Synthesis, crystal structure, and alkali metal picrate extraction capabilities of molecular clips based on diphenylglycoluril and benzocrown ethers

Article abstract of DOI:10.1016/j.tet.2012.04.009

A convenient method for the synthesis of a series of molecular clips based on the diphenylglycoluril framework and benzocrown ether moieties by the reaction of bis(cyclomethoxymethylene)diphenylglycoluril with benzocrown ethers in polyphosphoric acid is proposed. X-ray diffraction analysis of molecular clips with the benzo-12-crown-4 and benzo-15-crown-5 fragments showed that both compounds are chloroform solvates with the stoichiometry clip:chloroform 1:1. By theoretical and experimental methods the existence of obtained clips in an anti-anti conformation was proved. The complexation properties of the obtained molecular clips were examined toward alkali metal and ammonium ions by FABMS spectrometry and extraction experiments.

Full text of DOI:10.1016/j.tet.2012.04.009

Tetrahedron 68 (2012) 4757e4764
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis, crystal structure, and alkali metal picrate extraction capabilities of
molecular clips based on diphenylglycoluril and benzocrown ethers
Tatiana Yu. Bogaschenko a, Alexander Yu. Lyapunov a, Leonid S. Kikot’ a, Alexander V. Mazepa a,
,
Mark M. Botoshansky b, Marina S. Fonari c, Tatiana I. Kirichenko a
*
a Department of Fine Organic Synthesis, A.V. Bogatsky Physico-Chemical Institute, National Academy of Sciences of Ukraine, Lustdorfskaya doroga 86, 65080 Odessa, Ukraine
b Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Technion City, 32000 Haifa, Israel
c
ꢀ
Institute of Applied Physics, Academy of Sciences, Chis¸inau MD 2028, Republic of Moldova
a r t i c l e i n f o
a b s t r a c t
Article history:
A convenient method for the synthesis of a series of molecular clips based on the diphenylglycoluril
framework and benzocrown ether moieties by the reaction of bis(cyclomethoxymethylene)diphenyl-
glycoluril with benzocrown ethers in polyphosphoric acid is proposed. X-ray diffraction analysis of
molecular clips with the benzo-12-crown-4 and benzo-15-crown-5 fragments showed that both com-
pounds are chloroform solvates with the stoichiometry clip:chloroform 1:1. By theoretical and experi-
mental methods the existence of obtained clips in an antieanti conformation was proved. The
complexation properties of the obtained molecular clips were examined toward alkali metal and am-
monium ions by FABMS spectrometry and extraction experiments.
Received 28 December 2011
Received in revised form 14 March 2012
Accepted 2 April 2012
Available online 7 April 2012
Keywords:
Crown ether
Molecular clips
Diphenylglycoluril
Extraction
Ó 2012 Elsevier Ltd. All rights reserved.
Crystal structure
1. Introduction
approaches, a large number of tetrakis derivatives of diphenylgly-
coluril was obtained. They represent U-shaped molecular receptors
Creating synthetic receptors that can effectively bind organic
and inorganic, neutral and charged substrates requires a fine tuning
of their topological and electronic properties.1 The basis of the re-
ceptor/substrate interaction are specific, mostly nonvalent in-
teractions: relatively strong and therefore often dominant
hydrogen bonding, ion pair interactions, hydrophobic effect, non-
covalent interaction of arenes with other aromatic molecules
containing as donor centers aromatic, heterocyclic, and polyoxy-
ethylene fragments, and combinations thereof.5
We have previously described the new representatives of bis(-
benzocrown ethers),6 in which two benzocrown ethers are bound
by the diphenylglycoluril fragment (first described by Nolte et al.).7
Bis(crown ethers) are interesting because the interaction of in-
dividual crown ether units within their structure can act in-
dependently (the statistical complex formation) or with the
appearance of both positive and negative cooperative or allosteric
effects.8 Positive effects are usually observed during the formation
of sandwich type complexes of bis(crown ethers) with the large
metal cations (Fig. 1a), which can’t fit into the cavity of the separate
(
p
e
p
and SeO/
p
p interactions) or with positively charged ions
(catione
interactions).2 Besides commonly used cyclic and
therefore well preorganized receptors, such as crown ethers,3a,b
calixarenes,3c cyclophanes,3d and compounds of similar type,
a promising group in this respect are the non-cyclic receptors
having a molecular pseudocavity with geometric parameters,
which are easily to change. These receptors can be considered as
molecular tweezers or clips that selectively bind electron-deficient
neutral aromatic and aliphatic substrates, as well as organic and
inorganic cations.4 Lately, special attention has been drawn to
conformationally rigid compounds containing a glycoluril frag-
ment, diphenylglycoluril in particular. Using a variety of synthetic
* Corresponding author. Tel.: þ38 0487662095; fax: þ38 0487659602; e-mail
Fig. 1. Schematic representation of cooperative effect: (a, b) positive and (c) negative/
independent guest interaction.
