Nitro derivatives of N-alkylbenzoaza-15-crown-5: Synthesis, structures, and complexation with metal and ammonium cations

Article abstract of DOI:10.1007/s11172-010-0222-0

A number of N-alkylnitrobenzoaza-15-crown-5 with the macrocycle N atom conjugated with the benzene ring were obtained. The structural and complexing properties of these compounds were compared with those of model nitrobenzo- and N-(4-nitrophenyl)aza-15-cr

Full text of DOI:10.1007/s11172-010-0222-0

Russian Chemical Bulletin, International Edition, Vol. 59, No. 6, pp. 1192—1206, June, 2010
1192
Nitro derivatives of Nꢀalkylbenzoazaꢀ15ꢀcrownꢀ5:
synthesis, structures, and complexation with metal and ammonium cations*
S. N. Dmitrieva,a M. V. Churakova,a N. A. Kurchavov,a A. I. Vedernikov,a L. G. Kuz´mina,b
A. Ya. Freidzon,a A. A. Bagatur´yants,a Yu. A. Strelenko,c J. A. K. Howard,d and S. P. Gromova
aPhotochemistry Center, Russian Academy of Sciences,
7A ul. Novatorov, 119421 Moscow, Russian Federation.
Fax: +7 (495) 936 1255. Eꢀmail: spgromov@mail.ru, gromov@photonics.ru
bN. S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences,
31 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 954 1279
cN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328
dDepartment of Chemistry, University of Durham,
South Road, Durham DH1 3LE, the United Kingdom.
A number of Nꢀalkylnitrobenzoazaꢀ15ꢀcrownꢀ5 with the macrocycle N atom conjugated
with the benzene ring were obtained. The structural and complexing properties of these comꢀ
pounds were compared with those of model nitrobenzoꢀ and Nꢀ(4ꢀnitrophenyl)azaꢀ15ꢀcrownꢀ5
using Xꢀray diffraction, 1H NMR spectroscopy, and DFT calculations. The macrocyꢀ
clic N atom of benzoazacrown ethers are characterized by a considerable contribution
of the sp3ꢀhybridized state and a pronounced pyramidal geometry; the crownlike conformaꢀ
tion of the macrocycle is preorganized for cation binding, which facilitates complexation.
The stability constants of the complexes of crown ethers with the NH4+, EtNH3+, Na+, K+,
Ca2+, and Ba2+ ions were determined by 1H NMR titration in MeCNꢀd3. The most staꢀ
ble complexes were obtained with alkalineꢀearth metal cations, which is due to the higher
charge density at these cations. The characteristics of the complexing ability of Nꢀalkylꢀ
nitrobenzoazaꢀ15ꢀcrownꢀ5 toward alkaline earth metal cations are comparable with analoꢀ
gous characteristics of nitrobenzoꢀ15ꢀcrownꢀ5 and are much better than those of
Nꢀ(4ꢀnitrophenyl)azaꢀ15ꢀcrownꢀ5.
Key words: benzoazacrown ethers, synthesis, structures, complexation, metal cations, amꢀ
1
monium ions, stability constants, Xꢀray diffraction analysis, H NMR spectroscopy, quantum
chemical calculations, density functional theory.
The most important property of crown compounds
is their ability to form stable complexes with metal
ions, organic cations, and neutral polar molecules.
Because of this ability, crown compounds are employed
as selective ligands for metal cations (also in extraction
processes), ionꢀselective electrodes, photosensitive
systems, etc.
The synthesis of azacrown compounds with various
combinations of the N and O atoms in the macrocycle is
still of relentless interest.1—3 Of particular interest from
the viewpoint of using azacrown fragments as part of phoꢀ
tosensitive ligands are those in which the N atom is conjuꢀ
gated with a chromophore. Such azacrown compounds
absorb at much longer wavelengths than crown ether deꢀ
rivatives, which is essential in photometric and fluoresꢀ
cence analyses, photocontrolled extraction, photoconꢀ
trolled ion transportation across membranes, as well as for
the design of photosensitive molecular devices. At present,
substituted phenylazacrown ethers are most commonly
used for these purposes; however, they have an essential
drawback: their constants of complexation with metal ions
are low. In this respect, benzoannulated derivatives of azaꢀ
crown ethers can enjoy considerable advantages. Despite
their simple structures, 1ꢀazaꢀ2,3ꢀbenzocrown ethers are
poorly studied because most of their functional derivatives
are scarcely accessible.3 Earlier,4 we have obtained formyl
and nitro derivatives of Nꢀmethylbenzoazacrown comꢀ
pounds by stepwise transformation of the macrocycles of
benzocrown ethers. This new strategy of the synthesis of
functionalized azacrown ethers seems to be a promising
* Dedicated to Academician I. L. Eremenko on his 60th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1167—1181, June, 2010.
1066ꢀ5285/10/5906ꢀ1192 © 2010 Springer Science+Business Media, Inc.

NꢀAlkylnitrobenzoazaꢀ15ꢀcrownꢀ5
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
1193
alternative to the currently existing routes to 1ꢀazaꢀ2,3ꢀ
benzocrown ethers.4
amines containing hydrocarbon radicals with different
lengths and branching degrees. The resulting nitrogenꢀ
containing podands have been employed for the synthesis
of Nꢀmethylbenzoazacrown ethers (e.g., 1a) in which the
macrocycle N atom is conjugated with the benzene ring.7—9
Here we extended this approach to the synthesis of
Nꢀalkylnitrobenzoazaꢀ15ꢀcrownꢀ5 1 (Scheme 1).
In the present work, we obtained Nꢀalkylnitrobenꢀ
zoazacrown ethers 1b—d and compared the structural and
complexing characteristics of azacrown ethers 1a—d and
the model compounds nitrobenzoꢀ (2) and Nꢀ(4ꢀnitroꢀ
phenyl)azaꢀ15ꢀcrownꢀ5 (3) using Xꢀray diffraction,
1H NMR spectroscopy, and DFT calculations. The staꢀ
bility constants of complexes of these crown ethers with
alkali metal, alkalineꢀearth metal, and ammonium ions
were determined using 1H NMR titration.
By heating nitrobenzocrown ether 2 with alcoholic soꢀ
lutions of alkylamines according to a modified procedure,6
we obtained nitrogenꢀcontaining podands 4b—f. The presꢀ
ence of the secondary amino group and the terminal hydrꢀ
oxy group in their molecules allows intramolecular cyꢀ
clization into previously unknown Nꢀalkylnitrobenzoazaꢀ
crown ethers. For successful cyclization of azapodands
4b—f into benzoazacrown ethers, first we should modify
their hydroxy group by exchanging it for a good leaving
group. To do this, we treated podands 4b—f with SOCl2
in the presence of pyridine to give chlorides 5b—f in
88—94% yields. Then the Cl atom in compounds 5b—f
was replaced by an iodine atom; the yields of iodides 6b—f
were 88—98%. Cyclization of the latter under the action
of NaH produced the target Nꢀalkylnitrobenzoazacrown
ethers 1. The yields of azacrown ethers 1b—f are given in
Table 1. For comparison, the yield of Nꢀmethylbenzoazaꢀ
crown ether 1a obtained earlier9 is also included. The vinyl
ethers, which are formed via HI elimination9 as byꢀprodꢀ
ucts in the cyclization of the iodides, were not isolated in
this work.
1: R = Me (a), Et (b), Pr (c), CH2Ph (d)
We found that an increase in the length and bulkiness
of the substituent at the N atom of iodineꢀcontaining poꢀ
dands 6 lowers the yields of benzoazacrown ethers 1 and,
on the whole, increases the cyclization time of iodides 6.
For instance, the maximum yield (53%) was achieved for
Results and Discussion
Synthesis of nitrobenzoazacrown ethers. Earlier,5,6 we
have found that nitrobenzocrown ethers undergo nucleoꢀ
philic opening of the macrocycle in the presence of alkylꢀ
Scheme 1
R = Me (a), Et (b), Pr (c), PhCH2 (d), Pri (e), PhMeCH (f)

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Dmitrieva et al.
Table 1. Conditions for the cyclization of iodides 6a—f
under the action of NaH in THF and the yields of the
corresponding nitrobenzoazacrown ethers 1a—f
Table 2. Yields and highꢀresolution mass spectra of
compounds 1b—d, 5b—f, and 6b—f
Comꢀ Yield
pound (%)
[M]+, m/z
Found
Molecular
formula
Iodide
R
t/h
T/°C Yield of 1 (%)
Calculated
6a
Me
0.5
2.5
10
2.5
125
8
95
17
170
70
64
25
64
64
25
64
25
64
25
25
80
74
53
48
44
46
41
0
1ba
1c
1d
5b
5c
5d
5e
5f
53
48
46
94
92
94
91
88
98
95
95
92
88
340.1628
340.1635
354.1783
354.1791
402.1787
402.1791
376.1403
376.1401b
390.1550
390.1557b
438.1550
438.1557b
390.1550
390.1557b
452.1718
452.1714b
468.0755
468.0757
482.0912
482.0914
530.0919
530.0914
482.0913
482.0914
544.1070
544.1071
C16H24N2O6
C17H26N2O6
C21H26N2O6
C16H25ClN2O6
C17H27ClN2O6
C21H27ClN2O6
C17H27ClN2O6
C22H29ClN2O6
C16H25IN2O6
C17H27IN2O6
C21H27IN2O6
C17H27IN2O6
C22H29IN2O6
6b
6c
Et
Pr
6d
6e
6f
PhCH2
Pri
0
0
PhMeCH
Note. t is the reaction time; T is the temperature.
Nꢀethylnitrobenzoazacrown ether 1b, which is much lowꢀ
er than the yield of Nꢀmethylnitrobenzoazacrown ether 1a
(80%). The yields of nitrobenzoazacrown ethers 1b—d with
the substituents Et, Pr, and CH2Ph differ insignificantly
(53, 48, and 46%, respectively). Podands 6e,f containing
the bulkiest substituents (isopropyl and αꢀphenylethyl) at
the N atom did not undergo cyclization into products 1e,f.
The cyclization at room temperature results in slightly
lower yields of the target nitrobenzoazacrown ethers 1
compared to the cyclization in boiling THF, the reaction
time being substantially longer (TLC).
Apparently, the mechanism of the cyclization of iodꢀ
ides 6 into nitrobenzoazacrown ethers 1 can be described
as follows: a strong base such as NaH abstracts the proton
from iodide 6 to form reactive arylamide anion 7, which
undergoes cyclization into the final product unless a bulky
Nꢀsubstituent presents considerable steric hindrances at
the reactive site (Scheme 2).
Model Nꢀ(4ꢀnitrophenyl)azaꢀ15ꢀcrownꢀ5 3 was obtained
in 86% yield by a reaction of azaꢀ15ꢀcrownꢀ5 with an
excess of 1ꢀfluoroꢀ4ꢀnitrobenzene in the presence of
triethylamine according to a modified procedure.10
The structures of the compounds obtained were deterꢀ
mined by 1H and 13C NMR spectroscopy, IR spectroꢀ
scopy, and mass spectrometry (including highꢀresolution
mass spectrometry) and confirmed by elemental analysis
data (Tables 2—4).
6b
6c
6d
6e
6f
a Found (%): C, 56.41; H, 7.21; N, 8.19. C16H24N2O6.
Calculated (%): C, 56.46; H, 7.11; N, 8.23.
b For the ion with 35Cl.
Xꢀray diffraction study. Single crystals of model crown
ethers 2 and 3 and a complex of benzoazacrown ether 1a
with barium perchlorate were studied; the structures of
these compounds are shown in Fig. 1. The structure of free
azacrown ether 1a has been examined earlier.9 In the
present work, we compared the conformational features of
these compounds; for convenience, we used the same numꢀ
bering of atoms in the benzocrown ether system that is
different from the IUPAC rules. It is worth noting that the
crystal structure of compound 2 has been loosely deterꢀ
Scheme 2

