Imidazolium-based [14]heterophanes as models for anion recognition

Article abstract of DOI:10.1002/ejoc.200600269

The significance of the reported dicationic [1₄]imidazoliophanes 4·2X relies on their ability to bind anions in polar media. Thus, imidazolium units represent the main structural motifs in the formation of unconventional (C-H)⁺...Cl<

Full text of DOI:10.1002/ejoc.200600269

FULL PAPER
DOI: 10.1002/ejoc.200600269
Imidazolium-Based [14]Heterophanes as Models for Anion Recognition
Ermitas Alcalde,*[a] Neus Mesquida,[a][‡] and Lluïsa Pérez-García[a]
Keywords: Macrocycles / Cyclophanes / Hydrogen bonds / Anion recognition / NMR spectroscopy
The significance of the reported dicationic [14]imid-
azoliophanes 4·2X relies on their ability to bind anions in po-
lar media. Thus, imidazolium units represent the main struc-
tural motifs in the formation of unconventional (C–H)+···Cl–
change using a strongly basic anion-exchange resin (OH–
form) and their structures have been examined by NMR
spectroscopy. Solution studies in CD3CN and [D6]DMSO by
1H NMR spectroscopy have revealed the importance of the
charge-assisted hydrogen bonds which become the nonco- hydrogen bonds in controlling anion recognition.
valent forces driving the anionic interactions exhibited by di-
cations 4·2X. Herein, we report the “3+1” convergent synthe-
sis of the title macrocycles 4a–d·2X; their counteranion ex-
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
of the [14]imidazoliophanes 4·2X to bind chloride anions
Introduction
has been exploited during their synthesis.[9d]
Over the last few years, imidazolium-based frameworks
have been developed as part of the advances in N-heterocy-
clic carbene (NHC)[2] and anion recognition chemistry[3,4]
and room-temperature ionic liquids (RILs).[5] Among them,
recent developments in anion recognition include advances
in anion templating and the design of artificial anion recep-
tors, which frequently rely on cationic moieties.[4] In these
positively charged systems, the primary noncovalent driving
forces for binding are either electrostatic interactions or
electrostatic interactions in combination with hydrogen
bonding forces,[6] that is, by forming N–H···anion bonds[4a]
or a novel type of charged hydrogen bond, (C–H)+···
anion.[7,8]
As part of our ongoing research of imidazolium-based
frameworks,[7,9] we have examined cyclophanes 1·2X and
2[9b] together with dicationic pincers 3·2X (Figure 1);[9c] for
bis(betaines) 2 and dications 1·2X, quaternary imidazolium
units were selected because of the recognized chemical sta-
bility of the methyleneimidazolium azolate betaine building
blocks.[10] Maintaining the two imidazolium moieties
present in the heterophanes 1·2X, dicationic [14]imid-
azoliophanes 4·2X arise as models for intermolecular inter-
actions driven by unconventional (C–H)+···X hydrogen
bonds[7] (Figure 1). Dication 4a·2Cl·2H2O was the first re-
ported example of nonclassical (C–H)+···Cl– hydrogen
bonds between the C–H group of the imidazolium rings
and the chloride anions in the solid state,[1,7] and the ability
[a] Laboratori de Química Orgànica, Facultat de Farmàcia, Uni-
versitat de Barcelona,
Avda. Joan XXIII s/n, 08028 Barcelona, Spain
E-mail: ealcalde@ub.edu
[‡] See ref.[1]
Figure 1. Imidazolium molecular motifs within [14]heterophane
frameworks. The molecular structure of 4a·2Cl·2H2O shows non-
classical (C–H)+···Cl– hydrogen bonds (see ref.[7]).
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
3988
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Imidazolium-Based [14]Heterophanes as Models for Anion Recognition
FULL PAPER
From dicationic prototypes 4·2X, a variety of imid-
azolium-linked scaffolds have been investigated for anion
binding driven by this new type of (C–H)+···halide hydro-
gen bond.[8] The behavior in the gas phase of simple sys-
tems containing two imidazolium quaternary moieties, for
example, 4·2X (M·2X), has been examined by using posi-
tive-ion ESI-MS and direct electrospray mass spectrometric
evidence has been obtained for singly charged imidazolylid-
ene ions [M – H]+ and the regiospecific deuteriated counter-
parts have produced the corresponding imidazolylidene spe-
cies [M – D]+.[11,12] In parallel, metal complexes of NHC-
linked cyclophanes and pincers related to dications 4·2X
and 3·2X have been reported, giving rise to active catalytic
model systems for several reactions.[2,13]
The present study focuses on the convergent “3+1” syn-
thesis of the title dications 4a–d·2X and their counteranion
exchange using a strongly basic anion-exchange resin (OH–
form). The structures of these model imidazolium-based cy-
clophanes were examined by NMR spectroscopy and solu-
tion studies by 1H NMR spectroscopy in CD3CN and [D6]-
DMSO revealed the importance of the hydrogen bonds in
controlling anion binding.
