Comparative study of azobenzene and stilbene bridged crown ether p-tert-butylcalix[4]arene

Article abstract of DOI:10.1016/j.tet.2004.11.020

Photo-switchable calixarenes consisting of a stilbene or azobenzene bridge, spanning the narrow rim as a switching unit, were synthesized through reductive coupling of o-, m- and p-bis-benzaldehyde and bis-nitrobenzene-substituted calix[4]arenes. Both cis- and trans-stilbenes were produced from the reductive coupling of the o- and m-bis-benzaldehyde with the cis isomer being predominant for both regioisomers, whilst the coupling of p-bis-benzaldehyde gave only cis product. On the other hand, the only isolable product obtained from the reductive coupling of bis-o- and bis-m-nitrobenzene was the corresponding trans-azobenzene and the coupling product from bis-p-nitrobenzene was not stable. Each of the synthesized compounds showed a photostationary state in their cis-trans isomerization. The complexation of alkali metal ions was observed for only the o-azobenzene derivative suggesting that the lone pair of N-atom in the azo bridge participates in this process.

Full text of DOI:10.1016/j.tet.2004.11.020

Tetrahedron 61 (2005) 1317–1324
Comparative study of azobenzene and stilbene bridged crown
ether p-tert-butylcalix[4]arene
Rojrit Rojanathanes,a Bongkot Pipoosananakaton,a Thawatchai Tuntulani,a
Worawan Bhanthumnavin,a James B. Orton,b Simon J. Cole,b Michael B. Hursthouse,b
Martin C. Grosselb and Mongkol Sukwattanasinitta,
*
aDepartment of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
bSchool of Chemistry, University of Southampton, Southampton, UK
Received 28 July 2004; revised 12 October 2004; accepted 5 November 2004
Available online 15 December 2004
Abstract—Photo-switchable calixarenes consisting of a stilbene or azobenzene bridge, spanning the narrow rim as a switching unit, were
synthesized through reductive coupling of o-, m- and p-bis-benzaldehyde and bis-nitrobenzene-substituted calix[4]arenes. Both cis- and
trans-stilbenes were produced from the reductive coupling of the o- and m-bis-benzaldehyde with the cis isomer being predominant for both
regioisomers, whilst the coupling of p-bis-benzaldehyde gave only cis product. On the other hand, the only isolable product obtained from the
reductive coupling of bis-o- and bis-m-nitrobenzene was the corresponding trans-azobenzene and the coupling product from bis-p-
nitrobenzene was not stable. Each of the synthesized compounds showed a photostationary state in their cis–trans isomerization. The
complexation of alkali metal ions was observed for only the o-azobenzene derivative suggesting that the lone pair of N-atom in the azo bridge
participates in this process.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
a desired cation using the electron-rich pocket of donor
atoms.6 Since their discovery crown ether based ion
receptors have been exploited extensively. Synthetic cation
channels containing crown ether rings, called hydraphiles,
have been reported recently.7 These hydraphile channels
can kill Escherichia coli bacteria effectively via incorpor-
ation into the surface membrane, thus disturbing sodium ion
transport rate across the bacteria cell membrane.
On a cell membrane, there are plenty of specific receptors
that control the diffusion of molecules or ions in and out of
the cell; these include the potassium channel,1 maltoporin2
and sucroporin,3 which control the diffusion of potassium
ion, maltose and sucrose respectively. To specifically
complex each particular molecule or ion, the shape and
size of the receptor must exclusively fit with the preferred
guest. An extraordinary natural molecule that is always
chosen as an example of a receptor because of its extremely
high binding specificity, is valinomycin, which can
specifically complex potassium ions.4,5 This cyclic
molecule is composed of numerous oxygen donor atoms
forming a nice pocket that fits perfectly around a potassium
ion guest.
Beside the donor atoms themselves, the pre-organized
structure of the binding pocket is also a vital factor of
binding properties. Calix[4]arene has become one of the
most interesting platforms on which to construct a selective
receptor molecule because of its four pre-organized
conformations; cone, partial-cone, 1,2 alternating-cone
and 1,3 alternating-cone.8 The very first application of this
well-ordered molecule as a cation receptor was calix[4]-
arene crown ether, which can be used to trap a cesium ion as
a result of its optimal fit.9 Many receptors developed
nowadays are calixarene-based but there is a crucial
drawback of such a perfect fit host-guest pairs. The stronger
the binding, the more difficult it becomes to regenerate the
receptor after use. A proper attachment of a molecular
switching unit to the receptor molecule should overcome
this problem. There are many switching systems available,
but among them, the photo-switching mode is one of the
Aspiring to mimic or at least understand such natural
processes, chemists have tried to design and synthesize
novel molecules having particularly desired functions. The
crown ether family is an appealing class of structures, which
has been developed to mimic valinomycin by entrapment of
Keywords: Calixarene; Diazobenzene; Stilbene; Ionophore.
* Corresponding author. Tel.: C66 22 187620; fax: C66 22 1875298;
e-mail: smongkol@chula.ac.th
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.11.020

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R. Rojanathanes et al. / Tetrahedron 61 (2005) 1317–1324
most easy-to-operate systems.10 Azobenzene and stilbene
are widely used because of their facile cis–trans photo-
isomerization.11 Additionally, another appealing advantage
potentially gained from switchable receptors is that
amphiphilic-binding may be achieved.12,13 During isomer-
ization the binding cavity is altered and the binding property
is then switched. This may be from binding to unbinding or
from binding of one ion to another as a result of the change
in the size and shape of the binding pocket before and after
isomerization.
The m-stilbene derivatives were prepared under modified
McMurry conditions to give both cis- and trans-stilbenes in
28% total yield (Table 1). This reaction also gave 20% of
the corresponding pinacol byproduct. The coupling reaction
of the o- and p-bisbenzaldehydes gave higher yields of the
stilbenes o-1 and p-1 (67 and 51% respectively) without any
observable pinacol product. Both cis- and trans-stilbenes
were obtained from the coupling reactions involving the o-
and m-bis-benzaldehydes but that for the p-isomer gave only
cis-stilbene. It is important to note here that McMurry
coupling proceeded successfully despite the presence of
phenolic O H groups in the starting materials.