address: Ti-kirichenko@rambler.ru (T.I. Kirichenko).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.04.009

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T.Yu. Bogaschenko et al. / Tetrahedron 68 (2012) 4757e4764
macrocycle, or by interaction of bis(crown ethers) with bifunctional
guest molecules, such as diamines or dicarboxylates (Fig. 1b).
We now report the syntheses of a series of molecular clips 1e5
based on the diphenylglycoluril framework and benzocrown ether
moieties; and preliminary data of the alkali metal binding prop-
erties by these host molecules, which have been evaluated via
picrate extraction and fast atom bombardment ionizationemass
spectrometric (FABMS) methods.
clips.7 On other hand, the presence of the eCOeN(H)eCH2eOe
fragment allows us to consider 8 and 9 to be classic Einhorn re-
agents. This was a reason for the synthesis based on the above-
mentioned conditions of the new type of molecular clips containing
fragments of benzocrown ethers, as shown on Scheme 1.
Molecular clips (1e5) were synthesized by heating at 80 ꢀS the
mixture of 1 equiv 8 (method C) or 9 (method S) and 2.1 equiv of
corresponding benzocrown ether in PPA for 30 min. Using bisether
8 as starting reagent allows considerably higher yields of target
products (>70%) compared to tetraol 9 (w40%).6a Possible expla-
nation of this fact is the elimination of formaldehyde in the con-
ditions of reaction with formation of linear polycondensation
products, which decreases the yields of target compounds.
Another synthesis of glycoluril derivatives is alkylation of
diphenylglycoluril 11 by reactive halides in the presence of strong
bases (method D). Many compounds including benzene derivatives
were obtained in this way. Utilizing 40,50-bis(bromomethyl)benzo-
15-crown-5 we have obtained clip 2 with a relatively low yield of
35%. This result clearly justifies the formation of the products of
4,5-disubstitution in the conditions of methods AeS. The disad-
vantage of the method lies in the necessity of the synthesis of the
series of bis(bromomethyl) derivatives of crown ethers while it is
much more convenient to modify 11.
2. Results and discussion
2.1. Synthesis
For the first time, the synthesis of molecular clip 2 based on the
diphenylglycoluril and benzocrown ether was described by Nolte
et al. with 92% yield (method A).7 Using a similar reaction with
veratrole, the authors7 obtained product 6 with only 40% yield,
although the yield decrease compared to 2 is not explained.
This way, we can make the conclusion that the optimal way of
obtaining clips 1e5 is method C because it allows obtaining
products with high yields from available reagents.
However, despite the high yield mentioned by the authors of
compound 2, we were able to obtain a molecular clip based on
C18S6 3 only with 50% yield.6b In this case, the isolation of the
product is considerably complicated by the necessity to remove the
intermediate complex 3 from the tin salts. The main disadvantages
of the following method are utilizing a relatively hard to get tet-
rachloride 7, its hydrolytic instability and complications with iso-
lation of target compounds from the Lewis acid adducts.
Previously we have shown that polyphosphoric acid (PPA) is an
excellent catalyst and medium for the synthesis of various amido-
methyl derivatives of benzocrown ethers in the ChernyakeEinhorn
reaction conditions.9 Meanwhile, products of 4,5-disubstitution in
the benzene ring are obtained with high yields after short (up to
30 min) heating of the mixture of reagents in PPA.
The 1H NMR spectra of 1e5 in CDCl3 shows one singlet for the
protons of the catechol moieties at
d
¼6.80 ppm, indicating that
there is only one type of aromatic proton; NCH2 protons gave rise to
one characteristic AB pattern (4.1 and 4.7 ppm, J¼15.9 Hz). The C2v
symmetry for these molecules is also confirmed by single signals
for the C]O and NCH2 groups in the 13C NMR spectra. Protons of
the phenyl groups show a multiplet signal at
d
¼7.00e7.20 ppm that
indicates existence of molecular clips in antieanti (aa) conforma-
tion with adjacent crown ether moieties.10
2.2. Computational studies
In order to perform an estimation of the structure of the
obtained molecular clips 1e5, we have performed molecular
modeling using the method of statistical mechanics, Monte Carlo
Synthetic precursors of tetrachloride 7, tetraol 9, and its bisether
8, are also widely used reagents for building various molecular
Scheme 1. The synthetic approaches to the diphenylglycoluril based molecular clips.

