Urea-functionalized resorcinarenes: Preparation, self-folding, and their CD phenomena caused by chiral urea termini through intramolecular hydrogen bonding interactions

Article abstract of DOI:10.1246/cl.2004.994

Self-folding resorcinarenes bearing optically active urea moieties showed unique circular dichroism (CD) phenomena on the macrocyclic skeleton, which were caused by their chiral urea termini through intramolecular hydrogen bonding interactions in chlorofo

Full text of DOI:10.1246/cl.2004.994

994
Chemistry Letters Vol.33, No.8 (2004)
Urea-functionalized Resorcinarenes: Preparation, Self-folding, and Their CD Phenomena
Caused by Chiral Urea Termini through Intramolecular Hydrogen Bonding Interactions
Osamu Hayashida,ꢀ Jun-ichi Ito,y Shinji Matsumoto,y and Itaru Hamachi
Institute for Materials Chemistry and Engineering, Kyushu University, Hakozaki, Higashi-ku, Fukuoka 812-8581
yDepartment of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University,
Hakozaki, Higashi-ku, Fukuoka 812-8581
(Received May 31, 2004; CL-040614)
Self-folding resorcinarenes bearing optically active urea
urea derivative 7-S having a S-configuration by using 4-hexyl-
phenol in place of 2 in a manner similar to that applied to the
synthesis of 1-S. In general, small urea molecules tend to form
self-assemblies by hydrogen bonding interactions in apolar or-
ganic solvents.6 First, hydrogen-bonding properties of 1-S in
chloroform solutions (1.3 mM) were evaluated by FT-IR meas-
urements,7 as compared with those for the mono-urea derivative
7-S (10 mM) (1 M ¼ 1 mol dmꢁ3). The absorption frequencies
originating from N–H deformation band and C=O stretching vi-
brations of 1-S shifted to the higher and lower wavenumbers
(ꢀN{H, 1565 and ꢁC=O, 1658 cmꢁ1, respectively), in comparison
with those for 7-S (ꢀN{H, 1554 and ꢁC=O, 1668 cmꢁ1, respective-
ly), indicating the formation of hydrogen bonds7 for urea and
amide residues of 1-S. Kobayashi and Seki reported similar re-
sults for the hydrogen bonding formation of urea derivatives
by the identical methods.7 A similar character in the hydrogen-
bonding properties of another macrocyclic urea 1-R was also
confirmed by the identical methods. Combined these results sug-
gest that 1 forms intramolecular hydrogen bonds by bundling the
urea and amide residues in a cyclic fashion to give a self-folding
cavitand in chloroform, as schematically shown in Figure 1.
When all of the urea or amide residues are oriented in the same
direction, the cyclic hydrogen bonding belts are formed cooper-
atively.
moieties showed unique circular dichroism (CD) phenomena
on the macrocyclic skeleton, which were caused by their chiral
urea termini through intramolecular hydrogen bonding interac-
tions in chloroform. These characteristic CD bands were disap-
peared upon complexation with anions such as chloride and bro-
mide.
Resorcinarenes1 such as 2 are starting materials for synthe-
ses of various open-ended cavitands.2 In particular, resorcinar-
enes with amide- or urea-functionalized groups have been
known to form intramoleclar hydrogen bonding belts and give
a self-folding cavitand3 in apolar organic solvents. However,
limited studies have been reported on the development of chiral
self-folding cavitands.4 On these grounds, we became interested
in the resorcinarene-besed self-folding cavitands capable of pro-
viding an asymmetric internal cavity. Resorcinarene bearing
eight optically active urea moieties 1-R and 1-S were designed
by introducing (R)- and (S)-methylbenzylurea residues, respec-
tively, onto each OH groups of 2 through an alkyl spacer having
amide linkage. In this context, we report preparation and self-
folding of 1-R and 1-S as well as their unique circular dichroism
(CD) phenomena on the macrocycles caused by chiral urea ter-
mini through intramolecular hydrogen bonding interactions in
chloroform. In addition, their spectral changes were also inves-
tigated upon complexation with anion as a guest.
*
*
*
*
*
*
*
*
*
*
*
*
NH
NH
HN
HN
NH
NH
NH
NH
Cl–
*
O
O
–
*
O
O
*
*
Cl
XO
OX
X =
6
Cl–
XO
XO
OX
e
CD silent
at 280 nm
inherent CD
at 280 nm
H
N
H
N
R
R
R
R
(CH )
CH2CONH
CH2CONH
1-R:
2
6
6
*
CH3
f
–
•
1
1 Cl
O
O
OX
Figure 1. Schematic representations for 1 and the complex of 1
with chloride. Each black oval stands for a urea moiety.
