Anion binding by meta ureido-substituted thiacalix[4]arenes

Article abstract of DOI:10.1016/j.tet.2011.08.062

The regioselective nitration of 25,26,27,28-tetrapropoxythiacalix[4]arene (1,3-alternate) led to the formation of mono- and dinitro derivatives bearing NO₂ groups in the meta positions at the same side of the molecule. Their reduction and subse

Full text of DOI:10.1016/j.tet.2011.08.062

Tetrahedron 67 (2011) 8367e8372
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Anion binding by meta ureido-substituted thiacalix[4]arenes
a
b
a
a,
*
ꢀ
ꢁ
ꢁ
ꢀ
ꢁ c
ꢁ
Ondrej Kundrat , Vaclav Eigner , Petra Curínova , Jan Kroupa , Pavel Lhotak
a
ꢁ
Department of Organic Chemistry, Institute of Chemical Technology, Technicka 5, 16628 Prague 6, Czech Republic
Department of Solid State Chemistry, Institute of Chemical Technology, Technicka 5, 16628 Prague 6, Czech Republic
Institute of Chemical Process Fundamentals, v.v.i., Academy of Sciences of the Czech Republic, Rozvojova 135, 165 02 Prague 6, Czech Republic
b
ꢁ
c
ꢁ
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 15 April 2011
Received in revised form 3 August 2011
Accepted 22 August 2011
Available online 27 August 2011
The regioselective nitration of 25,26,27,28-tetrapropoxythiacalix[4]arene (1,3-alternate) led to the for-
mation of mono- and dinitro derivatives bearing NO2 groups in the meta positions at the same side of the
molecule. Their reduction and subsequent condensation with arylisocyanates gave the new types of
anion receptors with a so far unknown meta-substitution pattern. In a highly HB-competitive solvent like
DMSO, the novel ligands showed good complexation abilities. Moreover, as can be documented by higher
complexation constants, achiral receptors 9a, 9b are better preorganized for anion binding than corre-
sponding stereoisomers 10a, 10b. Our results indicate that anion receptors based on meta-substituted
thiacalixarenes possess complexation abilities fully comparable with common para-substituted
analogues.
Keywords:
Calixarene
meta-Nitration
Recognition
Anion binding
X-ray crystallography
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
immobilized in the cone or 1,3-alternate5 conformations, which
were proven as very efficient ligands for the complexation of anions
Calix[n]arenes1 are used frequently as molecular scaffolds in the
synthesis of various ligands and receptors. As macrocyclic com-
pounds with well-established basic chemistry, they offer an almost
unlimited degree of freedom in regioselective or stereoselective
derivatisation with many applications in the design of novel func-
tional molecules. One of them, anion complexation, has been rec-
ognised as an important part of supramolecular chemistry. The
principal role of anions in biological systems, various chemical
processes, or environmental pollution issues can be demonstrated
by the vast literature focused on this topic published recently.2
Not surprisingly, calix[4]arene derivatives represent a very
popular macrocyclic skeleton for the design of anion receptors.3
The unique three-dimensional tuneable shape of the molecule
makes this compound especially versatile for the preparation of
neutral anion receptors, where successful binding of anions re-
quires high degree of preorganisation, interaction directionality
and complementarity. Thus, the introduction of amide or urea/
thiourea moieties onto the calixarene skeleton enables the design
of neutral anion receptors, which possess highly directional hy-
drogen bonds from suitably preorganised eNHe functions.
possessing different geometries. The characteristic feature of all
these receptors is the fact that they are based on para-substituted
calixarene derivatives (which is a consequence of general calixar-
ene reactivity). Very recently, we have described unusual regiose-
lectivity of thiacalix[4]arene6 derivatives enabling the introduction
of various substituents into the meta positions of the thiacalixarene
skeleton. Thus, regioselective formylation, chloromethylation or
nitration7 opens the door for completely novel substitution pattern,
essentially inaccessible in classical calixarene chemistry so far.
Here we report on the synthesis and complexation ability of
ureido-thiacalix[4]arenes having one or two arylurea units
appended to the upper rim of the thiacalixarene skeleton. As the
ureido functions are placed at the meta positions of thiacalixarenes,
this kind of receptor is unprecedented in calixarene chemistry.
2. Results and discussion
Tetrapropoxy derivative 1, immobilized in the 1,3-alternate
conformation, was prepared by a known procedure8 using alkyl-
ation of the starting thiacalix[4]arene with PrI/K2CO3 in acetone.
The nitration of 1 was carried out in a CHCl3eglacial acetic acid
mixture using aqueous 65% HNO3 as the nitration agent.7a Mono-
nitro derivative 2 was prepared on a gram-scale in a 74% yield by
reaction with 80 equiv of HNO3. Similarly, using higher excess of
HNO3, dinitro derivatives 3 and 4 were obtained (both in 26%
yields) after column chromatography of the crude reaction mixture
During our on-going research on anion recognition, we have
reported4 a series of new bis- to tetrakis-(ureido)calix[4]arenes
* Corresponding author. Tel.: þ420 220445055; fax: þ420 220444288; e-mail
addresses: pavel.lhotak@vscht.cz, lhotakp@vscht.cz.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.062

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O. Kundrat et al. / Tetrahedron 67 (2011) 8367e8372
8368
on silica gel. Nitro derivatives 2e4 were then reduced with
SnCl2$2H2O in refluxing ethanol to give amino derivatives 5, 6 and 7
in 88, 95 and 95% yields, respectively. Target receptors 8e10 were
obtained by the reaction of amines with appropriate isocyanates (p-
tolyl or p-nitrophenyl) in dichloromethane at room temperature
and they were isolated in 60e71% yields.
