Photoinduced hinge-like molecular motion: Studies on xanthene-based cyclic azobenzene dimers

Article abstract of DOI:10.1021/jo0513616

Molecular devices incorporating azobenzene units represent active components of smart systems, as they are capable of exhibiting photoregulated cooperative molecular motion. Herein, we describe the synthesis, X-ray crystal analysis, and photochemical and thermal studies of a xanthene based cyclic azobenzene dimer and its precursor. The trans-trans isomer of the azobenzene dimer upon photoirradiation transforms to the eis-eis isomer through an intermediate trans-cis isomer. The X-ray crystal structures of the trans-trans isomer (open) and the cis-cis isomer (closed) provide unambiguous proof for the hinge-like molecular motion in this class of molecules. The inferences drawn from photochemical and thermal studies shed light on the effect of varied substitution and cyclic structures on the different transitions. The lifetime of the cis-cis isomer is estimated to be 6.43 years, whereas the trans-cis isomer is short-lived (2.73 min) at 303 K. A rational explanation for the relative stability of the different isomers is derived from the isokinetic plot and theoretical calculations.

Full text of DOI:10.1021/jo0513616

Photoinduced Hinge-Like Molecular Motion: Studies on
Xanthene-Based Cyclic Azobenzene Dimers
S. Anitha Nagamani, Yasuo Norikane, and Nobuyuki Tamaoki*
Molecular Smart System Group, Nanotechnology Research Institute, National Institute of Advanced
Industrial Science and Technology (AIST), Tsukuba Central 5, Higashi 1-1-1,
Tsukuba, Ibaraki 305-8565, Japan
n.tamaoki@aist.go.jp
Received July 1, 2005
Molecular devices incorporating azobenzene units represent active components of smart systems,
as they are capable of exhibiting photoregulated cooperative molecular motion. Herein, we describe
the synthesis, X-ray crystal analysis, and photochemical and thermal studies of a xanthene based
cyclic azobenzene dimer and its precursor. The trans-trans isomer of the azobenzene dimer upon
photoirradiation transforms to the cis-cis isomer through an intermediate trans-cis isomer. The
X-ray crystal structures of the trans-trans isomer (open) and the cis-cis isomer (closed) provide
unambiguous proof for the hinge-like molecular motion in this class of molecules. The inferences
drawn from photochemical and thermal studies shed light on the effect of varied substitution and
cyclic structures on the different transitions. The lifetime of the cis-cis isomer is estimated to be
6.43 years, whereas the trans-cis isomer is short-lived (2.73 min) at 303 K. A rational explanation
for the relative stability of the different isomers is derived from the isokinetic plot and theoretical
calculations.
Introduction
the molecular motion is driven by chemical, electrochemi-
cal, or photochemical forces have great potential in
molecular scale information processing.
The miniaturization of components used in the con-
struction of working devices is being pursued currently
by the bottom up approach, starting from the smallest
compositions of matter. In this realm, chemists have
extended the concept of macroscopic devices to a molec-
ular level.1 A molecular level device can be constructed
by a single molecule or a number of molecular compo-
nents that are designed so as to perform a regulated
molecular motion as a consequence of appropriate exter-
nal stimulation. To date, there exists many reports on
two-state systems, ranging from classical cis-trans
isomerization to more elaborate rotaxanes, catenanes,
and biomolecular constructs.2,3 These devices in which
In the literature, there are reports on different kinds
of molecular motions, and among them, the molecular
hinge-like motion has attracted the most attention.
Studies on a T4 lysozyme (an enzyme that dissolves
bacterial membranes) have shown the existence of a
hinge-like receptor, which controls the activity of the
enzyme.4a The X-ray structure of a transmembrane helix
having proline residues suggests that proline could
(2) Balzani, V.; Gomez, L. M.; Stoddart, J. F. Acc. Chem. Res. 1998,
31, 405-414.
(3) (a) Sauvage, J. P. Acc. Chem. Res. 1998, 31, 611-619. (b) Mao,
C. D.; Sun, W. Q.; Shen, Z. Y.; Seeman, N. C. Nature 1999, 397, 144-
146.
(4) (a) Dobson, C. M. Nature 1990, 348, 198-199. (b) Cordes, F. S.;
Bright, J. N.; Samson, M. S. P. J. Mol. Biol. 2002, 323, 951-960. (c)
Schwarzinger, S.; Wright, P. E.; Dyson, H. J. Biochemistry 2002, 41,
12681-12686.
* Corresponding author. Phone: 81-298-61-4671; fax: 81-298-61-
4673.
(1) Balzani, V.; Credit, A.; Raymo, F. M.; Stoddart, J. F. Angew.
Chem., Int. Ed. 2000, 39, 3348-3391.
