Improved functionality and control in the isomerization of a calix[4]arene-capped azobenzene

Article abstract of DOI:10.1016/j.tetlet.2010.12.107

An improved azobenzene core capped by two calix[4]arene units isomerizes readily between trans and cis configurations via photochemical and/or thermal means. In addition, the presence of acid (particularly HCl) increases the rate of thermal cis→trans conv

Full text of DOI:10.1016/j.tetlet.2010.12.107

Tetrahedron Letters 52 (2011) 1117–1120
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Improved functionality and control in the isomerization
of a calix[4]arene-capped azobenzene
⇑
Paul A. Bonvallet , Max R. Mullen, Paul J. Evans, Kristen L. Stoltz, Erica N. Story
Department of Chemistry, The College of Wooster, 943 College Mall, Wooster, OH 44691, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
An improved azobenzene core capped by two calix[4]arene units isomerizes readily between trans and cis
configurations via photochemical and/or thermal means. In addition, the presence of acid (particularly
HCl) increases the rate of thermal cis?trans conversion. These enhancements to the functional response,
control, and understanding of calixarene-capped azobenzene isomerization are important for future
application in the dynamic encapsulation of small chemical species.
Received 16 December 2010
Accepted 28 December 2010
Available online 7 January 2011
Keywords:
Azobenzene
Ó 2011 Elsevier Ltd. All rights reserved.
Calixarene
Photoisomerization
Thermal isomerization
Stimuli-responsive material
Stimuli-responsive materials undergo controllable chemical or
physical changes in response to external input.1 Compared to
chemical signaling, light stimulus is particularly appealing because
its energy is easily tuned and it drives processes rapidly and
reversibly without the buildup of byproducts. The photoirradiation
of compounds containing light-sensitive structural units has been
shown to lead to dramatic changes in their color,2 physical phase,3
rate of reaction,4 and mode of self-assembly.5 Azobenzene is em-
ployed in many of these systems because of its robust and well-
established interconversion between trans and cis configurations
under specific photochemical and thermal conditions.1a,6
Arduini noted that azo dimer 1 is apparently locked in the trans
configuration7 and fails to undergo the trans?cis photoisomeriza-
tion reaction typical of azobenzene and its derivatives under UV
irradiation.1a,6 If the compound were capable of free isomerization,
it could be employed as a molecular container with the ability to
Arduini et al. reported a clamshell-shaped compound 1 having
two calix[4]arene-bis(crown-3) components joined by an azo link-
age (Fig. 1).7 It binds effectively (Ka ꢀ 800–3700 MÀ1) with a range
of pyridinium and tetraalkylammonium ions.7 Replacing the azo
unit with various linkers (compounds 2–4) modulates the binding
affinity according to the steric bulk of each guest-ion pair and the
cavity volume dictated by the spacing between calixarene caps.
The association constants with pyridinium guests are substantially
larger in the series of dimeric calixarenes (Ka ꢀ 300–7000 MÀ1
)
than in the parent calixarene 5 (Ka ꢀ 100 MÀ1). The authors attri-
bute this enhancement to the synergistic, convergent effect of
the two calixarene hemispheres in the dimer.7 A similar trend
has been observed in calix[4]arenes bearing propoxy substituents,
in which dimers with short linkers (6–7) bind more tightly to
pyridinium ions than the parent monomer (9).8
⇑
Corresponding author. Tel.: +1 330 263 2610.
E-mail address: pbonvallet@wooster.edu (P.A. Bonvallet).
Figure 1. Dimeric and monomeric calix[4]arenes.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.12.107

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P. A. Bonvallet et al. / Tetrahedron Letters 52 (2011) 1117–1120
insensitive to solvent polarity (see Supplementary data), indicating
that solvent–solute interactions are similar and that changes in the
dipole moment upon excitation are minimal. A weak n?p⁄ transi-
tion at longer wavelength was anticipated but not observed, even
at high concentration, likely due to overlap with the dominant peak.
