New interlocked molecules generated from a podand containing urea units and imidazolium salts using an anion template

Article abstract of DOI:10.1016/j.tetlet.2003.11.064

A podand containing urea units (L) was found to form interlocked structures with 2,5-dihexylamide imidazolium salts (3·X), 2,5-dihexyl imidazolium salts (4·X), and 2,5-dihexyl benzoimidazolium salts (5·X), where X=Cl^-, Br^-, and PF₆ ^- using anions as templates. The binding ability of L and guest molecules was evaluated by ¹H NMR titrations in CDCl₃. It was found that L could form complexes with guest molecules in the following order, 3·X>5·X>4·X. Stabilities of the complexes also depended on shape of the templated anions: Cl^->Br ^-?PF₆^-. Hydrogen bonding and π-π stacking interactions played an important role in the self-assembling of these interlocked molecules.

Full text of DOI:10.1016/j.tetlet.2003.11.064

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 663–666
New interlocked molecules generated from a podand containing
urea units and imidazolium salts using an anion template
Boosayarat Tomapatanaget,a Thawatchai Tuntulani,a,* James A. Wisnerb
and Paul D. Beerb
aSupramolecular Chemistry Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University,
Bangkok 10330, Thailand
bDepartment of Chemistry, Inorganic Chemistry Laboratory, University of Oxford, Oxford OX 3QR, UK
Received 16 October 2003; revised 1 November 2003; accepted 14 November 2003
Abstract—A podand containing urea units (L) was found to form interlocked structures with 2,5-dihexylamide imidazolium salts
(3ÆX), 2,5-dihexyl imidazolium salts (4ÆX), and 2,5-dihexyl benzoimidazolium salts (5ÆX), where X ¼ Clꢀ, Brꢀ, and PF6 using anions
ꢀ
as templates. The binding ability of L and guest molecules was evaluated by 1H NMR titrations in CDCl3. It was found that L could
form complexes with guest molecules in the following order, 3ÆX > 5ÆX > 4ÆX. Stabilities of the complexes also depended on shape of
the templated anions: Clꢀ > BrꢀꢁPF6ꢀ. Hydrogen bonding and p–p stacking interactions played an important role in the self-
assembling of these interlocked molecules.
ꢀ 2003 Elsevier Ltd. All rights reserved.
Template synthesis has provided important advances in
developing strategies for the synthesis of complex
molecular architectures. Chemists employ cationic and
neutral molecules as templates for synthesizing supra-
molecular species such as rotaxanes, catenanes, and
other interlocked molecules.1;2 Anions have recently
been used as templates in synthetic chemistry.3 Stod-
podand diurea compound. This receptor is able to
organize itself in a cleft-like structure and assemble
imidazolium compounds. In this paper we demonstrate
that anion templating, hydrogen bonding, and p–p
stacking interactions play an important role in produc-
ing new interlocked molecules. The podand containing a
diurea receptor L was prepared in our group.9 It con-
tains two urea units as an anion binding site using
hydrogen bonding interactions and a polyethyleneglycol
unit as a cation binding site. The host and guests
described herein are shown in Chart 1.
4
5
€
dart and Vogtle are pioneers in synthesizing rotaxanes
and pseudorotaxanes using anions as templates.
Recently, Beer and co-workers have reported the chlo-
ride-directed assembly of a [2]pseudorotaxane by orga-
nizing a macrocyclic ligand and an amide pyridinium
molecule in an orthogonal fashion.6;7
Compound 3 was synthesized by refluxing a chloroform
solution of N-hexylchloroacetamide 110 and hexylcarb-
oxamide methyl imidazole 211 prepared by generating
the sodium imidazole salt from imidazole and NaH in
dry THF and subsequently coupling it with the N-hexyl-
chloroacetamide 1. The reaction provided a white pre-
cipitate of 3ÆClꢀ in 61% yield.12 In the case of 3ÆBrꢀ and
3ÆPF6ꢀ, they were obtained by anion exchanges between
3ÆClꢀ in methanol and saturated NH4Br and NH4PF6 in
aqueous solution yielding white solids of 3ÆBrꢀ and
Interestingly, the imidazolium cation has similar prop-
erties to the pyridinium cation such as holding a positive
charge and possessing ionic liquid properties. Imidazo-
lium units display main structural motifs for the for-
mation of uncoventional C–Hꢂ ꢂ ꢂClꢀ hydrogen bonding
interactions.8 Herein, we are interested in self-assembly
recognition of azoaromatic onium compounds and a
ꢀ
3ÆPF6 in 89% and 90% yields, respectively. The prep-
aration of 3ÆX, where X ¼ Clꢀ, Brꢀ, and PF6ꢀ, is shown
Keywords: Podand; Imidazolium salt; Anion template; Interlocked
molecule.
