Complex formation of pyridine-azacrown ether amide macrocycles with proton and heavy metal ions in aqueous solution

Article abstract of DOI:10.1002/poc.3526

This research concerns the analysis of the proton and metal ion binding of amide macrocycles of different structures and sizes by potentiometric, ¹H NMR and X-ray diffraction methods. Protonated ligands exist as a 3D network structures. The ligands form 1:1 complexes with heavy metal ions (Cu²⁺, Cd²⁺, Pb²⁺, Zn²⁺, and Ni²⁺) in aqueous solutions and demonstrate the high selectivity towards Cu²⁺ cations. The pyridine-2,6-dicarbamide fragment provides structural rigidity to crown ether, resulting the molecule has an open cavity and faster kinetics of metal complexes formation.

Full text of DOI:10.1002/poc.3526

Research article
Received: 19 May 2015,
Revised: 13 November 2015,
Accepted: 16 November 2015,
Published online in Wiley Online Library: 22 December 2015
(wileyonlinelibrary.com) DOI: 10.1002/poc.3526
Complex formation of pyridine-azacrown ether
amide macrocycles with proton and heavy
metal ions in aqueous solution
a,c
a,b
a
Yury Fedorov *, Olga Fedorova , Alexander Peregudov ,
c,d
c
a
Stepan Kalmykov , Bayirta Egorova , Dmitry Arkhipov ,
Anastasia Zubenko and Maxim Oshchepkov
a
a,b
This research concerns the analysis of the proton and metal ion binding of amide macrocycles of different structures and
1
sizes by potentiometric, H NMR and X-ray diffraction methods. Protonated ligands exist as a 3D network structures. The
2
+
2+
2+
2+
2+
ligands form 1:1 complexes with heavy metal ions (Cu , Cd , Pb , Zn , and Ni ) in aqueous solutions and
demonstrate the high selectivity towards Cu
2
+
cations. The pyridine-2,6-dicarbamide fragment provides structural
rigidity to crown ether, resulting the molecule has an open cavity and faster kinetics of metal complexes formation.
Copyright © 2015 John Wiley & Sons, Ltd.
Keywords: pyridine-azacrown ether compounds; complex formation; NMR-spectroscopy; potentiometric titration method; X-ray analysis
complex formation, we compare the obtained data for ligand 2
for those for ligand 1.
Polyazamacrocyclic ligands have been extensively investigated
INTRODUCTION
because of their ability to form complexes with different metal
ions or anionic species with considerable potential in such areas
RESULTS AND DISCUSSION
as catalysis, modeling of metalloenzyme, molecular recogni-
[
1–4]
tion.
Because most of the applications of macrocycles are as-
Amidopyridine macrocycles 2–4 (Scheme 1) have been prepared
by the modified method described previously.
[
6–8]
sociated with their ability to form complexes with ions, the main
goal in macrocyclic ligand design is to synthesize compounds
that are able to discriminate between ions. The metal ion selec-
tivity is influenced by the nature, arrangement of donor atoms
The proton-
ation constants of 1–4 and stability constants of its complexes
2+
2+
2+
2+
2+
2+
with Cu , Cd , Pb , Zn , Ni , and Fe were determined by
potentiometric methods. The values of the stability constants
for the metal complexes of 1–4 studied in this work, determined
in water, are compiled in Table 1.
[
5]
and also the ring size. There is at present a need for the inves-
tigation of selective coordination properties in novel systems
suitable for particular practical purposes.
Macrocycle 2 has one pyridine center for proton coordination;
the value of its protonation constant is low enough (log β = 1.9).
Ligand 1 showed the ability to coordinate three protons. Firstly,
This paper presents the synthesis of
a novel amide
1
macrocycles 1–4 (Scheme 1), the potentiometric, H- NMR, and
X-ray structural analysis and the binding properties towards tran-
sition and heavy metal cations. Taking into account the peculiar
structural characteristics of amide macrocycles, they may exhibit
a range of interesting and potentially useful molecular recogni-
*
Correspondence to: Yury Fedorov, A. N. Nesmeyanov Institute of
Organoelement Compounds of Russian Academy of Sciences, Vavilova, 28,
Moscow, 119991, GSP-1, Russia.
2+
tion properties. However, only one example concerning the Fe
complex of amide macrocycle has been reported earlier.
E-mail: fedorov@ineos.ac.ru
[6,7]
a Y. Fedorov, O. Fedorova, A. Peregudov, D. Arkhipov, A. Zubenko, M.
