Switchable fluorescent and solvatochromic molecular probes based on 4-amino-N-methylphthalimide and a photochromic diarylethene

Article abstract of DOI:10.1002/ejoc.200800125

New fluorescent photochromic compounds (1-H and 1-Boc) have been synthesized and characterized in different solvents. The fluorescence emission can be switched on and off with visible light and UV, respectively, by means of the photochromic reaction. The emission wavelength and efficiency strongly depend on the polarity of the solvent. The compounds show a positive solvatochromic effect in the emission maxima, and their fluorescence quantum yield decreases as the solvent's polarity increases (from cyclohexane to dioxane). In solvents more polar than dioxane the emission is too weak and therefore undetectable, and thus 1-H and 1-Boc behave as normal photochromic compounds. The photochromic reaction is also sensitive to the environment. A decrease of more than an order of magnitude was found for the quantum yield of the colouring reaction (Φ_OF→CF) for 1-H in ethanol compared with cyclohexane, and an about threefold decrease in Φ_OF→CF was observed for the compound 1-Boc in polar solvents (compared with apolar solvents). For both compounds the ring-opening reaction was found not to dependent on the solvent. The novel fluorescent molecular switches 1-H and 1-Boc are able to probe the polarity of their microenvironment. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800125

FULL PAPER
DOI: 10.1002/ejoc.200800125
Switchable Fluorescent and Solvatochromic Molecular Probes Based on
4-Amino-N-methylphthalimide and a Photochromic Diarylethene
Sergey F. Yan,[a] Vladimir N. Belov,[a] Mariano L. Bossi,*[a] and Stefan W. Hell[a]
Keywords: Fluorescent probes / Photochromism / Solvatochromism / Molecular switches / 4-Aminophthalimide / Diaryl-
ethenes
New fluorescent photochromic compounds (1-H and 1-Boc)
have been synthesized and characterized in different sol-
vents. The fluorescence emission can be switched “on” and
“off” with visible light and UV, respectively, by means of the
photochromic reaction. The emission wavelength and effi-
ciency strongly depend on the polarity of the solvent. The
compounds show a positive solvatochromic effect in the
emission maxima, and their fluorescence quantum yield de-
creases as the solvent’s polarity increases (from cyclohexane
to dioxane). In solvents more polar than dioxane the emission
is too weak and therefore undetectable, and thus 1-H and 1-
Boc behave as “normal” photochromic compounds. The pho-
tochromic reaction is also sensitive to the environment. A de-
crease of more than an order of magnitude was found for the
quantum yield of the colouring reaction (ΦOFǞCF) for 1-H in
ethanol compared with cyclohexane, and an about threefold
decrease in ΦOFǞCF was observed for the compound 1-Boc
in polar solvents (compared with apolar solvents). For both
compounds the ring-opening reaction was found not to de-
pendent on the solvent. The novel fluorescent molecular
switches 1-H and 1-Boc are able to probe the polarity of their
microenvironment.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
of optical devices due to the thermal irreversibility of the
ring-closing reaction and their photochemical and photo-
physical fatigue resistance.[11] In particular, 1,2-bis(3-thi-
enyl)perfluorocyclopentenes can be reversibly switched be-
tween a colorless open form (OF) and a colored closed form
(CF), with UV and green light, respectively (Scheme 1).
Introduction
Photochromic materials are receiving an increasing inter-
est as opto-addressable rewritable memory devices and re-
versible optical switches.[1] One of their main advantages is
the possibility to miniaturize devices to the size of a single
molecule, resulting in very fast response times in the pico-
second range.[2] The light-induced changes of different
physicochemical properties can be used as a readout signal.
