Triangular assembly through charged hydrogen bonds in polar solvent

Article abstract of DOI:10.1021/jo061543f

(Chemical Equation Presented) We have demonstrated a triangular assembly driven by 12 charged hydrogen bonds and π-π interactions. This assembly is stable even in polar solvents because of its charged hydrogen-bond nature. Helical arrangement of the complex is confirmed by its crystal structure. A solution structure is assigned to the D₃ isomer corresponding to the solid-state structure by temperature-dependent ¹H NMR experiments.

Full text of DOI:10.1021/jo061543f

Triangular Assembly Through Charged
Hydrogen Bonds in Polar Solvent
structure. These structural features encouraged many supramo-
lecular chemists to construct various three-dimensional assembly
structures. In the early days, various types of box- or capsule-
like structures were constructed using neutral hydrogen bonds.2
However, most of these systems work in nonpolar solvents
because of the relatively weak nature of hydrogen bonds in polar
solvent systems. Recently, different approaches involving
†
‡
‡
Ho Yong Lee, Dohyun Moon, Myoung Soo Lah, and
,
†
Jong-In Hong*
Department of Chemistry, College of Natural Sciences, Seoul
National UniVersity, Seoul 151-747, Korea, and Department of
Chemistry and Applied Chemistry, College of Science,
Hanyang UniVersity, Ansan, Kyunggi-Do 426-791, Korea
multiple ionic interactions have been widely studied to develop
capsule-like structures that are operative in polar solvents.3
Another type of an interesting supramolecular structure using
calixarene building blocks is the double rosette assembly
jihong@snu.ac.kr
4
reported by Reinhoudt and co-workers. They found that calix-
[
4]arenes substituted with two melamine units at the upper rim
ReceiVed July 25, 2006
form box-like assemblies together with barbituric acid and
cyanuric acid derivatives. These assemblies show unique
properties in terms of asymmetric induction, noncovalent
synthesis, and guest encapsulation. Here, we report on the
double rosette-type assembly driven by charged hydrogen
bonding and π-π interactions between tris(imidazoline) 1 and
calix[4]arene dicarboxylic acid (2) in polar solvent.
5
6
7
Modeling predicted that 2:3 self-assembly of tris(imidazoline)
(1) and bidentate carboxylic acid (2) would give a triangular
assembly. We used cone-shaped calix[4]arene (2) substituted
with two alternating carboxylic acids oriented in the same
direction on the upper rim as a bidentate carboxylic acid
(
2) (a) Shimizu, K. D.; Rebek, J., Jr. Proc. Natl. Acad. Sci. U.S.A. 1995,
9
2, 12403-12407. (b) Castellano, D.; Rudkevich, M. J., Jr.; Rebek, J., Jr.
J. Am. Chem. Soc. 1996, 118, 10002-10003. (c) Mogck, O.; Pons, M.;
B o¨ hmer, V.; Vogt, W. J. Am. Chem. Soc. 1997, 119, 5706-5712. (d)
Schalley, C.; Castellano, A. R. K. M.; Brody, S.; Rudkevich, M.; Siuzdak,
G.; Rebek, J., Jr. J. Am. Chem. Soc. 1999, 121, 4568-4579. (e) Rinc o´ n, A.
M.; Prados, P.; Mendoza, J. D. J. Am. Chem. Soc. 2001, 123, 3493-3498.
(
3) (a) Lee, S. B.; Hong, J.-I. Tetrahedron Lett. 1996, 37, 8501-8504.
(
b) Zadmard, R.; Junkers, M.; Schrader, T.; Grawe, T.; Kraft, A. J. Org.
Chem. 2003, 68, 6511-6521. (c) Brewster R. E.; Shuker, S. B. J. Am. Chem.
Soc. 2002, 124, 7902. (d) Corbellini, F.; Costanzo, L. D.; Crego-Calama,
M.; Geremia, S.; Reinhoudt, D. N. J. Am. Chem. Soc. 2003, 125, 9946-
9947. (e) Schmuck, C.; Wienand, W. J. Am. Chem. Soc. 2003, 125, 452-
459. (f) Sansone, F.; Baldini, L.; Casnati, A.; Chierici, E.; Faimani, G.;
Ugozzoli, F.; Ungaro, R. J. Am. Chem. Soc. 2004, 126, 6204. (g) Zadmard,
R.; Schrader, T.; Grawe, T.; Kraft, A. Org. Lett. 2002, 4, 1678-1690. (h)
Grawe, T.; Schrader, T.; Zadmard, R.; Kraft, A. J. Org. Chem. 2002, 67,
3755-3763. (i) Kim, H.-J.; Sakamoto, S.; Yamaguchi, K.; Hong, J.-I. Org.