The solvent is held by two nonsymmetrical hydrogen bonds from
ureido NH functions with O/H distances 2.20 and 2.72 A, re-
ꢂ
spectively (Fig. 2a). It indicates that the eNHe group connected
directly to the p-nitrophenyl moiety is more acidic than the other,
and consequently, creates stronger hydrogen bond towards the
oxygen atom in THF. An unexpected intermolecular interaction was
observed for p-nitrophenylureido moieties. These units are strictly
coplanar to each other forming dimer with interplanar distance
The structures of novel compounds were confirmed by the
combination of 1H NMR and MS analysis. Thus, the ESI MS of de-
rivative 9a showed a signal at m/z 983.34, corresponding to the
diureido compound with a sodium cation [MþNa]þ. Similarly,
compounds 8a and 8b exhibited molecular peaks [MþH]þ at m/z
813.34 and 844.20, respectively, proving the presence of only one
arylureido group in the molecule. The expected feature of the 1H
NMR spectra of all meta-substituted derivatives should be the oc-
currence of two doublets in aromatic region with a coupling con-
stant of 8.4e8.5 Hz. These doublets correspond to characteristic
signals from the meta-substituted thiacalixarene rings. Whereas
this expected splitting pattern is well observable in amino de-
rivatives 5e7 (Fig. 1), the 1H NMR spectra of final receptors are
frequently too complicated due to overlapping with the signals of
p-tolyl or p-nitrophenyl moieties. Anyhow, compound 9a possesses
two typical doublets at 7.73 and 7.38 ppm, while nitrourea de-
rivative 10b shows doublets at 7.75 and 7.18 ppm (CDCl3/
CD3OD¼4:1).
ꢂ
3.33 A where the carbonyl C atom is situated exactly above the C1
atom of p-nitrophenyl moiety.
Fig. 2. Crystallographic structure of compound 8b, (a) complex with THF; (b) packing
motif with
pep interactions of p-nitrophenylureido moieties (THF and second thia-
calix[4]arene molecule partly deleted for better clarity).
The 1H NMR titration experiments towards selected anions were
performed in DMSO-d6. As the complexation phenomenon is based
on the hydrogen bonding interactions of ureido eNHe groups with
anions, the resulting complexation constants are rather small if
compared with less competitive solvents (e.g., CDCl3). On the other
hand, using the HB-competitive solvent was necessary to avoid
extensive oligomerization of compounds 8e10 due to the in-
termolecular hydrogen bonds. As shown in Fig. 3a, the 1H NMR
spectrum of compound 10b in CDCl3 exhibits very intricate and
highly diffused peak patterns indicating nonspecific HB in-
teractions of the molecules. These interactions can be smoothly
destroyed by addition of CD3OD (Fig. 3b). Unfortunately, this led
simultaneously to the disappearance of ureido eNHe signals,
which are usually used as the indicators of complexation phe-
nomenon. Thus, the DMSO-d6 solutions of our receptors (Fig. 3c)
represent the best choice, as the corresponding 1H NMR spectra of
8e10 are well resolved (only monomeric structures are present)
and the signals of ureido functions are well observable in the low-
field part of the spectra.
Fig. 1. Partial 1H NMR spectra of 6 and 7 showing a typical splitting pattern of meta-
substituted thiacalix[4]arenes (300 MHz, 298 K, CDCl3).
The final unequivocal structural evidence was obtained using
single crystal X-ray crystallography. Albeit we were unable to grow
suitable monocrystals for diureido derivatives 9 and 10, mono-
ureido compound 8b was obtained in a suitable quality after the
crystallization from THF/EtzOH mixture. As shown in Fig. 2, com-
pound 8b crystallizes in Pꢀ1 space group with one molecule of THF.

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O. Kundrat et al. / Tetrahedron 67 (2011) 8367e8372
8369
Table 1
a
Binding constants K [Mꢀ1
]
of receptors 8e10 towards selected anions. 1H NMR ti-
trations (300 MHz, DMSO-d6, 298 K)
Anion
8a
8b
9a
9b
10a
10b
PhCOOꢀ
170ꢁ40
820ꢁ170 230ꢁ40 1300ꢁ230 130ꢁ40 360ꢁ40
CH3COOꢀ 180ꢁ50 2900ꢁ890 430ꢁ60
920ꢁ100 200ꢁ10 660ꢁ150
Clꢀ
25ꢁ5
6ꢁ1
50ꢁ10
18ꢁ5
280ꢁ40
12ꢁ1
270ꢁ70
14ꢁ3
27ꢁ7
9ꢁ1
150ꢁ10
22ꢁ6
Brꢀ
H2POꢀ4
230ꢁ50 1070ꢁ130 140ꢁ35 db
180ꢁ50 106ꢁ36
a
All anions were used as tetra-n-butylammonium (Bu4Nþ) salts.
Unclear stoichiometry.
b
Fig. 3. 1H NMR spectra of derivative 9a in CDCl3 (green), CDCl3/CD3OD mixture (red),
and DMSO-d6 (blue); (300 MHZ, 298 K).
