Synthesis of redox-active biscalix[4]quinones and their electrochemical properties

Article abstract of DOI:10.1016/S0040-4039(02)02520-0

Biscalix[4]arenes, 7 and 8, have been synthesized by a one-pot coupling method and a stepwise approach, respectively. One-pot reaction in a pressurized vessel resulted in the symmetric biscalix[4]arene 7 in high yield. Oxidation of compounds 7 and 8 by Tl(CO₂CF₃)₃ in CF₃COOH yielded biscalix[4]quinones, 9 and 10, respectively. Preliminary electrochemical studies by cyclic voltammetry of 9 and 10 show significant changes of their voltammograms upon addition of Na⁺.

Full text of DOI:10.1016/S0040-4039(02)02520-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 33–36
Synthesis of redox-active biscalix[4]quinones and their
electrochemical properties
Kriengkamol Tantrakarn, Chalita Ratanatawanate, Tipsukhon Pinsuk, Orawon Chailapakul and
Thawatchai Tuntulani*
Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
Received 15 September 2002; revised 28 October 2002; accepted 8 November 2002
Abstract—Biscalix[4]arenes, 7 and 8, have been synthesized by a one-pot coupling method and a stepwise approach, respectively.
A one-pot reaction in a pressurized vessel resulted in the symmetric biscalix[4]arene 7 in high yield. Oxidation of compounds 7
and 8 by Tl(CO CF ) in CF COOH yielded biscalix[4]quinones, 9 and 10, respectively. Preliminary electrochemical studies by
2
3 3
3
+
cyclic voltammetry of 9 and 10 show significant changes of their voltammograms upon addition of Na . © 2002 Elsevier Science
Ltd. All rights reserved.
Sensing technology and sensors have advanced in the
past decade. Chemists play a very important role in the
substituents at the other o-phenoxy groups can also be
varied. Upon oxidation, we expect to obtain various
kinds of biscalix[4]quinones possessing a different num-
ber and various positions for the quinone moieties. This
should lead to new selectivity and sensitivity for the
compounds.
1
development of chemical sensors. Typically, a chemical
sensor composes of two important parts: a receptor
2
unit and a signaling unit. The signaling unit can give
either electrochemical or optical responses. The most
popular signaling units used by chemists are ferrocene
3
,4
and p-quinone. The fabrication of sensory units and
sensors can be carried out in a suitable way for sensing
metal ions, anions or organic molecules.
Biscalix[4]arene 7 has been synthesized in one step.
Nucleophilic substitution reactions of p-tert-butyl-
calix[4]arene (1) with bromoethyl tosylate (3) using
7
K CO as base yielded compound 7 in 41% yield. This
2
3
Calix[4]arene is one of the most versatile molecular
building blocks suitable for attaching both receptor and
sensory units to the same molecules. Many calix[4]arene
reaction also produced bisbromoethoxy calix[4]arene in
23% yield. This result implies that the coupling process
occurred in a stepwise manner in which bisbro-
moethoxy calix[4]arene was produced in the first step.
Subsequent nucleophilic substitution with another unit
of calix[4]arene resulted in 7. Janssen et al. found that
the use of pressure for selective alkylation of
calix[6]arene resulted in a high yield of the alkylated
3
4
derivatives containing ferrocene and p-quinone have
been synthesized and their binding and sensing proper-
ties towards metal ions and anions have been studied.
However, calix[4]quinones, in particular, are superior to
ferrocenes because of the direct involvement of the
calixarene framework. Therefore, one can design and
construct a molecular sensor from a calix[4]quinone
using its available oxygen atoms as donors for binding
8
products. Ostaszewski and Jurczak also reported the
use of high pressure in the synthesis of simple and
chiral bicyclic cryptands and diazacoronands that pro-
5
9
alkali cations. This should enhance both the selectivity
duced the desired products in high yield. The high-
and sensitivity of the sensors. A number of biscalixare-
nes have been synthesized and their binding studies
with metal ions have been reported. It is of interest to
synthesize different biscalix[4]arenes using ethylene
bridges connecting lower rim phenoxy groups. The
pressure approach was thus used in the synthesis of 7
aiming to increase the cyclization rate. The reaction
between 1 and bromoethyl tosylate (3) in acetonitrile in
6
the presence of K
CO
in a pressurized vessel which
at 50 psi and heated at 100°C
yielded 7 in 69% yield as shown in Eq. (1). Compound
was thus obtained in a very high yield upon applying
2
3
was compressed with N
2
10
7
Keywords: biscalixarene; quinone; cyclic voltammetry.
high pressure, and bisbromoethoxy calix[4]arene was
not found in the reaction.
