Effect of hydroxyl groups in receptors bearing disulfonamide on anion recognition in acetonitrile-d3

Article abstract of DOI:10.1016/S0040-4039(02)01543-5

To elucidate the roles of hydroxyl group on anion-recognition chemistry, receptors bearing disulfonamide and hydroxyl groups were prepared and their anion-binding properties were evaluated in acetonitrile.

Full text of DOI:10.1016/S0040-4039(02)01543-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7059–7061
Effect of hydroxyl groups in receptors bearing disulfonamide on
anion recognition in acetonitrile-d3
Shin-ichi Kondo,* Takashi Suzuki and Yumihiko Yano
Department of Chemistry, Faculty of Engineering, Gunma University, Kiryu, Gunma 376-8515, Japan
Received 28 May 2002; revised 25 July 2002; accepted 26 July 2002
Abstract—To elucidate the roles of hydroxyl group on anion-recognition chemistry, receptors bearing disulfonamide and hydroxyl
groups were prepared and their anion-binding properties were evaluated in acetonitrile. © 2002 Elsevier Science Ltd. All rights
reserved.
Anion recognition by artificial receptors has been grow-
ing in the field of host–guest chemistry due to biological
and environmental significance.1 Naturally occurring
anion-binding peptides for phosphate and sulfate anions
are known to have amide NꢀH of the peptides and
hydroxyl groups of serine and threonine residues in the
binding sites.2 Although hydrogen-donating effects of
NꢀHs of amide,3 urea,4 thiourea,5 and sulfonamides6 on
anion binding have been extensively investigated in
model systems, the roles of hydroxyl groups have been
less studied.7,8 Davis and co-workers have reported that
rigid steroid-based anion receptors bearing hydroxyl
groups bind anionic species in non-polar organic solvents
such as CDCl3 and hydrocarbons.8a,b Hamilton et al.
have reported that receptors having both urethane NꢀHs
and hydroxyl groups exhibit considerably large binding
constants for acetate anion in acetonitrile.8c However, it
has remained whether such cooperative hydrogen bonds
work on other anion species such as phosphate, sulfate,
and halide anions. This prompted us to examine the
effect of the cooperative hydrogen bonds on binding
constants for these anions in acetonitrile by employing
the receptors as shown in Scheme 1.
Receptors 1 and 2 were prepared from the correspond-
ing disulfonyl chloride with 2-aminoethanol or 1-
aminobutane
in
N,N-dimethylformamide,
and
characterized by 1H NMR and elemental analysis.†
Receptors 3 and 4 were prepared similarly by using
tosyl chloride. Binding behavior of 1 for anion species
(tetra(n-butyl)ammonium salts) was examined by 1H
NMR titration method. To eliminate higher order com-
plexation (host:guest=2:1 and so on), acetonitrile was
used instead of less polar solvents such as chloroform.
Dilution experiment of 1H NMR for 1 in MeCN-d3
([1]=10–1.67×10−3 mol dm−3) showed no spectral
Scheme 1.
Keywords: anion recognition; hydroxyl group; sulfonamide; hydrogen bond.
* Corresponding author. Tel.: +81-277-30-1231; fax: +81-277-30-1236; e-mail: kondo@chem.gunma-u.ac.jp
†
Selected analytical data: 1: mp 80.5°C. 1H NMR (300 MHz, MeCN-d3) l 8.24 (s, 1H), 8.04 (d, 2H, J=7.9 Hz), 7.75 (t, 1H, J=7.9 Hz), 5.83
(bs, 2H), 3.46 (q, 4H, J=5.6 Hz), 2.96 (q, 4H, J=5.6 Hz), 2.82 (t, 2H, J=5.6 Hz). Anal. calcd for C10H16N2O6S2: C, 37.03; H, 4.97; N, 8.64.
