Preparation of new azobenzene crown ether p-tert-butylcalix[4]arenes and their roles as switchable ionophores for Na+ and K+ ions

Article abstract of DOI:10.1016/S0040-4039(00)01550-1

New azobenzene crown ether p-tert-butylcalix[4]arenes (6 and 7) have been synthesized by reductive coupling reactions between two nitrobenzene groups. Their isomerization and switchable binding properties towards Na⁺ and K⁺ were stud

Full text of DOI:10.1016/S0040-4039(00)01550-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9095–9100
Preparation of new azobenzene crown ether
p-tert-butylcalix[4]arenes and their roles as switchable
ionophores for Na+ and K+ ions
Bongkot Pipoosananakaton,a Mongkol Sukwattanasinitt,a Nongnuj Jaiboon,a
Narongsak Chaichitb and Thawatchai Tuntulania,*
aDepartment of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
bDepartment of Physics, Faculty of Science, Thammasat University at Rangsit, Pathumthani 12121, Thailand
Received 6 September 2000; accepted 14 September 2000
Abstract
New azobenzene crown ether p-tert-butylcalix[4]arenes (6 and 7) have been synthesized by reductive
coupling reactions between two nitrobenzene groups. Their isomerization and switchable binding proper-
1
ties towards Na+ and K+ were studied by H NMR spectroscopy. The results showed that Na+ preferred
to bind the cis form of 6 while K+ preferred to bind the trans isomer. © 2000 Published by Elsevier
Science Ltd.
Keywords: azobenzene; calixarene; isomerization; switchable ionophore.
Azobenzenes make up an interesting class of compounds that exhibit photoresponsive
properties. They have been incorporated into a number of supramolecular frameworks to
produce ionophores for transports and photo-switchable receptors.1 We are interested in
constructing a switchable molecular system which can selectively bind Na+ or K+ mimicking the
biological Na+/K+ pump.2 According to a report by Swager and co-workers, it was found that
bithiophene calix[4]arenes containing six ethereal oxygen donors were able to bind Na+ and K+
to different extents.3 In the same manner, we anticipated that an azobenzene crown calix[4]arene
would also form complexes with both Na+ and K+, and the binding abilities could then be
switchable. We therefore synthesized two azobenzene crown ether calix[4]arenes (6 and 7) and
studied their isomerization properties.
* Corresponding author.
0040-4039/00/$ - see front matter © 2000 Published by Elsevier Science Ltd.
PII: S0040-4039(00)01550-1

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One way to synthesize compounds 6 and 7 would be to attach two ethoxy nitrobenzene
groups into the calix[4]arene framework. Reductive coupling of nitrobenzene groups would then
be carried out to afford the azobenzene crown ether calix[4]arenes. This synthetic approach is
depicted in Scheme 1. Nitrobenzene calix[4]arenes, 4 and 5, were synthesized by nucleophilic
substitution reactions of 2-(2-bromoethoxy)nitrobenzene, 3,4 with p-tert-butylcalix[4]arene, 1,5
and dimethoxy p-tert-butylcalix[4]arene, 2,6 respectively. In a typical reaction, 1 (6.48 g, 10.00
mmol) and potassium carbonate (1.45 g, 10.49 mmol) were mixed in acetonitrile (230 mL) and
refluxed for 3 hours. Compound 3 (4.92 g, 20.00 mmol) was then added slowly into the reaction
mixture which was then refluxed further for 4 days. Upon separation and crystallization,
sugar-like crystals of 4 were obtained (6.50 g, 66%).7 A similar reaction between 2 and 3
produced 5 in 20% yield.8 It should be noted that the yield of 5 was significantly lower than that
of 4 due to the steric congestion of the methoxy group which may decelerate the reaction rate.
1
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While the H NMR spectrum of 4 was quite simple, the H NMR spectrum of 5 showed
complicated broad signals signifying the existence of conformational isomerism of the
calix[4]arene framework similar to the tetramethoxy calix[4]arene due to the lack of intramolec-
ular hydrogen bonding.9 Subsequently, reductive coupling reactions of 4 and 5 were carried out.
A mixture of 4 (0.70 g, 0.71 mmol) in isopropanol (8 mL), sodium hydroxide (0.28 g, 7.00 mmol)
in H2O (4 mL) and zinc (0.20 g, 3.06 mmol) was stirred and refluxed under nitrogen for 48
hours. After standard workup and purification on a silica gel column using 15% ethyl
acetate/hexane as eluant, 6 was able to crystallize from hot methanol to give orange crystals
(0.05 g, 8%).10 A similar coupling reaction of 5 afforded 7 as orange crystals in 12% yield.11 The
1H NMR spectrum of 7 was quite well resolved, compared to that of 5. This implies that the
calix[4]arene compartment of 7 becomes more rigid and stays in a cone conformation upon the
formation of the azobenzene crown ether ring.
Scheme 1. Reagents and conditions: (i) when R=H: K2CO3, CH3CN, reflux, 4 days; when R=CH3: K2CO3, KOH
i
(3 pellets), CH3CN, reflux, 4 days; (ii) PrOH, NaOH/H2O, Zn, reflux, 2 days
We were able to obtain crystals of both 6 and 7. However, only crystals of 6 were suitable for
single crystal X-ray analysis. The X-ray structure12 of 6 in Fig. 1 shows that the azobenzene unit
is in the trans form and a molecule of ethyl acetate has been included into the calix[4]arene unit
,
pointing the ꢀCH2CH3 moiety into the upper rim cavity. The NꢁN distance is 1.179 (6) A. The