T.Yu. Bogaschenko et al. / Tetrahedron 68 (2012) 4757e4764
4759
(MMFF force field, Spartan’06 software).11 The resulting data in-
dicates that stable conformations for 1e5 are structures with aa
orientation of crown ether fragments relative to the phenyl groups,
which lead to polyether fragments being spatially closely spaced
(Fig. 2). This has to facilitate the formation of stable sandwich
complexes due to the fixation of the substrate’s molecule between
sidewalls of the molecular clip containing donor centers.
the relative compounds12 and approximately obeys the Cm sym-
metry: the dihedral angle between the diazacyclopentane rings is
69.5ꢀ in 1 and 69.2ꢀ in 2. The seven-membered diazacycloheptane
fragments fused with the five-membered rings take the chair
conformation, the dihedral angle between the planes of the ben-
zene rings of the two fragments of benzocrown ethers is 36.2ꢀ in 1
and 36.8ꢀ in 2.
Fig. 2. Energy-minimized structures of molecular clips 1e5. Hydrogen atoms are omitted for clarity.
2.3. X-ray crystallography
The calculated data was confirmed by single crystal X-ray dif-
fraction analysis carried out for molecular clips 1 and 2 (Figs. 3 and
4). Both compounds are chloroform solvates with the stoichiometry
clip:chloroform¼1:1. Compound 1$CHCl3 crystallizes in the
centrosymmetric monoclinic space group C2/c while the crown
molecule occupies a general position in the unit cell. Two crystal-
lographically different chloroform molecules both reside on the 2-
fold axes. Compound 2$CHCl3 crystallizes in the centrosymmetric
monoclinic space group P21/c with crown and chloroform mole-
cules residing on general positions. Similar to the previous reported
by us on the complex of molecular clip 3 with sodium picrate,6a in
both macrocyclic molecules two fragments of benzocrown ether
are in aa conformation relative to the phenyl groups of diphenyl-
glycoluril, that determines their U-shapes. The geometry of the
diphenylglycoluril fragment does not differ significantly from
Fig. 4. ORTEP drawing of complex 2$CHCl3 with partial labeling scheme. Thermal el-
lipsoids are shown with the 30% probability level.
In the crystal solid, molecules of 1 are coupled into self-included
dimers in such a way that one of the crown-moieties of each
molecule is located within the clip of another molecule through the
intermolecular CeH/O interactions including carbonyl and ether’s
ꢁ
oxygen atoms, C(8)/O(11)(1ꢁx, y, 0.5ꢁz)¼3.306(7) A [H(8B)/
ꢁ
ꢁ
O(11)¼2.37 A], C(9B)/O(7)(1ꢁx, y, 0.5ꢁz)¼3.208(7) A [H(9B)/
ꢁ
O(7)¼2.53 A]. This results in a sequence of four 12-membered rings
in the form of a channel (Fig. 5). These dimeric associates are fur-
ther stacked in the columns along the crystallographic c-axis with
the
CeH/O
[S(17B)/O(7B)(0.5ꢁx,
0.5ꢁy,
1ꢁz)¼3.410,
Fig. 3. ORTEP drawing of bis-crown 1 with partial labeling scheme. Thermal ellipsoids
are shown with the 50% probability level. The disordered CHCl3 molecules are omitted.
ꢁ
H/O¼2.49 A] interactions between those related by the inversion

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T.Yu. Bogaschenko et al. / Tetrahedron 68 (2012) 4757e4764
Fig. 5. Side view of self-included dimer 1. H-bonds are shown by dotted lines; sym-
metry transformation for O(7A): 1ꢁx, y, 0.5ꢁz. (left) Top view. H-atoms are omitted for
clarity. (right).
centers dimers. The chloroform molecules occupy the channels
between these columns and are held within these channels via
predominantly van der Waals interactions (Fig. 6).
