Novel oxazabicycles as a new class of photochromic colorants

Article abstract of DOI:10.1021/ol702482c

(Chemical Equation Presented) A new photochromic colorant with an oxazabicyclic moiety has been synthesized by an efficient method. It turns pale red upon UV irradiation and undergoes reverse reaction while being heated. This work may open an exciting new

Full text of DOI:10.1021/ol702482c

ORGANIC
LETTERS
2007
Vol. 9, No. 25
5287-5290
Novel Oxazabicycles as a New Class of
Photochromic Colorants
Ding-Yah Yang,*,† You-Sheng Chen,† Pei-Yu Kuo,† Jiun-Ting Lai,†
Chang-Ming Jiang,‡ Chin-Hung Lai,‡ Yong-Hong Liao,‡ and Pi-Tai Chou*,‡
Department of Chemistry and Center for Nanoscience and Technology, Tunghai
UniVersity, Taichung 407, Taiwan, and Department of Chemistry, National Taiwan
UniVersity, Taipei 106, Taiwan
yang@thu.edu.tw; chop@ntu.edu.tw
Received October 11, 2007
ABSTRACT
A new photochromic colorant with an oxazabicyclic moiety has been synthesized by an efficient method. It turns pale red upon UV irradiation
and undergoes reverse reaction while being heated. This work may open an exciting new avenue for future development of the photochromic
dyes with novel molecular structures.
Owing to their practical applications in ophthalmic lenses,
organic photochromic dyes have long attracted great atten-
tion.1,2 Extensive investigations have been carried out on
bisdiarylethenes,3 bispyrans,4 bisbenzodihydropyrenes,5 and
bishydroindolizines.6 While modifications of the existing
photochromes may still generate compounds with unprec-
edented properties, new classes of organic photochromic dyes
with novel molecular structures should be developed for use
as suitable materials for optical memory media, photooptical
switch components, and other applications.
In our continuing efforts to develop new therapeutic agents
for anti-coagulation therapy in humans by inhibiting the
activity of vitamin K 2,3-epoxide reductase (VKOR), we
recently discovered a conformationally restricted VKOR in-
hibitor with a coumarin-containing dioxobicyclic and oxaza-
bicyclic skeleton.7 Upon ultraviolet irradiation of oxazabi-
cycle 1 (see Scheme 1), a mixture of quinoline-containing
derivatives 2 and 3 as well as 4-hydroxycoumarin were
detected. This result suggested that the photoreaction of 1
should involve a C-O bond cleavage at the junction of the
two heterocycles, along with a subsequent aromatization.
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9897. (d) Chen, B. Z.; Wang, M. Z.; Luo, Q. F.; Tian, H. Synth. Met. 2003,
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Rebiere-Galy, N.; Frigoli, M.; Moustrou, C.; Samat, A.; Guglielmetti, R.
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1732. (b) Mitchell, R. H.; Ward, T. R.; Chen, Y.; Wang, Y.; Weerawarna,
S. A.; Dibble, P. W.; Marsella, M. J.; Almutair, A.; Wang, Z. Q. J. Am.
Chem. Soc. 2003, 125, 2974-2988. (c) Mitchell, R. H.; Ward, T. R.; Wang,
Y.; Dibble, P. W. J. Am. Chem. Soc. 1999, 121, 2601-2602.
(6) Bleisinger, H.; Scheidhauer, P.; Du¨rr, H.; Wintgens, V.; Valat, P.;
Kossanyi, J. J. Org. Chem. 1998, 63, 990-1000.
(7) (a) Chen, D.-U.; Kuo, P.-Y.; Yang, D.-Y. Bioorg. Med. Chem. Lett.
2005, 15, 2665-2668. (b) Wang, J.-F.; Liao, Y.-X.; Kuo, P.-Y.; Gau, Y.-
H.; Yang, D.-Y. Synlett 2006, 17, 2791-2794.
† Tunghai University.
‡ National Taiwan University.
(1) Crano, J. C.; Guglielmetti, R. J. Organic Photochromic and Ther-
mochromic Compounds; Plenum Press: New York, 1999.
(2) (a) Willner, I. Acc. Chem. Res. 1997, 30, 347-356. (b) Feringa, B.
L. Molecular Switches; Wiley-VCH: Weinheim, Germany, 2001. (c) Duerr,
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Amsterdam, 2003.
10.1021/ol702482c CCC: $37.00
© 2007 American Chemical Society
Published on Web 11/15/2007