NꢀAlkylnitrobenzoazaꢀ15ꢀcrownꢀ5
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
1195
Table 3. IR and 1H NMR spectra of compounds 1b—d, 5b—f, and 6b—f
Comꢀ
pound
IR (KBr),
ν/cm–1
1H NMR (CDCl3),
δ (J/Hz)
1b
1c
1d
5b
5c
5d
1498 (NO2)
1510 (NO2)
1494 (NO2)
1.20 (t, 3 H, Me, J = 7.1); 3.41 (q, 2 H, CH2N, J = 7.1); 3.56 (t, 2 H, NCH2CH2O, J = 7.0);
3.68, 3.71 (both m, 4 H each, 4 CH2O); 3.87 (t, 2 H, NCH2CH2O, J = 7.0); 3.93 (m, 2 H,
CH2CH2OAr); 4.20 (m, 2 H, CH2OAr); 6.73 (d, 1 H, H(14), J = 9.2); 7.65 (d, 1 H, H(17),
J = 2.5); 7.80 (dd, 1 H, H(15), J = 9.2, J = 2.5)
0.91 (t, 3 H, Ме, J = 7.3); 1.61 (m, 2 H, CH2); 3.30 (t, 2 H, CH2N, J = 7.6); 3.56 (t, 2 H,
NCH2CH2O, J = 7.2); 3.67, 3.70 (both s, 4 H each, 4 CH2O); 3.86 (t, 2 H, NCH2CH2O, J = 7.2);
3.92 (m, 2 H, CH2CH2OAr); 4.20 (m, 2 H, CH2OAr); 6.70 (d, 1 H, H(14), J = 8.6); 7.65 (d, 1 H,
H(17), J = 1.9); 7.79 (dd, 1 H, H(15), J = 8.9, J = 1.9)
3.65 (t, 2 H, NCH2CH2O, J = 6.9); 3.67, 3.74 (both m, 4 H each, 4 CH2O); 3.97 (t, 2 H, NCH2CH2O,
J = 6.9); 3.98 (m, 2 H, 2 CH2CH2OAr); 4.27 (m, 2 H, CH2OAr); 4.64 (s, 2 H, NCH2Ph); 6.66 (d,
1 H, H(14), J = 9.2); 7.23 (m, 3 H, H(2´), H(4´), H(6´)); 7.31 (m, 2 H, H(3´), H(5´)); 7.69 (d, 1 H,
H(17), J = 2.3); 7.71 (dd, 1 H, H(15), J = 9.2, J = 2.3)
3414 (NH);
1497 (NO2)
1.31 (t, 3 H, Me, J = 7.4); 3.28 (q, 2 H, CH2N, J = 7.3); 3.61 (t, 2 H, CH2Cl, J = 5.8); 3.66
(s, 4 H, 2 CH2O); 3.70 (m, 4 H, 2 CH2O); 3.74 (t, 2 H, CH2CH2Сl, J = 5.8); 3.88 (m, 2 H,
CH2CH2OAr); 4.22 (m, 2 H, CH2OAr); 5.18 (br.s, 1 H, NH); 6.48 (d, 1 H, H(6), J = 8.9);
7.65 (d, 1 H, H(3), J = 2.4); 7.89 (dd, 1 H, H(5), J = 8.9, J = 2.5)
3413 (NH);
1497 (NO2)
1.02 (t, 3 H, Me, J = 7.4); 1.70 (m, 2 H, CH2); 3.20 (t, 2 H, CH2N, J = 7.1); 3.61 (t, 2 H,
CH2Cl, J = 5.9); 3.66, 3.70 (both m, 4 H each, 4 CH2O); 3.74 (t, 2 H, CH2CH2Сl, J = 5.9); 3.88
(m, 2 H, CH2CH2OAr); 4.22 (m, 2 H, CH2OAr); 5.24 (br.s, 1 H, NH); 6.48 (d, 1 H, H(6),
J = 9.1); 7.65 (d, 1 H, H(3), J = 2.1); 7.89 (dd, 1 H, H(5), J = 9.1, J = 2.1)
3410 (NH,
OH); 1494
(NO2)
3.59 (t, 2 H, CH2Cl, J = 5.8); 3.63 (s, 4 H, 2 CH2O); 3.66, 3.69 (both m, 2 H each, 2 CH2O);
3.72 (t, 2 H, CH2CH2Cl, J = 5.8); 3.89 (m, 2 H, CH2CH2OAr); 4.26 (m, 2 H, CH2OAr);
4.48 (br.s, 2 H, NCH2Ph); 6.47 (d, 1 H, H(6), J = 8.9); 7.26 (m, 1 H, H(4´)); 7.31—7.38
(m, 4 H, H(2´), H(3´), H(5´), H(6´)); 7.69 (d, 1 H, H(3), J = 2.4); 7.84 (dd, 1 H, H(5),
J = 8.9, J = 2.4)
5e
5f
3400 (NH);
1497 (NO2)
1.20 (d, 6 H, 2 Me, J = 6.7); 3.56 (m, 2 H, CH2Cl, J = 5.8); 3.61 (s, 4 H, 2 CH2O); 3.64
(m, 7 H, 3 CH2O, CHN); 3.82 (m, 2 H, CH2CH2OAr); 4.15 (m, 2 H, CH2OAr); 6.42
(d, 1 H, H(6), J = 8.8); 7.57 (d, 1 H, H(3), J = 2.5); 7.80 (dd, 1 H, H(5), J = 8.8, J = 2.5)
3409 (NH);
1498 (NO2)
1.61 (d, 3 H, Me, J = 7.0); 3.61 (t, 2 H, CH2Cl, J = 5.9); 3.66 (m, 4 H, CH2O); 3.69—3.76
(m, 6 H, 3 CH2O); 3.94 (m, 2 H, CH2CH2OAr); 4.27 (m, 2 H, CH2OAr); 4.60 (q, 1 H, CHN,
J = 7.0); 6.30 (d, 1 H, H(3), J = 8.8); 7.26 (m, 1 H, H(4´)); 7.30—7.35 (m, 4 H, H(2´), H(3´),
H(5´), H(6´)); 7.67 (d, 1 H, H(6), J = 2.1); 7.71 (dd, 1 H, H(4), J = 8.8, J = 2.1)
6b
6c
6d
3401 (NH);
1496 (NO2)
1.28 (t, 3 H, Ме, J = 7.0); 3.24 (t, 2 H, CH2I, J = 7.0); 3.28 (q, 2 H, CH2N, J = 7.0); 3.65
(s, 4 H, 2 CH2O); 3.70 (m, 4 H, 2 CH2O); 3.73 (t, 2 H, CH2CH2I, J = 7.0); 3.89 (m, 2 H,
CH2CH2OAr); 4.22 (m, 2 H, CH2OAr); 5.17 (br.s, 1 H, NH); 6.48 (d, 1 H, H(6), J = 8.7);
7.64 (d, 1 H, H(3), J = 2.2); 7.89 (dd, 1 H, H(5), J = 8.7, J = 2.2)
3402 (NH);
1496 (NO2)
1.70 (m, 2 H, CH2); 3.21 (t, 2 H, CH2I, J = 7.3); 3.25 (t, 2 H, CH2N, J = 6.7); 3.66, 3.71
(both m, 4 H each, 4 CH2O); 3.74 (t, 2 H, CH2CH2I, J = 7.3); 3.89 (m, 2 H, CH2CH2OAr);
4.23 (m, 2 H, CH2OAr); 5.23 (br.s, 1 H, NH); 6.49 (d, 1 H, H(6), J = 8.7); 7.65 (d, 1 H,
H(3), J = 2.2); 7.90 (dd, 1 H, H(5), J = 8.7, J = 2.2)
3415 (NH);
1496 (NO2)
3.23 (t, 2 H, CH2I, J = 7.0); 3.63 (s, 4 H, 2 CH2O); 3.66 (m, 2 H, CH2O); 3.70 (m, 2 H,
CH2O); 3.72 (t, 2 H, CH2CH2I, J = 7.0); 3.90 (m, 2 H, CH2CH2OAr); 4.27 (m, 2 H,
CH2OAr); 4.49 (s, 2 H, NCH2Ph); 5.71 (br.s, 1 H, NH); 6.48 (d, 1 H, H(6), J = 9.0); 7.27
(m, 1 H, H(4´)); 7.31—7.36 (m, 4 H, H(2´), H(3´), H(5´), H(6´)); 7.71 (d, 1 H, H(3), J = 2.0);
7.86 (dd, 1 H, H(5), J = 9.0, J = 2.0)
6e
6f
3399 (NH);
497 (NO2)
1.32 (d, 6 H, 2 Me, J = 6.5); 3.25 (t, 2 H, CH2I, J = 7.1); 3.66 (s, 4 H, 2 CH2O); 3.68—3.78
(m, 7 H, CHN, 3 CH2O); 3.91 (m, 2 H, CH2CH2OAr); 4.26 (m, 2 H, CH2OAr); 6.71 (d, 1 H,
H(6), J = 8.8); 7.71 (d, 1 H, H(3), J = 2.3); 7.90 (dd, 1 H, H(5), J = 8.8, J = 2.3)
3418 (NH);
1497 (NO2)
1.59 (d, 3 H, Me, J = 6.7); 3.21 (t, 2 H, CH2I, J = 6.9); 3.61 (m, 4 H, 2 CH2O); 3.63 (m, 6 H,
2 CH2O, CH2CH2I); 3.91 (m, 2 H, CH2CH2OAr); 4.26 (m, 2 H, CH2OAr); 4.58 (q, 1 H, CHN,
J = 6.7); 6.29 (d, 1 H, H(6), J = 8.9); 7.22 (m, 1 H, H(4´)); 7.26—7.32 (m, 4 H, H(2´), H(3´),
H(5´), H(6´)); 7.65 (d, 1 H, H(3), J = 2.3); 7.69 (dd, 1 H, H(5), J = 8.9, J = 2.3)