Oshchepkov
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy
of Sciences, Vavilova, 28, Moscow 119991, GSP-1, Russia
Amide macrocycles 2–4 can be easily prepared with high
yields by a reaction of the corresponding diamine and dimethyl
[
8]
pyridine-2,6-dicarboxylate. From a structural point of view,
these receptors derive from the α,ω-diamine containing oxygen
or nitrogen heteroatoms able for metal ion binding and pyridine
residue as additional coordination center. The presence of the
crown-ether moieties in the composition of receptors confers
them a certain degree of flexibility that is however limited by
the presence of a relatively rigid chelate subunit containing a
pyridine group. Due to synthetic availability amide macrocycles
are potentially applicable as ligand for heavy and transition
metal ions. The information on this topic has not been found be-
fore in literature. To study the role of amide group on the
b O. Fedorova, M. Oshchepkov
Mendeleev University of Chemistry and Technology of Russia, Miusskaya sqr.,
9., 125047, Moscow, Russia
c Y. Fedorov, S. Kalmykov, B. Egorova
Department of Chemistry, M. V. Lomonosov Moscow State University, Build. 3,
1
Leninskie Gory, 119991, Moscow, Russia
d S. Kalmykov
NRC “Kurchatov Institute”, Akademika Kurchatova sqr., 1, Moscow 123182,
Russia
J. Phys. Org. Chem. 2016, 29 244–250
Copyright © 2015 John Wiley & Sons, Ltd.

COMPLEX FORMATION OF PYRIDINE-AZACROWN ETHER AMIDE MACROCYCLES
This preorganization of the macrocycle positively effects
on the process of complexation with metal cations, because
there are no additional energy for conformational
macrocycle transformation before complex formation.
The size of macrocyclic cavity in 4 can be estimated
by the N…N distance measurements: N1…N4 5.525(3)
Ǻ, N2…N5 5.618(3) Ǻ, N3…N6 5.438(3) Ǻ, N3…N5
4
.840(3) Ǻ (Fig. 1(a)). Conformation of cycle 4 is shown
Scheme 1. Structures and numbering of the atoms of the compounds 1–4
in Fig. 1(b) along the median plane of the pyridine-2,6-
dicarbamide fragment; deviations of N atoms from the
plane are equal to: N3 0.319(4) Ǻ, N4 0.620(4) Ǻ, N5
À0.990(4) Ǻ.
the protonation of macrocyclic N atoms occurs with formation of
+
+
stable forms 1ÁH (log β = 9.25) and 1Á(H )
2
(log β = 17.00). The
third hydrogen atom coordinates with pyridine residue to form
The pyridine-2,6-dicarbamide fragment in 4 is nearly flat; tor-
sion angles N1–C1–C2–N2 and N1–C12–C11–N6 are equal to
+
1
Á(H )
3
(log β = 18.9).
[
6]
Ligands 3 and 4 have five and six basic centers, respectively,
1.7(3)° and 2.3(3)°, respectively (Fig. 1(b)). It is known , that this
fragment in Compound 3 is not planar (corresponding torsion
angles are equal to 11.87° and À9.19°, respectively). To analyze
this structural feature, quantum chemical calculations of isolated
molecules 3 and 4 were carried out (see detailed description in
the Supporting Information).
but only two constants have been determined by the potentio-
metric technique. Compounds 3 and 4 exhibit relatively high
value for the first protonation constant and moderate (in case
of 3) or fairly high (in case 4) values for the second. Based on
the observation described for ligands 1 and 2, we can suggest
that in Compounds 3 and 4 the protonation of aliphatic N atoms
only proceeds leading to the formation of species with high
enough stability (Table 1).
The pyridine-2,6-dicarbamide fragment in 3 is twisted
(corresponding torsion angles are equal to 4.69° and À6.49°),
while in 4 it is nearly planar (À0.17° and 0.99°). This fact could
be explained by the steric hindrance caused by the relatively
small size of the macrocyclic ring 3 compared with 4. It should
be noted that molecules 3 and 4 are more planar in the gas
phase compared with crystal. That distinction is caused by
the crystal packing effects. Geometrical parameters of
Single-crystals of 4, 3ÁHClO and 4Á(HClO ) suitable for X-ray
4
4 2
determination were grown from MeCN solutions at room tem-
perature (Figs 1–7 and S1 and quantum-chemical calculations
in the Supporting Information). The pyridine-2,6-dicarbamide
fragment is responsible for structural rigidity of crown ether,
thereby leading to open cavity.