Found C, 37.06; H, 4.93; N, 8.26; 2: mp 100–101°C. 1H NMR (300 MHz, CDCl3) l 8.40 (t, 1H, J=1.6 Hz), 8.06 (dd, 1H, J1=7.9 Hz, J2=1.6
Hz), 7.69 (t, 1H, J=7.9 Hz), 4.94 (bs, 2H), 2.97 (q, 4H, J=6.7 Hz), 1.46 (quint, 4H, J=7.3 Hz), 1.29 (m, 4H), 0.86 (t, 6H, J=7.3 Hz). Anal.
calcd for C14H24N2O4S2: C, 48.25; H, 6.94; N, 8.04. Found C, 48.42; H, 6.92; N, 8.04%.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01543-5

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S. Kondo et al. / Tetrahedron Letters 43 (2002) 7059–7061
change, indicating that dimerization of receptor 1 is
negligible in experimental concentration range. Fig. 1
1
shows the result of H NMR titration of 1 with Cl− in
MeCN-d3. Upon addition of Cl−, large downfield shifts
of OH protons (Dl 1.64 ppm), sulfonamide NH pro-
tons (Dl 1.71 ppm), and 2-C-H proton of benzene ring
(Dl 0.51 ppm) were observed. This result strongly
suggests that the hydroxyl groups are involved in
hydrogen-bonding formation. Although the similar
downfield shifts of OH and NH protons were observed
for AcO− and H2PO4 , the changes of the shifts were
−
not determined accurately because of broadening. Stoi-
chiometry of host–guest complexation was confirmed to
be 1:1 by a Job plot obtained from the chemical shift of
2-C-H of the benzene ring, as shown in Fig. 2. Negative
ion mode of electron-spray ionization mass spec-
troscopy revealed 1:1 complex formation for 1 and 2
Figure 3. Plots of chemical shift (2-CH) of 1 (closed circle)
and 2 (closed square) on the concentration of AcO− in
MeCN-d3 at 298 K. [Host]=5.0×10−3 mol dm−3
.
−
Table 1. Association constants and binding free energies
for complexation of receptors and anions in acetonitrile-d3
with all the anions used except for ClO4 and no higher
order complex was not observed.
Anion
Ka/dm3 mol−1 (−DG at
298 K/kJ mol−1 a
DDG (kJ mol−1
)
Binding constants of the receptors with the anion spe-
cies were determined by non-linear least square calcula-
tion following the chemical shifts of 2-C-H of the
)
1
2
1
benzene ring by H NMR titration, as shown in Fig. 3.
AcO−
H2PO4
23,80091,600
(25.0)
585919 (15.8)
9.2
The results are summarized in Table 1. Receptor 1 is
more efficient than 2 for all the anion species, indicat-
−
1,890910 (18.7)
240913 (13.6)
928935 (16.9)
23692 (13.5)
2.5 (2.3)
209923 (13.2)
6295 (10.2)
124914 (11.9)
5292 (9.8)
B1b
5.5
3.4
5.0
3.7
−
HSO4
Cl−
Br−
I−
−
ClO4
B1b
B1b
a Measured by 300 MHz 1H NMR at 298 K. [Receptor]=5.0×10−3
mol dm−3. Tetra(n-butyl)ammonium salts were used for all anions.
b Shift was too small to determine the association constant.
1
Figure 1. Partial H NMR spectra on titration of 1 with Cl−
in MeCN-d3 at 298 K. [1]=5.0×10−3 mol dm−3, (a) 1 only; (b)
1 and 1 equiv. of Cl−; (c) 1 and 2 equiv. of Cl−. The
resonances corresponding to 2-CH of benzene ring (Ha), NH
(Hb), and OH (Hc) are marked, respectively.
Scheme 2.
ing clearly that the hydroxyl groups involved in the
complexation as hydrogen-bond donors. It is noted that
receptor 1 showed good selectivity for AcO− compared
with other anions. The anion-binding ability of recep-
tors 1 and 2 are in the order of AcO− (pKa=4.76
in water)>H2PO4 (2.16)>Cl− (−6.1)>Br- (−9)HSO4
−
−
(−3.1)>I− (−10)>ClO4 (−7.3). This order can be
explained by both basicity and shape of the anions. The
effect of the hydroxyl groups on the binding constants
can be evaluated by DDG, as shown in Table 1. Much
larger DDG (9.2 kJ mol−1) for AcO− suggests the bind-
ing mode as shown in Scheme 2. Such a tendency was
also observed for AcO− binding of receptors 3 and 4.