We report herein the synthesis of two series of photo-
switchable calix[4]arene derivatives. One series incorpor-
ates a stilbene and the other an azobenzene switching unit as
a bridge across the narrow rim of the calixarene platform.
Photoisomerization and complexation properties of the
synthesized compounds are also compared.
Table 1. Products from the synthesis of stilbene and azobenzene crown
ether calixarenes
Products
% Yield
cis
trans
o-1
m-1
p-1
o-2
m-2
p-2
57
20
51
0
0
0
10
8
0
2. Results and discussion
2.1. Synthesis
8
59a
0
a via high-pressure method.
Three positional isomers, o-, m- and p-stilbene crown ether
p-tert-butylcalix[4]arenes (1) were synthesized from the
corresponding bis-benzaldehydes by the McMurry coupling
(Scheme 1).14,15 The bis-benzaldehydes were prepared from
the corresponding (2-bromoethoxy)benzaldehydes by
nucleophilic substitution of p-tert-butylcalix[4]arene with
the corresponding (2-bromoethoxy)benzaldehyde.
The predominant preference for formation of cis over trans
products in the McMurry coupling suggests that the pre-
organized structure of the starting bis-benzaldehyde p-tert-
butylcalix[4]arene may play an important role in controlling
the geometry of the products. The short ethylene glycol
linkages attached to the small and rigid lower rim of the
p-tert-butylcalix[4]arene are unlikely to allow formation of
the threo orientation of the two benzaldehyde moieties
(Fig. 1) resulting in no evidence for formation of the trans-
product.
Scheme 1. Synthesis of stilbene crown ether calixarenes.
Figure 1. The proposed orientations, erythro and threo, of the two
benzaldehyde groups that would lead to the formation of cis and trans
products.
Analogously, all of the isomers of the azobenzene crown
ether calixarenes (2) were synthesized by reductive
coupling of the corresponding bis-nitrobenzenes
(Scheme 2), these latter having been prepared by nucleo-
philic substitution of the corresponding (2-bromoethoxy)-
nitrobenzene analogues.12
In the synthesis of the o-azobenzene crown ether calixarene
at ambient pressure, only trans isomer was isolated in 8%
yield. The cis isomer could not be obtained in a pure form
because of its rapid thermal isomerization. In the case of the
m-isomer a higher yield of the azobenzene product was
observed compared to that obtained for the o-isomer
because the high-pressure method was used (Table 1). The
p-isomer however seemed to be unstable as the color of the
solution at the end of the reaction changed rapidly from
bright orange to dark brown upon exposure to air and
moisture and none of the desired product could be isolated.
2.2. Characterization of products
Since all of the cis- and trans-stilbene derivatives possess a
C2 symmetry axis, the coupling between two vinylic protons
Scheme 2. Synthesis of azobenzene crown ether calixarenes.

R. Rojanathanes et al. / Tetrahedron 61 (2005) 1317–1324
1319
in 1H NMR, which would normally be used for distinguish-
ing between cis and trans isomers, does not exist. The
assignment of cis and trans geometries was thus initially
based on the chemical shift of vinylic protons and the UV–
Vis absorption spectra using the parent cis and trans
unsubstituted stilbenes as references. According to the
chemical shifts observed for unsubstituted stilbenes, the cis
geometry was assigned to the isomer possessing the vinylic
protons with lower chemical shift values (Table 2). This
assignment is consistent with the data from UV–Vis spectra
that showed shorter lmax and lower extinction coefficients
for all cis isomers.
Fortunately, both azobenzene derivatives (o-2 and m-2)
could be obtained as single crystals suitable for X-ray
crystallography. The solid-state structures of these azo-
benzene derivatives revealed that both compounds were the
trans isomers (Fig. 3).
2.3. Isomerization study
Whilst none of the stilbene crown ether p-tert-butylcalix[4]-
arenes reported here isomerized in ambient light, they
readily did so under UV irradiation (medium pressure
mercury lamp). The cis and trans isomer-percentages for
each derivative at the photostationary state were determined
by 1H NMR spectroscopy using the ratios of the peak areas
of the best resolved resonances corresponding to each
geometric isomer (Fig. 4).
Table 2. 1H NMR (in CDCl3) and electronic absorption (in CH2Cl2) data of
the synthesized stilbene-calix derivatives in comparison with stilbene
Compound
d for vinylic
proton (ppm)
lmax (nm)
3 (cmK1 MK1
)
The resonances of the corresponding protons in the cis and
trans forms of each regioisomer (aromatic protons ortho to
vinylic carbon for o-1, t-butyl protons for m-1, ethylene
glycolic protons for p-1, methylene bridge protons in o-2
and ethylene glycolic protons for m-2) were selected for the
ratio calculation. The photo-stationary states were observed
for all isomers and the percentages of cis and trans isomers
cis-o-1
trans-o-1
7.25
7.74
292
291
333
286
291
308
320
283
223
276
227
294
307
19,321
30,106
28,492
20,955
27,488
24,866
24,629
16,632
20,600
10,900
21,000
33,200
32,100
cis-m-1
6.71
7.24
trans-m-1
1
cis-p-1
cis-stilbene
6.68
6.57
were obtained from the H NMR data (Table 3).
For stilbene derivatives, the same photostationary state was
reached, no matter which geometrically pure isomer, cis or
trans, was used as the starting material. However, in the
case of the azobenzene analogues, the irradiation was
performed on the only available, trans isomer.
trans-stilbene
7.15
The structural assignments were confirmed by X-ray
crystallography. The proposed cis-o-1 was successfully
isolated as a single crystal (Fig. 2). The X-ray data was in
agreement with the proposed structure.
Unlike the stilbene derivatives, the azobenzene calixarenes
isomerized even in the absence of light because of the usual
thermal isomerization of the diazo (N]N) unit.16 While the
photoisomerization of both stilbenes and azobenzenes under
a medium pressure Hg lamp took minutes, the thermal
isomerization of the azobenzenes was much slower, taking
over a week to reach the equilibrium. Both thermal and
photochemical isomerizations of the azobenzene derivatives
produced the same final cis:trans product ratios implying
that, under our experimental conditions, the product ratio
from the photoizomerization directly correlates with the
relative thermal stability of each isomer.
