New strapped calix[4]pyrrole based receptor for anions

Article abstract of DOI:10.1016/j.ica.2011.02.004

Calix[4]pyrrole bearing catechol-derived diether strap linked via alkyl chains has been synthesized and characterized for the first time. The strap with 1,2-diether link is providing a relatively constrained geometry on its side of the calix[4]pyrrole moi

Full text of DOI:10.1016/j.ica.2011.02.004

Inorganica Chimica Acta 372 (2011) 281–285
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Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
New strapped calix[4]pyrrole based receptor for anions
a
Ritwik Samanta a, Sanjeev P. Mahanta a, Sauradip Chaudhuri a, Pradeepta K. Panda a,b, , Akkaladevi Narahari
⇑
a School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
b Advanced Centre of Research in High Energy Materials (ACRHEM), University of Hyderabad, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Available online 2 March 2011
Calix[4]pyrrole bearing catechol-derived diether strap linked via alkyl chains has been synthesized and
characterized for the first time. The strap with 1,2-diether link is providing a relatively constrained geom-
etry on its side of the calix[4]pyrrole moiety. As a result only one isomer (cis-type) of the receptor formed
during reaction. The crystal structure reveals two molecules of methanol bound to the host. This
calix[4]pyrrole also exhibits enhanced binding towards halide anions compared to simple calix[4]pyrrole
apart from showing binding towards dihydrogenphosphate and acetate ions. The association constants
are quite similar to that found for orcinol strapped calix[4]pyrrole towards halide anions in general,
but having a higher preference for chloride than bromide ion in particular. Further it shows very strong
preference towards fluoride ion.
Dedicated to Prof. S.S. Krishnamurthy.
Keywords:
Calix[4]pyrrole
Strapped calix[4]pyrrole
Anion binding receptor
Ó 2011 Elsevier B.V. All rights reserved.
1. Introduction
Calix[4]pyrrole 1 is a tetrapyrrolic macrocycle known for more
than hundred years [1]. However, recently it was observed that it
can also act as a host for both anions and neutral molecules [2].
These attributes are of great attraction to researchers in the last
two decades. In order to modulate the anion binding behavior of
the macrocycle, a large number of derivatives have been reported
by varying functional groups at the meso-carbons and b-pyrrole
position(s) and also by inversion of core (using N-confused pyrrole
approach) [3]. Enhanced binding could be achieved through single
side strapping of calix[4]pyrrole moiety by Lee’s group [4] and fur-
ther detailed studies were carried out in association with Sessler’s
group [5]. These calix[4]pyrroles were strapped using flexible
straps via 1,3-linkage to benzene derivatives and 2,5-heteroarenes
having diester, diether and diamide based alkyl chains [5,6]. Fur-
thermore porphyrins, binaphthol and coumarin were also used as
probes to study their binding abilities [7]. These strapped deriva-
tives possess large binding domains which help in modulating
their properties [4–7]. These receptors apart from displaying en-
hanced binding toward halides; show some selectivity toward
fluoride and chloride ions.
Recently, Gale and co-workers reported a 1,2,3-triazole strapped
calix[4]pyrrole along this line via click chemistry, which acts as a
good membrane transporter towards chloride ion [8a]. Very
recently Gale’s group reported another sets of strapped
calix[4]pyrroles where, two 1,2,3-triazoles were bridged through
alkyl chains of different length to tune their transport properties
[8b]. Among the strapped calix[4]pyrroles, only the furan strapped
calixpyrrole found to bind two methanol molecules [5c] whereas in
case of
3 one methanol bind to two adjacent NHs of the
calix[4]pyrrole moiety in 1,2-alternate fashion and the other one
H-bonded to another macrocycle in the solid state. In case of the
bis-triazole derivative, an additional methanol molecule is bound
to one of the already H-bonded methanol [8b]. Here, we wish to
⇑
Corresponding author at: School of Chemistry, University of Hyderabad,
Gachibowli, P.O. Central University, Hyderabad 500 046, India. Tel.: +91 40 2313
4818; fax: +91 40 2301 2460.
report the synthesis of
a new calix[4]pyrrole with flexible
catechol-derived diether strap on one side, its structure and anion
binding properties. This mode of strapping is expected to possess a
E-mail
addresses:
pkpsc@uohyd.ernet.in,
pradeepta.panda@gmail.com
(P.K. Panda).
0020-1693/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2011.02.004

