4-Hexylresorcinol-derived hydroxyazobenzocrown ethers as chromoionophores

Article abstract of DOI:10.1016/j.tet.2009.10.054

The synthesis of novel chromoionophoric azobenzocrowns with a hydroxyl group in the para position to the azo moiety has been described. The interactions of the obtained colored macrocycles with selected alkali and alkaline earth metal cations were investi

Full text of DOI:10.1016/j.tet.2009.10.054

Tetrahedron 65 (2009) 10671–10678
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
4-Hexylresorcinol-derived hydroxyazobenzocrown ethers as chromoionophores
*
_
Elzbieta Luboch , Ewa Wagner-Wysiecka, Tomasz Rzymowski
Department of Chemical Technology, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-233 Gdan´sk, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of novel chromoionophoric azobenzocrowns with a hydroxyl group in the para position to
the azo moiety has been described. The interactions of the obtained colored macrocycles with selected
alkali and alkaline earth metal cations were investigated in acetonitrile by UV–vis spectroscopy.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 6 July 2009
Received in revised form
1 October 2009
Accepted 15 October 2009
Available online 20 October 2009
Keywords:
Azobenzocrown ethers
Williamson reaction
Hydroxyazobenzene%quinone-hydrazone
tautomerism
Metal cation complexation
UV–vis spectroscopy
Colorimetric assays
Chromoionophores
1. Introduction
documented, and the cavity–cation diameter fit plays an important
role. Numerous chromoionophores belonging to this type were
Crown ethers incorporating an azobenzene residue as part of
the macrocycle are interesting metal complexing reagents.1 Mac-
rocycles with inherent 2,20-azobenzene2–4 or 4,40-azobenzene5
residues were obtained and investigated. A set of macrocycles
containing an azophenol residue was also obtained. Incorporation
of an azophenol residue leads to chromoionophores belonging to
proton dissociable (anionic) compounds. These chromoionophores
possess either a peripheral azo unit with an OH group directed into
the cavity,6 or a –N]N– group constituting part of the macro-
cycle.7–11 In the last case, the phenolic OH is, in most cases, located
on the molecule periphery cf.7–9 or is directed inside the macro-
cycle as in the case of p-alkylphenol derivatives.10 There are also
known resorcinol derivatives,11 in which one OH group is directed
inside the cavity and the another outside.
Complexation of cations by azophenol derivatives of macrocyclic
compounds is favored under basic conditions, because the
interaction of anionic species formed upon proton abstraction with
cations is stronger. Azophenolic crown ethers with an OH group
directed inside the cavity require less basic conditions to replace the
proton by the cation due to competition. This effect is well
found to selectively interact especially with lithium cations in
organic solvents.6d Cram’s spherand12 also selectively binds lithium
cations in dioxane-water solution, but the complexation process is
very slow. For phenol crown ethers with two inherent azo units,
lithium complexation in dioxane-water proceeds with the spectro-
scopic inherent time scale.10 Application of a mixed solvent system is
convenient from a practical point of view, because for lithium de-
termination, an aqueous sample should only be diluted with di-
oxane. Nitro and dinitro derivatives of phenylazophenol crown
ethers were also studied with special emphasis to the spectroscopic
separations of bands for free ligands and their complexes.1
For para or ortho hydroxyazobenzenes, tautomerization to the
quinone-hydrazone form is known to occur.13 The physical proper-
ties of azo dyes (e.g., color) are closely related to this tautomerism. In
their UV–vis spectrum, the absorption maximum of the hydrazone
form is typically shifted toward longer wavelength values in relation
to the azo form.14 In the solid state, o- and p-hydroxyazobenzenes
exist mainly in the azo form, whereas naphthalene derivatives are in
the hydrazone form or as a mixture of both hydrazone and azo form.
The tautomeric equilibrium is affected by a solvent. In general, the
hydrazone form is favored in more polar solvents.15,16
Tautomerization studies of 4-(40-substituted-phenylazo)-1-
naphthols17 by Kishimoto showed that electron donating sub-
stituents in the para position to the azo unit stabilize the azo form
* Corresponding author. Tel.: þ48 58 347 1759; fax: þ48 58 347 1949.
