Selenacalix[3]triazines: Synthesis and host-guest chemistry

Article abstract of DOI:10.1039/c1cc15473g

The heteracalixarene series (N/O/S) has been expanded with Se-bridged cyclotrimeric macrocycles. Selenacalix[3]triazines were synthesized by convenient one-pot nucleophilic aromatic substitution reactions and they showed peculiar supramolecular features.

Full text of DOI:10.1039/c1cc15473g

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Chemical Communications
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Volume 48 | Number 1 | 4 January 2012 | Pages 1–164
ISSN 1359-7345
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W. Dehaen et al.
Selenacalix[3]triazines: synthesis and host–guest chemistry
1359-7345(2012)48:1;1-B

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Selenacalix[3]triazines: synthesis and host–guest chemistryw
Joice Thomas,a Wim Van Rossom,a Kristof Van Hecke,b Luc Van Meervelt,b Mario Smet,a
Wouter Maesac and Wim Dehaen*a
Received 2nd September 2011, Accepted 29th September 2011
DOI: 10.1039/c1cc15473g
The heteracalixarene series (N/O/S) has been expanded with
Se-bridged cyclotrimeric macrocycles. Selenacalix[3]triazines
were synthesized by convenient one-pot nucleophilic aromatic
substitution reactions and they showed peculiar supramolecular
features. The N tridentate binding pocket was capable of
coordinating both copper ions and anions.
Organoselenium chemistry is intensively studied because of
its potential impact on cancer prevention, inflammation
protection, immune response and photodynamic therapy.4
Encouraged by the importance of natural selenoproteins,
many organo-Se compounds have been designed to mimic
the functions demonstrated by natural enzymes such as
glutathione peroxidase and towards antithyroid drugs.5 Macro-
cycles containing Se are attractive targets for several reasons.6
The larger atomic radius of Se leads to an increased cavity size
and it may impose electronic and structural characteristics that
are quite different from those of O-, N- or S-containing macro-
cycles. The enhanced s-donating ability of Se can strengthen its
complexation ability towards transition metals and electron
acceptors. The presence of Se atoms also imposes a novel
derivatization pathway by reversible oxidation to selenoxides
or selenones, which enables these molecules to bind different
guest species in their different oxidation states.
The introduction of heteroatoms replacing the methylene
linkages of traditional calixarenes is an efficient approach to
modulate the macrocycle’s properties. The resulting hetera-
calixarenes are particularly attractive for applications in
supramolecular chemistry since the bridging heteroatoms enable
us to tune the ring size and host conformation, and provide
additional binding sites towards a perfect (induced) fit of a
desirable guest.1–3 Among the heteracalixarenes (mostly S, N
and O, but also Si, Ge, Sn and P) the thia analogues have been
studied most and they are widely recognized as receptors for
small organic compounds and heavy/transition metals.1b,c On the
other hand, reports on the synthesis and applications of aza- and
oxacalixarenes have steadily increased during the last decade.1d–f
Azacalixarene cyclooligomers have been explored as powerful
hosts towards fullerene binding and for selective adsorption of
CO2 in the solid state.2 Modern oxacalixarene research has
mainly been focused on the development of novel synthetic
procedures and postmacrocyclization modifications of the calix-
arenoid framework, although the enlarged scope of O-bridged
calix(hetero)aromatics has triggered the first initiative towards
supramolecular applications.3 Up to now, there has been no
information on the expansion of heteracalixarene chemistry from
the smaller group via elements (O/S) to the subsequent third or
fourth-row ‘‘isologues’’ of the chalcogen series (Se/Te).
The peculiar features of Se considered together with the
significant difference in physical properties of the heteracalixarene
series prompted us to design and construct calixarenoid
macrocycles containing bridging Se atoms.6e The general
synthetic strategy is based on the nucleophilic aromatic
substitution (SNAr) reaction of in situ generated Se bisnucleophiles
with electrophilic halogenated heterocycles. As their highly
electron deficient nature ensures excellent reactivity in SNAr
reactions, 2,4-dichloro-1,3,5-triazine building blocks were applied
(Scheme 1).1f,g
The first synthetic trial involved the addition of NaSeH
(freshly prepared by reaction of a 1 : 2 molar ratio of Se
powder and NaBH4 suspended in EtOH) to a solution of
2-butyl-4,6-dichloro-1,3,5-triazine (1a) in THF, yielding
selenacalix[3]-triazine 2a in a very poor yield (4%). By
optimizing the SNAr conditions the yield was increased
spectacularly to 75%.7 Another profound advantage of the
synthetic protocol is the easiness of purification of the cyclotrimer
a Molecular Design and Synthesis, Department of Chemistry,
Katholieke Universiteit Leuven, Celestijnenlaan 200F, 3001 Leuven,
Belgium. E-mail: wim.dehaen@chem.kuleuven.be;
Tel: +32 16327439
b Biomolecular Architecture, Department of Chemistry, Katholieke
Universiteit Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium
c Design & Synthesis of Organic Semiconductors (DSOS), Institute
for Materials Research (IMO), Hasselt University, Universitaire
Campus, Agoralaan – Building D, 3590 Diepenbeek, Belgium
w Electronic supplementary information (ESI) available: Synthetic
procedures and characterization data, 1H and 13C NMR spectra,
X-ray crystallographic data for 2c, 3c, and 4c, and additional details
on the metal salt and anion titrations. CCDC 808717, 808718, 816095.
For ESI and crystallographic data in CIF or other electronic format