These receptors associate with AcO− in 1:1 complexa-
tion and Ka and DG values of 3 and 4 for AcO− were
703 (DG=16.3 kJ mol−1) and 39 dm3 mol−1 (DG=9.1 kJ
mol−1), respectively.
−
Figure 2. A Job plot for complexation of 1 with AcO−
1
determined by H NMR in MeCN-d3 at 298 K. [1]+[AcO−]=
5.0×10−3 mol dm−3
.

S. Kondo et al. / Tetrahedron Letters 43 (2002) 7059–7061
7061
In conclusion, we have demonstrated that a simple
disulfonamide bearing hydroxyl group 1 shows remark-
able anion-binding ability in MeCN-d3. The hydroxyl
groups of the receptor act as hydrogen-bond donors in
anion recognition even in such a polar solvent as
MeCN-d3. The present results are useful information
for design of more sophisticated receptors. It is note-
worthy that chiral recognition of optically active car-
boxylate such as amino acids is expected by a chiral
receptor bearing hydroxyl groups, which is easily
obtained from chiral aminoalcohols.
4. (a) Hamann, B. C.; Branda, N. R.; Rebek, J., Jr. Tetra-
hedron Lett. 1993, 43, 6837–6840; (b) Raposo, C.;
Almaraz, M.; Martin, M.; Weinrich, V.; Mussons, M. a.
L.; Alcazar, V.; Caballero, M. C.; Moran, J. R. Chem.
Lett. 1995, 759–760; (c) Jeong, K.-S.; Park, J. W.; Cho, Y.
L. Tetrahedron Lett. 1996, 37, 2795–2798; (d) Torre, M.
F.d.l.; Campos, E. G.; Gonza´rez, S.; Mora´n, J. R.;
Caballero, M. C. Tetrahedron 2001, 57, 3945–3950; (e)
Budka, J.; Lhota´k, P.; Michlova´, V.; Stibor, I. Tetrahedron
Lett. 2001, 42, 1583–1586.
5. (a) Smith, P. J.; Reddington, M. V.; Wilcox, C. S. Tetra-
hedron Lett. 1992, 33, 6085–6088; (b) Fan, E.; Arman, S.
A. V.; Kincaid, S.; Hamilton, A. D. J. Am. Chem. Soc.
1993, 115, 369–370; (c) Bu¨hlmann, P.; Nishizawa, S.; Xiao,
K. P.; Umezawa, Y. Tetrahedron 1997, 53, 1647–1654; (d)
Lee, K. H.; Hong, J.-I. Tetrahedron Lett. 2000, 41, 6083–
6087; (e) Snellink-Rue¨l, B. H. M.; Antonisse, M. M. G.;
Engbersen, J. F. J.; Timmerman, P.; Reinhoudt, D. N.
Eur. J. Org. Chem. 2000, 165–170; (f) Gunnlaugsson, T.;
Davis, A. P.; Glynn, M. Chem. Commun. 2001, 2556–2557;
(g) Kato, R.; Nishizawa, S.; Hayashita, T.; Teramae, N.
Tetrahedron Lett. 2001, 42, 5053–5056.
Acknowledgements
This work was supported in part by a Grant-in-Aid for
Scientific Research from the Ministry of Education,
Culture, Sports, Science, and Technology of Japan.
References
6. (a) Kavallieratos, K.; Bertao, C. M.; Crabtree, R. H. J.
Org. Chem. 1999, 64, 1675–1683; (b) Kavallieratos, K.;
Sachleben, R. A.; Berkel, G. J. V.; Moyer, B. A. Chem.