Solutions of 8 handled under ambient laboratory conditions contain
a small amount of cis isomer that is detectable by NMR (Fig. 2a). Stor-
age of these solutions in the dark for about one day leads to the dis-
appearance of cis-8 (Fig. 2b) via the slow cis?trans thermal reaction
typical of azobenzene (Scheme 1).6,16
Bandpass irradiation of trans-8 at k = 384 12 nm in CDCl3 for
35 min causes the intensity of its 1H NMR signals to diminish dra-
matically, accompanied by the appearance of new resonances as-
cribed to cis-8 (Fig. 2c). Longer irradiation times fail to produce
further changes, indicating a photostationary state with a trans:cis
ratio of 35:65. A difference spectrum after irradiation (taking into
account the relative abundance of the two isomers) provides a pre-
dicted NMR spectrum of pure cis-8 as shown in Figure 2d. Upon ex-
tended time in the dark, the signals for cis-8 disappear completely
and those for trans-8 are restored to their original intensity
(Fig. 2e). Trans-8 can be regenerated in under 1 h by irradiating
at k > 520 nm, although the cis isomer persists in a small steady
state concentration of ca. 10% (see Supplementary data).
Interconversion between trans and cis forms of 8 can also be
tracked by UV–visible spectroscopy. The peak at 384 nm (trans-8)
shrinks dramatically upon bandpass irradiation at k = 384
12 nm accompanied by the emergence of two distinct bands at
262 and 352 nm and a weak, featureless absorption in the visible
region at wavelengths longer than 470 nm (Fig. 3a). These features
are assigned to cis-8 by analogy to the photochemistry established
by NMR. They are similar to the parent cis-azobenzene, which has a
Scheme 1. Synthesis of azo-linked compound 8.
switch between closed (cis) and open (trans) forms in response to
light. The principle of using light to modulate the affinity of host
compounds for guest species has received considerable attention
for applications in drug delivery,9 ion transport and separation,10
switchable sensors,11 and functional supramolecular assemblies.12
Adapting Arduini’s compound (1) by flanking the azo linker
with phenylene units could enhance its photochemical response.
This new compound (8) would likely retain the strong synergistic
binding characteristic of calixarene dimers while providing a great-
er degree of steric and structural flexibility that improves its po-
tential for undergoing trans/cis isomerization. The additional
conjugation of the azo unit is anticipated to shift its predominant
electronic absorption to longer wavelengths, making 8 more likely
to photoisomerize under near-UV irradiation. In accord with these
predictions, and in an expansion of the pioneering work of Arduini,
we report herein the synthesis of compound 8 along with a
description of its interconversion between trans and cis forms by
photochemical and thermal means. Enhancing the control and
understanding of this key isomerization reaction is an important
precondition for its eventual application in the dynamic encapsula-
tion, storage, and release of small chemical species.
prominent peak in the near-UV as well as a p?
p⁄ transition that is
The two-step synthesis of compound 8 was accomplished in
11% overall yield (Scheme 1) using the well-established strategy
of azo bond formation from the reductive coupling of a nitro pre-
cursor.13 The commercial availability of bromide 10 led to our
selection of propoxy groups, as opposed to the bis(crown-3) ethers
found in compounds 1–5, as substituents along the narrow rim of
the calixarene. Although the Suzuki cross-coupling reaction of 10
with 4-nitrophenylboronic acid proceeds in low yield, reductive
coupling of nitro compound 11 with sodium bis(2-methoxyeth-
oxy)aluminumhydride (Red-Al) readily affords 8 as a powder. All
attempts at crystal growth were unsuccessful.
As with azobenzene,6,14 the trans form of 8 predominates in solu-
tion. This isomer is distinguished by an intense orange color and a
Figure 2. Partial, normalized 1H NMR spectra of 8 (600 MHz, 12 mM in CDCl3, rt).
