A bidentate halogen-bonding bromoimidazoliophane receptor for bromide ion recognition in aqueous media

Article abstract of DOI:10.1002/anie.201006916

A bidentate halogen-bonding bromoimidazoliophane receptor selectively binds bromide ions in competitive aqueous media (see picture, gray=carbon, blue=nitrogen, brown=bromine). The bromide ions are bound by cooperative convergent bromine atom/halogen-bondi

Full text of DOI:10.1002/anie.201006916

DOI: 10.1002/anie.201006916
Anion Recognition
A Bidentate Halogen-Bonding Bromoimidazoliophane Receptor for
Bromide Ion Recognition in Aqueous Media**
Antonio Caballero, Nicholas G. White, and Paul D. Beer*
The term halogen bonding is used in analogy with well-known
hydrogen bonding and is the noncovalent bonding interaction
between halogen atoms that function as electrophilic centers
(Lewis acids) and neutral or anionic Lewis bases.[1] The origin
of the attraction is attributed to a positive region on the
halogen atom that corresponds to the electronically depleted
halogen bonding receptor–anion association in solution, we
describe herein the synthesis of a novel bidentate halogen-
bonding bromoimidazoliophane receptor which, by coopera-
tive action of two preorganized halogen-bonding bromine
donor atoms, is capable of selectively binding bromide ions
strongly in competitive aqueous solvent media. Importantly,
by comparison the protic imidazoliophane receptor analogue
is a nonselective weak binder of halide ions.
À
outer lobe of the R X s bond. The resulting positive electro-
static potential lies on the surface of the halogen atom,
À
located at the terminus of the R X axis (s hole), while a band
2-Bromo-4,5-dimethyl-1H-imidazole (1) was synthesized
in a stepwise procedure from 4-methyl-5-imidazolemethanol
hydrochloride.[15] Alkylation of bromoimidazole 1 with meta-
xylyl dibromide 2 in the presence of NaOH provided the
bisimidazole compound 3. The coupling of 3 with dibromide 2
afforded two imidazoliophane conformers anti 42+·2BrÀ and
syn 52+·2BrÀ in good yield (82%), which were separated by
repeated recrystallization in methanol. Presumably the steric
demands of the bromine atom imidazolium substituents
inhibit intramolecular ring rotation, which results in the
isolation of the two conformers; the ratio between the anti
and the syn isomer was 68:32 respectively. The bromide salts
readily underwent anion exchange to the corresponding
hexafluorophosphate salts on addition of aqueous NH4PF6
(Scheme 1).
of negative charge remains around the equator of the halogen
atom. The intermolecular force known as halogen bonding
arises from the interaction of the positively charged s hole
with electron-donating species, thus resulting in a strongly
linear geometry that maximizes the interface of opposite
charges.[2] To date, almost all the investigations into halogen
bonding have been conducted in the solid state, where the
noncovalent interaction has been imaginatively exploited in
the crystal engineering[3] of magnetic, conducting, and liquid-
crystalline materials.[4] In contrast, halogen bonding in the
solution phase is still in its infancy and only a few studies in
solution have been reported recently,[5] which is surprising
given its potentially powerful analogy to ubiquitous hydrogen
bonding.[6]
The development of abiotic receptors for anions has
received considerable attention in recent years,[7] stimulated
by the important roles of these ions in a range of chemical,
biological,[8] medical,[9] and environmental processes.[10] Com-
plementary electrostatic, hydrogen-bonding, Lewis acid–
base,[11] and more recently, anion–p interactions[12] have all
been exploited in the construction of a wide variety of highly
efficient complexing reagents for anions. By virtue of a
The corresponding protic imidazoliophane receptor
62+·2PF6 (Scheme 2) was synthesized by following an
À
analogous procedure using 4,5-dimethyl-1H-imidazole as
the starting material. In contrast to the bromoimidazolio-
phanes, as expected[14] only one conformer species was
detected and isolated.
Single crystals suitable for X-ray diffraction structural
analysis were obtained for the anti isomer 42+, and the
À
positive charge and relatively acidic C H groups, the
imidazolium motif in particular has proven to be a potent
anion-recognizing site to be incorporated into molecular