The 1H NMR titrations were carried out using a constant calix-
arene host concentration (0.5e2.0 mM) and an increasing concen-
tration of appropriate anion to obtain different host/anion ratios (1
to 20:1). All anions (BzOꢀ, AcOꢀ, Clꢀ, Brꢀ and H2POꢀ4 ) were added in
the form of tetrabutylammonium (TBA) salts to minimise any pos-
sible interference of cation due to undesirable interactions with
calixarene cavities. The results obtained are summarised in Table
1.In all cases, the large complexation-induced shifts (CIS >2 ppm)
were observed for the NH protons of the urea moiety. It suggests that
these groups are responsible for the binding of anions via co-
operative hydrogen bonding interactions. The complexation con-
stants for the anions were determined by analyzing the binding
isotherms (obtained from NMR data) using the original nonlinear
curve-fitting program (program OPIUM).9 The titration curves
(Fig. 4) suggest the formation of complexes with 1:1 stoichiometry.
All titration experiments confirmed the expected fact that receptors
possessing electron-withdrawing p-nitrophenylgroups (8b, 9b,10b)
form complexes with higher association constants than receptors
having p-tolyl substituents (8a, 9a, 10a). Thus, compare K10b
(AcOꢀ)¼650ꢁ160 for receptor 10b with the same constant for p-
tolyl derivative 10a-K10a (AcOꢀ)¼200ꢁ10 molꢀ1 dm3. Rather un-
expected results were obtained in the case of diureido receptors 9
and 10. It is known that receptors with two or even more ureido
moieties on the upper rim of calixarene create stronger complexes
with anions (1:1 stoichiometry) than corresponding monourea
derivatives. This effect is based on the preorganisation of ureido
moieties, which can bind an anion by cooperative hydrogen bond-
ing. However, no significant differences in the complexation con-
stants were observed for mono- or di-ureido receptors in the case of
meta-substituted derivatives 8e10. Thus, the highest association
constant for acetate was found for compound 8b having only one
ureido group (K8b¼2900ꢁ890 molꢀ1 dm3), while achiral 9b and
chiral 10b analogues possess much lower complexation constants:
K9b¼920ꢁ100 molꢀ1 dm3 and K10b¼660ꢁ150 molꢀ1 dm3, re-
spectively. This anomalous behaviour could be explained by the long
distance and the wrong mutual geometry of both ureido functions in
chiral derivatives (10a and 10b). On the other hand, in the case of
achiral receptors 9a and 9b the neighbouring propoxygroupinvokes
a steric hindrance to the system, which effectively obstructs the
cooperative binding from both ureido functions.
Fig. 4. 1H NMR titration of receptor 9a with Bu4Nþ benzoate (DMSO-d6, 300 MHz,
298 K).
3. Conclusions
In conclusion, the direct nitration of alkylated thiacalix[4]arene
enabled the construction of novel class of calixarene-based re-
ceptors with so far inaccessible meta-substitution pattern. These
compounds, possessing arylureido moieties, are capable of anion
binding and showed very good complexation ability even in highly
HB-competitive solvent, such as DMSO. As can be documented by
respective complexation constants, achiral receptors 9a, 9b are
better preorganized for the anion binding than the corresponding
chiral regioisomers 10a, 10b.
4. Experimental
4.1. General
Melting points are uncorrected and were determined using
Heiztisch MikroskopdPolytherm A (Wagner and Munz, Germany).
The IR spectra were measured on an FT-IR spectrometer Nicolet 740
in KBr. Mass spectra were measured using ESI technique on QeTOF
(Micromass) spectrometer. Elemental analyses were measured on
PerkineElmer 240, Elementar vario EL (Elementar, Germany) or
Mitsubishi TOXe100 instruments.1H NMR spectra were recorded
on a Varian Gemini 300 spectrometer. Dichloromethane (DCM)
used for the reactions was dried with CaH2 and stored over mo-
lecular sieves. The courses of reactions were monitored by TLC
using TLC aluminium sheets with Silica gel 60 F254 (Merck).
The synthesis of all three nitro derivatives 2e4 (Scheme 1) has
been recently published by our group.7a
4.1.1. 4-Amino-25,26,27,28-tetrapropoxythiacalix[4]arene (1,3-alter-
nate) 5. Nitroderivative 2 (260 mg, 0.37 mmol) was dissolved in
50 ml of ethanol and refluxed with SnCl2$2H2O (830 mg,
3.66 mmol) overnight. The course of reaction was checked by TLC
(hexane/DCM¼1:2 v/v). Then the solvent was evaporated under

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O. Kundrat et al. / Tetrahedron 67 (2011) 8367e8372
Scheme 1. Preparation of ureido-substituted receptors 8e10.
reduced pressure, the solid residue dissolved in DCM and washed
with 1 M KOH and then with water (3ꢂ50 ml). The organic layer
was dried over MgSO4 and the solvent was evaporated under vac-
uum. The title compound was obtained (220 mg, 88%) as grey solid,
which was used in the next step without further purification. 1H
72.2, 23.2, 23.1, 10.6, 10.0. IR (KBr) nmax (cmꢀ1): 3444, 2961, 2919,
2874, 2851, 1603, 1457, 1433, 1378, 1231. EA for C36H42N2O4S4 calcd:
C, 62.21; H, 6.09; N, 4.03; S,18.45%; found: C, 62.01; H, 5.88; N, 3.90;
S, 18.01%. MS ESIþ m/z 695.21[MþH]þ.
