Anion recognition by 1,2,3-triazolium receptors: Application of click chemistry in anion recognition

Article abstract of DOI:10.1021/ol702457w

(Chemical Equation Presented) Cyclic and acyclic bile acid-based 1,2,3-triazolium receptors which show remarkable ability to recognize anions through C-H...X^- hydrogen bond interactions have been synthesized using click chemistry.

Full text of DOI:10.1021/ol702457w

ORGANIC
LETTERS
2008
Vol. 10, No. 2
165-168
Anion Recognition by 1,2,3-Triazolium
Receptors: Application of Click
Chemistry in Anion Recognition
Anjul Kumar and Pramod S. Pandey*
Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas,
New Delhi 110016, India
pramod@chemistry.iitd.ac.in
Received October 9, 2007
ABSTRACT
−
Cyclic and acyclic bile acid-based 1,2,3-triazolium receptors which show remarkable ability to recognize anions through C
−H‚‚‚
X
hydrogen
bond interactions have been synthesized using click chemistry.
The application of click chemistry developed by Meldal1 and
Sharpless2 involving the Cu(1)-catalyzed 1,3-dipolar cy-
cloaddition of an azide and a terminal alkyne is rapidly
growing, especially in the areas of biological, materials, and
medicinal chemistry.3 Besides the advantages of its high
efficiency, regioselectivity, and compatibility with reaction
conditions, the unique properties of the 1,4-disubstituted
1,2,3-triazole ring in terms of its ability to participate in
hydrogen bond and dipole-dipole interactions has made click
chemistry even more attractive. The ability of the N(3) atom
of 1,2,3-triazole to act as a hydrogen bond acceptor and the
polarized C(5) proton as a hydrogen bond donor makes it
an amide/peptide bond mimic.4 Consequently, click chem-
istry has gained much importance in peptide chemistry for
the design of peptide analogues and â-turn peptide mimics.5
ingly some triazole-based receptors and dendrimers for the
recognition of metals have been reported.6 Interestingly, the
(3) (a) Moses, J. E.; Moorhouse, A. D. Chem. Soc. ReV. 2007, 36, 1249.
(b) Fournier, D.; Hoogenboom, R.; Schubert, U. S. Chem. Soc. ReV. 2007,
36, 1369. (c) Lutz, J. F. Angew. Chem., Int. Ed. 2007, 46, 1018. (d) Bock,
V. D.; Hiemstra, H.; Maarseveen, J. H. V. Eur. J. Org. Chem. 2006, 1, 51.
(e) Wang, Q.; Chan, T. R.; Hilgraf, R.; Fokin, V. V.; Sharpless, K. B.;
Finn, M. G. J. Am. Chem. Soc. 2003, 125, 3192. (f) Link, A. J.; Tirrell, D.
A. J. Am. Chem. Soc. 2003, 125, 11164. (g) Ladmiral, V.; Mantovani, G.;
Clarkson, G. J.; Cauet, S.; Irwin, J. L.; Haddleton, D. M. J. Am. Chem.
Soc. 2006, 128, 4823. (h) Gupta, S. S.; Raja, K. S.; Kaltgrad, E.; Strable,
E.; Finn, M. G. Chem. Commun. 2005, 34, 4315. (i) Lu, G.; lam, S.; Burgess,
K. Chem. Commun. 2006, 15, 1652. (j) Billing, J. F.; Nilsson, U. J. J. Org.
Chem. 2005, 70, 4847. (k) Diaz, D. D.; Rajagopal, K.; Strable, E.; Schneider,
J.; Finn, M. G. J. Am. Chem. Soc. 2006, 128, 6056. (l) Bodine, K. D.; Gin,
D. Y.; Gin, M. S. J. Am. Chem. Soc. 2004, 126, 1638. (m) Punna, S.;
Kuzelka, J.; Wang, Q.; Finn, M. G. Angew. Chem., Int. Ed. 2005, 44, 2215.
(n) Gao, H.; Matyjaszewski, K. Macromolecules 2006, 39, 4960. (o) Lutz,
J.-F.; Borner, H. G.; Weichenhan, K. Macromolecules 2006, 39, 6376. (p)
Wu, P.; Feldman, A. K.; Nugent, A. K.; Hawker, C. J.; Scheel, A.; Voit,
B.; Pyun, J.; Frechet, J. M. J.; Sharpless, K. B.; Fokin, V. V. Angew. Chem.,
Int. Ed. 2004, 43, 3928. (q) Kolb, H. C.; Sharpless, K. B. Drug DiscoVery
Today 2003, 8, 1128. (r) Whiting, M.; Tripp, J. C.; Lin, Y.-C.; Lindstrom,
W.; Olson, A. J.; Elder, J. H.; Sharpless, K. B.; Fokin, V. V. J. Med. Chem.
2006, 49, 7697.
Recently, the role of 1,2,3-triazole in the formation of
stable metal complexes has also been realized and accord-
(1) Tornoe, C. M.; Christensen, C.; Meldal, M. J. J. Org. Chem. 2002,
67, 3057.
(2) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem., Int. Ed. 2002, 41, 2596.
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10.1021/ol702457w CCC: $40.75
© 2008 American Chemical Society
Published on Web 12/15/2007