E-mail address: elub@chem.pg.gda.pl (E. Luboch).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.054

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E. Luboch et al. / Tetrahedron 65 (2009) 10671–10678
while electron accepting groups stabilize the hydrazone form. The
equilibrium depends on solvent; in DMSO and DMF, the com-
pounds exist in dissociated form.
The phenylazophenol%quinone-phenylhydrazone tautomeri-
zation also occurs in the case of macrocyclic azophenol chro-
moionophores, cf.6a
It was stated that macrocyclic p-hydroxyazobenzene derivative -
compound 1 (Fig. 1), with an inherent azo unit, in the solid state18
and in solvents of different polarity (chloroform, acetonitrile,
acetone, or methanol) exists in the quinone-hydrazone form. The
azophenol form was observed (w30%) only in DMSO.7 The
quinone-hydrazone form is stabilized in this case by hydrogen
bonds inside the cavity (Fig. 2).
addition of the weak base, triethylamine, exists in the quinone-
hydrazone form. However, in acetonitrile and in the absence of
base, lithium perchlorate forms complexes with both tautomers.
Addition of triethylamine to this mixture shifts the equilibrium
toward one complex, probably the ionized ligand.
This paper presents a simple method for the synthesis of new 13-
and 16-membered azobenzocrown ethers, with an inherent azo unit
and with a hydroxyl group in the para position to it, i.e., derivatives of
4-hexylresorcinol. In addition, a nitro group was introduced to the
benzene residue without the hydroxyl substituent. For the synthe-
sized compounds, spectroscopic properties and interaction studies
with metal cations important from a biological or medicinal point of
view were carried out. The 4-hexylresorcinol building block was
chosen to study the synthetic effect of an o-alkyl residue to the OH
group, andtheNO2 groupwaschosentostudytheeffectofanelectron
acceptinggrouponcationcomplexationand spectroscopic properties
e.g., the position of absorption band maximum.
n
n
O
O
O
O
O
O
H
OH
O
N
N
N
N
2. Results and discussion
2.1. Synthesis
1 n = 1
2 n = 2
3 n = 3
Azobenzocrown ethers 1–3 were previously obtained in multi-
step reactions including reductive macrocyclization of the re-
spective dinitropodands7,8 with sodium stannite (Na2SnO2) in
acetone/water mixture. Alternatively, hydroxyazomacrocycles may
be synthesized in a reaction analogous to a Wallach rearrange-
ment.9 Attempts to obtain the above hydroxyazobenzocrowns
(1–3) by Williamson reaction of the 2,20-dihydroxyazobenzene
with ditosylates as the last step formed only traces of crowns from
the reaction mixture, in which polymeric products dominated.
In contrast to the above completely ineffective synthesis, the
Williamson reaction of 5-n-hexyl-2,20,4-trihydroxyazobenzene
with 1,7-ditosyl-1,4,7-trioxaheptane yielded 12% of 13-membered
crown 4. Analogously, reaction of 5-n-hexyl-2,20,4-trihydroxy-40-
nitro-azobenzene with the same ditosyl derivative or 1,10-ditosyl-
1,4,7,10-tetraoxadecane produces 13- and 16-membered nitro
crowns 5 and 6 with 10 and 7% yield, respectively. The more favored
cyclization reaction course of the hexyl substituted substrate than
in the case of the 2,20-dihydroxyazobenzene could be attributed to
the presence of the hexyl group that sterically hinders alkylation of
the adjacent resorcinol OH group. The synthesis of functionalized
azobenzocrown ethers 4, 5, and 6 is shown in Scheme 1. In such
solvents as: chloroform, DMSO, methanol, acetone or acetonitrile
compound 5 exists in the quinone-hydrazone form.
Figure 1. Tautomeric equilibrium for hydroxyazobenzocrown ethers.
O
O
O
H
O
N
N
Figure 2. Hydrogen bonds inside the cavity of azobenzocrown 1.