Absorbtion (color) changes are most evident, thus giving
the name to this class of compounds.[3] Other properties
such as refractive index[4] or infrared absorption[5] have also
been used with the aim to perform a non-destructive read-
out. Particular effort has been made to obtain more com-
plex and useful devices with multiple readout signals. Mod-
ulation of other properties such as fluorescence,[6] redox po-
Scheme 1. Photochromism of 1,2-bis(thiophen-3-yl)hexafluorocy-
tentials,[7] chiroptical[8] or magnetic[9] properties has been clopentenes.
successfully achieved, as well as photoinduced supramolec-
ular control of a self-assembled material.[10] Fluorescence is
of particular interest due to its high sensitivity and selectiv-
The common lack of fluorescence of most PC com-
ity in one side, and the ability to provide non-invasive read- pounds was overcome by binding them with various fluoro-
out with high spatial information on the other.
phores whose signal can be modulated by the PC moiety
The diarylethene family has been by far the preferred through various mechanisms. The most commonly used
group of photochromic compounds (PC) in the preparation mechanism relies on a resonance energy transfer (RET)
from the fluorophore selectively to the CF of the photo-
[a] Department of NanoBiophotonics, Max-Planck Institute for
chromic switch.[12] The two residues may be attached with-
Biophysical Chemistry,
out any linker[13] or through a spacer. Another interesting
Am Fassberg 11, 37077 Göttingen, Germany
Fax: +49-551-2012505
strategy is to use the changes in the electron density distri-
E-mail: mbossi@gwdg.de
bution between the OF and the CF to directly influence the
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
fluorescent properties of the fluorophore.[14]
Eur. J. Org. Chem. 2008, 2531–2538
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2531

S. F. Yan, V. N. Belov, M. L. Bossi, S. W. Hell
FULL PAPER
Derivates of 4-aminophthalimide show a very efficient group of Ar2 is also a part of the aminophthalimide fluoro-
blue fluorescence with relatively large Stokes shifts.[15,16] phore. Therefore, its fluorescence properties may be per-
They are commonly used as environmentally sensitive mo- turbed by the strong acceptor group – the pyridine ring –
lecular probes,[17] because their emission maxima and quan- only in the CF, because the electron density on the amino
tum yields are influenced by the medium polarity and its group is substantially reduced. In the OF, the push and pull
hydrogen-bond-donating capability.[15,18,19] For instance, groups are electronically disconnected, and therefore dif-
fluorescent quantum yields of compounds 2a–c (Figure 1) ferent emission properties are expected (quantum yields,
strongly depend on the solvent polarity: in less polar sol- spectra, etc.), as well as a different chemical reactivity (e.g.
vents these values increase dramatically (from 1% in chloro- hydrolytic stability of the phthalimide ring). As a result, the
form up to 56% in hex-1-ene for compound 2c and from fluorescence signal of the molecular switches can be revers-
0.5% in ethyl acetate up to 44% in hex-1-ene for 2b).[15] ibly modulated with light stimuli. Moreover, the solvent de-
Moreover, the emission maxima (λem) and the Stokes shift pendence of the emission properties of the aminophthal-
depend on the solvent polarity as well.
imide fluorophore is conserved in the prepared adducts,
which may serve as molecular probes for environmental
conditions.
Results and Discussion
Figure 1. Fluorescent derivatives of 4-amino-N-methylphthalimide.
1. Synthesis
The target molecule 1 could be built-up in several ways.
The easily available starting compounds 4[21] and 5[21,22]
(Figure 2) offer two synthetic pathways: the sequential con-
struction of the bonds 1, 2 and 3 (in that order), or in the
order 1, 3 and then 2 (Scheme 2).
In this work we present two novel fluorescent molecular
switches (Scheme 2) with a multifunctional response: these
compounds possess both a photoswitchable fluorescent sig-
nal and an environment sensing ability. The switches are
based on a 4-amino-N-methylphthalimide fluorophore, and
a “push-pull” diarylethene compound. The latter was pre-
pared by introducing an electron-acceptor group in one
of the aryl substituents (Scheme 1, Ar1 = pyrid-4-yl as a
“pull” group) and an electron-donor group in the other one
(Ar2 = p-aminophenyl as a “push” group). In the resulting
diarylethene 1 the direct polar conjugation of both groups
is only possible in the CF.[20] This means that the electron
density distribution can be modulated through the photo-
chromic reaction. In the molecular switches 1, the amino
Figure 2. Starting materials and building blocks 2d, 3–5.
The bond 1 may be formed either by the Ullmann[23] or
by the Knochel reaction.[24] Preparation of the intermediate
2b (Scheme 3) according to Ullmann required iodobenzene
and 4-acetylamino-N-methylphthalimide (2d).[23] The latter
was synthesized from compound 3 by the reduction[25] and
acylation of the intermediately formed 2a.[23] Under various
arylation conditions, either 4-(diphenylamino)-N-methyl-
phthalimide (2c) or its mixture with 2b was obtained.