Lett. 2003, 5, 1051-1054.
We have demonstrated a triangular assembly driven by 12
charged hydrogen bonds and π-π interactions. This as-
sembly is stable even in polar solvents because of its charged
hydrogen-bond nature. Helical arrangement of the complex
is confirmed by its crystal structure. A solution structure is
(
4) (a) Vreekamp, R.; van Duyhoven, H. J. P. M.; Hubert, M.; Verboom,
W.; Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl. 1996, 35, 1215-1218.
(b) Timmerman, P.; Vreekamp, R. H.; Hulst, R.; Verboom, W.; Reinhoudt,
D. N.; Rissanen, K.; Udachin, K. A.; Ripmeester, J. Chem. Eur. J. 1997, 3,
3
assigned to the D isomer corresponding to the solid-state
1
structure by temperature-dependent H NMR experiments.
1823.
(5) (a) Prins, L. J.; Huskens, J.; de Jong, F.; Timmerman, P.; Reinhoudt,
D. N. Nature 1999, 398, 498-502. (b) Ishi-i, T.; Crego-Calama, M.;
Self-assembly has been employed as a powerful tool for
constructing various types of supramolecular structures based
on the simultaneous assembly of preorganized building blocks.
Consequently, there is continuous interest in designing preor-
ganized building blocks. Calixarenes have been widely used as
Timmerman, P.; Reinhoudt, D. N.; Shinkai, S. J. Am. Chem. Soc. 2002,
1
24, 14631-14641. (c) Prins, L. J.; Timmerman, P.; Reinhoudt, D. N. J.
Am. Chem. Soc. 2001, 123, 10153-10163.
6) (a) Crego-Calama, M.; Hulst, R.; Fokkens, R.; Nibbering, N. M. M.;
(
Timmerman, P.; Reinhoudt, D. N. Chem. Commun. 1998, 1021-1022. (b)
Prins, L. J.; de Jong, F.; Timmerman, P.; Reinhoudt, D. N. Nature 2000,
408, 181-184. (c) Timmerman, P.; Prins, L. J. Eur. J. Org. Chem. 2001,
1
building blocks because of their unique structure, easy func-
tionalization of the lower and upper rims, and bowl-shaped
3
191-3205. (d) Prins, L. J.; Verhage, J. J.; de Jong, F.; Timmerman, P.;
Reinhoudt, D. N. Chem. Eur. J. 2002, 8, 2302-2313.
(7) (a) Mateos-Timoneda, M. A.; Kerckhoffs, J, M. C. A.; Crego-Calama,
M.; Reinhoudt, D. N. Angew. Chem., Int. Ed. 2005, 44, 3248-3253. (b)
Kerckhoffs, J. M. C. A.; van Leeuwen, F. W. B.; Spek, A. L.; Kooijman,
H.; Crego-Calama, M.; Reinhoudt, D. N. Angew. Chem., Int. Ed. 2003, 42,
5717-5722. (c) Kerckhoffs, J. M. C. A.; ten Cate, M. G. J.; Mateos-
Timoneda, M. A.; van Leeuwen, F. W. B.; Snellink-Ruel, B.; Spek, A. L.;
Kooijman, H.; Crego-Calama, M.; Reinhoudt, D. N. J. Am. Chem. Soc.
2005, 127, 12697-12708.
*
To whom correspondence should be addressed. Tel: +82 2 880 6682.
Fax: +82 2 889 1568.
†
Seoul National University.
Hanyang University.
‡
(
1) (a) CalixarenesssA Versatile Class of Macrocyclic Compounds;
Vicens, J., B o¨ hmer, V., Eds.; Kluwer: Norwell, MA, 1991. (b) Calixarenes
001; Asfari, Z., B o¨ hmer, V., Harrowfield, Vicens, J., Eds.; Kluwer:
Norwell, MA, 2001.
2
(8) Larsen, M.; Jørgensen, M. J. Org. Chem. 1996, 61, 6651-6655.