receptor framework design.[13] Inspired by the polyimidazo-
lium receptor systems reported to date[14] and with the aim of
contributing to the meagre quantitative data reported on
[*] Dr. A. Caballero, N. G. White, Prof. P. D. Beer
Chemistry Research Laboratory, Department of Chemistry
University of Oxford, Mansfield Road, Oxford, OX1 3TA (UK)
Fax: (+44)1865-272-690
E-mail: paul.beer@chem.ox.ac.uk
[**] A.C. thanks the European Union for a Marie Curie Postdoctoral
Fellowship. N.G.W. thanks the Clarendon Fund and Trinity College
for a studentship. We thank Oxford University Crystallography
Service for instrument use. We also thank Dr. Amber L. Thompson
and Dr. Christopher J. Serpell for assistance with X-ray crystal
structure refinement.
À
À
Scheme 1. Synthesis of the receptors 42+·2PF6 and 52+·2PF6
.
Reagents and conditions: a) NaOH (1m in water), acetonitrile, reflux,
yield: 80%; b) 1,3-bis(bromomethyl)benzene, acetonitrile, 828C, yield:
82%; c) wash with saturated NH4PF6 (aq).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201006916.
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Communications
Scheme 2. Structure of the imidazoliophane 62+·2PF6
.
À
syn isomer 52+ as both the bromide and hexafluorophosphate
salts. As expected, halogen-bonding interactions in the
hexafluorophosphate salts are negligible—with no halogen
bonding (defined as a Br···X distance less than the sum of
Br+ X van der Waals (vdW) radii) observed in the structure
of the anti isomer and a very weak halogen-bonding inter-
action observed in the syn isomer (93% of sum of vdW radii,
Table 1).
Table 1: Details of halogen bonding in the solid state.
À
C Br
[ꢀ]
Compound
Br···X
[ꢀ]
Br···X vdW
Radii [%]
C-Br···X Angle
[8]
42+·2PF6À (anti)
1.842(4)
1.845(3)
1.861(4)
1.878(4)
–
–
–
À
52+·2PF6 (syn)
42+·2BrÀ (anti)
52+·2BrÀ (syn)
3.078(2)
3.191(1)
3.217(1)
93
86
87
160.56(12)
174.16(14)
166.81(12)
Figure 1. Views of the anti isomers of macrocycle 4 as the bromide
(left) and hexafluorophospate (right) salts. Hydrogen atoms and
solvent molecules are omitted for clarity; thermal ellipsoids are shown
at 50% probability. Only one of the two symmetry-equivalent hexafluor-
phosphate ions is shown. Gray=carbon, blue=nitrogen, brown=
bromine, purple=phosphorus, yellow=fluorine
Conversely, both the anti and syn bromide structures show
significant halogen bonding (Table 1). In the case of the
anti structure, each bromoimidazolium group interacts with
one bromide ion (Figure 1), while in the case of the
syn isomer, bidentate halogen bonding between two bromoi-
midazolium groups and one bromide ion is observed, with the
second bromide ion involved only in hydrogen bonding to
methanol solvent molecules (Figure 2).
The halogen bonding in the syn structure is less linear than
may be expected (166.81(12)8) compared to the angle of 1748
in the anti isomer and the mean angle of 1748 for previously
reported bromoimidazolium bromide halogen bonds.[6c] This
finding is presumably due to steric demands on the bromoi-
midazolium rings that prevent them rotating fully inwards and
also due to repulsion between the two electropositive
bromine atoms of the bromoimidazolium groups.
The strength of the halogen bonds can be inferred from
À
the increase in the imidazolium C Br distance from
1.842(4) ꢀ in the anti hexafluorophosphate salt (with no
halogen bonding), to 1.845(3) ꢀ in the syn hexafluorophos-
phate salt (with extremely weak halogen bonding) to
1.861(4) ꢀ in the monodentate anti bromide salt to
1.878(4) ꢀ in the syn halogen bond. The observed trend is
À
consistent with weakening of the C Br bond by electron
[16]
À
donation from the bromide ion into the C Br s* orbital,
despite the fact that the syn halogen bond is less linear.
The syn structure has a calixlike shape, because the
bromoimidazolium rings point towards a bromide ion, thus
leading to an open cleft on the other side of the macrocycle
(bromoimidazolium–bromoimidazolium mean plane angle =
Figure 2. Perspective (left) and space-filling packing (right) views of
the syn isomer of the bromide macrocycle. Hydrogen atoms, methanol
solvates, and the noncoordinated bromide ion are omitted for clarity.
Thermal ellipsoids are shown at 50% probability. Gray=carbon,
blue=nitrogen, brown=bromine
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Angew. Chem. Int. Ed. 2011, 50, 1845 –1848

