properties.
Finally, comparison between ligands 8 and 9 indicates that
substitution of nitrogen atoms by oxygen atoms give rise
to higher extraction, which can be related to the hard charac-
ter of the alkaline cations that make stronger interactions
with the harder oxygen atoms than the softer nitrogen atoms.
In addition, ligand 4 extracts preferably K+ that agrees with
the relation cavity size/cation radium. By contrast, both
ligands 8 and 9 show a small K+ extraction that could be
related to the smaller cavity of this ligand due to the presence
of the two ester groups. As it is shown in Figure 4, extraction
of Li+ by ligands 4 and 8 is very similar. The small size of
this cation allows it to form strong complexes using only
four oxygen atoms. For this reason it fits as well in ligand
4 as in ligand 8.
Figure 5. CVs of (a) a 2.0 mM 11 solution in 0.10 M Bu4NPF6/MeCN. (b)
A 2.0 mM 4 solution in 0.10 M Bu4NPF6/MeCN. Potential scan rate
100 mV/s.
2.4. Electrochemical experiments
experiments performed at glassy carbon electrodes, thus
denoting that no adsorption processes occur. The voltammet-
ric behaviour at platinum and glassy electrodes in DMSO
solutions was almost identical to that described in MeCN.
All three pairs Ia/Ic, IIa/IIc and IIIa/IIIc, can be described
as essentially reversible one-electron-transfer processes as
judged by the variation of anodic-to-cathodic peak potential
separation with the potential scan rate, EpaꢂEpc. The value
of this parameter tends to 60 mV at low sweep rates, as ex-
pected for a one-electron reversible process. The response
of this bis(dimethylamino)biphenyl-containing receptor is
consistent with that reported for the oxidation of aromatic
compounds.19 Thus, the parent neutral ligand, L, is revers-
ibly oxidized to the corresponding radical cation Lꢃ+ and a
dication, L2+, in two successive one-electron-transfer steps.
Consistently, the value of the peak current function (peak
current/(sweep rate)1/2) determined for the receptors studied
here was almost identical to that reported for different biphe-
nyl-type receptors at the same concentration. These corre-
spond to the Ia/Ic and IIa/IIc couples. The presence of an
additional couple IIIa/IIIc is rationalized taking into account
that the overall oxidation process is accompanied by a signif-
icant stereochemical modification: there is a transition from
the dihedral neutral molecule, to the planar dication. Ac-
cordingly, the first electron-transfer step yields a nonplanar
cation radical (Lꢃ+) that undergoes to some extent a relatively
slow pre-organization process.20 Under similar conditions,
ligand 4 shows the Ia/Ic (0.62 V) and IIa/IIc (0.91 V) cou-
ples but not the pair IIIa/IIIc. The absence of these peaks
suggests that the oxidation process of ligand exclusively
occurs through the nonplanar dication. In addition, a new
couple (IVa/IVc) around 1.5 V due to the oxidation of the
o-phenylenediamine appears (Fig. 5b).
The electrochemical response of compound 4 in MeCN
solution has been studied, as well as the electrochemistry
of such macrocyclic receptor in the presence of an excess
of different metal ions, namely, Li+, Na+, K+, Mg2+, Ca2+,
Ba2+, Ni2+ and Zn2+. The electrochemical response at glassy
carbon and platinum electrodes is dominated by two succes-
sive one-electron-transfer processes involving the oxidation
of the diaminobiphenyl moiety above +1.0 V versus AgCl/
Ag. The obtained results were compared with those previ-
ously reported for ligand 117 (Chart 2) and the correspond-
ing potential data are shown in Table 3.
As shown in Figure 5, corresponding to a 10ꢂ3 mM solution
of 11 in 0.10 M Bu4NPF6/MeCN, the CV response of that
receptor at platinum electrode consists of three overlapped
anodic peaks at +0.74 (Ia), +0.92 (IIa), and +1.09 V (IIIa)
coupled with their cathodic counterparts at +0.72 (Ic),
+0.84 (IIc). The voltammetric profile varies slowly with
the potential scan rate and remains essentially identical for
NMe2
O
O
O
O
N
11
NMe2
Chart 2.