NMR (CDCl3, 300 MHz, 298 K)
d
(ppm): 7.44 (d, J¼7.6 Hz, 1H, arH),
4.1.3. 4,16-Diamino-25,26,27,28-tetrapropoxythiacalix[4]arene (1,3-
alternate) 7. Dinitroderivative 4 (368 mg, 0.487 mmol) was dis-
solved in ethanol (50 mL) and SnCl2$2H2O (1.10 g, 4.87 mmol) was
added. The reaction mixture was then heated to reflux overnight.
After cooling, the solvent was evaporated and a solution of 1 M
NaOH was added to bring pH to 10. The mixture was extracted with
DCM, the organic phase was washed with water, dried over MgSO4
and evaporated to dryness. Product 7 (322 mg) was obtained in
a 95% yield. Mp 200e202 ꢃC 1H NMR (CDCl3/CD3OD, 300 MHz,
7.37 (m, 4H, arH), 7.22 (d, J¼8.5 Hz, 1H, arH), 6.44 (d, J¼8.2 Hz, 1H,
arH), 3.85 (m, 8H, eOeCH2e), 1.55e1.20 (m, 8H, eOCH2eCH2e),
0.75 (m, 9H, eCH3), 0.68 (t, J¼7.6 Hz, 3H, eCH3). 13C NMR (CDCl3,
75 MHz, 298 K)
d (ppm): 161.94, 159.99, 159.07, 147.64, 134.01,
133.43, 133.11, 132.82, 132.49, 132.43, 132.16, 129.90, 129.35, 128.87,
128.77, 128.69, 122.75, 122.69, 122.54, 117. 86, 116.62, 114. 07, 71.86,
71.36, 71.14, 22.96, 22.62, 22.45, 22.36, 10.28, 10.09, 9.96, 9.81. IR
(KBr) nmax (cmꢀ1): 3375, 3053, 2959, 2873, 1600, 1561, 1473, 1457,
1431, 1380, 1315, 1235. MS-ESIþ m/z: 680.17 [MþH]þ (100%).
298 K)
d
(ppm): 7.46 (d, J¼7.7 Hz, 2H, arH), 7.40 (d, J¼7.7 Hz, 2H,
arH), 7.21 (d, J¼8.3 Hz, 2H, arH), 6.76 (t, J¼7.8 Hz, 2H, arH), 6.29 (d,
J¼8.3 Hz, 2H, arH), 4.02e3.67 (m, 8H, eOeCH2e), 2.05e1.76 (m, 2H,
eOCH2eCH2e), 1.70e1.37 (m, 6H, eOCH2eCH2e), 0.82 (t, J¼7.4 Hz,
4.1.2. 4,18-Diamino-25,26,27,28-tetrapropoxythiacalix[4]arene (1,3-
alternate) 6. Derivative 3 (338 mg, 0.448 mmol) was dissolved in
ethanol (50 mL) and SnCl2$2H2O (1.01 g, 4.48 mmol) was added.
The reaction mixture was then heated to reflux overnight. After
cooling, the solvent was evaporated and a solution of 1 M NaOH
was added to bring pH to 10. A product was extracted with DCM,
the organic phase was washed with water, dried over MgSO4 and
evaporated to dryness. Product 6 (296 mg) was obtained in a 95%
yield and was used in the next step without further purification. Mp
12H, eCH3).13C NMR (CDCl3/CD3OD, 75 MHz, 298 K)
d (ppm): 162.5,
159.6, 134.9, 134.7, 130.1, 129.2, 122.8, 122.7, 116.5,114.7, 109.9, 109.7,
73.07, 72.8, 23.4, 23.1, 10.6, 10.2 ppm. IR (KBr) nmax (cmꢀ1): 3471,
2962, 2934, 2874, 1601, 1457, 1433, 1378, 1316, 1232. EA for
C36H42N2O4S4 calcd: C, 62.21; H, 6.09; N, 4.03; S, 18.45%; found: C,
62.01; H, 5.88; N, 3.90; S, 18.01%. MS ESIþ m/z 717.19 [MþNa]þ.
120e123 ꢃC. 1H NMR (CDCl3/CD3OD, 300 MHz, 298 K)
d
(ppm): 7.47
4.2. Synthesis of receptors 8a,bdgeneral procedure
(d, J¼8.1 Hz, 2H, arH), 7.36 (d, J¼7.7 Hz, 2H, arH), 7.20 (d, J¼8.4 Hz,
2H, arH), 6.78 (q, J¼7.4 Hz, 2H, arH), 6.31 (d, J¼8.4 Hz, 2H, arH),
4.02e3.78 (m, 4H, eOeCH2e), 3.75e3.67 (m, 2H, eOeCH2e), 3.61
(t, J¼7.3 Hz, 2H, eOeCH2e), 1.61e1.31 (m, 8H, eOCH2eCH2e),
0.96e0.68 (m, 12H, eCH3). 13C NMR (CDCl3/CD3OD, 75 MHz, 298 K)
Aminothiacalixarene 5 (100 mg, 147 mmol) was dissolved in
20 ml of dry DCM and stirred under nitrogen with appropriate
isocyanate (0.441 mmol) for 4 days at room temperature. To quench
the reaction, methanol (30 ml) was added and the mixture was
stirred for 15 min. Solvents were then removed under reduced
d
(ppm): 162.2, 160.5, 158.9, 148.5, 130.1, 129.1, 116.9, 114.1, 72.4,

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O. Kundrat et al. / Tetrahedron 67 (2011) 8367e8372
8371
pressure and the resulting solid was triturated with 40 ml of MeOH/
DCM¼40:1 mixture. The product in the form of white precipitate
was collected by filtration, washed with methanol and dried.