2.4. Complexation study
Picrate salt extraction was chosen for the complexation
study. The complexation can be observed by several
techniques: color change, 1H NMR, and UV–Visible
spectroscopy. To our surprise, (1H NMR) complexation
studies using each of the compounds synthesized revealed
that only o-2 showed any evidence for complexation with
sodium and potassium picrate (Fig. 5).
Figure 2. X-ray crystallographic structure of cis-o-1.
The complexation results suggested that the lone pair
electrons on nitrogen of the diazo group participated in the
binding with the metal ions. Thus, only o-2, which possesses
at least one nitrogen lone pair of electrons pointing into the
crown ether biding cavity, can form a host-guest complex. It
is also interesting to point out here that the complexation of
o-2 with NaC and KC ion shifted the thermal equilibrium
between the cis and trans isomers in opposite directions.
In the synthesis of azobenzene derivatives, only one product
was isolated for each regioisomer, o-2 and m-2. Since only
one stereoisomer of each azobenzene derivative is available
and, in the absence of protons on the nitrogen atoms
providing an NMR probe, the assignment of cis and trans
geometry was only possible through X-ray crystallography.

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R. Rojanathanes et al. / Tetrahedron 61 (2005) 1317–1324
Figure 3. X-ray crystallographic structure of trans-o-2$CH3CO2CH2CH3 and trans-m-2.
The complexation with KC resulted in the equilibrium shift
toward the trans isomer (compare Fig. 5c with b) while the
complexation with NaC moved the equilibrium toward the
cis isomer (compare Fig. 5d with b).
Unfortunately, we have not been able to crystallize the o-2
metal complex as a single crystal to confirm our hypothesis
about the participation of the nitrogen lone pair in the
complexation. However, we have studied the complexation
of the model compounds, calixarene derivatives 3 and 4
with sodium and potassium picrates. When solid sodium (or
potassium) picrate was added to the colorless solution of 4
in CH2Cl2, the solution turned yellow and the UV–Visible
spectrum showed a strong absorption band of the picrate ion
Figure 4. 1H NMR signals used for calculation of cis/trans ratio at the
photostationary state: (a) aromatic protons ortho to vinylic carbon in o-1;
(b) t-butyl protons in m-1; (c) ethylene glycolic protons in p-1;
(d) methylene bridge protons in o-2; and (e) ethylene glycolic protons in
m-2.
Table 3. The percentages of cis and trans isomers at the photostationary
states
Compound
% Isomer at photostationary state
cis
trans
o-1
m-1
p-1
o-2
m-2
15
70
75
36
13
85
30
25
64
87
Figure 5. 1H NMR spectra of: (a) trans-o-2; (b) cis- and trans-o-2 at the
photostationary state; (c) o-2 with potassium picrate; and (d) o-2 with
sodium picrate. (picZpicrate, cZcis, tZtrans).

R. Rojanathanes et al. / Tetrahedron 61 (2005) 1317–1324
1321
4. Experimental
4.1. Data for compounds
4.1.1. Synthesis of bis-benzaldehyde. In a 1 L, two-necked,
round-bottomed flask equipped with a magnetic stirring bar
and
a reflux condenser, p-tert-butyl-calix[4]arene
(7.8 mmol, 5.00 g) and K2CO3 (57.9 mmol, 8.00 g) were
dissolved in CH3CN (300 mL). The mixture was stirred for
30 min at room temperature and (2-bromoethoxy)-benzal-
dehyde (17.5 mmol, 4.00 g) was then added dropwise. The
mixture was refluxed for 60 h and then allowed to cool to
room temperature. The mixture was filtered and washed
with acetone and CH2Cl2. The filtrate was combined and the
solvent was evaporated under reduced pressure. The
resulting residue was dissolved in CH2Cl2 (150 mL) and
then extracted with aqueous HCl (2 M, 4!25 mL). The
organic phase was separated and dried over anhydrous
Na2SO4. The solvent was removed under reduced pressure.
The product was further purified by crystallization in
CH2Cl2/CH3OH yielding a white solid as the product.
o-isomer (5.5 mmol, 5.16 g, 70%). 1H NMR (200 MHz,
CDCl3) d 1.00 (s, 18H), 1.24 (s, 18H), 3.29 (d, 4H, JZ
13.0 Hz), 4.29 (d, 4H, JZ13.0 Hz), 4.38–4.40 (m, 8H), 6.85
(s, 4H), 7.00 (s, 4H) 6.94–7.04 (m, 4H), 7.50 (s, 4H), 7.45–
7.55 (m, 2H), 7.82 (dd, 2H, JZ7.5, 2.0 Hz), 10.48 (s, 2H);
13C NMR (50 MHz, CDCl3) d 31.1, 31.7, 31.8, 33.8, 34.0,
67.5, 73.6, 112.4, 121.0, 125.2, 125.2, 125.8, 127.7, 128.2,
132.6, 135.8, 141.7, 147.3, 149.8, 150.3, 160.8, 190.2.
Figure 6. UV–Vis spectra of 3 and 4 in CH2Cl2 in the presence of sodium
picrate salt added as a solid.
around 375 nm (Fig. 6), although there were minimal
changes in the 1H NMR spectrum upon complex formation.
The mixture of 3 and sodium (or potassium) picrate in
CH2Cl2, on the other hand, showed no absorption band
corresponding with picrate anion. These results indicated
that while compound 4 which contains eight oxygen donor
atoms complexed with sodium and potassium ions,
compound 3 which contains only six oxygen donor atoms
complexed with neither ions. The results thus support our
hypothesis that the presence of six ethereal oxygen donor
atoms in this calixarene-based system is not sufficient for
the binding of alkali metal cations.
m-isomer (4.7 mmol, 4.42 g, 60%). Mp (decompose)Z
184.8–185.3 8C. 1H NMR (200 MHz, CDCl3) d 1.00 (s,
18H), 1.27 (s, 18H), 3.32 (d, 4H, JZ13.0 Hz), 4.30–4.40
(m, 12H), 6.85 (s, 4H), 7.04 (s, 4H) 7.20–7.45 (m, 8H), 9.93
(s, 1H); 13C NMR (50 MHz, CDCl3) d 31.1, 31.7, 31.7, 33.8,
34.0, 66.9, 73.7, 113.4, 122.4, 123.6, 125.2, 125.7, 127.8,
130.2, 132.8, 137.8, 141.5, 147.1, 149.7, 150.5, 159.2,
192.1; IR (neat) nmax 3336 (phenolic O–H stretching), 3050,
2958, 2869 (aldehydic C–H stretching), 2731 (aldehydic
C–H stretching), 1697 (aldehydic C]O stretching), 1597,
1485, 1450, 1265 cmK1; Anal. Calcd for C62H72O8: C,
78.78; H, 7.68; Found: C, 76.80; H, 7.95.