Table 3. Peak potential data in V versus AgCl/Ag for ligands 4 and 11 in
MeCN solution (0.10 M Bu4NPF6)
The most remarkable facts for compounds 11 and 4 were
their different behaviours in the presence of Zn2+ and
Cd2+. For ligand 11, the preferred way for the oxidation
was through the nonplanar radical cation and thus, peak III
disappeared totally and overlapping of peaks II and I was ob-
served. The small size of this ligand precludes the rotation
toward the planar radical cation. By contrast, the larger size
of ligand 4 allows the transition metal cations to be located
close to the softer nitrogen atoms of the o-phenylenediamine
moiety and now the oxidation through the planar geometry is
Ligand
Anodic peaks
IIa
Cathodic peaks
Ia
IIIa
Ic
IIc
IIIc
4
+0.62
+0.58
+0.91
+0.82
+0.85
+0.88
+0.92
+0.81
+0.86
—
—
+1.02
+1.04
+1.09
—
+0.51
+0.49
+0.74
+0.67
—
—
4+K+
4+Zn2+
4+Cd2+
11
+0.75
+0.85
+0.72 +0.84
+0.96
0.99
—
+0.74
11+Zn2+
11+Cd2+
+0.72
+0.77
—
—
—
From CVs at 100 mV/s at platinum electrode.

11976
A. M. Costero et al. / Tetrahedron 62 (2006) 11972–11978
3. Conclusions
Several new coronands derived from 4,40-disubstituted bi-
phenyl have been synthesized. Extraction experiments
with alkaline cations demonstrated that these ligands
showed the expected behaviour. Thus, ligand 4 was the
best extractant for potassium salts. In relation to the electro-
chemical properties of the studied ligands, it is possible to
conclude that the oxidation mechanism is strongly depen-
dent on the cation and the cavity size. Thus, with small cat-
ions or with soft cations that are close to the nitrogen atoms
the planar radical cation can be observed. By contrast with
larger cations like K+ the formation of this type of cation rad-
ical is precluded and consistently with that coordination, the
couple IIIa/IIIc disappears.
In relation to the sensing properties of these ligands we can
conclude that 3 showed to be a selective fluorescent sensor
for Hg2+. The new band observed in the fluorescent spectra
of this ligand in the presence of mercury salts can be related
to the formation of an excimer as it has been observed in
other related compounds. Finally, it can be concluded that
the presence of six oxygen atoms in the cavity gives rise to
the stronger complexes with this mercury whereas ligand 4
where two oxygen atoms have been substituted by nitrogen
give rise to its stronger complexes with Cd2+ and Ni2+.
4. Experimental
4.1. General methods
All commercially available reagents were used without fur-
ther purification. Water sensitive reactions were performed
under argon. Column chromatography was carried out on
silica gel Merck 60 (230–400 mesh) and on SDS activated
neutral aluminium oxide (0.05–0.2 mm; activity degree 1).
IR spectra were recorded on a Perkin–Elmer 1750 FT-IR
and a Bruker Equinox 55 FT-IR. NMR spectra were recorded
with Bruker Avance 300/500 and Varian Unity-300/400
spectrometers. Chemical shifts are reported in parts per
million downfield from TMS. Spectra were referenced to
residual undeuterated solvent. High resolution mass spectra
were taken with a Fisons VG-AUTOSPEC and those using
the electrospray ionizing technique were recorded on an
HPLC-MS with ion trap Bruker 3000-Esquire Plus. UV
spectra were run at 20 ꢄC (thermostated) on a Shimadzu
UV-2102 PC. Fluorescence spectra were carried out in a
Varian Cary Eclipse Fluorimeter.
Figure 6. CVs of (a) a 2.0 mM 11+4 times excess of Zn2+ solution in 0.10 M
Bu4NPF6/MeCN. (b) A 2.0 mM 11+4 times excess of Cd2+ solution in
0.10 M Bu4NPF6/MeCN. (c) A 2.0 mM 4+4 times excess of Zn2+ solution
in 0.10 M Bu4NPF6/MeCN. (d) A 2.0 mM 4+4 times excess of Cd2+ solution
in 0.10 M Bu4NPF6/MeCN. Potential scan rate 100 mV/s.
possible (Fig. 6). When the cation is large enough to be
coordinated by the six donor atoms (for example, K+, radio
˚
1.33 A) the dihedral/planar interconversion of the radical
cation is precluded and only peaks I and II appear in the
cyclovoltamogramme (Fig. 7).