shown in the graphic abstract. Spectroscopically, with the
increase of exposure time, a new absorption band with the
peak wavelength around 500 nm gradually increased. Al-
though an isosbestic point was lacking during photolysis,
the absorbance at 500 nm showed a smooth, continuous
growth and reached a plateau (see inset of Figure 1), implying
the stationary conversion to the 500 nm absorbing species.
Scheme 1. Photodissociation of Oxazabicycle 1 upon UV
Irradiation
We thus speculate that this skeleton may have the potential
to function as a new class of photochromic systems if the
subsequent aromatization process can be prohibited. As for
a strategic design, incorporation of two alkyl groups (i.e.,
dimethyl groups) at the C(9)-position of this oxazabicyclic
skeleton may prevent the undesired aromatization reaction
upon UV irradiation. Herein, we report the efficient synthesis
of novel oxazabicycles 7a-e, in which 7c is demonstrated
to represent a new class of photochromic colorant.
Scheme 2 shows the preparation of gem-dimethyl-substi-
tuted oxazabicycles 7a-e. It began with a MgSO4-mediated
Figure 1. Absorption spectra of 7c in CH3CN obtained with differ-
ent exposure times, 0 to 160 min, with increments of 10 min. Inset:
Increase of absorbance at 500 nm with respect to irradiating time.
Scheme 2. Preparation of Gem-Dimethyl-Substituted
Oxazabicycles 7a-e
Isolation of the photogenerated product proved to be
difficult since it reverted easily back to the original form
under weakly acidic conditions on the silica gel column.
Alternatively, upon methylation of the photogenerated
product with diazomethane, the resulting methylated deriva-
tive 8 was stable enough to be isolated for further charac-
terization (Scheme 3). The X-ray crystal structure of 8 (see
Figure S1 in the Supporting Information) clearly presents
the similarities to 7c in its mainframe, except for the cleavage
of the O(8)-C(1) bond (see Scheme 1 for the numerical
sequence, which is renamed to the O(3)-C(17) bond in
Figure S1) in the oxazabicyclic moiety and the methylation
at the O(8) site (see Scheme 3). The results lead us to
conclude that 7c may simply undergo the O(8)-C(1) bond
condensation of p-anisidine and substituted benzaldehydes
4a-e to afford the imines 5a-e, followed by a Yb(OTf)3-
catalyzed coupling with isobutyraldehyde to give the cyclized
alcohols 6a-e.8 The reaction of 6a-e with 4-hydroxycou-
marin in the presence of a catalytic amount of p-toluene-
sulfonic acid under reflux conditions yielded the target
compounds 7a-e (see Supporting Information for detailed
characterization). The aforementioned three reaction steps
could all be acid-catalyzed, and the bond formation during
the construction of the bicyclic skeleton was highly efficient.
Among the prepared compounds, the oxazabicycle 7c,
which contained a nitro substituent at the ortho position of
the bridgehead benzene ring, exhibited salient photochromic
behavior. Upon ultraviolet irradiation (320 nm), the oxazabi-
cycle 7c in CH3CN turned from colorless to pale red, as
Scheme 3. The Photochromic Properties and Related
Structures of Compound 7c
(8) Annunziata, R.; Cinquini, M.; Cozzi, F.; Molteni, V.; Schupp, O.
Tetrahedron 1997, 53, 9715-9726.
5288
Org. Lett., Vol. 9, No. 25, 2007