(a) Both trans (major) and cis (minor) isomers are observed under ambient light
conditions. (b) Cis-8 is undetectable after 22 h in the dark. (c) Irradiation at
k = 384 12 nm for 35 min produces a photostationary mixture of trans and cis
isomers. (d) A weighted difference spectrum after irradiation reveals the spectrum
of pure cis-8. (e) Cis-8 is converted back to trans-8 upon standing in the dark for
3.9 d. The singlet at 7.26 ppm is residual CHCl3.
characteristic
p
?
p⁄ transition (384 nm,
e
ꢀ35,000 MÀ1 cmÀ1
,
CHCl3) in its UV–visible spectrum. Due to the additional conjugation
of the azo unit in 8, this band is red-shifted by 65 nm relative to
azobenzene in the same solvent.15 Aside from a small (7 nm)
blue-shift in hexane, the absorption maximum is almost completely

P. A. Bonvallet et al. / Tetrahedron Letters 52 (2011) 1117–1120
1119
less intense and blue-shifted relative to its trans isomer.6 The slight
increase in absorption in the visible region is consistent with the
weak n?p⁄ band of azobenzene, which is more intense in the cis
form than in the trans one for reasons related to symmetry and
spectroscopy selection rules.6 An estimated UV–visible spectrum
of cis-8, calculated by treating the photostationary state spectrum
as a 35:65 combination of trans and cis isomers, respectively, is
shown as the black dotted curve in Figure 3a.
The trans-8 peak at 384 nm shrinks to a constant 31% of its ori-
ginal intensity upon photoirradiation. The composition of the
photostationary state is comparable to that in the NMR experi-
ments, although it is reached more quickly in the UV–visible
experiments (60 s vs 35 min) due to the significantly lower con-
centration. The original intensity of the trans-8 signal at 384 nm
is restored upon standing in the dark for prolonged periods (see
Supplementary data) as the slow thermal cis?trans isomerization
occurs. Alternatively, irradiation of the cis/trans mixture at
k > 520 nm for 18 min promotes a more rapid cis to trans conver-
sion, albeit to a photostationary state (similar to that observed in
the NMR experiments) in which the concentration of trans-8 is re-
stored to 90% of its original intensity (Fig. 3b). The full intensity at
384 nm is restored slowly upon standing in the dark for several
days. Isosbestic points at 339 nm and 470 nm are observed in both
the photochemical disappearance and reemergence of trans-8, sug-
gesting a clean interconversion between only two species. The
photoequilibrium is repeatable for many cycles with no evidence
of degradation (Fig. 3c).
The strong absorption of trans-8 relative to cis-8 at 384 nm al-
lows the rate of thermal cis to trans conversion to be measured.
The concentration of cis-8 is directly proportional to
DA, defined
as A0 À At in which A0 is the absorption at 384 nm for an all-
trans-8 sample and At is the instantaneous absorption at any time
after photochemical irradiation. Analogously to azobenzene,6,16 the
disappearance of cis-8 and corresponding growth of trans-8 in the
dark follows first-order kinetics as indicated by the linear relation-
ship between ln (DA) and time (Fig. 4). The rate constant of this
thermal cis?trans reaction varies only slightly in different solvents
across a wide range of polarity (Table 1, entries 1–5). This trend is
qualitatively consistent with the results of Khayer and Sander, in
which the isomerization of azobenzene in the dark is accelerated
by a factor of 1.2–1.7 as the solvent polarity decreases.17
The rate of cis?trans isomerization increases moderately in
dichloromethane and dramatically in chloroform (Table 1, entries
5 and 6). This result was unexpected, given that the polarity and
viscosity of these solvents are intermediate compared to the others
employed. We hypothesize that traces of HCl, produced from the
decomposition of chlorinated solvents upon prolonged exposure
to atmospheric oxygen,18 accelerates the thermal isomerization.
Experimental16,19 and computational20 evidence shows that this
reaction is faster in acidic solution than in neutral or basic solution
due to protonation of the azo group. Correspondingly, conditioning
the chloroform prior to preparing solutions of 8 has a marked effect
on the reaction kinetics. Washing the chloroform with aqueous HCl
further accelerates the reaction, while washing with aqueous
NaHCO3 retards it (Table 1, entries 7–9). The pH of organic solvents
is difficult to measure directly, but secondary evidence indicates
that the chloroform becomes slightly more acidic or less acidic
upon treatment with these washes (see Supplementary data).