*
Corresponding author.
0
040-4039/03/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02520-0

3
4
K. Tantrakarn et al. / Tetrahedron Letters 44 (2003) 33–36
CH OH into its CH Cl solution. The compound 4 was
3
2
2
subsequently reduced with 3 equiv. of LiAlH in dry
4
12
THF at 0°C to yield the dialcohol 5 in 97% yield. To
facilitate the nucleophilic substitution reaction, the
–
OH groups were changed to methylsufonate (mesyl)
groups by the addition of methanesulfonyl chloride (3.0
equiv.) in the presence of Et N (3 equiv.) and a catalytic
3
1
3
amount of DMAP. The disulfonyl ester 6
was
obtained in 96% yield. The compound 6 acts as a
building block for constructing both symmetric and
unsymmetric biscalix[4]arenes. Finally, the coupling
reaction of 1 and 6 in CH CN using K CO as base
3
2
3
resulted in the symmetric biscalix[4]arene 7 in 24%
yield. It is clearly seen that in the case of the symmetric
biscalix[4]arene, the one-pot synthetic approach gives
much higher yields than that of the stepwise synthesis.
Nevertheless, the stepwise synthesis is good for prepar-
ing unsymmetric biscalixarenes. The coupling reaction
(
1)
The one-pot synthesis is only suitable for preparing a
symmetric biscalix[4]arene. To synthesize unsymmetric
biscalix[4]arenes for further fabrication to bis-
calix[4]quinones having different quinone moieties,
however, needs stepwise synthetic approaches. Com-
pounds 7 and 8 can be prepared in a stepwise manner
as shown in Scheme 1.
14
of 6 and 2 in THF using NaH as base resulted in the
15
unsymmetric biscalix[4]arene 8 in 18% yield. The oxi-
dation of compounds 7 and 8 using Tl(CF CO ) in
3
2 3
CF COOH resulted in yellowish biscalix[4]tetra-
3
16
quinone, 9 (21%), and biscalix[4]arenediquinone, 10
(56%), respectively.
17
The diethyl ester calix[4]arene 4 was synthesized
according to the published procedure with slight mod-
ification. The reaction of 1 with ethyl bromoacetate
2.5 equiv.) in CH CN using K CO as base and reflux-
ing for 4 h resulted in compound 4 which can be easily
separated from the mixture in 85% yield by addition of
1
1
Echegoyen and co-workers have shown that there are
marked perturbations of the quinone redox couples of
(
3
2
3
5
calix[4]quinones on addition of sodium cations. We
thus investigated the electrochemical properties of com-
Scheme 1.

K. Tantrakarn et al. / Tetrahedron Letters 44 (2003) 33–36
35
Figure 2. Voltammogram of 10 in 20% DCM in CH CN using
3
tetrabutylammonium tetrafluoroborate (TBABF ) as support-
4
ing electrolyte at various scan rates.
+
On addition of Na (1 equiv.) to the solution of 10, a new
wave at −0.880 V appears in the voltammogram. How-
+
Figure 1. Voltammogram of 9 in 20% DCM in CH CN using
3
ever, upon adding excess Na , the current of the wave
tetrabutylammonium tetrafluoroborate (TBABF ) as support-
4
at −0.880 V increases, waves 1 and 2 disappear and a
quasi-reversible wave at −1.334 V appears in the voltam-
mogram (Fig. 3). In addition, wave 3 at −1.754 V
becomes reversible. Biscalix[4]quinone 10 thus shows a
ing electrolyte at a scan rate of 50 mV/s.
pounds 9 and 10 by cyclic voltammetry in 20% DCM in
+
significant change of its CV waves upon complexing Na .
CH CN using tetrabutylammonium tetrafluoroborate
3
18
(
TBABF ) as supporting electrolyte. Compound 9
4
In summary, we have synthesized two new bis-
calix[4]arenes (7 and 8) and two biscalix[4]quinones (9
showed two broad quasi-reversible redox waves 1 and 2
at −1.235 and −1.790 V, respectively (Fig. 1) indicating
a complicated electron transfer mechanism which was
quite similar to the behavior of the biscalix[4]arene
tetraquinone possessing a longer spacer reported by Beer
1
9
and co-workers. Interestingly, upon addition of 1
+
−
equiv. of Na (ClO4 as counter cation), a new reversible
reduction wave at −0.885 V appears in the voltam-
mogram and the quasi-reversible reduction wave 2 shifts
more anodically while wave 1 shifts insignificantly.