R = (CH2)10CH3
H
N
H
N
(CH )
1-S:
2
XO
OX
*
CH3
X =
2 :
H
The asymmetric character of the present octa-urea 1-R/1-S
was examined by CD spectroscopy at 298 K. A chloroform solu-
tion of compound 1-S showed positive CD bands at 254, 261,
and 267 nm as well as a negative band at 280 nm as shown in
Figure 2. No concentration-dependency on the CD spectra of
1-S was observed at least within the concentration range of
15 mM–0.76 mM, indicating that 1-S exists in a monomeric
state.8 In addition, mono-urea 7-S shows similar signed CD
bands at 255, 261, and 268 nm with ca. 1/8 lessened intensity
of 1-S (Figure 2). These results suggest that the CD bands in a
shorter wavelength range are originally attributable to the opti-
cally active urea residues. On the other hand, the negative CD
band at 280 nm indicates that the originally achiral macrocyclic
skeleton of 1-S gains inherent chirality through the asymmetric
a BrCH2CO2C(CH3)3, K2CO3. b TFA.
c (6-Aminohexyl)carbamic acid tert-
butyl ester, BOP, triethylamine. d TFA.
e (R)-α-methylbenzyl isocyanate,
triethylamine. f (S)-α-methylbenzyl
isocyanate, triethylamine.
a
b
c
3 : CH2CO2C(CH3)3
4 : CH2CO2H
5 : CH2CONH (CH2)
6 NHCO2C(CH3)3
d
+
−
6 :
(CH )
CF3CO2
NH3
CH2CONH
2
6
Scheme 1. Preparation of urea-functionalized resorcinarenes.
H
H
CH2CONH (CH2)6
N
N
7-S: CH3(CH2)5
O
O
CH3
Resorcinarenes bearing eight (R)- and (S)-methylbenzyl-
urea residues 1-R and 1-S were prepared by following the reac-
tion sequence given in the Scheme 1.5 We also prepared mono-
Copyright ꢀ 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.8 (2004)
995
cyclic hydrogen bonding belts around the urea terminus in
chloroform. The formation of intramolecular hydrogen bonds
of 1-S is responsible for the unique CD phenomena, because
the CD band of 1-S at 280 nm was weakened to ca. 42% in inten-
sity in chloroform–methanol (92:8 v/v) and completely disap-
peared in chloroform–methanol (3:97 v/v). Methanol acts as a
competitor for the intramolecular hydrogen bonding formations.
A similar asymmetric character was observed for 1-R having in-
verted CD signs in chloroform (Figure 2).
ing constants (K) for 1:1 host–guest complexes were evaluated
on the basis of the computer-aided least squares curve fitting
methods applied to the NMR data (K; 1000 and 600 Mꢁ1 for
chloride and bromide, respectively). Interestingly, the CD bands
of 1-S at 280 nm was weakened to ca. 70% in intensity in the
presence of chloride (3 equiv.) and disappeared in the presence
of an excess amount of chloride (36 equiv.) These results sug-
gested that the encapsulated guest anions disrupted the formation
of intramolecular hydrogen bonds of 1-S, as schematically
shown in Figure 1, so that the resulting complexes did not show
any CD phenomena at 280 nm. Similar complexation behavior
of 1-R with the anions was also confirmed by the identical meth-
ods (Figure 2d).
3000
(a)
(b)
1500
In conclusion, resorcinarene-type hosts bearing eight (R)-
and (S)-methylbenzylurea residues 1-R and 1-S form a self-fold-
ed conformation originating from the intramolecular hydrogen-
bonding interactions and exhibit the unique CD phenomena on
the macrocyclic skeleton in chloroform. The guest-binding be-
havior toward anions such as chloride and bromide were moni-
(c)
(d)
0
(b)
θ
-1500
-3000
(a)
(d)
1
tored by the changes in CD band intensity as well as H NMR
250
300
Wavelength / nm
350
spectroscopy. The guest-binding sites of these hosts are close
to the chiral residues, so that these hosts are expected to perform
chiral recognition toward molecular anions. Further studies are
currently in progress along this line.
Figure 2. CD spectra of 1-S (a), 1-R (b), 7-S (c), and 1-R in the
presence of chloride (36 equiv.) (d) in chloroform at 298 K.
An intrinsic potential of 1 to act as a host9 for anion inclu-
sion has been investigated by 1H NMR and CD10 spectroscopy.
