Anion complexation by triazolium "ligands": Mono- and bis-tridentate complexes of sulfate

Article abstract of DOI:10.1021/ol100776x

By utilizing click chemistry and methylation, the triazolium motif was employed to design tridentate "ligands" that bind by electron acception instead of electron donation. As electronically inverted ligands they are able to complex sulfate ions by hydrog

Full text of DOI:10.1021/ol100776x

ORGANIC
LETTERS
2010
Vol. 12, No. 12
2710-2713
Anion Complexation by Triazolium
“Ligands”: Mono- and Bis-tridentate
Complexes of Sulfate
Benjamin Schulze,† Christian Friebe,† Martin D. Hager,† Wolfgang Gu¨nther,†
Uwe Ko¨hn,† Burkhard O. Jahn,† Helmar Go¨rls,‡ and Ulrich S. Schubert*,†,§
Laboratory of Organic and Macromolecular Chemistry, Friedrich-Schiller-UniVersity
Jena, Humboldtstr. 10, 07743 Jena, Germany, Laboratory of Inorganic and Analytic
Chemistry, Friedrich-Schiller-UniVersity Jena, Lessing-Str. 8, 07743 Jena, Germany,
and Laboratory for Macromolecular Chemistry and Nanoscience, EindhoVen
UniVersity of Technology, P.O. Box 513, 5600 MB EindhoVen, The Netherlands
ulrich.schubert@uni-jena.de
Received April 3, 2010
ABSTRACT
By utilizing click chemistry and methylation, the triazolium motif was employed to design tridentate “ligands” that bind by electron acception
instead of electron donation. As electronically inverted ligands they are able to complex sulfate ions by hydrogen bonding and electrostatic
interactions. The formation of mono- or bis-tridentate complexes could be achieved by controlling the degree of methylation with the appropriate
reagents and was proven by NMR spectroscopy and computational methods.
In supramolecular chemistry, pincer-type ligands have at-
tracted particular interest as exemplarily shown by terpyri-
dine. Consequently, the copper(I)-catalyzed azide alkyne 1,3-
dipolar cycloaddition (CuAAC)-one of the prime examples
of the concept of highly efficient and modular reactions
named click chemistry1-has been applied in the synthesis
of analogous tridentate ligands, the so-called tripy,2 coordi-
nating metal ions via triazoles. Recently, click chemistry was
successfully applied in anion coordination, and the triazole
and triazolium moieties have been shown to act as efficient
C-H hydrogen bond donors as well.3 We intended to expand
the scope of tridentate “clicked” ligands in terms of anion
complexation by hydrogen bonding and electrostatic interac-
tions. Since anions can be structured, biorelevant, and
nucleophilic, the respective ligands might have potential for
template-directed assembling, sensing and recognition of
anions, and organocatalysis.4 Furthermore, they show a
dynamic coordination behavior that allows fast switching
processes and stimuli responses, respectively.
† Laboratory of Organic and Macromolecular Chemistry, Friedrich-
Schiller-University Jena.
So far, triazoles have been employed in anion recognition
‡ Laboratory of Inorganic and Analytic Chemistry, Friedrich-Schiller-
University Jena.
(2) (a) Li, Y.; Huffman, J. C.; Flood, A. H. Chem. Commun. 2007, 2692.
(b) Meudtner, R. M.; Ostermeier, M.; Goddard, R.; Limberg, C.; Hecht, S.
Chem.sEur. J. 2007, 13, 9834. (c) Schulze, B.; Friebe, C.; Hager, M. D.;
Winter, A.; Hoogenboom, R.; Go¨rls, H.; Schubert, U. S. Dalton Trans. 2009,
787.
§ Eindhoven University of Technology.
(1) (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int.
Ed. 2001, 40, 2004. (b) Tornøe, C. W.; Meldal, M. Chem. ReV. 2008, 108,
2952.