It was found that the tautomerization equilibrium is affected by
the size of the macrocycle; the larger the cavity size the lower the
tendency to exist in the quinone-hydrazone form probably due to
weaker hydrogen bonds. Compound 2 (Fig. 1) in chloroform and in
acetonitrile exists, like 1, inthequinone-hydrazoneform, butinDMSO
only the azophenol form was found. 19-Membered compound 3 ex-
clusively exists in the azophenol form, e.g., in DMSO and chloroform,
while in acetonitrile the abundance of this form is no less than 75%.8
The 1H NMR and UV–vis spectroscopic studies of compounds
1–3 were carried out to examine the influence of metal cation
complexation on the tautomeric equilibrium.6,7 The 1H NMR
spectra shows that compound 1 in pure acetonitrile and upon
HO
OH
OH
NH2
OH
NaNO2
HCl
+
]
N2
R
R
n
n
R
OH
N
OH
O
O
N
R
TosO
O
OTos
N
O
N
THF, t-BuOK
OH
OH
7 R = H, quantitatively
8 R = NO2, quantitatively
4 R = H,
n = 1, 12%
5 R = NO2 , n = 1, 10%
6 R = NO2 , n = 2, 7%
Scheme 1. The synthesis of azobenzocrown ethers with peripheral hydroxyl groupdderivatives of 4-hexylresorcinol.

E. Luboch et al. / Tetrahedron 65 (2009) 10671–10678
10673
2.2. Spectroscopy: interaction with metal cations
solution in the presence of lithium salt, only one tautomeric form,
probably the ionized hydrazone, is present.
Metal cation complexation properties of crowns 4–6 were in-
vestigated by UV–vis and 1H NMR spectroscopy, in neutral
acetonitrile (in acetonitrile compounds 4–6 exist in the quinone-
hydrazone form) and in acetonitrile containing triethylamine. The
influence of concentrations of triethylamine on spectroscopic
changes was studied using UV–vis spectroscopy. 1H NMR spec-
troscopy allowed the azo-hydrazone equilibrium tracing and
studies of interactions with metal cations, however in a narrow
range of concentrations of amine and metal salts.
In the absence of the organic base in the UV–vis spectra of
compound 4, no noticeable changes were observed in the presence
of alkali metal perchlorates. Similarly, no significant influence of
triethylamine concentration on the location or intensity of the
absorption band of the ligand in the UV–vis spectra was found.
However, it was found that compound 4, in acetonitrile, selectively
binds a lithium cation in the presence of sodium and potassium
cations upon addition of triethylamine.
To establish the optimal amount of triethylamine, spectra in the
presence of 500-fold excess of lithium perchlorate (amount
enabling achievement of the limiting spectrum) and different
amounts of triethylamine were registered. It was found that addi-
tion of about 14,000-fold excess of triethylamine to crown (mol/
mol), results in the best band separation. Under these conditions
the value of the stability constant of the lithium complex with
ligand 4, log KLiw2.5, was estimated on the basis of a titration
experiment. More surplus of amine does not strongly effect
changes in the absorption spectra. The dependence of the amount
of triethylamine on changes of the absorption spectra upon lithium
complexation is shown in Figure 3a.
Analogous experiments were carried out for compound 5 with
a nitro group in the para position to the azo group, localized in the
neighboring benzene unit than the OH group (Scheme 1).
In pure acetonitrile, only in the presence lithium salt, small
changes in absorption spectra were observed. Thus, metal cation
complexation was studied in the presence of triethylamine. It was
found that even a 1000-fold excess of triethylamine does not cause
changes in ligand UV–vis spectrum, but addition of an organic base
plays an important role in lithium complexation. Absorption
spectra in the presence of a 500-fold excess of alkali metal
perchlorates and different amounts of organic base were registered.
The spectra in the presence of lithium and sodium salts are shown
in Figure 4.
The most favorable changes, e.g., the least influence from so-
dium cation on selective lithium complexation, in UV–vis spectra
were obtained upon a 4000-fold excess of amine addition (not
shown here). In this case, separation of bands for free ligand and its
lithium complex equals 95 nm and complexation is accompanied
by a color change from yellow to violet-pink (Fig. 5).
Lithium cation complexation by 5 was also studied using 1H
NMR spectroscopy. Addition of an excess of lithium perchlorate in
neutral acetonitrile causes only a small shift of the signals for the
hydrazone form toward higher ppm values (the azophenol form
was not observed in this case). Figure 6 shows the 1H NMR spectra
in the range of 3–13 ppm for 5 in d-acetonitrile, in the presence of
triethylamine, and both in the presence of an organic base and
lithium perchlorate. Addition of triethylamine causes no changes
in the 1H NMR spectrum, whereas in the presence of lithium
perchlorate the signals of the aromatic protons are broadened
(except for the proton in the ortho position to the nitro group, para
to the alkoxy) and shifted downfield (especially the proton in the
ortho position to the hexyl residue (7 ppm), for which position
changes are probably connected with ionization of the molecule).