Therefore, we decided to use the Knochel reaction for the
synthesis of the iodide 6-H. The Grignard reagent p-
IC6H4MgCl and the nitro compound 3 may give the re-
quired compound 6-H directly and save the iodination step,
but the monoiodide 6-H was not detected in this reaction
mixture. Substitution of p-IC6H4MgCl by PhMgCl afforded
the amine 2b, which, even after optimization, was isolated
only in low yield (Scheme 3).[26]
Bond 2 was constructed by the Suzuki reaction[27] of the
iodide 6-H (prepared from 2b) with the boronic acid 4, but
the substance 7-H was isolated in a very low yield (probably
because of the hydrolysis of the phthalimide cycle with hot
Scheme 2. Target compounds 1-R (wavy lines denote strategical
bonds for construction of the whole molecule).
2532
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2531–2538

Switchable Fluorescent and Solvatochromic Molecular Probes
Scheme 3. Synthesis of compounds 2b, 6-R and 7-R (1–2–3 strategy).
aqueous Na2CO3). Unfortunately, the next bond (3) did not 2. Physical Properties
form, if the heptafluoride 5 reacted with the lithiation prod-
uct of the thiophene 7-H.[22] Protection of the free NH
group, which could slow down the Suzuki reaction and in-
Photochromism of Compounds 1-H and 1-Boc
The photochromic properties of the target compounds
hibit the next step (7-H + 5Ǟ1) afforded the compound 6- were studied in diluted solutions (≈ 10–5 ) in different sol-
Boc[28] but, quite unexpectedly, it did not react with the vents. The solutions were placed in 1 cm cuvettes, irradiated
boronic acid 4 in the presence of Pd(dba)2, Ph3P, and aque- with UV or visible light whilst stirring, and the changes in
ous Na2CO3 in THF. Another catalytic system, in dioxane the absorbance were recorded in a UV/Vis spectrophotome-
proved to be extremely efficient in the Suzuki reaction.[29] ter. The solutions were not degassed. The initial solutions
In this case, the reaction proceeded faster, with 75% conver- with the pure open isomers had a different appearance: the
sion, but we were not able to separate the initial substance solutions of compound 1-H were pale yellow due to the
6-Boc from the product 7-Boc (or to reach the full conver- absorption band of the 4-aminophthalimide residue centred
sion). Luckily, the compound 6-H was transformed into 7- at 370 nm in cyclohexane (Figure 3); in compound 1-Boc
H in the presence of Pd(dba)2, tBu3P and Cs2CO3, with this band is blue-shifted, and appears as a shoulder at about
98% conversion (Scheme 3). However, the protected bro- 335 nm. The absorption band of the photochromic moiety
mide 7-Boc (obtained from 7-H) could not be further trans- in the open form is not shifted and is found at 283 and
formed into the target compound 1-Boc with the heptafluo- 285 nm in 1-Boc and 1-H, respectively. Irradiation in the
ride 5.
UV (313 nm) resulted in a rapid appearance of the charac-
Therefore, the second strategy for the preparation of the teristic absorption band of the closed form in the visible
target substances 1, by forming the bonds 1, 3 and then 2 region, and the solutions became coloured. The absorption
(Scheme 4), was used. For that, an intermediate 9-SiMe3 maximum of the closed form was observed at 573 nm for
was synthesized from 8[30] and 5, the silyl group was re- 1-H and 577 nm for 1-Boc, respectively, with a larger ab-
moved, and, finally, the two building blocks (9-H and 6- sorption coefficient in the case of 1-H. In both cases nearly
Boc) were connected in the course of the multistep pro- a full conversion in the photostationary state of (≈ 95% de-
cedure. As a result, the desired compound 1-Boc was iso- termined by HLPC) was reached in cyclohexane. Subse-
lated with satisfactory yield. At the very end it was neces- quent irradiation of the solutions with visible green light
sary to remove the Boc group, but all deprotection proto- (550 nm) resulted in a complete conversion to the corre-
cols (HCl in dioxane,[31] TMSOTf, CF3COOH with Et3- sponding open isomer. This process could be repeated sev-
SiH,[32] Bu4NF in THF[33]) failed. Therefore, the same pro- eral times (Ͼ10) with no sign of photochemical damage.