10.1021/ol100776x  2010 American Chemical Society
Published on Web 05/19/2010

in terms of triazolophanes3a-c and triazole foldamers3d-f
where a lot of weak C-H · · · X interactions were ac-
cumulated. Very recently, the anion binding capacity was
enhanced by preorganization to form a neutral tridentate
hydrogen bond donor.5 Alternatively, triazolium salts with
strongly increased CH-acidity have been used as anion
receptors6 and within the template synthesis of a [2]rotaxane.7
Furthermore, a [2]catenane has been synthesized by using
pyridinium nicotinamide as hydrogen bond donor and sulfate
as the templating anion.8 Both templates were primarily
based on hydrogen bonds as well as electrostatic interactions,
but required elegantly designed second sphere interactions
such as additional hydrogen bonds and π-stacking.9 There
are further interesting examples of 2:1 sulfate complexes,
but the ligand syntheses lack facility.10
Scheme 2. Synthesis of the Anion Coordinating Ligands
The “activation” for the sulfate complexation could be
performed selectively by choosing the appropriate reagents.
Methyl iodide just leads to single methylation, while Meer-
wein’s salt easily affords double methylation.
Our approach is to use strong hydrogen bonding as well
as electrostatic interactions offered by the triazolium moieties.
A direct motivation was to make use of the functional groups
that are readily installed within the ligand synthesis by
CuAAC, but that point in opposite directions in a metal
complex (Scheme 1). Essentially, coordination via the
The degree of methylation of 3 and 4 was proven
unambiguously by single crystal X-ray diffraction (Figure
1). In the solid state, no tridentate interactions could be found
Scheme 1. Classical and Electronically Inverted Ligands
Figure 1. Solid-state structures of 3 (left) and 4 (right) (ellipsoids
at 50% propability level; hydrogen atoms, solvents molecules, and
tetrafluoroborate anion omitted for clarity).
triazole or triazolium protons would lead to functional groups
pointing in the same direction and the choice of a tetrahedral
anion might allow the formation of an octahedral bis-
tridentate complex that can be considered as a directed
template. Thereby, a singly charged ligand should support
the formation of a charge neutral bis-complex with a doubly
charged anion.
with the given counterions tetrafluoroborate and iodide,
respectively. While ligand 4 features already a syn-syn
conformation with respect to the potential hydrogen-bonding
protons, ligand 3 shows an anti-syn conformation but can
easily flip in solution since 3 shows at least C2-symmetry in
1H NMR experiments. However, due to the steric demand
in particular of the methyl groups, the triazolium rings are
twisted out of plane by 33° for 3 and 38° for 4 in the free
ligand, respectively.
The synthesis of the building blocks 1 and 2 could be
achieved most easily under click conditions (Scheme 2).1a
(3) (a) Li, Y.; Flood, A. H. Angew. Chem., Int. Ed. 2008, 47, 2649. (b)
Li, Y.; Flood, A. H. J. Am. Chem. Soc. 2008, 130, 12111. (c) Li, Y.; Pink,
M.; Karty, J. A.; Flood, A. H. J. Am. Chem. Soc. 2008, 130, 17293. (d)
Juwarker, H.; Lenhardt, J. M.; Pham, D. M.; Craig, S. L. Angew. Chem.,
Int. Ed. 2008, 47, 3740. (e) Juwarker, H.; Lenhardt, J. M.; Castillo, J. C.;
Zhao, E.; Krishnamurthy, S.; Jamiolkowski, R. M.; Kim, K.-H.; Craig, S. L.
J. Org. Chem. 2009, 74, 8924. (f) Meudtner, R. M.; Hecht, S. Angew. Chem.,
Int. Ed. 2008, 47, 4926.
The anion coordination behavior of 3 and 4 could be
determined qualitatively and quantitatively. A continuous
variation plot (Job plot) of 3 and tetrabutylammonium sulfate
1
(TBA2SO4) obtained from H NMR spectroscopy revealed
(4) (a) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40, 486.
(b) Lankshear, M. D.; Beer, P. D. Coord. Chem. ReV. 2006, 250, 3142. (c)
Schreiner, P. R. Chem. Soc. ReV. 2003, 32, 289.
the formation of a 1:1 complex.12 For solubility reasons,
acetonitrile-d3/methanol 4:1 was used as solvent mixture with
nondeuterated methanol, since the triazolium protons rapidly
undergo deuterium exchange as they are strongly CH-acidic.