Moreover, the signal of the OH proton at w12.6 ppm disappears.
For 16-membered crown 6 in the same way as for compound 5,
only small changes in the absorption spectra were observed in the
presence of alkali metal perchlorates in pure acetonitrile.
Under such conditions, ‘free’ ligand and its lithium complex
bands are separated by 46 nm and no interference from sodium and
potassium cations is observed (Fig. 3b).
In compound 4, the alkyl (n-hexyl) residue and the hydroxyl
group are located at the same benzene residue. For comparison,
when an alkyl substituent (e.g., n-pentadecyl) is present in the
neighboring benzene ring, the complex absorption band is shifted
only by about 20 nm.19
Based on 1H NMR spectroscopic measurements it was estab-
lished that in neutral acetonitrile, in the presence of 10-fold lithium
perchlorate excess, the hydrazone and azo forms of compound 4
exist in a 3:1 ratio (1:1 for compound 17). In basic acetonitrile
Thus, also in this case, metal cation interaction was studied in
the presence of an organic base. The spectra of ligand 6 in the
presence of different amounts of triethylamine were registered. The
results are shown in Figure 7. Interestingly, for 16-membered
L
A
Li+
Na+
K+
a
0,6
b
0,6
0,5
0,4
0,3
0,2
0,1
0,0
0,5
0 eq Et3N
140 eq Et3N
680 eq Et3N
1400 eq Et3N
14000 eq Et3N
0,4
0,3
0,2
"free" ligand
ligand + Et3N
ligand + Et3N + LiClO4
ligand + Et3N + NaClO4
ligand + Et3N + KClO4
30000 eq Et3N
0,1
0,0
400
500
600
400
500
600
[nm]
[nm]
Figure 3. a) Dependence of amount of triethylamine on changes of absorption spectra of compound 4 (CL¼17.5
mol); b) Changes in absorption spectra of compound 4 (CL¼17.5 M) in the presence of alkali metal perchlorates: (500-fold excess to crown mol/mol) and triethylamine (A) (excess
to crown w14,000 mol/mol) in acetonitrile. Inset: color changes of ligand (L) 4 solution in the presence of triethylamine and metal perchlorates.
mM) upon lithium complexation (500-fold excess to crown; mol/
m

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E. Luboch et al. / Tetrahedron 65 (2009) 10671–10678
a
0,6
0,5
0,4
0,3
0,2
0,1
0,0
b
0,6
0 eq Et3N
140 eq Et N
0,5
680 eq Et33N
1400 eq Et3N
0,4
0,3
0,2
0,1
0,0
14000 eq Et N
30000 eq Et33N
400
500
600
700
400
500
600
700
[nm]
[nm]
Figure 4. The dependence of triethylamine amount on changes of absorption spectra of compound 5 (CL¼17,5
mM) upon interaction with: a) lithium b) sodium in acetonitrile. 500-
Fold salts excess to crown mol/mol. Solution colors correspond to (from left): 0, 140, 680, 1400 and 14,000 equiv of triethylamine.
crown 6, the effect of addition of the organic base is the strongest
compared to the smaller, 13-membered analogs. The presence of
triethylamine probably causes proton abstraction from the hydra-
zone form, which is easier, in this case, due to a weaker hydrogen
bond.
A series of experiments with different concentration of trie-
thylamine showed that the optimal amount of organic base needed
for selective response toward metal cations is 140 equiv (mol/mol
to ligand). Changes in the absorption spectra in the presence of
500-fold excess of lithium, sodium or potassium salts without
amine and in the presence of different amounts of triethylamine are
shown in Figure 8.
The changes in absorption spectra and the accompanying
changes of solution color for compound 6 in the presence of
500-fold excess of alkali metal perchlorates and 140 equiv of tri-
ethylamine are shown in Figure 9a. Under these conditions the
difference in absorption maxima position between the ligand
spectrum and the spectra registered in the presence of metal salts
are 80, 106 and 112 nm for lithium, sodium, and potassium, re-
spectively. This means that lithium, sodium, and potassium cations
can be distinguished. An increase of the amine concentration and
keeping a 500-fold excess of metal salts results in the formation of
a blue–violet potassium complex (Fig. 9b).