1
in Scheme 1. All compounds were characterized by H
NMR and electrospray ionization mass spectro-
* Corresponding author. Tel.: +66-2-2187643; fax: +66-2-2541309;
e-mail: tthawatc@chula.ac.th
metry.12;13 Compounds 3ÆClꢀ, 3ÆBrꢀ, and 3ÆPF6 show
ꢀ
0040-4039/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.11.064

664
B. Tomapatanaget et al. / Tetrahedron Letters 45 (2004) 663–666
O
O
N
N
O
O
H
H
OCH3
O
L
OCH3
O
H
H
N
N
O
Hexyl
N
N
Hexyl
N
N
O
O
-
-
X
X
Hexyl
N
N Hexyl
NH
HN
X-
4
X : Cl, Br and PF6
3
5
Chart 1.
Cl
O
O
Cl
NEt3, CH2Cl2
+
RNH2
Cl
1
(98%)
NHR
+
THF
+
NH
N
NNa
THF
NaH
N
N
N
CHCl3
Reflux
N
O
N
Cl
O
O
O
+
Cl-
3.Cl-
NHR
1
NHR
NHR
NHR
2
NH4PF6
(60%)
NH4Br
(61%)
-
R = hexyl
3.Br-
3.PF6
(90%)
(89%)
Scheme 1. Synthesis of imidazolium guests.
the NH signal at ca. 8.4–8.5 ppm. The three ligands have
similar NMR spectra as observed from the –NCHN–
and –NCHCHN– signals at 9.08 and 7.65, 9.05 and 7.65
as well as at 9.03 and 7.64 ppm, for 3ÆClꢀ, 3ÆBrꢀ, and
3ÆPF6ꢀ, respectively. However, the melting points of
3ÆClꢀ, 3ÆBrꢀ, and 3ÆPF6ꢀ were found to be distinguishable
being 160, 132, and 139 ꢁC, respectively. Compounds
4ÆBrꢀ and 5ÆBrꢀ were generated by coupling imidazole
or benzoimidazole and excess hexylamine in the pres-
ence of excess K2CO3 in dried acetone.14 Compounds
4ÆX and 5ÆX, where X ¼ Clꢀ and PF6ꢀ, were obtained
from anion exchanges using NH4Cl and NH4PF6,
respectively.6
Upon addition of guest molecules 3ÆX, 4ÆX, and 5ÆX,
where X ¼ Clꢀ and Brꢀ and monitoring complexation
processes by 1H NMR spectroscopy, NMR spectra
displayed significant shifts of signals of both L and
guests. However, where X ¼ PF6ꢀ, no change was
observed in the NMR spectra of mixtures of L with 3ÆX,
1
4ÆX, and 5ÆX. H NMR spectra of L, 3ÆBrꢀ and a 1:1
mixture of the two compounds are illustrated in Figure
1. Proton labels are shown in Figure 2. Interestingly, all
proton signals of the guest 3ÆBrꢀ (Hw, Hx, Hy, and Hz)
shift upfield while those of the host L (aromatic and urea
protons) shift downfield. Hydrogen bonding interac-
tions between protons Hx and Hz with Brꢀ was allocated
to the urea protons (Hg and Hi) of L resulting in a
decrease of hydrogen bonding interactions of protons
Hx and Hz with the anion and upfield shifts of the sig-
nals. In contrast, the urea protons of L (Hg and Hi)
display large downfield shifts because of the hydrogen
bonding interactions with Brꢀ. Furthermore, the signal
Hw of 3ÆX displays an upfield shift upon addition of
more guest species. It is probably due to the anisotropic
deshielding effect of the aromatic ring belonging to L.6
The effect of p–p stacking on the aryl protons of both
the imidazole and benzene rings of L causes the upfield
Compounds 3ÆX, 4ÆX, and 5ÆX are all ion-pairing guests,
which possess positively charged imidazolium rings with
the proton at the 2-position of the imidazolium ring able
to hydrogen bond to anions. Only compound 3ÆX
incorporates an anion binding cleft due to the amide
protons in addition to the ion pairing and the proton at
the 2-position. This allows an anion to locate within its
hydrogen bonding cleft in nonpolar solvents. All ligands
and the guest molecules dissolve very well in CDCl3,
which is a noncompetitive solvent.