4.1.1. Synthesis of N,N0-dimethyl-N,N0-bis(ethoxyetha-
nol)-o-phenylenediamine (6). N,N0-Dimethyl-o-phenylene-
diamine (2.795 g, 20.4 mmol) was added over a solution of
2-(2-chloroethoxy)ethanol (17.2 ml, 204 mmol), potassium
carbonate (18 g, 130.5 mmol) and sodium iodide (5 mg) in
dry toluene (160 ml). The mixture was refluxed using
a Dean–Stark until the thin layer chromatography did not
show starting material (72 h). After the reaction was finished,
the mixture was allowed to cool at room temperature and fil-
tered off. Solvent was evaporated under reduced pressure and
the remaining oil was distilled (230 ꢄC, 0.4 mmHg) to give 6
as a yellow oil (5.601 g, 88%). IR (KBr): 3350 (OH), 2859,
Figure 7. CVs of a 2.0 mM 4+K+ solution in 0.10 M Bu4NPF6/MeCN.
Potential scan rate 100 mV/s.
1588 (C]C), 1493, 1449, 1118 (C–O–C), 748 cmꢂ1
.

A. M. Costero et al. / Tetrahedron 62 (2006) 11972–11978
11977
1H NMR (CDCl3) d (ppm): 6.92 (4H, m, Ar–H), 3.64 (4H, t,
J¼5.9 Hz, CH2–O), 3.59 (4H, t, J¼5.9 Hz, CH2–O), 3.48
(4H, t, J¼5.9 Hz, CH2–OH), 3.42 (4H, t, J¼5.9 Hz, CH2–
NR2), 2.8 (6H, s, N–CH3). 13C NMR (CDCl3) d (ppm):
145.0, 122.0, 119.2, 72.3, 68.5, 61.5, 52.4, 40.3. HRMS
(EI): M+ calcd for C16H24N2O4 312.2050; found 312.2037.
preparation of 8, N,N0-dimethyl-N,N0-bis(ethoxyethanol)-
o-phenylenediamine (6) (0.395 g, 1.27 mmol) and 4,40-di-
nitro-2,20-bis(chlorocarbonyl)-biphenyl 7 (0.467 g, 1.27 mmol)
gave ligand 9 after chromatographic purification (neutral
alumina, CH2Cl2/MeOH 97:3) as a pale brown oil
(0.1338 g, 18%). IR (KBr): 3005, 2867, 1727 (C]O),
1608 (C]C), 1524 (N]O), 1348 (N]O), 1270, 1122,
1
4.1.2. Synthesis of 2,20-(4,40-dinitrobiphenyl)-10,11-
benzo-2,19-dicarboxy-22-crown-6 (8). The reaction was
carriedoutunderdryconditions. Twosolutionswereprepared.
748 cmꢂ1. H NMR (CDCl3) d (ppm): 8.96 (2H, d, J¼
2.4 Hz, Ar–H), 8.44 (2H, dd, J1¼2.4 Hz, J2¼8.4 Hz, Ar–
H), 7.38 (2H, d, J¼8.4 Hz, Ar–H), 6.92 (4H, m, Ar–H),
4.19 (4H, t, J¼4.5 Hz, CH2OOC), 3.54–3.29 (12H, m,
CH2–N+CH2–O), 2.75 (6H, s, (CH3)2N). 13C NMR (CDCl3)
d (ppm): 164.7, 148.1, 147.8, 145.8, 131.1, 130.9, 126.6,
122.5, 119.8, 119.8, 69.0, 68.4, 65.5, 53.1, 40.3. HRMS
(EI): M+ calcd for C30H32N4O10 608.2118; found 608.2155.
Solution A: 1,2-Bis(5-hydroxy-3-oxy-1-pentyloxy)benzene
5 (0.286 g, 1 mmol) in dry dichloromethane (18 ml).
Solution B: 4,40-Dinitro-2,20-bis(chlorocarbonyl)-biphenyl
(7) (0.406 g, 1.1 mmol) in dry dichloromethane (18 ml).