In the 1H NMR spectrum of compound 6, the NH proton was not
observable after adding the amine. Signal of the proton at 7.0 ppm,
in basic acetonitrile, is partly shifted to 7.4 ppm, which probably
corresponds to the ionized form. The changes in the 1H NMR
spectra in the presence of lithium and sodium perchlorates and
triethylamine in acetonitrile are shown in Figure 10. In the presence
of these cations, the signal of the proton at 7.0 ppm disappears, and
changes in positions of both the aromatic and ether signals are
observed. Addition of a potassium salt, 30-fold excess, (spectrum
not shown here) causes only a small increase of ionization degree,
which is concluded from observation of the increasing integration
of signal at 7.4 ppm.
The response for magnesium and calcium ions was also in-
vestigated under selected conditions. For 13-membered crowns 4
and 5, the need for using a large excess of amine causes pre-
cipitation of a colored solid in the presence of magnesium and
calcium perchlorates.
L
A
Li+
Na+
K+
For the 16-membered crown 6, where a smaller amount of or-
ganic base is used, significant changes in absorption spectra were
observed in the presence of a calcium salt, whereas for magnesium,
changes were negligible. The interaction with calcium ions is
manifested by a color change from yellow to red (Dl¼74 nm) in the
presence of 25 equiv of triethylamine. Precipitation of solid occurs
upon higher concentration of amine (140 equiv) and is almost
complete in the presence of about 1400 equiv of triethylamine. The
changes in absorption spectra for compound 6 in the presence of
magnesium and calcium are shown in Figure 11.
ligand
ligand + Et3N
0,5
0,4
0,3
0,2
0,1
0,0
ligand + Et N + LiClO4
ligand + Et3N + NaClO4
ligand + Et3N + KClO4
3
3. Conclusions
The steric hindrance caused by the n-hexyl residue in 5-n-hexyl-
2,20,4-trihydroxyazobenzene decreases the reactivity of the neigh-
boring OH group in the alkylation reaction causing a higher efficiency
of azobenzocrowns ether synthesis with peripheral hydroxyl group
(compounds 4–6) in the synthetic procedure. Using nitroderivative of
hydroxyphenylazoresorcinol enables a simple synthesis of hydroxy-
azobenzocrowns with two peripheral groups, i.e., nitro and hydroxyl
groups at two opposite sides of the conjugated chromophoric system.
400
500
600
700
]
[nm
Figure 5. Changes in absorption spectra for compound 5 (CL¼17.5
mM) in the presence
of 500-fold excess of alkali metal perchlorates and 4000 equiv of triethylamine (A) in
acetonitrile. Inset: color changes of ligand 5 solution in the presence of triethylamine
and metal perchlorates.

E. Luboch et al. / Tetrahedron 65 (2009) 10671–10678
10675
13
12
11
10
9
8
7
6
5
4
13
12
11
10
9
8
7
6
5
4
13
12
11
10
9
8
7
6
5
4
Figure 6. Plots of 1H NMR spectra (d-acetonitrile) of: 5 (top); 5 in the presence of triethylamine (middle) and both in the presence triethylamine and lithium perchlorate (bottom).
The synthesized 13-membered macrocycles 4 and 5 selectively bind
the lithium cation in the presence of sodium and potassium cations in
basic (Et3N) acetonitrile solution. The presence of magnesium and
calcium salts does not affect selectivity. The hexyl residue increases
the tendency of the mentioned compounds to exist in the hydrazone
form. It also causes slightly larger bathochromic shift upon lithium
cation complexation compared with analogous unsubstituted crown
(compound 1). The most significant color and spectral changes, in the
visible range, in the presence of this cation were found for 13-mem-
beredhydroxyazobenzoazocrownwithanitro substituent inbenzene
ring (compound 5); separation of bands in this case is 95 nm. It was
demonstrated that changes upon lithium complexation are de-
pendent on the kind of substituent in benzene ring(s) and their lo-
cation. The 16-membered crown 6 interacts with more, among those
investigated, metal cations: lithium, sodium and calcium. This means
that the crown ether of the larger macrocycle is more sensitive, but
less selective. The chromoionophoric behavior of the synthesized
compounds potentially allows their application, under selected con-
ditions, for construction of optical sensors.
