Trapped bifluoride

Article abstract of DOI:10.1002/anie.200504066

(Figure Presented) The quest is over: A tricyclic amide-based anion receptor has been synthesized by connecting two monocyclic precursors. The receptor is highly selective for the binding of the elusive bifluoride anion HF₂^-, and the adduct represents the first structural example of an encapsulated bifluoride. The bifluoride lies midway between the two macrocycles making up the tricycle and is held by four hydrogen-bonding contacts with the macrocyclic amides.

Full text of DOI:10.1002/anie.200504066

Angewandte
Chemie
Anion Sensor
DOI: 10.1002/anie.200504066
Trapped Bifluoride**
Sung Ok Kang, Douglas Powell, Victor W. Day, and
Kristin Bowman-James*
In memory ofBernard Dietrich
Since Jean-Marie Lehn first reported the structure of an
encapsulated triatomic azide in a bicyclic azacryptand known
as bis-tren, researchers have sought to do the same for
another triatomic anion, bifluoride.[1–3] Lehn, Martell, and co-
workers reported physical data that indicated such an
encapsulation in an azacryptand similar to bis-tren;[3] how-
ever, crystallographic corroboration has, to our knowledge,
remained elusive. We have isolated and structurally charac-
terized a number of fluoride complexes with both monocyclic
and bicyclic amine-based[4] and amide-based[5] anion recep-
tors. Despite finding bifluoride in the crystal lattice in a
number of the amine-based macrocycles and cryptands, we
had not encountered an encapsulated bifluoride. Recently,
[*] Dr. S. O. Kang, Dr. D. Powell, Dr. V. W. Day, Prof. K. Bowman-James
Department ofChemistry
University ofKansas
1251 Wescoe Hall Drive, Lawrence, KS 66045 (USA)
Fax: (+1)785-864-5396
E-mail: kbjames@ku.edu
[**] We thank the National Science Foundation for support of this work
(CHE-0316623) and for purchase of the X-ray diffractometer (CHE-
0079282).
Supporting information for this article (including details of the
synthesis ofthe precursors to 1) is available on the WWW under
http://www.angewandte.org or from the author.
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however, in a quest to expand the dimensionality of our anion
chloride (Scheme 1, step d). After removing the Boc groups,
1 was obtained in 30% yield by coupling two macrocycles at
the two unprotected amine sites using dibromoethane
(Scheme 1, steps e and f). Crystals of free ligand 1 suitable
for X-ray diffraction were grown by slow evaporation from
CHCl3. Crystals of the bifluoride complex were grown from a
solution of CH3CN/CHCl3 and 1 in the presence of excess
nBu4N+FÀ.[9]
Although the isolation of a bifluoride complex was not
necessarily anticipated, fluoride is known to be a strong base
in organic solvents; for example, it abstracts a b-hydrogen
atom from anhydrous tetra-n-butylammonium salts to yield 1-
butene, tri-n-butylamine, and tetra-n-butylammonium
bifluoride.[10] Fluoride has also been observed to abstract
hydrogen from amide-based macrocycles[11] and cryptands,[5]
as well as urea-,[12] thiourea-,[13] and pyrrole-based[14] acyclic
anion hosts, often with the observation of bifluoride in the
1H NMR spectra. Even pure tetra-n-butylammonium fluoride
contains small amounts of bifluoride. Regardless of the source
of either the hydrogen ion or bifluoride, the isolation of the
bifluoride complex indicates selectivity of 1 for bifluoride
over fluoride, at least in the crystalline form.