Results and Discussion
Synthesis
The dications 4a–d·2X were prepared according to a
“3+1” convergent approach, and the coupling of the trinu-
cleating protophanes 5a–d with the 1,3-bis(halomethyl)ben-
zene 6 or 7 produced the dications 4a–d·2X in Ն47%
(Scheme 1). For 4b·2X, the macrocyclization reaction was
improved by using the more reactive 1,3-bis(bromomethyl)-
benzene (8). Protophanes 5a,b were obtained in Ն72% yield
by treatment of 1,3-bis(chloromethyl)benzene (6) with imid-
azoles 9 or 10, and reaction of 1,3-bis(bromomethyl)-5-tert-
butylbenzene (7) with imidazoles 9 or 10 gave 5c,d in Ն49%
yield (Scheme 1). Physical data for all the new compounds
reported are listed in Table 1.
Scheme 1. “3+1” Convergent synthesis of imidazoliophanes 4·2X.
(M·4PF6), whereas exchanging the counteranion to afford
the tetrachloride macrocycle (M·4Cl) conferred aqueous
solubility upon the tetracation but rendered it insoluble in
Counteranion Exchange Using a Strongly Basic Anion-
Exchange Resin (OH– Form)
Exploiting our standard protocol,[9,10] the counteranions Me2CO, MeCN and MeNO2.[14a] Similar hydrophobic be-
of dications 4a–d·2X were changed by the use of a strongly havior was also observed when the tetracation macrocycle
basic anion-exchange resin (OH– form) followed by imme- counteranion was located within [2]catenane and rotaxane
diate collection of the eluates in acid solution in aq. HPF6, systems.[14b] Moreover, hydrophobic and hydrophilic ILs are
aq. HCl, aq. HBr or aq. CH3CO2H to pH = 3 (Scheme 2 of practical interest and the physical properties of these sim-
and Table 1). The anion exchange proceeded through the ple imidazolium salts can be modulated especially by
corresponding quaternary imidazolium hydroxides 4a–d· changing the counteranions, with the hexafluorophosphate
2OH (see below).
anion notably increasing the lipophilicity of ILs.[14c] Ac-
The hexafluorophosphate counteranion enhances the cordingly, the hexafluorophosphate counteranion notably
solubility of the positively charged frameworks in relatively increased the solubility of dicationic cyclophanes 4a–d·2X
nonpolar solvents; Stoddart and co-workers observed that in organic solvents and dications 4a–d·2PF6 were much
the solubility in organic solvents of the tetracationic cyclo- more soluble in acetonitrile and alcohols than their corre-
bis(paraquat-p-phenylene) (M·4X) increased considerably sponding dichloride or dibromide counterparts. Note that
when the counteranions were hexafluorophosphates dicationic macrocycles containing proton-ionizable 1H-
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E. Alcalde, N. Mesquida, L. Pérez-García
FULL PAPER
Table 1. Physical data for the macrocyclic salts 4a–d·2X and protophanes 5b–d.
Compd.
Yield [%][a]
M.p. [°C]
Ͼ300
Solvent[b]
Molecular formula[c]
4a·2Cl
4a·2PF6
5b
4b·2Br
4b·2Cl
4b·2PF6
5c
4c·2Br
4c·2Cl
4c·2PF6
5d
4d·2Br
4d·2Cl
4d·2PF6
4d·2AcO
66
91
72
59
47
84
54
57
100
99
49
48
100
99
100
MeCN
C22H22N4Cl2·2H2O
C22H22N4P2F12·H2O
C30H46N4·H2O
C38H54N4Br2·0.75HBr
C38H54N4Cl2·1.75HCl
C38H54N4P2F12·4.5H2O
C18H22N4
Ͼ300
–
–
–
[d]
262–264
266
228–230
72
293
278–280
Me2CO
–
toluene
iPrOH
MeCN
C30H38N4Br2·2H2O
C30H38N4Cl2·3.5H2O·0.5CH3CN
C30H38N4P2F12·H2O
C34H54N4·0.25H2O
C46H70N4Br2·1.5H2O
C46H70N4Cl2·2.5H2O
C46H70N4P2F12·H2O
C50H76N4O4·4.5H2O
Ͼ300
–
–
–
[d]
278–280
236–238
–
MeCN
–
288–290
[e]
[a] Yields were not optimized. [b] Recrystallization solvent. [c] Satisfactory microanalyses were obtained ( 0.4% for C, H, N). [d] Oily
compound. [e] Foamy compound.
and in the solid state; after very short periods of time in
solution products of decomposition and alteration were ob-
served by 1H NMR spectroscopy, ca. 20% for 4c,d·OH and
ca. 90% for 4a·OH. In contrast, dication 4b·2OH appeared
1
to be rather stable and showed a clean H NMR spectrum
in [D6]DMSO (see NMR spectroscopy and Figure 3); the
relative stability of these dications in solution follows the
relative order 4b·2OH Ͼ 4c·2OH Ϸ 4d·2OH ϾϾϾ
4a·2OH.
