Convenient synthesis of tripodal-pyrrole receptor and anion binding properties

Article abstract of DOI:10.1007/s10847-009-9700-0

Pyrrole-based tripodal receptors have been synthesized and characterized. The synthesis utilized an unusual direct nucleophilic substitution of tris-(bromomethyl)-2,4,6-trimethybenzene with pyrrole. The anion binding studies indicate that the acetate anio

Full text of DOI:10.1007/s10847-009-9700-0

J Incl Phenom Macrocycl Chem (2010) 66:209–212
DOI 10.1007/s10847-009-9700-0
ORIGINAL ARTICLE
Convenient synthesis of tripodal-pyrrole receptor and anion
binding properties
•
•
•
Seong-Jin Hong Jaeduk Yoo Seung-Doo Jeong
Chang-Hee Lee
Received: 22 June 2009 / Accepted: 4 November 2009 / Published online: 19 November 2009
Ó Springer Science+Business Media B.V. 2009
Abstract Pyrrole-based tripodal receptors have been
synthesized and characterized. The synthesis utilized an
unusual direct nucleophilic substitution of tris-(bromo-
methyl)-2,4,6-trimethybenzene with pyrrole. The anion
binding studies indicate that the acetate anion binds pref-
erentially with synthesized receptors over other anions.
demonstrated the potential utilities as recognition motif for
various guest molecules [16]. Most of the reported systems
utilize stilbazolium [17], oxazoline [18], trifluoroacetoph-
enone [19] and imidazole [20, 21]. However, there are
limited reported examples of tripodal anion receptors
utilizing pyrroles as hydrogen bond donors [22–24].
Accordingly, we are currently examining to develop new
pyrrole-based receptor tripodal systems, which potentially
bind with multi-oxo anions possibly with high selectivity.
With these regards, we report herein a convenient syn-
thesis of new tripodal receptor bearing three pyrroles on the
side of 1,3,5-trisubstituted-2,4,6-trimethylbenzene scaffold.
The receptor is based on pyrrole as hydrogen bonding donor
and benzene as cavitand scaffold. Direct nucleophilic
substitution of alkyl halide with pyrrole is rare. Although
the C-alkylation of pyrrole on C2 position using reactive
alkyl halides such as allyl and benzyl has been reported [25, 26],
there is only few report for the regioselective one-pot pyr-
role alkylation from simple alkyl halides and pyrrole [27].
Keywords Anion recognition Á Tripodal receptor Á
Pyrrole Á Tri-substituted benzene
The development of selective recognition for anions has
received considerable interests in supramolecular chemis-
try due to increasing importance of anions in expanding
areas such as the environment and biology [1–4]. A useful
way of recognition of anions is to exploit the non-covalent
interaction between host and guest. In general, most of the
anion receptors commonly possess amide, urea, amidinium
or pyrrole, which are capable of binding anion via hydro-
gen bonding [5]. Recently, we also have reported several
model systems based on the calix[4]pyrroles. The system,
so called ‘strapped-calix[4]pyrroles’ have shown signifi-
cant enhancement in affinity and even in selectivity toward
various anionic species [6–11]. Since pyrrole-based anion
receptors developed by us and others [12–15] possess high
affinity with various anions, we are interested in incorpo-
ration of pyrrole moiety to the tripodal arm as recogni-
tion elements. The tripodal receptor systems have been
Experimental
Proton NMR spectra (400 MHz) were recorded using TMS
as the internal standard. High and Low resolution FAB
mass spectra were obtained on an AUTO SPEC M-363
high-resolution mass spectrometer. Column chromatogra-
phy was performed over silica gel (Merck, 230–400 mesh).
All other reagents were obtained from Aldrich and used as
received unless noted otherwise.
S.-J. Hong Á J. Yoo Á S.-D. Jeong Á C.-H. Lee (&)
Department of Chemistry and Institute of Molecular Science &
Fusion Technology, Kangwon National University, Chun-Chon
200-701, Korea
e-mail: chhlee@kangwon.ac.kr
URL: http://cc.kangwon.ac.kr/*chhlee
Synthesis of compound 2 and 3
To the solution of compound 1 (1.00 g, 2.51 mmol) and
K2CO3 (1.04 g, 7.53 mmol) in CH2Cl2 (5 mL) was added
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J Incl Phenom Macrocycl Chem (2010) 66:209–212
Scheme 1 Synthesis of
receptor 1
HN
HN
Br
Br
K2CO3
CH2Cl2
+
+
N
H
NH
NH
H
N
Br
NH
2. 17%
3. ~1%
1
pyrrole (17.4 mL, 251 mmol). The whole mixture was
allowed to stir for 4 h at room temperature. The reaction
was combined with water (50 mL), then the mixture was
extracted with CH2Cl2 (30 mL 9 3). The organic layer
