J . Org. Chem. 2001, 66, 7849-7853
7849
2-Am id op yr r oles a n d 2,5-Dia m id op yr r oles a s Sim p le An ion
Bin d in g Agen ts
Philip A. Gale,* Salvatore Camiolo, Graham J . Tizzard, Christopher P. Chapman,
Mark E. Light, Simon J . Coles, and Michael B. Hursthouse
Department of Chemistry, University of Southampton, Southampton, SO17 1BJ , UK
philip.gale @soton.ac.uk
Received August 9, 2001
Four new 2-amidopyrroles and 2,5-diamidopyrroles have been synthesized and their anion
complexation properties investigated. The crystal structures of these receptors have been elucidated
and reveal hydrogen bonding in the solid state leading to dimer and network formation. Selectivity
1
for oxo-anions has been demonstrated by H NMR titration techniques.
In tr od u ction a n d Ba ck gr ou n d
in order to assess the anion complexation ability of this
moiety alone.
Recent developments in the area of anion recognition
and sensing have produced a variety of new selective
receptors for anions.1 However, the great variety of
anionic species and their importance in the environment
(pollutant anions from over use of agricultural fertilizers
cause eutrophication of lakes and inland waterways2), in
biological systems (misregulation of anion transport is
responsible for a number of medical conditions including
cystic fibrosis3), and in the clinic (the maintenance of
sulfate anion concentration in dialysis patients continues
to be problematic4) presents a continuing challenge to
design selective receptors. The anion coordination ability
of receptors containing pyrrole groups has been an area
of increasing interest in the past decade. This area of
chemistry has been led by Sessler and co-workers who
have produced a variety of expanded porphyrins5 and
polypyrrolic6 macrocycles capable of binding anions. A
smaller subset of receptors containing both a pyrrole and
an amide moiety have been described.7 Many of these
systems are quite complex, for example Sessler and
Vo¨gtle’s elegant catenane for oxo-anion complexation.8
More recently, Schmuck has shown that guanidinium
groups that contain an appended pyrrole-amide moiety
are useful in the selective complexation of amino acids.9
We decided to ‘extract’ the pyrrole amide unit and
synthesize a variety of simple pyrrole-amide ligands 1-4
Discu ssion
5-Methyl-3,4-diphenyl-1H-pyrrole-2-carboxylic acid eth-
yl ester was synthesized via a Paal-Knorr reaction
(5) Sessler, J . L.; Cyr, M. J .; Lynch, V.; McGhee, E.; Ibers, J . A. J .
Am. Chem. Soc. 1990, 112, 2810-2813. Shionoya, M.; Furuta, H.;
Lynch, V.; Harriman, A.; Sessler, J . L. J . Am. Chem. Soc. 1992, 114,
5714-5722. Kra´l, V.; Furuta, H.; Shreder, K.; Lynch, V.; Sessler, J . L.
J . Am. Chem. Soc. 1996, 118, 1595-1607. Kra´l, V.; Andrievsky, A.;
Sessler, J . L. J . Am. Chem. Soc. 1995, 117, 2953-2954. Sessler, J . L.;
Andrievsky, A.; Kra´l, V.; Lynch, V. J . Am. Chem. Soc. 1997, 119, 9385-
9392. Furuta, H.; Cyr, M. J .; Sessler, J . L. J . Am. Chem. Soc. 1991,
113, 6677-6678. Sessler, J . L.; Kra´l, V.; Genge, J . W.; Thomas, R. E.;
Iverson, B. L. Anal. Chem. 1998, 70, 2516-2522. Sessler, J . L.; Genge,
J . W.; Kra´l, V.; Iverson, B. L. Supramol. Chem. 1996, 8, 45-52. Iverson,
B. L.; Shreder, K.; Kra´l, V.; Sessler, J . L. J . Am. Chem. Soc. 1993,
115, 11022-11023. Sessler, J . L.; Weghorn, S. J . Expanded, Contracted
and Isomeric Porphyrins; Elsevier: Oxford, 1997.