10.1021/jo0513616 CCC: $30.25 © 2005 American Chemical Society
Published on Web 10/19/2005
9304
J. Org. Chem. 2005, 70, 9304-9313

Studies on Xanthene-Based Cyclic Azobenzene Dimers
SCHEME 1a
introduce an anisotropic molecular hinge in the helix,
which is believed to assist in its channel and reception
activities.4b Molecular hinge-like motion occurs during the
protein folding of apomyglobin in its urea denatured
state.4c Many thermally operated systems have been
synthesized to mimic the functioning of the molecular
hinge in biological systems. These systems that also find
wide use as hosts for guest complexation use either
cyclohexene, dioxa[2.2]orthocyclophane, or diazacyclo-
hexene rings to provide the conformational flexibility.5a-c
It is well-known that light offers many advantages as
a means for manipulating systems of either microscopic
or macroscopic size. As photons can be applied with
extreme temporal and spatial resolution, molecular as-
semblies with optical triggers are ideal systems for the
construction of molecular devices. Azobenzene has been
the most widely used optical trigger over the last few
decades for the design and synthesis of a large variety
of photoresponsive systems. This is because of the
pronounced change in geometry and polarity upon its
light-induced reversible isomerization, high photostabil-
ity, and good quantum yields.6
Recently, we have reported on a novel xanthene-based
cyclic azobenzene dimer, symmetrically substituted with
four t-butyl groups exhibiting a reversible hinge-like
molecular motion upon photoirradiation.7 The two azo
linkages in the trans-trans isomer photoisomerize co-
operatively to form the cis-cis isomer, and this transition
was intensity dependent as the intermediate trans-cis
isomer was short-lived (τ ) 28 s). The bulky t-butyl
groups rendered this molecule insoluble in common
organic solvents, and hence, crystallization was cumber-
some. Seeking a structural modification, we present here
the synthesis, characterization, photochemical, and ther-
mal isomerization studies on an analogous cyclic azoben-
zene dimer and its precursor devoid of the bulky t-butyl
groups. The purpose of this study is to first obtain the
crystal structures of the trans-trans and cis-cis isomers
of the cyclic azobenzene dimer, which would indeed
provide unambiguous proof for the hinge-like molecular
motion. Second, the unique structural feature of the cyclic
azobenzene dimer is that the two azobenzene units are
linked by an oxygen atom at the ortho position and a
carbon atom at the meta position. The oxygen linkers
bring about a conjugation throughout the cyclic structure.
The noncyclic precursor has a single azobenzene unit
with a similar substitution pattern. Hence, the different
properties of the cyclic azobenzene dimer and its precur-
sor are compared to reinforce the bond between molecular
structure and isomerization properties in variedly sub-
stituted azobenzenes.
a (i) n-BuLi, dry DMF‚THF, rt, 73%; (ii) Jones reagent, acetone,
rt, 95%; (iii) diphenylphosphorazide, benzyl alcohol, TEA, toluene,
85 °C, 87%; (iv) KOH, EtOH, 77°C, 98%; (v) MnO2, benzene, 80°C,
52%; and (vi) t-BuOK, t-BuOH, DMSO, rt, 17%.
Results and Discussion
(i) Synthesis. The reaction sequence adopted to
synthesize the target molecules is depicted in Scheme 1.
Details of the reactions are described in the Experimental
Procedures. 9,9-Dimethyl xanthene was treated with
n-BuLi/DMF in THF to yield the dialdehyde 6,8a which
was oxidized to the diacid 5 with Jones reagent.8b
A
Curtius reaction using diphenylphosphoryl azide in
toluene transformed 5 to the rearranged dibenzyl ester
4, which on base hydrolysis gave the key intermediate
diamine 3 in quantitative yield.8c The diamine was
oxidized in a stepwise manner to avoid polymerization.
In the first step, MnO2 oxidation gave the monoazo-
bisamine 2(t), which was cyclized using t-BuOK to obtain
the target cyclic azobenzene dimer 1(t,t).
(ii) Molecular Structural Details Derived from
X-ray Crystal Analysis. The X-ray results of all the
isomers of 1 and 2 show that the xanthene units have a
nonplanar structure (bent angle ) 154°), and hence, it
can be fitted into an imaginary rigid block with the
dimensions l ) 8.5 Å, b ) 5.1 Å, and w ) 1.6 Å (Figure
1a).
In the case of 2, as the two xanthene blocks are
connected by one azo linkage, molecular motion along the
vertical and horizontal axis of the azo linkage is allowed.
Figure 1b shows the X-ray structure of the trans isomer
of 2. The torsion and dihedral angle of different bonds
(Table 1) indicates nearly coplanarly arranged xanthene
blocks. Thus, a part of the xanthene unit, which happens
to be substituents at the 2,2′ and 3,3′ positions of the
azobenzene unit, is displaced away from the adjacent ring
system, thus inducing only little distortion to planarity
when compared to trans-azobenzene.9
Compound 2(t) isomerizes to give the cis isomer 2(c)
in chloroform or toluene upon exposure to 366 nm
irradiation. Compound 2(c) was isolated by silica gel
(5) (a) Ashton, P. R.; Brown, G. R.; Isaacs, N. S.; Giuffrida, D.;
Kohneke, F. H.; Mathias, J. P.; Slawin, A. M.; Smith, Z. D. R.; Stoddart,
J. F.; Williams, D. J. J. Am. Chem. Soc. 1992, 114, 6330-6353. (b)
Mataka, S.; Mitoma, Y.; Sawada, T.; Thiemann, T.; Taniguchi, M.;
Tashiro, M. Tetrahedron 1998, 54, 5171-5186. (c) Warrener, R. N.;
Butler, D. N.; Liu, L.; Margetic, D.; Russell, R. A. Chem.sEur. J. 2001,
15, 3406-3414.
(8) (a) Kelly, C.; Mark, V.; Vanessa, Y.; Simon, C.; Alan, F. Biorg.
Med. Chem. Lett. 2000, 10, 1147-1151. (b) Dunayevskiy, Y. M.; Vouros,
P.; Wintner, E. A.; Shipps, G. W.; Carell, T.; Rebek, J. Proc. Natl. Acad.
Sci. U.S.A. 1996, 93, 6152-6157. (c) Buhlmann, P.; Nishizawa, S.; Xiao,
K. P.; Umezawa, Y. Tetrahedron 1997, 53, 1647-1654.
(9) Bouwstra, J. A.; Schouten, A.; Kroon, J. Acta Crystallogr. 1983,
C39, 1121-1123.
(6) (a) Rau, H. Studies in organic chemistry: Photochromism,
molecules, and systems; Durr, H., Bonas-Laurent, H. Eds.; 1990. (b)
Feringa, B. L. Molecular Switches; Wiley VCH GmBH: Weinheim,
Germany, 2001.
(7) Norikane, Y.; Tamoaki, N. Org. Lett. 2004, 6, 2595-2598.
J. Org. Chem, Vol. 70, No. 23, 2005 9305

Nagamani et al.