The bifluoride complex crystallized as the hydrated tetra-
n-butylammonium salt, nBu4N[1(FHF)]·3H2O.[9] Although
the free-base and bifluoride-complexed forms of tricycle 1
both possess rigorous crystallographic C2 symmetry in their
solid-state structures, the conformation of the complexed
tricycle approximates quite closely D2 symmetry. The four
diamido pyridine groups adopt a pseudo-S4 up-down-up-
down arrangement (Figure 1a); this pseudo-S4 axis passes
through the two fluorine atoms of the bifluoride anion. The
crystallographic C2 axis is perpendicular to this pseudo-S4 axis
and passes through the bifluoride hydrogen atom as well as
ligands, we synthesized a tricyclic receptor 1 consisting of two
monocyclic macrocycles joined by two bridging ethylene
linkages. Our goal was to use this higher-dimensioned ligand
as a receptor for ditopic anions. The crystal structure of what
we anticipated would be the fluoride complex revealed
instead an encapsulated bifluoride ion, thus making this the
first example of bifluoride encapsulation within a multicyclic
receptor.
The key to the design of this new anion receptor was to
link two tetraamido macrocycles at two points, and to explore
binding proclivities of the resulting tricycle for ditopic anion
guests. The tetraamido ligands chosen are known to be
excellent frameworks for binding simple anions,[6] but only a
few tricyclic polyamide systems have been reported to
date.[7,8] Although these more complex receptors show
promise for binding multiatomic and multitopic anions,
crystal-structure data have been lacking. Hence, the synthesis
and structural characterization of the tricyclic ligand 1 and its
bifluoride complex not only open a new area in anion-
inclusion chemistry, but also provide much needed crystallo-
graphic information. Here we report the synthesis of the new
tricyclic receptor 1, the resulting anion-binding data, and the
crystal structures of both the free base and the bifluoride
complex, which display amazingly similar structural features.
The tricycle 1 consists of two tetraamido macrocycles
bridged by two ethylene spacers. The monocyclic precursor to
1 was synthesized by using selective protection and depro-
tection techniques. First the terminal amines of diethylenetri-
amine (dien) were protected with phthaloyl groups, followed
by protection of the central secondary amine with di-tert-
butyldicarbonate (Boc anhydride), and lastly deprotection of
the terminal amines (Scheme 1, steps a–c). The macromono-
cycle was formed by condensation of two Boc-protected
triamines with two molecules of pyridine-2,6-dicarbonyl
À
the midpoints of the two ethylene C C bonds between the
tetraamido macrocycles. The macrocycle binds the bifluoride
through four amide hydrogen bonds.
The remaining four amido protons
are involved in intraligand hydrogen
bonds. Each of the four diamidopyr-
idine arms of the tricycle contains a
three-atom hydrogen bonding net-
work between one of the amide
hydrogen atoms and the lone pairs
of electrons on its adjacent pyridine
and
amine
nitrogen
atoms
(N7···H4(N4)···N1 and N16···H19-
(N19)···N22 in Table 1). The circle-
like pattern resulting from these
hydrogen bonds is clearly seen in
Figure 1a. Although the constrained
À
geometry makes the N H···N angles
quite acute, the distances are normal
for NH···N hydrogen bonds, and this
pattern is also present in the solid-
state structure of the free base.
While these four-atom (3N and
1H) groupings are not required to
be coplanar, they are, to within
0.01Š in the [ 1(FHF)]À complex.
Scheme 1. Synthesis ofthe tricyclic ligand 1: a) phthalic anhydride, CH3CN; b) (Boc)2O, CHCl3/CH3CN;
c) NH2NH2·H2O, EtOH; d) pyridine-2,6-dicarbonyl chloride, NEt3, CH2Cl2; e) TFA, CH2Cl2; f) BrCH2CH2Br,
K2CO3, CH3CN. Boc=tert-butoxycarbonyl, TFA=trifluoroacetic acid.
1922
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Chemie
Table 1: Selected hydrogen bond lengths and angles for the bifluoride
complex of 1 and free base 1.