was dried (Na2SO4) and the solvent was removed in vacuo.
The residue was purified by column chromatography on
silica (hexanes/EtOAc = 4/1) to afford compound 2
(0.15 g, 17%) and 3 (3 mg, 1%) as white solid. Spectro-
scopic data for 2: 1H NMR (400 MHz, CDCl3) d 2.27
(s, 9H), 4.06 (s, 6H), 5.80 (s, 3H), 6.11–6.13 (m, 3H), 6.61–
6.63 (m, 3H), 7.72 (brs, 3H); 13C NMR (100 MHz, CDCl3)
d 16.47, 29.12, 105.55, 108.53, 116.19, 129.87, 134.06,
134.56; EI MS Calcd. for C24H27N3 357.22, Found 357.00;
1
for 3: H NMR (400 MHz, CDCl3) d 2.24 (s, 3H), 2.29
Fig. 1 1H NMR spectral change of receptor 2 (8.96 mM) upon
titration with AcO- (as its tetrabutylammonium salt) in CDCl3 at
25 °C
(s, 6H), 3.92 (s, 2H), 4.06 (s, 4H), 5.82 (s, 2H), 6.02–6.03
(m, 1H), 6.11–6.13 (m, 2H), 6.29 (s, 1H), 6.59–6.61 (m, 2H),
6.69–6.71 (m, 1H), 7.26 (brs, 2H) 7.96 (brs, 1H); 13C NMR
(100 MHz, CDCl3) d 16.38, 16.46, 28.41, 29.08, 105.39,
108.48, 108.59, 115.39, 116.01, 117.73, 122.27, 130.18,
133.57, 133.64, 134.25, 137.08; EI MS calcd. for C24H27N3
357.22, Found 357.00.
(Fig. 1). Anion concentration-dependent shifts of signals
were observed upon titration with anions (F-, Cl-, Br-,
AcO- and H2PO4-, as their tetrabutylammonium salts, at
25 °C). Typical spectral changes upon titration with anion
were shown in Fig. 1.
Upon addition of tetrabutylammonium acetate to a
solution of 2 (8.96 mM) in CDCl3, significant complexa-
tion-induced downfield shift of the pyrrolic NHs and slight
upfield shifts of b-pyrrole protons were observed. The
pyrrole N–H protons originally observed at 7.72 ppm were
shifted to 9.26 ppm in the presence of 10 equivalents of
acetate anion.
Results and discussion
As shown in Scheme 1, direct nucleophilic substitution
reaction of 1,3,5-trisbromomethyl-2,4,6-trimethylbenzene
[28] 1 with pyrrole in the presence of K2CO3 afforded
desired products 2 in 17% yield and small amount of
compound 3 was also identified. The identity of the syn-
thesized receptors 2 and 3 was fully confirmed by proton
NMR spectroscopy and high resolution mass spectrometry.
As shown in Fig. 2, addition of the tetrabutylammonium
acetate induced the largest chemical shifts changes com-
pared with other anions. In the case of the fluoride anion,
the NH signal was broadened after *5 equivalents of
anion were added. Based on the corresponding binding
isotherm, association constant (Ka) was then calculated
using a nonlinear curve fitting with a 1:1 association model
[29, 30]. Unfortunately, the poor interaction abilities were
observed with low stability constants of *10 M-1. The
affinity constants for fluoride, chloride, bromide, and
dihydrogenphosphate were lower than *5 M-1. However,
the system displayed somewhat selective toward acetate
anion and fluoride anion over other anions. Quantitative
data were not obtained due to the small differences in
binding affinity.
1
The H NMR spectrum of receptor 2 showed one set of
pyrrolic NH protons at 7.72 ppm along with three sets of
pyrrolic protons. The single Ar-CH3 proton appeared at
2.27 ppm and single benzylic protons shown at 4.06 ppm
clearly reveal that compound 2 is C3 symmetry. In the case
of compound 3, two different signals of pyrrole N–H
protons were observed at 7.26 and 7.96 ppm with 2/1
integration ratio, which clearly indicate that one of the
three appended pyrroles on the rim of benzene has different
connection.
The study of the anion binding properties of receptor 2
was carried out in CDCl3 using proton NMR spectroscopy
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J Incl Phenom Macrocycl Chem (2010) 66:209–212
211
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Fig. 2 1H NMR titration profiles of receptor 2 (8.96 mM) with
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fluoride anion, the NH signal was broadened after *5 equivalents of
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In conclusion, pyrrole-based tripodal for anion receptor
attached on the upper rim of benzene scaffold was syn-
thesized. Although the poor interaction abilities were
observed, the receptor 2 showed higher affinity toward
acetate anion over other anions. We are currently focused
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anion selectivity and sensitivity.
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Acknowledgments This work was supported by the grant from
Korea Research Foundation (C00477) and BK21. The Vascular
System Research Center (VSRC) at KNU is acknowledged for
support.
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