Anion receptors based on ureido-substituted thiacalix[4]arenes and calix[4]arenes

Article abstract of DOI:10.1016/j.tet.2008.08.030

The regioselective nitration of 25,27-dipropoxythiacalix[4]arene was carried out as a key step in the synthesis of thiacalix[4]arene derivative bearing two arylureido functions on the upper rim. The preorganisation of ureido units using the thiacalix[4]arene/calix[4]arene moieties as a molecular scaffold gave novel anion receptors. These compounds, albeit based on hydrogen bonding interactions, show good complexation ability even in highly HB-competitive solvent, such as DMSO. Direct comparison of otherwise identical structures 6a and 7a revealed remarkable dominance of the thiacalix[4]arene derivative over its classical analogue in anion binding.

Full text of DOI:10.1016/j.tet.2008.08.030

Tetrahedron 64 (2008) 10075–10079
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Anion receptors based on ureido-substituted thiacalix[4]arenes and calix[4]arenes
a
a
b
c
a,
*
´
´
´
Jan Kroupa , Ivan Stibor , Michaela Pojarova , Marcela Tkadlecova , 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
Department of Analytical Chemistry, Institute of Chemical Technology, Technicka 5, 16628 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 29 April 2008
Received in revised form 18 July 2008
Accepted 7 August 2008
Available online 14 August 2008
The regioselective nitration of 25,27-dipropoxythiacalix[4]arene was carried out as a key step in the
synthesis of thiacalix[4]arene derivative bearing two arylureido functions on the upper rim. The pre-
organisation of ureido units using the thiacalix[4]arene/calix[4]arene moieties as a molecular scaffold
gave novel anion receptors. These compounds, albeit based on hydrogen bonding interactions, show
good complexation ability even in highly HB-competitive solvent, such as DMSO. Direct comparison of
otherwise identical structures 6a and 7a revealed remarkable dominance of the thiacalix[4]arene de-
rivative over its classical analogue in anion binding.
Keywords:
Thiacalixarene
Self-Assembly
X-ray crystallography
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
nitration. Unfortunately, the tetranitro derivative is very insoluble
in common organic solvents, which makes subsequent shaping of
The chemistry of thiacalixarenes, more than a decade since their
first appearance,1 still does not fully meet expectations. Despite
their very interesting complexation and molecular recognition
abilities,2 thiacalixarenes are only seldom used in the design of
more elaborate receptors and host molecules. Not surprisingly, the
introduction of four sulfur atoms imparts many novel features if
compared with the chemistry of classical calixarenes3 possessing
methylene bridges. As a result, the broader application of thiaca-
lixarenes in supramolecular chemistry is still limited by fragmen-
tary knowledge of their chemistry and the absence of general
derivatization methods, otherwise well established for –CH2– an-
alogues. Hence, a deeper understanding of their derivatisation
could make thiacalixarenes very useful building blocks for the
design of novel receptors.
Nitro-substituted calix[4]arenes act as common intermediates
for the preparation of amino-substituted derivatives (via re-
duction). Accordingly, the nitration of classical calix[4]arenes is
a well-established reaction that can be carried out either directly4
or via the ipso-substitution5 procedure. On the other hand, the
nitration in thiacalix[4]arene series is not so easy, since the oxi-
dation of sulfur bridges can occur as a competitive reaction.6 As we
have shown, this weak point can be circumvented using thiaca-
lixarene with pre-oxidised bridges (sulfones).7 The preparation of
tetranitrothiacalix[4]arene was described recently using direct8
the molecule (alkylation/acylation on the lower rim) difficult, and
in fact, no such procedure has been reported so far.
Anion complexation has been recognised as an important part of
supramolecular chemistry as documented by numerous reviews
and books published recently.9 Among them the calixarene-based
receptors for anion recognition represent a well-established re-
search topic.10 The introduction of urea moieties onto the calixar-
ene skeleton enables the construction of neutral well-preorganised
anion receptors designed for complexation via directional
hydrogen bonding from the urea functions.11 During our ongoing
research into anion recognition12 we have attempted the synthesis
of similar receptors based on thiacalixarenes to demonstrate the
usefulness of this novel system. In this paper, we report the syn-
thesis and complexation behaviour of the first anion receptor based
on upper-rim substituted thiacalix[4]arene.