yield 71%. 1H NMR (CDCl3/CD3OD, 300 MHz, 298 K)
d
(ppm): 8.12 (d,
J¼9.0 Hz, 2H, arH), 8.05 (d, J¼9.0 Hz, 4H, arH), 7.77 (d, J¼8.7 Hz, 2H,
arH), 7.52 (d, J¼9.0 Hz, 4H, arH), 7.40 (d, J¼7.8 Hz, 2H, arH), 7.33 (dd,
J¼8.2 and 2.1 Hz, 2H, arH), 6.83e6.74 (m, 2H, arH), 3.95e3.71 (m,
8H, eOeCH2e), 1.34e1.24 (m, 6H, eOCH2eCH2e), 1.07e0.94 (m,
2H, eOCH2eCH2e), 0.72 (t, J¼7.7 Hz, 3H, eCH3), 0.65 (t, J¼7.5 Hz,
6H, eCH3), 0.42 (t, J¼7.4 Hz, 3H, eCH3). 13C NMR (CDCl3/CD3OD,
4 . 2 . 1. 4 - N 0- ( 4 - m e t h y l p h e n y l ) u r e i d o - 2 5 , 2 6 , 2 7 , 2 8 -
tetrapropoxythiacalix[4]arene (1,3-alternate) 8a. Mp >300 ꢃC
(decomp.), yield: 63%. 1H NMR (CDCl3, 300 MHz, 298 K)
d (ppm):
7.96 (s, 1H, eNHe), 7.84 (d, J¼8.5 Hz, 1H, arH), 7.36 (m, 6H, arH),
7.29 (d, J¼7.9 Hz, 1H, arH), 7.22 (d, J¼8.5 Hz, 2H, arH), 7.12 (d,
J¼7.9 Hz, 2H, arH), 6.81 (t, J¼7.6 Hz, 2H, arH), 6.80 (t, J¼7.6 Hz, 1H,
arH), 6.51 (s, 1H, eNHe), 4.05e3.68 (m, 7H, eOeCH2e), 3.38 (q, 1H,
eOeCH2e), 2.29 (s, 3H, ar-CH3), 1.41e1.10 (m, 8H, eOCH2eCH2e),
0.71 (q, J¼7.6 Hz, 6H, eCH3), 0.62 (q, J¼7.3 Hz, 6H, eCH3). 13C NMR
300 MHz, 298 K) d (ppm): 202.9, 175.8, 164.7, 149.9, 146.1, 142.7,
137.0, 132.9, 132.6, 129.3, 127.2, 122.4, 121.7, 76.7, 75.4, 27.6, 26.8,
26.1, 14.2. IR (KBr) nmax (cmꢀ1): 3364, 2964, 2876, 1722, 1598, 1567,
1496, 1364, 1331, 1301, 1254. EA for C50H50N6O10S4 calcd: C, 58.69;
H, 4.93; N, 8.21; S, 12.53%; found: C, 58.31; H, 4.46; N, 7.94; S,
12.28%. MS ESIþ m/z 1061.21 [MþK]þ.
(CDCl3, 75 MHz, 298 K)
d (ppm): 160.93, 160.00, 159.68, 158.72,
152.80, 139.41, 134.75, 134.65, 133.46, 132.98, 132.54, 132.27, 132.13,
131.56, 129.92, 129.24, 129.13, 128.76, 128.59, 128.05, 122.88, 122.71,
122.69, 122.34, 122.04, 118.27, 114.62, 71.69, 71.11, 70.78, 22.80,
22.46, 22.18, 20.86, 10.18, 10.04, 9.87, 9.63. IR (KBr) nmax (cmꢀ1):
2962, 2875, 1663, 1609, 1574, 1544, 1506, 1465, 1430, 1382, 1366,
1311, 1290, 1250, 1232, 1200. MS-ESIþ m/z: 813.34 [MþH]þ (100%).