Commun. 2000, 187–188; (c) Kavallieratos, K.; Moyer, B.
A. Chem. Commun. 2001, 1620–1621; (d) Valiyaveettil, S.;
Engbersen, J. F. J.; Verboom, W.; Reinhoudt, D. N.
Angew. Chem., Int. Ed. Engl. 1993, 32, 900–901; (e)
Morzherin, Y.; Rudkevich, D. M.; Verboom, W.; Rein-
houdt, D. N. J. Org. Chem. 1993, 58, 7602–7605; (f) Davis,
A. P.; Perry, J. J.; Williams, R. P. J. Am. Chem. Soc. 1997,
119, 1793–1794.
7. (a) Motomura, T.; Aoyama, Y. J. Org. Chem. 1991, 56,
7224–7228; (b) Manabe, K.; Okamura, K.; Date, T.;
Koga, K. J. Am. Chem. Soc. 1992, 114, 6940–6941; (c)
Lee, D. H.; Lee, H. Y.; Hong, J.-I. Org. Lett. 2001, 3, 5–8;
(d) Lee, D. H.; Lee, H. Y.; Lee, K. H.; Hong, J.-L. Chem.
Commun. 2001, 1188–1189; (e) Lee, K. H.; Lee, H. Y.; Lee,
D. H.; Hong, J.-I. Tetrahedron Lett. 2001, 42, 8665–8668;
(f) Arduini, A.; Giorgi, G.; Pochini, A.; Secchi, A.; Ugoz-
zoli, F. J. Org. Chem. 2001, 66, 8302–8308.
1. (a) Bianchi, A.; Bowman-James, K.; Garcia-Espana, E.
Supramolecular Chemistry of Anions; Wiley-VCH: New
York, 1997; for recent reviews: (b) Lehn, J.-M. Angew.
Chem., Int. Ed. Engl. 1988, 27, 89–112; (c) Schmidtchen, F.
P.; Berger, M. Chem. Rev. 1997, 97, 1609−1646; (d)
Antonisse, M. M. G.; Reinhoudt, D. N. Chem. Commun.
1998, 443−447; (e) Gale, P. A. Coord. Chem. Rev. 2000,
199, 181−233; (f) Beer, P. D.; Gale, P. A. Angew. Chem.,
Int. Ed. 2001, 40, 486–516.
2. (a) Luecke, H.; Quiocho, F. A. Nature 1990, 347, 402–406;
(b) He, J. J.; Quiocho, F. A. Science 1991, 251, 1479–1481;
(c) Pflugrath, J. W.; Quiocho, F. A. Nature 1985, 314,
257–260; (d) Pflugrath, J. W.; Quiocho, F. A. J. Mol. Biol.
1988, 200, 163–180.
3. (a) Ishida, H.; Suga, M.; Donowaki, K.; Ohkubo, K. J.
Org. Chem. 1995, 60, 5374–5475; (b) Bisson, A. P.; Lynch,
V. M.; Monahan, M.-K. C.; Anslyn, E. V. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 2340–2342; (c) Kavallieratos, K.;
Sachleben, R. A.; Berkel, G. J. V.; Moyer, B. A. Chem.
Commun. 2000, 187–188; (d) Hossain, M. A.; Llinares, J.
M.; Powell, D.; Bowmna-James, K. Inorg. Chem. 2001, 40,
2936–2937; (e) Mahoney, J. M.; Beatty, A. M.; Smith, B.
D. J. Am. Chem. Soc. 2001, 123, 5847–5848; (f) Choi, K.;
Hamilton, A. D. J. Am. Chem. Soc. 2001, 123, 2456–2457.
8. (a) Davis, A. P.; Gilmer, J. F.; Perry, J. J. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 1312–1315; (b) Davis, A. P.; Perry,
J. J.; Wareham, R. S. Tetrahedron Lett. 1998, 39, 4569–
4572; (c) Albert, J. S.; Hamilton, A. D. Tetrahedron Lett.
1993, 34, 7363–7366.