3. Conclusion
p-isomer (4.3 mmol, 4.05 g, 55%). 1H NMR (200 MHz,
CDCl3) d 1.18 (s, 18H), 1.50 (s, 18H), 3.49 (d, 4H, JZ
13.0 Hz), 4.80–4.52 (m, 8H), 4.54 (d, 4H, JZ13.0 Hz), 7.02
(s, 4H), 7.19 (d, 4H, JZ8.5 Hz), 7.24 (s, 4H), 7.42 (s, 2H),
10.06 (s, 2H); 13C NMR (50 MHz, CDCl3) d 31.0, 31.5,
31.7, 33.8, 34.0, 66.9, 73.5, 115.1, 125.2, 125.7, 127.8,
130.2, 131.9, 132.6, 141.6, 147.2, 149.6, 150.4, 163.5,
190.8.
We have successfully synthesized and fully characterized
two series of photoswitchable calix[4]arenes incorporating
different regioisomers of stilbene and azobenzene bridges.
The cis–trans isomerization study indicates that the stilbene
derivatives are isomerized only under UV irradiation while
the azobenzene derivatives undergo either thermally or
photochemically induced isomerization. Only the o-azo-
benzene derivative shows complexation with sodium and
potassium ions presumably as a result of the participation of
the nitrogen atom of the diazo group in coordination with
these ions. The results represent a rare example of the
coordination of the nonpolar diazo nitrogen to an alkali-
metal cation. This complexation also induces a thermal
equilibrium shift between cis and trans isomers of the
azobenzenes. The present findings will lead to the design
and synthesis of new, more effective, photoswitchable
ionophores for sodium and potassium ions.
4.1.2. Synthesis of bis-nitrobenzene. In a 500 mL, round-
bottomed flask equipped with a magnetic stirring bar and a
reflux condenser, a mixture of potassium carbonate
(0.43 mmol,
6.0 g),
(2-bromoethoxy)nitrobenzene
(40.64 mmol, 10.0 g)and p-tert-butyl calyx[4]arene
(18.85 mmol, 8.0 g) were stirred in CH3CN (200 mL). The
mixture was kept stirring at reflux temperature overnight.
The reaction mixture was allowed to cool to room
temperature and the solvent was evaporated under reduced
pressure. The resulting residue was dissolved in CH2Cl2

1322
R. Rojanathanes et al. / Tetrahedron 61 (2005) 1317–1324
(150 mL) and then extracted with water for several times.
The combined organic phase was separated and dried over
anhydrous Na2SO4. The solvent was removed under
vacuum. The product was further purified crystallisation
using CH2Cl2/MeOH solvent system. The purified product
was obtained as a yellow crystal.
(6 C(CH3)3), 31.9 (4 Ar2CH2), 33.8 (2 C(CH3)3), 34.0 (2
C(CH3)3), 67.8 (2 OCH2), 74.1 (2 OCH2), 113.4 (2 stilbene-
ArC), 120.8 (2 stilbene-ArC), 125.1 (4 calix-ArC), 125.4 (2
CH]CH), 125.7 (4 calix-ArC), 127.7 (4 calix-ArC), 127.9
(2 stilbene-ArC), 129.0 (2 stilbene-ArC), 129.5 (2 stilbene-
ArC), 133.3 (4 stilbene-ArC), 141.0 (2 calix-ArC), 147.0 (2
calix-ArC), 149.6 (2 calix-ArC), 150.8 (2 calix-ArC), 155.7
(2 stilbene-ArC); Anal. Calcd for C62H72O6$CH2Cl2: C,
75.88; H, 7.38; Found: C, 76.12; H, 7.25: mpZ292–294 8C
(decomposed).
1
o-isomer (12.44 mmol, 12.2 g, 66%). H NMR (200 MHz,
CDCl3) d 0.99 (s, 18H), 1.26 (s, 18H), 3.31 (d, 4H, JZ
13.0 Hz), 4.33 (s, 8H), 4.35 (d, 4H, JZ13.0 Hz), 6.85 (s,
4H), 7.03 (s, 4H), 7.24 (ddd, 2H, JZ8.0, 2.0, 1.0 Hz), 7.35
(s, 2H), 7.40 (t, 2H, JZ8.0 Hz), 7.74 (t, 2H, JZ2.0 Hz),
7.81 (ddd, 2H, 8.0, 2.0, JZ1.0 Hz); 13C NMR (50 MHz,
CDCl3) d 31.1, 31.7, 31.7, 33.9, 34.0, 67.4, 73.4, 109.1,
116.2, 122.2, 125.2, 125.8, 127.8, 130.0, 132.8, 141.8,
147.5, 149.1, 149.5, 150.3, 159.1; Anal. Calcd for
C60H70N2O10: C, 73.60; H, 7.21; N, 2.386; Found: C,
73.62; H, 7.27; N, 2.73: mpZ205–207 8C.
