Hydrogen-bonding pyrrolic amide cleft anion receptors

Article abstract of DOI:10.1016/S0040-4039(01)00896-6

The use of simple 2,5-diamidopyrrole derivatives as anion receptors has been investigated. Reaction of 3,4-diphenylpyrrole-2,5-dicarboxylic acid chloride with n-butylamine or aniline has produced two new amidic cleft anion receptors 1 and 2. The anion-coo

Full text of DOI:10.1016/S0040-4039(01)00896-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5095–5097
Hydrogen-bonding pyrrolic amide cleft anion receptors
Philip A. Gale,* Salvatore Camiolo, Christopher P. Chapman, Mark E. Light and
Michael B. Hursthouse
Department of Chemistry, University of Southampton, Southampton SO17 1BJ, UK
Received 21 March 2001; accepted 24 May 2001
Abstract—The use of simple 2,5-diamidopyrrole derivatives as anion receptors has been investigated. Reaction of 3,4-
diphenylpyrrole-2,5-dicarboxylic acid chloride with n-butylamine or aniline has produced two new amidic cleft anion receptors 1
1
and 2. The anion-coordination ability of these species has been determined by H NMR titration techniques. Crystal structures
of 1 and 2 have been elucidated, revealing a continuous hydrogen bonding network formed by 1 and dimerization of 2 via NH···O
and CH···O hydrogen bonds. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
The anion coordination ability of receptors containing
pyrrole groups has been an area of increasing interest in
the last decade. Recent developments in the area of
anion recognition and sensing have produced a variety
of new selective complexation agents for anionic
guests.1 However, the great variety of anionic species
and their importance in the environment, in biological
systems and potential medical applications presents a
continuing challenge to design selective receptors.2 The
pioneering work of Sessler in the area of anion com-
plexation by pyrrolic macrocycles,3 of Beer4 and
Reinhoudt5 on amidic hydrogen bond donating anion
receptors, of Crabtree on anion coordination by amide
cleft species6 and the recent work of Schmuck on
carboxylate recognition by guanidinium substituted
pyrrole amides7 led us to speculate whether simple
pyrrole based amide cleft species would function as
efficient anion receptor species.8 In order to test this
hypothesis, two new pyrrolic cleft species 1 and 2 were
prepared from 3,4-diphenylpyrrole-2,5-dicarboxylic
acid chloride and their anion binding abilities studied
3,4-Diphenylpyrrole-2,5-dicarboxylic acid was prepared
via literature methods.9 The acid chloride was prepared
by refluxing the bis acid in thionyl chloride overnight
followed by rigorous drying under high vacuum. The
1
by H NMR titration techniques.
Figure 1. The X-ray crystal structure of 1 (butyl and phenyl
groups omitted for clarity) displaying a hydrogen bonding
network in the solid state.
* Corresponding author. E-mail: philip.gale@soton.ac.uk
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00896-6

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P. A. Gale et al. / Tetrahedron Letters 42 (2001) 5095–5097
Single crystals of compounds 1 and 2 were obtained
from CH2Cl2/EtOH and acetonitrile, respectively.13
Both compounds are involved in hydrogen bonding
arrays in the solid state. The two independent
molecules in crystals of 1 differ only in the conforma-
tion of the butyl chains and form pseudo centro-sym-
metric dimers via chemically equivalent hydrogen
bonds. The oxygen atoms then each accept a second
hydrogen bond to bridge the dimers into chains that
extend along the c axis (Fig. 1). Both independent
molecules in the crystal structure of 2 form centro-sym-
metric dimers via both NꢀH···O hydrogen bonds, and
CꢀH···O hydrogen bonds (Fig. 2).
bis acid chloride was then dissolved in dry
dichloromethane and 2.0 equiv. of either butylamine or
aniline (to produce compounds 1 or 2, respectively)
added with excess triethylamine and the reaction stirred
overnight. The resulting solution was reduced in vacuo
and the residue purified by column chromatography to
yield compounds 110 and 211 in 18 and 47% respective
yields.12
The association constants of compounds 1 and 2 with a
variety of putative anionic guests were measured using
1H NMR titration techniques by following shifts in the
amide NH proton resonance.14 In all cases the data was
indicative of 1:1 receptor:anion complex formation,
which was confirmed by Job plot analysis. The results
are shown in Table 1 and reveal that both 1 and 2
selectively bind oxo-anions in preference to fluoride,
chloride or bromide.
3. Conclusions
Receptors 1 and 2 are easy to make selective receptors
for oxo-anions. We are currently working to incorpo-
rate these pyrrolic cleft systems into a variety of more
complex anion receptor and sensor systems for selective
complexation and detection of oxo-anions. The results
of this work will be published in due course.
Figure 2. X-ray crystal structure of 2 showing dimerization
via two NH···O and two CH···O hydrogen bonds in the solid
state.
Table 1. Association constants of 1 and 2 (M−1) with
various anionic guest species at 25°Ca
Acknowledgements
P.A.G. would like to thank the Royal Society for a
University Research Fellowship and the EPSRC for a
project studentship (to S.C.).
Compound
Aniona
Solvent
Ka (M−1 b
)
1
1
1
1
Fluoridec
Chloridec
Bromide
Dihydrogen
phosphate
Benzoate
Fluoride
CD3CN
CD3CN
CD3CN
CD3CN
85
138
B10
357
References
1
2
CD3CN
DMSO/H2O
0.5%
DMSO/H2O
0.5%
DMSO/H2O
0.5%
DMSO/H2O
0.5%
2500
74
1. (a) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001,
40, 486–516; (b) Gale, P. A. Coord. Chem. Rev. 2001, 213,
79–128; (c) Gale, P. A. Coord. Chem. Rev. 2000, 199,
181–233.
2. Supramolecular Chemistry of Anions; Bianchi, A. K.;
Bowman-James, K.; Garcia-Espan˜a, E. Eds.; Wiley-
VCH: New York, 1997.
3. Sessler, J. L.; Gale, P. A. In The Porphyrin Handbook,
Kadish, K. M.; Guilard, R.; Smith, K. M., Eds.; Aca-
demic Press: San Diego, CA and Burlington, MA, 2000;
Vol. 6, pp. 257–278; Andrievsky, A.; Ahuis, F.; Sessler,
J. L.; Vo¨gtle, F., Gudat, D.; Moini, M. J. Am. Chem.
Soc. 1998, 120, 9712–9713.
4. Beer, P. D. Chem. Commun. 1996, 689–696.
5. Antonisse, M. M. G.; Reinhoudt, D. N. Chem. Commun.
1998, 443–448.
2
2
2
2
Chloride
Bromide
11
B10
1450
560
Dihydrogen
phosphate
Benzoate
DMSO/H2O
0.5%
a Anions added as tetrabutylammonium salts dried under high vac-
uum with heating at 70°C for 24 h prior to use. Acetonitrile water
content=0.03%. Solubility problems prevented studies on com-
pound 2 to be conducted in acetonitrile solution.
b Errors estimated to be <15%.
c The amount of water present in the acetonitrile can have a dramatic
effect on fluoride/chloride selectivity. In the presence of 0.5% water,
fluoride is bound with a stability constant of 37.5 M−1, whereas
chloride is bound more weakly (K=12.5 M−1).
6. Kavallieratos, K.; de Gala, S. R.; Austin, D. J.; Crabtree,
R. H. J. Am. Chem. Soc. 1997, 119, 2325–2326.
7. Schmuck, C. Chem. Eur. J. 2000, 6, 709–718.