FIGURE 1. Chemical structure (a) and crystal structure of 2(t) with displacement ellipsoids shown at the 50% probability level
with the dotted lines showing the H-bonding (b).
FIGURE 2. Chemical structure (a) and crystal structure of 2(c) with displacement ellipsoids shown at the 50% probability level
with the dotted lines showing the H-bonding (b).
TABLE 1. Torsion Angles and Bond Angle of Azobenzene Units in Hinge Molecule and Its Precursor
compound
type
CNNC
NNCC
NNC
CCOC
Trans isomer
17.4
trans-azo-benzene
180.0
114.1
2(t)
-176.1
-176.5, 7.2
113.9, 113.7
117.0, 112.6
112.3, 116.6
146.4, -147.5
150.9, -150.2
154.9, -156.2
26.4, -24.9
173.4, -175.1
-5.5, 7.8
-8.2, -170.2
-167.4, 14.8
-143.5, -40.1
31.0, -152.5
159.1, -24.4
1(t,t)
conformer A
conformer B
178.9
-179.1
Cis isomer
cis-azo-benzene
8.0
8.6
53.3
121.9
2(c)
56.4, -131.4
55.9, -131.4
112.4, -74.2
109.3, -79.6
121.9, 120.9
-159.9, 156.3
150.3, -146.7
151.5, 27.5
1(c,c)
-3.3
119.7, 120.1
151.8, 27.1
column chromatography from an irradiated solution after
attaining a photostationary state using 366 nm light.
Crystallization from a mixture of chloroform and hexane
gave yellow crystals suitable for X-ray analysis. The
different dihedral and bond angles (Table 1) derived from
the crystal structure of 2(c) (Figure 2b) are very close to
that of cis-azobenzene, revealing that there exists no
pronounced effect of the ortho and meta substitutions.10
The interplanar angle at the upper part of the xanthene
blocks is 100°, whereas at the bottom part, it is 118°
(Figure 2a), which indicates a slightly distorted overall
molecular structure. In each xanthene block, there exists
a H-bond between the H of the free amine and the O of
the xanthene unit. An additional bond in 2(c) is between
the H of amine of one xanthene block and the O of the
other xanthene block, which is in near proximity because
of isomerization,11 thus accounting for two and three
H-bonds in 2(t) and 2(c), respectively. This opportunity
(10) Mostad, A.; Romming, C. Acta Chem. Scand. 1971, 25, 3561-
3568.
9306 J. Org. Chem., Vol. 70, No. 23, 2005

Studies on Xanthene-Based Cyclic Azobenzene Dimers
FIGURE 3. Chemical structure (a) and crystal structure of 1(t,t) conformer A with displacement ellipsoids shown at the 50%
probability level (b).
FIGURE 4. Chemical structure (a) and crystal structure of 1(c,c) with displacement ellipsoids shown at the 50% probability
level (b).
for the formation of an additional H-bond may be the
driving force for the stabilization of the present confor-
mation in 2(c) over the one in which the amino groups
are oriented in opposite directions.
angle s for sNdNs bonds in both the conformers is 179°,
thus steering the two xanthene blocks to coplanarity.
The lifetime of 1(c,c) was long enough for isolation and
crystallization. Compound 1(t,t) isomerized to give 1(t,c),
which further isomerized to 1(c,c) in chloroform or
toluene upon exposure to 366 nm irradiation. Compound
1(c,c) was isolated by silica gel column chromatography
from an irradiated solution after attaining photostation-
ary state using 366 nm light. Crystallization from a
mixture of dichloromethane and hexane gave orange
crystals suitable for X-ray analysis. In 1(c,c) (Figure 4b),
the two azobenzene units were placed in a cyclic structure
without bringing about much change in the CsNdN
angles (120°) or the CsNdNsC dihedral angle (-3.3°)
as compared to that of cis-azobenzene. The molecule has
a mirror plane passing through the center of the xan-
thene unit. The interplanar angle between the two
xanthene blocks is 112° (Figure 4a), which confirms the
uniformly bent structure of 1(c,c). The crystal structures
of 1(t,t) and 1(c,c), which represent the open and closed
states, provide unambiguous proof for the hinge-like
molecular motion (Figures 3a and 4a). The distance
between the carbon atoms at the para-positions of both
the azobenzene units in 1(t,t) is 9.0 Å, and the same in
1(c,c) is 5.9 Å, thus leading to a 35% reduction in the
In the case of 1, two azo linkages are used for
connecting the two xanthene blocks. Efficient motion of
the two azo linkages must occur in a cooperative fashion
along the vertical axis to bring about the unique hinge-
like molecular motion between the 1(t,t) and 1(c,c)
isomers. X-ray crystal analysis of 1(t,t) revealed that
there are two kinds of conformers in a unit cell. They
mainly differ in the extent of bending at the xanthene
units and hence vary in the length and width of the
xanthene blocks (conformer A: l ) 8.5 Å and w ) 1.6 Å;
conformer B: l ) 9.0 Å and w ) 0.9 Å). Figure 3b shows
the X-ray structure of conformer A, and the representa-
tive bond angles are compiled in Table 1. The torsional
(11) Jeffrey, G. A.; Saenger, W. Hydrogen Bonding in Biological
Structures; Springer-Verlag: Berlin, 1991. The H-bonds have been
identified based on the distance between the proton and the acceptor
(i.e., d(H‚‚‚O)) and the angle made between the donor-proton-acceptor
atoms (i.e., θ(N-H‚‚‚O)). H-bonds are present between a H (H3 and
H4) of the free amine and the O (O1 and O2) of the xanthene unit,
and the distance d(H‚‚‚O) is 2.33 Å and the angle θ(NsH‚‚‚O) is 103°
in both 2(t) and 2(c). The additional H-bond in 2(c) has d(H‚‚‚O) of
2.45 Å and an angle θ(NsH‚‚‚O) of 136°.