Structure and NMR Spectroscopy
The distinctive structural aspects of dicationic cy-
clophanes 4·2X have been examined both in the gas phase
by positive-ion electrospray mass spectrometry and in the
solid state by X-ray crystallography.[7,11] Accordingly,
macrocycles 4·2Cl (M·2Cl) gave clean positive-ion ESI spec-
tra; at low cone voltage Vc, the base peak corresponds in
each case to the doubly charged ion [M]2+ resulting from
the loss of the two Cl– counterions. When the cone voltage
was increased to 80 V, the base peak corresponded to the
singly charged ion [M – H]+.[11]
Notably, the single-crystal X-ray diffraction analysis of
dication 4a·2Cl·2H2O typified the first example of the non-
Scheme 2.
classic (C–H)+···Cl– hydrogen bonds between the imid-
azolium rings and chloride anions; the shortest hydrogen
1,2,4-triazole fragments, such as heterophanes 1·2X, are bond interaction was H10···Cl1 (2.54 Å, θ = 157°) (see Fig-
fairly insoluble compounds irrespective of the nature of ure 1). The hydrogen-bonding networks within the solid-
their counteranions.[9b]
state aggregates show that the chloride anions and water
At this point, the stability of the dicationic hydroxides molecules are located among the dications in a channel
4a–d·2OH was then examined. The anion exchange for fashion.[7]
macrocycles 4a–d·2X proceeds through the corresponding
The IR spectra of dications 4a–d·2X showed characteris-
–
quaternary imidazolium hydroxides (4a–d·2OH) and the el- tic absorption bands of the counteranions, Cl–, Br–, PF6
uates had to be immediately collected in acid solution (see and AcO–. The 1H NMR spectra of 4a–d·2X (X = Cl–, Br–,
Scheme 2). Note that azolylimidazolium salts with different PF6 ) showed a sharp singlet due to the methylene hydrogen
–
interannular spacers have been found to be very unstable, atoms indicating a high degree of conformational flexibility
especially in the solid state, when the counteranion is hy- comparable to that in dications 1·2X and bis(betaines) 2.[9b]
droxide.[9,10] Prior to acidification, the eluates gave yellow- The association behavior was examined in the concentra-
to-red solids and 4a,c,d·2OH were unstable both in solution tion range of 0.5–38 m (Table 2) and the variation in the
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Imidazolium-Based [14]Heterophanes as Models for Anion Recognition
FULL PAPER
1
Table 2. Concentration dependence of 4a–d·2X as determined by H NMR spectroscopy.[a]
Compd.
Solvent
[4a–d·2X] [m]
Nonaggregating [4a–d·2X]max [m]
4a·2Cl
4a·2PF6
4b·2Cl
4b·2PF6
4c·2Br
4c·2Cl
4c·2PF6
4d·2Br
4d·2Cl
4d·2PF6
4d·2AcO
[D6]DMSO
1.51–38.10
1.36–18.60
0.71–23.63
1.33–17.84
1.39–25.11
0.59–25.55
0.48–18.61
1.33–19.62
0.95–18.29
1.27–11.86
0.56–20.22
2.93
[b]
2.85
[b]
12.55
1.09
ca. 2[c]
9.90
ca. 9[d]
[b]
0.56
0.36
4d·2Br
4d·2Cl
4d·2PF6
4d·2AcO
CD3CN
0.36–6.05[e]
0.40–6.37[e]
1.49–14.14
0.37–22.28
0.40
[b]
0.37
[a] Aggregation occurred when the chemical shift difference (∆δ) was Ͼ 0.1 ppm. [b] Aggregation was not observed. [c] ∆δ Յ 0.1 ppm for
1.53–2.89 m. [d] ∆δ Յ 0.1 ppm for 4.76–9.71 m. [e] At higher concentrations the compound was insoluble.
Table 3. Selected 1H NMR spectroscopic data for [14]imid-
azoliophanes 4a–d·2X and protophanes 5a–d in [D6]DMSO at
300 MHz.[a]
Table 4. Selected 13C NMR spectroscopic data for [14]metaimid-
azoliophanes 4a–d·2X and protophanes 5a–d in [D6]DMSO at
50.3 MHz.
Compd.
Conc. [m][a]
δ [ppm]
24-H[b]
23-H[b]
–CH2–
4a·2Cl[c]
4a·2PF6
4b·2Cl
1.51
1.36
9.42
9.24
9.32
9.37
9.49
9.34
9.36
9.34
9.45
9.46
9.33
9.42
9.59
7.09
6.95
6.57
6.61
6.51
6.60
6.69
6.67
6.76
6.48
6.41
6.48
6.54
5.42
5.41
5.51
5.51
5.14–5.73
5.50
5.42
5.42
5.41
5.55
Compd.