[1(FHF)]À
d(D···A) [Š] <(DHA) [8] d(D···A) [Š] <(DHA) [8]
1
D-H···A
N4-H4···N1
N4-H4···N7
N19-H19···N16 2.896(4)
N19-H19···N22 2.734(4)
N13-H13···F1
N28-H28···F1
N13-H13···O4
F1-H1···F1[a]
2.839(2)
2.755(3)
98(2)
2.814(2)
2.710(2)
2.689(1)
2.576(1)
104(1)
108(1)
111(2)
115(2)
111(2)
114(4)
102(3)
155(3)
154(2)
2.754(3)
2.724(3)
2.905(1)
159(2)
2.475(4)
168(4)
[a] Symmetry transformations used to generate equivalent atoms: x,
Ày+1, Àz+1.
between the amide hydrogen atom and the lone pairs of
electrons on the adjacent pyridine and amine nitrogen atoms
are still observed. The principal difference between the
complexed and uncomplexed tricycle involves an approx-
imately 1808 rotation of two amide groups, which places the
corresponding amide oxygen atoms inside the ligand cavity
and enables them to form hydrogen bonds to other amide
hydrogen atoms and serve as surrogate anions. The F···O4*
separation for the superimposed structures in Figure 1c is
0.75 Š. The proton for each of these two rotated amide
groups forms a hydrogen bond to an external water molecule.
1
The bifluoride complex was further characterized by H
and 19F NMR spectroscopy, which indicates that the anion
remains inside the cavity even in solution (Figure 2). In the
1H NMR spectrum recorded in [D6]DMSO, the signal of the
encapsulated bifluoride hydrogen atom is seen as a triplet as a
result of coupling of the hydrogen atom with the adjacent
fluoride ions with IF = 1/2. This signal is shifted 2.1 ppm
downfield to d = 17.5 ppm (JHF = 128 Hz) compared to free
bifluoride, which occurs at d = 15.4 ppm in [D6]DMSO
(Figure 2a). In the 19F NMR spectrum, the signal assigned
to unbound bifluoride at d = À145.3 ppm is shifted upfield to
d = À152.1 ppm (Dd = 6.8 ppm) in [1(FHF)]À (Figure 2b).
Figure 1. Crystal structures ofa) the bilfuoride complex of 1, b) the
free base of 1, and c) the superposition of the bifluoride and free-base
structures seen from the same viewpoint. The bifluoride complex in
(c) is shown with darker colors and solid bonds, and the free base is
shown with lighter colors and dotted bonds. The water molecules of
hydration are not shown.
The four remaining amides are hydrogen-bonded to the
bifluoride. The F···F separation is 2.475(4) Š with the hydro-
gen symmetrically situated between the two fluoride ions on
the twofold axis. The F···H···Fangle is almost linear at 168(4)8.
The free base (1) crystallized as the hexahydrate, with six
water molecules (three per asymmetric unit) just outside of
the cavity (Figure 1b).[9] The tricycle again possesses rigorous
crystallographic C2 symmetry with an S4-like arrangement of
the diamidopyridine groups. The structural similarities for the
tricycle in the hexahydrated free base and complexed forms
are quite striking, as shown in the tricycle superposition in
Figure 1c. The four three-atom hydrogen-bonding networks
Figure 2. (a) 1H NMR and (b) 19F NMR spectra of nBu4N+FHFÀ and
[1(FHF)]À in [D6]DMSO.
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Communications
(m, 16H; CH2), 2.79 ppm (m, 24H; CH2); 13C NMR (400 MHz,
CDCl3) d = 163.8 (C = O), 149.1, 138.5, 124.6 (Ar), 54.7, 53.0,
38.1ppm (CH 2); FAB MS: m/z = 989.7 [MH]+. Elemental analysis
(%) calcd for C48H60N16O8·CH2Cl2·H2O: C 53.89, H 5.91, N 20.52;
found: C 53.69, H 5.66, N 20.77.
The signal is broad, possibly as a result of unresolved coupling
with both the amide and bifluoride hydrogen atoms.