1
0.1021/jo061543f CCC: $33.50 © 2006 American Chemical Society
Published on Web 10/25/2006
J. Org. Chem. 2006, 71, 9225-9228
9225

SCHEME 1
8
(
Scheme 1). NBS bromination of tetrapropoxycalix[4]arene
The assembly 12‚23 was also characterized by MALDI-TOF
mass spectrometry. The spectrum shows a peak at m/z 2983 of
followed by treatment of the resulting 5,11,17,23-
tetrabromotetrapropoxycalix[4]arene with excess n-BuLi in THF
at -78 °C and quenching with CO2 led to the selective
conversion to 5,17-dibromo-11,23-dicarboxy-25,26,27,28-
tetrapropoxycalix[4]arene (2) in the cone conformation.
+
the assembly [12‚23 - 2CO2] . The major peak at m/z 2083 is
+
assigned to [12‚22‚Na - 4 CO2] and another peak at m/z 2001
+
to [1‚22‚Na] .
1
The H NMR spectrum of a 2:3 mixture of 1 and 2 in CDCl3/
CD3OD (v/v ) 1:1) shows a highly symmetric one-set signal,
suggesting the formation of a symmetric structure (Figure 1).
The aromatic proton (Ha) of 1 is strongly shifted downfield
(∆δHa ) 1.46 ppm), coupled with an upfield shift of the aromatic
proton (Hb) of 2 substituted with carboxylic acid (∆δHb ) -0.39
ppm). The shifts are the result of proton transfer from the
carboxylic acid to the tris(imidazoline) base. Methylene protons
of 1 at ∼4 ppm become broadened. This signal change comes
from protonation and hindrance of free rotation of 1 upon
complexation.
1H NMR spectrum changes were monitored adding 1 to 2 in
CDCl3/CD3OD (v/v ) 1:1) (Figure 1). As 1 was added to 2, a
new set of peaks assigned to the 2:3 assembly appeared. Signals
corresponding to the assembled structure became major ones
at a 2:3 ratio of 1 and 2 as the signals of free 2 mostly
disappeared. At a 1:3 ratio of 1 and 2, we cannot observe peaks
of free 1, which was mostly used for constructing the assembly.
When an excess of 1 was added, signals of free 1 remained at
the same position. At a 4:3 ratio of 1 and 2, there are only two
sets of signals assigned to the complex and free 1. This indicates
that exchange between the complex and free ligands is slow on
the NMR time scale. Also, there are no intermediate structures
such as partial assemblies (1:1, 2:2, 1:3, etc.) or oligomeric
species. The assembly works in a wide range of polarities from
neat CHCl3 to CHCl3/MeOH ) 1:2 (v/v). However, a more polar
solvent system cannot be used because of solubility issues.
1
FIGURE 2. Partial H NMR spectra upon adding 1 to 2 ([1] ) 5 mM
3 3
and [2] ) 30 mM) in CDCl /CD OD (v/v ) 1:1) at room temperature.
: Complex of 1 and 2, ]: free 1, and *: free 2.
[
Two-dimensional NOESY experiments were performed to
locate the spatial proximity of various protons of complex 12‚
23. NOE connectivities were observed for the methylene protons
of 1 with aromatic protons (Hb and Hc) of 2. The presence of
these NOE connectivities provides strong evidence for the fact
that 1 and 2 form a close contact structure in solution.
Crystals suitable for X-ray diffraction analysis were obtained
by slow evaporation of a 2:3 mixture of 1 and 2 in a 1:1 (v/v)
mixture of CHCl3 and MeOH. The crystal structure reveals that
FIGURE 1. 1H NMR spectral changes upon complexation in CDCl
226 J. Org. Chem., Vol. 71, No. 24, 2006
3
3
/CD OD (v/v ) 1:1) at room temperature. (a) 1, (b) 2, and (c) 1
2
3
‚2 .
9

assembly (distances between terminal methyl carbon atoms of
the propyl group at the corners of 12‚23) are approximately 2.5
nm long. Two central tris(imidazolinium)s are stacked by π-π
interactions. The two central benzene rings of 1 lie nearly
parallel to each other with an interplane distance of 3.45 Å,
which leaves little space for guest encapsulation in the solid-
state structure like Reinhoudt’s double rosette. One central
benzene ring of 1 is twisted by about 50° with respect to the
adjacent benzene ring. Charge-charge repulsion between
positively charged imidazoliniums causes them to stack with a
staggered mode. As a result, the overall structure of the assembly
displays chirality (P or M), even though there is no chiral center.