4.1.5. Synthesis of 2,20-TMB-N,N0-dimethyl-2,19-dicar-
boxy-9,12-diaza-10,11-benzo-22-crown-6 (2). Following
the same procedure employed in the synthesis of 1, ligand
9 (0.2137 g, 0.35 mmol) by reductive methylation, gave
compound 2 as a yellow oil without further purification
(0.167 g, 80%). IR (KBr): 3002, 2868, 1714 (C]O), 1613
(C]C), 1495, 1125, 752 cmꢂ1. 1H NMR (CDCl3) d (ppm):
7.23 (2H, d, J¼8.4 Hz, Ar–H), 6.92 (4H, m, Ar–H), 6.88
(2H, d, J¼3 Hz, Ar–H), 6.64 (2H, dd, J¼8.4 Hz, J¼3 Hz,
Ar–H), 4.68 (4H, dd, CH2OOC), 4.17 (4H, dd, O–
CH2CH2OOC), 3.67–3.34 (8H, CH2–O+CH2–N), 2.97 (12H,
s, CH3N), 2.95 (6H, s, CH3N). 13C NMR (CDCl3) d (ppm):
152.7, 144.8, 132.6, 132.2, 125.9, 123.1, 117.0, 117.0, 107.2,
106.3, 69.0, 66.2, 64.6, 64.3, 39.2, 35.8. HRMS (EI): M+ calcd
for C34H44N4O6 604.3261; found 604.3232.
Both solutions were added dropwise, simultaneously and at
the same rate over a stirring, cold (0 ꢄC) solution of an-
hydrous potassium carbonate (0.692 g, 5 mmol) and tetra-
butylammonium iodide (4 mg) in dry dichloromethane
(165 ml). The solution was stirred during 5 days at room
temperature. Then, the suspension was filtered off, washed
with ethyl acetate and the solvent was evaporated under vac-
uum. Purification by column chromatography (silica gel,
CH2Cl2/MeOH 99:1) gave 8 as an orange oil (0.214 g,
37%). IR (KBr): 3418, 2928 (CH2), 1731 (C]O), 1607
1
(C]C), 1504 (N]O), 1360 (N]O), 746 cmꢂ1. H NMR
(CDCl3) d (ppm): 8.90 (2H, d, J¼2.1 Hz, Ar–H), 8.43 (2H,
dd, J1¼2.1 Hz, J2¼8.1 Hz, Ar–H), 7.42 (2H, d, J¼8.1 Hz,
Ar–H), 6.90–6.82 (4H, m, Ar–H), 4.36–4.20 (4H, m, CH2–
O), 4.11–4.06 (4H, m, CH2–O), 3.76–3.58 (8H, m, CH2–
O). 13C NMR (CDCl3) d (ppm): 149.3, 147.8, 131.4,
131.2, 126.8, 125.9, 123.5, 122.2, 120.4, 115.1, 70.1, 69.6,
69.1, 65.7. HRMS (EI): M+ calcd for C28H26N2O12
582.1486; found 582.1483.
