Participation of benzene hydrogen bonding upon anion binding

Article abstract of DOI:10.1021/ol0515309

(Chemical Equation Presented) A m-xylene-bridged imidazolium receptor, 1, has been designed and synthesized. The receptor 1 utilizes two imidazole (C-H)⁺...anion hydrogen bonds and one benzene hydrogen...anion hydrogen bond. The major driving force of complexation between the receptor 1 and anions comes from two imidazole (C-H) ⁺...anion hydrogen bonds. However, both NMR experiments and ab initio calculations show that the benzene hydrogen attracts the anion guests, clearly indicating benzene (C-H)...anion hydrogen bonding.

Full text of DOI:10.1021/ol0515309

ORGANIC
LETTERS
2
005
Participation of Benzene Hydrogen
Bonding upon Anion Binding
Vol. 7, No. 18
3
993-3996
†
‡
‡
,†
Sungjae In, Seung Joo Cho, Kyu Hwan Lee, and Jongmin Kang*
Department of Applied Chemistry, Sejong UniVersity, Seoul 143-747, Korea, and
Korea Institute of Science and Technology, Seoul 130-650, Korea
kangjm@sejong.ac.kr
Received June 30, 2005
ABSTRACT
+
A m-xylene-bridged imidazolium receptor, 1, has been designed and synthesized. The receptor 1 utilizes two imidazole (C
−
H) - - -anion hydrogen
bonds and one benzene hydrogen- - -anion hydrogen bond. The major driving force of complexation between the receptor 1 and anions comes
+
from two imidazole (C
−
H) - - -anion hydrogen bonds. However, both NMR experiments and ab initio calculations show that the benzene
hydrogen attracts the anion guests, clearly indicating benzene (C−H)- - -anion hydrogen bonding.
Hydrogen bonds are important anion recognition elements
due to their directionality. As anions display a wide range
of geometries, directionality of hydrogen bonds is frequently
utilized to achieve complementarity between anions and
receptors. Most hydrogen bonding anion receptors utilize a
hydrogen bond interactions are also reported even though
the interaction energy is expected to be much smaller than
that of imidazole (C-H) - - -anion hydrogen bonds. Jeong
+
et al. showed that the 1-alkylpyridinium receptor has a high
affinity for carboxylate ion in polar solvents. They attributed
the high affinity to aromatic C-H hydrogen bonding to the
1
N-H- - -anion or O-H- - -anion hydrogen bond, and
4
C-H- - -anion hydrogen bonds are rarely utilized for anion
binding even though C-H- - -anion hydrogen bonds play an
carboxylate ion. Gale et al. found that one of the ferrocene
hydrogens participates in anion binding when a ferrocene
2
important role in nature. Only recently have 1,3-disubstituted
moiety is attached to one of the meso-positions of calix[4]-
5
imidazolium groups been introduced as new anion binding
pyrrole. Abouderbala et al. reported that aromatic hydrogens
+
hydrogen bond moieties by forming a (C-H) - - -anion
adjacent to anions formed hydrogen bonds with anions when
two or three hydrogen bonding arms attached to aryl core.6
Lee et al. also demonstrated that a strapped calix[4]pyrrole
that contained not only four pyrrole hydrogens but also an
aromatic hydrogen in a strap form hydrogen bonds with
hydrogen bond between C(2)-H in the imidazolium ring
3
and the guest anion. In addition, aromatic C-H- - -anion
†
Sejong University.
Korea Institute of Science and Technology.
‡
7
fluoride and chloride ions. In addition, Yoon et al. reported
(
1) (a) Llinares, J. M.; Powell, D.; Bowman-James, K. Coord. Chem.
ReV. 2003, 240, 57. (b) Bondy, C. R.; Loeb, S. J. Coord. Chem. ReV. 2003,
40, 77. (c) Ilioudis, C. A.; Steed, J. W. J. Supramol. Chem. 2001, 1, 165.