The calix[4]arene units are organized into a pinched cone
conformation suitable for a 2:3 assembly. The phenyl rings
substituted with carboxylic acid in calix[4]arene are parallel to
each other with an interplane distance of 5.47 Å. The O-N
distance forming Coulombic hydrogen bonds lies between 2.65
and 2.80 Å. Presumably, π-π stacking of the central phenyl
rings of 1 and the charged hydrogen bonds between carboxylate
and imidazolinium are the major driving forces for spontaneous
assembly of the 2:3 mixture of 1 and 2 into a helical structure.
2:3 assembly of 1 and 2 can be present as two conformational
isomers in solution: the D3 isomer (staggered and chiral as
shown in the solid-state structure) and the D3h isomer (eclipsed
9
and achiral). Since one set of signals of the aromatic protons
of calix[4]arene was obtained at room temperature, we examined
low-temperature NMR of 1:3 mixture of 1 and 2 to find a major
isomer in solution (Figure 4). As the temperature drops, aromatic
protons of free 2 become sharp, while aromatic protons of 2
corresponding to the complex 12‚23 split into two sets without
showing D3h isomer signals, which indicates that the D3 isomer
is dominant in solution. Temperature-dependent NMR of a ∼2:3
mixture of 1 and 2 shows a similar pattern to the 1:3 mixture.
FIGURE 3. Crystal structures of 1
2
3
‚2 . C (gray), O (red), N (blue),
Br (yellow), and H (white). Hydrogen bonds are indicated in green
dotted lines. All hydrogen atoms except for two hydrogen atoms in
the imidazolinium group are omitted for clarity.
1
and 2 are held together by 12 Coulombic H-bonds forming a
triangular assembly (Figure 3). Sides of an overall triangular
1
FIGURE 4. Partial views of temperature-dependent H NMR spectra. 1:3 mixture of 1 and 2 (left, 25, 10, 0, -20, and -40 °C) and 2:3 mixture
of 1 and 2 (right, 25, 0, -20, and -40 °C).
J. Org. Chem, Vol. 71, No. 24, 2006 9227

We can only observe the D3 isomer and residual signals of free
substituted by carboxylic acid), 6.83 (s, 12H, aromatic protons of
2 substituted by bromine), 4.21 (d, 12H, J ) 13.08, ArCH Ar of
), 3.87 (broad t, 12H, OCH CH CH of 2), 3.68 (broad s, 24H,
NCH CH N of 1), 3.39 (broad t, 12H, OCH CH CH of 2), 2.95
d, 12H, J ) 13.24, ArCH Ar of 2), 1.73 (broad m, 12H, 12H,
OCH CH CH of 2), 1.68-1.58 (m, 12H, OCH CH CH of 2), 0.81
broad t, 18H, OCH CH CH of 2), 0.69 (broad t, 18H, OCH CH
2
.
2
2
2
2
3
In conclusion, we have demonstrated a triangular assembly
2
2
2
2
3
driven by 12 charged hydrogen bonding and π-π interactions.
This assembly is stable even in polar solvents because of its
charged hydrogen-bond nature. Helical arrangement of the
complex is confirmed by its crystal structure. A solution
structure is assigned to the D3 isomer corresponding to the solid-
(
2
2
2
3
2
2
3
(
2
2
3
2
2
-
3
CH of 2).
13
C NMR (125 MHz, CDCl
3
+ MeOD-d (v/v ) 1:1)): 174.48,
3
1
state structure by temperature-dependent H NMR experiments.
1
1
61.65, 158.73, 157.72, 139.98, 134.53, 132.58, 131.98, 130.76,
30.06, 125.37, 115.17, 77.67, 77.34, 49.65, 49.48, 49.31, 49.14,
Experimental Section
48.97, 48.80, 48.63, 46.27, 46.00, 31.69, 24.14, 23.55, 11.13, 10.21.