2. Results and discussion
While the alkylation of classical calix[4]arene gives distally
dialkylated compounds always in the cone conformation,3 two
separable conformers can be isolated in the case of thiacalix[4]ar-
ene.13 Thus, dialkylation of 1 with propyl iodide in MeCN gave
a mixture of cone 2 and 1,2-alternate 2a0 (Scheme 1) where both
conformers can be obtained by column chromatography on silica
gel in 53% and 15% yields, respectively. During our ongoing research
on the thiacalixarene series, we wondered if these isomers can be
used for the subsequent regioselective derivatisation of thiacalix-
arenes without mutual interconversion.14 In the case of compound
* Corresponding author. Tel.: þ420 220445055; fax: þ420 220444288.
´
E-mail address: lhotakp@vscht.cz (P. Lhotak).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.08.030

10076
J. Kroupa et al. / Tetrahedron 64 (2008) 10075–10079
2a the best result was achieved using concd HNO3 in acetic acid/
CHCl3 mixture. After 3 h reflux under these conditions the dinitro
derivative 3a (cone) was isolated in 68% yield as the main product.
The corresponding 1,2-alternate conformation 3a0 was obtained
similarly starting from 2a0, albeit in lower yield (44%). As both nitro
derivatives 3a and 3a0 are stable under common conditions they
can be used independently for further synthesis.
The final evidence for the structure of 3a0 was obtained by single
crystal X-ray diffraction analysis (suitable monocrystals were
obtained by slow evaporation of an EtOAc/CH2Cl2 solution). The
molecule adopts a 1,2-alternate conformation with two nitro groups
pointing to the opposite sides of the molecule (Fig. 1a). A rather
unusual structural motif was found in the crystal packing of 3a0
(Fig. 1b). The neighbour molecules are interconnected by hydrogen
bonding interactions between the oxygen atom of nitro group and
meta-hydrogen of the corresponding phenolic units (O/H
distance¼2.54 Å).
NO2
O2N
Calixarenes bearing ureido functions on the upper rim are
known as anion receptors acting through hydrogen bonding in-
teractions.10–12 Hence, compound 3a immobilised in the cone
conformation was chosen for the synthesis of thiacalixarene-based
anionic receptor bearing two ureido moieties. The corresponding
reaction pathway is depicted in Scheme 2. Dinitro derivative 3a was
reduced using SnCl2 in refluxing ethanol to give amino-substituted
thiacalixarene 4a, which was subsequently condensed with p-tolyl
isocyanate. The resulting receptor 6a was isolated in 40% yield. To
compare the influence of the thiacalix[4]arene skeleton on a bind-
ing process, the corresponding derivatives of classical calix[4]arene
7a and 7b were prepared using a similar synthetic strategy.
The complexation ability of derivatives 6a and 7a,b towards
selected anions (Clꢀ, Brꢀ, acetate, benzoate) was measured by
standard 1H NMR titration experiments (DMSO-d6) using a con-
stant thiacalixarene concentration (0.1–2.0 mM) and increasing
concentrations of the appropriate anion to obtain different host/
guest ratios (0.1–40). All anions were used as tetrabutylammonium
salts to avoid possible complexation of cationic species by the
thiacalixarene cavity.
ii)
ii)
S
O
S
S
S
S
S
S
S
O
Pr
O
Pr
O
H
O
O
H
O
H
O
2a
3a
H
Pr
Pr
i)
+
+
H
O
H
O
O2N
Pr
Pr
S
O
O
O
H
4
S
S
S
S
S
S
S
S
1
O
O
O
O
2a'
3a'
Pr
Pr
H
O2N
H
Scheme 1. (i) K2CO3/n-PrI/MeCN, reflux, 7 days (2a, 53%; 2a0, 15%); (ii) 65% HNO3/
CHCl3–AcOH, reflux, 3 h (3a, 68%; 3a0, 44%).
The structures of the novel nitro derivatives were confirmed by
1H NMR analysis. Thus, compound 3a possesses one singlet of nitro-
substituted phenyl ring (
d 8.57 ppm), doublet and triplet due to the
unsubstituted ring ( 7.20 and 6.74 ppm) with typical interaction
d
constant (J¼7.7 Hz) in the aromatic part of spectrum. The theoret-
ically possible 1,3-alternate conformation (having the same split-
ting pattern) was excluded by NOE experiments. Surprisingly, the
splitting pattern of the 1,2-alternate conformer 3a0 is identical to
that of 3a (e.g., only one singlet for nitro-substituted ring at
Despite the application of highly HB-competitive solvent,
DMSO-d6, the addition of corresponding anions to the solution of
6a resulted in large down-field shifts of urea –NH– signals proving
strong hydrogen bonding interactions with the anion. Thus, the
originally almost unresolved –NH signals of free receptor 6a
(8.57 ppm) split into two resolved signals, which gradually moved
d
8.40 ppm) and does not correspond to the expected spectrum of
1,2-alternate. This phenomenon was recently observed in distally
disubstituted thiacalixarenes9 and it is consistent with fast ex-
change between two 1,2-alternate conformations.