cedure was applied for the direct coupling of substances 9-
Similar photochromic behaviour was observed for both
H and 6-H, without any protection of the amino group. compounds in other solvents. The absorption bands of the
Thus, both target substances 1-H and 1-Boc were obtained CF were slightly red-shifted in polar solvents, to a maxi-
by the Negishi coupling reaction[34] at the key step.
mum of 10 nm in ethanol (compared with cyclohexane), but
Scheme 4. Assembling of the target compounds 1-R according to the 1–3–2 strategy (TMPP = 2,2,6,6-tetramethylpiperidine; TMSOTf
= trimethylsilyl trifluoromethylsulfonate; TFA = trifluoroacetic acid).
Eur. J. Org. Chem. 2008, 2531–2538
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2533

S. F. Yan, V. N. Belov, M. L. Bossi, S. W. Hell
FULL PAPER
pounds,[12] in this case the emission occurs at wavelengths
between the absorption of the OF and the CF, where nei-
ther one of the isomers have a significant absorption. A
perfect correlation between the emission and the absorption
of the close form (visible band) can be observed for com-
pound 1-Boc in Figure 5. At least ten complete cycles were
performed for both compounds in this solvent without
signs of fatigue in the absorption, or the emission spectra.
In more polar solvents some signs of photoinduced decom-
position were observed after a few irradiation cycles, evi-
denced by the presence of increasing amounts of blue fluo-
rescent product(s) (emission maxima at 430–460 nm). In all
the cases, compound 1-Boc was more resistant to this
irreversible photobleaching than compound 1-H. However,
a decrease of the maximum absorption in the visible band
of the CF in the photostationary state under irradiation
with UV light was not observed, indicating that the amount
of photoproduct is relatively small, but the product(s) emit
with a high efficiency as compared with the studied com-
pounds 1.
Figure 3. Absorption spectra of the open (full lines) and close
(dashed lines) forms of compounds 1-H (black lines) and 1-Boc
(red lines) in cyclohexane.
the position of the absorption band of the OF was rather
insensitive to the solvent. The most distinct changes were
observed in the cyclization quantum yields (ΦOFǞCF). An
increase in the solvent polarity resulted in a drastic decrease
of ΦOFǞCF for compound 1-H: in ethanol this value was
found to be 28 times lower than in cyclohexane. A less pro-
nounced (2.5-fold) decrease was observed for compound 1-
Boc in the same solvents. On the contrary, the quantum
yield for the ring-opening reaction (ΦCFǞOF) was found to
be almost the same for both compounds (within an experi-
mental error) in all the solvents. The results obtained for
compounds 1-H and 1-Boc are summarized in Table 1.
Fluorescence Properties and Switching
The photochromic reaction not only resulted in the col-
our changes mentioned above (mainly governed by the vis-
ible absorption band of the CF), but also in a drastic
change in the fluorescence signal. Figure 4 shows the fluo-
rescent modulation observed for compounds 1-H and 1-Boc
in cyclohexane. A contrast in the signal of about 20 was
found for both compounds between the pure OF (spectra
normalized to one at the maximum wavelength) and the
photostationary state reached under irradiation with UV
Figure 4. Fluorescence changes upon irradiation with UV (313 nm)
and visible light (550 nm) for compounds 1-H (left) and 1-Boc
(right). The arrows indicate the directions of the changes. The high-
est spectra correspond to the pure OF, and the lowest to the photo-
stationary state (PSS). Excitation was performed at 370 nm for 1-
H, and at 350 nm for 1-Boc.