4.3.3. 4,16-Bis[N0-(4-tolyl)ureido]-25,26,27,28-tetrapropoxythiacalix
[4]arene (1,3-alternate) 10a. Mp 164e166 ꢃC, yield: 68%. 1H NMR
(CDCl3/CD3OD, 300 MHz, 298 K)
d
(ppm): 7.77 (d, J¼8.7 Hz, 2H,
arH), 7.28e7.25 (m, 4H, arH), 7.16 (dd, J¼8.7 and 1.4 Hz, 4H, arH),
6.97 (d, J¼8.2 Hz, 6H, arH), 6.72 (t, J¼7.7 Hz, 2H, arH), 3.85e3.75 (m,
2H, eOeCH2e), 3.72e3.64 (m, 4H, eOeCH2e), 3.41e3.33 (m, 2H,
eOeCH2e), 2.17 (s, 6H, ar-CH3), 1.25e1.18 (m, 4H, eOCH2eCH2e),
1.08e0.98 (m, 4H, eOCH2eCH2e), 0.60e0.50 (m, 12H, eCH3). 13C
4.2.2. 4-N0-(4-nitrophenyl)ureido-25,26,27,28-tetrapropoxythiacalix
[4]arene (1,3-alternate) 8b. Mp >300 ꢃC (decomp.), yield: 64%. 1H
NMR (CDCl3/CD3OD, 300 MHz, 298 K) d (ppm): 164.8, 162.7, 143.9,
NMR (CDCl3, 300 MHz, 298 K)
d
(ppm): 8.17 (d, J¼9.1 Hz, 2H, arH),
140.0, 137.2, 133.6, 133.1, 132.4, 127.0, 125.4, 124.5, 122.2, 75.5, 75.4,
26.7, 26.2, 24.8, 14.1, 13.7. IR (KBr) nmax (cmꢀ1): 3319, 2963, 2936,
2875, 1678, 1610, 1574, 1546, 1504, 1432, 1365, 1222. EA for
C52H56N4O6S4 calcd: C, 64.97; H, 5.87; N, 5.83; S, 13.34%; found: C,
64.40; H, 5.33; N, 5.49; S, 13.04%. MS ESIþ m/z 978.34 [(MþH2O)]þ.
7.89 (s, 1H, eNHe), 7.65 (d, J¼8.2 Hz, 1H, arH), 7.60 (d, J¼9.1 Hz, 2H,
arH), 7.56 (s,1H, eNHe), 7.41 (m, 6H, arH), 7.31 (d, J¼7.9 Hz,1H, arH),
6.83 (t, J¼7.6 Hz, 3H, arH), 4.08e3.77 (m, 6H, eOeCH2e), 3.64 (q, 2H,
eOeCH2e), 1.52e1.17 (m, 8H, eOCH2eCH2e), 0.75 (m, 6H, eCH3),
0.69 (t, J¼7.6 Hz, 3H, eCH3), 0.63 (t, J¼7.6 Hz, 3H, eCH3). 13C NMR
(CDCl3, 75 MHz, 298 K)
d
(ppm): 161.39, 160.03, 159.78, 159.25,
4.3.4. 4,16-Bis[N0-(4-nitrophenyl)ureido]-25,26,27,28-
158.80, 151.70, 145.00, 142.57, 138.86, 134.80, 134.14, 134.01, 133.45,
133.43, 132.65, 132.14, 129.61, 129.05, 128.97, 128.91, 128.81, 127.86,
125.11,124.14,123.16,122.99,118.21,116.25, 72.97, 72.12, 71.16, 22.89,
22.68, 22.37, 22.28,10.17, 9.87, 9.70. IR (KBr) nmax (cmꢀ1): 2963, 2876,
1721,1616,1598,1559,1508,1498,1465,1430,1381,1366,1331,1300,
1257, 1231, 1176. MS-ESIþ m/z: 844.20 [MþH]þ (43%).
tetrapropoxythiacalix[4]arene (1,3-alternate) 10b. Mp 236e239 ꢃC,
yield: 60%. 1H NMR (CDCl3/CD3OD, 300 MHz, 298 K)
d (ppm): 8.00
(d, J¼8.9 Hz, 4H, arH), 7.76 (d, J¼8.5 Hz, 2H, arH), 7.50 (d, J¼8.9 Hz,
4H, arH), 7.28 (d, resonance overlapped with solvent signal, 4H,
arH), 7.19 (d, J¼8.9 Hz, 2H, arH), 6.71 (t, J¼7.6 Hz, 2H, arH),
3.86e3.78 (m, 2H, eOeCH2e), 3.72e3.65 (m, 4H, eOeCH2e),
3.49e3.41 (m, 2H, eOeCH2e), 1.22e0.98 (m, 8H, eOCH2eCH2e),
0.57e0.46 (m, 12H, eCH3). 13C NMR (CDCl3/CD3OD, 300 MHz,
4.3. Synthesis of receptors 9 and 10dgeneral procedure
298 K)
d (ppm): 164.8, 162.7, 156.3, 150.2, 146.1, 143.3, 136.4, 133.0,
Diamino derivatives 6 or 7 (70 mg, 0.100 mmol) were dissolved
in dry DCM (10 ml) and stirred under nitrogen with 6 equiv of the
corresponding isocyanate (0.600 mmol) at room temperature for 2
days. To quench the reaction, methanol (30 mL) was added and the
mixture was stirred for 1 h. The solvents were then removed under
reduced pressure and the resulting solid was triturated with
methanol (40 mL) in an ice bath. The product was filtered off,
washed with methanol and dried.
132.3, 129.3, 126.1, 121.9, 75.5, 75.4, 26.7, 26.2, 14.1, 13.5. IR (KBr)
nmax (cmꢀ1): 3354, 2964, 2936, 2876, 1717, 1598, 1559, 1455, 1433,
1365, 1330, 1302, 1257, 1222, 1192 cmꢀ1. EA for C50H50N6O10S4
calcd: C, 58.69; H, 4.93; N, 8.21; S, 12.53%; found: C, 58.42; H, 4.60;
N, 8.03 S, 12.22%. MS ESIþ m/z 1040.28 [MþH2O]þ.