dendrimers developed by Astruc et al.6g also showed the
ability of binding oxo anions through the 1,2,3-triazole ring
localized inside the dendrimers. However, to our knowledge,
the potential of the 1,2,3-triazolium ring7 to act as a hydrogen
bond donor for anion recognition has not yet been explored.
As compared to 1,2,3-triazole, the 1,2,3-triazolium ring is
expected to be a better hydrogen bond donor for anion
recognition.
Scheme 1
The chemistry of anion recognition has developed rapidly
in the past few years due to its biological and medical
significance. Many receptors based on different types of
sensing moieties involving N-H‚‚‚X-, O-H‚‚‚X-, and (C-
H)+‚‚‚X- hydrogen bond interactions have been developed.8
In recent years, bile acids have attracted considerable interest
as building blocks for the construction of receptors for anion
recognition because of their unique structural features.9 Our
ongoing interest9i,j in developing new types of steroid-based
receptors for anion recognition and the interesting properties
of the 1,2,3-triazole ring prompted us to design bile acid-
based triazolium receptors for anion recognition.
Herein, we report for the first time the synthesis and anion-
binding properties of 1,2,3-triazolium-based receptors in
which the C-5 proton of the triazolium ring actively
participates in the recognition of anions through C-H‚‚‚X-
hydrogen bond interactions. We used click chemistry involv-
ing the 1,3-dipolar cycloaddition of steroidal diazide and
alkynes for the construction of cyclic and acyclic triazolium
receptors. The synthesis of cyclic receptors 5a and 5b based
on deoxycholic acid has been outlined in Scheme 1. The
steroidal diazido compound, methyl 3R,12R-bis(azidoacetyl)-
deoxycholate 2, was obtained by the treatment of methyl
(5) (a) Angell, Y. L.; Burgess, K. Chem. Soc. ReV. 2007, 36, 1674. (b)
Oh, K.; Guan, Z. Chem. Commun. 2006, 29, 3069. (c) Angell, Y.; Burgess,
K. J. Org. Chem. 2005, 70, 9595.
3R,12R-bis(bromoacetyl)deoxycholate9i 1 with sodium azide
in DMF, which on subsequent treatment with m-bis(prop-
argyloxy)benzene10 3a and p-bis(propargyloxy)benzene10 3b
in t-BuOH in the presence of CuSO4 and sodium ascorbate
(click reaction) gave cycloadducts 4a and 4b, respectively,
in high yields. The methiodide salts of cyclic receptors 5a
and 5b were obtained by methylation of 4a and 4b with
methyl iodide, which were further anion exchanged with
NH4PF6 in MeOH/CHCl3 to give their PF6- salts. The acyclic
receptor 7 was synthesized by the reaction of di-azido
compound 2 with 2 equiv of phenylacetylene followed by
methylation and then anion exchange with NH4PF6 in similar
reaction conditions (Scheme 2).
(6) (a) Bronisz, R. Inorg. Chem. 2005, 13, 4463. (b) Li, Y.; Huffman, J.
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2007, 48, 7274. (g) Ornelas, C.; Aranzaes, J. R.; Cloutet, E.; Alves, S.;
Astruc, D. Angew. Chem., Int. Ed. 2007, 46, 872.
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Acta Chem. Scand. 1967, 21, 1234. (c) Begtrup, M. Acta Chem. Scand.
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Koren, A. O. Heterocycl. Chem. 2002, 39, 1111.
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(b) Gale, P. A. Acc. Chem. Res. 2006, 39, 465. (c) Katayev, E. A.; Ustynyuk,
Y. A.; Sessler, J. L. Coord. Chem. ReV. 2006, 250, 3004. (d) Kang, S. O.;
Hossain, M. A.; Bowman-James, K. Coord. Chem. ReV. 2006, 250, 3038.
(e) Lankshear, M. D.; Beer, P. D. Coord. Chem. ReV. 2006, 250, 3142. (f)
Filby, M. H.; Steed, J. W. Coord. Chem. ReV. 2006, 250, 3200. (g) Yoon,
J.; Kim, S. K.; Singh, N. J.; Kim, K. S. Chem. Soc. ReV. 2006, 35, 355. (h)
Kang, S. O.; Begum, R. A.; Bowman-James, K. Angew. Chem., Int. Ed.
2006, 45, 7882.
(9) (a) Davis, A. P. Coord. Chem. ReV. 2006, 250, 2939. (b) Virtanen,
E.; Kolehmainen, E. Eur. J. Org. Chem. 2004, 16, 3385. (c) Clare, J. P.;
Ayling, A. J.; Joos, J.-B.; Sisson, A. L.; Magro, G.; Perez-Payan, M. N.;
Lambert, T. N.; Shukla, R.; Smith, B. D.; Davis, A. P. J. Am. Chem. Soc.
2005, 127, 10739. (d) Fang, L.; Chan, W.-H.; He, Y.-B.; Kwong, D. W. J.;
Lee, A. W. M. J. Org. Chem. 2005, 70, 7640. (e) Liu, S.-Y.; Fang, L.; He,
Y.-B.; Chan, W.-H.; Yeung, K.-T.; Cheng, Y.-K.; Yang, R.-H. Org. Lett.
2005, 7, 5825. (f) Ghosh, S.; Choudhary, A. R.; Row, T. N. G.; Maitra, U.
Org. Lett. 2005, 7, 1441. (g) Sisson, A. L.; Clare, J. P.; Davis, A. P. Chem.
Commun. 2005, 42, 5263. (h) Kim, K. S.; Kim, H.-S. Tetrahedron 2005,
61, 12366. (i) Khatri, V. K.; Upreti, S.; Pandey, P. S. Org. Lett. 2006, 8,
1755. (j) Chahar, M.; Upreti, S.; Pandey, P. S. Tetrahedron 2007, 63, 171.
The anion binding property of 5a-(PF6)2, 5b-(PF6)2, and
1
7-(PF6)2 was studied by monitoring the H NMR spectral
changes caused by the addition of tetrabutylammonium salts
of the anions to a CDCl3 solution containing the receptors.
Upon addition of Bu4NX (X ) F, Cl, Br, I, CH3COO, H2-
PO4) to receptors, significant downfield shifts (δ 1.3-0.9
ppm) were observed for the C(5)-H proton of each triazolium
moiety suggesting the complexation of the anion with
triazolium C(5)-protons by forming C-H‚‚‚X- hydrogen
bonds. In addition, significant downfield shifts were also
(10) Srinivasan, M.; Sankararaman, S.; Hopf, H.; Dix, I.; Jones, P. G. J.
Org. Chem. 2001, 66, 4299.
166
Org. Lett., Vol. 10, No. 2, 2008