282
R. Samanta et al. / Inorganica Chimica Acta 372 (2011) 281–285
relatively constrained binding domain and hence may display
some interesting host guest chemistry.
2.3. Synthesis
2.3.1. Synthesis of 7-[2-(6-oxo-heptyloxy)phenoxy]-2-heptanone (5)
A mixture of catechol (330 mg, 3 mmol) and K2CO3 (4.14 g,
30 mmol) in acetone (80 mL) was stirred well for about 1 h, and then
7-bromo-2-heptanone [10] (2.89 g, 15 mmol) was added. The
mixture was refluxed for 3 days and then filtered and solvent was
removed. The crude product was purified by column chromatogra-
phy over silica gel with increasing ratio of ethyl acetate in hexane.
The excess bromoketone is removed first (15% ethyl acetate in
hexane) and the desired product was collected as the next major
band and vacuum dried to give compound 5 as a viscous liquid
which solidifies when kept in refrigerator (700 mg; 70%). IR (neat):
2. Experimental
2.1. Materials
All analytical reagents were purchased from commercial
sources and used as received and all solvents were dried and puri-
fied as described by Armarego and Chai [9].
m
(cmÀ1) 2944–2865, 1715; 1H NMR (CDCl3): d in ppm 6.88 (s, 4H),
2.2. Methods
3.98 (t, 4H, J = 12 Hz), 2.46 (t, 4H, J = 16 Hz), 2.14 (s, 6H), 1.82 (m,
4H), 1.65 (m, 4H), 1.50 (m, 4H); 13C NMR (CDCl3): d in ppm 209.00,
149.23, 121.28, 114.36, 69.06, 43.7, 29.95, 29.24, 25.75, 25.64.
LC–MS m/z, M+H: 335.4 (Calc. for C20H31O4+H = 335.2).
NMR spectra were recorded on a BRUKER-AVANCE 400 MHz FT
NMR spectrometer at room temperature. Mass spectral determina-
tions were carried out using Shimadzu-LCMS-2010 mass spec-
trometer. IR spectra were recorded on JASCO FT/IR-5300. Crystal
data was collected on Oxford Gemini A Ultra diffractometer with
dual source. The binding constants were measured by isothermal
titration calorimetry studies using the instrument VP-ITC from
MicroCal, LLC, MA, USA.
2.3.2. Synthesis of 1,2-bis[6,6-di (pyrrol-2-yl)heptyloxy]benzene (6)
To a mixture of 5 (650 mg; 1.94 mmol) and pyrrole (5.35 mL;
77.72 mmol), trifluoroacetic acid (150
lL; 1.94 mmol) was added
at about 60 °C. The mixture was stirred for about 1.5 h and the
Scheme 1. Reagents and reaction conditions: (i) 7-bromo-2-heptanone, K2CO3, dry acetone, reflux; (ii) pyrrole, TFA, 60 °C; and (iii) acetone, BF3-etherate, room temperature.
Fig. 1. Ortep diagram of 4Á(MeOH)2 with the displacement ellipsoid drawn at 35% probability level, showing 1,2-alternate conformation of pyrrole units and the two bound
methanol molecules (left) and orientation of the strap with respect to the calix[4]pyrrole moiety (right). Hydrogen atoms, disordered atoms and methanol molecules (for right
only) have been omitted for clarity.