Fig. 7. Crystal packing of 2$CHCl3.
relative binding selectivity of structurally similar hosts toward
different guests. This general method has been used previously to
assess the alkali metal binding properties of a wide range of hosts,
such as crown ethers,14d lariat ethers,14e bis(crown ethers),14f and it
provides the basis for the results reported herein.
The solutions of the mixture of corresponding clips 1e5 with
metal picrate (1 and 3 equiv) in 3-nitrobenzyl alcohol were ana-
lyzed (Table 1).
Even with an excess of metal picrate, in the mass spectra of all
cases showed that the most intensive peak is the one correspond-
ing to the single-charged ion of the complex with ratio 1:1. For the
compound 1 the peak corresponding to the complex with the
structure [1þ2Na]þ is observed with minor intensity only with an
excess of sodium picrate. For bis(benzo-15-crown-5) 2, formation
of such complex is observed only with sodium picrate and its rel-
ative contribution is increasing with the increase of the concen-
tration of sodium picrate in the mixture. Formation of the complex
with a 1:2 ratio is observed in clips 3e5 only with an excess of
picrate. For 3 and 4, contribution of such complexes is decreasing
with the increase of the cation size, but in the case of 5 there is no
such dependence. Since the ratio of peak intensities of ions of
structurally similar complex particles is correlated with their sta-
bility,14 we can make the conclusion that in the conditions of the
mass-spectral experiment, the most stable complexes are the ones
with a 1:1 ratio. Obtained intensity ratios [M]:[MþMe]:[Mþ2Me]
reflect the tendencies of selectivity and bonding ability of clips 1e5
toward alkali metal picrates.
Fig. 6. Crystal packing of 1$CHCl3. H-atoms in the disordered chloroform molecules
were not found.
In the crystal structure of 2$CHCl3 the chloroform molecule is
located deep in the cavity of the molecular clip being held there via
ꢁ
intermolecular interactions, Cl(3)/O(14)¼3.250(6) A and C(8B)/
ꢁ
ꢁ
Cl(1)¼3.44(2) A [H(8B2)/Cl(1)¼2.72 A]. Only a few examples of
the chloroform inclusion in the pseudocavity formed by two crown
ether fragments with the formation of crystalline complexes are
known so far.13
These 1:1 aggregates, related by the glide plane, stack along the
þ
The intensity of the complex ions of clips 1e5 with the NH4
crystallographic c-axis with significant
pep interactions between
cation is considerably lower than with cations of alkali metals.
Complex with a 1:2 ratio is only observed with an excess of am-
monium picrate for the molecular clip 4. The possible reason is that
the main contribution in the complex stabilization is achieved by
hydrogen bonds O/HeNH3þ. Highly polar and solvating 3-
nitrobenzyl alcohol results to suppression of these interactions.
Cation extraction as an ion pair is a widely common method in
hosteguest chemistry of estimating the efficiency of interaction of
macrocyclic receptors with a substrate. The most commonly metal
picrates are used for these purposes, which allow a fast and easy
spectrophotometrical15 determination of extracted cation quantity.
Thereby, estimation of the complex formation ability of molecular
clips 1e5 was performed on the basis of the extraction results of
cations of alkali metals from the aqueous phase into the chloroform
ligand solution. For the sake of correct comparison, extractability of
adjacent aromatic fragments. It is indicated because the dihedral
angle between the nearly parallel aromatic rings is 0.35ꢀ, and the
ꢁ
distance between the centroids of the aromatic rings being 3.560 A
(Fig. 7).
Thus, the theoretical and experimental data suggest the struc-
tural readiness of the molecular clips 1e5 to the complex formation
with different substrates.
2.4. Complexation studies
FABMS has proven to be a versatile method for the analysis of
supramolecular complexes formed in solution and transported into
the gas phase for detection.14 Based upon the intensities of com-
plexes in the resulting mass spectra, it is possible to estimate the

T.Yu. Bogaschenko et al. / Tetrahedron 68 (2012) 4757e4764
4761
Table 1
Extractability of bis(crown ethers) 2e5 is considerably higher
than for the corresponding benzocrown ethers. It is probably the
result of formation of more stable complexes. Particularly notable
changes are observed for bis(benzo-18-crown-6) 3 and bis(benzo-
21-crown-7) 4. Extractability of potassium, rubidium, and cesium
picrates for 3, and rubidium, and cesium for 4 is over 100%, which
clearly indicates the formation of complexes with 1:2 ratio along
with ligand:cation complexes with 1:1 ratio. Formation of such
complexes is described by us in the mass-spectral experiment
conditions, and also in the crystalline state for the complex of 3
with sodium picrate.6a For bis(crown ethers) 2e5 more potent in-
teractions with large cations, such as potassium, rubidium, and
cesium are also observed in comparison to the small sodium cation.