B. Tomapatanaget et al. / Tetrahedron Letters 45 (2004) 663–666
665
the threading of the cations through the cavity of the
podand.
In the case of 4ÆX and 5ÆX, interactions with L are
1
similar to those of 3ÆX. Considering H NMR titration
spectra of L and 4ÆClꢀ, it was found that both NH
protons of L shifted downfield corresponding to
hydrogen bonding interactions with anions. Addition-
ally, aromatic protons shifted significantly indicating the
p–p stacking interactions between aromatic rings and
the imidazolium ring belonging to L and 4ÆClꢀ, respec-
tively. In the case of the complex of L and 5ÆClꢀ, the
aromatic protons of the benzoimidazolium ring of 5ÆX
showed significant upfield shifts due to the anisotropic
effect from the aromatic ring of L.
Association constants of complexes between L and 3ÆX,
ꢀ
4ÆX and 5ÆX where X ¼ Clꢀ, Brꢀ, and PF6 were mea-
1
sured by H NMR titrations monitoring the NH urea
protons of L. Titration curves of L with 3ÆX, 4ÆX, and
5ÆX are depicted in Figure 3. A Jobs plot indicated a
stoichiometry of 1:1 for the host and guest molecules.
Association constants of the self-assembly between two
molecules can be calculated by the EQNMR program.15
The association constants of complexation for L with
guest molecules are shown in Table 1. Both Clꢀ and Brꢀ
counter-ions have strong hydrogen-bonding interactions
with the host L and act as templates for the formation of
interlocked molecules. Among the guests, 3ÆX, 4ÆX, and
5ÆX, where X ¼ Clꢀ, show higher binding constants with
L than those where X ¼ Brꢀ. Formation of these inter-
locked molecules thus prefers a spherical template to an
octahedral template.
1
Figure 1. H NMR spectra of (a) L, (b) a 1:1 mixture of L and 3ÆBrꢀ,
and (c) 3ÆBrꢀ in CDCl3 at 400 MHz (298 K).
OMe
O
O
w
N
N
O
O
N
H
H
N
Hz
Hx
O
Cl
+
N
2.5
y
j
Hz
3Cl-
q
k
Hi N
Hg
N
3Br-
p
O
N
O
2
4Cl-
O l
o
n
O
4Br-
OMe m
1.5
5Cl-
5Br-
1
∆δ (ppm) of 3.Cl-; Hx : -1.07, Hy: -0.18 ppm, Hz: -0.49 ppm
∆δ (ppm) of L; Hi: +1.18 ppm, Hg: +0.68 ppm, Hj: +0.17 ppm,
Hk: +0.06 ppm, Hl: -0.14 ppm
0.5
0
Figure 2. The proposed structure of the complex between L and 3ÆClꢀ,
consistent with the cross relationship from ROSEY and the shifted
signals of L and 3ÆClꢀ.
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
Mole ratios
Figure 3. Titration curves of L and guest molecules in CDCl3.
Table 1. The association constants (Mꢀ1) in CDCl3 at 298 K
shifts of protons Hy and Hw. The template effect is even
more pronounced in the case of the Clꢀ counter ion,
which gives larger shifts of all proton signals.