+
However, adding excess Na results in the disappearance
of both waves 1 and 2 and the appearance of an+
irreversible wave at −1.466 V. This may indicate that Na
forms a more stable complex with the reduced form of
9.
Cyclic voltammograms (CV) of compound 10 exhibit
three waves 1, 2 and 3 at −1.092, −1.201 and −1.754 V,
respectively (Fig. 2). This voltammogram is similar to the
calixdiquinone esters and amides reported by Beer and
2
0
colleagues. The first two couples indicate two one-elec-
tron transfer processes. Wave 3 is an irreversible wave
probably involving a reduction of the quinone to its
radical form and subsequent protonation to the
hydroquinone. However, upon increasing the scan rate,
two new irreversible oxidation waves appear at −0.750
and −0.337 V. This may signify that wave 3 represents
a two-electron transfer reduction process. The result
suggests that 10 undergoes an electron transfer, electron
transfer and chemical reaction (EEC) mechanism.
+
Figure 3. Voltammogram of 10 upon addition of Na in 20%
DCM in CH CN using tetrabutyl ammonium tetrafluoroborate
(TBABF ) as supporting electrolyte at a scan rate of 50 mV/s.
3
4

3
6
K. Tantrakarn et al. / Tetrahedron Letters 44 (2003) 33–36
and 10). We also show that the use of pressure increases
the yield of the symmetric biscalix[4]arene 7. Cal-
ixquinones 9 and 10 exhibit interesting electrochemical
obtained a white solid of 7. The product was recrystal-
lized in dichloromethane upon addition of methanol to
1
afford a white crystalline solid (2.16 g, 69%). 7: H NMR
+
properties and show a promising ability to sense Na .
spectrum (200 MHz, CDCl ) l 7.65 (s, 4H, ArOH), 7.00
3
We are currently pursuing electrochemical studies of
the compounds synthesized towards other alkali metal
ions and the results will be reported in due course.
(s, 8H, m-HArOH), 6.82 (s, 8H, m-HArOCH CH ArH),
2
2
4.55 (s, 8H, ArOCH CH OAr), 3.55 and 4.50 (d each,
2
2
JH–H=14.0 Hz, 16H, Ar CH Ar), 1.25 (s, 36H, HOAr-t-
2
C H ), 0.99 (s, 36H, ROAr-t-C H ). FAB MS (m/z):
4
9
4
9
+
+
4
1
8
367.8 [M +NH ]. Anal. calcd for 7 (C H O ): C,
92 116
8
Acknowledgements
1.86; H, 8.66. Found: C, 81.86; H, 8.86.
11. Collins, E. M.; McKervey, M. A.; Madigan, E.; Moran,
M. B.; Owens, M.; Ferguson, G.; Harris, S. J. J. Chem.
This work was financially supported by the Thailand
Research Fund (Grant no. RSA/06/2544). Authors
thank Professor Jeremy Kilburn for the ESI MS results.
Soc., Perkin Trans. 1 1991, 3137.
1
1
2. 5: H NMR spectrum (200 MHz, CDCl ) l 9.23 (s, 2H,
3
ArOH), 7.07 (s, 4H, m-HOArH), 7.01 (s, 4H, m-
ROArH), 5.2 (s, 2H, -CH CH OH), 4.29 (t, 8H,
2
2
ArOCH CH OH), 3.43 and 4.30 (d, JH–H=14.0 Hz, 8H,
2
2
References
ArCH Ar), 1.20 (s, 18H, ROAr-t-C H ), 1.19 (s, 18H,
2
4
9
HOAr-t-C H ).
3. 6: H NMR spectrum (200 MHz, CDCl ) l 7.06 (s, 4H,
4
9
1
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3
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2
3
4.64 (m, 4H, MsCH CH O), 3.36 (m, 8H, ArCH Ar and
2
2
2
MsOCH CH O), 4.24 (d, J
=13 Hz, 4H, ArCH Ar),
2
2
H–H
2
3.23 (s, 6H, SO CH ), 1.28 (s, 18H, HOAr-t-C H ), 0.90
2 3 4 9
(
s, 18H, ROAr-t-C H ).