Both compounds displayed a marked positive solvatoch-
light, indicating that the emission efficiency of the close iso- romic effect in the emission spectra, accompanied by a re-
mer is negligible. Unlike most of the reported com- duction of the fluorescence quantum yield (ΦFLUO) with
Table 1. Physical properties of compounds 1-H and 1-Boc in different solvents. Quantum yield for the cyclization (ΦOǞC) and ring-
opening reaction (ΦCFǞOF), absorption maximum of the visible band of the closed form (λCF), fluorescence switching ratio (SR), maxi-
mum of fluorescence emission (λEM), and fluorescence quantum yield (ΦFLUO). The empirical parameter ET(30) defining solvent’s polarity
is also provided.[a]
[b]
[b]
[b]
Solvent
ET(30)[a]
[kcal mol–1] 1-H
ΦOFǞCF
ΦCFǞOF
1-Boc 1-H
Switching ratio (SR) λCF [nm]
λEM [nm]
1-H
% ΦFLUO
1-H
1-Boc
1-H
1-Boc
1-H
1-Boc
1-Boc
1-Boc
Cyclohexane
Tetrachloromethane 32.4
30.9
0.50
–
0.13
0.13
0.63
0.011
–
0.016
0.013
0.013
0.013
0.012
0.015
0.014
0.015
0.014
20
–
10
13
7
20
17
17
20
17
17
577
–
573
577
581
582
581
581
582
578
575
452
478
501
508
514
526
440
462
474
482
487
498
526
23.0
12.8
8.6
5.5
4.4
4.5
10.2
5.7
4.7
4.4
3.6
0.8
[c]
[c]
[c]
[c]
0.57
0.48
0.50
0.38
0.30
0.21
0.28
0.26
p-Xylene
Toluene
Benzene
Dioxane
THF
33.1
33.9
34.3
36.0
37.4
45.6
51.9
0.009
0.009
0.008
0.013
0.009
0.009
0.008
588
589
587
586
589
589
588
0.09
0.046
0.026
0.022
0.018
4
–
1.6
[d]
[d]
[d]
–
–
Ͻ0.5
[d]
[d]
[d]
[d]
[d]
[d]
Acetonitrile
Ethanol
–
–
–
–
–
–
[d]
[d]
[d]
[d]
[d]
[d]
–
–
–
–
–
–
[a] From ref.[36]. [b] Uncertainties are about 5%. [c] Photoinduced irreversible secondary reaction. [d] Non or very poorly fluorescent.
2534 Eur. J. Org. Chem. 2008, 2531–2538
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Switchable Fluorescent and Solvatochromic Molecular Probes
tive planar and an inactive twisted one); the relative ener-
gies of these conformations depend on the solvent po-
larity.[37] The same tendency was found for the compounds
presented here (see Table 1), with a more pronounced
change in ΦOFǞCF in the case of 1-H. We attribute the dif-
ferences observed between 1-H and 1-Boc to the different
electron-donor properties of the p-aminophenyl substituent
in the diarylethene. The urethane group in the compound
1-Boc decreases the electron density on the nitrogen atom,
making this compound less sensitive to changes in the po-
larity of the environment.
Figure 5. Photoswitching of compound 1-Boc in cyclohexane. The
absorption in the visible band (filled symbols, left axis) and the
emission at the maximum (hollow symbols, right axis) are plotted
as a function of the irradiation time during the complete first cycle,
and then only in the photostationary states after irradiation with
UV (circles) and visible light (squares), for a total of 10 cycles.
increasing solvent’s polarity, in agreement with the data for
other 4-aminophthaleimides[15,16,35] (Table 1), the only ex-
ception being the increase observed in ΦFLUO for com-
pound 1-Boc from cyclohexane to tetrachloromethane
[ET(30) = 30.9 and 32.4 kcalmol–1 respectively]. Red shifts
in the emission maxima of 75–85 nm were observed for
both compounds with a relatively small change in polarity
of 6.5 kcalmol–1 measured in the one-parameter [ET(30)]
empirical scale, derived from the absorption of Reichardt’s
betaine dyes.[36]
Figure 6. Photoswitching of the fluorescence of compound 1-Boc
in different solvents (excitation wavelength: 370 nm). The switching
contrast obtained in the signal between the pure OF and the photo-
stationary state (PSS-313) was for all cases greater than 17 (IF–0
IF–PSS).
