Cooperativity of H-bonding and anion-π interaction in the binding of anions with neutral π-acceptors

Article abstract of DOI:10.1039/c2cc34748b

A rare anion-π complex between bromide and a neutral receptor is reported and related receptor systems are studied with a series of anions. The interaction is observed in the solid state and in solution, and further evidence for it is obtained by a computational study. This journal is The Royal Society of Chemistry 2012.

Full text of DOI:10.1039/c2cc34748b

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COMMUNICATION
Cooperativity of H-bonding and anion–p interaction in the binding of
anions with neutral p-acceptorsw
Michael Giese,a Markus Albrecht,*a Tim Krappitz,a Marius Peters,a Verena Gossen,a
Gerhard Raabe,a Arto Valkonenb and Kari Rissanenb
Received 3rd July 2012, Accepted 23rd August 2012
DOI: 10.1039/c2cc34748b
A rare anion–p complex between bromide and a neutral receptor is
reported and related receptor systems are studied with a series of
anions. The interaction is observed in the solid state and in solution,
and further evidence for it is obtained by a computational study.
Due to their crucial role in biological and chemical processes
Fig. 1 Part of crystal structure of 1 showing the pentafluorobenzamide
anions have become the focus of intense recognition and sensing
studies.1 Common anion receptors are based on electrostatic
and the bromide (the TBA cation was removed for clarity).
attraction, hydrogen-bridges, hydrophobic effects or ion pair
recognition and are more or less specific.2 In recent years anion–p
hydrogen bond withdraws the BrÀ from the center of the
interaction was identified as an interesting new binding motif.3
electron-deficient arene (Fig. 1). Furthermore, there is an
additional intermolecular N–HÁ Á ÁBrÀ hydrogen bond from
Many theoretical4 and structural studies3 have proven the existence
the adjacent molecule [NÁ Á ÁBrÀ = 3.392(3) A]. The contacts
of this weak interaction. However, the relevance and strength of
anion–p interactions in solution still remain elusive.5
between the carbon atoms of the pentafluorophenyl group and
the bromide are in between 3.650(3) and 4.164(3) A and the
In 2008 we started systematic studies on anion–p interactions in
pentafluorophenylammonium and -phosphonium salts.6 Initial
distance to the centroid of the C6F5 substituent is 3.67 A.
Due to the low solubility of pentafluorobenzamide in
results revealed a certain flexibility in the position of the anion
chloroform the N-phenylbenzamides 2a–c were synthesized
above the electron-deficient arene, which can be controlled by
using directing substituents.7 The spatial structure of the anion
seems not to have an effect on the anion–p interaction.8 However,
anions which are of low stability or even unstable in the gas phase
like the tetraiodide dianion can be stabilized in the crystal lattice
by the support of electron-deficient arenes.9 Just recently our
results showed for the first time that the anion position depends
on the fluorination degree of the arene in the solid state.8
(see ESIw) by reacting amine 3a or 3b with pentafluorobenzoyl
chloride (4a) or 3,5-dichlorobenzoyl chloride (4b) in the
presence of pyridine.
In order to determine the binding constants for 2a or 2b in
chloroform the stoichiometry was checked using the Job plot
(Fig. 2a).10 By following the amide proton signal in the
1H NMR spectra a 1 : 1 complex for 2a as well as for 2b
was observed for various anions (ClÀ, BrÀ, IÀ, BF4À). Corre-
sponding results can be obtained by following other signals in
the 1H or 19F NMR spectra. The titration with TBABF4 shows
a different (2 : 1) ratio of receptor to anion (Fig. 2b and c).
The NMR titrations were performed in CDCl3 using 0.01 M
solutions of the receptors 2a and 2b. The TBA salts were added as
0.04 M solutions in chloroform. The binding constants were
calculated by analyzing the titration curves via non-linear regression
and are summarized in Table 1 (for full details see ESIw).10
A diagram for 2a showing the binding constants for various
anions reveals a decreasing binding constant in the order
In the present work anion–p interactions are studied by
co-crystallizing a series of pentafluorophenyl derivatives with
tetrabutylammonium halides (TBAX, X = ClÀ, BrÀ, IÀ,
PF6À, BF4À). Pentafluorobenzamide with tetraethylammonium
bromide (1) crystallizes in the monoclinic space group P21/n
(Fig. 1). In the solid state the bromide is fixed by N–HBrÀ
hydrogen bonds [NÁ Á ÁBrÀ = 3.431(3) A] close to the p-system
of the uncharged receptor. On the other hand, this directing
a Institut fur Organische Chemie, RWTH Aachen, Landoltweg 1,
¨
52074 Aachen, Germany. E-mail: markus.albrecht@oc.rwth-aachen.de;
Fax: +49 241 809 2385; Tel: +49 241 809 4678
À
ClÀ > BrÀ > IÀ (Fig. 3a). The binding constants for BF4
b Department of Chemistry, Nanoscience Center, University of Jyvaskyla,
¨
Survontie 9, 40014 Jyvaskyla, Finland. E-mail: kari.t.rissanen@jyu.fi;
¨
(135–153 MÀ1) are somewhat higher than for iodide while
¨
Fax: +358 14 260 2672; Tel: +358 50 562 3721
¨
À
PF6 has very similar values. It should be noticed that the
À
w Electronic supplementary information (ESI) available: Details of
experimental procedures, solution investigations, crystallographic
studies and computational investigations. CCDC 872223 and
872224. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c2cc34748b
complex stoichiometry of the PF6 complex is not clear and
that this value is estimated for a 1 : 1 complex. A deviation
from the general trend is observed for the binding constants
calculated by following the ortho-fluorine signals. This might
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 9983–9985 9983