4.1.6. Synthesis of 2,20-TMB-10,11-benzo-22-crown-6 (3).
In a two-neck round bottom flask, under argon, a stirred
solution of 1,2-bis(5-hydroxy-3-oxy-1-pentyloxy)benzene
(5) (0.286 g, 1 mmol) and NaH 60% mineral oil (0.120 g,
3 mmol) in THF (50 ml) was refluxed for 2 h. 2,20-Bis(chloro-
methyl)-4,40-bis(dimethylamine)biphenyl (10) (0.335 g,
1 mmol) and sodium iodide (5 mg) in THF (50 ml) was
added dropwise over this solution. The mixture was heated
for 48 h and quenched with water. THF was removed under
vacuum, the aqueous layer was extracted with ethyl acetate
(3ꢁ25 ml) and organic layers were washed with brine, dried
with anhydrous sodium sulfate and evaporated under re-
duced pressure. Column chromatography (silica gel, EtOAc
to EtOAc/MeOH 95:5) gave compound 3 as pale yellow oil
(0.2036 g, 37%). IR (KBr): 3080, 2867 (CH3, CH2), 1681
4.1.3. Synthesis of 2,20-TMB-10,11-benzo-22-crown-6 (1).
An heterogeneous solution of 8 (0.384 g, 0.66 mmol), form-
aldehyde (0.3 ml, 30% in water) and Pd/C 10% (0.1 g) in an-
hydrous ethanol (50 ml) was stirred under hydrogen (30 lib/
inch2). The mixture was followed by thin layer chromato-
graphy until the reaction was finished (45 min), then the
reaction was filtered off and the solid was washed with HCl
10%. The aqueous layer was basified accurately with potas-
sium carbonate, extracted with ethyl acetate (3ꢁ25 ml) and
washed with brine. Organic layers were joined, dried with
anhydrous sodium sulfate. The solvent was evaporated under
reduced pressure to give compound 1 as a yellow-orange
solid without further purification (0.323 g, 85%). Mp: 66–
68 ꢄC. IR (KBr): 3060, 2874, 1722 (C]O), 1608 (C]C),
1
(C]O), 1608 (C]C), 1126 (C–O–C), 744 cmꢂ1. H NMR
(CDCl3) d (ppm): 6.93 (2H, d, J¼8.5 Hz, Ar–H), 6.87 (6H,
m, Ar–H), 6.67 (2H, dd, J1¼2.5 Hz, J2¼8.5 Hz, Ar–H), 4.35
(4H, s, CH2–O), 4.11 (4H, t, J¼3.9 Hz, CH2–O), 3.83–3.49
(12H, m, CH2–O), 2.96 (12H, s, (CH3)2N). 13C NMR
(CDCl3) d (ppm): 150.2, 149.5, 137.9, 131.4, 128.6, 121.9,
114.9, 112.7, 111.7, 71.8, 71.2, 70.3, 70.1, 69.8, 41.1. HRMS
(EI): M+ calcd for C32H42N2O6 550.3043; found 550.3056.
1
1503, 1255 (C–O), 741 cmꢂ1. H NMR (CDCl3) d (ppm):
7.28 (2H, d, J¼2.8 Hz, Ar–H), 7.09 (2H, d, J¼9.0 Hz, Ar–
H), 6.92–6.82 (6H, m, Ar–H), 4.24 (4H, t, J¼5.1 Hz, CH2–
O), 4.09 (4H, m, CH2–O), 3.75 (4H, m, CH2–O), 3.61 (4H,
m, CH2–O), 2.96 (6H, s, (CH3)2–N). 13C NMR (CDCl3)
d (ppm): 168.9, 149.5, 142.4, 132.1, 131.1, 122.0, 122.0
115.6, 115.0, 113.9, 70.0, 69.7, 69.5, 64.5, 40.9. HRMS
(EI): M+ calcd for C32H38N2O8 578.2628; found 578.2628.
4.1.7. Synthesis of 2,20-TMB-N,N0-dimethyl-9,12-diaza-
10,11-benzo-22-crown-6 (4). Proceeding as in the synthesis
of 3, N,N0-dimethyl-N,N0-bis(ethoxyethanol)-o-phenylene-
diamine (6) (0.312 g, 1 mmol) and 2,20-bis(chloromethyl)-
4,40-bis(dimethylamine)biphenyl (10) (0.335 g, 1 mmol)
gave compound 4 after chromatographic purification (neutral
alumina, hexane/EtOAc 50:50 to EtOAc) as a brown oil
4.1.4. Synthesis of 2,20-(4,40-dinitrobiphenyl)-N,N0-di-
methyl-2,19-dicarboxy-9,12-diaza-10,11-benzo-22-
crown-6 (9). Using the same procedure employed in the

11978
A. M. Costero et al. / Tetrahedron 62 (2006) 11972–11978
(0.276 g, 48%). IR (KBr): 3080, 2852, 2792, 1607.82, 1493
(C]C), 1448, 1347, 1118, 1090 and 804 (C–N) cmꢂ1
References and notes
.
1H NMR (CDCl3) d (ppm): 6.94–6.89 (8H, m, Ar–H), 6.67
(2H, dd, J1¼3.0 Hz, J2¼8.4 Hz, Ar–H), 4.33 (4H, s, CH2–
O), 3.58–3.42 (12H, m, CH2–O), 3.3 (4H, t, J¼6.6 Hz,
CH2–N), 2.96 (12H, s, (CH3)2N), 2.73 (6H, s, CH3–N).