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Dmitrieva et al.
Table 4. 13C NMR and mass spectra of compounds 1b—d, 5b—f, and 6b—f
Comꢀ
pound
13C NMR (CDCl3),
MS,
m/z (Irel (%))a
δ (J/Hz)
1b
1c
1d
12.10 (Ме); 46.56 (CH2N); 52.18 (NCH2CH2O); 68.54 (CH2O); 69.21
(CH2O); 69.54 (CH2O); 70.02 (CH2O); 70.08 (CH2O); 70.15 (CH2O);
70.71 (CH2O); 107.68 (C(17)); 114.66 (C(14)); 118.36 (C(15)); 138.94
(C(16)); 146.25, 148.72 (C(13а), C(17а))
340 [M]+ (81), 339 (100), 325 (20),
309 (12), 209 (11), 196 (11), 195 (54),
194 (18), 193 (37), 179 (13)
11.36 (Ме); 20.01 (CH2); 53.01 (NCH2CH2O); 54.24 (CH2N); 68.58
(CH2OAr); 69.27 (CH2CH2OAr); 69.51 (NCH2CH2O); 70.05 (CH2O);
70.14 (CH2O); 70.22 (CH2O); 70.70 (CH2O); 107.76 (C(17)); 114.93
(C(14)); 118.32 (C(15)); 138.96 (C(16)); 146.35 (C(13a)); 148.77 (C(17a))
354 [M]+ (57), 353 (49), 326 (26),
325 (100), 295 (12), 237 (14), 209 (19),
207 (13), 193 (19), 179 (20)
52.82 (NCH2CH2O); 56.00 (NCH2Ph); 68.73 (CH2OAr); 69.29 (CH2O);
69.70 (CH2O); 70.01 (CH2O); 70.18 (2 CH2O); 70.92 (CH2O); 107.74
(C(17)); 115.94 (C(14)); 118.16 (C(15)); 126.99 (C(2´), C(6´)); 127.10
(C(4´)); 128.60 (C(3´), C(5´)); 137.27 (C(1´)); 139.49 (C(16)); 146.43
(C(13a)); 148.81 (C(17a))
402 [M]+ (74), 372 (31), 165 (29),
147 (37), 120 (31), 106 (33), 105 (31),
92 (40), 91 (100), 65 (30)
5b
5c
5d
14.30 (Me); 37.50 (CH2N); 42.66 (CH2Cl); 68.60 (CH2O); 69.40 (CH2O);
70.57 (CH2O); 70.61 (CH2O); 70.66 (2 CH2O); 71.30 (CH2O); 106.61, 106.78 167 (16), 151 (17), 149 (23), 135 (21),
(C(3), C(6)); 120.46 (C(5)); 136.61 (C(4)); 144.04, 144.75 (C(1), C(2))
378 [M]+ (2)b, 376 [M]+ (16)c, 182 (20),
107 (42), 78 (12), 65 (32), 63 (100)
392 [M]+ (12)b, 390 [M]+ (40)c, 361 (15),
11.66 (Мe); 22.45 (CH2); 42.95 (CH2Cl); 44.89 (CH2N); 68.84 (CH2O);
69.61 (CH2O); 70.74 (CH2O); 70.83 (3 CH2O); 71.50 (CH2O); 106.84, 106.95 196 (17), 195 (17), 193 (28), 167 (20),
(C(3), C(6)); 120.55 (C(5)); 136.59 (C(4)); 144.29, 145.20 (C(1), C(2))
109 (21), 107 (63), 65 (32), 63 (100)
29.66 (MeN); 31.49 (СН2S); 31.63 (СН2S); 32.04 (СН2S); 35.99 (СН2S);
60.93 (СН2OH); 68.34 (СН2OAr); 70.32 (2 СН2O); 71.18 (СН2O);
71.39 (СН2O); 106.02 (C(6)); 106.38 (C(3)); 120.36 (C(4)); 136.83
(C(5)); 143.96 (C(1)); 145.44 (C(2))
420 [M]+ (12), 255 (25), 254 (28), 253
(100), 225 (93), 149 (44), 109 (27),
105 (94), 87 (49), 61 (92), 60 (29)
5e
5f
42.91 (CH2Cl); 47.25 (NCH2Ph); 69.10 (CH2O); 69.64 (CH2O); 70.79
(CH2O); 70.89 (3 CH2O); 71.54 (CH2O); 107.37, 107.69 (C(3), C(6));
120.43 (C(5)); 127.29 (C(2´), C(6´)); 127.80 (C(4´)); 129.04 (C(3´),
C(5´)); 137.47, 137.94 (C(1´), C(4)); 144.58, 144.84 (C(1), C(2))
392 [M]+ (17)b, 390 [M]+ (46)c, 375 (27),
207 (19), 196 (14), 195 (13), 181 (20),
109 (19), 107 (66), 64 (31), 63 (100)
24.66 (Me); 42.95 (CH2Cl); 53.45 (CHN); 69.10 (CH2O); 69.67 (CH2O);
70.85 (CH2O); 70.95 (3 CH2O); 71.52 (CH2O); 107.26 (C(3)); 109.21 (C(6));
120.12 (C(5)); 125.93 (C(2´), C(6´)); 127.66 (C(4´)); 129.09 (C(3´), С(5´));
137.56 (C(4)); 144.48 (C(1), С(1´)); 144.57 (C(2))
454 [M]+ (8)b, 452 [M]+ (21)c, 439 (6),
437 (15), 107 (14), 106 (10), 105 (100),
79 (5), 77 (6), 65 (7), 63 (24)
6b
6c
6d
2.78 (CH2I); 14.32 (Me); 37.82 (CH2N); 68.58 (CH2O); 69.40 (CH2O); 70.14 468 [M]+ (53), 209 (7), 199 (20), 193 (6),
(CH2O); 70.51 (CH2O); 70.65 (2 CH2O); 71.89 (CH2O); 106.59, 106.76 (C(3), 182 (22), 181 (14), 167 (11), 155 (100),
C(6)); 120.35 (C(5)); 136.56 (C(4)); 144.00, 144.72 (C(1), C(2))
135 (12), 78 (10)
2.74 (CH2I); 11.08 (Me); 21.83 (CH2); 44.21 (CH2N); 68.27 (CH2O); 68.95
(CH2O); 69.69 (CH2O); 70.18 (3 CH2O); 71.41 (CH2O); 106.31, 106.16
(C(3), C(6)); 119.87 (C(5)); 135.88 (C(4)); 143.64, 144.56 (C(1), C(2))
482 [M]+ (47), 452 (7), 199 (17),
196 (13), 195 (8), 193 (14), 167 (16),
155 (100), 149 (6), 119 (6)
2.41 (CH2I); 46.44 (NCH2Ph); 68.32 (CH2O); 68.85 (CH2O); 69.60 (CH2O); 530 [M]+ (21), 514 (3), 513 (12),
70.01 (CH2O); 70.10 (2 CH2O); 71.33 (CH2O); 106.92, 106.56 (C(3), C(6));
119.65 (C(5)); 126.50 (C(2´), C(6´)); 127.00 (C(4´)); 128.25 (C(3´), C(5´));
136.33, 137.21 (C(1´), C(4)); 143.82, 144.12 (C(1), C(2))
442 (3), 287 (3), 199 (8), 155 (52),
92 (11), 91 (100), 78 (3)
6e
6f
2.77 (CH2I); 22.58 (2 Me); 43.87 (CHN); 68.66 (CH2O); 69.49 (CH2O);
70.22 (CH2O); 70.64 (CH2O); 70.74 (2 CH2O); 71.96 (CH2O); 107.01
(C(3), C(6)); 120.43 (C(5)); 136.37 (C(4)); 143.94, 143.99 (C(1), C(2))
482 [M]+ (44), 467 (13), 199 (17),
196 (11), 195 (6), 181 (17), 165 (7),
155 (100), 153 (6), 78 (7)
544 [M]+ (34), 530 (3), 529 (13),
269 (3), 199 (6), 165 (2), 155 (24),
106 (9), 105 (100), 79 (3)
2.80 (CH2I); 24.40 (Me); 53.20 (CHN); 68.92 (CH2OAr); 69.45
(CH2CH2OAr); 70.18 (CH2O); 70.60 (CH2O); 70.73 (2 CH2O);
71.91 (CH2O); 107.12 (C(3)); 108.98 (C(6)); 119.86 (C(5)); 125.66
(C(2´), C(6´)); 127.41 (C(4´)); 128.84 (C(3´), С(5´)); 137.39 (C(4));
143.21 (C(1), С(1´)); 144.43 (C(2))
a The molecular ion peak and the ten most intense peaks are cited.
b For 37Cl.
c For 35Cl.