see DOI: 10.1039/c1cc15473g
Scheme 1 Synthetic pathway towards selenacalix[3]triazines 2a–c.
Chem. Commun., 2012, 48, 43–45 43
c
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simply by precipitation directly from the reaction mixture in water.
Curiously, only the selenacalix[3]arene macrocycle was formed
under all conditions.7 To vary the substitution pattern, functional
moieties were introduced prior to macrocyclization. The corres-
ponding trimeric cyclooligomer 2b (R = OPh) was prepared in a
similarly high yield (70%; Scheme 1). Under the same conditions
the reaction of triazine precursor 1c (R = NEt2) and NaSeH
resulted in an unsatisfactory yield of selenacalix[3]arene 2c (4%).
An appreciable amount of unreacted starting material remained in
the reaction mixture, which can be attributed to the (further)
increase in electron density. A substantially improved conversion
(55% 2c) was achieved by optimizing the concentration, reaction
time and temperature.7 Calix[3]triazines 2a–c showed good
solubility in a variety of organic solvents and were adequately
characterized by NMR spectroscopy (1H, 13C and 77Se) and (high
resolution) mass spectrometry.
Fig. 2 ORTEP representation of CuII complex 3c. Thermal displacement
ellipsoids are shown at the 50% probability level.
Cu and Rh via their pyridine lone pairs.8c,e The binding
potential of the selenacalix[3]triazines has initially been
evaluated using macrocycle 2c. Reaction of 2c with one
equivalent of CuBr2 in THF at RT resulted in precipitation
of the monomeric complex [2c–CuBr2] (3c) as a green solid in
high yield (94%). The molecular structure of the complex was
unambiguously determined by X-ray crystallography (Fig. 2).
In comparison with the structure of the free ligand 2c, the
macrocycle adopts a less planar conformation. The CuII ion
coordinates tridentately to the three interior triazine N atoms
and the coordination environment is completed by the two BrÀ
anions. The corresponding CuI complex 4c was synthesized in an
analogous way and the solid-state structure shows very similar
features (see ESIw).
To gain more insight on the complex formation in solution
UV/Vis titrations were performed (in MeCN). Calix[3]arene 2c
exhibits a main broad absorption band centered at 259 nm
(e = 3.15 Â 104 MÀ1 cmÀ1), while upon titration with CuIIBr2
a bathochromic shift to 273 nm and a concurrent increase in
absorbance (e = 6.17 Â 104 MÀ1 cmÀ1) was observed
(see ESIw). A clear isosbestic point could be seen at l = 262 nm,
indicating an equilibrium between the free ligand and its CuII
complex. Titration curves were fitted to a 1 : 1 stoichiometry model,
as determined via single-crystal X-ray analysis, using HypSpec
software and an association constant Kass Z 106 MÀ1 was
obtained (Table 1).9 Titration of 2c with CuIBr gave an almost
identical shift and increase in intensity (e = 6.72 Â 104 MÀ1 cmÀ1).
However, more equivalents of the Cu salt were required and
therefore a lower affinity (Kass = 2.4 Â 104 MÀ1) was derived
(Table 1) (see ESIw).
The successful formation of selenacalix[3]triazines with high
yield and selectivity rather than linear oligomeric or polymeric
materials was achieved by carefully optimizing the appropriate
SNAr reaction parameters.7 The absence of evidence for the
formation of larger cyclic oligomers suggests that the trimeric
macrocycles may be the thermodynamically favoured products
from a reversible dynamic process of ring opening and cyclization.
This contrasts the trend in oxacalixarene chemistry in which
oxacalix[3]arenes have never been observed so far and the
oxacalix[4]arene represents the thermodynamic sink.1e,f,3
Heteracalix[3]arenes are known in the thia- and azacalixarene
field, in which they are usually obtained in small amounts from
one pot reactions affording a mixture of calixarenes of different
ring sizes, and they have shown peculiar supramolecular features.8
Single crystals of selenacalix[3]triazine 2c were grown to
elucidate its solid-state structure. A distorted coplanar conformation
was observed, i.e. the three triazine units are tilted with respect
to the plane formed by the bridging Se atoms, with two of the
rings inclined below the plane (12.31 and 20.51) and one above
the plane (9.31) (Fig. 1). The macrocycles are stacked on top of
each other, forming columns along the [010] direction
(see ESIw).
The most appealing property of calixarenes is their tendency
to form host–guest complexes with a variety of organic and
inorganic species. A limited number of (mostly azine-based)
heteracalix(het)arene macrocycles have previously been shown
to form complexes with metal ions, both in solution and in the
solid state.2,3,8d Thiacalix[3]pyridines have been shown to bind
Anion recognition by artificial macrocyclic receptors has
attracted a lot of attention due to the increased awareness of
the vital importance of anions in many biological and
Table 1 Association constants Kass [MÀ1] for the 1 : 1 complexation
between hosts 2a–c and metal salts or anionic guests in dry MeCNa
À
À
CuBr2 CuBr
HSO4 H2PO4
HCO3 AcOÀ
À
ClÀ
0c
2a
2b
—
—
—
—
0c
0c
30
950
545
5240
3260
8.6 Â 104 0c
2c Z 106b 2.4 Â 104 Z 106b 1.2 Â 104 0c
0c
0c
a
Calculated on the basis of UV/Vis titration data using HypSpec.9b
Values are the average of at least three separate l’s and are considered
reproducible to 10%. This value is Z 106 MÀ1. As such the stability
constant is at the upper limit of what can be determined by this
b
Fig. 1 ORTEP representation of 2c, as determined by X-ray crystallo-
graphy. Thermal displacement ellipsoids are shown at the 50%
probability level.
c
technique and should be treated with caution. No notable spectral
changes.
c
44 Chem. Commun., 2012, 48, 43–45
This journal is The Royal Society of Chemistry 2012