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Fig. 3 (a) Binding constants for 2a obtained by following the signal
in the NMR for various anions (ClÀ, BrÀ, IÀ, BF4À, PF6À). (b)
Comparison of the binding constants of 2a and 2b for various anions
(ClÀ, BrÀ, IÀ, BF4À, PF6À).
hydrogen bonds are broken and the phenylbis(pentafluoro-
benzamide) complex becomes soluble.
Job plots confirm a 1 : 1 ratio for 2c with chloride, bromide
and iodide in deuterated acetonitrile. For hexafluorophosphate
no significant shifting of the signals could be observed in the
NMR spectra. The binding constants obtained for 2c are
summarized in Table 2.
Fig. 2 (a) Representative Job plots for 2a with various anions (ClÀ,
BrÀ, IÀ, PF6À) added as n-Bu4N salts in CDCl3. (b) Selected 1H-NMR
spectra for the addition of n-Bu4NCl to a solution of 2a in CDCl3.
(c) Resulting titration curves obtained by following the shifting of the
NH-signal for 2a during the addition of TBA salts.
The binding constants for 2c and various anions confirm the
expected binding order of ClÀ > BrÀ > IÀ (Table 2). In this case
the ortho-fluorine signals lead to slightly higher values. The binding
constants for 2c in CD3CN are significantly higher than for 2a in
CDCl3. This mainly arises from the strong anion binding capability
of two amide hydrogens, which is further enhanced by the electron-
withdrawing effect of the pentafluorophenyl groups. In addition,
cation solvation is stronger in CD3CN leaving a ‘‘free’’ anion (and
not an ion pair) for binding to the receptor. Moreover, binding of
the anions is further strengthened by direct anion–p interactions. It
should be noticed that due to the different solubility of 2a and 2b
the binding constants were determined in different solvents. Never-
theless, the higher binding constant for 2c in CD3CN compared to
the binding constants of 2a and 2b determined in CDCl3 is even
more surprising due to the stronger solvation of the anion in polar
acetonitrile. However, there are two different opportunities for 2c
to interact with an anion (see Scheme 1, A and B). In A the anion is
bound to a cleft by hydrogen bonds via the two amidic protons and
anion–p interactions to the two C6F5 moieties, while B allows the
Table 1 Binding constants Ka [MÀ1] for the 1 : 1 complexes of 2a and
2b with various anions TBAX, X = ClÀ, BrÀ, IÀ, PF6À). The binding
constants were determined by following the amide proton in the
1H NMR in CDCl3 (errors are estimated to be lower than 20%)
ClÀ
BrÀ
IÀ
BF4
PFÀ
Àa
6
2a
2b
237
163
173
114
99
82
135
102
89
74
a
Estimated for a 1 : 1 complex stoichiometry.
be due to intramolecular interactions of the ortho-fluorine
atoms with the amide protons. For 2b an analogous trend
was observed. The binding constants are slightly higher for
receptor 2a (Table 1, Fig. 3b). There are two possible explana-
tions for this behaviour: the cooperativity of NH–anion and
anion–p interaction or the acidification of the NH-group by
the electron-withdrawing C6F5—compared to the C6H5 unit.
Proton NMR is able to confirm the H-bonding, but we cannot
definitely confirm anion–p interactions in solution.
Attempts to perform similar studies in solution for 2c failed
due to the very low solubility of 2c in chloroform. Interest-
ingly, 2c becomes soluble in chloroform by adding 1.0 eq. of
TBACl. Solid state structure of 2c revealed the stacking of the
molecules by N–HÁ Á ÁOQC hydrogen bonds of the amide
groups (see ESIw). The strong double N–HÁ Á ÁOQC H-bonds
form robust columns resulting in the low solubility of 2c. By
adding the tetrabutylammonium salt to the solution the
Table 2 Binding constants Ka [MÀ1] for the 1 : 1 complexes of 2c
with various anions (ClÀ, BrÀ, IÀ). The binding constants were
determined by following the proton signals in the 1H NMR in CD3CN
(errors are estimated to be lower than 20%)
ClÀ
BrÀ
IÀ
NH
3345
3198
3060
4683
3401
3660
637
645
606
800
602
625
182
203
148
134
156
186
Hortho
Hmeta
Fortho
Fmeta
Fpara
c
This journal is The Royal Society of Chemistry 2012
9984 Chem. Commun., 2012, 48, 9983–9985

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the amide proton by the electron-withdrawing C6F5-unit. So far
we were not able to clarify this point sufficiently. However, the
differences in the binding constants between 2a and 2b are quite
small and might be insignificant. Nevertheless, for receptor 2c with
various anions, an attractive interaction between the anion and the
pentafluorophenyl moieties can be expected in solution.
Scheme 1 Binding motifs for the interaction of 2c with an anion.
Notes and references
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optimized at the HF/6-311++G** level of theory.
anion to interact only with one H-bond and one electron-deficient
unit. In order to determine whether A or B is the preferred
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A01. Therefore, 2c would most likely adopt the structure of
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In conclusion we were able to show that pentafluorobenzamides
are appropriate systems for studying anion–p interactions in the
solid state as well as in solution. To the best of our knowledge the
crystal structure of 1ÁBrÀ is the first example of anion–p
interactions between an uncharged pentafluorophenyl deriva-
tive and an anion. Moreover, our investigations in solution
show a slight difference between an electron-rich and -poor
system, which can be explained by a cooperative effect of
N–HÁÁÁanion and anion–p interaction and the enhanced acidity of
¨
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c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 9983–9985 9985