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Auffinger, P.; Louise-May, S.; Westof, E. J. Am. Chem. Soc. 1996, 118,
181. (c) Desiraju, G. R. Acc. Chem. Res. 1991, 24, 290. (d) Steiner, T.;
2
Kim, J. K.; Lee, J. W.; Kim, K. S.; Yoon, J. Org. Lett. 2003, 5, 2083. (d)
Yoon, J.; Kim, S. K.; Singh, N. J.; Lee, J. W. Yang, Y. J.; Chellappan, K.;
Kim, K. S. J. Org. Chem. 2004, 69, 581. (e) Kim, S. K.; Kang, B.-G.;
Koh, H. S.; Yoon, Y. J.; Jung, S. J.; Jeong, B. Lee, K.-D.; Yoon, J. Org.
Lett. 2004, 6, 46557.
(4) Jeong, K.-S.; Cho, Y. L. Tetrahedron Lett. 1997, 38, 3279.
(5) Gale, P. A.; Hursthouse, M. B.; Light, M. E.; Sessler, J. L.; Warriner,
C. N.; Zimmerman, R. S. Tetrahedron Lett. 2001, 42, 6759.
(6) Abouderbala, L. O.; Belcher, W. J.; Boutelle, M. G.; Cragg, P. J.;
Steed, J. W.; Turner, D. R.; Wallace, K. J. Proc. Natl. Acad. Sci. U.S.A.
2002, 99, 5001.
(
1
Saenger, W. J. Am. Chem. Soc. 1992, 114, 10146. (e) Sharma, C. V. K.;
Desiraju, G. R. J. Chem. Soc., Perkin Trans. 2 1994, 2345. (f) Steiner, T.
J. Chem. Soc., Perkin Trans. 2 1995, 1315. (g) Chaney, J. D.; Goss, C. R.;
Folting, K.; Santarsiero, B. D.; Hollingworth, M. D. J. Am. Chem. Soc.
1
996, 118, 9432.
3) (a) Ihm, H.; Yun, S.; Kim. H. G.; Kim. J. K.; Kim. K. S. Org. Lett.
002, 4, 2897. (b) Yun, S.; Ihm H.; Kim, H. G.; Lee, C.-I.; Indrajit, B.;
(
2
Oh, K. S.; Gong, Y. J.; Lee, J. W.; Yoon, J. Lee, H. C.; Kim, K. S. J. Org.
Chem. 2003, 68, 2467. (c) Kim, S. K.; Singh, N. J.; Kim, S. J.; Kim, H. G.;
(7) Yoon, D.-W.; Hwang H.; Lee, C.-H. Angew. Chem., Int. Ed. 2002,
41, 1757.
1
0.1021/ol0515309 CCC: $30.25
© 2005 American Chemical Society
Published on Web 08/06/2005

that 9-H of anthracene in which two phenyl urea groups
are immobilized on the 1,8-positions formed a strong
8
hydrogen bond with anions. We have synthesized m-xylene-
bridged imidazolium receptor 1, which utilizes two imidazole
+
(
C-H) - - -anion hydrogen bonds and one aromatic hydro-
gen- - -anion hydrogen bond. We report herein the synthesis
and binding properties of m-xylene-bridged receptor 1 with
various anions.
For the synthesis of m-xylene-bridged imidazolium recep-
tor 1a, 2 equiv of 4-nitroimidazole was reacted with R,R′-
dibromo-m-xylene to give the compound 7 in 44% yield.
Then, the xylene-bridged imidazole 7 was refluxed with 30
equiv of diethyl sulfate for 24 h. Anion exchange with
ammonium hexafluorophosphate gave receptor 1a bearing
two imidazolium rings in the 1- and 3-positions of m-xylene
in 64% yield. In the cases of receptors 1b and 1c, the starting
materials were 5-nitro-m-xylene 2 and 3,5-dimethylanisole
Figure 1. Job plot of 1 with tetrabutylammonium chloride ([)
and hydrogen sulfate (2).