J. Org. Chem, Vol. 70, No. 23, 2005 9307

Nagamani et al.
FIGURE 5. 1H NMR spectra of 1(t,t) in 1,1,2,2-tetrachloroethane-d2 before (a) and after (b) irradiation. For labeling, see the
structures of 1(t,t) and 1(c,c) given beside the spectra.
length of the molecule. These two states are reversible
on photoirradiation and have a high thermal stability as
the azo linkages act cooperatively to stabilize the respec-
tive configurations.
In 1, the aliphatic (methyl) protons appear as singlets
in both trans and cis isomers, indicating that these are
least affected by the isomerization because of their
greater distance and lack of conjugation from the azo
unit. In general, the protons at the ortho position of the
azo group have maximum shift as compared to that of
the meta or para positions. In 1(c,c), the ortho protons
are shifted upfield by 1.25 ppm, whereas the meta and
para protons are shifted approximately by 0.4 ppm, which
concurs with the values obtained for several substituted
azobenzenes.
(iii) NMR Spectral Changes. NMR assignments
clearly indicate a difference in chemical shifts between
the proton resonances of the cis and trans isomers, which
are expected from an empirical standpoint.12 The reasons
are the following: (i) the two aromatic rings are initially
remote from one another (trans) but encounter each other
closely as a result of photoisomerization (cis) and (ii)
protons that were initially only subject to the local
deshielding effect of their own aromatic ring within the
ring plane (trans) now encounter the additional shielding
effect of the remote out-of-plane aromatic ring (cis). The
NMR spectral changes obtained for 2 after irradiation
are similar to several substituted azobenzenes (see
Supporting Information for details).
Figure 5a shows the 1H NMR spectrum of 1 (in 1,1,2,2-
tetrachloroethane-d2) in the aromatic region, which can
be attributed to a single form of the molecule 1(t,t). On
the basis of symmetry considerations, the two doublets
at 7.66 and 7.46 ppm representing the two sets of two
aromatic protons belong to the H1 and H3 protons, and a
triplet at 7.18 ppm integrating for one set of two aromatic
protons belongs to the H2 protons. The spectrum obtained
upon photoirradiation with 366 nm light for 5 min is as
shown in Figure 5b. The signals corresponding to 1(c,c)
appear upfield as compared to that of the 1(t,t), and
signals corresponding to the short-lived isomer 1(t,c)
were not observed. A doublet at 6.97 ppm integrating for
one set of two aromatic protons belongs to the H3*
protons, one triplet at 6.83 ppm integrating for one set
of two aromatic protons belongs to the H2* protons, and
one doublet at 6.41 ppm integrating for one set of two
aromatic protons belongs to the H1* protons. Integration
of the signals corresponding to 1(t,t) and 1(c,c) gives a
composition of 80% of 1(t,t) and 20% of 1(c,c).
(iii) Absorption Spectra. Figures 6a and 7a show the
absorption spectra of 2(t) and 1(t,t) in toluene, respec-
tively. The absorption maxima of 2(t) are 395 nm (ꢀ )
8000 M-1 cm-1) and 326 nm (ꢀ ) 11 000 M-1 cm-1), while
those of 1(t,t) are 365 nm (ꢀ ) 15 000 M-1 cm-1) and 320
nm (ꢀ ) 29 000 M-1 cm-1). The absorption spectra of the
trans isomers of both the compounds are similar, and
they differ from that of azobenzene itself, which exhibits
absorption maxima at 444 nm (n-π*, ꢀ ) 440 M-1 cm-1
)
and 316 nm (π-π*, ꢀ ) 22 000 M-1 cm-1).13 The cyclic
structure brings about a hypsochromic shift for both the
π-π* bands as compared to the acyclic analogue. The
molar extinction coefficient of 2(t) is almost half of that
of 1(t,t), which is reasonable as 2(t) has only one
azobenzene unit, whereas in 1(t,t) two azobenzene units
form the cyclic structure. The molar extinction coefficient
of azobenzene for the π-π* transition seems to be
intermediate to that of 2(t) and 1(t,t), indicating that
the specific substitution pattern influences the electronic
and steric interactions, thus affecting the absorption. The
special features of the absorption spectra of 1(t,t) are the
splitting of the π-π* band and the absence of any distinct
n-π* band. Upon photoirradiation, there is a decrease
in the absorption of both the π-π* bands without any
concomitant increase in the n-π* band. Normally for
azobenzene, the spectra are characterized by a low
intensity (symmetry forbidden) n-π* band in the 400-
500 nm region and a very intense (symmetry allowed)
(12) Tait, K. M.; Parkinson, J. A.; Bates, S. P.; Ebenezer, W. J.;
Jones, A. C. J. Photochem. Photobiol., A 2003, 154, 179-188.
(13) Forber, C. L.; Kelusky, E. C, Bunce, N. J.; Zerner, M. C. J. Am.
Chem. Soc 1985, 107, 5884-5890.
9308 J. Org. Chem., Vol. 70, No. 23, 2005

Studies on Xanthene-Based Cyclic Azobenzene Dimers
FIGURE 6. Changes in the absorption spectra of 2(t) in toluene upon irradiation at (a) 366 nm: a, 0 min; b, 20 s; c, 40 s; d, 1
min; e, 1.5 min; and f, 2 min. (b) 436 nm: f, 0 min; g, 10 s; h, 20 s; and i, 30 s. (c) Absorption spectra of pure 2(c) measured by
a photodiode array detector attached to a HPLC system. (d) Absorption changes observed at 326 nm after alternating the irradiations
at 366 nm (3 min) and 436 nm (1 min) over 16 complete cycles.