Figure 1. (a) X-ray structure of 3a0, (b) hydrogen bonding interactions in the crystal packing of 3a0.

J. Kroupa et al. / Tetrahedron 64 (2008) 10075–10079
10077
R
R
NO2
X
NH2
O2N
H2N
HN
HN
NH
O
O
(i)
(ii)
X
X
X
X
NH
X
X
X
O
O
O
H
O
H
O
O
H
O
H
O
R
N=C=O
Pr
Pr
Pr
Pr
6a, X = S, R = Me
7a, X = CH2, R = Me
7b, X = CH2, R = NO2
X
X
X
5a, R = Me
5b, R = NO2
X
3a, X = S
3b, X = CH2
4a, X = S
4b, X = CH2
O
O
O
O
Pr
H
Pr
H
Scheme 2. (i) SnCl2/EtOH, reflux, overnight (4a, 49%); (ii) 4a or 4bþ5a,b/CH2Cl2, rt, 4 days (6a, 40%; 7a, 59%; 7b, 38%).
up to 11.86 and 12.08 ppm (upon addition of 7 equiv of acetate).
These unusually high complexation induced chemical shifts
Table 1
a
Binding constants K [Mꢀ1
]
of receptors 6a and 7a,b towards selected anionsb
(D
CIS¼3.29 and 3.51) clearly indicate strong binding of the anion
Anion
6a 7a 7b
via cooperative hydrogen bonds (NH/Anion) operating simulta-
neously from both ureido fragments. The plot of induced chemical
shifts (NH signals) versus anion concentration gave typical titration
curves corresponding to the formation of 1:1 complexes (Fig. 2).
The stoichiometry of complexation was further confirmed by Job
plot analysis of selected systems. The corresponding complexation
constants (Table 1) were calculated using an original non-linear
regression curve-fitting program.15
Clꢀ
40ꢂ1.5
24ꢂ1.6
48ꢂ2.4
Brꢀ
4.6ꢂ0.5
510ꢂ110
910ꢂ180
3.6ꢂ0.8
260ꢂ35
430ꢂ40
5.0ꢂ1.2
1170ꢂ80
2450ꢂ350
PhCOOꢀ
CH3COOꢀ
a
1H NMR titration (300 MHz, DMSO-d6, 298 K).
b
All anions were used as tetra-n-butylammonium (Bu4Nþ) salts.
3. Conclusions
As follows from Table 1, the complexation ability of 6a towards
halide anions is rather poor, and inversely proportional to halide’s
diameter (KCl¼40 Mꢀ1 vs KBr¼5 Mꢀ1 vs KI¼0 Mꢀ1). On the other
hand, complexation of carboxylate anions is much stronger with
In conclusion, we have carried out the first regioselective ni-
tration of 25,27-dipropoxythiacalix[4]arenes immobilised both in
the cone and in the 1,2-alternate conformations. Dinitro thiaca-
lix[4]arene was transformed into diureido derivative, which shows
remarkably better complexation ability towards selected anions if
compared with the corresponding classical calix[4]arene analogue.
preference for acetate (Kacetate¼910 Mꢀ1
)
over benzoate
(Kbenzoate¼510 Mꢀ1). The same trends can be seen for calix[4]arene
derivatives 7a and 7b. Interestingly, direct comparison of otherwise
identical structures 6a and 7a revealed remarkable dominance of
thiacalix[4]arene derivative over its classical analogue in anion
binding. As follows from Table 1, the corresponding complexation
constants of thiacalixarene 6a towards all selected anions are ap-
proximately doubled compared with those for classical calix[4]ar-
ene 7a (e.g., K6a¼40 Mꢀ1 vs K7a¼24 Mꢀ1 for Clꢀ or K6a¼510 Mꢀ1 vs
K7a¼260 Mꢀ1 for benzoate). The possible explanation of this phe-
nomenon could lie in the differences between the thiacalixarene
and calixarene diameters where the bigger cavity of thiacalix[4]-
arene probably enables better cooperation of both ureido functions.
Anyhow, the complexation data show interesting differences in
behaviour of both systems, thus indicating the usefulness of the
thiacalix[4]arene moiety as a promising building block in the de-
sign and construction of molecular receptors.
4. Experimental
4.1. General
Melting points were determined on a Boetius block (Carl Zeiss
Jena, Germany) and are not corrected. The IR spectra were mea-
sured on an FT-IR spectrometer Nicolet 740 in CHCl3 and/or in KBr.