Ka (Mꢀ1
Brꢀ
)
In addition, interactions between the host and guests
were supported by a ROSEY NMR spectrum of L
and 3ÆClꢀ in CDCl3. The cross relation peaks of Hy
and OCH3 protons, Hw and Hk, Hl and Hx as well as Hk
and Hz signified weak interactions in the spectrum as
shown in Figure 2. These interactions are indicative of
Clꢀ
PF6
ꢀ
a
a
a
L:3ÆX
L:4ÆX
L:5ÆX
3460.0
892.4
1231.0
3157.0
545.0
973.8
a No peak shifts were observed.

666
B. Tomapatanaget et al. / Tetrahedron Letters 45 (2004) 663–666
into the mixed solution of hexylamine (1.50 g, 4.9 mmol)
and freshly distilled triethylamine (0.5 g, 4.5 mmol) in
dichloromethane (45 mL) at 0 ꢁC. The mixture was kept
stirring at 0 ꢁC under N2 for 2 h. The reaction mixture was
allowed to warm to room temperature. The solution was
then washed with aq 2 M HCl (4 · 50 mL). The organic
layers were combined and dried with MgSO4. The solvent
Additionally, the association constants of the complexes
agree with the proposed structures corresponding to the
highest Ka values of L with 3ÆX because the anion
encounters seven hydrogen bonding interactions from
the host L and the imidazolium amide unit as well as the
C–H—X interaction while the complexes of L and 4ÆX
and 5ÆX were subjected to only five hydrogen bonding
interactions.16 Association constants of L and 5ÆX are
higher than those of L and 4ÆX because of the
enhancement of binding from p–p stacking interactions
between the benzene rings of L and the benzoimidazo-
lium ring of 5ÆX.
was subsequently evaporated to give
a white solid
1 (1.47 g, 98%). 1H NMR (300 MHz, CDCl3, TMS): d
6.45 (s, br, –NH–, 1H), 3.97 (s, ClCH2CO, 2H), 3.26–
3.19 (q, J ¼ 6:9 Hz, –NHCH2CH2–, 2H), 1.47 (m,
–NHCH2CH2CH2–, 2H), 1.23 (m, –CH2CH2CH2–, 6H),
0.82 (m, –CH3, 3H); ESI-TOF m=z 178.21 [M+Hþ].
11. A solution of imidazole (0.5 g, 7.4 mmol) in THF (20 mL)
was added dropwise into a solution of NaH (0.18 g,
7.4 mmol) in THF (20 mL) under N2 at 0 ꢁC. The reaction
mixture was stirred until gas production stopped. A
solution of N-hexylchloroacetamide 1 (0.79 g, 6.70 mmol)
in THF (20 mL) was added into the solution of sodium
imidazole and the mixture was stirred at room tempera-
ture under N2 overnight. Precipitated NaCl was then
filtered off. The solution was partitioned with CH2Cl2 and
water. The organic phase was extracted with water several
times and then dried with MgSO4. The solvent was
removed by a rotary evaporator to afford yellow solid 2
In summary, self-assembly studies of the host L and
1
guest molecules were carried out by H NMR titrations
in CDCl3. The NH resonances of the urea unit of the
ligand were monitored. Large downfield shifts attributed
to hydrogen bonding interactions between NH protons
of L and anionic species of guest molecules were
observed. The results revealed that L selectively bound
guest molecules in the following order, 3ÆX > 5ÆX > 4ÆX.
The binding ability also corresponded to the shape of the
anion template (Clꢀ > BrꢀꢁPF6ꢀ), numbers of hydro-
gen bond donating sites and p–p stacking interactions. In
addition, we have demonstrated that the anion recogni-
tion step has oriented the nonmacrocyclic ligand
orthogonally to the cation to provide an interpenetrated
geometry and produce interlocked architectures.