/
The emission in more polar solvents [ET(30) Ͼ 37
kcalmol–1] becomes too week (ΦFLUO Ͻ 0.003) for both
compounds. The absorption band of the aminophthalimide
The mechanism of fluorescence modulation may be
(AP) residue was also red-shifted for compound 1-H, but rather complex and probably more than one effect contrib-
this shift is smaller (maximum 20 nm by changing cyclohex- utes to it. In principle, at least two effects can be considered.
ane to ethanol). In the case of compound 1-Boc, the AP First, the changes in the charge density on the nitrogen at
band (shoulder at 335 nm) did not experience any signifi- the position 4 of the phthalimide, between the two isomers
cant change with the variation of the solvent.
(see Scheme 2) should result in a very important contri-
Photoswitching of the fluorescence signal was also ob- bution. Second, a possible energy transfer process from the
served in different solvents for both compounds upon light emissive state, centred at the aminophthalimide part of the
irradiation. The results are summarized in Table 1, defined molecule (in the CF), to the state responsible for the red
as the ratio between the fluorescent signal of the pure open absorption band of the CF, centred in the diarylethene moi-
isomer (IF–0) and the one obtained in the photostationary ety may also have a contribution. The latter should be of
state (IF–PSS) after irradiation with UV light (SR = lower incidence because the emission maxima is located at
IF–0/IF–PSS). In the case of compound 1-Boc, an excellent a wavelength of minimal absorbance of the CFs (see Fig-
signal modulation of 17 to 20-fold was obtained indepen- ures 3 and 4), but it cannot be completely ruled out due to
dent of the solvent polarity, from cyclohexane to dioxane the close proximity between the donor and the acceptor.
(Figure 6). On the contrary, compound 1-H showed a large Moreover, the red-shifts experimented in polar solvents by
decrease in the switching ratio, i.e. from 20 (95% of signal the emission maxima are higher than the one observed in
modulation) in cyclohexane to 4 (76% modulation) in diox- the absorption of the CF. Therefore the energy transfer effi-
ane. These results can be explained by the changes observed ciency from the fluorophore (donor) to the closed form (ac-
in the conversion in the photostationary state (αPS), which ceptor) should increase with solvent polarity, and this effect
are also in agreement with the behaviour of ΦOFǞCF ob- should be more pronounced for amine 1-H (emission shift
served in different solvents. While αPS remains approxi- from 452 nm in cyclohexane to 526 nm in dioxane) than for
mately constant in all the solvents for compound 1-Boc (αPS the N-protected 1-Boc (emission shift from 440 nm to
= 0.93–0.97), a decrease from 0.95 in cyclohexane to 0.55 498 nm in the same solvents). The observed changes for SR
in ethanol was observed for 1-H. A decrease in ΦOFǞCF point in the opposite direction. Therefore, energy transfer
and αPS with increasing solvent polarity was ascribed to the cannot be the main mechanism responsible for the fluores-
presence of two conformations in the excited state (a reac- cence modulation of compounds 1.
Eur. J. Org. Chem. 2008, 2531–2538
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2535

S. F. Yan, V. N. Belov, M. L. Bossi, S. W. Hell
FULL PAPER
5 µm, 250ϫ4 mm, 1 mL/min; preparative column: Eurospher-100–
5 C18, 5 µm, 250ϫ8 mm, 4 mL/min; solvent A: water + 0.1%
v/v trifluoroacetic acid (TFA); solvent B: MeCN + 0.1% v/v TFA.
Analytical TLC was performed on MERCK ready-to-use plates
with silica gel 60 (F254). Column chromatography: MERCK silica
gel, grade 60, 0.04–0.063 mm; fraction collector RETRIEVER® II
(ISCO). Elemental analyses were carried out at Mikroanalytisches
Laboratorium des Instituts für Organische und Biomolekulare
Chemie der Georg-August-Universität Göttingen. Organic solu-
tions were dried with MgSO4. All reactions were carried out with
magnetic stirring.