3
. These starting materials were brominated by N-bromo-
succinimide to give compounds 5 and 6. Receptors 1b and
c were synthesized from these materials following the same
zolium groups (H in Figure 2) originally resonating at δ )
b
1
7.54 was shifted to δ ) 8.14 upon addition of chloride
procedure used to obtain receptor 1a (Scheme 1). All
anions, while those of the other aromatic protons remained
almost unchanged. Job plot experiments showed 1:1 binding
stoichiometry (Figure 1). The association constant calculated
from the chemical shift change of H was 1130 ( 97. The
a
Scheme 1. Synthetic Procedure for Anion Receptors 1
large downfield shift of the inner aromatic proton is
consistent with the presence of a hydrogen bond interaction
between the inner aromatic proton and chloride anion in
addition to the expected normal hydrogen bond interaction
a
between the H and halide anion. The two positively charged
imidazolium rings would affect the sandwiched aromatic ring
hydrogen to be slightly positively charged, and so the
interaction between the aromatic hydrogen and anion can
exist. Here, we reasoned that if a slight positive charge in
the sandwiched aromatic hydrogen enabled the aromatic
hydrogen to participate in hydrogen bonding with anions,
variation of the partial positive charge in the sandwiched
compounds were characterized by H NMR, 13C NMR, and
1
high-resolution mass spectrometry.
The complexation ability of compound 1 was measured
1
by standard H NMR titration experiments in 10% DMSO-
6 3
d in CD CN using a constant host concentration (4 mM)
and increasing concentrations of anions (0.1-10 equiv). The
9
chemical shift data were analyzed by EQNMR. The addition
of tetrabutylammonium anion salts to the solution of receptor
1
6 3
in 10% DMSO-d in CD CN resulted in downfield shifts
of the C(2) proton of imidazolium moieties along with the
inner aromatic proton located between the two imidazolium
groups. In the case of receptor 1a, addition of tetrabutylam-
monium chloride moved the C(2) proton of the imidazolium
Figure 2. Optimized geometry of free host 1a (a) and its Br-
complex (b). Imidazole moieties rotate upon complexation. All
hydrogen atoms except the three shown above have been omitted
ring (H
a
in Figure 2) from 9.23 to 10.64 ppm. In addition,
the inner aromatic proton located between the two imida-
for clarity. H
close to the anion. There are two H
a
is the hydrogen atom attached to the imidazole ring
s. H is the hydrogen atom in
(
8) Kwon, J. Y.; Jang, Y. J.; Kim, S. K.; Lee, K.-H.; Kim, J. S. Yoon,
J. J. Org. Chem. 2004, 69, 5155.
9) Hynes, M. J. J. Chem. Soc., Dalton. Trans. 1993, 311.
a
b
the benzene moiety closest to the anion upon complexation.
(
3994
Org. Lett., Vol. 7, No. 18, 2005

inner aromatic hydrogen should affect the binding constant
with anions. Furthermore, the dependence of the binding
constant on the partial positive charge of the aromatic
hydrogen would be good evidence of participation of the
aromatic hydrogen in the binding event. Therefore, we have
synthesized receptors 1b and 1c and measured their binding
a
Table 2. Comparison of Binding Energies of Both NMR
Experiments and ab Initio Calculations
1b
1a
1c
NMR-
Cl
-3.95 (0.52)
-3.57 (0.56)
-3.94 (0.48)
-4.16 (0.31)
-3.67 (0.46)
-4.22 (0.20)
-4.47 (0.00)
-4.13 (0.00)
-4.42 (0.00)
1
-
constants by standard H NMR titration. In the cases of
Br
-
HSO
4
receptors 1b and 1c, the C(2) proton of the imidazolium ring
moved from 9.20 to 10.68 ppm and from 9.27 to 10.72 ppm
with chloride ion, respectively. In addition, the inner aromatic
proton located between the two imidazolium groups origi-
nally resonating at δ ) 7.09 was shifted to δ ) 7.70 (∆ )
ab initio
(B3LYP/6-31G**)
-
Cl
-172.62 (2.15) -173.30 (1.47) -174.77 (0.00)
-171.31 (2.12) -171.92 (1.51) -173.43 (0.00)
-171.57 (1.60) -172.12 (1.05) -173.17 (0.00)
-
Br
-
HSO
4
a
Units are in kcal/mol. Data in parentheses are relative binding energies
with respect to the most stable one among three hosts (1a-c). Ab initio
calculations were performed in the gas phase. The relative binding energies
of hosts (1a-c) are in good correlation between NMR and calculation
results. Anions are always bound most strongly by the host with the electron-
withdrawing substituent (1c).