* To whom correspondence should be addressed. Phone: 44-23-8059-
3332; Fax: 44-23-8059-6805.
(1) Gale, P. A. Coord. Chem. Rev. 2000, 199, 181-233. Gale, P. A.
Coord. Chem. Rev. 2001, 213, 79-128. Beer, P. D.; Gale, P. A. Angew.
Chem., Int. Ed. 2001, 40, 486-516. Schmidtchen, F. P.; Berger, M.
Chem. Rev. 1997, 97, 1609-1646. Beer, P. D.; Smith, D. K. Prog. Inorg.
Chem. 1997, 46, 1-96. Atwood, J . L., Holman, K. T.; Steed, J . W. Chem.
Commun. 1996, 1401-1407. Davis, A. P.; Gilmer, J . F.; Perry J . J .
Angew. Chem., Int. Ed. Engl. 1996, 35, 1312-1315. Supramolecular
Chemistry of Anions; Bianchi, A.; Bowman-J ames, K.; Garc´ıa-Espan˜a,
E. Eds.; Wiley-VCH: New York, 1997. Sessler, J . L.; Allen, W. E.
Chemtech 1999, 29, 16-24.
(6) Gale, P. A.; Sessler, J . L.; Kra´l, V. Chem. Commun. 1998, 1-8.
Anzenbacher, P., J r.; J ursikova, K.; Lynch, V. M.; Gale, P. A.; Sessler,
J . L. J . Am. Chem. Soc. 1999, 121, 11020-11021. Sessler, J . L.; Gale,
P. A. In The Porphyrin Handbook; Kadish, K. M.; Smith, K. M.;
Guilard, R., Eds.; Academic Press: San Diego, CA and Burlington, MA,
2000; Vol. 6, pp 257-278. Miyaji, H.; Sato, W.; Sessler, J . L. Angew.
Chem., Int. Ed. 2000, 39, 1777-1780. Gale, P. A.; Sessler, J . L.; Allen,
W. E.; Tvermoes, N. A.; Lynch, V. Chem. Commun. 1997, 665-666.
Sessler, J . L.; Andrievsky, A.; Gale, P. A.; Lynch, V. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 2782-2785.
(2) Moss, B. Chem., Ind. 1996, 407-411.
(3) Chloride Trasport Coupling in Biological Membranes and Epi-
thelia; Gerenscer, G.; Ed.; Elsevier: Amsterdam, 1984; Boat, T. F.;
Welsh, M. J .; Beaudet, A. L. In The Metabolic Basis of Inherited
Disease, 6th ed.; Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D.,
Eds.; McGraw-Hill: New York, 1989; p 2649.
(7) Scherer, M.; Sessler, J . L.; Gebauer, A.; Lynch, V. Chem.
Commun. 1998, 85-86. Scherer, M.; Sessler, J . L.; Moini, M.; Gebauer,
A.; Lynch, V. Chem. Eur. J . 1998, 4, 152-158.
(4) Brunetti, M.; Terracina, L.; Timio, M.; Saronio, P.; Capodicasa,
E. J Nephrol. 2001, 14, 27-31. Kajiyama, H.; Nojima, Y.; Mitsuhashi,
H.; Ueki, K.; Tamura, S.; Sekihara, T.; Wakamatsu, R.; Yano, S.;
Naruse, T. J . Am. Soc. Nephrol. 2000, 11, 923-7.
(8) Andrievsky, A.; Ahuis, F.; Sessler, J . L.; Vo¨gtle, F.; Gudat, D.;
Moini, M. J . Am. Chem. Soc. 1998, 120, 9712-9713.
(9) Schmuck, C.; Chem. Eur. J . 2000, 6, 709-718. Schmuck, C.
Chem. Commun. 1999, 843-844.
10.1021/jo016020g CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/19/2001