1
(0.47 g, 60%). H NMR (300 MHz, CDCl3, TMS): d 7.43
(s, –NCHN–, 1H), 7.06 (s, –NCHCHNCH–, 1H), 6.88 (s,
–NCHCHNCH2–, 1H), 5.54 (s, br, –NH–, 1H), 4.57 (s,
–NCH2CO–, 2H) 3.18–3.11 (m, –NHCH2CH2–, 2H),
1.38–1.33 (m, –NHCH2CH2CH2–, 2H), 1.21–1.13 (m,
–CH2CH2CH2–, 6H), 0.82–0.77 (m, –CH3, 3H); ESI-TOF
m=z 210.25 [M+Hþ].
12. A solution of chloromethylhexyl carboxamide (1) (2.70 g,
15.1 mmol) in CHCl3 (20 mL) was added dropwise into a
solution of hexylcarboxamide methylimidazole (2) (0.79 g,
3.77 mmol) in CHCl3 (20 mL) and stirred under N2
atmosphere. The reaction mixture was heated at reflux
under N2 atmosphere for 3 days. A white solid precipitated
during that time. The reaction was allowed to cool to
room temperature. The white solid (3ÆClꢀ) was filtered and
dried (2.30 g, 61%). 1H NMR (300 MHz, DMSO-d6,
TMS):d 9.08 (s, –NCHN–, 1H), 8.51 (t, J ¼ 5:4 Hz,
–NH–, 2H), 7.65 (s, –NCHCHN–, 2H), 5.00 (s,
–NCH2CO–, 4H), 3.08 (q, J ¼ 6:6 Hz, NHCH2CH2–,
4H), 1.41 (m, –NHCH2CH2CH2–, 4H), 1.25 (m,
–CH2CH2CH2–, 12H), 0.86 (m, –CH36H); ESI-TOF MS
(m=z): 351.51 [M+Hþ]. Mp: 160 ꢁC.
Acknowledgements
This work was supported financially by the Thailand
Research Fund (RSA4680013) and the Ratchadaph-
iseksomphot Endowment Fund. The authors thank Mr.
Suprachai Rittikulsittichai for the host molecule L and
the National Center for Genetic Engineering and Bio-
technology (BIOTEC) for the NMR results.
References and notes
1. Hoss, R.; Vogtle, F. Angew. Chem., Int. Ed. Engl. 1994, 33,
375.
1
13. Characterization for 3ÆBrꢀ: H NMR (300 MHz, DMSO-
2. Linton, B.; Hamilton, A. D. Chem. Rev. 1997, 97, 1669.
3. Vilar, R. Angew. Chem., Int. Ed. 2003, 42, 1460.
4. Fyfe, M. C. T.; Glink, P. T.; Menzer, S.; Stoddart, J. F.;
White, A. J. P.; Williams, D. J. Angew. Chem., Int. Ed.
1997, 36, 2068.
d6, TMS): d 9.05 (s, –NCHN–, 1H), 8.38 (t, J ¼ 5:4 Hz,
–NH–, 2H), 7.65 (s, –NCHCHN–, 2H), 4.90 (s,
–NCH2CO–, 4H), 3.11 (q, J ¼ 6:3 Hz, –NHCH2CH2–,
4H), 1.42 (m, –NHCH2CH2CH2–, 4H), 1.26 (m,
CH2CH2CH2–, 12H), 0.87 (m, –CH3, 6H). ESI-TOF
MS (m=z): 351.51 [M+Hþ]. Melting point: 132.0 ꢁC.
Characterization for 3ÆPFꢀ6 : 1H NMR (300 MHz,
DMSO-d6, TMS): d 9.03 (s, –NCHN–, 1H), 8.36 (t,
J ¼ 5:4 Hz, –NH–, 2H), 7.64 (s, –NCHCHN–, 2H), 4.97
(s, –NCH2CO–, 4H), 3.10 (q, J ¼ 6:6 Hz, –NHCH2CH2–,
4H), 1.39 (m, –NHCH2CH2CH2–, 4H), 1.25 (m,
–CH2CH2CH2–,12H), 0.86 (m, –CH3, 6H). ESI-TOF
MS (m=z): 351.51 [M+Hþ]. Mp: 139.3 ꢁC.
€
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€
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