4.4. NMR titration experiments
The 1H NMR titration experiments were performed using
a constant calixarene host concentration (0.5e2.0 mM) and in-
creasing concentration of appropriate guest to obtain different
host/guest ratios (1 to 20:1) in DMSO-d6 as solvent using a Varian
Gemini 300 spectrometer (300 MHz, 298 K). The corresponding
binding constants (Table 1) were calculated using the original non-
linear regression curve-fitting program.8
4.3.1. 4,18-Bis[N0-(4-tolyl)ureido]-25,26,27,28-tetrapropoxythiacalix
[4]arene (1,3-alternate) 9a. Mp 182e185 ꢃC, yield: 61%. 1H NMR
(CDCl3/CD3OD, 300 MHz, 298 K)
d
(ppm): 7.74 (d, J¼8.7 Hz, 2H,
arH), 7.39 (d, J¼7.8 Hz, 2H, arH), 7.30 (dd, J¼8.7 and 2.3 Hz, 4H, arH),
7.19 (d, J¼8.3 Hz, 4H, arH), 7.00 (d, J¼8.3 Hz, 4H, arH), 6.80e6.71 (m,
2H, arH), 3.92e3.71 (m, 8H, eOeCH2e), 2.20 (s, 6H, ar-CH3),
1.34e1.24 (m, 6H, eOCH2eCH2e), 1.05e0.95 (m, 2H,
eOCH2eCH2e), 0.71e0.62 (m, 9H, eCH3), 0.44 (t, J¼7.7 Hz, 3H,
4.5. X-ray crystallography
eCH3). 13C NMR (CDCl3/CD3OD, 300 MHz, 298 K)
d (ppm): 165.0,
164.2, 161.7, 157.5, 143.5, 140.1, 136.9, 133.5, 133.1, 132.6, 127.3, 126.9,
126.1, 121.9, 76.1, 75.3, 33.8, 26.7, 26.0, 14.2, 13.2. IR (KBr) nmax
(cmꢀ1): 3339, 2964, 2935, 2875, 1699, 1609, 1574, 1545, 1507, 1433,
1364, 1290, 1250, 1221. EA for C52H56N4O6S4 calcd: C, 64.97; H, 5.87;
N, 5.83; S, 13.34%; found: C, 64.54; H, 5.30; N, 5.67; S, 13.05%. MS
ESIþ m/z 983.30 [MþNa]þ.
4.5.1. Crystallographic data for C43H45N3O7S4$0.5C4H8O$0.5C2-
H5OH. M¼903.20, triclinic system, space group Pꢀ1, a¼11.0289(11)
¼89.396(9)ꢃ,
b
¼81.766(8)ꢃ,
ꢂ
ꢂ
ꢂ
A, b¼11.1273(15) A, c¼20.7232(18) A,
a
3
ꢀ3
m
ꢃ
ꢂ
g
¼63.438(12) , Z¼2, V¼2247.2(5) A , Dc¼1.335 g cm
,
(Cu K
a)¼
2.403 mmꢀ1, crystal dimensions of 0.15ꢂ0.21ꢂ0.36 mm. Data were
collected at 170(2) K on a Xcalbur OnyxCCD diffractometer with
graphite monochromated Cu Ka radiation. The structure was solved
4.3.2. 4,18-Bis[N0-(4-nitrophenyl)ureido]-25,26,27,28-
tetrapropoxythiacalix[4]arene (1,3-alternate) 9b. Mp 205e207 ꢃC,
by direct methods9,10 using the CRYSTALS suite of programs10,11 and
anisotropically refined by full matrix least squares on F squared

ꢁ
O. Kundrat et al. / Tetrahedron 67 (2011) 8367e8372
8372
Garrido, S. E.; Garric, J. Chem. Soc. Rev. 2008, 37, 151e190; (d) Cametti, M.;
Rissanen, K. Chem. Commun. 2009, 2809e2829; (e) Sessler, J. L.; Gale, P. A.; Cho,
W. S. Anion Receptor Chemistry; The Royal Society of Chemistry: Cambridge,
2006; (f) Recognition of Anions; Vilar, R., Ed.; Springer GmbH: Berlin, 2008; (g)
Gale, P. A.; Beer, P. D. Angew. Chem., Int. Ed. 2001, 40, 486e516; (h) Supramo-
lecular Chemistry of Anions; Bianchi, A., Bowman-James, K., Garcia-Espana, E.,
Eds.; Wiley-VCH: New York, NY, 1997.
value to final R¼0.0757 and Rw¼0.238 using 9234 independent
reflections (Qmax¼80.2ꢃ), 604 parameters and 51 restrains. The
positions of mixed solvent were found from the electron density
maps. Mixed solvents were then placed in appropriate positions,
and all distances between neighbouring atoms and angles were
fixed. Site occupancies were assigned resulting in similar thermal
parameters for both solvent molecules. The hydrogen atoms were
placed in calculated positions for carbon and solvent atoms. For
nitrogen atoms hydrogen atoms were found from differential
electron density maps and refined with soft restrains to regularize
their geometry. The structure was deposited into Cambridge
Structural Database under number CCDC 819648.
3. For review on calixarene-based anion receptors see: (a) Kalchenko, V. I. Pure Appl.
Chem. 2008, 80,1449e1458; (b) Matthews, S. E.; Beer, P. D. Supramol. Chem. 2005,
ꢁ
17, 411e435; (c) Lhotak, P. Top. Curr. Chem. 2005, 255, 65e96 see Ref 2b; (d)
Calixarenes; Matthews, S. E., Beer, P. D., Eds.; 2001; pp 421e439 see Ref 1c.