Conclusion and Outlook
We have designed and characterized new compounds
that display environmentally dependent emission colors
(fluorescence spectra), that can be optically modulated be-
tween “on” and “off” states with a high signal ratio between
the fluorescent and non fluorescent states. Thus, these mo-
lecular switches may be used for probing the microenviron-
ment, e.g. intracellular objects, organelles, or in particular,
used as membrane potentials probes. Their switching be-
havior makes the probes also useful in intracellular tracking
experiments, to individualize the structure to be followed,
or to provide subdiffraction resolution in far field micro-
scopy based on the use of the molecular states of the fluo-
rescent probes.[38] For that, the N-methyl group of the
phthalimide fragment should be transformed into the
CH2COOR group and bound with a ligand, which should
serve as a recognition site for the (biological) object, the
polarity of which is to be probed. The key intermediate of
the present study – the organo-zink compound prepared
from the thiophene 9-H – is compatible with a tert-butyl
ester group (R = tBu in CH2COOR mentioned above). The
N-(tert-butoxycarbonyl)methyl derivative of the iodide 6
may easily be synthesized and used as a starting material
for the preparation of the (amino) reactive modifications of
the environmentally sensitive probes presented here.
N-Methyl-4-(phenylamino)phthalimide (2b): In a dry 100 mL flask,
a solution of PhMgCl (2.0  in THF, 7.2 mL, 14 mmol) was diluted
with dry THF (20 mL). Compound 3 (1.24 g, 6.00 mmol) in dry
THF (30 mL) was added to the solution of PhMgCl at –50 °C.
After stirring at –50 °C for 2 h, EtOH (4 mL) was added, followed
by the freshly prepared solution of NaBH4 (228 mg, 6.00 mmol) in
dry DMF (10 mL), which was introduced dropwise. Then dry FeCl2
(1.52 g, 12.0 mmol) was added. After stirring overnight at room
temperature, the reaction mixture was poured into water (100 mL)
and extracted with diethyl ether (3ϫ100 mL). The combined or-
ganic solutions were washed with brine (100 mL), dried and con-
centrated in vacuo. The residue was purified by chromatography
on SiO2 (100 g) with hexane/EtOAc mixture (2:1) as an eluent, and
the title compound was isolated as a yellow solid (0.398 g, 26%);
m.p. 178 °C (MeOH) (ref.[15] 175 °C). 1H NMR (200 MHz, CDCl3):
3
4
δ = 3.10 (s, 3 H), 6.31 (br. s, 1 H), 7.09 (dd, J = 8.3, J = 2.1 Hz,
3
1 H), 7.13–7.21 (m, 4 H), 7.28–7.37 (m, 2 H), 7.63 (d, J = 8.2 Hz,
1 H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 23.7 (Me), 108.9
(CH), 118.6 (CH), 121.6 (2ϫCH), 122.0, 124.4 (CH), 125.1 (CH),
129.9 (2ϫCH), 135.0, 140.0, 150.0, 168.7 (CO), 168.9 (CO) ppm.
MS (EI): m/z (%) = 252 (100) [M+].
Experimental Section
General Remarks: UV/Vis absorption spectra were recorded on a
Varian Cary 4000 UV/Vis spectrophotometer, and fluorescence
spectra on a Varian Cary Eclipse fluorescence spectrophotometer.
Sealed quartz cuvettes of 1 cm path length were used in all experi-
ments. Photochromic reactions were performed with stirring by ir-
radiation with a 200 W Mercury lamp (LOT-Oriel GmbH & Co.
KG, Darmstadt, Germany) equipped with a monochromator and
a system of filters to select the appropriate wavelengths. The analy-
sis of the kinetic data to extract the values of the quantum efficienc-
ies of the isomerization reactions (ΦOǞC and ΦCǞO) is described
elsewhere.[39] As a reference, solutions of compound 1,2-bis(2,4-di-
methyl-5-phenylthiophene-3-yl)perfluorocyclopentene[40] in hexane
were used. All reactions were carried out with magnetic stirring in
Schlenk flasks equipped with septa under argon using a standards
manifold with vacuum and argon lines. NMR spectra were re-
corded at 25 °C with Varian MERCURY 300 and Bruker AM 250
spectrometers at 300 (1H) and 75.5 MHz (13C and APT), as well as
at 250 (1H) and 62.9 MHz (13C and DEPT), respectively. All spec-
tra are referenced to tetramethylsilane as an internal standard (δ =
0 ) using the signals of the residual protons of CHCl3 (δ =
7.26 ppm) in CDCl3 or [D5]DMSO (δ = 2.50 ppm) in [D6]DMSO.