P. A. Gale et al. / Tetrahedron Letters 42 (2001) 5095–5097
5097
8. Interestingly, N-unsubstituted pyrrole groups with amide
moieties in the and positions are present in
analysis 2+ 1/3 H2O calcd C, 77.73; H, 5.15; N, 9.07.
Obs. C, 77.90; H, 4.76; N, 8.80.
2
4
pyrronamycins, novel antitumor antibiotics: Asai, A.;
Sakai, Y.; Ogawa, H.; Yamashita, Y.; Kakita, S.; Ochiai,
K.; Ashizawa, T.; Mihara, A.; Mizukami, T.; Nakano, H.
J. Antibiot. 2000, 53, 66–69.
12. The moderate yields of these reactions are attributed to
the formation of other species (see Boatman R. J.; Whit-
lock, H. W. J. Org. Chem. 1976, 41, 3050–3051). The
crystal structure of a four-component condensation by-
product was elucidated (see Ref. 13).
9. Friedman, M. J. Org. Chem. 1965, 30, 859–863.
10. Spectroscopic data for compound 1: 1H NMR (300 MHz,
DMSO-d6): l 0.91 (t, 6H, J=7.26, CH3), 1.23 (m, 4H,
CH2CH3), 1.37 (m, 4H, CH2), 3.20 (m, 4H, NCH2), [7.10
(t, 2H, J=5.46, Ar), 7.18 (m, 4H, Ar), 7.30 (m, 4H, Ar),
+obscured amide CONH, 2H], 12.03 (s, 1H, NH). 13C
NMR (75.48 MHz, CDCl3): l 13.7, 19.9, 31.2, 39.0,
124.1, 125.7, 128.1, 128.9, 130.9, 133.6, 160.4. +ve ESMS
(857.6 2 M+ Na+). Elemental analysis: 1+1/2 H2O: calcd:
C, 73.21; H, 7.56; N, 9.85. Obs. C, 72.82; H, 7.37; N,
9.75.
13. Crystallographic data (excluding structure factors) for the
structures in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplemen-
tary publication numbers CCDC 160246 (compound 1),
CCDC 160248 (compound 2) and CCDC 160247 (by-
product (see Ref. 12)). Copies of the data can be
obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK [fax: +44 (0)
1223-336033 or e-mail: deposit@ccdc.cam.ac.uk]. After
the original submission of this manuscript, a similar
hydrogen-bonding motif to that observed in compound 2
has been reported in a methyl 5-amidopyrrole-2-carboxy-
late (see: Schmuck, C.; Lex, J. Eur. J. Org. Chem. 2001,
1519–1523).
11. Spectroscopic data for compound 2: 1H NMR (300 MHz,
DMSO-d6): l 7.15 (t, 2H, J=7.29, Ar), 7.34 (m, 14H,
Ar), 7.55 (d, 4H, J=8.19, Ar), 9.37 (s, 2H, CONH), 12.67
(s, 1H, NH). 13C NMR (75.48 MHz, DMSO-d6): 119.3,
123.5, 124.7, 126.8, 127.2, 127.8, 128.7, 130.5, 133.7,
138.5, 158.6. +ve ESMS (937.4 2 M+ Na+). Elemental
14. Hynes, M. J. J. Chem. Soc., Dalton Trans. 1993, 311–312.
.