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relative torsion angle of C(48)ꢀN(2)ꢀN(1)ꢀC(54) is 178.35° suggesting that the azobenzene unit
is almost flat. The ethereal and hydroxy oxygen atoms are preorganized for binding cations.
Recently, Thue´ry and co-workers have reported the crystal structure of 2,2%-azobenzene-substit-
uted calix[4]arene-crown-6 which possessed longer glycolic units and the azobenzene unit in a
trans form.13
Figure 1. Crystal structure of 6. Hydrogen atoms were omitted for clarity
Nakamura and colleagues have demonstrated the use of UV spectrophotometry to study
photoisomerization of azobenzocrown ethers.14 Unfortunately, both trans and cis plus trans
forms of our compounds gave almost the same UV spectra. We, therefore, studied photoisomer-
ization of 6 and 7 using 1H NMR spectroscopy. Typically, an NMR tube containing 6 or 7 (3.28
mmol) in CDCl3 (0.7 mL) was placed in a photo-reactor (quartz) and irradiated with a 180 W
1
mercury low-pressure lamp for at least 4 hours. The isomerization process was followed by H
NMR using a Bruker 400 MHz NMR spectrometer. The 1H NMR spectra of 6 and 7 before and
after irradiation are depicted in Fig. 2. The following signals belonging to the cis isomer of 6
appear distinctively in the spectrum after irradiation: t-Bu (1.21 and 1.19 ppm), ArCH2Ar (3.31
and 4.35), ROArH (6.97), HOArH (7.06) and ArOH (8.41). The ratio of cis and trans can then
be estimated from the integral area of the signals to be 36:64. Interestingly, we found that upon

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standing in the dark at room temperature for several days, compound 6 in CDCl3 also
underwent trans to cis isomerization. This result correlates with the observation of Vicens and
colleagues in which azobenzene calixcrowns containing one glycolic unit were stable as the cis
isomers.15 However, thus far, we cannot isolate the cis isomer of 6.
1
Figure 2. H NMR spectra of 6 (a) before, (b) after irradiation and 7 (c) before and (d) after irradiation
1
The H NMR spectrum of 7 also changed dramatically after irradiation and upon standing in
the dark for several hours. However, we cannot conclusively say that the cis–trans isomerization
has occurred since we do not have a crystal structure of 7 to substantiate the isomer of the
1
azobenzene moiety before irradiation. However, a H NMR spectrum of 7 in Fig. 2(d) shows
t
complicated signals of aromatic, methylene bridge and Bu protons which may result from
various conformations of the calix[4]arene unit. We suspect that 7 may just undergo conforma-
tional change rather than the cis–trans isomerization.
Owing to the complicated conformational behavior of 7, only the switchable binding property
of 6 towards Na+ and K+ was investigated. The picrate salts of Na+ and K+ ions were employed
in complexation studies. The metal salts were added into the ligand in CDCl3 before and after
UV irradiation.16 1H NMR spectra (Fig. 3) of complexes of 6 after addition of sodium and
potassium picrates possessed two doublet signals at 3.26 and 4.20 ppm (Jꢀ13 Hz) indicating
that 6 maintained the cone conformation of calix[4]arene after complexation with the metal ions.
The spectrum in Fig. 3(a) shows a singlet signal due to picrate protons at 8.64 ppm. The broad
peak of the glycolic protons of the trans isomer at 4.44 ppm separates from those of the cis
isomer at 4.40 ppm and multiplet signals appear around 6.82–6.93 ppm. Furthermore, the
doublet peaks of the methylene bridge protons of the trans form at 3.26 ppm and the cis form
at 3.32 ppm shift slightly from those of the free ligand. It was found from the integration that
the amount of the cis isomer increased from 36 to 47%. Addition of potassium picrate into 6
results in an appearance of a singlet signal due to the picrate protons at 8.92 ppm (Fig. 3(b)).
The intensity of the signals corresponding to the cis isomer decreases dramatically. The
integration showed that the percentage of cis isomer decreased from 36 to 10%, and on the other
hand, the amount of the trans isomer increased to 90%. However, upon standing under the
room light, the amount of the cis form gradually increased to 25% after standing for 19 days,