NꢀAlkylnitrobenzoazaꢀ15ꢀcrownꢀ5
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
1197
C(9)
O(4)
C(8)
C(6)
O(5)
C(5)
C(10)
C(7)
C(11)
O(5)
O(1)
C(3)
C(2)
C(4)
N(2)
O(6)
O(7)
C(15)
O(3)
C(4)
C(3)
C(16)
C(1)
N(1)
C(14)
C(2)
C(5)
N(1)
O(4)
O(3)
O(2)
C(12)
C(13)
C(12)
C(1)
C(6)
O(6)
C(7)
C(13)
C(14)
C(8)
O(1)
O(2)
2
C(11)
O(5´)
N(2´)
C(9)
C(12´)
O(2´)
O(1´)
C(10)
C(13´)
C(11´)
O(4´)
O(6´)
O(3´)
C(8´)
N(1´)
C(7´)
C(14´)
C(15´)
C(10´)
O(4´)
N(1´)
O(3´)
Cl(3)
Ba(2)
C(9´)
O(1´)
C(16´)
Cl(4)
Cl(2)
C(7´)
Ba(1)
Cl(1´)
Cl(1)
C(2´)
C(3´)
C(4´)
O(5´)
C(1´)
C(6´)
C(5´)
O(6´)
O(5)
O(2)
O(3)
N(2´)
O(5″)
N(2″)
O(6″)
O(4)
O(1)
N(1)
3
N(2)
O(6)
C(7)
1a•Ba(ClO4)2
Fig. 1. Structures 2, 3 (two crystallographically independent molecules), and 1a•Ba(ClO4)2 (two independent complexes). The
hydrogen atoms in structure 1a•Ba(ClO4)2 are omitted for simplicity; the minor components of the disordered fragments are indicated
with unfilled lines. The atomic thermal displacement ellipsoids are given with 30% probability for 1a•Ba(ClO4)2 and with 50%
probability for the other structures. The coordination bonds are indicated with dashed lines.
mined earlier.11 The low accuracy of that study was due,
among other factors, to the disorder of the crown ether
chain between the O(3) and O(4) atoms in roomꢀtemperꢀ
ature Xꢀray diffraction. To obtain more accurate data, we
cooled single crystals to 120 K, thus eliminating the dyꢀ
namic component of the above disorder of the polyether
chain in compound 2.
In structure 2, the angles at the O(1) and O(5) atoms
conjugated with the benzene fragment are 117.8(1)° and
118.0(1)°, respectively, which most likely corresponds to
the sp2ꢀhybridized state of these atoms. The shortened
O(1)—C(2) and O(5)—C(7) bond lengths (1.353(2) Å
either) compared to the other O—C bond lengths
(1.415(2)—1.438(2) Å) and the nearꢀzero or nearꢀ180°
torsion angles CAr—CAr—O—C suggest the strong conjuꢀ
gation of the O(1) and O(5) atoms with the benzene ring.
Unlike the other O atoms of the macrocycle, the O(3)
atom is outside the cavity of the latter and its lone electron
pairs (LEP) are oriented outward. Such a conformation of
the macrocycle in the crystal is unfavorable for coordinaꢀ
tion of metal or ammonium cations to all heteroatoms of
the macrocycle.
The independent part of the crystal cell of compound 3
contains two crystallographically independent molecules
with different conformations of the polyether chain, which
clearly demonstrates the high conformational flexibility of

1198
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Dmitrieva et al.
azacrown ethers of this type. The independent molecules
have similar geometrical parameters. The N atoms of the
macrocycles are in planar configurations: the sums of their
bond angles are 359.5(3)° and 360.0(3)°. These planes are
virtually coplanar with the benzene rings: the correspondꢀ
ing dihedral angles are only 4.6° and 2.6°. Obviously, the
LEP of the nitrogen atoms are efficiently conjugated with
the πꢀsystem of the benzene ring, which is confirmed
by the shortened C(1)—N(1) and C(1´)—N(1´) bond
lengths (1.362(5) and 1.350(5) Å, respectively) and by the
pronounced paraꢀquinonoid distribution of the bond
lengths in the benzene ring by analogy with that found in
N,Nꢀdimethylꢀ4ꢀnitroaniline.12 Thus, based on the plaꢀ
nar geometry of the N atom of the macrocycle, the effiꢀ
cient conjugation of its LEP with the benzene ring, and
the elongated conformation of the macrocycle, which preꢀ
cludes simultaneous coordination of all heteroatoms to
metal cations, one can predict that complexes of phenyꢀ
lazacrown ether 3 would be unstable.
barium cation is too large to completely penetrate into the
cavity of the 15ꢀmembered macroheterocycle, so it is nearꢀ
ly above the center of the macrocyclic cavity of compound
1a ("birdꢀinꢀnest" model). The deviations of Ba(1) and
Ba(2) from the meanꢀsquare plane passing through all
heteroatoms of the nearest macrocycle are 1.78 and 1.67 Å,
respectively. The distances Ba...O(macrocycle) are within
2.749(6)—2.882(5) Å; the distances Ba...N are 3.154(7)
and 3.000(7) Å. Thus, with allowance for the van der Waals
radii of the O and N atoms (~1.4 and 1.5 Å, respectively),
all heteroatoms of macrocycle 1a can be regarded as alꢀ
most equally coordinated to the barium cation. The angles
Ba...O—C and Ba...N—C are 104.9(10)°—132.8(13)° and
103.3(4)°—111.8(6)°, respectively; this is not very favorꢀ
able for coordination of the sp2ꢀ or sp3ꢀhybridized hetꢀ
eroatoms of the macrocycle to the metal cation. Apparꢀ
ently, this is due to the limited possibility of conforming
the 15ꢀmembered macroheterocycle to the coordination
demands of a large metal cation.
Interestingly, the N(1)—C(7) bond length in free nitroꢀ
benzoazacrown ether 1a is only 1.386(6) Å,9 although the
N(1) atom has a pyramidal bond configuration (the sum
of its bond angles is 349.4(3)°). This suggests that the
sp2ꢀhybridized state contributes relatively greatly to the
N(1) atom in compound 1a, probably because of the very
efficient conjugation of its LEP with the strong electronꢀ
withdrawing nitro group in the paraꢀposition. This can
make the aforesaid LEP less "switchable" to the coordinaꢀ
tion with a metal cation and, consequently, decrease
the stabilities of the resulting complexes of this ligand
(see below).
The sums of the bond angles at the N(1) and N(1´)
atoms are 335.6(7)° and 337.0(6)°, respectively. Thereꢀ
fore, the nitrogen atoms in the complex are sp3ꢀhybridized
to a higher degree than those in free crown ether 1a
(349.4(3)°) and form stronger coordination bonds to the
metal cation. This is also evident from the lengthened
bonds N(1)—C(7) and N(1´)—C(7´) (1.410(10) and
1.438(9) Å, respectively) compared to those in free crown
ether 1a (1.386(6) Å). The bond angles at the O(1) and
O(1´) atoms conjugated with the benzene ring are 117.8(6)°
and 117.0(5)°, which suggests their predominant sp2ꢀhyꢀ
bridized state as in the free ligand (117.2(3)°).
The poor quality of a single crystal of the complex
1a•Ba(ClO4)2 leaves Xꢀray diffraction data highly inacꢀ
curate, which precludes correct comparison of the geoꢀ
metrical parameters of compound 1a in the individual state
and in the complex. Nevertheless, the experimental accuꢀ
racy suffices to reveal conformational changes in the macꢀ
rocycle of 1a upon the complexation.
The complex 1a•Ba(ClO4)2 is binuclear since the
bridging anions Cl(2)O4, Cl(3)O4, and Cl(4)O4 form coꢀ
ordination bonds simultaneously to both independent metꢀ
al cations. This is characteristic of barium perchlorꢀ
ate complexes with benzoazaꢀ15ꢀcrownꢀ5.13 The anions
Cl(1)O4 and Cl(4)O4 are disordered over two posiꢀ
tions with populations of 0.72 : 0.38 and 0.57 : 0.43, reꢀ
spectively. That is why the coordination numbers of Ba(1)
and Ba(2) vary from 10 to 12 and their coordination polyꢀ
hedra are irregular. The polyether chains in both indepenꢀ
dent complexes are partly disordered over two positions
with populations of 0.59 : 0.41 and 0.58 : 0.42. The nitro
group in one complex is also disordered (0.55 : 0.45). Apꢀ
parently, such a high degree of disorder of many compoꢀ
nents of the crystal is responsible for its poor quality.
The structures of two independent complexes
1a•Ba(ClO4)2 in the binuclear complex are similar. The
It is interesting to compare the conformations of free
and coordinated benzoazacrown ether 1a. Superposiꢀ
tion of structure 1a and two independent complexes
1a•Ba(ClO4)2 with complete coincidence of their benꢀ
zene fragments is shown in Fig. 2. It can be seen that the
conformation of the crown ether changes only slightly,
thus suggesting preorganization of this ligand for binding
metal cations.
Ba(2)
Ba(1)
N(1)
O(7)
O(3)
N(2)
O(4)
O(1)
O(2)
O(6)
Fig. 2. Molecules of free compound 1a (thick lines) and coorꢀ
dinated compound 1a in two independent complexes with
Ba(ClO4)2 (thin lines) when their benzene fragments are superꢀ
posed. The atoms of the minor conformers of 1a and the perꢀ
chlorate anions are omitted.

NꢀAlkylnitrobenzoazaꢀ15ꢀcrownꢀ5
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
1199
NMR studies. Earlier,4,13 we have demonstrated that
benzomonoazacrown ethers and their derivatives containꢀ
ing the tertiary N atom conjugated with the benzene ring
form sufficiently stable guest—host complexes with alkali,
alkalineꢀearth, heavy metal, and ammonium ions, which
will make them highly efficient as ionophores in promisꢀ
ing optical chemosensory compounds. It was interesting
to compare the quantitative stability parameters of comꢀ
plexes of nitrobenzoazacrown ethers with Groups I and II
metal cations and ammonium ions, to reveal the structurꢀ
al features of the resulting complexes and their selectivity
toward various ions, and to compare the complexing
ability of nitrobenzoazacrown ethers containing various
Nꢀalkyl substituents with that of related compounds.
The NOESY spectra of free benzoazacrown ethers 1a—d
exhibit intense cross peaks between the NCH2 (NMe) proꢀ
tons of the substituents and the benzene H(3) proton,
which is ortho to the N atom of the macrocycle (see, e.g.,
Fig. 3). In contrast, the coupling of the H(3) proton with
the NCH2 protons of the macrocycle is insignificant. Apꢀ
parently, in solution, the H(3) proton approaches the proꢀ
tons of the Nꢀalkyl substituent; i.e., the conformation of
the 15ꢀmembered benzoazacrown ether in the vicinity of
the N atom of the macrocycle is nearly identical with that
found earlier9 for crystal structure 1a. The data obtained
suggest that the conjugation of the N atom of the macroꢀ
cycle with the benzene ring in benzoazacrown ethers can
be somewhat weakened and, consequently, its LEP can be
donated for coordination bonding to a metal or ammoniꢀ
um cation.
The NMR study of nitrobenzoazacrown ethers 1a—d
and model compounds 2 and 3 in MeCNꢀd3 revealed subꢀ
stantial downfield shifts ΔδH of the signals for most of the
protons of these ligands upon the addition of an excess of
metal (Na, K, Ca, or Ba) or (ethyl)ammonium perchlorꢀ
ate. Such a behavior is typical of inclusion complexes in
which the Mn+ ion is bound to all heteroatoms of the
macrocycle by hydrogen bonds and/or ion—dipole interꢀ
actions (Scheme 3), thus displacing the electron densities
from all ligand atoms toward the cation (the electronꢀ
withdrawing effect of the cation). A general trend is the
larger shifts ΔδH (up to 0.7 ppm) for the complexes with
doubly charged cations compared to those with singly
charged cations, which is obviously due to the higher
charge densities on the alkalineꢀearth metal cations.
Analysis of the NOESY spectra of benzoazacrown
ethers 1a—d in the presence of excesses of calcium and
barium cations showed that the conformation of the macꢀ
H(3)
H(6)
H(4)
NCH3
3.00
NCH2CH2
3.50
4.00
CH2OAr
δ
δ
7.00
7.50
Fig. 3. Fragment of the NOESY spectrum of benzoazacrown ether 1a (MeCNꢀd3, 30 °C).