[
6]
amide groups in structure 4 completely match those in 3
-3
Table 1. Protonation and stability constants (log β) of the complexes of 1–4 with divalent metal ions, 25.0°C, μ = 0.10 mol dm in
KNO3
Cation
R, nm
Species
log β
[
5]
1
2
3
4
+
3+
H
[L H
3
2
]
]
18.9 ± 0.1
17.00 ± 0.02
9.25 ± 0.02
—
—
—
—
2+
[
L H
11.8 ± 0.1
8.2 ± 0.1
À9.7 ± 0.2
À1.7 ± 0.2
5.5 ± 0.2
À4.0 ± 0.1
5.4 ± 0.2
8.8 ± 0.2
—
15.4 ± 0.6
8.6 ± 0.4
À13.4 ± 0.2
À1.7 ± 0.2
6.0 ± 0.1
À2.8 ± 0.9
5.7 ± 0.5
10.8 ± 0.6
15.4 ± 0.4
+
[
L H]
1.9 ± 0.08
2
+
a
a
Ni
0.069
0.073
[L Ni H ]
[ ]
[ ]
-
2
+
[
L Ni H ]
-1
2+
[
L Ni]
2
+
Cu
[L Cu H ]
—
—
—
—
—
-2
+
[
[
[
L Cu H ]
5.1 ± 0.1
12.98 ± 0.06
—
-1
2+
L Cu]
L Cu H]
3+
2
+
-
a
a
Zn
0.074
[L Zn H ]
L Zn H ]
[ ]
[ ]
À22.24 ± 0.07
À11.58 ± 0.07
À3.6 ± 0.1
-3
[
[
[
À11.9 ± 0.1
À3.5 ± 0.07
4.1 ± 0.2
-2
+
L Zn H ]
-1
2+
L Zn]
3.9 ± 0.1
2
+
a
a
a
Fe
0.078
0.095
[ ]
[ ]
[ ]
2
+
-
Cd
[L Cd H ]
L Cd H ]
—
—
—
—
—
—
—
—
—
—
À23.9 ± 0.2
À11.9 ± 0.1
À3.3 ± 0.1
3.6 ± 0.5
À13.2 ± 0.1
À2.12 ± 0.03
—
—
-3
[
[
[
À13.04 ± 0.08
À3.68 ± 0.07
4.2 ± 0.1
À13.5 ± 0.1
À2.77 ± 0.05
4.93 ± 0.06
-2
+
L Cd H ]
-1
2+
L Cd]
9.96 ± 0.04
À11.38 ± 0.07
0.26 ± 0.06
10.11 ± 0.04
2
+
Pb
0.119
[L Pb H-2
]
+
[
[
L Pb H-1]
2+
L Pb]
a
The formation of precipitates of hydroxyl complexes prevents the potentiometric analysis.
J. Phys. Org. Chem. 2016, 29 244–250
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/poc

Y. FEDOROV ET AL.
Figure 1. General view of 4, thermal ellipsoids are drawn at the 50%
probability level. MeCN molecule is omitted for clarity
(
1
C = O 1.225(3)À1.232(3) Å, C-N 1.333(3)À1.338(3) Å, Camide-СPy
.507(4)À1.515(4) Å).
The molecules of 4 form stacks by π…π interaction between
the pyridine-2,6-dicarbamide fragments (plane-to-plane distance
.330(4) Å) and N–H…N bonds (N3…N4 3.178(3) Å). Two adja-
3
cent stacks are organized in a herringbone manner (Fig. 2) due
to the C–H…O contacts (C14…O2 3.312(3) Å).
Figure 4. Macrocycle conformation in 3 · HClO
b) – at 120 K. View along the pyridine ring plane, hydrogens are omitted
for clarity
4
, (a) – at 293 K and
(
Recently, another polymorph of 3 · HClO at 293 K was de-
4
[9]
scribed. Unlike the published structure in which H-atom is dis-
tributed between two amine nitrogen atoms, in the crystal
structure of 3 · HClO4 at 120 K, the H-atom is localized at N3
The pyridine-2,6-dicarbamide fragment in 3 · HClO is strongly
4
(
Fig. 3). Comparison of macrocycle conformation in different
twisted (torsion angles N1–C1–C2–N2 and N1–C10–C9–N5 are
equal to 29.5(4)° and 23.2(4)°, respectively, Fig. 4(b)) due to
N–H…O bonding with perchlorate anions.
These interactions lead to cation–anion col-
umns (Fig. 5(a)), which are bound by the N–
H…O bonds and C–H…O contacts (Fig. 5(b)).
polymorphs of 3 · HClO is shown in Fig. 4.
4
Interaction between crown ether 4 and
perchloric acid results in diprotonated product
4
Á(HClO ) . In contrary to the solution, in the
4
2
crystal of 4Á(HClO
4 2
) at 120 К, the H-atoms are
localized at the N3 and N5 atoms (Fig. 6(a)).
The pyridine-2,6-dicarbamide fragment in 4
4 2
(HClO ) is slightly twisted; torsions N1–C1–
C2–N2 and N1–C12–C11–N6 are equal to 11.4
(
2)° and À13.8(2)°, respectively. The macrocycle
has folded conformation, angle between N6–
N1–N2 plane and N6–N5–N4–N3–N2 mean
plane equals to 140.14(7)°. The geometry of
amide groups is the same as for 4 and
· HClO . The large number of H-bonds in structure of 4Á
4 2
HClO ) forms a 3D network (Fig. 7).