The association constant of the 1:1 complex could be
(5) Lee, S.; Hua, Y.; Park, H.; Flood, A. H. Org. Lett. 2010, 1, 2100.
(6) Kumar, A.; Pandey, P. S. Org. Lett. 2008, 10, 165.
(7) Mullen, K. M.; Mercurio, J.; Serpell, C. S.; Beer, P. D. Angew.
Chem., Int. Ed. 2009, 48, 4781.
(8) Huang, B.; Santos, S. M.; Felix, V.; Beer, P. D. Chem. Commun.
2008, 4610.
1
obtained by H NMR titration of 3 with TBA2SO4 (Figure
(9) Sambrook, M. R.; Beer, P. D.; Wisner, J. A.; Paul, R. L.; Cowley,
A. R.; Szemes, F.; Drew, M. G. B. J. Am. Chem. Soc. 2005, 127, 2292.
(10) (a) Chmielewski, M. J.; Zhao, L.; Brown, A.; Curiel, D.; Sambrook,
M. R.; Thompson, A. L.; Santos, S. M.; Felix, V.; Davis, J. J.; Beer, P. D.
Chem. Commun. 2008, 3154. (b) Kobiro, K.; Inoue, Y. J. Am. Chem. Soc.
2003, 125, 421.
2) and by analyzing the relatively large triazolium proton
downfield shift with the WinEQNMR2 software11 and was
(11) Hynes, M. J. J. Chem. Soc., Dalton Trans. 1993, 311.
Org. Lett., Vol. 12, No. 12, 2010
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Figure 2.
1H NMR spectra of 3 upon titration with tetrabutyl-
Figure 4.
1H NMR spectra of 4 upon titration with tetrabutyl-
ammonium sulfate (TBA2SO4) in acetonitrile-d3 at 298 K.
ammonium sulfate (TBA2SO4) in acetonitrile-d3/methanol 4:1 at
298 K.
determined to be log K ) 4.39 ( 0.28 or K ≈ 24,000 M-1,
respectively.12
uents are shifted to higher field with a maximum shift at 0.5
equiv of TBA2SO4 and recover in the course of the titration,
whereas the triazole, phenyl, and triazolium signals are
downfield-shifted only. Obviously, the protons of the outer
phenyl rings selectively respond to the complexation in a
bis-tridentate fashion and remain nearly unchanged in the
free ligand and in the 1:1 complex. The signals involved in
the hydrogen bonding respond similarly on both coordination
modes, but with a less pronounced downfield shift for the
2:1 complex since the two ligands compete in binding to
the same anion. By titration of TBA2SO4 with 4, the order
of the formed complexes is changed, and thus also the shifts
of protons participating in hydogen bonds show a charac-
teristic migration resulting from an initial 1:1 complexation
and the successive formation of a 2:1 complex.12 Again, the
set of protons that contribute to the hydrogen bonding can
only be explained by a tridentate coordination in each case.
The association constants could be calculated by fitting the
titration curve of the aromatic 4-bromo-2,6-dimethylphenyl
protons with the WinEQNMR2 software11 and were determined
to be log K1 ) 3.73 ( 0.07 (K1 ≈ 5,400 M-1), log K2 ) 3.1 (
0.2 (K2 ) 1,300 M-1), and log K1K2 ) 6.84 ( 0.15 (K1K2 ≈
7,000,000 M-2).12 Again, the overall sulfate binding is relatively
strong, and the difference of K1 and K2 reflects qualitatively
the same coordination behavior as in terpyridine complexes of
zinc(II), i.e., a 2:1 stoichiometry of host to guest yields a 2:1:1
ratio of 2:1 complex to 1:1 complex to free ligand. With respect
to the ligand, the ratio is 4:1:1, and a maximum yield of 70%
can be expected from a template synthesis in acetonitrile at a
concentration of 10-3 M if dynamic effects are negligible as
found in the report of Beer and co-workers.8 This might be
improved by removing the iodide with silver sulfate and by
using a less polar solvent such as dichloromethane to provoke
the formation of the uncharged bis-complex.