1200
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
Dmitrieva et al.
Scheme 3
Table 5. Stability constants of the complexes of crown ethers 1—3
with ammonium, ethylammonium, and metal perchloratesa
Ligand
logK1 (logK2)b
+
+
NH4
EtNH3
Na+
K+
Ca2+
Ba2+
1a
1b
1c
1d
2
1.7
1.6
1.5
1.5
2.1
1.8
1.4
1.5
1.4
1.3
1.7
1.2
2.7
2.7
2.5
2.3
3.4
2.6
1.9
1.7
1.8
1.9
2.7
0.7
3.8
3.8
4.0
3.4
4.2
2.3
4.2 (1.6)
3.2 (2.2)
3.1
2.7 (1.4)
4.1 (3.5)
1.4
3
a 1H NMR titration in MeCNꢀd3, 30 °C.
b K1/L mol–1 = [L•Mn+]/([L]•[Mn+]), K2/L mol–1 = [L2•Mn+]/
/([L]•[L•Mn+]); the constants were determined with an accuꢀ
racy of 20%.
formylbenzeneꢀcontaining crown ethers13 (by ~0.3—0.5
order of magnitude). We also found that the complexing
ability of these crown ethers depends on the cation nature,
size, and charge, the substituent at the N atom of the
macrocycle, and probably the degree of conjugation of
this N atom with the benzene ring.
Mn+ is the metal or (ethyl)ammonium ion (n = 1, 2)
rocyclic fragment near the N atom remains virtually unꢀ
changed upon the complexation. This confirms the high
preorganization of the macrocycles in the title compounds
for binding the metal cations.
The crown ethers studied form more stable complexes
with smaller cations of the alkaline and alkalineꢀearth
metals and more stable complexes with the NH4+ ion comꢀ
The abilities of nitrobenzoazacrown ethers to form
complexes with metal and (ethyl)ammonium perchloraꢀ
+
pared to the EtNH3 ion. The stability constants of the
1
complexes with the doubly charged cations are substanꢀ
tially (up to 100 times) higher than the stability constants
of the complexes with the singly charged cations. Obviꢀ
ously, the higher charge density on the smaller metal catꢀ
ions or on the doubly charged cations compared to the
singly charged ones and the absence of electronꢀdonating
tes were quantitatively estimated by H NMR titration.
The stability constants of the resulting complexes were
calculated with the HYPNMR program14 from experiꢀ
mental plots of the chemical shifts of the ligand protons
vs. the added amount of the salt; these stability constants
correspond to the formation of the complexes of the forꢀ
mula L•Mn+
+
substituents in NH4 favor stronger ion—dipole interacꢀ
tions between the heteroatoms of the macrocycle and the
cation in its cavity. The much higher stability constants of
the complexes of all the ligands studied with Na+ ions
compared to K+ ions suggest that the cavity of the crown
ether and the metal ion radius should match in size for the
formation of stronger bonds between them.
We found that most of the nitrobenzocrown ethers
studied form sandwich complexes with Ba2+ ions of the
formula L2•Ba2+ because of the large size of the Ba2+
cation (its ionic radius is 1.34 Å). The presumed sandwich
complexes with potassium cations, whose ionic radius is
also large (1.33 Å), seem to be very unstable (logK2 ≤ 0.5)
and cannot be detected by NMR titration.
For nitrobenzoazacrown ethers 1a,b,d, the signals of
the protons of all types in the 1H NMR spectra of both the
1 : 1 and sandwich complexes are equally shifted downꢀ
field. Apparently, the steric hindrances presented by the
Nꢀalkyl group preclude two aromatic fragments from apꢀ
proaching each other and they are most likely oriented in
opposite directions in complex 12•M2+ (see Scheme 3).
In contrast, the signals of the aromatic protons in sandꢀ
L + Mn+
L•Mn+
,
(1)
where L is the crown compound, Mn+ is the metal or
(ethyl)ammonium cation (n = 1, 2), and K1/L mol–1 is the
stability constant of the 1 : 1 complex. For metal cations
with large ionic radii, we also considered possible formaꢀ
tion of sandwich complexes of the formula L2•Mn+
L•Mn+ + L
L2•Mn+
,
(2)
where K2/L mol–1 is the stability constant of the 2 : 1
complex. For comparison, we studied the complexation
between the aforementioned salts and the nearest strucꢀ
tural analogs of nitrobenzoazacrown ethers, viz., benzoꢀ
crown ether 2 and phenylazacrown ether 3 with the same
size of the macrocycle. The results obtained are given
in Table 5.
The presence of the electronꢀwithdrawing nitro group
in the compounds studied somewhat lowers the stability
constants of their complexes compared to those of similar

NꢀAlkylnitrobenzoazaꢀ15ꢀcrownꢀ5
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
1201
wich complex 22•Ba2+ are shifted upfield relative to the
signals of the free ligand, thus suggesting that the benzene
rings in this complex prefer to lie above one another.
With an increase in the length of the Nꢀalkyl substituꢀ
ent in nitrobenzoazacrown ethers 1, the complexes with
barium cations become somewhat less stable, while the
complexes with the singly charged cations and the Ca2+
ions are almost insensitive to the substituent length. Note
that the complexes of crown ether 1 with singly charged
cations are similar in stability with analogous complexes
of the nearest structural analog (viz., phenylazacrown ether
3), while compound 2 forms appreciably more stable comꢀ
plexes with cations M+. In this respect, nitro derivatives 1
differ from benzeneꢀunsubstituted benzoazacrown ethers
and their formyl derivatives: their complexes with the catꢀ
ions in question are much more stable than similar comꢀ
plexes of related Nꢀphenylazaꢀ15ꢀcrownꢀ5.13 This beꢀ
havior of compounds 1 can be explained by two factors:
first, the coordination bond N...M+ is weakened because
of the strong electronꢀwithdrawing effect of the NO2 group
and, second, the substituent at the N atom presents steric
hindrances to its coordination to the large Ba2+ ion. The
second reason is indirectly confirmed by the inability of
crown ether 1c, which contains a bulky nꢀpropyl substituꢀ
ent, to form stable sandwich complexes.
Nevertheless, the specific properties of the tertiary N
atom in compounds 1, whose LEP is conjugated with the
benzene ring not very efficiently, allow this atom to doꢀ
nate its LEP for coordination bonding to a doubly charged
metal cation. In contrast, our Xꢀray diffraction experiꢀ
ments (see above) showed that the geometrical parameꢀ
ters of the N atom in phenylazacrown ether 3 suggest its
sp2ꢀhybridized state and very strong conjugation with the
benzene ring, which, in combination with a higher flexiꢀ
bility of the macrocycle, makes this compound less effiꢀ
cient as a macrocyclic ligand for M2+. It should also be
noted that compounds 1 are only slightly inferior to crown
ether 2 in the complexing ability toward alkalineꢀearth
metal cations.
Quantum chemical calculations. Quantum chemical
calculations help to reveal the structural features of comꢀ
pounds for which Xꢀray diffraction data are lacking. For
molecules in solution, indirect structural information can
be obtained from 2D NMR spectra. In combination with
quantum chemical calculations, this becomes a powerꢀ
ful tool for the examination of noncrystalline molecular
structures.
Our previous DFT calculations of the structures of
crown ethers and their complexes show15—19 that the calꢀ
culated structures agree well with Xꢀray diffraction data
on the bond lengths, the bond angles, and the conformaꢀ
tions of the macrocycle. Thus, we hope that the calculated
structures of Nꢀmethylnitrobenzoazaꢀ15ꢀcrownꢀ5 1a and
its aqua complexes with Ba2+ (four to six water moleꢀ
cules coordinated, together with the cation, on one side of
the meanꢀsquare plane of the crown ether) and Ca2+ (three
water molecules coordinated in the same way) will also be
reliable. According to our calculations and analysis of nuꢀ
merous experimental data,20,21 Ca2+ and Ba2+ ions in
the cavities of various 15ꢀcrownꢀ5 protrude from the
meanꢀsquare plane of the macrocycle, forming halfꢀsandꢀ
wich structures. Additional ligands (solvent molecules or
counterions) are coordinated by the cation in such a way
that both the cation and these ligands are on the one side
of the meanꢀsquare plane of the macrocycle.
The solvation shell of the cation in acetonitrile conꢀ
sists of not only solvent molecules and may include water
(present as an impurity in the solvent) and counterions. In
our models, we studied in detail the complexes with such
additional ligands as water molecules, which fill vacancies
in the inner coordination sphere of the cation, and perꢀ
formed special calculations for acetonitrile molecules.
These calculations, as well as previous calculations for
perchlorate anions,22,23 showed that the presence of addiꢀ
tional ligands substantially changes the conformation
of the macrocycle in the complex compared to the catꢀ
ion—crown ether complex, regardless of the nature of the
additional ligands. Aqua complexes enjoy a greater variety
of conformations because many structures are stabilized
by hydrogen bonds between water molecules and the
O atoms of the crown ether. With acetonitrile and perꢀ
chlorate anions, this is obviously not the case.
The most stable calculated structures of free crown
ether 1a are consistent well with Xꢀray diffraction data.9
The conformers selected by the energy criterion (relative
conformation energy* <3 kcal mol–1) can be conventionꢀ
ally broken down into two groups differing in the structure
of the fragment ArNR2. The first group includes the conꢀ
formers in which the distance between the H(3) proton of
the benzene ring and the Nꢀmethyl group is ~2 Å; the
second group includes the conformers in which the H(3)
proton approaches the Nꢀmethylene group of the macrocycle.
Although all the conformers under consideration satisfy
the energy range <3 kcal mol–1, the energies of the strucꢀ
tures of the first group are lower. Therefore, they should
dominate in equilibrium mixtures, which agrees well with
the experimental NOESY data (see above). The structure
of the most stable conformer of 1a is shown in Fig. 4, a. In
this structure, the pyramidal character of the N atom of
the macrocycle (defined as a deviation of the sum of the
bond angles at the N atom from 360°) is ~7° (against ~10°
in the experimental structure). This suggests considerable
conjugation of this N atom with the aromatic ring.
The conformers of the complexes of Nꢀmethylbenzoꢀ
azaꢀ15ꢀcrownꢀ5 with Ca2+ and Ba2+ cations can be
broken down into two groups also differing in the structure
of the fragment ArNR2.
* The energies of the conformers relative to the energy of the
most stable structure.