Figure 2. Crystal packing of 4, MeCN molecules and hydrogens are omitted for clarity
3
4
(
Thus, the crystals show that in both compounds 3ÁHClO
4
and
4Á(HClO
4 2
)
pyridine N-atom is not involved into coordination
with proton. One or two protons seem to bond with donor
N-atoms of the ligands 3 and 4 similarly to what we suggested
from potentiometric data.
For the determination of complex formation constants,
solutions of perchlorates of various metals and ligands 1–4
with different concentrations of the components were titrated
with NaOH. The complex formation constants were calculated
[
10]
using Hyperquad software.
During the determination of
stability constant values, the protonation constants for
ligand 4 were fixed, and the formation constants of the hy-
droxy species were considered as known, and no attempts
were made to adjust their values. In the study of metal ion
Figure 3. General view of 3 · HClO
4
, thermal ellipsoids are drawn at the
50% probability level
wileyonlinelibrary.com/journal/poc
Copyright © 2015 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2016, 29 244–250

COMPLEX FORMATION OF PYRIDINE-AZACROWN ETHER AMIDE MACROCYCLES
complexation with ligands 1–4, the formation of hydroxy spe-
cies with limited solubility in water hamper equilibrium con-
2
+
2+
2+
stant determination. For Fe and ligands 1–4, Ni or Zn
and ligands 1, 2 a precipitate formation made impossible to
obtain reliable constants for the ML or ML(OH) species. The
potentiometric titration curves are presented in Figs S2–S27
in the Supporting Information. In all cases, hydroxy complexes
2
+
of different compositions are founded, while for Cu M(HL)
species are also obtained. All ligands form complexes ML, ex-
2
+
cept the case of ligand 3 interactions with Pb when only the
hydroxyl complexes are observed.
The values presented in Table 1 show that the complexes of
the divalent metal ions with ligands 3 and 4 are less stable rela-
tive to those for ligand 1. At the same time, the complex forma-
tion of ligand 2 with metal ions has not been determined. As
only pyridine can coordinate with cations, we can conclude that
it is not sufficient for ion’s binding. The introduction of amide
group into the macrocycles also decreases the ability of ligand
to coordinate cations.
2
+
2+
Within the series of studied metal ions Zn , Cd , and
Figure 5. Crystal packing of 3 · HClO
along the b-axis
4
: (a) – along the c-axis and (b) –
2+
Pb , the values of the stability constants are relatively close,
2+
while strong coordination was observed for Ni ; and in case
2
+
of Cu , the highest values of stability constants were found.
It is also important that increasing of the number of ali-
phatic N-atoms that are able to interact with cations from
two (in 3) to three (in 4) leads to remarkable increase of
complex stability.
1
13
2+
2+
The H and C NMR spectra of ligands 1–4 with Pb , Cd ,
+
and H in D O solution were collected and analyzed (Figs
2
S28–S48 and Table S2, S3 in the Supporting Information).
These complexes were chosen because they demonstrate
spectra of good quality for analysis. The spectra were assigned
1
1
on the basis of 2D H, H COSY, HMQC, and HMBC
experiments.
2+
Coordination of the Pb ions to 1 resulted in a downfield shift
of the aliphatic and pyridine protons as compared with the free
ligand (Fig. 8). This was most noticeable for H(1) and H(2), which
shifted from 7.79 and 7.33 ppm to 8.09 and 7.62 ppm, respec-
Figure 6. General view of 4Á(HClO
4 2
) , thermal ellipsoids are drawn at the 50%
probability level, second parts of disordered perchlorate anions are omitted for clarity
2+
tively in 1·Pb .
The signal H4/H4′ methylene
protons showed germinal cou-
pling, as a result of the protons
being in different chemical en-
vironments, as one of the
methylene protons was orien-
tated toward one of the other
ligands of the plane of the ring,
while the other pointed out
away from the plane of the
ring. The methylene protons H
(
4)/H(4′) yield an AB spin pat-
2
1
tern ( J4,4′ = 15.7 Hz) in the
H
NMR spectrum, while the pro-
tons of the crown moiety give
AA′BB′ spin patterns (Fig. 8).
This is indicative of a relatively
2
+
rigid structure of 1·Pb in solu-
tion, probably because of the
presence of bonding interac-
tions between the metal ion
and nitrogen and oxygen
atoms of the crown moiety.