δ [ppm]
C-23[a]
C-24[a]
–CH2–
0.71
[e]
4b·2Br[d]
4b·OH
4a·2Cl[b]
4a·2PF6
4b·2Cl
136.4
136.4
137.2
136.8
136.7
136.4
136.3
136.4
137.0
136.7
136.7
137.7
127.1
126.0
124.3
123.9
123.6
123.1
122.7
123.5
121.5
121.1
121.1
121.8
52.0
52.1
49.7
49.7
49.8
52.2
52.2
52.2
50.0
50.1
50.1
49.9
[e]
4b·2PF6
4c·2Cl
1.33
0.59
1.39
0.48
0.95
1.33
1.27
0.56
4b·2Br[b]
4b·2PF6
4c·2Cl
4c·2Br[f]
4c·2PF6
4d·2Cl
4c·2Br
4c·2PF6
4d·2Cl
4d·2Br
4d·2PF6
4d·2OAc
4d·2Br
4d·2PF6
4d·2OAc
5.50
5.49
5.49
2Ј-H
2-H
–CH2–
5a
5b
–
–
–
–
7.72
7.46
7.71
7.45
7.19
6.82
6.94
6.61
5.16
5.05
5.14
5.04
C-2Ј
C-2
–CH2–
5c
5a[b]
5b
137.7
136.2
137.6
136.2
126.9
125.2
124.1
122.3
49.5
47.6
49.8
47.9
5d[d]
5c
[a] At nonaggregating concentrations. [b] The equivalent proton
atoms are abbreviated as follows: 23-H = 23,25-H; 24-H = 24,26-
H. [c] Assignment by NOESY. [d] Recorded at 500 MHz. [e] At a
concentration of ca. 2 m. [f] Assignment by NOE.
5d[b]
[a] The equivalent carbon atoms are abbreviated: C-23 = C-23,25;
C-24 = C-24,26. [b] Assignment by hetcor (hmqc, hmbc).
Eur. J. Org. Chem. 2006, 3988–3996
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E. Alcalde, N. Mesquida, L. Pérez-García
FULL PAPER
chemical shift was studied for protons 23,25-H and 24,26-
H; the chemical shifts of the macrocycles 4a–d·2PF6 re-
mained essentially constant upon changing the concentra-
tion from ca. 1 to ca. 18 m.
Selected 1H NMR spectroscopic data at 300 MHz
(298 K) in [D6]DMSO under nonaggregation conditions are
listed in Table 3 and 13C NMR spectroscopic data in
Table 4.
1
Qualitative H NMR observations have shown the im-
portance of the imidazolium structural motifs for anion
binders 4·2X. At nonaggregating concentrations, the proton
chemical shifts of the imidazolium protons 23-H and 25-H
together with 24-H and 26-H (the aromatic fragments) were
the most affected mainly due to structural factors, the na-
ture of the counteranion and solvent polarity. Representa-
tive data are gathered in Table 5 and Figure 2. The presence
of substituents led to significant shielding of these protons,
possibly due to diminished conformational flexibility. For
example, in [D6]DMSO the ∆δ(24,26-H) between 4d·2Cl
and 4a·2Cl was –0.61 ppm (183 Hz) and this effect was
maintained on changing the counteranion, ∆δ(24,26-H) be-
tween 4d·2PF6 and 4a·2PF6 being –0.47 ppm (141 Hz) (see
Figure 2a).
1
Table 5. Selected H NMR spectroscopic data for 4a–d·2X in [D6]-
DMSO and CD3CN.
Compd.[a]
Conc. [m]
δ [ppm]
23,25-H
24,26-H
4a·2Cl
4a·2PF6
4b·2Cl
4b·2PF6
4c·2Br
4c·2Cl
1.51
1.36
0.71
1.33
1.39
0.59
0.48
9.42
9.24
9.32
9.34
9.34
9.36
9.45
7.09
6.95
6.57
6.60
6.67
6.69
6.76
4c·2PF6
Figure 2. 1H NMR chemical shift variations of 23,25-H and/or
24,26-H (300 MHz): (a) 4a–d·2Cl in [D6]DMSO; (b) 4a·2PF6/
4a·2Cl in [D6]DMSO and 4d·2X in CD3CN; (c) 4d·2Br and
4d·2CH3CO2 in [D6]DMSO and CD3CN; (d) 4d·2PF6 in [D6]-
DMSO and CD3CN.
Compd.[a]
Conc. [m]
23,25-H
24,26-H
4d·2Br
4d·2Cl
4d·2PF6
4d·2AcO
1.33
0.95
1.27
0.56
9.33
9.46
9.42
9.59
6.41
6.48
6.48
6.54
Compd.[b]
Conc. [m]
23,25-H
24,26-H
tween 4d·2CH3CO2 and 4d·2PF6 ∆δ(23,25-H) = +1.09 ppm
(327 Hz) and ∆δ(24,26-H) = +0.65 ppm (195 Hz) (see Fig-
ure 2b).