4. Experimental
4.1. General
All solvents were of analytical reagent grade. Tetrahydrofuran
was distilled over LiAlH4 and stored over molecular sieves. For
spectrophotometric measurements HPLC grade solvents were used.
The reagents from Aldrich (2-amino-5-nitrophenol and 4-hexyl-
resorcinol) were used without further purification. Silica gel 60
(63–200 mm) (Merck) was used for column chromatography. TLC:
aluminium sheets covered with 60F254 were from Merck,
dichloromethane–acetone (10:1) was used as mobile phase. 1H
NMR spectra were recorded on Varian instrument at 500 MHz.
Chemical shifts are reported as
d [ppm] values in relation to TMS.
FTIR spectra were recorded on Mattson Genesis II instrument.
UV–vis spectra were recorded on UNICAM UV 300 apparatus. Mass
spectrometry was conducted on an AMD-604 apparatus (EI
method, 70 eV) and Mariner (ESI method).
0,6
0,5
0 eq Et3N
140 eq Et N
680 eq Et33N
0,4
4.2. Synthesis
1400 eq Et3N
14000 eq Et N
5-n-Hexyl-2,20,4-trihydroxyazobenzene (7) and 5-n-hexyl-2,20,4-
30000 eq Et33N
0,3
trihydroxy-40-nitro-azobenzene (8).
A suspension of 2-amino-
phenol (1.76 g, w16 mmol) or 2-amino-5-nitrophenol (90%, 2.46 g,
w16 mmol) in water (40 mL) was cooled and acidified with conc.
hydrochloric acid (4 mL). The formed solution was diazotized with
sodium nitrite (1.1 g in 8 mL cold water) and the reaction mixture
was kept at 5 ꢀC for 10 min. The obtained diazonium salt was added
dropwise to an ice-cold solution of 4-hexylresorcinol (3.1 g,
16 mmol) and NaOH (2.0 g) in water (40 mL). The reaction mixture
was stirred at 5 ꢀC for 1 h. The mixture was acidified (HCl) and the
precipitated solid was separated, washed with 0.1 M HCl and water,
and dried in vacuum at room temperature. The crude compounds
(quantitative yields) were used for synthesis of macrocycles. Mp
180–182 ꢀC (7) and 175–176 ꢀC (8).
0,2
0,1
0,0
400
500
600
700
[nm]
Figure 7. Changes in absorption spectra of compound 6 in acetonitrile (CL¼17,5
m
M) in
the presence of different amounts of triethylamine. Solution colors correspond to 0,
140, 680, 1400 and 14,000 equiv of triethylamine, respectively.

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E. Luboch et al. / Tetrahedron 65 (2009) 10671–10678
c
0,6
0,5
0,4
0,3
0,2
0,1
0,0
a
0,6
0,5
0,4
0,3
0,2
0,1
0,0
0,6
b
0,5
0,4
0,3
0,2
0,1
0,0
400
500
600
400
500
600
400
500
600
[nm]
[nm]
[nm]
Figure 8. Changes in absorption spectra of compound 6 (CL¼17.5
mM) in the presence of 500-fold excess of: a) lithium, b) sodium and c) potassium perchlorates and different
amounts of triethylamine in acetonitrile. Solution colors correspond to (from left): 0, 140, 680, 1400 and 14,000 equiv of triethylamine, respectively.
4.2.1. Compound 7. 1H NMR (d-DMSO): 0.86 (3H, t, J¼6.6 Hz); 1.23–
1.35 (6H, m); 1.48–1.57 (2H, m); 2.47 (2H, t, J¼7.8 Hz); 6.34 (1H, s);
6.95 (1H, t, J¼7.6 Hz); 6.99 (1H, d, J¼7.3 Hz); 7.24 (1H, dt, J1¼7.6 Hz,
J2¼1.5 Hz); 7.44 (1H, s); 7.72 (1H, dd, J1¼7.8 Hz, J2¼1.5 Hz); 11.4 (1H,
br s); 12.7 (1H, br s). MS (EI) m/z: 314 (Mþ).
was dissolved in methylene chloride and chromatographed on
column using methylene chloride, methylene chloride/acetone
mixtures and finally methylene chloride/acetone mixture (10:1) as
eluents. The fractions containing the azobenzocrown ether were
evaporated. Crystallization from acetone–hexane mixture gave
compounds (dark orange solids): 4 (yield 12%, mp 120–121 ꢀC,
Rf¼0.22), 5 (yield 10%, mp 190–191 ꢀC, Rf¼0.44) or 6 (yield 7%, mp
195–196 ꢀC, Rf¼0.33), respectively.