cleavage upon electronic excitation, presumably forming a
zwitterionic species 7z (see Scheme 3, vide infra).
also noteworthy that when irradiating the product 7z by 500
nm light (5 mW/cm2) for a period of 3 min, which is much
shorter than the 7z f 7c thermal recovery time at 298 K,
nearly no change of the spectrum was observed, indicating
that 7z is not transformed into 7c upon electronic excitation.
During the thermal recovery process, we noticed that the
absorbance around 500 nm after the thermal bleaching did
not return to zero as the product 7c should have (see Figures
1 and 2a for comparison). Under the same photolysis period,
the same residual absorbance was observed upon performing
the 7z f 7c process in various temperatures ranging from
20 to 60 °C. We thus discarded the possibility of thermal
equilibrium between 7c and 7z, concluding instead the gen-
eration of side products. This viewpoint is also supported
by a theoretical approach, in which 7c is more stable than
7z (zwitterionic form) by >30 kcal/mol (vide infra). The
temperature-independent side product formation during the
reverse 7z f 7c reaction also eliminates the possibility of
its origin being thermal decomposition of 7z. Instead, the
side product was produced during the photoinduced 7c f
7z process. In addition to the major 7z formation, it is plaus-
ible that, similar to the ultraviolet irradiation of oxazabicycle
1, the photoreaction of 7c, at a small percentage, involves a
C-O bond cleavage at the junction of the two heterocycles,
along with a subsequent aromatization. Being solely de-
pendent on the change of 500 nm absorbance from 7z, the
first four (1) f (2) f (1) (see Scheme 3) cycles are depicted
in the inset of Figure 2a. After the fourth cycle, the 7z
production decreases to ∼50% of its first photoconversion.
In the dark, the proposed ring-opened form 7z in CH3CN
thermally decays away with the disappearance (i.e., turning
colorless) of the 500 nm band, as shown in Figure 2a. Upon
UV (e.g., 320 nm) irradiation of the colorless product, the
photoproduct turns pale red again with the appearance of
the 500 nm band characteristics for 7z. The results support
the thermally assisted 7z f 7c reverse ring-closure process.
To gain more insight into the corresponding photochromism,
the reverse 7z f 7c reaction was carried out at various
temperatures, and the decay kinetics of 7z were monitored
with the 500 nm absorbance, A, as a function of the
monitoring time. The first-order decay dynamics are sup-
ported by a straight line plot of ln A versus time at various
temperatures (Figure 2b). Taking krev to be the rate constant
for the 7z f 7c reaction, an Arrhenius plot of ln krev as a
function of 1/T reveals a straight line (see inset of Figure
2b). Accordingly, an activation energy and frequency factor
of 14.2 kcal/mol and 2.1 × 106 s-1 is deduced. The relatively
small frequency factor implies that the reverse reaction (i.e.,
the cyclization bond formation) involves specific reorienta-
tion and hence a large reduction of the entropy factor. It is
Figure 3. The HOMO/LUMO of 7c.
To gain further insight into the reaction thermodynamics,
we carried out a molecular simulation utilizing the density
function theory (DFT) method. Under the full geometry
optimization (B3LYP/6-31G*),9 7c was calculated to be
lower in energy than 7z by 34.83 kcal/mol. Applying the
TDMPW1K method,10,11 the S0f S1 transitions were calcu-
lated to be 28 090 (356 nm) and 13 158 cm-1 (760 nm) for
7c and 7z, respectively, the results of which, especially for
7z, are significantly lower in energy than the respective peak
wavelength at ∼310 and ∼500 nm extracted from the
absorption spectroscopy. For further improvement, using
IEFPCM model (see Supporting Information) to consider the
solvent effect of acetonitrile,12 the S0 f S1 transition of 7z
is shifted from 13 158 to 18 762 cm-1 (533 nm), while it
Figure 2. (a) Thermal bleaching of 7z (in CH3CN) around 500
nm at 60 °C from 0 to 36 min with increments of 2 min. Inset:
Absorbance at 500 nm in the first four cycles, in which each cycle
consists of 3 h UV irradiation and 90 min thermal bleaching at
60 °C. (b) The plot of ln A500nm versus decay time at various
temperatures. Inset: The plot of ln krev versus 1/T.
Org. Lett., Vol. 9, No. 25, 2007
5289