4d·2Br
4d·2Cl
4d·2PF6
4d·2AcO
0.36
0.40
1.49
0.37
9.43
9.48
8.87
9.96
6.80
6.81
6.32
6.97
Owing to solvent effects,[4a,9c,15] dications 4d·2X exhib-
ited greater deshielding of the acidic 23-H and 25-H pro-
tons in a less polar solvent, for example, 4d·2Br for which
∆δ(23,25-H) (in CD3CN/[D6]DMSO) = +0.1 ppm (30 Hz)
and 4d·2CH3CO2 for which ∆δ(23,25-H) (in CD3CN/[D6]-
[a] 1H NMR (300 MHz) data in [D6]DMSO. [b] 1H NMR
(300 MHz) data in CD3CN.
As a consequence of the hydrogen bonding of the anions DMSO) = +0.37 ppm (111 Hz) (see Figure 2c). When the
present in the dicationic macrocycle 4a–d·2X, the signals of counteranions were hexafluorophosphates, the dications 42+
the acidic imidazolium 23-H and 25-H atoms were shifted showed very weak or no hydrogen bonding between the
–
downfield up to about 10 ppm in comparison with the usual PF6 counteranions; similar behavior has been reported for
[9b]
[9c]
values of the chemical shifts for these imidazolium protons the heterophanes 1·2PF6
and protophanes 3·2PF6
in
in azolophanes (e.g., 1·2X) and in a variety of N-azolylimid- solution and has been confirmed in the solid state by X-ray
azolium salts with different spacers.[9,10] Depending on the diffraction analysis of protophane 3c·2PF6 (see Figure 1; R
nature of the anion, large differences in the chemical shifts = H, RЈ = tBu). On the whole, the title imidazolium-based
were observed; for instance, in [D6]DMSO between 4a·2Cl dicationic cyclophanes 4a–d·2X are simple prototypes for
and 4a·2PF6 ∆δ(23,25-H) = +0.18 ppm (54 Hz) and noncovalent intermolecular ion interactions driven by hy-
∆δ(24,26-H) = +0.14 ppm (42 Hz), while in CD3CN be- drogen bonds, taking into account both the operation of
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Imidazolium-Based [14]Heterophanes as Models for Anion Recognition
FULL PAPER
the chloride template effect in the formation of these Complexation Studies
macrocyclic dications though a “3+1” macrocyclization re-
The anion-binding behavior of dication 4d·2PF6 was
then examined by 1H NMR spectroscopy.[1,7a,16] Significant
changes in δH were induced by the addition of various tetra-
butylammonium salts (ca. 6 m) to a solution of dication
4d·2PF6 (ca. 3 m) either in [D6]DMSO or CD3CN and the
major deshielding effect was observed at the ring protons
23,25-H and 24,26-H, respectively (Figure 4). The host
4d·2PF6 showed a preference for the anions in the order of
action[9d] and their structural properties.
1
A meaningful H NMR result deals with the macrocycle
4b·2OH, which exhibits two pairs of doublets in a ratio of
1:1 for the methylene spacer signals, which is indicative of
a partial cone conformation. Addition of 5% trifluoroacetic
acid to the NMR solution sample gave a singlet for the
methylene protons as a result of the conversion of 4b·2OH
into the corresponding bis(trifluoroacetate) 4b·2CF3CO2
(Figure 3). Significantly, modulation of the nature of the
counteranion can be applied as a “brake” in a reversible
manner to the conformational equilibria.
–
–
F– Ͼ H2PO4 Ͼ CH3CO2 Ͼ CN– Ͼ Cl– Ͼ Br– Ͼ I– ϾϾ
–
PF6 in [D6]DMSO, whereas in CD3CN the trend was CN–
–
–
–
Ͼ CH3CO2 Ͼ F– Ͼ H2PO4 Ͼ Cl– Ͼ Br– Ͼ I– ϾϾ PF6 .
The largest chemical shift difference observed after the ad-
dition of 1 equiv. of TBA·CH3CO2 in CD3CN to 4d·2X cor-
responds to 23,25-H with ∆δ = +1.61 ppm (483 Hz) and to
24,26-H with ∆δ = +0.83 ppm (249 Hz), whereas under
anion saturation conditions the maximum chemical shift
registered for 23,25-H is ∆δ = +2.02 ppm (606 Hz) and for
24,26-H is ∆δ = +0.81 ppm (243 Hz).
Figure 3. Dication 4b·2OH: (a) Partial cone conformations; (b) 1H
NMR spectra of 4b·2Cl, 4b·2OH and 4b·2CF3CO2 in [D6]DMSO
at 200 MHz between δ = 5 and 6 ppm.