1H NMR spectra were recorded on a Varian Gemini 300 spec-
trometer. Dichloromethane used for the reaction was dried with
CaH2 and stored over molecular sieves. The purity of the substances
and the courses of reactions were monitored by TLC using TLC al-
uminium sheets with Silica gel 60 F254 (Merck). Preparative TLC
chromatography was carried out on 20ꢁ20 cm glass plates covered
by Silica gel 60 GF254 (Merck).
Starting compound 3b5a was prepared according to known
procedure.
4.2. Synthesis of 5,17-dinitro-25,27-dipropoxy-
thiacalix[4]arene-26,28-diol (cone) 3a
Thiacalixarene 2a (460 mg, 0.687 mmol) was dissolved in
240 ml of CHCl3, and a mixture of glacial acetic acid (5 ml) and 65%
HNO3 (3.9 ml) was then slowly added at room temperature to the
solution. The reaction mixture was gradually warmed to reflux and
stirring was continued for next 3 h at this temperature. The re-
action mixture was then cooled down to room temperature and an
aqueous NaHCO3 (5% w/w) was added to neutralise the mixture.
After separation, the organic layer was washed with water
(3ꢁ100 ml) and dried over MgSO4. After filtration the solvent was
removed on vacuum evaporator and the remaining solid was rep-
recipitated from CH2Cl2/methanol mixture. The product 3a
Figure 2. 1H NMR titration curve for 6a with Bu4NþAcꢀ (300 MHz, 298 K, DMSO-d6).

10078
J. Kroupa et al. / Tetrahedron 64 (2008) 10075–10079
(360 mg, 68% yield) was obtained as orange solid after filtration.
Mp: 309–311 ꢃC (decomp.). 1H NMR (CDCl3, 300 MHz)
(ppm): 8.76
4.6. Synthesis of 5,17-bis[N0-(4-methylphenyl)ureido]-25,27-
dipropoxythiacalix[4]arene-26,28-diol (cone) 6a
d
(s, 2H, –OH), 8.57 (s, 4H, H-arom(NO2)), 7.20 (d, 4H, J¼7.6 Hz, m-H-
arom), 6.74 (t, 2H, J¼7.7 Hz, p-H-arom), 4.29 (t, 4H, J¼6.6 Hz, –O–
Diaminothiacalixarene 4a (0.164 mmol) was dissolved in 20 ml of
dryDCMandstirredundernitrogenwithisocyanate5a(0.984 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 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: 40%, mp: >350 ꢃC (decomp.). 1H
CH2–), 2.08 (m, 4H, –OCH2–CH2–), 1.21 (t, 6H, J¼7.3 Hz, –CH3). 13
C
NMR (CDCl3, 75 MHz)
d (ppm): 163.9, 159.4, 139.5, 137.4, 132.1,
127.8, 125.9, 123.0, 79.7, 23.2, 10.5. IR (KBr)
n
cmꢀ1: 3435, 2968,
1635, 1589, 1567, 1520, 1429, 1385, 1340, 1232. MS-ESIþ m/z 670.0
[M]þ (100%). Anal. Calcd for C30H26N2O8S4: C, 53.72; H, 3.91; N,
4.18; S, 19.12%. Found: C, 53.60; H, 3.71; N, 4.11%.
NMR (DMSO-d6, 300 MHz)
d (ppm): 8.57 (s, 2H, –NH–), 8.56 (s, 2H,
4.3. Synthesis of 5,17-dinitro-25,27-dipropoxy-
–NH–), 7.78 (s, 4H, H-arom), 7.38(2H, s, –OH), 7.34(d, 4H,J¼8.1 Hz,H-
arom), 7.08 (d, 4H, J¼8.1 Hz, H-arom), 7.02 (d, 4H, J¼8.0 Hz, H-arom),
6.70 (t, 2H, J¼7.6 Hz, p-H-arom), 4.30 (t, 4H, J¼6.4 Hz, –O–CH2–), 2.24
(s, 6H, Ar–CH3), 1.89 (m, 4H, –OCH2–CH2–), 1.08 (t, 6H, J¼7.4 Hz,
thiacalix[4]arene-26,28-diol (1,2-alternate) 3a0
This compound was prepared analogously to 3a (see above) in
44% yield. Mp: 312–314 ꢃC (decomp.). 1H NMR (CDCl3, 300 MHz)
–CH2–CH3). 13C NMR (DMSO-d6, 75 MHz)
d (ppm): 157.95, 152.64,
d
(ppm): 8.60 (s, 2H, OH), 8.40 (s, 4H, H-arom(NO2)), 7.62 (d, 4H,
152.20, 136.99, 135.05, 131.64, 130.59, 129.06, 128.63, 126.49, 125.30,
121.74,118.33, 76.67, 22.80, 20.23,10.29. IR (KBr)
2924, 1654, 1594, 1543, 1517, 1451, 1427, 1406, 1385, 1313, 1225. MS-
ESIþ m/z: 899.19 [MþNa]þ. Anal. Calcd for C46H44N4O6S4: C, 62.99; H,
5.06; N, 6.39; S, 14.62%. Found: C, 62.60; H, 4.91; N, 6.19%.