FIGURE 7. Changes in the absorption spectra of 1(t,t) in toluene upon irradiation at (a) 366 nm: a, 0 min; b, 2 min; c, 3 min;
d, 5 min; and e, 7 min. (b) 436 nm: e, 0 min; f, 30 s; g, 1 min; and h, 2 min. (c) Absorption spectra of pure 1(c,c) measured by a
photodiode array detector attached to a HPLC system. (d) Absorption changes observed at 320 nm after alternating the irradiations
at 366 nm (8 min) and 436 nm (3 min) over 16 complete cycles.
π-π* band at the 300-340 nm region. Upon photoirra-
diation as a consequence of trans-cis isomerization, the
intensity of the π-π* band is decreased with a concomi-
tant increase of that of the n-π* band.
Usually, all azobenzenophanes have an auxiliary band
of moderate intensity in the 380 nm region, Rottger et
al. attributed the origin of these bands to the interactions
of the transition moments.14 Figure 7a,b shows that the
auxiliary band in the present case is more distinct when
compared to that of other azobenzenophanes. As a similar
spectral pattern and changes are observed in the non-
cyclic 2(t) (Figure 6a,b), one can rule out the role of a
cyclic structure in bringing out such an effect. So, the
specific substitution on the azobenzene unit plays a major
role. In most of the reported cyclic azobenzene dimers,
(14) Rottger, D.; Rau, H. J. Photochem. Photobiol., A 1996, 101, 205-
214.
J. Org. Chem, Vol. 70, No. 23, 2005 9309

Nagamani et al.
the azobenzene units are connected through one or more
insulating methylene units; thus, the azobenzene units
act independently.15 In the present case, each azobenzene
unit acts as a substituent on the other because they are
conjugated through the ortho oxygen linkers. 2,2′-
Dimethoxyazobenzene exhibits a typical splitting of the
π-π* band and is explained based on the steric inhibition
to planarity in these systems, which arises because of
the bulky ortho substituent.16 But, the X-ray results of
1(t,t) and 2(t) show that the azobenzene units are not
distorted from planarity to a large extent. So, it is
probable that the splitting of the π-π* band in the
absorption spectra stems from the electronic effect of the
ortho oxygen substituent as suggested by Morris and
Brode.17 Figures 6c and 7c show the absorption spectra
of the pure cis isomers 2(c) and 1(c,c) in toluene,
respectively. It is evident that the peak positions of the
cis isomers are similar to that of the trans isomers. So,
it is perceivable that at the photostationary state the
absorption of the trans isomer dominates, and the spectra
of the trans rich and cis rich states differ only in the
absorption intensity.
(iv) Photochemical Isomerization. The absorption
spectral changes that occur for 2(t) and 1(t,t) on pho-
toisomerization are as shown in Figures 6a,b and 7a,b.
Both compounds behave in a similar manner. Upon
irradiation with 366 nm light, there is a gradual decrease
in the intensity of absorption of both the π-π* bands,
and upon irradiation with 436 nm light, the absorption
intensity is recovered back (52% for 2(t) and 95% for 1-
(t,t)). The photostationary state composition was deter-
mined using NMR analysis. Compound 2(t) upon 366 nm
irradiation isomerizes to 2(c), yielding a photostationary
state composition of 26% of 2(t) and 73% of 2(c) within
2 min. Compound 1(t,t) isomerizes to 1(t,c), which
further isomerizes to 1(c,c), and a photostationary state
composition of 67% of 1(t,t) and 32% of 1(c,c) was
reached within 7 min. The recovery of 2(t) from 2(c) by
436 nm irradiation is much lower than that of 1(t,t) from
1(c,c), probably because of (i) a higher quantum yield of
the forward isomerization and (ii) a higher molar extinc-
tion coefficient of 2(t). By alternating the irradiation
wavelengths between 366 and 436 nm, we verified that
the photochemical trans-cis and cis-trans processes
could be repeated between the 366 and 436 nm photo-
stationary states for more than 16 cycles (Figures 6d and
7d).
FIGURE 8. Comparison of the rate constants of the different
transitions for 1 and 2.
state was estimated. The extinction coefficient of 2(c) was
estimated to be 5000 M-1 cm-1 (326 nm) and 3600 M-1
cm-1 (395 nm), and that for 1(c,c) was 3800 M-1 cm-1
(365 nm) and 7200 M-1 cm-1 (320 nm). As the intermedi-
ate 1(t,c) was short-lived, an accurate calculation of its
concentration and hence its molar extinction coefficient
was not feasible. Assuming that azobenzene units absorb
independently in 1(t,c), we calculated the ꢀ of 1(t,c) as
an average value of the molar extinction coefficients of
1(t,t) and 1(c,c); hence, ꢀ of 1(t,c) at 365 nm was 9400
M-1 cm-1 and at 320 nm was 18 000 M-1 cm-1. Making
use of these values of molar extinction coefficients and
the initial portion of the A320 and time plots, the quantum
yields were evaluated. For the cyclic azobenzene dimer,
Φtt-tc was evaluated to be 0.01, whereas for its precursor,
Φt-c was found to be 0.16. The lower value of the
quantum yield for the cyclic azobenzene dimer may be
due to (i) the lack of an apparent energy minimum for
the different transition state geometries between 1(t,t)
and 1(t,c) and (ii) probably the isomerization is through
a transition state having close resemblance to 1(t,t)
geometry.
(v) Thermal Isomerization. The thermal cis-trans
isomerization of the transition 2(c) to 2(t) was deter-
mined by monitoring the increase of absorbance at λmax
in the absorption spectra. The first-order rate constant
(k) of the reaction was found to be 1.3 × 10-5 s-1 at 303
K. Compound 1(c,c) isomerizes in a stepwise manner,
initially to 1(t,c), which further isomerizes to 1(t,t). The
transition from 1(c,c) to 1(t,c) is very slow and proceeds
with a first-order rate constant k ) 5.01 × 10-9 s-1 at
303 K, which was monitored by the temporal increase in
concentration of 1(t,t) with temperature by NMR analy-
sis. Compound 1(t,c) isomerizes very quickly to 1(t,t)
with a first-order rate constant k ) 8.53 × 10-3 s-1 at
303 K, which was independently determined by following
the increase of absorbance at λmax within 5 min just after
366 nm irradiation using a photodiode array detector.