On the whole, the simple imidazolium-based cyclophanes
4·2X can be considered as models for intermolecular anion
interactions driven by hydrogen bonds since there is a good
parallel between the experimental trends observed in liquid
solution and in the solid state as well as in the gas phase
by ESI-MS in the negative mode. As a consequence, we
decided to delve into the anion-receptor behavior of the tar-
geted dications. Macrocycle 4d·2PF6 was selected as the
model as a result of its solubility in both nonpolar solvents,
such as chloroform, and polar solvents, for example, aceto-
nitrile and dimethyl sulfoxide, despite its insolubility in
water. The concentration dependence of the chemical shift
was studied for protons 23-H and 25-H together with 24-H
and 26-H. In [D6]DMSO, no aggregation was observed in
the range of 1.27–11.86 m, whereas in CD3CN no aggre-
gation was observed between 1.49 and 14.14 m; in aggre-
gation and binding studies, the experimental error was
evaluated to be ∆δ Յ 0.1 ppm.
1
Figure 4. H NMR chemical shift deshielding ∆δ at 300 MHz for
23,25-H and 24,26-H for ca. 3 m 4d·2PF6 after the addition of
1 equiv. of different TBA·X salts in [D6]DMSO and CD3CN.
Eur. J. Org. Chem. 2006, 3988–3996
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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3993

E. Alcalde, N. Mesquida, L. Pérez-García
FULL PAPER
25 °C in a vacuum oven overnight. Microanalyses were performed
with a Carlo Erba 1106 analyzer.
Next we examined the ability of the model heterophane
4d·2PF6 based on imidazolium units to act as a molecular
recognition motif for anions and its quantitative complex-
ation with five tetrabutylammonium salts (TBA·X) was
studied in polar solvents ([D6]dimethyl sulfoxide and [D3]-
Materials: 1,3-Bis(chloromethyl)benzene (6), 1,3-bis(bromomethyl)-
benzene (8) and 1H-imidazole (9) were purchased from commercial
sources. 1,3-Bis(bromomethyl)-5-tert-butylbenzene (7)[18] and 4,5-
dibutylimidazole hydrochloride (10·HCl)[19] were prepared as de-
scribed in the literature. Counterion exchange was performed by
treatment of the [14]heterophanes 4a–d·2X with a strongly basic
anion-exchange resin followed by immediate collection of the elu-
ates in acid solutions (either with aq. HCl, aq. HBr, aq. HPF6 or
aq. CH3CO2H) to pH = 3 according to a standard protocol.[9,10]
Protophane 5a (Scheme 1):[20] A suspension of 1H-imidazole (9;
2.0 g, 29.4 mmol) and finely powdered 85% potassium hydroxide
(2.5 g, 37.9 mmol) in dry acetonitrile (200 mL) was vigorously
stirred under nitrogen at room temperature for 1 h. A solution of
1,3-bis(chloromethyl)benzene (6; 2.6 g, 14.7 mmol) in dry acetoni-
trile (50 mL) was then added dropwise and the mixture stirred at
room temperature for 6 h. The reaction mixture was cooled, filtered
and the solvent removed to dryness. The resulting oil was dissolved
in dichloromethane (100 mL) and washed with water (3×100 mL)
The organic layer was dried (anhydrous Na2SO4), filtered and the
solvent evaporated to provide protophane 5a.
1
acetonitrile) by H NMR titration (see Table S6 and Fig-
ure S5 in the Supporting Information). In several cases the
stoichiometry of solution complexation was 1:1 which was
determined by the mol ratio method. Among the 1:1 com-
plexes, the maximum association constant (Ka) was ob-
served for the complex formed between 4d·2PF6 and
TBA·CH3CO2: Ka = 359 42 –1, –∆G° = 14.5 0.3 kJ/
mol.[1,17]
Conclusions
Dicationic [14]imidazoliophanes 4·2X are simple proto-
types for the examination of the intermolecular interactions
driven by hydrogen bonds in which the halide
counteranions, for example, X = Cl, are noncovalently
bound to the macrocyclic framework. For their preparation,
a “3+1” convergent stepwise synthesis was applied and, by
exploiting our standard protocol, the counteranions of di-
cations 4a–d·2X were changed by the use of a strongly basic
anion-exchange resin (OH– form) followed by immediate
collection of the eluates in acid solution; the anion ex-
change proceeded through the corresponding quaternary
imidazolium hydroxides 4a–d·2OH. Their structures were
Protophane 5b (Table 1): A suspension of 4,5-dibutylimidazole hy-
drochloride (10·HCl; 1.8 g, 8.3 mmol) and finely powdered 85%
potassium hydroxide (1.4 g, 21.5 mmol) in dry acetonitrile (60 mL)
was vigorously stirred under nitrogen at room temperature for 1 h.