Upon addition of chloride (as a tetrabutylammonium salt) to a
This study was supported by Shorai Foundation for Science
and Technology. We thank reviewers for their valuable com-
ments on the CD spectra of 1.
1
CDCl3 solution containing 1-S, the H NMR signal due to the
urea protons of 1-S were sharpened and underwent substantial
downfield shifts in the presence of chloride, showing a simple
saturation behavior for the complexation as shown in Figure 3.
References and Notes
a) A. G. S. Hogberg, J. Am. Chem. Soc., 102, 6046 (1980). b) A. G. S.
¨
1
Hogberg, J. Org. Chem., 45, 4498 (1980). For a review, see: c) P.
¨
Timmerman, W. Verboom, and D. N. Reinhoudt, Tetrahedron, 52,
2663 (1996).
D. J. Cram, Science, 219, 1177 (1983).
(a)
4.90
2
3
a) D. M. Rudkevich, G. Hilmersson, and J. Rebek, Jr., J. Am. Chem.
Soc., 120, 12216 (1998). b) J. W. M. Nissink, H. Boerrigter, W.
Verboom, D. N. Reinhoudt, and J. H. van der Maas, J. Chem. Soc., Per-
kin Trans. 2, 1998, 2541. c) D. M. Rudkevich and J. Rebek, Jr., Eur. J.
Org. Chem., 1999, 1991. d) T. Haino, D. M. Rudkevich, A. Shivanyuk,
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4.85
(b)
4.80
4
5
0.0
5.0
5.2
5.0
4.8
δ / ppm
4.6
4.4
4.2
+
−
[Bu N Cl ] / mM
4
1-R; 600 MHz 1H NMR (CDCl3, 298 K) ꢀ 0.86, 1.23–1.28, 1.35, 1.75,
2.0, 3.0, 3.2, 4.46, 4.81, 5.7–6.4, 7.15, 7.2. MS (FAB) m=z 3533
½M þ Hꢂþ. Found: C, 69.68; H, 8.86; N, 8.99%. Calcd for
.
Figure 3. Partial 1H NMR spectra of 1-S in CDCl3 at 298 K in
the absence (a) and presence of chloride (36 equiv.) (b). Inset;
the corresponding NMR titration curve.
C
208H312N24O24 3H2O: C, 69.55; H, 8.94; N, 9.37%. 1-S; 600 MHz
1H NMR (CDCl3, 298 K) ꢀ 0.86, 1.23–1.28, 1.35, 1.75, 2.0, 3.0, 3.2,
4.46, 4.81, 5.7–6.4, 7.15, 7.2. MS (FAB) m=z 3533 ½M þ Hꢂþ. Found:
.
C, 69.81; H, 8.80; N, 9.12%. Calcd for C208H312N24O24 3H2O: C,
0.06
0.03
69.55; H, 8.94; N, 9.37%.
A. D. Carr, R. Melendez, S. J. Geib, and A. D. Hamilton, Tetrahedron
Lett., 39, 7447 (1998).
6
7
8
T. Kobayashi and T. Seki, Langmuir, 19, 9297 (2003).
Monomeric dispersion of 1 was also suggested by NMR spectroscopy
without showing any detectable concentration-dependency on the
chemical shifts of urea protons of 1 within the concentration range
of 0.1–2.4 mM.
0.5
1.0
0
f = [1-S] / ([1-S] + [Cl-])
Figure 4. Job plot for a combination of 1-S and chloride.
9
P. D. Beer and P. A. Gale, Angew. Chem., Int. Ed., 40, 486 (2001).
10 Resorcinarene 2 binds chiral alcohols in chloroform and the resulting
host–guest complexes show CD bands with split Cotton effects: K.
Kobayashi, Y. Asakawa, Y. Kikuchi, H. Toi, and Y. Aoyama, J. Am.
Chem. Soc., 115, 2648 (1993).
The stoichiometry for the complex was confirmed to be 1:1
host–guest11 by Job plot (Figure 4). These results indicate again
that 1 has a self-folding cavity suitable for binding an anion
within, as schematically shown in Figure 1. Similar complexa-
tion behavior of 1-S was also confirmed with bromide. The bind-
ꢁ
ꢁ
.
.
11 MS peaks for the complexes of 1-S Cl and 1-S Br were directly
detected by FAB spectrometry; m=z 3568 ½M þ Clꢂꢁ, 3613 ½M þ Brꢂꢁ.
Published on the web (Advance View) July 5, 2004; DOI 10.1246/cl.2004.994