trans-o-1. 1H NMR (200 MHz, CDCl3) d 1.06 (s, 18
C(CH3)3), 1.18 (s, 18 C(CH3)3), 3.21 (d, 4 Ar2CH2, JZ
12.5 Hz), 4.23 (d, 4 Ar2CH2, JZ12.5 Hz), 4.51 (broad, 4
OCH2), 4.68 (broad, 4 OCH2), 6.82 (d, 2 stilbene-ArH, JZ
8.0 Hz), 6.93 (m, 4 calix-ArH and 2 stilbene-ArH), 6.97 (s, 4
calix-ArH), 7.15 (t, 2 stilbene-ArH, JZ8.0 Hz), 7.50 (d, 2
stilbene-ArH, JZ8.0 Hz), 7.74 (s, 2 CH]CH), 8.43 (s, 2
OH); 13C NMR (200 MHz, CDCl3) d 31.2 (6 C(CH3)3), 31.6
(6 C(CH3)3), 32.1 (4 Ar2CH2), 33.8 (2 C(CH3)3), 34.1 (2
C(CH3)3), 66.6 (2 OCH2), 73.6 (2 OCH2), 111.1 (2 stilbene-
ArC), 120.8 (2 stilbene-ArC), 125.0 (4 calix-ArC), 125.9 (4
calix-ArC), 127.5 (4 calix-ArC), 127.5 (2 CH]CH), 127.7
(2 stilbene-ArC), 128.0 (2 stilbene-ArC), 129.6 (2 stilbene-
ArC), 133.7(4calix-ArC), 141.2(2calix-ArC), 147.4 (2calix-
ArC), 149.3 (2 calix-ArC), 150.7 (2 calix-ArC), 155.9 (2
stilbene-ArC); Anal. Calcd for C62H72O6: C, 81.54; H, 7.95;
Found: C, 81.41; H, 7.94: mpZ278–280 8C (decomposed).
1
m-isomer (13.28 mmol, 13.0 g, 70%). H NMR (200 MHz,
CDCl3) d 0.99 (s, 18H), 1.26 (s, 18H), 3.31 (d, 4H, JZ
13.0 Hz), 4.33 (s, 8H), 4.35 (d, 4H, JZ13.0 Hz), 6.85 (s,
4H), 7.03 (s, 4H), 7.24 (ddd, 2H, JZ8.0, 2.0, 1.0 Hz), 7.35
(s, 2H), 7.40 (t, 2H, JZ8.0 Hz), 7.74 (t, 2H, JZ2.0 Hz),
7.81 (ddd, 2H, 8.0, 2.0, JZ1.0 Hz); 13C NMR (50 MHz,
CDCl3) d 31.1, 31.7, 31.7, 33.9, 34.0, 67.4, 73.4, 109.1,
116.2, 122.2, 125.2, 125.8, 127.8, 130.0, 132.8, 141.8,
147.5, 149.1, 149.5, 150.3, 159.1.
1
p-isomer (15.1 mmol, 14.8 g, 80%). H NMR (200 MHz,
cis-m-1. 1H NMR (200 MHz, CDCl3) d 1.09 (s, 18
C(CH3)3), 1.25 (s, 18 C(CH3)3), 3.32 (d, 4 Ar2CH2, JZ
12.5 Hz), 3.94 (broad, 4 OCH2), 4.12 (broad, 4 OCH2), 4.38
(d, 4 Ar2CH2, JZ12.5 Hz), 6.69 (broad, 2 stilbene-ArH),
6.71 (s, 2 CH]CH), 6.89 (m, 4 stilbene-ArH), 6.97 (s, 4
calix-ArH), 7.02 (s, 4 calix-ArH), 7.24 (t, 2 stilbene-ArH,
JZ8.5 Hz), 8.08 (s, 2 OH); 13C NMR (200 MHz, CDCl3) d
31.2 (6 C(CH3)3), 31.7 (6 C(CH3)3), 31.7 (4 Ar2CH2), 33.8
(2 C(CH3)3), 34.1 (2 C(CH3)3), 66.2 (2 OCH2), 73.7 (2
OCH2), 111.8 (2 stilbene-ArC), 117.0 (2 stilbene-ArC),
121.5 (2 stilbene-ArC), 125.0 (4 calix-ArC), 125.7 (4 calix-
ArC), 127.3 (4 calix-ArC), 129.6 (2 CH]CH), 130.9 (2
stilbene-ArC), 133.5 (4 calix-ArC), 138.3 (2 stilbene-ArC),
140.9 (2 calix-ArC), 147.2 (2 calix-ArC), 149.2 (2 calix-
ArC), 151.1 (2 calix-ArC), 158.2 (2 stilbene-ArC); Anal.
Calcd for C62H72O6: C, 81.54; H, 7.95; Found: C, 81.48; H,
7.92: mpZ264–265 8C.
CDCl3) d 0.96 (s, 18H), 1.27 (s, 18H), 3.30 (d, 4H, JZ
13.0 Hz), 4.31 (s, 8H), 4.35 (d, 4H, JZ13.0 Hz), 6.80 (s,
4H), 6.98 (d, 4H, JZ9.0 Hz), 7.05 (s, 4H), 7.07 (s, 2H), 8.18
(d, 4H, JZ9.0 Hz); 13C NMR (50 MHz, CDCl3) d 31.0,
31.5, 31.7, 33.9, 34.0, 67.4, 73.5, 114.8, 125.2, 125.7, 125.9,
127.7, 132.5, 141.8, 141.8, 147.3, 149.4, 150.4, 163.5.
4.1.3. Synthesis of 1. Typically, TiCl4 (3.17 mmol, 0.60 g)
was charged into a two-necked, round-bottomed flask under
a N2 atmosphere. Anhydrous THF (30 mL) was added
dropwise and activated Zn powder (6.35 mmol, 0.41 g) was
added cautiously. After 1 h reflux, the bisbenzaldehyde
(1.06 mmol, 1.00 g) in THF (10 mL) was added dropwise.