cmꢀ1: 3386, 2964,
J¼7.7 Hz, m-H-arom), 7.10 (t, 2H, J¼7.7 Hz, p-H-arom), 3.92 (t, 4H,
n
J¼6.6 Hz, –O–CH2–), 1.40 (m, 4H, –OCH2–CH2–), 0.54 (t, 6H, J¼
6.9 Hz, –CH3). 13C NMR (CDCl3, 75 MHz)
d (ppm): 162.5, 158.8, 139.8,
136.3, 128.4, 127.1, 126.0, 121.8, 77.1, 22.5, 9.6. IR (KBr)
2966, 1589, 1563, 1517, 1429, 1383, 1336, 1253. Anal. Calcd for
30H26N2O8S4: C, 53.72; H, 3.91; N, 4.18; S,19.12%. Found: C, 53.35; H,
n
cmꢀ1: 3436,
C
4.7. Synthesis of 5,17-bis[N0-(4-methylphenyl)ureido]-25,27-
dipropoxycalix[4]arene-26,28-diol (cone) 7a
3.68; N, 4.03%.
Prepared by the same procedure as described for 6a using 4b
and 5a as starting compounds. Yield: 59%, mp: >350 ꢃC (decomp.).
4.4. Synthesis of 5,17-diamino-25,27-dipropoxy-
thiacalix[4]arene-26,28-diol (cone) 4a
1H NMR (DMSO-d6, 300 MHz)
d (ppm): 8.38 (br s, 2H, –NH–), 8.25
(br s, 2H, –NH–), 8.15 (br s, 2H, –OH), 7.30 (d, 4H, J¼7.6 Hz, H-arom),
7.18 (s, 4H, H-arom), 7.04 (m, 8H, H-arom), 6.81 (t, 2H, J¼7.4 Hz,
H-arom), 4.19 (d, 4H, J¼12.6 Hz, Ar–CH2–Ar ax.), 3.94 (t, 4H,
J¼5.6 Hz, –O–CH2–CH2–), 3.39 (d, 4H, J¼12.6 Hz, Ar–CH2–Ar eq.),
2.23 (s, 6H, Ar–CH3), 2.00 (m, 4H, –CH2–CH3), 1.31 (t, 6H, J¼7.2 Hz,
Compound 3a (60 mg, 0.09 mmol) was dissolved in 20 ml of
ethanol and refluxed with SnCl2$2H2O (205 mg, 0.9 mmol) over-
night. The end of reaction was checked by TLC (DCM). Then solvent
was evaporated under reduced pressure, the solid residue dissolved
in DCM and washed with 1 M aqueous KOH and then with water.
The organic layer was dried over MgSO4, after filtration the solvent
was removed under vacuum. The product was obtained as a grey
solid (25 mg, 45%), which was used in the next step without further
purification. Mp: 229–232 ꢃC (decomp.). 1H NMR (CDCl3, 300 MHz)
–CH2–CH3). 13C NMR (DMSO-d6, 75 MHz)
d (ppm): 152.74, 151.81,
147.85, 137.41, 133.85, 131.10, 130.22, 129.10, 128.81, 127.89, 125.21,
119.42, 118.08, 78.10, 30.61, 23.06, 20.33, 10.83. IR (KBr)
n
cmꢀ1
:
3405, 2962, 2925, 1656, 1604, 1548, 1516, 1484, 1458, 1385, 1313,
1245,1201. MS-ESIþ m/z:827.31[MþNa]þ. Anal.CalcdforC50H52N4O6:
C, 74.60; H, 6.51; N, 6.96%. Found: C, 74.92; H, 6.24; N, 7.11%.