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and reached 42% in 30 days. We do not have a definite explanation for the increasing
concentration of the cis isomer. However, it is possible that K+ firstly formed a complex with the
trans form of 6 and increased the percentage of the trans form. Later, the thermal trans to cis
isomerization took place and increased the amount of the cis form. The result also implies that
the stability of the trans-6·K complex is not very strong.
1
Figure 3. Partial H NMR (400 MHz, CDCl3) of 6 in the presence of (a) Na+ (b) K+. * Denotes signals of the solvent
We have demonstrated that 6 can possibly be used as a switchable ionophore for Na+ and K+
ions in which the cis form of 6 is suitable for binding Na+ while the trans form is appropriate
for K+. We are currently investigating conformational behaviors of compound 7 upon binding
alkali metal ions and developing 6 and 7 to be switchable sensors for Na+ and K+ ions. The
results will then be reported in due course.
Acknowledgements
The authors would like to thank Professor Somsak Ruchirawat for his permission to use a
photo-reactor and a mercury lamp at Chulabhorn Research Institute. This work was financially
supported by the National Annual Budget (1999).
References
1. Balzani, V.; Scandola, F. Supramolecular Photochemistry; Ellis Horwood: New York, 1991; pp. 199–215 and
references cited therein.
2. Kaim, W.; Schwederski, B. Bioinorganic Chemistry: Inorganic Elements in the Chemistry of Life; John Wiley &
Sons: New York, 1994; pp. 281–284.
3. Marcella, M. J.; Newland, R. J.; Carroll, P. J.; Swager, T. M. J. Am. Chem. Soc. 1995, 117, 9842.