The mixture was refluxed for additional 15 h and it was
allowed to cool to room temperature. A solution of K2CO3
(15% w/v) was added to quench the excess TiCl4. The
precipitate was filtered over celite and washed with acetone
and CH2Cl2. The filtrate was evaporated to give the residue
which was dissolved in CH2Cl2 (20 mL) and then extracted
with water (3!25 mL). The organic phase was dried over
anhydrous Na2SO4 and the solvent was removed to give the
crude product. The cis and trans isomers was separated by
column chromatography using 5% ethyl acetate in hexane as
eluent (cis isomers have a higher Rf value).
trans-m-1. 1H NMR (200 MHz, CDCl3) d 0.83 (s, 18
C(CH3)3), 1.31 (s, 18 C(CH3)3), 3.29 (d, 4 Ar2CH2, JZ
13.5 Hz), 4.25 (t, 4 OCH2, JZ5.0 Hz), 4.41 (d, 4 Ar2CH2,
JZ13.5 Hz), 4.57 (t, 4 OCH2, JZ5.0 Hz), 5.84 (s, 2 OH),
6.60 (s, 4 calix-ArH), 6.87 (t, 2 stilbene-ArH, JZ8.5 Hz),
7.06 (s, 4 calix-ArH), 7.14 (d, 2 stilbene-ArH, JZ7.5 Hz),
7.24 (s, 2 CH]CH), 7.25 (t, 2 stilbene-ArH, JZ7.5 Hz),
7.74 (s, 2 stilbene-ArH); 13C NMR (200 MHz, CDCl3) d
30.8 (6 C(CH3)3), 31.2 (4 Ar2CH2), 31.7 (6 C(CH3)3), 33.8
(2 C(CH3)3), 33.9 (2 C(CH3)3), 69.3 (2 OCH2), 75.0 (2
OCH2), 114.3 (2 stilbene-ArC), 118.0 (2 stilbene-ArC),
119.9 (2 stilbene-ArC), 125.3 (4 calix-ArC), 125.4 (4 calix-
ArC), 128.5 (4 calix-ArC), 128.9 (2 CH]CH), 129.8 (2
stilbene-ArC), 131.6 (4 calix-ArC), 139.1 (2 stilbene-ArC),
141.8 (2 calix-ArC), 146.7 (2 calix-ArC), 150.3 (2
calix-ArC), 150.8 (2 calix-ArC), 158.8 (2 stilbene-ArC);
cis-o-1. 1H NMR (200 MHz, CDCl3) d 1.03 (s, 18 C(CH3)3),
1.22 (s, 18 C(CH3)3), 3.25 (d, 4 Ar2CH2, JZ13.0 Hz), 4.16
(broad, 4 OCH2), 4.26 (broad, 4 OCH2), 4.35 (d, 4 Ar2CH2,
JZ13.0 Hz), 6.83 (t, 2 stilbene-ArH, JZ7.5 Hz), 6.88 (d, 2
stilbene-ArH, JZ7.5 Hz), 6.90 (s, 4 calix-ArH), 6.97 (s, 4
calix-ArH), 7.17 (t, 2 stilbene-ArH, JZ7.5 Hz), 7.25 (s, 2
CH]CH), 7.29 (d, 2 stilbene-ArH, JZ7.5 Hz), 7.70 (s, 2
OH); 13C NMR (200 MHz, CDCl3) d 31.1 (6 C(CH3)3), 31.7

R. Rojanathanes et al. / Tetrahedron 61 (2005) 1317–1324
1323
Anal. Calcd for C62H72O6: C, 81.54; H, 7.95; Found: C,
81.59; H, 8.00: mpZ281–283 8C (decomposed).
3.06; Found: C, 77.21; H, 7.51, N 2.72 mp: 195–197 8C
(decomposed).
cis-p-1. 1H NMR (200 MHz, CDCl3) d 0.85 (s, 18 C(CH3)3),
1.31 (s, 18 C(CH3)3), 3.28 (d, 4 Ar2CH2, JZ13.5 Hz), 4.17
(t, 4 OCH2, JZ4.0 Hz), 4.38 (d, 4 Ar2CH2, JZ13.5 Hz),
4.45 (t, 4 OCH2, JZ4.0 Hz), 6.29 (s, 2 OH), 6.66 (s, 4 calix-
ArH), 6.68 (s, 2 CH]CH), 6.85 (d, 4 stilbene-ArH, JZ
9.0 Hz), 6.93 (d, 4 stilbene-ArH, JZ9.0 Hz), 7.06 (s, 4
calix-ArH); 13C NMR (200 MHz, CDCl3) d 31.0 (6
C(CH3)3), 31.1 (4 Ar2CH2), 31.8 (6 C(CH3)3), 33.8 (2
C(CH3)3), 33.8 (2 C(CH3)3), 68.4 (2 OCH2), 74.8 (2
OCH2), 115.8 (4 stilbene-ArC), 125.2 (4 calix-ArC), 125.4
(4 calix-ArC), 128.1 (4 calix-ArC), 130.4 (4 stilbene-ArC),
130.8 (2 CH]CH), 131.3 (2 stilbene-ArC), 132.0 (4 calix-
ArC), 141.4 (2 calix-ArC), 146.8 (2 calix-ArC), 149.9 (2
calix-ArC), 150.5 (2 calix-ArC), 157.7 (2 stilbene-ArC);
Anal. Calcd for C62H72O6: C, 81.54; H, 7.95; Found: C,
81.57; H, 8.14: mpZ290–291 8C (decomposed).
trans-m-2. 1H NMR (200 MHz, CDCl3) d 0.83 (s, 18
C(CH3)3), 1.28 (s, 18 C(CH3)3), 3.26 (d, 4 Ar2CH2, JZ
13.0 Hz), 4.38 (t, 4 OCH2, JZ5.0 Hz), 4.34 (d, 4 Ar2CH2,
JZ13.0 Hz), 4.66 (t, 4 OCH2, JZ5.0 Hz), 6.07 (s, 2 OH),
6.61 (s, 4 calix-ArH), 7.03 (s, 4 calix-ArH), 7.08 (d, 2
azobenzene-ArH, JZ8.0 Hz), 7.39 (t, 2 azobenzene-ArH,
JZ8.0 Hz), 7.60 (d, 2 azobenzene-ArH, JZ8.0 Hz), 8.19 (s,
2 azobenzene-ArH); 13C NMR (200 MHz, CDCl3) d 30.9 (6
C(CH3)3), 31.2 (4 Ar2CH2), 31.7 (6 C(CH3)3), 33.8 (2
C(CH3)3), 33.8 (2 C(CH3)3), 69.1 (2 OCH2), 74.4 (2
OCH2), 110.9 (2 azobnzene-ArC), 116.2 (2 azobnzene-
ArC), 121.4 (2 azobnzene-ArC), 125.2 (4 calix-ArC), 125.5
(4 calix-ArC), 128.2 (4 calix-ArC), 129.8 (2 azobnzene-
ArC), 131.7 (4 calix-ArC), 141.6 (2 calix-ArC), 146.7 (2
calix-ArC), 150.4 (2 calix-ArC), 150.7 (2 calix-ArC), 153.7
(2 azobnzene-ArC), 159.4 (2 stilbene-ArC); Anal. Calcd for
C60H70N2O6: C, 78.74; H, 7.71; N, 3.06; Found: C, 78.41;
H, 7.78, N 3.01 mp: 351–352 8C.