The first-order rate plots of these transitions at different
temperatures (Figure 8) were used to calculate the
thermodynamic parameters of the back relaxation pro-
cess, namely, the activation energy (Ea), Arrhenius
parameter (A), activation enthalpy (∆Hq), the activation
entropy (∆Sq), and the Gibbs free energy of activation
(∆Gq). The values obtained for the different parameters
are tabulated (Table 2).
The photoisomerization quantum yields can be calcu-
lated by the temporal absorption spectra if the absorption
coefficients of the reacting molecules are known. As
described earlier with help of 1H NMR spectral data, the
composition of the isomers at the 366 nm photostationary
(15) (a) Norikane, Y.; Kitamoto, K.; Tamaoki, N. J. Org. Chem. 2003,
68, 8291-8304. (b) Tamaoki, N.; Koseki, K.; Yamaoka, T. Angew.
Chem., Int. Ed. Eng. 1990, 29, 105-106. (c) Tamaoki, N.; Ogata, K.;
Koseki, K.; Yamaoka, T. Tetrahedron 1990, 46, 5931-5942. (d)
Tamaoki, N.; Yamaoka, T. J. Chem. Soc., Perkin. Trans. 1991, 873-
878. (e) Tamaoki, N.; Yoshimura, S.; Yamaoka, T. Thin Solid Films
1992, 221, 132-139. (f) Rau, H.; Rottger, D. Mol. Cryst. Liq. Cryst.
1994, 246, 143-146. (g) Tauer, E.; Machinek, R. Liebigs Ann. 1996,
1213-1216. (h) Luboch, E.; Wagner-Wysiecka, V. C.; Kravtsov; Kessler,
V. Pol. J. Chem. 2003, 77, 189-196.
(16) Gore, P. H.; Wheeler, O. H. J. Am. Chem. Soc. 1961, 26, 3295-
3298.
(17) Morris, R. J.; Brode, W. R. J. Am. Chem. Soc. 1948, 70, 2485-
2488.
The thermodynamic parameters for the transition to
2(t) are comparable to that of cis-trans isomerization
9310 J. Org. Chem., Vol. 70, No. 23, 2005

Studies on Xanthene-Based Cyclic Azobenzene Dimers
TABLE 2. Thermodynamic Properties for the Different Transitions of 1 and 2
transition
Ea (kcal mol-1
)
A
∆H (kcal mol-1
)
∆S (cal K-1 mol-1
)
∆G (kcal mol-1
)
τ ) 1/k at 303 K
2(c) to 2(t)
1(t,c) to 1(t,t)
1(c,c) to 1(t,c)
18.5
14.3
22.0
3.2 × 108
1.7 × 108
2.3 × 108
17.9
13.7
21.2
-8.38
-9.15
-4.25
21.0
16.4
22.5
20.6 h
2.73 min
6.43 years
of several 2,2′-disubstituted azobenzenes.18 The thermal
isomerization of 1(t,c)-1(t,t) is 10 00 000 times faster
than 1(c,c)-1(t,c). This is mainly due to the extremely
low activation energy (Ea ) 14.3 kcal mol-1). The entropy
of activation is higher for the transition 1(c,c)-1(t,c) as
compared to that of 1(t,c)-1(t,t), which indicates a
modestly increased disorder at the transition state.
Compound 2(c) has a lifetime (τ) of 20.6 h (1/k) at 303
K. The most striking feature of 1 is that 1(c,c) has the
longest lifetime (τ) of 6.43 years (1/k) at 303 K among
the known cyclic azobenzene dimers.19 The lifetime of the
1(t,c) isomer devoid of the bulky t-butyl groups has
increased 8-fold as compared to the trans-cis isomer
having t-butyl groups indicating the major role played
by steric crowding in destabilizing the isomer.
A theoretical support was sought to evaluate the
relative stability of all the isomers of 1 and 2, and the
heats of formation were estimated by ab initio quantum
chemical calculations using the RHF/6-31G** method.19
The geometries of the molecular structures were fully
optimized. The calculations for 2 show that 2(t) is 10.0
kcal mol-1 more stable than 2(c). An experimental study
on the heat of combustion showed that trans-azobenzene
is about 10.0 kcal mol-1 more stable than cis-azoben-
zene.20 The values predicted for 2 match well with that
of azobenzene. The results pertaining to 1 (Figure 9) show
that 1(t,t) and 1(c,c) are 26.7 and 1.24 kcal mol-1 more
stable than 1(t,c). The relatively small energy difference
between 1(t,c) and 1(c,c) and an extraordinarily large
energy difference between 1(t,t) and 1(t,c) indicates that
1(t,c) may be destabilized by its distorted structure
conferred by the ring strains.
To compare the mechanism of thermal isomerization,
a general isokinetic plot or compensation rule is used,
which translates into a linear interdependence of ∆Hq
and ∆Sq. This particular trend is followed when isomer-
ization occurs via a common mechanism.21 Figure 10
shows the isokinetic plot for 1, 2, azobenzene, and its
dimers for which the thermodynamic properties are
reported. It is interesting to note that in all the com-
pounds except for the two points, which correspond to
the (t,c)-(t,t) process of 1 and that of the dibenzo-
FIGURE 9. Energy diagram of 1 estimated from the experi-
ment and theoretical calculations. Structures shown were
obtained from RHF/6-31G** calculations: (a) values calculated
theoretically and (b) experimental values.
azobenzenophanes, the compensation rule has been
found. The line corresponds to the various azobenzenes
that have been reported to isomerize by the inversion
mechanism. Scattering of the values around the straight
line is due to the effect of steric crowding and solvation
on rate. Thus, the inversion mechanism may be operative
in the thermal back relaxation of 1(c,c)-1(t,c) and 2-
(c)-2(t) transitions.