HCl has been shown to increase the rate of azobenzene cis?trans
isomerization more effectively than other acids, possibly due to
Figure 3. UV–visible data for 8 (CHCl3, 37 lM, rt). (a) Irradiation at k = 384 12 nm
causes trans?cis isomerization. (b) The process is reversed, to 90% completion,
upon irradiation at k > 520 nm. (c) Tracking the absorbance maximum of 8 through
multiple isomerization cycles (1 min k = 384 12 nm followed by 18 min
k > 520 nm) reveals no signs of degradation.
Figure 4. First order kinetics data, along with least-squares linear fit, for the
thermal cis-8?trans-8 reaction in the dark at 30.0 °C.

1120
P. A. Bonvallet et al. / Tetrahedron Letters 52 (2011) 1117–1120
Table 1
CHE-9977546 and CHE-0704026. We thank the Mass Spectrometry
Rates of the thermal cis-8?trans-8 reactiona
Center of the University of Akron and the Department of Macromo-
lecular Science and Engineering at Case Western Reserve Univer-
sity (NSF Grant CHE-0821515) for instrumental support.
Entry
Solvent
k (sÀ1
)
Rel. rate
1
2
3
4
5
6
7
8
9
Acetone
1,4-Dioxane
Hexane
CCl4
CH2Cl2
CHCl3, untreated
CHCl3, washed with 1 M NaHCO3
CHCl3, washed with deionized H2O
CHCl3, washed with 1 M HCl
2.1 Â 10À5
3.1 Â 10À5
3.5 Â 10À5
4.9 Â 10À5
7.7 Â 10À5
3.5 Â 10À4
7.1 Â 10À5
1.9 Â 10À4
1.5 Â 10À2
1
1.5
1.7
2.3
3.7
17
3.4
9.0
710
Supplementary data
Supplementary data (experimental procedures, additional NMR
and UV–visible spectra, and kinetics data) associated with this arti-
cle can be found, in the online version, at doi:10.1016/
j.tetlet.2010.12.107.
a
All reactions took place in the dark at 30.0 °C.
References and notes
1. (a)Smart Light-Responsive Materials: Azobenzene-Containing Polymers and Liquid
Crystals; Zhao, Y., Ikeda, T., Eds.; John Wiley & Sons: Hoboken, NJ, 2009; (b) Roy,
D.; Cambre, J. N.; Sumerlin, B. S. Prog. Polym. Sci. 2010, 35, 278–301; (c) Winnik,
F. M.; Whitten, D. G.; Urban, M. W.; Lopez, G. Langmuir 2007, 23, 1–2; (d)
Yerushalmi, R.; Scherz, A.; van der Boom, M. E.; Kraatz, H. J. Mater. Chem. 2005,
15, 4480–4487; (e) Luzinov, I.; Minko, S.; Tsukruk, V. V. Prog. Polym. Sci. 2004,
29, 635–698.
2. (a) Irie, M. Chem. Rev. 2000, 100, 1683–1684; (b)Photochromism: Molecules and
Systems; Dürr, H., Bouas-Laurent, H., Eds., revised ed.; Elsevier: Boston, 2003.
3. Zhao, Y.; Stoddart, J. F. Langmuir 2009, 25, 8442–8446.
an interaction of the chloride counterion with the protonated azo
compound.16b A similar trend is observed with 8, in which the
acceleration of the reaction is greater with HCl than with trifluoro-
acetic acid (see Supplementary data).
The rate constants from the variously-treated chloroform solu-
tions differ by as much as two orders of magnitude, raising an
intriguing possibility if cis-8 were able to encapsulate smaller
chemical species. The molecular container could be opened with
light (cis?trans at k > 520 nm) to release its included guest rapidly.
Alternatively, cis-8 could remain in the dark but behave as a time-
release capsule, opening slowly under acid-free conditions but
much more quickly in the presence of HCl (with half-lives of
2.7 h and 46 s, respectively). Thus the judicious selection of photo-
chemical input and/or pH environment to govern the isomerization
of 8 provides a range of stimuli for the controllable opening and
closing of the compound.