Figure 7. Crystal packing of 4Á(HClO
4
)
2
, second parts of disordered perchlorate anions are omitted for clarity
J. Phys. Org. Chem. 2016, 29 244–250
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/poc

Y. FEDOROV ET AL.
CONCLUSIONS
These studies have revealed that am-
ide macrocycles behave as receptors
for heavy metal cations and demon-
2
+
strate the selectivity towards the Cu
2+
cations. The Cu selectivity of ligands
, 3, and 4 can be interpreted taking
1
into account the characteristics of the
different ligands 1, 2, and 3 here con-
sidered. Thus, small different in values
1
2+
2
Figure 8. H NMR spectra of 1 and 1·Pb in D O, 600 MHz
2+
of stability constants of Cu com-
Thus, the asymmetric position of the metal ion inside the
plexes with ligands 1, 2, and 3 points out on suitable size of li-
2+
macrocyclic cavity induces chirality in 1 (Scheme 2).
gands to coordinate a single Cu ion involving three or four
nitrogen donors. In case of ligand 1, these are the nitrogen
atoms of pyridine residue and two N-atoms of macrocyclic moi-
ety. Obviously, that in ligands 2 and 3 N-amide atoms do not par-
2+
Changes in NMR spectrum observed upon the addition of Cd
to 1 demonstrate the formation of two conformers of complex
2
+
1
·Cd in ratio 3:2 (Fig. S36 in the Supporting Information). The
1
111(113)
3
1
2+
values of couple constants between H and
Cd are J( H,
Cd) = 10.12 MHz. Similar to
Pb , the addition of Cd to ligand 1 causes the formation of
ticipate in coordination with Cu c2+ation. Similar to protonation,
1
11(113)
3
1
111(113)
Cd) = 7.92 MHz and J( H,
only macrocyclic N-atoms bind Cu .
2
+
2+
X-ray diffraction analysis and potentiometric data showed that
in macrocycles 3 and 4 the proton coordination occurs mainly
through the interaction with N-atoms of aliphatic fragments. Pro-
tonated ligands 3 and 4 form a 3D network structures. In oppo-
site, according NMR observation in water solution, metal ions
interact with N-pyridine heteroatom as well as with N-atoms of
aliphatic fragments of macrocycle.
2
+
chiral 1·Cd complex.
Changes in the positions of resonance signals induced by ad-
2
+
2+
dition of Pb and Cd to the solution of 3 and 4 clearly
showed the difference in structures between complexes of 3,
4
, and 1. According to Fig. 9, the most pronounce changes in
2+
3·Pb were observed for macrocyclic proton signals in 3;
2+
2+
whereas, the shifting of aromatic proton signals is not remark-
In case of ligand 1, the metal complexes with Pb and Cd
2
+
.
able (for 3·Cd Figs S39, S40 in the Supporting Information).
can function as chiral building units. Their stereoisomers in labile
metal complexes are generated as a racemate coexisting in wa-
ter solution. From our knowledge, this is the first example of
cation-induced chirality observed for azacrown ether ligands.
The example of divalent transition metal complexes with chiral
N,O chelate Schiff-bases and heterocyclic azine ligands were
2+
2+
Thus, the more strong coordination of Pb and Cd takes
place through the binding of metal cations with aliphatic
N-atoms of macrocycle of 3.
2+
Similar conclusion can be carried out for complexes 4·Pb
2
+
and 4·Cd
(Figs S45–S48 in the Supporting Information).
[
11–14]
Another difference between 1 and compounds 3, and 4 is that
in case of ligands 3 and 4 the metal induced chirality has not
been found.
early described.
In spite of forming less stable complexes than those of
[
15,16]
amine macrocyclic compounds containing pyridine,
am-
ide macrocyclic ligands demonstrate structural rigidity to
crown ether due to the presence of the pyridine-2,6-
dicarbamide fragment, resulting the molecule has an open
cavity and faster kinetics of formation of metal complexes.
Other advantages of some properties of amide macrocycles
are water solubility, easy synthetic, and purification proce-
dures. Amide macrocycles can be used as platforms to ob-
tain N-substituted lariat ligands. The introducing of
additional coordination groups will improve the binding
properties of the amide macrocycles.
2+
Scheme 2. Stereoisomers of 1·Pb
EXPERIMENTAL SECTION
Materials
Compound
,12,18-triazabicyclo[12.3.1]-octadeca-1
18),14,16- triene (1) was prepared as
3,12-dimethyl-6,9-dioxa-
3
(
[
17]
described earlier.
Analytical grade
Cd(ClO · H O,Pb
·6H O, Ni(ClO
O and HClO 70%
aqueous solution (Aldrich), KNO
Cu(ClO
ClO ·3H
·6H O, Fe(ClO
4
)
2
· 6H
O, Zn(ClO
·H
2
O,
4
)
2
2
(
4
)
2
2
4
)
2
2
4
)
2
2
4
)
2
2
4
3
,
NaOH (Chimmed, Russia) were used
as received. All reagents and solvents
were purchased from commercially
1
2+
Figure 9. H NMR spectra of 3 and 3ÁPb in D
2
O, 600 MHz
wileyonlinelibrary.com/journal/poc
Copyright © 2015 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2016, 29 244–250

COMPLEX FORMATION OF PYRIDINE-AZACROWN ETHER AMIDE MACROCYCLES
À1
available sources and used as received.