+
Mass (MALDI-TOF): m/z 2983 [1
2
‚2
3
2 2
- 2CO ] ; m/z 2083 [1 ‚
5
,17-Dibromo-11,23-dicarboxy-25,26,27,28-tetrapropoxycalix-
4]arene (2). To a stirred of solution of 5,11,17,23-tetrabromo-
5,26,27,28-tetrapropoxycalix[4]arene (1 g, 1.1 mmol) in dry THF
100 mL) at -78 °C was added n-BuLi in hexane (2.76 mL, 4
equiv, 1.6 M). The yellow solution was stirred at -78 °C for 5
min, quenched with dry CO (g) (large excess), and stirred for 30
min. The reaction mixture was poured into ice-cold 1 M hydro-
chloric acid and extracted with CHCl three times. The organic
layer was washed with water and brine, MgSO -dried, and
+
+
2
2
‚Na - 4CO
Crystal Data of 1
24, MW ) 3080.53, colorless crystal 1.00 mm × 0.25 mm
0.20 mm, trigonal P3
2
] ; m/z 2001 [1
2
‚2‚Na] .
[
2
(
2
‚2 . Crystal structure of 1
3
2 3 174
‚2 : C156H -
Br
×
)
6 12
N O
2
21, a ) b ) 34.775 (1), c ) 31.201(1); V
3
3
32676(2) Å , Z ) 6, Fcalcd ) 0.939 Mg/m , µ(λ ) 0.82657 Å) )
2
1
.155 mm , 2θmax ) 48.9°; 131 468 measured reflections, 22 709
-1
unique of which 13 296 were observable [I > 2σ(I)]. The refinement
converged to a final R1 ) 0.1255 and wR2 ) 0.3215 for observed
reflections of I > 2σ(I). Structure refinement following modification
3
4
evaporated in vacuo. Recrystallization from THF/MeOH (v/v )
10
of the data with the SQUEEZE routine in PLATON: R1 ) 0.0778
1
:1) gave 2 as white crystals (460 mg, 50% yield).
H NMR (300 MHz, DMSO-d
(
I > 2σ(I)), wR2 ) 0.2136, GOF ) 1.002, max/min residual
1
6
) : δ 12.56 (s, 2H), 7.68 (s, 4H),
electron density 0.852/0.867 e Å. Crystallographic details are in
the Supporting Information.
3
6
4
6
.42 (s, 4H), 4.33 (d, 4H, J ) 13.2), 4.01 (t, 4H, J ) 7.9), 3.72 (t,
H, J ) 6.6), 3.38 (d, 4H, J ) 13.5), 1.89-1.84 (m, 8H), 1.07 (t,
H, J ) 7.2), 0.92 (t, 6H, J ) 7.2).
Acknowledgment. Financial support from the MOCIE
(Grant 10024945) is gratefully acknowledged. H.Y.L. thanks
the Ministry of Education for the award of the BK 21 fellow-
ship.
13
3
C NMR (75 MHz, CDCl ): δ 171.60, 158.97, 156. 81, 138.42,
133.21, 131.80, 129.87, 123.71, 115.04, 77.46, 76.90, 31.23, 23.80,
23.11, 11.16, 9.94.
+
HRMS (FAB): Calcd for C42
36.1553.
H
46Br
2
O
8
(M ): 836.1559, found:
8
Supporting Information Available: Spectral data of new
Preparation of Complex (1
2
‚2
obtained by two ways. For H NMR analysis, 1 and 2 were mixed
in 2:3 ratio in CDCl and CD OD (v/v ) 1:1). 1 and 2 were mixed
3
). The assembly (1
2
‚2
3
) can be
compounds and [1
materialisavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
2
‚2
3
] and crystallographic data of [1
2
3
‚2 ]. This
1
3
3
JO061543F
in a 2:3 ratio in EtOH and heated until the mixture became clear
and cooled down to room temperature, which gave a colorless
crystalline solid. A solid obtained by two methods shows the same
(9) (a) Prins, L. J.; Jolliffe, K. A.; Hulst, R.; Timmerman, P.; Reinhoudt,
D. N. J. Am. Chem. Soc. 2000, 122, 3617-3627. (b) Simanek, E. E.;
Wazeer, M. I. M.; Mathias, J. P.; Whitesides, G. M. J. Org. Chem. 1994,
1
13
property ( H NMR, C NMR, Mass).
1
H NMR (300 MHz, CDCl
3
+ MeOD-d
3
(v/v ) 1:1)): 9.37 (s,
5
9, 4904-4909.
6H, aromatic protons in 1), 7.05 (s, 12H, aromatic protons of 2
(10) Spek, A. L. Acta Crystallogr., Sect. A 1990, 46, 194-201.
9
228 J. Org. Chem., Vol. 71, No. 24, 2006