0.61 ppm) for 1b. In the case of receptor 1c, the inner
aromatic proton located between the two imidazolium rings
showed an even larger downfield shift from δ ) 7.96 to δ
)
8.76 (∆ ) 0.80 ppm) upon addition of chloride anions.
1
The association constant calculated from the H NMR
titration was 790 ( 32 for 1b and 1908 ( 272 for 1c. The
larger downfield shift for the inner aromatic hydrogen for
two imidizole rings (CIm-CIm) is 8.7 Å. When guest anions
are present, this structure completely reorganizes to accom-
modate the negatively charged guest, attracting two positively
charged imidazole moieties more closely. For example, the
Im-CIm becomes 7.1 Å for the Br complex (Figure 2b).
The reduction of CIm-CIm is clearly observed for all three
hosts for all the anion guests. The major driving force of
complexation between the receptor 1 and anions should
come from the two charged imidazole ring and anion
hydrogen bonding. This is clearly seen in the short distance
1
c and the increase in K
a
result in part from the increased
. The partial positive charge in
hydrogen bond ability of H
b
the aromatic hydrogen was increased by the nitro group in
the aromatic ring and decreased by the methoxy group in
the aromatic ring. We also measured the association constant
for other halides and hydrogen sulfate, which showed a 1:1
binding with receptor 1. The results are summarized in Table
-
C
1. As shown in Table 1, the magnitude of association
a a
and the large positive charge of H and C (the carbon
attached to H
a
) as shown in Table 3. However, as shown in
Table 1. Association Constants (M-1) of 1 with
a
Tetrabutylammonium Anions in 10 % DMSO-d
from H NMR Titration
6
in CD
3
CN
1
a
Table 3. Partial Charges of Anion, Three Hydrogens, and
Carbons Attached to Hydrogens
1a
1b
1c
Cl-
1130
496
339
790
420
254
780
1908
1068
365
anion
H
b
C
b
H
a
1
H
a
2
C
a
1
a
C 2
-
Br
1b
1a
1c
-
I
free NBO
MULL
Cl- NBO
0.266 -0.222 0.280 0.276 0.290 0.292
0.136 -0.134 0.219 0.226 0.339 0.338
-
HSO4
1260
1739
-0.808 0.252 -0.240 0.296 0.296 0.307 0.308
a
Errors in association constants are estimated to be less than 10%.
MULL -0.705 0.114 -0.149 0.210 0.210 0.373 0.374
Br- NBO
-0.787 0.252 -0.240 0.288 0.288 0.307 0.308
MULL -0.675 0.112 -0.151 0.214 0.213 0.361 0.362
constants is well correlated to the hydrogen acceptor ability
of aromatic C-H. That is, electron withdrawing group
-NO ) increase the association constant and electron
2
donating group (-OMe) decrease the association constant.
The molecular modeling from ab initio calculation shows
the details of complexation between the receptor 1 and the
guest anion. All structures were fully optimized by density
functional methods (Becke three parameters employing Lee-
Yang-Parr functionals, B3LYP) with the basis set of
-31G**. Calculations were carried out with the Gaussian-
3 suite of programs, and molecular structures were drawn
using the POSMOL package. Vibrational frequency analy-
ses were performed to confirm the minima. The partial
charges were calculated by both Mulliken and natural
population analysis12
free NBO
MULL
Cl- NBO
0.266 -0.183 0.282 0.284 0.291 0.291
0.140 -0.116 0.223 0.226 0.339 0.337
-0.807 0.253 -0.204 0.295 0.295 0.307 0.307
(
MULL -0.704 0.120 -0.136 0.208 0.208 0.374 0.374
-
Br
NBO
-0.786 0.253 -0.204 0.287 0.287 0.306 0.306
MULL -0.675 0.118 -0.139 0.212 0.212 0.361 0.361
free NBO
MULL
Cl- NBO
0.270 -0.162 0.286 0.286 0.292 0.293
0.143 -0.088 0.228 0.229 0.340 0.339
-0.803 0.262 -0.180 0.294 0.294 0.307 0.307
MULL -0.701 0.132 -0.109 0.205 0.205 0.337 0.337
-
Br
NBO
-0.783 0.260 -0.181 0.286 0.286 0.306 0.306
MULL -0.673 0.128 -0.111 0.211 0.211 0.363 0.363
6
0
1
0
a Charges are calculated with both the Mulliken charge scheme (MULL)
and natural population orbital analysis (NBO). See Figure 2 for H and
Hb. Ca is the carbon attached to Ha, and Cb is that attached to Hb. There
are two Has and two Cas.