Electrospray mass spectrometry was performed on a Finnigan
LTQ instrument.
(%): С, 56.23; Н, 7.55; N, 26.23. IR (KBr), n /cm : 3423 (NH),
2811 (СН); 1668 (С = О); 1531 (CNH), 1442 (СН-Py).
The IR spectra were recorded on a Frontier (Perkin Elmer)
spectrometer using the KBr tablet method at 20 ± 1°C.
Melting points were determined on a «Mel-temp II».
All reactions were monitored for completion by thin layer
chromatography performed on silica gel plates DC-Alufolien
Standard solutions
Approximately 0.1 M stock solutions of all metal perchlorates
were prepared in deionized water (18.2 MΩ). Cu(ClO
Cd(ClO ·H O, Pb(ClO ·3H O, Zn(ClO ·6H O, Ni(ClO
Fe(ClO · H O solutions were standardized by complexometric
titration with EDTA and using xylenol orange as indicator.
4
)
4
)
2
· 6H
·6H
2
O,
2
O,
4
)
2
2
4
)
2
2
4
)
2
2
2
4
)
2
2
Kieselgel 60 F254
.
[
19]
A carbonate-free solution of the titrant, NaOH (≈0.1 M), was
prepared with deionized water that was boiled and purged with
General procedure for the synthesis of macrocyclic amides
Compounds 2–4 were synthesized following the modified litera-
ture procedures.
argon while cooling to ensure removal of CO . This solution was
standardized potentiometrically with potassium hydrogen-
2
[18]
phthalate dried at 120°C using the Gran’s method and computer
[
20]
program GLEE
Standard HClO solution was prepared similarly by diluting the
7
for the evaluation of the titration end point.
Method А
4
A solution of dimethyl pyridine-2,6-dicarboxylate (0.51 mmol) in
ml of anhydrous methanol and a solution of α,ω-diamine
0.51 mmol) in 5 ml of anhydrous methanol were simultaneously
0% product and was standardized with the NaOH described
previously. Stock ligand solutions (≈0.01 M) were prepared using
deionized water.
5
(
added dropwise to a solution of 5 ml of methanol containing
sodium or potassium carbonate (2.25 mmol) upon intensive stir-
ring for 40 min. The reaction mixture was kept under stirring at
room temperature for 7 days. The solvent was evaporated in
vacuum, and the residue was dissolved in water and extracted
with chloroform (3 × 20 ml). The organic solvent was removed
in vacuum to obtain the final product after recrystallization
from acetonitrile.
Potentiometric equipment and measurements
All potentiometric titrations were made with a Titrando 808
autotitrator equipped with a Cole Parmer combined hydrogen
electrode (model 60061) and water jacketed titration vessel
maintained at 25.0 ± 0.1°C with a Cole-Parmer circulating bath.
The combined hydrogen electrode was calibrated as
hydrogen-ion concentration probe by titration of previously
standardized amounts of HClO with CO -free NaOH solution
and determining the equivalent point by the Gran’s method
a
Method B
4
2
Synthesis was carried out in the same manner without the addi-
tion of sodium carbonate (or potassium carbonate). The product
can be isolated by the following ways: after the completion of
the reaction, the solvent was evaporated in vacuum, and the res-
idue was dissolved in water and extracted with chloroform
[20]
using the program GLEE,
which gives the standard elec-
0
trode potential, E , and the slope, s. The ionic product of water
pKw = 13.78 at 25.0°C in 0.1 mol/dm KNO3
3
[21]
was kept
constant.
The potentiometric equilibrium measurements were per-
(
3 × 20 ml); the organic solvent was removed in vacuum to ob-
tain the final product after recrystallization from acetonitrile.
,9-Dioxa-3,12,18-triazabicyclo[12.3.1]octadeca-1(18),14,16-tri-
formed in 20 ml of ligands 1–4 solutions initially between
3
0
.001–0.002 and HClO 0.005–0.009 mol/dm , first in the absence
4
6
of metal ions and then in the presence of the metal ions for
which [L]:[M+] ratios vary between 1.3:1 and 2: 1. Titration solu-
tions were magnetically stirred and thermostatted at 25.0 ± 0.1°C
in a water-jacketed vessel. The ionic strength of the solutions in
ene-2,13-dione (2) was obtained as white crystals. The yield was
о
[8]1
7
7% (Method A). Mp is 175–180 С.
о
H-NMR (400 MHz, СDCl
3
, 25 C): 3.64 (q, 4Н, Н(5), J = 5.0), 3.72
(
8
t, 4Н, Н(6), J = 5.0), 3.74 (s, 4Н, Н(7)), 8.02 (t, 1Н, Н(1), J = 7.9),
.24 (d, 2Н, Н(2), J = 7.9), 8.83 (br.s, 2Н, CONH).