However, if for compounds 2 and 3 the highest extractability is for
ion Kþ, in the case of compounds 4 and 5 it increases with the in-
crease of the size of the metal cation and reaches its maximum for
ions Rbþ and Csþ, respectively. Bis(benzo-12-crown-4) 1 and
benzo-12-crown-4, as expected, interact weakly with the metal
ions, furthermore, extractability for 1 is even slightly lower. There is
almost no dependence on the size of the cation, but the highest
extractability in both cases is observed for the Csþ ion and the
lowestdfor Rbþ ion. Similar decrease of bis(benzocrown ethers)
extraction constants in comparison with their monocyclic analogs
is described for the complexes of non-sandwich type bis(benzoc-
rown ethers) with cations of alkali metals,15e when each crown
ether cycle acts as an individual unit, and the slight decrease of
extraction constants is explained by repulsion of two cations,
bonded by crown ether cycles (anti-cooperative effect). However,
formation of such complexes with bis(benzo-12-crown-4) 1 is
highly unlikely, which is proved by the mass-spectral experiment,
which didn’t note formation of a considerable amount of complexes
with a structure and ratio of ligand:cation 1:2 for compound 1 even
with an excess of metal picrates (Table 2).
Normalized peak intensity for clips 1e5 mixtures with alkali metal picrates
Compound Cation Clips to metal picrate ratio
1:1
1:3
[MþH]þ [MþMe]þ [Mþ2Me]þ [MþH]þ [MþMe]þ [Mþ2Me]þ
0
25
42
38
1
2
3
4
5
Na
K
Rb
Cs
100
75
58
62
23
86
100
100
94
79
94
93
96
97
69
85
84
90
92
65
97
94
98
90
51
0
0
0
0
0
11
0
0
0
10
16
32
71
0
0
0
0
7
0
0
0
4
30
0
0
6
3
100
90
84
68
29
76
100
100
100
93
69
87
93
96
70
84
87
81
85
68
86
85
92
82
60
Trace
0
0
0
0
24
0
0
0
0
31
13
7
Trace
0
16
13
13
12
9
14
15
8
NH4 77
Na
K
Rb
Cs
3
0
0
6
0
0
NH4 21
Na
K
Rb
Cs
6
7
4
3
Trace
0
0
0
0
3
1
1
NH4 31
Na
K
Rb
Cs
12
15
9
7
1
0
NH4 35
23
0
0
0
6
Na
K
Rb
Cs
3
6
2
Trace
Trace
Trace
Trace
0
10
NH4 49
12
0
40
monobenzocrown ethers B12C4, B15C5, B18C6, B21C7, and B24C8
was determined in identical conditions. Control of the extract-
ability was performed on the basis of spectrophotometrical de-
tection of residual concentration of metal picrates in aqueous
solution. Extractability of the investigated compounds was de-
termined as metal/ligand concentration ratios according to the
equation:
3. Conclusions
The current paper describes the facile synthesis of new molec-
ular clips, including benzocrown ether fragments and diphenyl-
glycoluril core. The X-ray structures for compounds 1 and 2,
showing an encapsulated CHCl3 molecule, were determined. The-
oretical and experimental studies show the existence of 1e5 in
conformation, in which benzocrown ether moieties have an
antieanti orientation. The complexation properties of the obtained
molecular clips were examined toward alkali metal and ammonium
ions by FABMS spectrometry and extraction experiments. The
obtained results by extraction experiments indicate that the ex-
tractabilities of 2e5 are much greater comparing to benzocrown
ethers. Molecular clip 3 shows distinct selectivity to Kþ. Our efforts
in this direction will be reported in timely manner.
À Á
ð½C0MPiꢂ ꢁ ½CxMPiꢂÞ
H O ꢃ 100
2
Extractability %
¼
½C0Lꢂ
CHCl3
where [C0MPi]dinitial concentration of metal picrate in the
aqueous phase, [CxMPi]dconcentration of metal picrate in the
aqueous phase after extraction, [C0L]dinitial concentration of li-
gand in the organic phase.
Since molecular clips 1e5 contain two potential sites for cation
binding, their maximal theoretical extractability is 200%, but for
benzocrown ethers it is 100%. Obtained results are presented in
Table 2 and Fig. 8.