d
(ppm): 7.01 (s, 4H, H-arom(NH2)), 6.83 (d, 4H, J¼8.5 Hz, m-H-
arom), 6.69 (s, 2H, –OH), 6.46 (t, 2H, J¼7.8 Hz, p-H-arom), 4.27 (t,
4H, J¼6.8 Hz, –O–CH2–), 3.54 (br s, 4H, –NH2), 1.96 (m, 4H, –OCH2–
CH2–), 1.10 (t, 6H, J¼7.3 Hz, –CH2–CH3). 13C NMR (CDCl3, 75 MHz)
4.8. Synthesis of 5,17-bis[N0-(4-nitrophenyl)ureido]-25,27-
dipropoxycalix[4]arene-26,28-diol (cone) 7b
d
(ppm): 158.1, 150.5, 138.0, 134.3, 129.6, 124.7, 123.2, 123.1, 80.0,
23.2, 10.4. IR (KBr) n
cmꢀ1: 3419, 2963, 2926, 1618, 1563, 1445, 1431,
1384, 1326, 1229. MS-ESIþ m/z: 633.07 [MþNa]þ.
Prepared by the same procedure as described for 6a using 4b
and 5b as starting compounds. Yield: 28%, mp: 259–261 ꢃC. 1H NMR
(DMSO-d6, 300 MHz) d (ppm): 9.30 (br s, 2H, –NH–), 8.48 (br s, 2H,
4.5. Synthesis of 5,17-diamino-25,27-dipropoxycalix[4]-
arene-26,28-diol (cone) 4b
–NH–), 8.36 (br s, 2H, –OH), 8.17 (d, 4H, J¼9.0 Hz, H-arom), 7.67 (d,
4H, J¼9.0 Hz, H-arom), 7.23 (s, 4H, H-arom), 7.04 (d, 4H, J¼7.5 Hz,
H-arom), 6.83 (t, 2H, J¼5.9 Hz, H-arom), 4.20 (d, 4H, J¼11.1 Hz, Ar–
CH2–Ar ax.), 3.95 (br t, 4H, –O–CH2–CH2–), 3.42 (d, 4H, J¼13.5 Hz,
Ar–CH2–Ar eq.), 2.01 (br m, 4H, –CH2–CH3), 1.31 (br t, 6H, –CH2–
Dinitrocalix[4]arene 3b (477 mg, 0.80 mmol) was dissolved in
150 ml of ethyl acetate, catalytic amount of Pd/C (10%) was added
and the mixture was stirred overnight under hydrogen atmosphere.
The course of reaction was checked by TLC (petroleum ether/
EtOAc¼3:1). After the starting compound (Rf¼0.8) has disappeared
from the reaction mixture, catalyst was filtered off over short Celite
column. Finally, solvent was removed on vacuum evaporator to
yield 400 mg (93%) of title compound16 as beige solid, which was
used in the next step without further purification. Mp: >300 ꢃC. 1H
CH3). 13C NMR (DMSO-d6, 75 MHz)
146.70, 140.65, 133.73, 130.19, 128.80, 127.96, 125.10, 119.92, 117.20,
117.18, 78.25, 30.58, 23.03, 10.79. IR (KBr)
cmꢀ1: 3392, 2964, 2931,
d (ppm): 152.00, 151.78, 148.45,
n
1681, 1612, 1599, 1552, 1506, 1484, 1461, 1329, 1304, 1249, 1211. MS-
ESIþ m/z: 889.28 [MþNa]þ. Anal. Calcd for C48H46N6O10: C, 66.50; H,
5.35; N, 9.69%. Found: C, 66.18; H, 5.61; N, 9.52%.
NMR (CDCl3, 300 MHz)
d
(ppm): 7.66 (s, 2H, OH), 6.91 (d, 4H,
4.9. Crystallographic data for 3a0
J¼7.5 Hz, m-H-arom), 6.74 (t, 2H, J¼7.4 Hz, p-H-arom), 6.46 (s, 4H,
(H2N)-H-arom), 4.29 (d, 4H, J¼13.0 Hz, Ar–CH2–Ar ax.), 3.93 (t, 4H,
J¼6.4 Hz, –O–CH2–), 3.23 (d, 4H, J¼12.9 Hz, Ar–CH2–Ar eq.), 2.97 (br
s, 4H, –NH2), 2.04 (m, 4H, –OCH2–CH2–), 1.26 (t, 6H, J¼7.4 Hz, –CH2–
C30H26N2O8S4, M¼670.81 g molꢀ1, triclinic system, space group
P-1, a¼8.390(2) Å, b¼9.280(3) Å, c¼10.512(3) Å,
a
¼113.86(3)ꢃ,
b
¼89.09(2)ꢃ,
g
¼101.38(3)ꢃ, Z¼1, V¼731.8(4) Å3, Dc¼1.522 g cmꢀ3
,
CH3). 13C NMR (CDCl3, 75 MHz)
d
(ppm): 151.9, 146.0, 137.8, 133.5,
m
(Cu K
a
)¼3.467 mmꢀ1, crystal dimensions of 0.13ꢁ0.27ꢁ0.51 mm.