Table 1. Association Constant (Ka)a for 1:1 Complexes of
Scheme 2
Hosts with Anions in CDCl3 at 298 K
Ka [M-1
]
anionsb
receptor 5a
receptor 5b
receptor 7
F-
560
270
220
100
60
370
690
450
200
25
360
390
200
110
30
Cl-
Br-
I-
CH3CO2
H2PO4
-
-
1100
1920
a Estimated error <10%. b Anions were used as tetrabutylammonium
salts.
affinity for fluoride ion with an association constant of 560
M-1. The observed selectivity trend was F- > Cl- > Br- >
I- > CH3COO-. No significant binding was observed with
-
H2PO4 ion in this case. However, receptor 5b showed
-
considerable affinity for the H2PO4 ion with a binding
constant of 1100 M-1, which may be due to the larger cavity
size of the receptor because of the para-substituted benzene
-
ring. The observed selectivity trend was H2PO4 > Cl- >
Br- > F- > I- > CH3COO-. Interestingly, the acyclic
receptor 7 showed much higher affinity and selectivity
-
toward H2PO4 ion as compared to the cyclic receptor 5b,
having a binding constant of 1920 M-1. The selectivity trend
-
was H2PO4 > Cl- > F- > Br- > I- > CH3COO-. The
-
higher affinity of the acyclic receptor for H2PO4 ion as
compared to the cyclic receptor 5b may be attributed to the
greater flexibility of the acyclic receptor for adapting the
suitable geometry required for the binding of a tetrahedral
observed for the bridging methylene protons indicating their
participation in hydrogen bonding with anions along with
C-5 triazolium protons (Figure 1). The Job’s plots analyses
-
H2PO4 anion (Figure 2).
Figure 2.
As there has been much interest12 in recent years in
-
designing artificial receptors for the H2PO4 ion due to its
1
biological importance, the present work will be of great
significance. More importantly, it also establishes the
potential of the 1,2,3-triazolium system as an anion-sensing
moiety and the importance of click chemistry for anion
recognition.
Figure 1. Partial H NMR spectra of (a) 7-2PF6 + 2.5 equiv of
TBACl and (b) 7-2PF6.
showed the formation of 1:1 complexes. The association
constants were determined by using WinEQNMR software11
and are presented in Table 1. Receptor 5a showed the highest
(11) Hynes, M. J. J. Chem. Soc., Dalton Trans. 1993, 311.
Org. Lett., Vol. 10, No. 2, 2008
167