remains nearly unchanged for 7c (350 nm). The large
solvation change in 7z further implies its zwitterionic
property. According to the calculation, the electronic excita-
tion between S0 and S1 of 7c is dominated by the HOMO f
LUMO excitation (Figure 3), in which the electron density
of HOMO is mainly located on the lone pair of O(8) atoms
and the p-methoxybenzamine moiety. Conversely, the elec-
tron density is transferred to the NO2 group in the LUMO.
The net change of the electron density during the HOMO
f LUMO transition is expected to cause the C-O bond
weakening and consequently cleavage. We also performed
a similar calculation on 7t, considered to be another possible
neutral product (see Scheme 3). The calculated S0f S1
transition of 28 570 cm-1 (350 nm) is much higher in energy
than that of the product (7z) absorption peak experimentally
resolved to be 500 nm. The result justifies the assignment
of 7z to a zwitterionic species, Theoretically, the 7c f 7z
formation involves only the cleavage of C(sp3)-O bonding
at the junction of the heterobicycle, while for 7t, if it were
the photoproduct, in addition to the bond cleavage, another
hydrogen transfer from N to O would be necessary, leading
to a dynamically unfavorable pathway.
“trapping” the 7z species. Note that similar hydrogen bonding
formation is not evident in other synthesized analogues
presented in this study.
We have also made attempts to analyze the product yield
in a more quantitative manner. Using a 30 mW/cm2 355 nm
Nd:YAG pulse laser to illuminate the entire volume of 3
mL of 7c solution (7.8 × 10-5 M in acetonitrile) for 100
min, we then observed that the absorbance at 500 nm was
increased from 0.003 to 0.172, corresponding to an increase
of 4.9 × 10-5 M of the 7z production. Taking the ratio of
the number of 7z molecules being produced versus the
number of photons being absorbed, the yield of 7z production
was then estimated to be 0.12 ( 0.02%.
Since the above photochromic phenomena, the associated
dynamics, and efficiency are independent of O2, the reaction
less likely takes place in the triplet manifold. To draw the
relative thermodynamics in the excited singlet state, we
simply added the observed S0 f S1 absorption peak in terms
of energy to the calculated energy for 7c and 7z. The result,
depicted in Scheme 4 of the Supporting Information, indi-
cates that 7c f 7z is thermodynamically favorable only by
∼1.0 kcal/mol along the S1 state. Alternatively, it is more
plausible that the photochromism proceeds via a nonadiabatic
(i.e., surface crossing) process from S1 (7c) to S0 (7z). Never-
theless, at this stage, whether the reaction takes place strictly
in the excited state or via crossing to the ground state poten-
tial energy surface is pending detailed dynamics approaches.
The oxazabicycle 7c reported here, to the best of our
knowledge, represents the first example of a heterobicyclic
molecule exhibiting satisfactory photochromic properties.
Although the overall photochromism cycle is relatively slow
and the maximum absorption at 500 nm (ꢀ ∼500 M-1 cm-1,
see Figure 1) is low, we believe that 7c or its analogues may
still merit future applications. For example, the 7z f 7c
reverse reaction is of importance in that the ∼34 kcal/mol
is chemically stored in 7z and may be re-exploited in the
presence of suitable catalysts. Moreover, in the current
system, both 7c and 7z are nonluminescent despite their
anchoring coumarin moiety. Thus, work focusing on the
improvement of the reaction reversibility as well as the
utilization of fluorescence based on coumarin analogues to
enhance the detection should be of great interest. We thus
believe that this work may open an exciting new avenue for
future development of the photochromic dyes with novel
molecular structures.
Among 7a-e only 7c exhibits the aforementioned pho-
tochromic properties. The fact that only the oxazabicycle with
a nitro substituent at the ortho position of the bridgehead
benzene ring exhibited the expected photochromic behavior
implied that the ortho substituent, but not meta and para, on
the bridgehead benzene ring plays an important role in the
photochemistry. We initially speculated that the increasing
steric hindrance between the ortho substituent and the nearby
methyl groups on the heterobicyclic skeleton made 7c more
susceptible to a C-O bond rupture than the corresponding
p-nitro-substituted 7b. However, neither the o-chloro-func-
tionalized (7d) nor the o-methoxy-substituted (7e) analogue
exhibits any photochromic behavior, suggesting that factors
other than the steric effect govern the photochromism. An
additional experiment was also performed and found no
photochromic property when the amino group (N(2)) on 7c
was methylated. The result thus drew our attention on the
possible role of hydrogen bonding formation between the
iminium hydrogen (N(2)-H) and nitrooxygen (N(10)-O).
The result of molecular simulation for 7c produced an
estimated distance between the oxygen atom on the o-nitro
group and the amino hydrogen atom of 2.39 Å (see Figure
S2 in the Supporting Information), while this distance for
7z even decreases to as short as 1.98 Å. It is thus reasonable
to propose that 7z can be further stabilized via enhancing
the intramolecular hydrogen bonding strength between the
iminium hydrogen and the nitrooxygen. This hypothesis is
supported by the result that 7z is calculated to be 34.2 kcal/
mol (adding CH3CN as the solvent) higher in energy than
7c, while based on a similar method, we calculated the energy
of zwitterionic product of 7b, if there were any, to be higher
in energy than 7b by 39.3 kcal/mol. In comparison, the
difference of ∼5 kcal/mol manifests the stabilization energy
given by the hydrogen bonding formation in 7z. We thus
tentatively propose that the strong N(2)-H-O-N(10) in-
tramolecular hydrogen bonding plays a certain role in
Acknowledgment. We thank the National Science Coun-
cil, Taiwan, for financial support.
Supporting Information Available: Additional experi-
mental details. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL702482C
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