4.1.4. Synthesis of 2. Ambient pressure method. In a 50 mL
round-bottomed flask equipped with a magnetic bar and a
reflux condenser, a mixture of 25,27-bis-2-(2-nitrophenol)-
ethoxy-p-tert-butylcalix[4]arene, (0.71 mmol, 0.70 g) in
isopropanol (8 mL), sodium hydroxide (7.0 mmol, 0.28 g)
in water (4 mL) and zinc (3.06 mmol, 0.20 g) was stirred. The
mixture was refluxed under nitrogen atmosphere for 48 h and
it was then allowed to cool to room temperature. The mixture
was filtered off and washed with CH2Cl2. The filtrate was
evaporated and the residue was dissolved in CH2Cl2 and then
extracted with 2 M HCl (2!20 mL). The organic phase was
dried over anhydrous Na2SO4 and the solvent was removed to
give the crude product, which was purified by column
chromatography using 15% ethyl acetate in hexane as eluent.
The trans isomers was collected and crystallized in CH2Cl2/
CH3OH mixture to give orange crystals.
4.2. Complexation study
1
For the H NMR study, the studied calixarene derivative
(10 mg) was dissolved in CDCl3 (0.7 mL) in an NMR tube
and the 1H NMR spectrum was collected. Sodium or
potassium picrate (20 mg) was added as a solid into the
solution. The mixture was sonicated for 1 h before the
spectrum was collected again. The color would turn to deep
yellow and a singlet signal of the aromatic picrate proton
could be observed around 9.0 ppm if complexation had
taken place. If the signal was not observed by 1H NMR, the
results was confirmed by UV–Vis which was the cases for
compounds 4 that the complexation was clearly observed in
UV–Vis spectra but barely seen from the 1H NMR spectra.
4.3. Isomerization study
High pressure method. In a 100 mL high-pressure glass tube
equipped with pressure gauge and a magnetic bar, a mixture
of 25,27-bis-2-(2-nitrophenol)ethoxy-p-tert-butylcalix[4]-
arene, (0.71 mmol, 0.70 g) in isopropanol (8 mL), sodium
hydroxide (7.0 mmol, 0.28 g) in water (4 mL) and zinc
(3.06 mmol, 0.20 g) was added and stirred. The reaction was
operated under 3 atm nitrogen atmosphere for overnight at
130 8C and it was then allowed to cool to room temperature.
The mixture was filtered off and washed with CH2Cl2. The
filtrate was evaporated to give the residue which was
dissolved in CH2Cl2 and then extracted with 2 M HCl (2!
20 mL). The organic phase was dried over anhydrous
Na2SO4 and the solvent was removed to give the crude
product, which was purified by column chromatography
using 5% ethyl acetate in hexane as eluent. The trans
isomers was separated and crystallized in CH2Cl2/CH3OH
mixture to give orange crystals.
The studied compound was dissolved in CDCl3 at
0.0060 mol and into an NMR tube. Using a Hanovia
450 W medium pressure murcury lamp equipped with a
cooling Jacket, the sample was irradiated at 30 cm away
1
from the lamp for a specific period of time. The H NMR
was checked. Once the NMR spectra were unchanged, the
cis:trans ratio of that specific analogue was determined by
NMR integration of a selected signal.
4.4. Crystallographic data
4.4.1. cis-o-1. C63H74Cl2O6, monoclinic, space group P21/c,
˚
˚
˚
aZ20.7486(5) A, bZ12.3713(4) A, cZ22.6335(5) A, bZ
109.373(2)8, UZ5480.8(3) A , DcZ1.210 Mg mK3, ZZ4,
3
˚
TZ120(2) K, colourless block, 0.24!0.18!0.12 mm3.
Data collection was carried out using a Bruker–Nonius
KappaCCD area detector and SHELXS-97 and SHELXL-97
programs were used for structure solution and refinement.
32,983 reflections collected, 12,074 independent [R(int)Z
0.0700], giving R1Z0.0931 for observed unique reflections
[F2O2s(F2)] and wR2Z0.3186 for all data. The max. and
min. residual electron densities on the final difference
trans-o-2. 1H NMR (400 MHz, CDCl3) d 1.03 (s, 18
C(CH3)3), 1.20 (s, 18 C(CH3)3), 3.20 (d, 4 Ar2CH2, JZ
13.0 Hz), 4.15 (d, 4Ar2CH2, JZ13.0 Hz), 4.38 (br t, 4
OCH2), 4.84 (br t, 4 OCH2), 6.86 (s, 4 calix-ArH), 6.92 (s, 4
calix-ArH), 7.08 (d, 2 azobenzene-ArH, JZ6.0 Hz), 7.16 (d,
2 azobenzene-ArH, JZ8.0 Hz), 7.34 (t, 2 azobenzene-ArH,
JZ6.0 Hz), 7.61 (s, 2 OH), 7.70 (d, 2 azobenzene-ArH, JZ
8.0 Hz); Anal. Calcd for C60H70N2O6: C, 78.74; H, 7.71; N,
Fourier map were 0.975 and K0.588e AK3, respectively.
The asymmetric unit contains a disordered molecule of
˚

1324
R. Rojanathanes et al. / Tetrahedron 61 (2005) 1317–1324
J. M.; Cohen, S. L.; Chait, B. T.; MacKinnon, R. Science 1998,
280, 69–77.
dichloromethane and exhibits conformational disorder in
one of the lower rim cage arms and rotational disorder in
one of the tertiary butyl groups. Supplementary data have
been deposited with the CCDC in CIF format with the
deposition number CCDC249144.