A solution of 1,3-bis(chloromethyl)benzene (6; 0.8 g, 4.1 mmol) in
dry acetonitrile (25 mL) was then added dropwise and the mixture
stirred at room temperature for 7 h. The reaction mixture was co-
oled, filtered and the solvent removed to dryness. The resulting oil
was dissolved in dichloromethane (150 mL) and washed with water
(3×150 mL). The organic layer was dried (anhydrous Na2SO4), fil-
tered and the solvent evaporated. The oily residue was purified by
column chromatography (Al2O3) with dichloromethane/ethanol
mixtures of increasing polarity as eluents to provide protophane
5b.
1
examined in solution by H NMR spectroscopy and there
is a good parallel between the experimental trends observed
in the solid state by X-ray crystallography of 4a·2Cl·2H2O
1
and in liquid solution by H NMR spectroscopy. Efforts
are currently being directed towards the use of imid-
azolium-linked systems for processes controlled either by
hydrogen-bonding networks or by their (imidazol-2-
ylidene)metal complexes.
Protophane 5c (Table 1): A suspension of 1H-imidazole (9; 2.0 g,
29.4 mmol) and finely powdered 85% potassium hydroxide (2.5 g,
37.9 mmol) in dry acetonitrile (200 mL) was vigorously stirred un-
der nitrogen at room temperature for 1 h. A solution of 1,3-bis(bro-
momethyl)-5-tert-butylbenzene (7; 4.6 g, 14.5 mmol) in dry acetoni-
trile (50 mL) was then added dropwise and the mixture stirred at
room temperature for 4 d. The reaction mixture was cooled, fil-
tered, and the solvent removed to dryness. The resulting oil was
dissolved in dichloromethane (200 mL) and washed with water
(3×250 mL). The organic layer was dried (anhydrous Na2SO4), fil-
tered, and the solvent evaporated. The oily residue was purified
by column chromatography (SiO2) with dichloromethane/ethanol
mixtures of increasing polarity as eluents to provide protophane
5c.
Experimental Section
General Methods: Melting points: CTP-MP 300 hot-plate appara-
tus with ASTM 2C thermometer (given in Table 1). IR (KBr disks):
1
Nicolet 205 FT spectrophotometer. H NMR: Varian Gemini 200
and 300 spectrometers (200 and 300 MHz) at 298 K. 13C NMR:
Varian Gemini 200 spectrometer (50.3 MHz) at 298 K. HMQC and
HMBC: Varian VXR 500 spectrometer (500 MHz). NMR spectra
were determined in [D6]dimethyl sulfoxide or [D3]acetonitrile and
chemical shifts are expressed in parts per million (δ) relative to the
central peak of [D6]dimethyl sulfoxide or [D3]acetonitrile. The pH
was monitored with a CRISON micro-pH 2001 apparatus. TLC
was performed on Merck precoated 60 F254 silica gel plates in
methanol/ammonium chloride (2 ⁾/nitromethane (6:3:1) as de-
veloping solvent; the spots were located with UV light and devel-
oped with a 10% aqueous solution of potassium iodide or a 3%
aqueous solution of hexachloroplatinic acid. Chromatography:
SDS silicium oxide 60 ACC (30–75 µm) and Merck aluminium ox-
Protophane 5d (Table 1): A suspension of 4,5-dibutylimidazole hy-
drochloride (10·HCl; 3.3 g, 15.0 mmol) and finely powdered 85%
potassium hydroxide (2.6 g, 39.0 mmol) in dry acetonitrile (90 mL)
was vigorously stirred under nitrogen at room temperature for 1 h.
A solution of 1,3-bis(bromomethyl)-5-tert-butylbenzene (7; 2.4 g,
7.5 mmol) in dry acetonitrile (50 mL) was then added dropwise and
the mixture stirred at room temperature for 24 h. The reaction mix-
ture was cooled, filtered and the solvent removed to dryness. The
resulting oil was dissolved in dichloromethane (100 mL) and
washed with water (3×200 mL). The organic layer was dried (anhy-
drous Na2SO4), filtered and the solvent evaporated. The oily resi-
due was purified by column chromatography (Al2O3) with dichlo-
ide 90 standardized.
A standard protocol was applied for
counteranion exchange using a strongly basic anion-exchange resin
(hydroxide form).[9c] When a rotary evaporator was used, the bath
temperature was 25 °C. In general, the compounds were dried at
3994
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Imidazolium-Based [14]Heterophanes as Models for Anion Recognition
FULL PAPER
romethane/ethanol mixtures of increasing polarity as eluents to
provide protophane 5d.