128.9, 128.6, 124.9, 115.8, 78.1, 31.3, 23.3, 10.7.
Data were collected at 150(2) K on a Xcalibur PX diffractometer

J. Kroupa et al. / Tetrahedron 64 (2008) 10075–10079
10079
9. For recent books and reviews on anion recognition see: (a) Sessler, J. L.; Gale,
P. A.; Cho, W. S. Anion Receptor Chemistry; The Royal Society of Chemistry:
Cambridge, 2006; (b) Anion Sensing, Topic in Current Chemistry; Stibor, I., Ed.;
Springer: Berlin, 2005; Vol. 255; (c) Gale, P. A. Coord. Chem. Rev. 2003, 240,
17–55; (d) Gale, P. A. Coord. Chem. Rev. 2006, 250, 3219–3244; Gale, P. A.;
Garcia-Garrido, S. E.; Garric, J. Chem. Soc. Rev. 2008, 37, 151–190; (e) Schottel,
B. L.; Chifotides, H. T.; Dunbar, K. R. Chem. Soc. Rev. 2008, 37, 68–83.
with graphite monochromated Cu Ka radiation. The structure was
solved by direct methods17 using the CRYSTALS suite of programs18
and anisotropically refined by full-matrix least-squares on F values
to final R¼0.0604 and Rw¼0.0724 using 11,645 independent re-
flections (qmax¼76.483ꢃ) and 199 parameters. At the end of re-
finement, hydrogen atoms were placed in calculated positions.
Crystallographic data were deposited in CSD under CCDC registra-
tion number 675371.
10. For review on calixarene-based anion receptors see: (a) Matthews, S. E.; Beer, P.
´
D. Calixarenes; 2001; pp 421–439 (see Ref. 3a); (b) Lhotak, P. Top. Curr. Chem.
2005, 255, 65–96; (c) Matthews, S. E.; Beer, P. D. Supramol. Chem. 2005, 17, 411–
435.
11. For some recent examples of urea-substituted calixarene-bases receptors see:
(a) Schazmann, B.; Alhashimy, N.; Diamond, D. J. Am. Chem. Soc. 2006, 128,
8607–8614; (b) Babu, J. N.; Bhalla, V.; Kumar, M.; Mahajan, R. K.; Puri, R. K.
Tetrahedron Lett. 2008, 49, 2772–2775; Quinlan, E.; Matthews, S. E.; Gunn-
laugsson, T. J. Org. Chem. 2007, 72, 7497–7503; Schazmann, B.; Diamond, D. New
J. Chem. 2007, 31, 587–592.
Acknowledgements
This research was partly supported by the Czech Science
Foundation (Grant 104/07/1242) and by MSMT Grant No. OC134.
12. (a) Stibor, I.; Dana, S. M. H.; Lhota´k, P.; Hodacova´, J.; Koca, J.; Cajan, M. Gazz.
´
´
Chim. Ital. 1997, 127, 673–685; (b) Budka, J.; Lhotak, P.; Michlova, V.; Stibor, I.
Tetrahedron Lett. 2001, 42, 1583–1586; (c) Stastny, V.; Lhota´k, P.; Michlova´, V.;
Supplementary data
´
Stibor, I.; Sykora, J. Tetrahedron 2002, 58, 7207–7211; (d) Dudic, M.; Lhotak, P.;
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2008.08.030.
Stibor, I.; Lang, K.; Proskova´, P. Org. Lett. 2003, 5, 149–152; (e) Zlatuskova, P.;
Stibor, I.; Tkadlecova´, M.; Lhota´k, P. Tetrahedron 2004, 60, 11383–11390; (f)
Lang, K.; Curinova, P.; Dudic, M.; Proskova, P.; Stibor, I.; Stastny, V.; Lhotak, P.
´
´
´
Tetrahedron Lett. 2005, 46, 4469–4472; (g) Lhota´k, P.; Svoboda, J.; Stibor, I.
References and notes
´
Tetrahedron 2006, 62, 1253–1257; (h) Stibor, I.; Budka, J.; Michlova, V.;
ˇ´
´
´
Tkadlecova´, M.; Pojarova´, M.; Curınova, P.; Lhotak, P. New J. Chem. 2008. doi:
10.1039/b802871k
1. Kumagai, H.; Hasegawa, M.; Miyanari, S.; Sugawa, Y.; Sato, Y.; Hori, T.; Ueda, S.;
Kamiyama, H.; Miyano, S. Tetrahedron Lett. 1997, 38, 3971–3972.