Binding studies of 1 with anions by using 1H NMR
techniques revealed amazingly selective binding and high
affinity for the ditopic FHFÀ ion (Ka = 5500) followed by
H2POÀ4 (740), N3À (340), and CH3COOÀ (100), with negligible
binding for HSOÀ4 , ClÀ, BrÀ, IÀ, NO3À, and ClO4À ions in
[D6]DMSO. The association constant value of 1 for bifluoride
in CDCl3 is close to the calculation limit by NMR methods
(Ka ca. 104–105; Figure 3). A complicated titration curve was
NMR studies: 1H NMR spectra were recorded on a Bruker
Avance 400 spectrometer at 400 MHz. Each titration involved 20
measurements in [D6]DMSO at room temperature. Aliquots from a
stock solution of the nBu4N+ salts (20 mm) were gradually added to
the initial solution of the ligand (2 mm). All proton signals were
referred to TMS. The association constants Ka were calculated by
EQNMR.[15] 19F NMR spectra were recorded on a Bruker Avance 400
spectrometer at 376.5 MHz, and the chemical shifts were recorded in
ppm relative to aqueous NaF at À122.4 ppm as an external standard.
All spectra were recorded at 238C.
Received: November 15, 2005
Published online: February 21, 2006
Keywords: anion recognition · bifluoride · host–guest systems ·
.
supramolecular chemistry · tricyclic receptors
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&
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Experimental Section
1: 1,2-Dibromoethane (1.00 mL, 11.6 mmol) was added to a solution
of the deprotected macromonocycle (0.20 g, 0.43 mmol) with K2CO3
(0.50 g, 3.62 mmol) in CH3CN (200 mL), and the reaction mixture was
refluxed for 2 days. The solvent was evaporated and water (100 mL)
was added to the residue. After stirring the mixture for 3 h, the
precipitate was isolated by filtration and dried. This crude product
was purified by column chromatography (basic Al2O3, 2% MeOH in
CH2Cl2) to give the pure macrotricycle 1 (30% yield). 1H NMR
(400 MHz, [D6]DMSO, 238C, TMS): d = 8.70 (brs, 8H; NH), 7.88 (t,
J(H,H) = 7.0 Hz, 4H; ArH), 7.79 (d, J(H,H) = 7.4 Hz, 8H; ArH), 3.35
[9] X-ray data for nBu4N+[1(FHFÀ)]·3H2O: C64H103F2N17O11, Mr =
1324.63, crystal dimensions 0.36 ” 0.30 ” 0.30 mm3, orthorhom-
bic, space group C2221, a = 14.611(2), b = 17.121(2), c =
28.675(3) Š, a = b = g = 908, V= 7173(2) Š3, Z = 4, 1calcd
=
1.227 gcmÀ3
0.089 mmÀ1
(43041measured), R1 (unweighted, based on F) = 0.074 for
8546 “observed” reflections having I > 2s(I) and 2q(MoKa
,
T= 100(2) K,
F(000) = 2848,
m(MoKa) =
,
1 051 R4int =( 0.043) independent reflections
)
1924
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Chemie
< 60.208; R1 (unweighted, based on F) = 0.084, wR2 (weighted,
based on F2) = 0.221and GOF (on F2) = 1.020 for all 10514
independent reflections having 2q(MoKa) < 60.208. X-ray data
for 1·6H2O: C48H72N16O14, Mr = 1097.22, crystal dimensions
0.36 ” 0.34 ” 0.10 mm3, monoclinic, space group C2/c, a =
17.116(2), b = 14.949(2), c = 22.082(3) Š, a = g = 908, b =
106.782(3), V= 5409(1) Š3, Z = 4, 1calcd = 1.347 gcmÀ3
, T=
100(2) K, F(000) = 2336, m(MoKa) = 0.101 mmÀ1, 7867 (Rint
=
0.028) independent absorption-corrected reflections (30720
measured), R1 (unweighted, based on F) = 0.049 for 6680
“observed” reflections having I > 2s(I) and 2q(MoKa) < 60.118;
R1 (unweighted, based on F) = 0.057, wR2 (weighted, based on
F2) = 0.132 and GOF (on F2) = 1.021 for all 7867 independent
absorption-corrected reflections having 2q(MoKa) < 60.118.
CCDC-289348 and CCDC-289349 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
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