,6,9,12,18-Pentaazabicyclo[12.3.1]octadeca-1(18),14,16-tri-
3
the cell was adjusted to 0.1mol/dm with KNO3. The
electromotive force values were measured after addition of
3
0.0100ml increments of standard NaOH solution. Data were col-
ene-2,13-dione (3) was obtained as white crystals. The yield
lected in the pH range 2.5–10.5. A minimum of two replicates
were performed.
The protonation constants of the ligands 1–4 and the stability
constants of the complexes were calculated from the
о
[7,9]1
was 74% (Method B). Mp is 211–213 С.
о
H-NMR (400 MHz, СDCl
3
, 25 C): 2.84 (s, 4Н. Н(7)), 2.95 (t, 4Н,
Н(6), J = 5.3), 3.5 (q, 4Н, Н(5), J = 5.3), 8.0 (t, 1Н, Н(1), J = 7.6),
1
3
8
(
(
.23 (d, 2Н, Н(2), J = 7.6), 9.11 (br.s, 2Н, CONH). C-NMR
[10]
electromotive force titration data with the Hyperquad program.
о
400 MHz, СDCl
2-С), 139.5 (1-С), 148.9 (3-С), 163.3 (4-С).
,6,9,12,15,21-Hexaazabicyclo[15.3.1]henicosa-1(21),17,19-tri-
ene-2,16-dione (4) was obtained as white crystals. The yield was
3
, 25 C): 39.3 (5-С), 47.9 (6-С), 50.0 (7-С), 124.1
NMR spectroscopy
3
1
13
H NMR, C NMR spectra were measured on a Bruker DRX-400
о
6
2% (Method B). Mp 140–142 С.
and Bruker DRX-600 NMR spectrometers and referenced to the
1
о
1
H-NMR (400 MHz, СDCl , 25 C): 2.76 (m, 4Н,.Н(8), J = 5.2), 2.26
residual solvent peak ( H δ(CHCl ) = 7.27 ppm, δ(D O) =
3
3
2
13
(t, 4Н, Н(7), J = 5.2), 2.90 (t, 4Н, Н(6)), J = 5.2), 3.63 (q, 4Н, Н(5)),
4.75 ppm) or to the solvent peak ( C δ(CDCl ) = 77.2 ppm). Pro-
3
J = 5.2), 7.99 (t, 1Н, Н(1), J = 7.8), 8.34 (d, 2Н, Н(2), J = 7.8), 8.69
ton signal assignments were made by first-order analysis of the
spectra and analysis of 2D 1H-1H correlation maps (COSY). The
spectra were assigned on the basis of 2D H- H COSY, HMQC,
and HMBC experiments.
The solution of azacrown ether ligands 1–4 (10.7 mmol) in 3 ml
D O was mixed with a solution of lead perchlorate, cadmium
2
1
3
о
(
br.t, 2Н, CONH). C-NMR (400 MHz, СDCl , 25 C): 38.7 (5-С),
3
1
1
4
9.0 (6-С), 49.7 (7-С), 50.4 (8-С), 124.9 (2-С), 138.7 (1-С), 149.0
3-С). 163.5 (4-С).
Electrospray ionization mass spectrometry, m/z: 321.5 [MH] .
Found (%): С, 56.21; Н, 7.57, N, 26.20. С Н N O . Calculated
(
+
15
24
6
2
J. Phys. Org. Chem. 2016, 29 244–250
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/poc

Y. FEDOROV ET AL.
perchlorate or perchloric acid (10.7 mmol) in 3 ml D O. The
[5] O. Fedorova, Y. Fedorov, M. Oshchepkov, M. Dobrovolskaya, J Phys
Org Chem. 2012, 25, 835–839.
2
resulting aqueous solution of the complex was analyzed by
NMR spectroscopy. Assignment of the signals was carried out
[
[
[
[
6] I. V. Korendovych, R. J. Staples, W. M. Reiff, E. V. Rybak-Akimova,
Inorg Chem. 2004, 43, 3930–3941.
7] I. V. Korendovych, M. Cho, P. L. Butler, R. J. Staples, E. V. Rybak-
Akimova, Org Lett. 2006, 8, 3171–3174.
1
1
using two-dimensional spectra of H- H COSY (Figs S35, S44,
and S46 in the Supporting Information).
8] D. Grykoa, D. T. Grykoa, H. Sierzputowska-Gracz, P. Pia Аtekc,
J. Jurczak, Helv Chim Acta. 2004, 87, 156–166.
9] I. V. Korendovych, M. Cho, O. V. Makhlynets, P. L. Butler, R. J. Staples,
E. V. Rybak-Akimova, J Org Chem. 2008, 73, 4771–4782.
Single crystal X-ray studies
All crystals were obtained by recrystallization from acetonitrile.
[
10] P. Gans, A. Sabatini, A. Vacca, Talanta. 1996, 43, 1739–1753.