4.2.2. Compound 8. 1H NMR (d-DMSO): 0.86 (3H, t, J¼7.1 Hz); 1.22–
1.35 (6H, m); 1.48–1.54 (2H, m); 2.43 (2H, t, J¼7.6 Hz); 6.00 (1H, s);
7.17 (1H, s); 7.75 (1H, s); 7.79 (2H, s); 11.5 (1H, br s); 14.6 (1H, br s).
MS (EI) m/z: 359 (Mþ).
4.2.4. Compound 4. 1H NMR (d-acetone): 0.91 (3H, t, J¼6.8 Hz);
1.28–1.42 (6H, m); 1.54 (2H, q, J¼7.4 Hz); 2.41 (2H, t, J¼7.4 Hz); 3.97
(2H, t, J¼4.3 Hz); 4.10–4.12 (2H, m); 4.18 (2H, t, J¼4.3 Hz); 4.29–4.31
(2H, m); 5.87 (1H, s); 7.03 (1H, s); 7.06 (1H, dt, J1¼7.6 Hz, J2¼1.3 Hz);
7.16 (1H, t, J¼7.2 Hz); 7.25 (1H, dd, J1¼7.6 Hz, J2¼1.2 Hz); 7.64 (1H,
dd, J1¼7.8 Hz, J2¼1.3 Hz); 12.48 (1H, s). IR (Nujol) cmꢁ1: 3277, 1636,
1599, 1570, 1523, 1261, 1238, 1189, 1128, 1090, 722 cmꢁ1. UV–vis
(acetonitrile): lmax¼435 nm, emax¼2.52ꢂ104. HRMS (EI) m/z:
384.2041 (calcd for C22H28N2O4 384.2049).
4.2.3. Hydroxyazobenzocrown ethers 4–6. To 5-n-hexyl-2,20,4-tri-
hydroxyazobenzene (0.74 g, 2.33 mmol) or 5-n-hexyl-2,20,4-tri-
hydroxy-40-nitro-azobenzene (0.85 g) potassium tert-butoxide
(0.78 g, 7 mmol) in dry THF (50 mL) was added. The mixture was
stirred for 0.5 h at room temperature and then 18-crown-6 (20 mg)
was added. After that, the appropriate ditosyl derivative (2.2 mmol)
in THF (50 mL) was added dropwise over 1 h. The reaction mixture
was maintained at 70 ꢀC for 24 h. The solid was removed by fil-
tration and washed with THF until colorless filtrate was obtained.
The filtrate was evaporated under reduced pressure, the residue
4.2.5. Compound 5. 1H NMR (d-acetone): 0.89–0.93 (3H, m); 1.30–
1.42 (6H, m); 1,51–1.58 (2H, m); 2.42 (2H, t, J¼7.6 Hz); 4.04 (2H, t,
Li+
Na+
K+
L
A
Li+
Na+
K+
L
A
"free" ligand
0,6
0,5
0,4
0,3
0,2
0,1
0,0
0,6
0,5
0,4
0,3
0,2
0,1
0,0
a
b
ligand + Et3N
ligand + Et3N + LiClO4
ligand + Et3N + NaClO4
ligand + Et3N + KClO4
400
500
600
700
400
500
600
700
[nm]
[nm]
Figure 9. Changes in absorption spectra for compound 6 in the presence of 500-fold excess of alkali metal perchlorates and a) 140 equiv and b) 1400 equiv of triethylamine in
acetonitrile. Inset: color changes of ligand 6 solution in the presence of triethylamine and metal perchlorates.