4 9
1
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1
1
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5. 8: H NMR spectrum (200 MHz, CDCl ) l 7.09–6.70 (m,
3
18H, HAr and ArOH), 4.78–4.12 (m, 22H, OCH CH O,
2 2
1
999, 40, 7343.
ArCH Ar and –OCH ), 3.40–3.15 (m, 8H, ArCH Ar),
2
3
2
5
. G o´ mez-Kaifer, M.; Reddy, P. A.; Gutsche, C. D.;
Echegoyen, L. J. Am. Chem. Soc. 1994, 116, 3580.
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nati, A.; Freriks, M.; Pochini, A.; Ugozzoli, F.; Ungaro,
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P.; de Mendoza, J. Synthesis 1993, 380.
1.30 (s, 18H, Ar-t-C H ), 1.25 (s, 18H, Ar-t-C H ), 0.92
4 9 4 9
+
4 9 4
+
(
s, 36H, Ar-t-C H ). ESI MS (m/z): 1395.2 (M +NH ).
6
7
1
1
6. 9: H NMR spectrum (200 MHz, CDCl ) l 7.10 (s, 8H,
3
ROArH), 5.86 (s, 8H, Hquinone), 4.39 (s, 8H,
OCH CH O), 4.52 and 3.00 (dd, JH–H=13.9 Hz, 16H,
2
2
8
ArCH Ar), 1.33 (s, 36H, Ar-t-C H ). ESI MS (m/z):
2
4
9
+
+
4 CO
−1
1203.4 (M +4H+NH ). IR (w ): 1664.86 cm . Anal.
calcd for 9 (C H O ·2H O): C, 74.98; H, 6.62. Found:
76
76 12
2
C, 74.99; H, 6.20.
9
. Jurczak, J.; Ostaszewski, R. J. Coord. Chem. Part B 1992,
2
1
1
7. 10: H NMR spectrum (200 MHz, CDCl ) l 7.15 (br s,
3
7, 201.
0. In a high pressure tube (Ace Glass Co., Catalog No.
648-29) equipped with valves and pressure gauge, p-tert-
12H, HArOR), 6.50 (s, 4H, Hquinone), 4.70–4.40 (m, 16H,
1
OCH CH O, ArCH Ar), 4.15 (s, 6H, -OCH ), 3.38–3.12
2
2
2
3
8
(
1
m, 8H, ArCH Ar), 1.30 (s, 36H, Ar-t-C H ), 0.80 (s,
2 4 9
8H, Ar-t-C H ). ESI MS (m/z): 1315.8 (M +4H+NH ).
butylcalix[4]arene, 1, (3.0 g, 4.62 mmol), catalytic amount
of 18-crown-6, bromoethyl tosylate, 3, (1.3 g, 4.62 mmol)
and K CO (1.3 g, 9.24 mmol) were suspended in anhy-
+
4 9 4
+
−
1
IR (wCO): 1657.14 cm . Anal. calcd for 10
C H O ·3H O): C, 76.64; H, 7.93. Found: C, 77.20;
2
3
(
drous acetonitrile (10 mL). The tube was then pressurized
86 100 10
2
H, 8.52.
with N at 50 psi. The mixture was stirred and heated at
2
1
8. CV experiments were carried out on an AUTOLAB
PGSTAT100 potentiostat using a glassy carbon working
electrode, a Ag/AgNO3 reference electrode and a plat-
inum auxiliary electrode. All experiments were performed
1
00°C for 4 days. The solution was allowed to cool to
room temperature. The pressure in the tube was then
released. The solvent was evaporated to dryness to yield
a
yellow residue. The residue was dissolved in
under N2.
dichloromethane (100 mL) and an aqueous solution of 3
M hydrochloric acid was subsequently added until the
pH of the solution reached pH 1. The mixture was
extracted with dichloromethane (3×50 mL). The com-
bined organic layer was dried over anhydrous Na SO ,
1
9. Webber, P. R. A.; Chen, G. Z.; Drew, M. G. B.; Beer, P.
D. Angew. Chem., Int. Ed. 2001, 40, 2265.
0. Beer, P. D.; Gale, P. A.; Chen, Z.; Drew, M. G. B.;
Heath, J. A.; Ogden, M. I.; Powell, H. R. Inorg. Chem.
1997, 36, 5880.
2
2
4
filtered and concentrated on rotary evaporator to