1202
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
a
Dmitrieva et al.
es the Nꢀmethyl group; in the second group, the H(3)
proton approaches the Nꢀmethylene group of the macꢀ
rocycle.
For the complexes cation—crown ether 1a containꢀ
ing no additional ligands, the calculated structures are
in conflict with NMR data. The most stable structure
(close to that found from Xꢀray diffraction experiꢀ
ments) agrees best (though still insufficiently) with the
experimental NOESY spectrum (H(3)...MeN, ~2.15 Å;
H(3)...H2CN, ~2.9 Å). With these distances, the NOESY
spectra would show not only the cross peak H(3)...MeN
but also a weak cross peak H(3)...H2CN. However, the
latter is absent from the spectra. In all the other calculated
structures, the distance H(3)...H2CN is shorter than or
equals H(3)...MeN, which would result in a noticeable
cross peak H(3)...H2CN and probably in a weak cross
peak H(3)...MeN.
b
Coordination of three (for Ca2+) or four to six water
molecules (for Ba2+) to the cation changes the fragment
RO—C6H3—NR2 only slightly compared to waterfree
structures; yet the conformation of the peripheral units of
the macrocycle undergoes some changes. The structures
with the lowest energies become consistent better with the
NOESY spectrum (H(3)...MeN, ~2.2—2.4 Å; H(3)...H2CN,
~3.3—3.7 Å). Such structures agree better with Xꢀray difꢀ
fraction data (when the anions are coordinated by the
cation) than do the structures containing no additional
ligands. Therefore, calcium and barium complexes with
azacrown ethers in solution should necessarily include
some additional ligands (usually solvent molecules). The
most stable structures of the aqua complexes of crown
ether 1a with Ca2+ and Ba2+ are shown in Figs 4, b and c.
The pyramidal character of the N atom of the macrocycle
is ~26° in the complexes with Ca2+ and ~21° or 24° in the
complexes with Ba2+. This suggests a virtually complete
loss of conjugation between this N atom and the benzene
ring in the complexes.
Ca
c
Ba
To sum up, a stepwise transformation of the macroꢀ
cycle of accessible nitrobenzoꢀ15ꢀcrownꢀ5 afforded
a number of Nꢀalkylnitrobenzoazaꢀ15ꢀcrownꢀ5 containꢀ
ing the N atom conjugated with the benzene ring. Usꢀ
ing quantum chemical calculations, we obtained the
3D structures of benzoazacrown ethers and their comꢀ
plexes and demonstrated that the complex should necꢀ
essarily contain additional ligands in the coordinaꢀ
tion sphere of the cation. Quantitative measurements
clearly showed that Nꢀalkylbenzoazacrown ethers easiꢀ
ly form complexes with alkalineꢀearth metal cations
and that these ligands are comparable in complexing
ability with nitrobenzoꢀ15ꢀcrownꢀ5 and are vastly superiꢀ
or to Nꢀ(4ꢀnitrophenyl)azaꢀ15ꢀcrownꢀ5. This can give
impetus to the design, on the basis of nitrobenzoazacrown
ethers, of promising chromoionophores with a great
optical response to the complexation with the aforesaid
metal cations.
Fig. 4. DFTꢀcalculated most stable conformers of Nꢀmethylꢀ
nitrobenzoazaꢀ15ꢀcrownꢀ5 1a (a) and its aqua complexes
with Ca2+ (b) and Ba2+ (c).
Here the difference is more distinct: the first group
includes the conformers in which the cation and
the Nꢀmethyl group are on the same side of the meanꢀ
square plane of the macrocycle, while the second group
includes the conformers in which they are on the oppoꢀ
site sides. In the first group, the H(3) proton approachꢀ

NꢀAlkylnitrobenzoazaꢀ15ꢀcrownꢀ5
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
1203
(2 CH2O); 69.36 (CH2O); 70.15 (CH2O); 70.42 (CH2O); 70.49
(CH2O); 70.53 (CH2O); 72.44 (CH2O); 106.48 (C(3), C(6));
120.34 (C(4)); 136.36 (C(5)); 144.00, 144.27 (C(1), C(2)). Highꢀ
resolution MS, found: m/z 358.1737 [M]+. C16H26N2O7. Calcuꢀ
lated: M = 358.1740.
2ꢀ(2ꢀ{2ꢀ[2ꢀ(5ꢀNitroꢀ2ꢀpropylaminophenoxy)ethoxy]ethoxy}ꢀ
ethoxy)ethanꢀ1ꢀol (4c). Yield 98% (cf. Ref. 6: oil). 13C NMR
(CDCl3), δ: 11.05 (Me); 21.79 (CH2); 44.26 (CH2N); 61.08
(CH2OH); 68.00 (CH2O); 68.94 (CH2O); 69.76 (CH2O); 70.08
(3 CH2O); 72.14 (CH2O); 106.11 (C(3), C(6)); 119.94 (C(4));
135.75 (C(5)); 143.68, 144.69 (C(1), C(2)). Highꢀresolution MS,
found: m/z 372.1890 [M]+. C17H28N2O7. Calculated: M =
= 372.1897.
2ꢀ(2ꢀ{2ꢀ[2ꢀ(2ꢀBenzylaminoꢀ5ꢀnitrophenoxy)ethoxy]ethoxy}ꢀ
ethoxy)ethanꢀ1ꢀol (4d). Yield 81% (cf. Ref. 6: oil). 13C NMR
(CDCl3), δ: 46.46 (NCH2Ph); 61.12 (CH2OH); 68.20 (CH2O);
68.97 (CH2O); 69.76 (CH2O); 70.04 (CH2O); 70.13 (CH2O);
70.17 (CH2O); 72.14 (CH2O); 106.32, 107.03 (C(3), C(6));
119.82 (C(4)); 126.62 (C(2´), C(6´)); 127.06 (C(4´)); 128.37
(C(3´), C(5´)); 136.46, 137.60 (C(1´), C(5)); 144.04, 144.45
(C(1), C(2)). Highꢀresolution MS, found: m/z 420.1894 [M]+.
C21H28N2O7. Calculated: M = 420.1896.
2ꢀ(2ꢀ{2ꢀ[2ꢀ(2ꢀIsopropylaminoꢀ5ꢀnitrophenoxy)ethoxy]ethꢀ
oxy}ethoxy)ethanꢀ1ꢀol (4e). Yield 96% (converted to the conꢀ
sumed compound 2, 81% conversion) (cf. Ref. 6: oil). 13C NMR
(CDCl3), δ: 22.10 (2 Me); 43.61 (CHN); 61.19 (CH2OH); 68.23
(CH2O); 69.06 (CH2O); 69.92 (CH2O); 70.16 (CH2O); 70.21
(2 CH2O); 72.22 (CH2O); 106.52, 106.72 (C(3), C(6)); 120.03
(C(4)); 135.88 (C(5)); 143.71, 143.76 (C(1), C(2)). Highꢀresoluꢀ
tion MS, found: m/z 372.1891 [M]+. C17H28N2O7. Calculated:
M = 372.1897.
Experimental
1
H NMR spectra were recorded on a Bruker DRX500
spectrometer (500.13 MHz) in CDCl3 and MeCNꢀd3 with the
solvent signals (δ 7.27 and 1.96, respectively) as the internal
standards. 13C NMR spectra were recorded on a Bruker DRX500
spectrometer (125.76 MHz) in CDCl3 with the solvent signal
(δ 77.00) as the internal standard. Chemical shifts and coupling
constants were measured to within 0.01 ppm and 0.1 Hz, respecꢀ
tively. To assign the signals of the protons and the C atoms, 2D
homonuclear (1H—1H COSY, NOESY) and heteronuclear techꢀ
niques (1H—13C COSY: HSQC, HMBC) were used. 2D Experiꢀ
ments were carried out with the standard parameters of the Brukꢀ
er software. The mixing time in the NOESY experiment was 300
μs; the HMBC experiment was optimized for the constant JH,C
= 8 Hz.
IR spectra were recorded on a Bruker IFSꢀ113V spectrophoꢀ
tometer in thin films with KBr. Mass spectra were measured on
Varian MATꢀ311A and Finnigan MATꢀ212 instruments; highꢀ
resolution mass spectra were recorded on a Finnigan MATꢀ212
instrument with perfluorokerosene as a standard (ionizing enerꢀ
gy 70 or 60 eV, direct inlet probe).
Elemental analysis of samples was carried out at the Microꢀ
analysis Laboratory of the A. N. Nesmeyanov Institute of Orgaꢀ
noelement Compounds, Russian Academy of Sciences. Melting
points were determined in capillaries on a MELꢀTemp II inꢀ
strument.
For column chromatography, SiO2 (Kieselgel 60, 0.063—0.100
or 0.063—0.200 mm, Merck) was used. The course of the reacꢀ
tions was monitored by TLC on DCꢀAlufolien Kieselgel 60 F254
plates (Merck).
2ꢀ[2ꢀ(2ꢀ{2ꢀ[5ꢀNitroꢀ2ꢀ(1ꢀphenylethyl)aminophenoxy]ethꢀ
oxy}ethoxy)ethoxy]ethanꢀ1ꢀol (4f). Yield 73% (converted to the
consumed compound 2, 36% conversion). 1H NMR (CDCl3), δ:
1.62 (d, 3 H, Me, J = 7.0 Hz); 3.58 (m, 2 H, CH2O); 3.66 (s, 4 H,
2 CH2O); 3.66—3.75 (m, 4 H, 2 CH2O); 3.92 (m, 2 H,
CH2CH2OAr); 4.27 (m, 2 H, CH2OAr); 4.58 (br.q, 1 H, CHN);
5.73 (br.s, 1 H, NH); 6.25 (d, 1 H, H(3), J = 8.9 Hz); 7.24 (m, 1 H,
H(4´)); 7.30—7.34 (m, 4 H, H(2´), H(3´), H(5´), H(6´)); 7.65
(d, 1 H, H(6), J = 2.4 Hz); 7.71 (dd, 1 H, H(4), J = 8.9 Hz,
J = 2.5 Hz). 13C NMR (CDCl3), δ: 24.43 (Me); 52.93 (CHN);
61.52 (CH2OH); 68.51 (CH2OAr); 69.39 (CH2CH2OAr); 70.18
(CH2O); 70.45 (2 CH2O); 70.60 (CH2O); 72.46 (CH2O); 106.70
(C(3)); 108.35 (C(6)); 119.93 (C(4)); 125.56 (C(2´), C(6´));
127.24 (C(4´)); 128.76 (C(3´), C(5´)); 136.86 (C(5)); 143.65
(C(1´)); 143.57 (C(2)); 144.14 (C(1)). IR (KBr), ν/cm–1: 3389
(NH, OH); 1489 (NO2). MS, m/z (Irel (%)): 434 [M]+ (17),
419 (13), 417 (5), 133 (3), 106 (9), 105 (100), 103 (4), 79 (19),
79 (7), 77 (5). Highꢀresolution MS, found: m/z 434.2055 [M]+.
C22H30N2O7. Calculated: M = 434.2053.
Synthesis of chlorides 5b—f (general procedure). A solution of
SOCl2 (3.2 mL, 43.9 mmol) in CHCl3 (5 mL) was slowly added
at 0 °C (ice bath) to a stirred solution of podand 4b—f (1.8 mmol)
and dry pyridine (0.16 mL, 2 mmol) in CHCl3 (15 mL). The
reaction mixture was refluxed for 6—7 h and cooled. A 5% aqueꢀ
ous solution of HCl (50 mL) was added and the product was
extracted with CHCl3. The combined extracts were washed with
5% aqueous Na2CO3 and water and concentrated in vacuo. The
residue was chromatographed on SiO2 with benzene—AcOEt
(1 : 1) as an eluent for 5b—f or with benzene—AcOEt (5 : 1 and
then 1 : 1) as eluents for 5e,f. Chlorides 5b—f were isolated as
4ꢀNitrobenzoꢀ15ꢀcrownꢀ5 (2) was purchased from the A. V.
Bogatsky Physicochemical Institute, National Academy
of Sciences of Ukraine (Odessa). Ethylamine (70% aqueous
solution), 1ꢀpropylamine, isopropylamine, benzylamine, 1ꢀpheꢀ
nylethylamine, and 4ꢀnitrofluorobenzene (Aldrich) were used
without further purification. The salts NH4ClO4, NaClO4,
KClO4, Ca(ClO4)2, and Ba(ClO4)2 (Aldrich) were dried in vacuo
at 60 (NH4ClO4) or 200 °C (the other salts); EtNH3ClO4 was
prepared by neutralization of 70% aqueous ethylamine with 70%
aqueous HClO4 (Aldrich) and dried in vacuo at 60 °C.
Synthesis of azapodands 4b—f (general procedure). A mixture
of crown ether 2 (313 mg, 1 mmol) and a 45% solution of an
amine (0.04 mol) in dry EtOH was heated in a sealed tube at
130 °C (oil bath) for 100 (for 4b,c) or 300 h (for 4d—f). The tube
was opened and the reaction mixture was concentrated in vacuo.
The podands were isolated from the mixtures of reaction prodꢀ
ucts in one of the following ways.
A. The residue containing compounds 4b—d was chromatoꢀ
graphed on SiO2 with AcOEt and then AcOEt—EtOH (5 : 1) as
eluents.
B. The residue containing compounds 4e,f was diluted with
water (50 mL) and acidified dropwise with conc. HCl to pH 3.
The product was extracted with CHCl3, the combined extracts
were concentrated in vacuo, and the residue was purified as deꢀ
scribed in the method A.
Podands 4b—f were isolated as yellow oils.
2ꢀ(2ꢀ{2ꢀ[2ꢀ(2ꢀEthylaminoꢀ5ꢀnitrophenoxy)ethoxy]ethoxy}ꢀ
ethoxy)ethanꢀ1ꢀol (4b). Yield 97% (cf. Ref. 6: oil). 13C NMR
(CDCl3), δ: 14.20 (Me); 37.45 (CH2N); 61.54 (CH2OH); 68.25