4. Experimental
4.1. General
Table 2
Extractability of alkali metal picrates by compounds 1e5, B12C4, B15C5, B18C6,
B21C7, B24C8, (%)a
Solvents were purified using standard procedures before use.16
Benzocrown ethers,17 diphenylglicoluril 11,18 tetrachloride 7,7 tet-
raol 9, and bisether 8,19 40,50-bis(bromomethyl)benzo-15-crown-5
1020 were prepared according to the literature procedures. Poly-
phosphoric acid was prepared by dissolving of 150 g P2O5 in 75 ml
85-% H3PO4. All other materials were reagent grade chemicals used
as received.
Silica gel 60 F254 (Merck) plates were used for TLC. Silica gel 60
(0.063e0.100 mm, Merck) was used for column chromatography.
The plates were inspected by UV light and, if required, developed in
I2 vapor. 1H and 13C NMR spectra were obtained on a Varian VXR-
300 (300 MHz and 75.5 MHz, respectively) spectrometer. All
Compound
Cation
Naþ
Kþ
13.7
Rbþ
4.5
85.4
111.6
112.5
34.7
10.6
12.5
53.8
13.95
20.2
Csþ
14.5
NHþ4
1
2
3
4
10.6
41.6
44.2
5.8
19.0
17.6
22.0
25.3
3.75
5.25
5.95
28.55
77.85
80.75
15.00
5.15
7.70
37.20
4.25
91.6
142.5
59.2
22.9
14.5
15.8
88.5
5.6
50.1
107.8
106.75
49.6
19.2
15.2
36.8
8.7
5
B12C4
B15C5
B18C6
B21C7
B24C8
10.6
19.9
3.85
a
Averaged values of three extraction experiments.

4762
T.Yu. Bogaschenko et al. / Tetrahedron 68 (2012) 4757e4764
Fig. 8. Dependence between alkali metal picrates extractability and the type of extragent.
chemical shifts are quoted in parts per million on the
d
scale with
(m, 10O, S6O5). 13C NMR (CDCl3):
d 44.8, 69.5, 70.7, 71.2, 85.3, 119.4,
TMS or residual solvent as an internal standard. The coupling
constants are expressed in Hertz.The melting points were de-
termined by the open capillary tube method and were uncorrected.
Electronic absorption spectra were obtained on a Specord M 40
spectrophotometer in quartz cells. Fast atom bombardment (FAB)
mass spectrometry was performed on a VG 70-70EQ mass spec-
trometer, equipped with an argon primary atom beam, and an m-
nitrobenzyl alcohol matrix was utilized. Elemental analysis was
carried out on a EuroVector EA3000 CHNS elemental analyzer.
128.1, 128.6, 128.7, 131.3, 133.6, 149.0, 157.7. MS, m/z (%): 791
([MþH]þ, 100). Anal. Calcd for C44H46N4O10$CHCl3: C, 59.38; H,
5.20; N, 6.16. Found: C, 59.48; H, 5.26; N, 6.24.
4.2.3. Molecular clip (2). The crude product was recrystallized from
MeOH/CHCl3 mixture (50:1) to give 2 as colorless crystals. Yield:
1.86 g, 80% (Method B); 0.93 g, 40% (Method C); 0.77 g, 35%
(Method D). Mp: 285e288 ꢀC (dec). 1H NMR (CDCl3):
d 3.66e3.78
(m, 16H, CH2O), 3.80e3.90 (m, 8H, CH2O), 3.99e4.21 (m, 8H, CH2O),
4.12 (d, 4O, J¼15.6 Hz, SO2N), 4.67 (d, 4O, J¼15.6 Hz, SO2N), 6.80
(s, 4O, S6O2), 7.04e7.17 (m, 10O, S6O5). 13C NMR (CDCl3):
d 44.9,
4.2. General procedure for the synthesis of molecular clips
68.9, 69.6, 70.5, 71.0, 85.3, 115.6, 128.2, 128.6, 128.7, 129.9, 133.7,
147.6, 157.7. MS, m/z (%): 879 ([MþH]þ, 100). Anal. Calcd for
C48H54N4O12$CHCl3: C, 58.95; H, 5.55; N, 5.61. Found: C, 59.01; H,
5.51; N, 5.73.