The concentration-weighted shift of a single signal for the
free ligand and the complex results from an exchange faster
than the NMR time scale. The large binding constant and
the fact that the maximum shift, i.e., the full complexation,
is nearly reached after the addition of 1 equiv of TBA2SO4
demonstrate a relatively strong sulfate binding even in the
presence of methanol. The symmetry within the spectrum
and the protons that are involved in the hydrogen bonding
indicate a tridentate complexation as depicted in Figure 2.
The Job plot of 4 with sulfate (Figure 3) in acetonitrile-d3
reveals the formation of a 2:1 complex beside a 1:1 complex.
Figure 3. Continuous variation plot (Job plot) of 4 and TBA2SO4
obtained from 1H NMR spectroscopy (aromatic 4-bromo-2,6-
dimethylphenyl protons).
The 1H NMR titration experiment (Figure 4) supports these
findings: the aromatic protons of the quasi-mesityl substit-
(12) See Supporting Information.
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Org. Lett., Vol. 12, No. 12, 2010

To consolidate the indirect image of the bis-tridentate
complex obtained by NMR investigations, although crystal-
lization attempts failed, and to exclude packing effects, we
conducted DFT calculations (B3LYP/SVP).12 The results are
depicted in Figure 6 and are consistent with the experimental
Figure 6. Calculated most stable structure for [42·SO4]. Left:
arrangement of the ligands. Right: hydrogen bonds, substituents
omitted for clarity.
findings of a 2:1 complex. As one could expect from the
distortion in the crystal structures of the ligands due to the
triazolium methyl groups, the sulfate is complexed less
ideally but still in the desired way to serve as template.
In conclusion, we applied the facile “click” synthesis with
the structural benefits of the triazole and triazolium moieties,
respectively, to design tridentate ligands that allow the
formation of relatively stable complexes with sulfate ions.
The formation of mono- and bis-complexes could be
controlled by the number of triazolium moieties within the
tridentate ligand. In particular, the formation of a bis-
tridentate complex of sulfate could be proven that meets the
demands for a [2]catenane template.
Figure 5. Selective NOESY spectra for [4·SO4]TBA (top, aceto-
nitrile-d3) and [42·SO4] (bottom, dichloromethane-d2) (sulfate omit-
ted; the excited protons are marked with a hollow arrow, and strong
and medium NOESY contacts are indicated with solid and dashed
arrows, respectively).
To prove a bis-tridentate coordination suitable for tem-
plation in solution, selective NOESY experiments were
conducted (Figure 5). Therefore, [42·SO4] was prepared using
4·I and Ag2SO4, whereas [4·SO4]TBA was obtained from a
1:10 mixture of 4·I and TBA2SO4. The methyl groups of the
quasi-mesityl substituents, which are not equivalent because
of the single site methylation, were excited, and the NOE
contacts were recorded.
For the 1:1 complex, only a strong contact to the adjacent
aromatic proton and medium contacts to the aromatic and aliphatic
triazolium protons on the same side of the molecule were visible.
In contrast, the 2:1 complex showed contacts to the central phenyl
ring and the other end of the molecule, which is only possible if
two ligands arrange in the desired orthogonal fashion. In addition,
the phase is inverted due to a doubled molar mass.
Acknowledgment. B.S. and C.F. are gratful to the Fonds
der Chemischen Industrie for Ph.D. scholarships. We also
thank G. Sentis (NMR spectroscopy), B. Lentvogt (elemental
analysis), A. Baumga¨rtel (MALDI-ToF MS), and Esra
Altuntas (high resolution ESI MS) for discussion and help
with the respective measurements.
Supporting Information Available: Experimental details,
spectral data, NMR spectra, binding studies, X-ray data and
DFT calculation data. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL100776X
Org. Lett., Vol. 12, No. 12, 2010
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