In summary, two advances have been made in the development
of a stimuli-responsive calixarene-capped azobenzene first at-
tempted by Arduini. First, the inclusion of phenylene spacers in
compound 8 makes the assembly responsive to light, isomerizing
cleanly between trans and cis forms. Second, the sensitivity of 8
to acid (particularly HCl) in the thermal cis?trans reaction in the
dark invites application as a time-release capsule that can be
programed to open over a prescribed timeframe according to solu-
tion pH. Future work on 8 will focus on its binding with electron-
deficient species to evaluate its potential as a light-responsive
molecular container.
4. Samachetty, H. D.; Lemieux, V.; Branda, N. R. Tetrahedron 2008, 64, 8292–8300.
5. (a) Yamauchi, K.; Takashima, Y.; Hashidzume, A.; Yamaguchi, H.; Harada, A. J.
Am. Chem. Soc. 2008, 130, 5024–5025; (b) Mulder, A.; Jukovic, A.; Huskens, J.;
Reinhoudt, D. N. Org. Biomol. Chem. 2004, 2, 1748–1755.
6. Ref. 2b, Chapter 4.
7. Arduini, A.; Pochini, A.; Secchi, A. Eur. J. Org. Chem. 2000, 2325–2334.
8. (a) Araki, K.; Shimizu, H.; Shinkai, S. Chem. Lett. 1993, 205–208; (b) Araki, K.;
Hisaichi, K.; Kanai, T.; Shinkai, S. Chem. Lett. 1995, 569–570; (c) Araki, K.;
Hayashida, H. Tetrahedron Lett. 2000, 41, 1209–1213.
9. Saha, S.; Leung, K. C.-F.; Nguyen, T. D.; Stoddart, J. F.; Zink, J. I. Adv. Funct. Mater.
2007, 17, 685–693.
10. Wang, Y.; Bie, F.; Jiang, H. Org. Lett. 2010, 12, 3630–3633.
11. Pipoosananakaton, B.; Sukwattanasinitt, M.; Jaiboon, N.; Chaichit, N.;
Tuntulani, T. Bull. Korean Chem. Soc. 2000, 21, 867–874.
12. Cooke, G.; Rotello, V. M. Chem. Soc. Rev. 2002, 31, 275–286.
13. Bigelow, H. G.; Robinson, D. B. Org. Synth. 1955, Coll. Vol. 3, 103-104.
14. Rau, H. Angew. Chem., Int. Ed. Engl. 1973, 12, 224–235.
15. Cook, A. H.; Jones, D. G.; Polya, J. B. J. Chem. Soc. 1939, 1315–1320.
16. (a) Hartley, G. S. J. Chem. Soc. 1938, 633–642; (b) Ciccone, S.; Halpern, J. Can. J.
Chem. 1959, 37, 1903–1910.
17. Khayer, K.; Sander, W. J. Bangladesh Acad. Sci. 2008, 32, 111–116.
18. (a) Chloroform; MSDS No. C2915 [Online]; Mallinckrodt Baker: Phillipsburg,
NJ, July 2, 2009. http://www.jtbaker.com/msds/englishhtml/c2915.htm
(accessed Sept 24, 2010); (b) Methylene chloride; MSDS No. M4420 [Online];
Mallinckrodt Baker: Phillipsburg, NJ, Aug 20, 2008. http://www.jtbaker.com/
msds/englishhtml/m4420.htm (accessed Sept 24, 2010).
19. Dunn, N. J.; Humphries, W. H.; Offenbacher, A. R.; King, T. L.; Gray, J. A. J. Phys.
Chem. A 2009, 113, 13144–13151.
20. Sokalski, W. A.; Go´ra, R. W.; Bartkowiak, W.; Kobylin´ ski, P.; Sworakowski, J.;
Chyla, A.; Leszczyn´ ski, J. J. Chem. Phys. 2001, 114, 5504.
Acknowledgments
This work was funded by the College of Wooster, the Copeland
Fund for Independent Study, the Wilson Fund, and NSF Grants