9100
4. Compound 3 was prepared from the reaction between o-nitrophenol and 1,2-dibromoethane in the same manner
as 2-(2%-bromoethoxy)benzaldehyde in: Seangprasertkij, R.; Asfari, Z.; Arnaud, F.; Weiss, J.; Vicens, J. J. Incl.
Phenom. 1992, 14, 141. For 3: lH (200 MHz; CDCl3) 3.65 (2 H, t, J 6.0, -OCH2CH2Br), 4.40 (2 H, t, J 6.0,
-OCH2CH2Br), 7.02–7.10 (2 H, m, aromatic), 7.52 (1 H, t, J 8.0, aromatic), 7.81 (1 H, d, J 8.0, aromatic); anal.
calc. for C8H8BrNO3: C, 39.05; H, 3.28; N, 5.69. Found C, 39.07; H, 3.21; N, 5.65. Mp: 164–165°C.
5. Gutsche, C. D.; Iqbal, M. Org. Synth. 1989, 68, 234.
6. Gutsche, C. D.; Dhawan, B.; Levine, J. A.; No, K. H.; Bauer, L. J. Tetrahedron 1983, 39, 409.
7. For 4: lH (200 MHz; CDCl3) 0.94 and 1.28 (18 H each, s, t-Bu protons), 3.28 (4 H, d, J 13.0, ArCH2Ar),
4.26–4.33 (8 H, m, ArCH2Ar and -OCH2CH2O-), 4.45–4.47 (4 H, m, -OCH2CH2O-), 5.19 (2 H, s, HOAr), 6.75
(4 H, s, HOArH), 6.95 (2 H, t, J 8.0, nitrobenzene), 7.03 (4 H, s, ROArH), 7.24 (2 H, d, J 8.0, nitrobenzene),
7.46 (2 H, t, J 7.0, nitrobenzene), 7.7 (2 H, d, J 8.0, nitrobenzene); anal. calc. for C60H70N2O10: C, 73.60; H, 7.21;
N, 2.86. Found C, 73.62; H, 7.27; N, 2.73. Mp: 205–207°C.
8. For 5: lH (200 MHz; CDCl3) 0.84 and 1.05 (9 H each, br s, CH3OArt-Bu), 1.28 (18 H, br s, ROArt-Bu),
3.00–3.40 (4 H, br, ArCH2Ar), 3.47 (6 H, s, -OCH3), 3.60–4.60 (12 H, br, ArCH2Ar and -OCH2CH2O-),
6.40–6.69 (4 H, br, CH3OArH), 6.92–7.30 (8 H, br, nitrobenzene and ROArH), 7.51 (2 H, t, J 7.0, nitrobenzene),
7.81 (2 H, d, J 8.0, nitrobenzene); anal. calc. for C62H74N2O10: C, 73.93; H, 7.40; N, 2.78. Found C, 73.92; H,
7.46; N, 2.76. Mp: 189–191°C.
9. van Hoorn, W. P.; Briels, W. J.; van Duynhoven, J. P. M.; van Veggel, F. C. J. M.; Reinhoudt, D. N. J. Org.
Chem. 1998, 63, 1299; Fisher, S.; Grootenhuis, P. D. J.; Groenen, L. C.; van Hoorn, W. P.; van Veggel, F. C.
J. M.; Reinhoudt, D. N.; Karplus, M. J. Am. Chem. Soc. 1995, 117, 1611; Shinkai, S.; Iwamoto, K.; Araki, K.;
Matsuda, T. Chem. Lett. 1990, 1263.
10. For 6 (trans form): lH (400 MHz; CDCl3) 1.03 and 1.20 (18 H each, s, t-Bu protons), 3.20 and 4.15 (4 H each,
d, JAB 13.0, ArCH2Ar), 4.38 and 4.84 (4 H each, br t, -OCH2CH2O-), 6.86 (4 H, s, ROArH), 6.92 (4 H, s,
HOArH), 7.08 (2 H, t, J 6.0, azobenzene), 7.16 (2 H, d, J 8.0, azobenzene), 7.34 (2 H, t, J 6.0, azobenzene), 7.61
(2 H, s, HOAr), 7.70 (2 H, d, J 8.0, azobenzene); anal. calc. for C60H70N2O6·C4H8O: C, 76.62; H, 7.84; N, 2.79.
Found C, 77.21; H, 7.51; N, 2.72. Mp: 195–197°C (decomp.). UV/vis [u (nm), m (dm3 mol−1 cm−1)]: 344, 19233;
446, 3167.
11. For 7: lH (400 MHz; CDCl3) 0.82 and 1.28 (18 H each, s, t-Bu protons), 3.10 and 4.23 (4 H each, d, JAB 12.0,
ArCH2Ar), 3.44 (6 H, s, -OCH3), 4.34 and 4.63 (8 H, m, -OCH2CH2O-), 6.42 (4 H, s, CH3OArH), 6.94 (2 H, m,
azobenzene), 7.01 (4 H, s, ROArH), 7.08 (4 H, m, azobenzene), 7.41 (2 H, m, azobenzene); anal. calc. for
C62H74N2O6: C, 78.95; H, 7.91; N, 2.97. Found C, 79.06; H, 7.91; N, 2.97. Mp: 228–230°C. UV/vis [u (nm), m
(dm3 mol−1 cm−1)]: 334, 19385; 440, 7714.
12. Crystallographic data (excluding structure factors) for 6·C4H8O2 have been deposited with the Cambridge
Crystallographic Data Center (CCDC 137509). Copies of the data can be obtained on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK (fax: +44 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).
13. Thue´ry, P.; Nierlich, M.; Saadioui, M.; Asfari, Z.; Vicens, J. Acta Crystallogr., Sect. C 1999, 55, 443.
14. Tahara, R.; Morozumi, T.; Nakamura, H. J. Phys. Chem. B 1997, 101, 7736.
15. Saadioui, M.; Asfari, Z.; Vicens, J.; Reynier, N.; Dozol, J. F. J. Incl. Phenom. 1997, 28, 223; Saadioui, M.; Asfari,
Z.; Vicens, J. Tetrahedron Lett. 1997, 38, 1187; Saadioui, M.; Asfari, Z.; Thue´ry, P.; Nierlich, M.; Vicens, J.
Tetrahedron Lett. 1997, 38, 5643.
16. The results obtained when metal picrates were added before and after irradiation of 6 are essentially the same.
.