2. Dutzler, R.; Wang, Y. F.; Rizkallah, P.; Rosenbusch, J. P.;
Schiemer, T. Structure 1996, 4, 127–134.
3. Forst, D.; Welte, W.; Wacker, T.; Diederichs, K. Nat. Struct.
Biol. 1998, 5, 6–8.
4.4.2. trans-o-2. C64H78N2O8, Monoclinic, space group Cc,
˚
4. Karle, I. L. J. Am. Chem. Soc. 1975, 97, 4379–4386.
5. Hamilton, J. A.; Sabesan, M. N.; Steinrauf, L. K. J. Am. Chem.
Soc. 1981, 103, 5880–5885.
˚
˚
aZ15.1260(3) A, bZ31.1347(3) A, cZ12.6692(3) A, bZ
3
K3
˚
98.4970(10)8, UZ5900.99(19) A , DcZ1.129 Mg m
,
ZZ4, TZ293(2) K, dark-orange block, 0.60!0.30!
0.30 mm3. Data collection was carried out using a Bruker
SmartCCD detector and SHELXS-97 and SHELXL-97
programs were used for structure solution and refinement.
21,046 reflections collected, 14,604 independent [R(int)Z
0.0190], giving R1Z0.0731 for observed unique reflections
[F2O2s(F2)] and wR2Z0.1982 for all data. The max. and
min. residual electron densities on the final difference
6. Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 7017–7036.
7. Leevy, W. M.; Donatto, G. M.; Ferdani, R.; Goldman, W. E.;
Schelesinger, P. H.; Gokel, G. W. J. Am. Chem. Soc. 2002,
124, 9022–9023.
8. (a) Simaan, S.; Biali, S. E. J. Org. Chem. 2003, 68, 7685–7692.
(b) Shimizu, S.; Moriyama, A.; Kito, K.; Sasaki, Y. J. Org.
Chem. 2003, 68, 2187–2194. (c) Arduini, A.; Pochini, A.;
Secchi, A.; Ugozzoli, F. Calixarenes 2001; The Royal Society
of Chemistry: Cambridge, 2001; pp 457–475.
Fourier map were 0.225 and K0.211e AK3, respectively.
˚
Supplementary data have been deposited with the CCDC in
CIF format with the deposition number CCDC137509.
9. (a) Kim, J. S.; Shon, O. J.; Lee, J. K. J. Org. Chem. 2002, 67,
1372–1375. (b) Ko, S. W.; Yang, Y. S.; Mun, J. H.; Park,
K.-M.; Lee, S. S.; Nam, K. C. Bull. Kor. Chem. Soc. 2002, 23,
1379–1380. (c) Guillon, J.; Leger, J-M. ; Sonnet, P.; Jarry, C.;
Robba, M. J. Org. Chem. 2000, 65, 8283–8289.
10. (a) Rurack, K.; Resch-Genger, U. Chem. Soc. Rev. 2002, 31,
116–127. (b) Tucker, J. H. R.; Collinson, S. R. Chem. Soc. Rev.
2002, 31, 147–156. (c) Irie, M. Chem. Rev. 2000, 100,
1685–1716.
4.4.3. trans-m-2. C60H70N2O6, Triclinic, space group P-1,
˚
˚
˚
aZ11.8283(3) A, bZ12.7292(4) A, cZ19.5738(8) A, aZ
82.2330(10)8, bZ74.9430(10)8, gZ66.7110(10)8, UZ
3
2612.32(15) A , DcZ1.163 Mg mK3, ZZ2, TZ120(2) K,
˚
dark-orange block, 0.40!0.20!0.15 mm3. Data collection
was carried out using a Bruker–Nonius KappaCCD area
detector and SHELXS-97 and SHELXL-97 programs were
used for structure solution and refinement. 39,735 reflec-
tions collected, 11,605 independent [R(int)Z0.1407],
giving R1Z0.0777 for observed unique reflections [F2O
2s(F2)] and wR2Z0.2157 for all data. The max. and min.
residual electron densities on the final difference Fourier
11. (a) Norikane, Y.; Kitamoto, K.; Tamaoki, N. J. Org. Chem.
2003, 68, 8291–8304. (b) March, J. Advanced Organic
Chemistry, 4th ed.; Wiley: New York, 1992; p. 1234.
12. (a) Pipoosananakaton, B.; Sukwattanasinitt, M.; Jaiboon, N.;
Chaichit, N.; Tuntulani, T. Bull. Kor. Chem. Soc. 2000, 21,
867–874. (b) Pipoosananakaton, B.; Sukwattanasinitt, M.;
Jaiboon, N.; Chaichit, N.; Tuntulani, T. Tetrahedron Lett.
2000, 41, 9095–9100.
map were 0.801 and K0.556e AK3, respectively. Sup-
˚
plementary data have been deposited with the CCDC in CIF
format with the deposition number CCDC249145.
13. Shinkai, S.; Honda, Y.; Ueda, K.; Manabe, O. Bull. Chem. Soc.
Jpn 1984, 57, 2144–2149.
14. (a) Agbaria, K.; Biali, S. E. J. Org. Chem. 2001, 66,
5482–5489. (b) McMurry, J. E. Acc. Chem. Res. 1983, 16,
405–411.
Acknowledgements
This work was financially supported by the Thailand
Research Fund (TRF) (RSA4580026), Ministry of
University Affairs (UDC39/2543), National Science and
Technology Development Agency (NSTDA) (CO-B-11-11-
09-202D) and an EPSRC studentship (to J. B. O.).
15. (a) Sukwattanasinitt, M.; Rojanathanes, R.; Jiwpanich, S.;
Tuntulani, T.; Ruangpornvisuti, V. Sci. Asia 2002, 28, 25–28.
(b) Sukwattanasinitt, M.; Rojanathanes, R.; Tuntulani, T.;
Sritana-Anan, Y.; Ruangpornvisuti, V. Tetrahedron Lett.
2001, 42, 5291–5293.
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Nakaji, T.; Ogawa, T.; Shigematsu, K.; Manabe, O. J. Am.
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References and notes
1. Doyle, D. A.; Morais, C. J.; Pfuetzner, R. A.; Kuo, A.; Gulbis,