2. For recent reviews on thiacalixarenes see: (a) Morohashi, N.; Narumi, F.; Iki, N.;
Hattori, T.; Miyano, S. Chem. Rev. 2006, 106, 5291–5316; (b) Lhotak, P. Eur. J. Org.
Chem. 2004, 1675–1692.
ꢀ
13. Dvorakova´, H.; Lang, J.; Vlach, J.; Sykora, J.; Cajan, M.; Himl, M.; Pojarova´, M.;
Stibor, I.; Lhota´k, P. J. Org. Chem. 2007, 72, 7157–7166.
14. For unusual conformational behaviour of thiacalixarenes, see e.g.: (a) Lang, J.;
Dvora´kova´, H.; Bartosova´, I.; Lhota´k, P.; Stibor, I.; Hrabal, R. Tetrahedron Lett.
´
´
´
´
1999, 40, 373–376; (b) Lhotak, P.; Kaplanek, L.; Stibor, I.; Lang, J.; Dvorakova, H.;
Hrabal, R.; Sykora, J. Tetrahedron Lett. 2000, 41, 9339–9344; (c) Cajan, M.;
Lhota´k, P.; Lang, J.; Dvora´kova´, H.; Stibor, I.; Koca, J. J. Chem. Soc., Perkin Trans. 2
3. For books on calixarenes see: (a) Calixarenes 2001; Asfari, Z., Bo¨hmer, V., Har-
rowfield, J., Vicens, J., Eds.; Kluwer Academic: Dordrecht, 2001; (b) Mandolini,
L.; Ungaro, R. Calixarenes in Action; Imperial College Press: London, 2000; (c)
Gutsche, C. D. In Calixarenes Revisited: Monographs in Supramolecular Chemistry;
Stoddart, J. F., Ed.; The Royal Society of Chemistry: Cambridge, 1998; Vol. 6.
4. Kelderman, E.; Derhaeg, L.; Heesink, G. J. T.; Verboom, W.; Engbersen, J. F. J.;
Hulst, N. F.; Persoons, A.; Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl. 1992, 31,
1075–1077.
´
´
´
´
2002, 1922–1929; (d) Lhotak, P.; Himl, M.; Stibor, I.; Sykora, J.; Dvorakova, H.;
Lang, J.; Petrickova´, H. Tetrahedron 2003, 59, 7581–7585.
15. The stoichiometry of complexes and the complexation constants were calcu-
lated using computer program OPIUM (Kyvala M.) freely available at: http://
www.natur.cuni.cz/wkyvala/opium.html.
16. (a) Liang, Z.; Liu, Z.; Jiang, L.; Gao, Y. Tetrahedron Lett. 2007, 48, 1629–1632; (b)
Struck, O.; Chrisstoffels, L. A. J.; Lugtenberg, R. J. W.; Verboom, W.; van Hummel,
G. J.; Harkema, S.; Reinhoudt, D. N. J. Org. Chem. 1997, 62, 2487–2493.
17. Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.; Giacovazzo, C.; Gua-
gliardi, A.; Moliterni, A. G. G.; Polidori, G.; Spagna, R. J. Appl. Crystallogr. 1999, 32,
115–119.
5. (a) Verboom, W.; Durie, A.; Egberink, R. J. M.; Egberink, J. M.; Asfari, Z.; Rein-
houdt, D. N. J. Org. Chem. 1992, 57, 1313–1316; (b) Jakobi, R. A.; Bo¨hmer, V.;
Gru¨ ttner, C.; Kraft, D.; Vogt, W. New J. Chem. 1996, 20, 493–501.
6. Lhota´k, P. Tetrahedron 2001, 57, 4775–4779.
´
7. Lhotak, P.; Svoboda, J.; Sykora, J.; Stibor, I. Tetrahedron Lett. 2002, 43, 7413–7417.
8. (a) Desroches, C.; Parola, S.; Vocanson, F.; Perrin, M.; Lamartine, R.; Letoffe,
J.-M.; Bouix, J. New J. Chem. 2002, 26, 651–655; (b) Hu, X.; Zhu, Z.; Shen, T.;
Shi, X.; Ren, J.; Sun, Q. Can. J. Chem. 2004, 82, 1266–1270.
18. Watkin, D. J.; Prout, C. K.; Carruthers, R. J.; Betteridge, P. Crystals, Issue 10;
Chemical Crystallography Laboratory: Oxford, UK, 1996.