R. Samanta et al. / Inorganica Chimica Acta 372 (2011) 281–285
283
Fig. 2. Hydrogen bonding pattern of compound 4Á(MeOH)2. Here disordered atoms were removed for clarity.
reaction was quenched with triethylamine (1 mL). Excess reagents
3. Results and discussion
were removed under reduced pressure to get the crude product,
which was purified by column chromatography over silica gel
(10% ethyl acetate in hexane) to obtain the pure product 6 (1 g,
The desired strapped calix[4]pyrrole 4 was synthesized in three
steps from catechol (Scheme 1) following Lee’s method [5a].
However, we have to modify the reaction conditions in order to
get the optimal yields. For example, reaction of catechol with
7-bromo-2-heptanone to obtain 5 was very sluggish and needed
very long time to undergo completion. Increasing the scale of reac-
tion needed further increase of time and the completion of reaction
65%). IR (neat):
m
(cmÀ1) 3341, 2926–2870; 1H NMR (CDCl3): d in
ppm 7.59 (s, 4H), 6.98 (s, 4H), 6.56 (s, 3H), 6.17–6.13 (m, 9H),
4.03 (t, 4H), 2.04 (t, 4H), 1.8 (m, 4H), 1.6 (s, 6H), 1.4 (m, 4H),
1.35 (m, 4H); 13C NMR (CDCl3): d in ppm 149.20, 138.37, 121.28,
117.26, 114.34, 107.58, 104.78, 69.27, 41.06, 38.99, 29.26, 26.58,
26.42, 24.17; LC–MS m/z (M+H)
36H46N4O2+H = 567.4).
:
567.6 (Calc. for
C
2.3.3. Synthesis of strapped calix[4]pyrrole (4)
To a solution of 6 (750 mg; 1.32 mmol) and acetone (150 mL),
BF3ÁOEt2 (1 L; 0.38 mmol) was added. The solution was stirred
l
at room temperature for 10 min, after which product formation
was confirmed by TLC. The reaction was quenched by triethyl-
amine (1 mL) and solvent was removed. The crude mass was sub-
jected to column chromatography over silica gel (10% ethyl acetate
in hexane) to obtain the product as a colored species, which upon
subsequent washing with methanol yielded the pure macrocycle 4
as an off white powder (27 mg, 8%). 1H NMR (CDCl3): d in ppm 7.42
(s, 4H), 6.89 (s, 4H), 5.94 (m, 8H), 3.97 (t, 4H, J = 16 Hz), 1.95 (t, 4H,
J = 16 Hz), 1.82 (s, 4H), 1.68 (s, 6H), 1.52–1.50 (m, 16H), 1.24 (m,
4H); 13C NMR (CDCl3): d in ppm 149.42, 137.73, 136.9, 121.31,
114.37, 104.31, 103.69, 69.23, 41.48, 39.47, 35.63, 30.24, 29.50,
28.53, 26.68, 25.37; LC–MS m/z (MÀH): 645.75 (Calc. for
C42H54N4O2ÀH = 645.42).
Table 1
Association constant Ka, and thermodynamic parameters for the binding of anions
with 4 as measured by ITC (isothermal titration calorimetry) at 303 K in acetonitrile
using the corresponding tetrabutlyammonium salts (TBA) and fluoride as the
trihydrate.
TBA-salt
Ka
D
G
D
H
TDS
(kcal molÀ1
)
(kcal molÀ1
)
(kcal molÀ1
)
Chloride [11a]
Bromide [11b]
Fluoridea
Chloride
Bromide
1.37 Â 106 À8.51
3.1 Â 104 À6.24
1.17 Â 106 À8.42
2.12 Â 106 À8.78
1.95 Â 104 À5.97
1.28 Â 105 À7.09
À7.43
À7.1
1.08
À0.86
2.15
À2.42
À6.42
À3.36
À7.51
À6.27
À11.2
À12.39
À10.45
À14.48
Acetate
Dihydrogenphosphate 1.07 Â 105 À6.97
a
Measured in 0.5% water in acetonitrile.
Fig. 3. ITC of 4 with TBAF in 0.5% water in acetonitrile.