[11] A. A. Mohamed, G. S. Masaret, A. H. M. Elwahy, Tetrahedron. 2007,
63, 4000–4010.
12] H. Miyake, Symmetry. 2014, 6, 880–895.
Recrystallization of 3 led to the crystals with the known unit cell
[6]
parameters. X-ray diffraction measurements were carried out
using Bruker APEX II CCD diffractometer at 120 K. The frames
were integrated and corrected for absorption by the APEX2 pro-
[
[
13] J.-M. Suk, V. R. Naidu, X. Liu, M. S. Lah, K.-S. Jeong, J Am Chem Soc.
2
011, 133, 13938–13941.
[22]
gram package. The details of crystallographic data and exper-
imental conditions are given in Table S1. The structures were
solved by the direct methods and refined by full-matrix
[
14] M. Enamullah, A. K. M. R. Uddin, G. Pescitelli, R. Berardozzi, G. Makhloufi,
V. Vasylyeva, A.-C. Chamayoud, C. Janiak, Dalton Trans. 2014, 43,
3313–3329.
2
[15] A. S. Fernandes, M. F. Cabral, J. Costa, M. Castro, R. Delgado, M. G. B. Drew,
V. Felix, Inorg Biochem. 2011, 105, 410–419.
16] B. Draho, J. Kotek, P. Hermann, I. Luke, Eva Toth. Inorg Chem. 2010,
least-squares technique against F in the anisotropic-isotropic
approximation. Hydrogen atoms were located from the
difference Fourier maps and refined in rigid body model; the
H(N) atoms were refined freely. All calculations were performed
[
49, 3224–3238.
[17] O. Fedorova, Y. Fedorov, M. Oshchepkov, J Electroanalysis. 2012, 8,
739–1744.
[
23]
[24]
1
using the SHELX-2014
Crystallographic data for the structural analysis of 4, 3ÁHClO
have been deposited with the Cambridge
and Olex2
program packages.
[
18] B. H. Northrop, F. Aric, N. Tangchiavang, J. D. Badji, J. F. Stoddart, Org
4
Lett. 2006, 8, 3899–3902.
19] R. Pribil, Analytical Applications of EDTA and Related Compounds,
Pergamon Press, Oxford, New York, Toronto, Sydney, Braunschweig,
and 4Á(HClO
4 2
)
[
Crystallographic Data Centre, CCDC Nos. 1040937-1040939.
1
972.
[
[
20] P. Gans, B. O`Sullivan. Talanta. 2000, 51, 33–37.
21] R. F. Jameson, M. F. Wilson, J Chem Soc Dalton Trans. 1972, 23,
Quantum chemical calculations
2
607–2610.
Computational studies were carried out using the Gaussian09
[
22] APEX2 software package, Bruker AXS Inc., 5465, East Cheryl Park-
[25]
program.
The structures of isolated molecules 3 and 4 were
way, Madison, WI 5317, 2005.
optimized using PBE0/6-311G(d,p) method/basis set with subse-
quent calculation of Hessian matrix. Optimized geometries of 3
and 4 are given in the Supporting Information.
[23] G. M. Sheldrick, Acta Cryst. 2008, A64, 112–122.
[
24] O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard, H. Puschmann,
J Appl Cryst. 2009, 42, 339–341.
[
25] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb,
J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson,
H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino,
G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda,
J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai,
T. Vreven, J. A. Montgomery Jr. , J. E. Peralta, F. Ogliaro, M. Bearpark,
J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi,
J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar,
J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross,
V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,
O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin,
K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg,
S. Dapprich, A. D. Daniels, Ö. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski,
D. J. Fox, Gaussian 09, Revision B.01Gaussian, Inc., Wallingford CT, 2010.
Acknowledgements
The authors thank the financial support from RFBR for S. K. (com-
plex formation study), A. P. , and M. O. grant nos. 13-03-01304,
1
5-03-04695, and 14-03-31932 (synthesis of the crown ether li-
gands) for financial support.
REFERENCES
[
[
[
[
1] J. S. Bradshaw, K. E. Krakowiak, R. M. Izatt, Aza-Crown
MacrocyclesWiley, New York, 1993.
2] K. E. Krakowiak, J. S. Bradshaw, D. J. Zamecka-Krakowiak, Chem Rev.
1
989, 89, 929–972.
3] K. B. Mertes, J. M. Lehn, in: Comprehensive Coordination Chemistry
Eds: G. Wilkinson ), , Pergamon, Oxford, 1987.
SUPPORTING INFORMATION
(
Additional supporting information can be found in the online
4] R. M. Izatt, J. S. Bradshaw, S. A. Nielson, J. D. Lamb, J. J. Christensen,
Chem Rev. 1985, 85, 271–339.
version of this article at the publisher’s website.
wileyonlinelibrary.com/journal/poc
Copyright © 2015 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2016, 29 244–250