408). This space is occupied by a halogen-bonded bromide ion
of an adjacent molecule, such that the calixes stack into one
another (see Figure 2 right and the Supporting Information).
The two anti structures do not have this arrangement, as the
bromoimidazolium rings are parallel to one another. A
similar calixlike structure is observed for the hexafluorophos-
phate salt of 52+ but with a far smaller angle between the
bromoimidazolium mean planes (238), presumably because
the hexafluorophosphate salt does not contain a bidentate
halogen-bonding interaction to “pull” the two bromoimida-
zolium rings towards one another. This stacking arrangement
is not observed in the hexafluorophosphate structure.
The 1H NMR spectra of the receptors 42+·2PF6 and
À
52+·2PF6À are very similar although slight differences in some
chemical shifts are present. Receptors 42+·2PF6 (anti) and
À
52+·2PF6À (syn) show four sets of signals, the first of which at
d = 2.21 ppm (anti) and d = 2.18 ppm (syn) attributed to a
methyl group. The two methylene protons have different
environments and appear as two doublets around d =
5.54 ppm and 5.65 ppm. The greatest difference in the
1H NMR spectra between the two isomers corresponds to
the internal phenyl proton (Ha) d = 6.02 ppm (anti) and d =
5.87 ppm (syn). The rest of the aromatic protons appear at the
same chemical shift in the two isomers (multiplet at d =
Figure 3. 1H NMR spectral changes observed in 52+·2PF6 syn in
À
CD3OD/D2O 9:1 during the addition of up to 2 equivalents of iodide
ions.
(see the Supporting Information). The association constants
were obtained by fitting the respective titration data
(Figure 4) to a 1:1 host–guest binding model using the
WinEQNMR program[17] (Table 2). The syn bromoimidazo-
7.65 ppm). Unlike the bromoimidazoliophanes 42+·2PF6
À
and 52+·2PF6À, the macrocycle 62+·2PF6 shows a sharp
liophane 52+·2PF6 exhibits an impressively high binding
À
À
singlet for the methylene protons at d = 5.49 ppm, a single
signal for the methyl group (d = 2.05 ppm) and the H2 of the
imidazolium ring (d = 9.06 ppm), thus indicating the rapid
interconversion of the different possible conformations on the
affinity for bromide ions (Ka = 889mÀ1) relative to the rest of
the halide ions, the trend of halide-binding strength being
bromide > iodide @ chloride > fluoride ions. In stark contrast
the association constant values determined for the hydrogen-
NMR timescale.
bonding receptor 62+·2PF6 are all significantly smaller in
À
The anion-binding properties of the receptors 42+·2PF6
,
magnitude when compared to the strength of the bromide-
binding affinity exhibited by halogen-bonding macrocycle
52+·2PF6À (syn).
À
52+·2PF6À, and 62+·2PF6À with fluoride, chloride, bromide, and
iodide ions from their tetrabutylammonium salts were inves-
1
tigated by H NMR titration experiments by the addition of
It is noteworthy that the hydrogen-bonding receptor
aliquots of the different anions to solutions of the receptors in
CD3OD/D2O 9:1.
62+·2PF6 shows little discrimination between chloride, bro-
À
mide, and iodide ions. Thus the incorporation of bromine
atoms into the bis(imidazolium) macrocyclic receptor frame-
Addition of even a large excess of halide ions to a solution
À
of the anti bromoimidazoliophane 42+·2PF6 caused no
changes in the 1H NMR spectrum of the receptor. In contrast
significant perturbations in the 1H NMR spectrum of the syn
isomer 52+·2PF6 were observed upon the addition of
À
chloride, bromide, and iodide ions. On closer inspection, the
1H NMR titration data revealed a moderate downfield shift
for the signals associated with the internal aromatic proton
(Ha), which ranges from Dd = 0.12 ppm for iodide to Dd =
0.02 ppm for chloride ions. A slight downfield shift was
observed only in one methylene proton resonance (Figure 3).
With the macrocycle 62+·2PF6 the addition of chloride,
À
bromide, and iodide ions caused significant downfield shifts of
À
the C H proton of the imidazolium ring (d = 0.13 ppm) and
the internal aromatic proton (Ha, d = 0.11 ppm). Interestingly,
the addition of equimolar and excess amounts of fluoride ions
to a solution of the syn 52+·2PF6 and 62+·2PF6 receptors
caused no significant changes.
À
À
The chemical shift of proton Ha was monitored during
À
anion addition to 52+·2PF6 (syn) and 62+·2PF6À. Job plot
Figure 4. 1H NMR titration curves for syn 52+·PF6À with tetrabutylam-
analysis of the titration data revealed a 1:1 receptor to anion
binding stoichiometry for chloride, bromide, and iodide ions
!
&
*
^
monium fluoride ( ), chloride ( ), bromide ( ), and iodide ( ) in
CD3OD/D2O 9:1 at 295 K.
Angew. Chem. Int. Ed. 2011, 50, 1845 –1848
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1847

Communications
Table 2: Association constants Ka for 52+·2PF6À (syn) and 62+·2PF6À with
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different halide ions.[a]
Receptor
Anion[b]
Ka [mÀ1 [c]
]
52+·PF6
FÀ
–
À
[c]
ClÀ
BrÀ
IÀ
<10
889 (37)
184 (15)
62+·PF6
FÀ
–
À
[c]
ClÀ
BrÀ
IÀ
133 (12)
130 (10)
102 (7)
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work dramatically influences the anion-recognition capabil-
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bromide ion recognition to take place in aqueous media.
In conclusion we have demonstrated that a bidentate
bromoimidazoliophane receptor is capable of selectively
binding bromide ions in competitive aqueous media by
cooperative convergent interactions between the bromine
atoms on the receptor and the bromide ion. Importantly the
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À
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À
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Received: November 4, 2010
Published online: January 14, 2011
Keywords: anions · halogen bonding · imidazoliophanes ·
.
receptors · supramolecular chemistry
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