But, the (t,c) to (t,t) transitions of 1 and 11 seem to
proceed by a different mechanism. The steric distortion
of (t,c) isomers of these systems is very high as the two
azobenzene units, one in the trans form (9.0 Å) and the
other in cis form (5.9 Å), have the restrictions of both
distance and angle imposed by the central pyran or
phenyl ring. As the isomerization starts from a trans-
cis isomer having a highly distorted structure, it can be
expected to opt for a different kind of mechanism for the
transition to get rid of the steric strains. Thus, the
thermodynamic parameters fall apart from the common
straight line representing the inversion mechanism.
(18) Nishimura, N.; Sueyoshi, T.; Yamanaka, H.; Imai, E.; Yama-
moto, S.; Hasegawa, S. Bull. Chem. Soc. Jpn. 1976, 49, 1381-1387.
(19) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A.;
Stratmann, R. E.; Burant, J.; Dapprich, S. C.; Millam, J. M.; Daniels,
A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.;
Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford,
S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y. C.; Morokuma, K. Q.;
Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.;
Cioslowski, J.; Ortiz, J. V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.;
Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Challacombe, M.; Gill, P. M. W.; Johnson, B. C.; Wong, M. W.; Andres,
J. L. W.; Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A.
Gaussian 98, Revision A.9; Gaussian, Inc: Pittsburgh, PA 1998.
(20) Corruccini, R. J.; Gilbert, E. C. J. Am. Chem. Soc. 1939, 61,
2925-2927.
Conclusions
We have provided unambiguous proof for the photo-
induced hinge-like molecular motion using the X-ray
crystal structures of 1(t,t) (open) and 1(c,c) (closed)
states. The two azo linkages in 1(t,t) cooperatively
isomerize to 1(c,c) via a short-lived 1(t,c) isomer. The
thermal isomerization of 1(t,c)-1(t,t) was found to be
10 00 000 times faster than 1(c,c)-1(t,c). The lifetime
of 1(c,c) was estimated to be 6.43 years; thus, 1(c,c) is
the longest lived cis-cis isomer of cyclic azobenzene
(21) Asano, T.; Okada, T.; Shinkai, S.; Shigematsu, K.; Kusano, Y.;
Manabe, O. J. Am. Chem. Soc. 1981, 103, 5161-5165.
J. Org. Chem, Vol. 70, No. 23, 2005 9311

Nagamani et al.
FIGURE 10. Isokinetic plot for ∆Hq - ∆Sq of the cis-trans thermal isomerization of cyclic azobenzene dimers.
9,9-Dimethyl-9H-xanthene-4,5-dicarboxylic Acid (5).
Freshly prepared Jones reagent was added dropwise to a
solution of 6 (1 g, 3.73 mmol) in acetone (10.0 mL) until the
reddish brown color persisted. The reaction mixture was
stirred at room-temperature overnight. Addition of water (10.0
mL) led to precipitation of the product as a white solid, which
dimers. The photochemical and thermal behavior of 2 is
similar to several 2,2′-disubstituted azobenzenes. Quan-
tum chemical calculations predict a relatively small
energy difference between 1(t,c) and 1(c,c), indicating
that 1(t,c) may be destabilized by its highly distorted
structure conferred by the ring strains. The isokinetic plot
revealed that the thermal isomerization of 2(c)-2(t) and
1(c,c)-1(t,c) followed inversion mechanisms, whereas
the transition 1(t,c)-1(t,t) proceeded by a different
mechanism. The cyclic structure restricts the rotation of
the phenyl units around the azo linkages, thus regulating
the motion of the molecular device. Thus, the knowledge
of correlation between the structure and the isomeriza-
tion property of variedly substituted azobenzenes can
make way for the better design of photoregulated mo-
lecular devices.
1
was filtered and dried. Yield ) 95%, mp ) 248 °C; H NMR
(300 MHz, CDCl3): 7.79 (dd, J1 ) 7.7 Hz, J2 ) 1.2 Hz, 2H,
Ar), 7.69 (dd, J1 ) 7.7 Hz, J2 ) 1. 2 Hz, 2H, Ar), 7.25 (t, J )
7.7H, 2H, Ar), 1.61 (s, 6H, 2 × CH3).
9,9-Dimethyl-9H-xanthene-4,5-diylbiscarbamic Acid
Dibenzyl Ester (4). Compound 5 (1 g, 3.2 mmol), diphen-
ylphosphorazide (0.7 g, 6.6 mmol), triethylamine (0.68 g, 6.6
mmol), benzyl alcohol (0.72 g, 6.66 mmol), and toluene (40.0
mL) were heated at 80 °C for 22 h. Upon evaporation of the
solvent, a pale yellow oil was obtained that was purified on a
silica gel column using hexane/ethyl acetate (9:1) as the eluent
to yield the product as a white crystalline solid. Yield ) 87%;
mp )110-112 °C; 1H NMR (300 MHz, CDCl3): 8.03 (brs, 2 H,
2 × NH), 7.36-7.05 (m, 16H, Ar), 5.14 (s, 4H, 2 × CH2Ph),
1.60 (s, 6H, 2 × CH3).
Experimental Procedures
9,9-Dimethyl-9H-xanthene-4,5-diamine (3). Compound
4 (1 g, 2.1 mmoles) was dissolved in EtOH (100 mL) saturated
with KOH and heated to 100 °C for 24 h. After neutralizing
the reaction mixture, the product was extracted into ethyl
acetate. The organic layer was dried over sodium sulfate and
evaporated to give a brown solid, which was purified on a silica
gel column using hexanes/ethyl acetate (4:1) as an eluent to
afford the product as light yellow solid. Yield ) 98%; mp
)148-151 °C; 1H NMR (300 MHz, CDCl3): 6.91 (t, J ) 7.7
Hz, 2H, Ar), 6.84 (dd, J1 ) 7.4 Hz, 2H, Ar), 6.65 (dd, J1 ) 7.6
Hz, J2 ) 1.7 Hz, 2H, Ar), 3.84 (brs, 4H, 2 × NH2), 1.6 (s, 6H,
2 × CH3).