In summary, we have synthesized bile acid-based cyclic
and acyclic 1,2,3-triazolium systems using the click chem-
istry of 1,3-dipolar cycloaddition of an azide and an alkyne.
These receptors display the remarkable ability of the 1,2,3-
triazolium ring to act as an anion-sensing moiety. The acyclic
receptor has been found to show very high selectivity for
the H2PO4 ion with respect to halide and acetate ions.
-
Acknowledgment. A.K. thanks the Council of scientific
and Industrial Research, New Delhi, for a research fellow-
ship.
(12) (a) Daniel, M.-C.; Ruiz, J.; Astruc, D. J. Am. Chem. Soc. 2003,
125, 1150. (b) Daniel, M.-C.; Ba, F.; Aranzaes, J. R.; Astruc, D. Inorg.
Chem. 2004, 43, 8649. (c) Kim, S. K.; Singh, N. J.; Kim, S. J.; Kim, H. G.;
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) Kwon, T. H.; Jeong, K.-S.
Tetrahedron Lett. 2006, 47, 8539. (f) Moon, K. S.; Singh, N.; Lee, G. W.;
Jang, D. O. Tetrahedron 2007, 63, 9106. (g) Xu, Z.; Kim, S.; Lee, K.-H.;
Yoon, J. Tetrahedron Lett. 2007, 48, 3797.
Supporting Information Available: Experimental de-
tails, analytical data for compounds, and binding isotherms.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL702457W
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Org. Lett., Vol. 10, No. 2, 2008