1204
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
Dmitrieva et al.
yellow oils. The yields and physicochemical characteristics of
compounds 5b—f are given in Tables 2—4.
and concentrated in vacuo. The residue was chromatographed
on SiO2 with benzene—AcOEt (1 : 1) as an eluent for 1b or with
benzene—AcOEt (5 : 1 and then 1 : 1) as eluents for 1c,d. Comꢀ
pound 1c was isolated as yellow oil; compounds 1b,d were isolatꢀ
ed as yellow powders, m.p. 73—75 (1b) and 119—121 °C (1d).
The yields and physicochemical characteristics of compounds
1b—d are given in Tables 1—4.
B. A mixture of iodide 6c,d (0.35 mmol), dry THF (15 mL),
and 60% NaH (0.28 g, 7.0 mmol) in paraffin was stirred at room
temperature for 125 (for 6c) or 95 h (for 6d). The same workup of
the reaction mixture as described in method A gave compound
1c as yellow oil and compound 1d as yellow powder. The yields
of the compounds are given in Table 1.
Synthesis of iodides 6b—f (general procedure). A solution of
compounds 5b—f (1.6 mmol) and NaI (4.8 g, 32 mmol) in dry
acetone (50 mL) was refluxed with stirring for 100 h. The reacꢀ
tion mixture was concentrated in vacuo, the residue was diluted
with water (50 mL), and the product was extracted with benzꢀ
ene. The combined extracts were concentrated in vacuo and the
residue was chromatographed on SiO2 with benzene—AcOEt
(1 : 1) as an eluent for 6b or with benzene—AcOEt (5 : 1 and then
1 : 1) as eluents for 6c—f. Iodides 6b—f were isolated as yellow
oils. The yields and physicochemical characteristics of comꢀ
pounds 6b—f are given in Tables 2—4.
Synthesis of benzoazacrown ethers 1b—d (general procedure).
A. A mixture of iodide 6b—d (0.35 mmol), dry THF (15 mL),
and 60% NaH (0.14 g, 3.5 mmol) in paraffin was refluxed with
stirring for 2.5—10 h. The reaction mixture was cooled and diꢀ
luted with water. The product was extracted with benzene and
CHCl3. The combined organic extracts were washed with water
13ꢀ(4ꢀNitrophenyl)ꢀ1,4,7,10ꢀtetraoxaꢀ13ꢀazacyclopentadeꢀ
cane (3). A mixture of 1,4,7,10ꢀtetraoxaꢀ13ꢀazacyclopentadeꢀ
cane (110 mg, 0.5 mmol), 1ꢀfluoroꢀ4ꢀnitrobenzene (213 mg,
160 μL, 1.5 mmol), triethylamine (153 mg, 210 μL, 1.5 mmol),
and MeOH (5 mL) was heated in a sealed tube at 120 °C (oil
bath) for 40 h. The reaction mixture was concentrated in vacuo
Table 6. Crystallographic parameters and the data collection and refinement statistics for compounds 2, 3,
and 1a•Ba(ClO4)2
Compound
2
3
1a•Ba(ClO4)2
Molecular formula
M/g mol–1
Crystal system
Space group
a/Å
b/Å
c/Å
α/deg
β/deg
C14H19NO7
313.30
C16H24N2O6
340.37
C15H22BaCl2N2O14
662.59
Orthorhombic
Pca21
15.0965(9)
4.8500(3)
19.7472(11)
90
Monoclinic
P21/c
24.361(7)
15.160(4)
8.906(2)
90
91.934(4)
90
3287.1(15)
8
Triclinic
P–1
10.5563(4)
13.4472(5)
16.1110(7)
90.005(2)
97.529(2)
92.111(2)
2265.72(16)
4
90
90
γ/deg
3
V/Å
1445.85(15)
4
Z
dcalc/g cm–3
1.439
1.376
1.942
F(000)
664
1456
1312
μ(MoꢀKα)/mm–1
Crystal size/mm
Scan mode/θ (deg) range
Ranges of h, k, l indices
0.116
0.105
2.063
0.26×0.23×0.14
ω/2.06—29.00
–20 ≤ h ≤ 20,
–6 ≤ k ≤ 1,
–25 ≤ l ≤ 25
6724
0.22×0.18×0.08
ω/0.84—29.00
–33 ≤ h ≤ 33,
–20 ≤ k ≤ 20,
–12 ≤ l ≤ 12
30888
0.26×0.24×0.22
ω/2.42—27.00
–13 ≤ h ≤ 13,
–17 ≤ k ≤ 17,
–20 ≤ l ≤ 20
17551
Number of measured
reflections
Number of independent
reflections
Number of reflections
3545
(Rint = 0.0202)
3164
8678
(Rint = 0.0671)
6005
9458
(Rint = 0.0284)
7977
with I > 2σ(I)
Number of parameters
refined
275
625
771
R Factors for I > 2σ(I)
R1 = 0.0357,
wR2 = 0.0900
R1 = 0.0421,
wR2 = 0.0937
1.089
R1 = 0.1020,
wR2 = 0.2484
R1 = 0.1346,
wR2 = 0.2603
1.071
R1 = 0.0595,
wR2 = 0.1548
R1 = 0.0698,
wR2 = 0.1590
1.134
for all reflections
GOOF on F 2
Residual electron
density (min/max)/e Å
–0.205/0.284
–0.394/0.615
–1.203/1.982
–3