1e5
4.2.1. Method A. molecular clip 2 was obtained in 50% yield as de-
scribed.6b Method B. A mixture of bisether 8 (1 g, 2.65 mmol) and
corresponding benzocrown ether (5.42 mmol) in PPA (30 g) was
stirred vigorously at 80e85ꢀS for 30 min. A deep purple color was
formed in 5 min. To the cooled reaction mixture was added water
(150 mL) and product was extracted with CHCl3 (3ꢃ50 mL). The
organic layer was washed with water until neutral (w3ꢃ50 mL)
and subjected to azeotropic drying. The solvent was removed at
reduced pressure and the residue was dissolved in a mixture of
CHCl3/MeOH (50:1, 100 mL) and filtered through SiO2 (w30 mL).
The solvent was removed at reduced pressure and the crude
product was purified as described below.
Method C. The procedure is similar to Method B, with exception
that tetraol 9 (1.1 g, 2.65 mmol) was used instead bisether 8.
Method D. A suspension of NaH (0.288 g, 12 mmol) in DMSO
(26 mL) was heated with stirring at 70ꢀS for 30 min. The resulting
mixture was cooled to room temperature and a solution of 11
(0.78 g, 2.65 mmol) in DMSO (40 mL) was added. Stirring was
continued for 20 min and then solution of 10 (5.92 g, 5.83 mmol) in
DMSO (40 mL) was added dropwise over 5 min and the resulting
mixture was stirred at room temperature for 24 h. The mixture was
poured into ice water (400 mL) and acidified with HCl to pHz2. The
resulting solid was filtered off, washed with water (3ꢃ50 mL). The
crude product was purified as described below.
4.2.4. Molecular clip (3). The crude product was recrystallized from
MeOH to give 3 as colorless needles. Yield: 50% (Method A); 2.00 g,
78% (Method B); 0.97 g, 38% (Method C). Mp: 231.5e233 ꢀC. 1H
NMR (CDCl3):
d 3.55e3.79 (m, 24H, CH2O), 3.80e3.95 (m, 8H,
CH2O), 3.98e4.27 (m, 8H, CH2O), 4.13 (d, 4O, J¼15.8 Hz, SO2N), 4.67
(d, 4O, J¼15.8 Hz, SO2N), 6.80 (s, 4O, S6O2), 7.00e7.20 (m, 10O,
S6O5). 13C NMR (CDCl3):
d 44.9, 69.1, 69.7, 70.7, 70.8, 70.8, 85.4,
115.8, 128.2, 128.6, 128.7, 130.0, 133.8, 147.6, 157.7. MS, m/z (%): 967
([MþH]þ, 100) Anal. Calcd for C52H62N4O14: C, 64.58; H, 6.46; N,
5.79. Found: C, 64.35; H, 6.41; N, 5.74.
4.2.5. Molecular clip (4). The crude product was purified by column
chromatography (CHCl3/MeOH, 100:1) and crystallized under
hexane layer to give 4 as off white powder. Yield: 1.45 g, 52%
(Method B). Mp: 83e85 ꢀC. 1H NMR (CDCl3):
d 3.58e3.94 (m, 40H,
CH2O), 4.02e4.23 (m, 8H, CH2O), 4.13 (d, 4O, J¼15.9 Hz, SO2N), 4.67
(d, 4O, J¼15.9 Hz, SO2N), 6.80 (s, 4O, S6O2), 7.02e7.18 (m, 10O,
S6O5). 13C NMR (CDCl3):