tetrabutylammonium salts (6 m) in [D6]DMSO (300 MHz) at
298 K. Data for 1H NMR titration experiments with the imid-
azoliophane 4d·2PF6 (3 m) and several tetrabutylammonium salts
in [D6]DMSO (300 MHz) at 298 K. 1H NMR spectroscopic data
for mixtures of imidazoliophane 4d·2PF6 (3 m) and several tetra-
butylammonium salts (6 m) in CD3CN (300 MHz) at 298 K. Data
for 1H NMR titration experiments with the imidazoliophane
4d·2PF6 (3 m) and several tetrabutylammonium salts in CD3CN
(300 MHz) at 298 K. Determination of the stoichiometry between
4d·2PF6 (R) and TBA·CN (S) in CD3CN (200 MHz) at 298 K by
Job’s method. Stoichiometry values by the mol ratio method be-
tween the receptor 4d·2PF6 and TBA·X in CD3CN and [D6]DMSO
(300 MHz) at 298 K (Table S6). Plots of the stoichiometry between
4d·2PF6 and TBA·CN in CD3CN. Scatchard plots for 1:1 complex-
Macrocycle 4a·2Cl (Table 1): A stirred solution of 1,3-bis(chloro-
methyl)benzene (6; 0.53 g, 3.0 mmol) in dry acetonitrile (50 mL)
was added dropwise to a suspension of protophane 5a (0.7 g,
3.0 mmol) in dry acetonitrile (550 mL) at 25 °C under nitrogen, and
the mixture was then maintained in a bath at about 85 °C for 4 d.
The solvent was removed by rotary evaporation and the solid resi-
due was triturated with dry acetone (3×5 mL) and filtered to af-
ford macrocycle 4a·2Cl.
Macrocycle 4b·2Cl (Table 1): A stirred solution of 1,3-bis(chloro-
methyl)benzene (6; 0.23 g, 1.3 mmol) in dry acetonitrile (50 mL)
was added dropwise to a solution of protophane 5b (0.62 g,
1.3 mmol) in dry acetonitrile (50 mL) at 25 °C under nitrogen and
the mixture was then maintained in a bath at about 85 °C for 2 d.
The solvent was removed by rotary evaporation and the solid resi-
ation between 4d·2PF6 and TBA·X (X = CH3CO2 or CN– or F–)
–
(Figure S5).Thermodynamic parameters for complexes formed be-
tween the imidazoliophane 4d·2PF6 and tetrabutylammonium salts
(TBA·X).
due was triturated with dry acetone (3×5 mL) and filtered to af-
ford macrocycle 4b·2Cl.
Macrocycle 4b·2Br (Table 1): A stirred solution of 1,3-bis(bromo-
methyl)benzene (8; 0.9 g, 3.4 mmol) in dry acetonitrile (100 mL)
was added dropwise to a solution of protophane 5b (1.5 g,
3.4 mmol) in dry acetonitrile (900 mL) at 25 °C under nitrogen and
the mixture was then maintained in a bath at about 85 °C for 24 h.
The solvent was removed by rotary evaporation and the solid resi-
due was triturated with dry acetone (3×5 mL) and filtered to af-
ford macrocycle 4b·2Br.
Acknowledgments
This research was supported by the Dirección General de Investiga-
ción (MEC and MCyT, Spain) through projects PB95-0268 and
BQU2002-0347 and by the Vicerrectorat de Recerca (2006), Uni-
versitat de Barcelona. Additional support came from the Comis-
sionat per a Universitats i Recerca de la Generalitat de Catalunya
through grants 97SGR75 and 2001SGR00082.
Macrocycle 4b·2OH (Scheme 2): A solution of macrocycle 4b·2Cl
(0.1 g, 0.16 mmol) in ethanol (90%, 50 mL) was passed through a
column packed with a strongly basic anion-exchange resin. The
eluates were concentrated to dryness to afford the hydroxide
4b·2OH.
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methyl)-5-tert-butylbenzene (7; 0.32 g, 1.0 mmol) in dry acetonitrile
(50 mL) was added dropwise to a solution of protophane 5c (0.3 g,
1.0 mmol) in dry acetonitrile (200 mL) at 25 °C under nitrogen and
the mixture was then maintained in a bath at about 85 °C for 4 d.
The solvent was removed by rotary evaporation and the solid resi-
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ford macrocycle 4c·2Br.
Macrocycle 4d·2Br (Table 1): A stirred solution of 1,3-bis(bromo-
methyl)-5-tert-butylbenzene (7; 0.7 g, 2.2 mmol) in dry acetonitrile
(50 mL) was added dropwise to a solution of protophane 5d (1.1 g,
2.2 mmol) in dry acetonitrile (600 mL) at 25 °C under nitrogen and
the mixture was then maintained in a bath at about 85 °C for 24 h.
The solvent was removed by rotary evaporation and the solid resi-
due was triturated with dry acetone (3×5 mL) and filtered to af-
ford macrocycle 4d·2Br.
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[14]metaimidazoliophanes 4a–d·2X. 1H NMR spectroscopic data
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Eur. J. Org. Chem. 2006, 3988–3996
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E. Alcalde, N. Mesquida, L. Pérez-García
FULL PAPER
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Received: March 28, 2006
Published Online: July 5, 2006
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Eur. J. Org. Chem. 2006, 3988–3996