NꢀAlkylnitrobenzoazaꢀ15ꢀcrownꢀ5
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
1205
and the residue was chromatographed on SiO2 (gradient elution
with benzene—AcOEt up to 60% of AcOEt). The yield of comꢀ
pound 3 was 148 mg (86%), yellow powder, m.p. 126—128 °C
(cf. Ref. 24: m.p. 127—130 °C).
crown ethers and their complexes with relative energies no highꢀ
er than 3 kcal mol–1. Comparison of the calculated structure
with the NOESY spectrum allowed the conclusion that one or
more conformers dominate in an equilibrium mixture.
Xꢀray diffraction experiments. Crystals of free crown ethers 2
and 3 were obtained by slow evaporation of their solutions in
CH2Cl2—hexane at room temperature. Crystals of a complex of
benzoazacrown ether 1a with barium perchlorate were obtained
by slow saturation of a solution of an equimolar mixture of the
ligand and Ba(ClO4)2 in MeCN with the benzene vapor.
The single crystals of all compounds were mounted under
cooled nitrogen (T = 120.0(2) K) on a Bruker SMARTꢀCCD
diffractometer and reflection intensities were measured (MoꢀKα
radiation, λ = 0.71073 Å, graphite monochromator, ω scan
mode). The experimental data were processed with the SAINT
program.25 For the complex 1a•Ba(ClO4)2, an absorption
correction was applied with the SADABS program. All strucꢀ
tures were solved by the direct methods and refined by the
leastꢀsquares method in the fullꢀmatrix anisotropic approxiꢀ
mation on F 2 for nonꢀhydrogen atoms. The H atoms at the
C atoms were located geometrically and refined isotropically for
compounds 2 and 3 and using a riding model for the comꢀ
plex 1a•Ba(ClO4)2.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 09ꢀ03ꢀ00429),
the Presidium of the Russian Academy of Sciences (Proꢀ
gram No. 7), and the Royal Society of Chemistry of the
United Kingdom (personal grants for L. G. Kuz´mina and
J. A. K. Howard).
References
1. K. E. Krakowiak, J. S. Bradshaw, D. J. ZameckaꢀKrakowꢀ
iak, Chem. Rev., 1989, 89, 929.
2. J. S. Bradshaw, K. E. Krakowiak, R. M. Izatt, Azaꢀcrown
Macrocycles, Ed. E. C. Taylor, J. Wiley and Sons, New York,
1993, 885 pp.
3. S. P. Gromov, S. N. Dmitrieva, M. V. Churakova, Usp.
Khim., 2005, 74, 503 [Russ. Chem. Rev. (Engl. Transl.), 2005,
74, 461].
All calculations were performed with the SHELXTLꢀPlus
program package26 (Bruker). Crystallographic parameters and
the data collection and refinement statistics are summarized in
Table 6. Atomic coordinates and other structural parameters for
the complex 1a•Ba(ClO4)2 and compounds 2 and 3 have been
deposited with the Cambridge Crystallographic Data Center*
(Nos. 733 455, 733 456, and 733 457, respectively).
1H NMR titration. Deuterated MeCN (water content <0.05%;
FGUP RNTs Prikladnaya Khimiya, St.ꢀPetersburg) was used as
a solvent. The molecular formulas and stability constants of the
complexes of the crown ethers with the salts Mn+(ClO4–)n were
determined by plotting the shifts of the signals of the ligand (L)
protons versus the concentration of the added salt. The total
concentration of L was maintained constant (~5•10–3 mol L–1);
the salt concentration was varied beginning with zero (the maxiꢀ
mum ratio Mn+/L was ~3). With NH4ClO4 and KClO4 as titrants,
the total concentration of L was maintained at ~1•10–3 mol L–1
4. S. P. Gromov, S. N. Dmitrieva, A. I. Vedernikov, M. V.
Churakova, Izv. Akad. Nauk, Ser. Khim., 2004, 1362 [Russ.
Chem. Bull., Int. Ed., 2004, 53, 1417].
5. S. P. Gromov, S. N. Dmitrieva, V. E. Krasnovskii, Izv. Akad.
Nauk, Ser. Khim., 1997, 540 [Russ. Chem. Bull. (Engl. Transl.),
1997, 46, 519].
6. S. P. Gromov, S. N. Dmitrieva, Izv. Akad. Nauk, Ser. Khim.,
1999, 542 [Russ. Chem. Bull. (Engl. Transl.), 1999, 48, 537].
7. S. P. Gromov, S. N. Dmitrieva, M. V. Churakova, A. Yu.
Turchanov, Izv. Akad. Nauk, Ser. Khim., 2002, 1232 [Russ.
Chem. Bull., Int. Ed., 2002, 51, 1335].
8. S. P. Gromov, S. N. Dmitrieva, M. V. Churakova, Synthesis,
2003, 593.
9. S. P. Gromov, S. N. Dmitrieva, M. V. Churakova, A. I.
Vedernikov, N. A. Kurchavov, L. G. Kuz´mina, N. A. Kaꢀ
taeva, J. A. K. Howard, Zh. Org. Khim., 2004, 1247 [Russ. J.
Org. Chem. (Engl. Transl.), 2004, 40, 1200].
10. D. Ataman, E. U. Akkaya, Tetrahedron Lett., 2002, 43, 3981.
11. R. D. Rogers, R. F. Henry, A. N. Rollins, J. Inclusion Phenꢀ
om., Macrocycl. Chem., 1992, 13, 219.
12. O. Ya. Borbulevych, R. D. Clark, A. Romero, L. Tan, M. Yu.
Antipin, V. N. Nesterov, B. H. Cardelino, C. E. Moore,
M. Sanghadasa, T. V. Timofeeva, J. Mol. Struct., 2002, 604, 73.
13. A. I. Vedernikov, S. N. Dmitrieva, L. G. Kuz´mina, N. A.
Kurchavov, Yu. A. Strelenko, J. A. K. Howard, S. P. Groꢀ
mov, Izv. Akad. Nauk, Ser. Khim., 2009, 954 [Russ. Chem.
Bull., Int. Ed., 2009, 58, 978].
because of the limited solubilities of these salts. The Δδ values
H
were measured to within 0.001 ppm. The stability constants of
the complexes were calculated with the HYPNMR program.14
Quantum chemical calculations. Full geometrical optimiꢀ
zation of free Nꢀmethylbenzoazaꢀ15ꢀcrownꢀ5, Nꢀmethylꢀ
nitrobenzoazaꢀ15ꢀcrownꢀ5 1a, and their aqua complexes with
Ca2+ and Ba2+ was carried out by the DFT method with the
functional PBE27 in the original threeꢀexponen t basis 3z with
the PRIRODA program.28 The resulting structures (conformers)
were rejected unless their relative conformation energies (with
respect to the most stable conformer) were less than 3 kcal mol–1
.
14. C. Frassineti, S. Ghelli, P. Gans, A. Sabatini, M. S. Moruzzi,
A. Vacca, Anal. Biochem., 1995, 231, 374.
15. A. A. Bagatur´yants, A. Ya. Freidzon, M. V. Alfimov, E. J.
Baerends, J. A. K. Howard, L. G. Kuz´mina, J. Mol. Struct.
(THEOCHEM), 2002, 588, 55.
16. A. Ya. Freidzon, A. A. Bagatur´yants, M. V. Alfimov,
Izv. Akad. Nauk, Ser. Khim., 2007, 395 [Russ. Chem. Bull.,
Int. Ed., 2007, 56, 407].
A typical error of the DFT method was ~1—2 kcal mol–1. Nonꢀ
specific (van der Waals) interactions of the flexible macrocyclic
molecule with its environment (e.g., a crystalline or solvating
one) produce effects of the same order of magnitude. That is the
reason why the conformation energy alone does not suffice to
specify the dominating structure among the conformers of the
* CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax: (+44)
1223 33 6033; eꢀmail: deposit@ccdc.cam.ac). These data can be
made available from the authors upon request.
17. A. Ya. Freidzon, A. A. Bagatur´yants, S. P. Gromov, M. V.
Alfimov, Izv. Akad. Nauk, Ser. Khim., 2003, 2505 [Russ.
Chem. Bull., Int. Ed., 2003, 52, 2646].

1206
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
Dmitrieva et al.
18. A. Ya. Freidzon, A. A. Bagatur´yants, S. P. Gromov, M. V.
Alfimov, Int. J. Quant. Chem., 2004, 100, 617.
24. W. Zeng, Yi. Du, H. Li, X. Lu, S. Qin, Org. Prep. Proc. Int.,
2003, 35, 228.
19. A. Ya. Freidzon, K. G. Vladimirova, A. A. Bagatur´yants,
S. P. Gromov, M. V. Alfimov, J. Mol. Struct. (THEOCHEM),
2007, 809, 61.
20. Cambridge Structural Database System, Version 5.30, 2009.
21. A. Yu. Tsivadze, A. A. Varnek, V. E. Khutorskii, Koordinatꢀ
sionnye soedineniya metallov s kraunꢀligandami [Metal Comꢀ
plexes with Crown Ligands], Nauka, Moscow, 1991, 397 pp.
(in Russian).
25. SAINT, Version 6.02A, Bruker AXS Inc., Madison, Wisconꢀ
sin (USA), 2001.
26. SHELXTLꢀPlus, Version 5.10, Bruker AXS Inc., Madison,
Wisconsin (USA), 1997.
27. J. P. Perdew, K. Burke, M. Ernzerhof, Phys. Rev. Lett., 1996,
77, 3865.
28. D. N. Laikov, Chem. Phys. Lett., 1997, 281, 151.
22. A. Ya. Freidzon, A. A. Bagatur´yants, S. P. Gromov, M. V.
Alfimov, Izv. Akad. Nauk, Ser. Khim., 2008, 2009 [Russ.
Chem. Bull., Int. Ed., 2008, 57, 2045].
23. V. G. Avakyan, S. P. Gromov, A. I. Vedernikov, S. N. Dmitꢀ
rieva, M. V. Alfimov, Izv. Akad. Nauk, Ser. Khim., 2004, 25
[Russ. Chem. Bull., Int. Ed., 2004, 53, 24].
Received June 3, 2009;
in revised form March 10, 2010