E. Luboch et al. / Tetrahedron 65 (2009) 10671–10678
10677
12.0
11.5
11.0
10.5
10.0
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
12.0
12.0
11.5
11.5
11.0
11.0
10.5
10.5
10.0
10.0
9.5
9.5
9.0
9.0
8.5
8.5
8.0
8.0
7.5
7.5
7.0
7.0
6.5
6.5
6.0
6.0
5.5
5.5
5.0
5.0
4.5
4.5
4.0
4.0
12.0
11.5
11.0
10.5
10.0
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
Figure 10. Plots of 1H NMR spectra d-acetonitrile) (from the top) of: 6; 6 in the presence of triethylamine, both in the presence of triethylamine and lithium perchlorate and both in
the presence triethylamine and sodium perchlorate.
J¼4.2 Hz); 4.12–4.16 (2H, m); 4.33–4.40 (4H, m); 5.94 (1H, s); 7.05
(1H, s); 7.75 (1H, d, J¼9.8 Hz); 8.06–8.11 (2H, m); 12.56 (1H, s). IR
(Nujol) cmꢁ1: 3255, 1637, 1592, 1575, 1528, 1508, 1321, 1283, 1254,
1238, 1189, 1167, 1132, 1079, 937, 724 cmꢁ1. UV–vis (acetonitrile):
lmax¼451 nm, emax¼3.20ꢂ104. HRMS (EI) m/z: 429.1906 (calcd for
C22H27N3O6 429.1900).
4.2.6. Compound 6. 1H NMR (d-acetone): 0.87–0.94 (3H, m); 1.28–
1.42 (6H, m); 1,50–1.58 (2H, m); 2.42 (2H, d, J¼7.0 Hz); 3.80 (4H, s);
4.02 (2H, s); 4.09 (2H, s); 4.43 (2H, s); 4.53 (2H, s); 5.99 (1H, s); 7.07
(1H, s); 7.86 (1H, d, J¼8.7 Hz); 7.92 (1H, s); 8.00 (1H, d, J¼8.7 Hz);
11.61 (1H, s). IR (Nujol) cmꢁ1: 3300, 1636, 1591, 1573, 1524, 1502,
1335, 1271, 1236, 1217, 1168, 1124, 1093, 1040, 950, 900, 880, 720.
UV–vis (acetonitrile): lmax¼451 nm, emax¼3.65ꢂ104. HRMS (ESI)
m/z: 496.2047 [MþNa]þ (calcd for C24H31N3O7Na 496.2054).
L
A
Mg2+ Ca2+ Ca2+ Ca2+
Et3N
0,6
0,5
0,4
0,3
0,2
0,1
0,0
4.3. UV–vis studies
The stock solutions of azobenzocrowns (10ꢁ4 M) and metal
perchlorates (10ꢁ2 M) were prepared by weighing the respective
quantities of them and dissolving in 10 mL volumetric flasks in
acetonitrile. Series of working solutions of constant concentration
of ligand, to which triethylamine and salt solutions were added in
demanded amounts keeping total volume constant (3 mL). Spectra
of such prepared solutions were registered.
The stability constant of complex of compound 4 with lithium
cation was calculated with the use of OPIUM20 program on the basis
of titration experiment data.
"free" ligand
ligand + Et3N
ligand + Et3N + MgClO4
ligand + Et3N + CaClO4
400
500
600
700
Acknowledgements
[nm]
Figure 11. Changes in absorption spectra for compound 6 (CL¼17.5
mM) in the pres-
The authors kindly acknowledged support from sources for
science in years 2008–2010, Grant Nr. N N204 223834. The authors
also thank Prof. J.F. Biernat for manuscript valuable discussions and
ence of 500-fold excess of magnesium or calcium perchlorates and 140 equiv or
25 equiv of triethylamine, respectively, in acetonitrile. Inset: color changes of ligand 6
solution in the presence of triethylamine and metal perchlorates. For calcium addi-
tionally in the presence of 140 and 1400 equiv of triethylamine.
_
Mrs. J. Zochowska for technical assistance.

10678
E. Luboch et al. / Tetrahedron 65 (2009) 10671–10678
1992, 45, 311; (f) Misumi, S. Kagaku to Kogyo (Tokyo) 1993, 46, 756 C.A. 1993,
References and notes
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ˇ
20. Kyvala, M.; Lukes, I.: Program Package "OPIUM" Available (free of charge) on
http://www.natur.cuni.cz/wkyvala/opium.html.