d 44.9, 69.1, 69.7, 70.4, 70.8, 71.0, 71.0, 85.2,
115.4, 128.0, 128.4, 128.5, 129.8, 133.4, 147.1, 157.4. MS, m/z (%): 1055
([MþH]þ, 100). Anal. Calcd for C56H70N4O16: C, 63.74; H, 6.69; N,
5.30. Found: C, 63.86; H, 6.68; N, 5.31.
4.2.6. Molecular clip (5). The crude product was purified by column
chromatography (CHCl3/MeOH, 100:1) to give 5 as light yellow oil,
which solidifies on standing. Yield: 1.76 g, 58% (Method B). 1H NMR
4.2.2. Molecular clip (1). The crude product was recrystallized from
MeOH/CHCl3 mixture (30:1) to give 1 as colorless crystals. Yield:
1.57 g, 75% (Method B); 0.75 g, 36% (Method C). Mp: 315 ꢀC (dec). 1H
(CDCl3):
d 3.56e3.94 (m, 48H, CH2O), 4.01e4.23 (m, 8H, CH2O), 4.13
NMR (CDCl3):
d
3.61e4.26 (m, 24H, CH2O), 4.13 (d, 4O, J¼15.9 Hz,
(d, 4O, J¼15.8 Hz, SO2N), 4.68 (d, 4O, J¼15.8 Hz, SO2N), 6.80 (s, 4O,
SO2N), 4.69 (d, 4O, J¼15.9 Hz, SO2N), 6.91 (s, 4O, S6O2), 7.03e7.18

T.Yu. Bogaschenko et al. / Tetrahedron 68 (2012) 4757e4764
4763
S6O2), 7.00e7.21 (m, 10O, S6O5). 13C NMR (CDCl3):
d
44.9, 69.3,
density for these solutions was measured at
l
¼354 nm and the
69.8, 70.7, 70.7, 70.7, 70.8, 71.1, 85.3, 115.8, 128.0, 128.4, 128.5, 129.9,
133.5, 147.3, 157.5. MS, m/z (%): 1143 ([MþH]þ, 100). Anal. Calcd for
C60H78N4O18: C, 63.03; H, 6.88; N, 4.90. Found: C, 62.96; H, 6.86; N,
4.77.
extractability in each case was calculated. For each experiment the
picrate extraction was performed 5 times on different samples, and
the average value was calculated. In the absence of molecular clips
no metal ion picrate extraction was detected.
4.3. X-ray crystal structure
4.6. FABMS evaluation of complexing ability of 1e5
The mixture of molecular clips 1e5 (5$10ꢁ6 mol) and corre-
sponding alkali metal picrate (5$10ꢁ6 or 1.5$10ꢁ5 mol) was dis-
solved in the minimal amount of 3-nitrobenzyl alcohol and this
solution was subjected to analysis. Spectra were recorded in posi-
tive mode, providing a primary argon atom beam at 8 keV.
Obtained spectral data is normalized to 100% total intensity for
macrocycle containing species ([MþH]þ, [MþMe]þ, [Mþ2Me]2þ
and [Mþ2MeþPi]þ).
Single crystals suitable for X-ray crystallography were grown by
crystallization of 1 and 2 from a MeOH/CHCl3 mixture. The X-ray
measurements were made on a Nonius Kappa CCD diffractometer
with graphite monochromated MoKa radiation using u rotation.
Both structures were solved by direct methods (SHELXS-97) and
refined on F2 by full-matrix least-squares techniques (SHELXL-
97).21 The non-hydrogen atoms were refined anisotropically. Hy-
drogen atoms were placed in calculated positions with isotropic
temperature factors and refined using a riding model. Chloroform
molecules in 1 are disordered around a twofold axis and were re-
fined as partially populated. Their hydrogen atoms are not local-
ized. Main crystallographic data are given in Table 3.
Acknowledgements
This article is dedicated to the memory of Prof. Nikolay G.
Lukyanenko (1947e2011), supervisor of this work, as well as to our
colleague Dr. Victor N. Pastushok (1954e2011), who took active
part in this research.
Table 3
Crystal and structure refinement data for 1$CHCl3 and 2$CHCl3
Parameter
1$CHCl3
2$CHCl3
Formula
fw
C45H47Cl3N4O10
910.22
C49H55Cl3N4O12
998.32
Supplementary data
Cryst system
Space group
Z
Monoclinic
C2/c
8
13.245(3)
27.674(6)
25.129(5)
97.18(3)
9139(3)
1.323
0.261
3808
7800
2824
Monoclinic
P21ꢁc
X-ray crystal data for molecular clips 1 and 2 (Table 3) is avail-
able. Crystallographic data for these structures in this paper have
been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication numbers CCDC 850842 and 850843.
Copies of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [e-mail: depos-
it@ccdc.cam.ac.uk]. Supplementary data associated with this article
can be found, in the online version, at doi:10.1016/j.tet.2012.04.009.
4
ꢁ
a (A)
8.2360(2)
32.1830(8)
19.6430(5)
113.3471(9)
4780.2(2)
1.387
0.259
2096
31,985/7492
2585
7492/1/614
0.863
ꢁ
b (A)
ꢁ
c (A)
b
(deg)
3
ꢁ
V (A )
Dc (gcmꢁ3
)
m
(mmꢁ1
)
F(000)
Reflns. collected/unique
Reflns. with [I>2 (I)]
s
References and notes
Data/restraints/params
7800/0/577
0.937
0.0709, 0.1517
0.2290, 0.2198
GOF on F2
€
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