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Notes and references
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Fig. 3 UV/Vis titration of 2c with (n-Bu)4N(HSO4) in MeCN. Inset:
À
variation of absorbance at l = 275 nm vs. equiv. of HSO4 added.
environmental systems.10 In this respect there is also a rising
interest in the supramolecular exploitation of anion–arene inter-
actions, caused by favorable interaction between anions and
neutral electron poor (het)arenes.11 Recent studies have indicated
that the p–acidic cavity of tetraoxacalix[2]arene[2]triazines is
capable of halide anion binding, both in solution and in the
solid state, due to a synergic effect of noncovalent halide–p and
lone pair–p interactions.3d,h,j As we envisioned that the p–electron
deficient cavity of the selenacalix[3]triazines could also be
capable of anion recognition, a preliminary investigation
towards their affinity for a small variety of putative anionic
guests was performed. UV/Vis titrations of host 2c with ClÀ,
AcOÀ or HCO3À in MeCN did not induce any notable spectral
changes. However, when hydrogen sulfate was titrated with
the host solution, a clear isosbestic point and a noticeable
bathochromic and hyperchromic shift were observed (Fig. 3).
The Job plot revealed a 1 : 1 (host : guest) stoichiometry (see
ESIw) and an association constant Kass Z 106 MÀ1 was
deriveÀd, pointing out the particularly high affinity of 2c for
HSO4 (Table 1). The complex could also be identified by
ESI-MS (see ESIwÀ). In addition, a weaker interaction with the
less acidic H2PO4 was also observed (Table 1). The type of
complex and the preferred binding motif (anion–arene versus
protonation) remain unknown, as solid-state evidence could
not be obtained. Additional UV/Vis titrations for
selenacalix[3]arenes 2a and 2b did not provide any firm
clarification regarding this issuÀe, as a reverse trend could be
distinguished (AcOÀ 4 HCO3 4 H2PO4À), while no inter-
action with HSO4À was observed (Table 1). The complexation
is obviously very sensitive to the substitution pattern, which
suggests two competitive mechanisms.7
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7 An upcoming study will focus on the synthetic details and
elaborate on the supramolecular and solid-state features of these
materials.
8 Heteracalix[3]arenes: (a) M. Mascal, J. L. Richardson, J. A. Blake
and W. Li, Tetrahedron Lett., 1997, 38, 7639; (b) A. Ito, Y. Ono and
K. Tanaka, J. Org. Chem., 1999, 64, 8236; (c) R. Tanaka, T. Yano,
T. Nishioka, K. Nakajo, B. K. Breedlove, K. Kimura, I. Kinoshita
and K. Isobe, Chem. Commun., 2002, 1686; (d) Y. Suzuki, T. Yanagi,
T. Kanbara and T. Yamamoto, Synlett, 2005, 263; (e) Y. Tsukahara,
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Y. Inoue, Y. Watanabe and T. Kanbara, Org. Lett., 2010, 12, 5242.
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In summary, selenacalix[3]triazines were synthesized selectively
in a high yield, representing the first examples of Se-bridged
heteracalixarenes and thereby enlarging the scope and supra-
molecular applications of heteroatom-bridged calix(hetero)-
aromatics. UV/Vis titration studies indicated high binding affinities
for the complexation of Cu salts and anionophoric properties
depending on the substitution pattern. Further elaboration of
the synthetic and supramolecular chemistry of selenacalixarenes
is currently actively being pursued within our group.
We thank the FWO, the KU Leuven and the Ministerie
voor Wetenschapsbeleid for continuing financial support.
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 43–45 45