9,9-Dimethyl-9H-xanthene-4,5-dicarbaldehyde (6). n-
Butyllithium (7.4 mL, in hexane, 11.9 mmol) was added
dropwise to a stirred and cooled solution of 9,9-dimethyl-9H-
xanthene (1 g, 4.76 mmol) in dry THF (50.0 mL) under an
atmosphere of dry nitrogen. The reaction mixture was stirred
at room temperature for 15 min, and then a previously cooled
solution of DMF (0.9 mL, 11.9 mmol) in THF (4.0 mL) was
added dropwise at 0 °C. The reaction mixture was slowly
allowed to warm to room temperature and was stirred for 1
h, and then diluted HCl (10.0 mL) was added. The reaction
mixture was then taken up in ether (2 × 50 mL), and the
combined ether extracts were washed with water (2 × 50 mL)
and dried over anhydrous sodium sulfate. The solvent was
removed in vacuo, and the pure product was isolated by column
chromatography on silica gel with hexane/ethyl acetate (9:1)
as eluent. The pure product was obtained as an off-white solid.
(E)-1,2-Bis(5-amino-9,9-dimethyl-9H-xanthene-4-yl)-
diazene (2). A benzene solution (200 mL) of a mixture of 3
(1.20 g, 3.40 mmol) and MnO2 (1.5 g) was refluxed in the dark
for 45 h. After cooling to room temperature, the reaction
mixture was filtered through Celite. The filtrate was evapo-
rated to dryness under reduced pressure, and the residue was
chromatographed on silica gel with hexane/ethyl acetate (9:1)
as eluent, to give 2 purely in its trans form as an orange solid.
1
Yield ) 73%; mp ) 178-182 °C; H NMR (300 MHz, CDCl3):
δ 10.69 (s, 2H, 2 × CHO), 7.82 (dd, J1 ) 7.5 Hz, J2 ) 1.6 Hz,
2H, Ar), 7.71 (dd, J1 ) 7.5 Hz, J2 ) 1.6 Hz, 2H, Ar), 7.26 (t, J
) 7.7H, 2H, Ar), 1.69 (s, 6H, 2 × CH3).
9312 J. Org. Chem., Vol. 70, No. 23, 2005

Studies on Xanthene-Based Cyclic Azobenzene Dimers
Yield ) 52%; mp ) >300 °C; 1H NMR (600 MHz, CDCl3): 7.66
(dd, J1 ) 8.6 Hz, J2 ) 2.4 Hz, 2H, Ar), 7.55 (dd, J1 ) 7.5 Hz,
J2 ) 1.2 Hz, 2H, Ar), 7.16 (t, J ) 8.0 Hz, 2H, Ar), 6.95 (t, J )
8.0 Hz, 2H, Ar), 6.84 (d, J ) 8.1 Hz, 2H, Ar), 6.68 (d, J ) 8.2
Hz, 2H, Ar), 4.11(brs, 4H, 2 × NH2) and 1.69 (s, 6H, 2 × CH3)
13C NMR (75 MHz, CDCl3): 147.8 (C), 141.3 (C), 138.3 (C),
135.3 (C), 132.6 (C), 130.3 (C), 128.6 (CH), 123.5 (CH), 122.7
(CH), 115.9 (CH), 114.6 (CH), 113.3 (CH), 34.5 (C), 31.6 (CH3).
ESIMS (m/z) [M + H] calcd for C30H28O2N4 477.52, found
477.41.
and evaporated to dryness under reduced pressure. The
residue was chromatographed on silica gel with hexane/
chloroform (3:2) as eluent, to give 1 purely in its trans-trans
form as a yellow solid. Yield in 17%; mp ) >300 °C; 1H NMR
(600 MHz, CDCl3): 7.79 (dd, J1 ) 7.9 Hz, J2 ) 1.6 Hz, 4H,
Ar), 7.55 (dd, J1 ) 7.7 Hz, J2 ) 1.6 Hz, 4H, Ar), 7.26 (t, J )
7.8 Hz, 4H, Ar), 1.74 (s, 12H, 4 × CH3); 13C NMR (75 MHz,
CDCl3): 143.9 (C), 140.9 (C), 131.3 (C), 128.5 (CH), 123.3 (CH),
123.1 (CH), 34.2 (C), 32.7 (CH3); ESIMS (m/z) [M + H] calcd
for C30H24O2N4 473.52, found 473.32.
(E,E) 1,16-Dioxa[1.1.1.1](2,2′,3,3′)31,31,32,32 Tetrameth-
yl Azobenzenophane (1). In the presence of dry oxygen,
potassium t-butoxide (32 mg, 0.28 mmol) in DMSO and t-butyl
alcohol (25 mL, 80:20) was vigorously stirred. From a dropping
funnel, 2 (50 mg, 0.071 mmol) in a mixture of DMSO and
t-butyl alcohol (25 mL, 80:20) was slowly added for 3 h at room
temperature. After stirring at room temperature for 40 h, the
reaction mixture was poured into ice water. Dilute hydrochloric
acid (10.0 mL) was added and extracted by chloroform. The
organic layer was washed by water and saturated with NaCl
solution. The organic layer was dried over anhydrous MgSO4
Acknowledgment. We gratefully thank Dr. Midori
Goto for the X-ray crystallography.
Supporting Information Available: General experiment-
al methods; X-ray crystal data for 2(t), 2(c), 1(t,t), and 1(c,c);
1
and H and 13C NMR spectra for structural characterization
and purity of the reported compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
JO0513616
J. Org. Chem, Vol. 70, No. 23, 2005 9313