284
R. Samanta et al. / Inorganica Chimica Acta 372 (2011) 281–285
Fig. 4. 1H NMR competition experiment in acetonitrile-d3: (1) free host 4; (2) 4 with 1 equiv. of TBACl; and (3) 4 with 1 equiv. each of TBACl and TBAFÁ3H2O.
was always monitored by thin layer chromatography. Use of DMF
as solvent and higher temperature led to decrease in yield along
with decomposition of the excess bromoketone used (which could
be reused otherwise). Conversion of 5 to 6 was smooth. However,
the condensation of 6 with acetone yielded the desired macrocycle
4 (8%) exclusively as the cis-isomer only in 10 min. Longer reaction
time not only reduced the yield further but also, led to coloration of
the product which was not possible to remove by methanol wash-
ing; however there was no indication of the formation of the trans-
isomer. All the compounds were characterized by 1H NMR, 13C
NMR spectroscopy and mass analysis. Single crystal obtained by
slow evaporation of 4 from dichloromethane and methanol mix-
ture, when subjected to X-ray diffraction analysis, not only estab-
lished the structural integrity but also revealed few interesting
attributes of the macrocycle (Fig. 1). The macrocycle 4 found to
bind two methanol molecules, where one was bound to the NHs
of calixpyrrole moiety by hydrogen bonding and the other one H-
bonded to the remaining two pyrrolic NHs directed towards the
strap and oxygens of catechol moiety (Fig. 2). This type of host
guest behavior for strapped calix[4]pyrroles was so far not
reported for the benzene-based derivatives [4–7] and only recently
observed in case of furan strapped derivative [5c]. Compound 4
adopts a 1,2-alternate conformation for pyrrole units with the
catechol based strap slightly tilted towards one-half of the
calix[4]pyrrole unit.
and lesser towards bromide ion [5a]. Assuming that slight change
in condition can led to serious error in evaluation of binding affin-
ity, still we could come to the above conclusion as it is already
known presence of water can only decrease the Ka. Though the
Ka for fluoride appears to be lesser than chloride (Table 1), this
may be attributed to the presence of water. We attempted to deter-
mine the Ka value for fluoride following competitive experiment
using 1H NMR spectroscopy [4], but when equimolar ratio of fluo-
ride anion was added to already complexed chloride solution
(1:1 M ratio in CD3CN), we observed complete ejection of chloride
ions with the onset of signals corresponding to fluoride complex
exclusively (Fig. 4). Therefore, exact Ka in pure acetonitrile could
not be evaluated. However we can still assume that the Ka for fluo-
ride must be higher than the diester strapped calix[4]pyrrole
(highest so far reported to our knowledge) in which case a 6.3:1 ra-
tio of fluoride to chloride complexation observed, although it was
measured in DMSO-d6 [3]. Moreover, we can further conclude that
the role played by the aromatic CH in 2 and other related systems
towards anion binding (although large shift on CH signal upon
encapsulation of anion was observed) may not be significant [5–
7]. Moreover, the relatively constrained binding domain due to
the catechol derived strap could stabilize the fluoride and chloride
more effectively than the bromide. Further we observe moderately
strong association constant toward acetate and dihydrogenphos-
phate (Table 1), which was not reported for other related strapped
calix[4]pyrroles. This may be attributed to the additional hydrogen
bonding of oxygen atoms of catechol (already we observed in
methanol adduct) to the periphery of the anions which might be
at appropriate structural environment. Only very recently Gale’s
group reported a bistriazole strapped calix[4]pyrrole which also
shows binding towards a larger set of anions through a highly flex-
ible strap [8b].
The anion binding properties of 4 were studied by 1H NMR titra-
tion technique using acetonitrile-d3 as the solvent. The anions were
used as their corresponding tetrabutylammonium (TBA) salts. Pre-
liminary study with halides shows that 4 converted to its bound
form with ꢀ1.2 equiv. of fluoride, chloride or bromide anions and
the complexation follow slow exchange kinetics on NMR time
scale, and hence the binding constants could not be evaluated
(Supplementary data). However, it can be concluded that the com-
plexes follow 1:1 stoichiometry. Further, iodide does not show any
binding to the host. We carried out isothermal titration calorimetry
(ITC) in acetonitrile (HPCL grade obtained from Aldrich used as
such) solvent at 303 K to evaluate the association constants. In
all cases we observed exothermic host guest complexation that is
compensated to some extent by unfavorable entropy contribution
(Table 1). Except for the fluoride ion, in which case binding mea-
surement was carried out using 0.5% water in acetonitrile as the
solvent which give reproducible data for evaluation of association
constant (Fig. 3). This can be explained by taking note that fluoride
remains in hydrated form in aqueous acetonitrile and hence its
binding to the host led to the increase in the entropy contribution.
Compared to 1 large enhancement of association constants were
observed for all anions in case of 4 [11]. However when compared
with 2 (although it was measured using rigorously dried acetoni-
trile), we found 4 has a relatively higher affinity towards chloride
4. Conclusions
In this work we have prepared a new catechol derived strapped
calix[4]pyrrole where the binding domain is more constrained
compared to the earlier reported ones by slightly optimizing Lee’s
method. Due to the unique structural environment, this receptor
hosts two methanol molecules in solid state which was not ob-
served before for the benzene derived strapped derivatives. This
observation also led us to believe that suitable design of strap
can also enhance the binding towards neutral guest molecules
apart from anions. Presently we are exploring this aspect in details.
Compound 4 displays relatively higher affinity towards chloride
than bromide ion compared to 2 along with very strong preference
for fluoride ion. Further we could calculate reliable Ka for 4 towards
fluoride using 0.5% water in acetonitrile using ITC. Compound 4

R. Samanta et al. / Inorganica Chimica Acta 372 (2011) 281–285
285
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Acknowledgments
This work is supported by DST, India and ACRHEM, University of
Hyderabad. R.S. and S.P.M. thank CSIR, India for financial support.
S.C. (I.S.M., Dhanbad, India) thanks UGC Networking Center,
University of Hyderabad for the opportunity to work in this project
and financial support.
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