13C NMR (CDCl3) d (ppm): 150.2, 145.9, 138.0, 131.3,
128.4, 122.4, 119.7, 112.3, 111.6, 71.7, 70.5, 70.0, 69.2,
53.3, 41.1, 40.4. HRMS (EI): M+ calcd for C34H48N4O4
576.3675; found 576.3679.
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procedure
The spectrum of free ligand (3.0 ml, 10ꢂ5 M) in acetonitrile
was recorded. Then, an aliquot of a solution 10ꢂ3 M in the
metallic salt and 10ꢂ5 M in the ligand was added (0.1 equiv),
the mixture was stirred for 30 s and the spectrum was re-
corded. This procedure was repeated several times until
the concentration of the salt was larger than the ligand and
no variation of the signals was observed. The plot of the var-
iation of the absorbance/emission versus the ratio between
the salt and the complex gave the titration curve and so the
stoichiometry of the complex. The constant value was calcu-
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´
6. (a) Costero, A. M.; Monrabal, E.; Andreu, C.; Martınez-Manez,
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ꢀ˜
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Amigo, J. M. J. Chem. Soc., Dalton Trans. 2000, 361–367;
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´
ꢀ˜
Manez, R.; Sancenon, F.; Soto, J. J. Chem. Soc., Dalton
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ꢀ
7. Costero, A. M.; Ban˜uls, M. J.; Aurell, M. J.; Ochando, L. E.;
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4.3. Electrochemical experiments
Electrochemical measurements were performed at 298 K in
a conventional three-electrode cell under argon atmosphere.
Nominal ca. 2.0 mM concentrations of the ligand were used
in dry MeCN and DMSO using tetrabutylammonium hexa-
fluorophosphate (0.10 M) as a supporting electrolyte. A 4
times excess of metallic salts was used in each case (triflate
salts for the transition metal cations and perchlorate for
alkaline cations). Experiments were performed using a
BAS CV 50 W equipment using a BAS MF2012 glassy
carbon electrode (GCE) (geometrical area 0.071 cm2), and
a BAS MF2014 platinum electrode (geometrical area
0.018 cm2) as a working electrode. A platinum wire auxiliary
electrode and a AgCl (3 M NaCl)/Ag reference electrode
separated from the test solution by a salt bridge only contain-
ing supporting electrolyte completed the electrode arrange-
ment. The potential of such reference electrode was ꢂ35 mV
versus the saturated calomel reference electrode (SCE).
9. Costero, A. M.; Sanchis, J.; Peransi, S.; Gil, S.; Sanz, V.;
ꢀ
Domenech, A. Tetrahedron 2004, 60, 4683–4691.
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12. Costero, A. M.; Sanchis, J.; Gil, S.; Sanz, V.; Williams, J. A. G.
J. Mater. Chem. 2005, 2848–2853.
13. (a) Varnes, A. W.; Dodson, R. B.; Wehry, E. L. J. Am. Chem.
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1305–1314.
4.4. Extraction experiments
15. Beeby, A. J.; Parker, D.; Williams, J. G. J. Chem. Soc., Perkin
Trans. 2 1996, 1565–1580.
16. Costero, A. M.; Andreu, C.; Monrabal, E.; Tortajada, A.;
These experiments were carried out as described in Ref. 9.
Acknowledgements
ꢀ
Ochando, L. E.; Amigo,J.M.Supramol. Chem. 1998, 9, 211–219.
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19. Perrin, C. L. Mechanisms of Organic Polarography. In Organic
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New York, NY, 1969; p 280.
The present research has been financed by DGCYT CTQ
2005-07562-C04-01 and from the Generalitat Valenciana
project GVACOMP2006-112. We acknowledge the Univer-
sitat de Valencia (S.C.I.E.) for most of the equipment em-
ployed. One of us (M.J.B.) acknowledges the Generalitat
Valenciana for a Ph.D. grant.
ꢀ
˜
20. Domenech, A.; Costero, A. M.; Banuls, M. J.; Aurell, M. J.
Electrochim. Acta 2005, 20, 4063–4075.
Supplementary data
21. SPECFIT/32Ô GLOBAL ANALYSIS SYSTEM, v.3.0,
Spectrum Associates, Marlborough, MA, USA, www.bio-logic.
info/rapid-kinetics/specfit.html.
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2006.09.084.