4. For some recent examples of urea-substituted calixarene-based receptors
ꢀ
ꢁ
from our group see: (a) Curínova, P.; Stibor, I.; Budka, J.; Sykora, J.; Lang, K.;
ꢁ
ꢁ
Lhotak, P. New J. Chem. 2009, 33, 612e619; (b) Stibor, I.; Budka, J.; Michlova,
ꢁ
ꢁ
ꢀ
ꢁ
ꢁ
V.; Tkadlecova, M.; Pojarova, M.; Curínova, P.; Lhotak, P. New J. Chem. 2008,
32, 1597e1607; (c) Kroupa, J.; Stibor, I.; Pojarova, M.; Tkadlecova, M.; Lhotak,
ꢁ
P. Tetrahedron 2008, 64, 10075e10079; (d) Lhotak, P.; Svoboda, J.; Stibor, I.
ꢁ
Tetrahedron 2006, 62, 1253e1257; (e) Lang, K.; Curinova, P.; Dudic, M.;
Acknowledgements
ꢁ
ꢁ
Proskova, P.; Stibor, I.; Stastny, V.; Lhotak, P. Tetrahedron Lett. 2005, 46,
4469e4472.
This research was partly supported by Czech Science Foundation
(203/09/0691) and by the Grant Agency of the Academy of the
Sciences of the CR (IAAX08240901). Grants MSM 6046137301 and
MSM 6046137302 from Ministry of Education, Youth and Sports of
the Czech Republic are also highly acknowledged.
5. For some examples of anion receptors based on urea-substituted calixarene in
the 1,3-alternate conformation see: (a) Schazmann, B.; Alhashimy, N.; Diamond,
D. J. Am. Chem. Soc. 2006, 128, 8607e8614; (b) Filby, M. H.; Dickson, S. J.;
Zaccheroni, N.; Prodi, L.; Bonacchi, S.; Montalti, M.; Chiorboli, C.; Paterson, M. J.;
Humphries, T. D.; Steed, J. W. J. Am. Chem. Soc. 2008, 130, 4105e4113; (c) Ryu, B.
J.; Jeon, N. J.; Nam, K. C. Bull. Korean Chem. Soc. 2010, 31, 3445e3447.
6. For reviews on thiacalixarenes, see: (a) Morohashi, N.; Narumi, F.; Iki, N.;
Hattori, T.; Miyano, S. Chem. Rev. 2006, 106, 5291e5316; (b) Lhotak, P. Eur. J. Org.
Chem. 2004, 1675e1692.
Supplementary data
€
7. (a) Kundrat, O.; Kroupa, J.; Bohm, S.; Budka, J.; Eigner, V.; Lhotak, P. J. Org. Chem.
€
2010, 75, 8372e8375; (b) Kundrat, O.; Cisarova, I.; Bohm, B.; Pojarova, M.;
Supplementary data related to this article can be found online at
doi:10.1016/j.tet.2011.08.062.
Lhotak, P. J. Org. Chem. 2009, 74, 4592e4596; (c) Kundrat, O.; Dvorakova, H.;
Eigner, V.; Lhotak, P. J. Org. Chem. 2010, 75, 407e411; (d) Kundrat, O.; Dvorakova,
H.; Cisarova, I.; Pojarova, M.; Lhotak, P. Org. Lett. 2009, 11, 4188e4191.
ꢁ
8. Lhotak, P.; Himl, M.; Pakhomova, S.; Stibor, I. Tetrahedron Lett. 1998, 39,
References and notes
8915e8918.
9. The biding constants were calculated using the computer program OPIUM
(Kyvala M.) freely available at: http://www.natur.cuni.cz/wkyvala/opium.html.
All our attempts to measure the stoichiometry of complexes using Job plot
analysis have failed as the small complexation constants did not lead to well
resolved maximum in the corresponding plots. Anyhow, the complexation
curves gave the best fit using 1:1 stoichiometry.
10. Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A.; Burla, M. C.; Polidori,
G.; Camalli, M. J. Appl. Crystallogr. 1994, 27, 435.
11. Betteridge, P. W.; Carruthers, J. R.; Cooper, R. I.; Prout, K.; Watkin, D. J. J. Appl.
Crystallogr. 2003, 36, 1487.
1. For books on calixarenes, see: (a) Gutsche, C. D. Calixarenes an Introduction, 2nd
ed.; The Royal Society of Chemistry, Thomas Graham House: Cambridge, 2008;
(b) Calixarenes in the Nanoworld; Vicens, J., Harrowfield, J., Backlouti, L., Eds.;
Springer: Dordrecht, 2007; (c) Calixarenes 2001; Asfari, Z., Bohmer, V., Har-
rowfield, J., Vicens, J., Eds.; Kluwer Academic: Dordrecht, 2001; (d) Mandolini,
L.; Ungaro, R. Calixarenes in Action; Imperial College: London, 2000.
2. For recent reviews/books on anion-recognition, see: (a) Amendola, V.; Fab-
brizzi, L. Chem. Commun. 2009, 513e531; (b) Anion Sensing Topics in Current
Chemistry Vol. 255; Stibor, I., Ed.; Springer: Berlin, 2005; (c) Gale, P. A.; Garcia-
€