11
a
The free host (Figure 2a) has two nitro groups near the
molecular center. This orientation keeps the two charged
imidazole moieties apart. The center to center distance of
b
Figure 2, the distance of H - - -bromide is small (3.3 Å)
enough for hydrogen bonding. Furthermore, the partial charge
of hydrogen is also significantly positive (0.27 for NBO
Org. Lett., Vol. 7, No. 18, 2005
3995

withdrawing group (1c) and electron-donating group (1b)
effects at the para position of H . It is expected that 1b will
have a less positive H compared to 1a, while that of 1c is
b
Table 4. Distances of Anion, Three Hydrogens, and Carbon
Attached to Hydrogen
b
more positive than that of 1a. NMR titration experiments
clearly show this substituent effect. As the benzene ring
becomes more positive, the absolute value of binding free
energy increases. In Table 2, the binding energies for both
NMR and ab initio calculations are compared. It is clear that
the relative binding energies for both NMR experiments and
ab initio calculation are in good correlation. That is, both
experiments and theory indicate that the electron-withdrawing
substituent makes the host a stronger binder of anions. In
Table 3, the electronic effect of substitution is also clear.
For example, the charge of chloride ion is -0.808 for
methoxy group substitution (host 1b). This means that the
charge of -0.192 is transferred to this electron-deficient host.
The magnitude of charge-transfer becomes slightly higher
for host 1a, while for nitro substitution (host 1c), this transfer
becomes -0.197. Likewise, we can see that electron deple-
1
b
1a
1c
anion-Hb
-
Cl
Br
3.249
3.297
3.238
3.258
3.163
3.250
-
anion-Cb
-
Cl
3.930
4.052
3.900
4.023
3.803
3.952
1
3
-
Br
anion-Ha1
-
Cl
2.154
2.310
2.143
2.305
2.123
2.289
-
Br
anion-Ha2
-
Cl
2.148
2.317
2.143
2.305
2.123
2.289
-
Br
center (imidazole 1)-center (imidazole 2)
free
8.435
7.030
7.036
6.457
8.681
7.094
7.068
6.468
8.756
7.195
7.209
7.454
Cl-
Br-
tion occurs for H
group. Because of the enhanced positive character for H
and C , for host 1c, there is more attraction between the anion
and H
b b
and C with an electron-withdrawing
HSO4-
b
a
Units are in Å.
b
b
, and the distance becomes shorter. For example, the
- - -Cl distance is 3.25 Å for host 1b, 3.24 Å for host
-
charge and 0.14 for Mulliken charge). This suggests that not
only two H - - -anion interactions but also a H - - -anion
H
b
a
b
1a, and 3.16 Å for host 1c.
interaction contribute to the binding of the anion and the
receptor.
In conclusion, although it may be small, the attraction
between H
b
and anion exists. The effect of para substitution
and anion
To further demonstrate the existence of a H
b
- - -anion
to H demonstrates the contribution of H
b
b
interaction upon anion binding, we calculated both electron-
hydrogen bonding interaction to the complexation.
(
10) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
Supporting Information Available: Optimized geom-
etries and energies of complexes in Table 2. This material
is available free of charge via the Internet at http://pubs.acs.org.
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K.
N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;
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S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A.
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G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
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OL0515309
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25, 1061.
(12) Reed, A. E.; Weinstock, R. B.; Weinhold, F. J. Chem. Phys. 1985,
83, 735.
(13) Absolute binding energies are very different between experimental
and theoretical results. This should come from the phase difference. The
experiments were performed in a mixed solvent system, while calculations
were performed in the gas phase. The discrepancy between theory and
experiment over the preference of the anion guest should also come from
this complicated solvation effect.
0
3, revision C.02; Gaussian, Inc.: Wallingford, CT, 2004.
3996
Org. Lett., Vol. 7, No. 18, 2005