Multiplicities of signals are described as follows: s = singlet, br.
s = broad singlet, d = doublet, t = triplet, q = quartet, m = mul-
tiplet. Multiplicities in the 13C NMR spectra were determined by
APT (Attached Proton Test) measurements. Low resolution mass
spectra (electro spray ionization, ESI) were obtained with LCQ
4-(4Ј-Iodophenylamino)-N-methylphthalimide (6-H): To a stirred
solution of 2b (770 mg, 3.06 mmol) and AcOK (300 mg,
3.06 mmol) in glacial AcOH (40 mL), a solution of ICl (6.72 mL,
3.36 mmol, 0.5  in AcOH) was added dropwise at room tempera-
ture. The reaction mixture was stirred for 30 h at 62 °C. After cool-
ing, a half of AcOH was evaporated in vacuo, and the residue was
poured into 2% aq. Na2SO3 (80 mL). The title product was filtered
off, washed with water and air-dried; yield 1.12 g (97%), m.p.
1
220 °C (MeOH). H NMR (200 MHz, [D6]DMSO): δ = 2.98 (s, 3
3
H), 7.05 (d, J = 8.4 Hz, 1 H), 7.15–7.90 (m, 5 H), 9.24 (br. s, 1 H)
ppm. 13C NMR (50.3 MHz, [D6]DMSO): δ = 23.5 (Me), 85.5 (CI),
108.4 (CH), 118.6 (CH), 121.0, 122.0 (2ϫCH), 125.0 (CH), 134.6,
138.3 (2ϫCH), 140.8, 149.4, 168.0 (C=O), 168.2 (C=O) ppm. MS
(EI): m/z (%) = 378 (100) [M+]. C15H11N2O2I (378.16): calcd. C
47.64, H 2.93, N 7.41; found: C 47.24, H 2.90, N 7.31.
N-Butoxycarbonyl-4-(4Ј-iodophenylamino)-N-methylphthalimide (6-
Boc): In a dry 50 mL flask, a mixture of 6-H (750 mg, 1.98 mmol)
and DMAP (97 mg, 0.79 mmol) was dissolved in dry THF (30 mL).
tert-Butyl pyrocarbonate (578 mg, 2.65 mmol) was added dropwise
at the room temperature, and the final solution was stirred for 3 h
at 60 °C. The solvent was removed in vacuo; the residue was dis-
solved in CH2Cl2 (20 mL), washed 0.1  aq. HCl (20 mL) and
brine. After drying, the solvent was removed in vacuo, and the title
compound was isolated by filtration through the silica gel (50 g)
spectrometer. High resolution mass spectra (ESI-HRMS) were ob- with hexane/EtOAc mixture (2:1) as an eluent (head fraction was
tained on APEX IV spectrometer. HPLC system (Knauer):
Smartline pump 1000 (2ϫ), UV detector 2500, column thermostat
4000, mixing chamber, injection valve with 20 and 100 µL loop
for the analytical and preparative columns, respectively; 6-ports/
discarded, as it contained excess of tert-butyl pyrocarbonate). After
removing of the eluent, a white solid was obtained; yield 937 mg
(99%); m.p. 171 °C (MeOH). 1H NMR (200 MHz, CDCl3): δ =
3
3
1.42 (s, 9 H), 3.13 (s, 3 H), 6.92 (d, J = 8.7 Hz, 2 H), 7.48 (dd, J
4
4
3
3-channel switching valve; analytical column: Eurospher-100 C18, = 8.1, J = 2.0 Hz, 1 H), 7.63 (d, J = 2.0 Hz, 1 H), 7.68 (d, J =
2536 Eur. J. Org. Chem. 2008, 2531–2538
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Switchable Fluorescent and Solvatochromic Molecular Probes
8.7 Hz, 2 H), 7.74 (d, 3J = 8.1 Hz, 1 H) ppm. 13C NMR (50.3 MHz, THF (5 mL) was added through a septum, and the yellow solution
CDCl3): δ = 23.9 (Me), 28.0 (3ϫMe), 82.9 (C-O), 91.9 (CI), 120.6 was stirred at room temperature for 10 min. Then this solution was
(CH), 123.8 (CH), 128.2, 129.6 (2ϫCH), 130.8 (CH), 133.3, 138.6 added dropwise with a syringe to the solution (or suspension) of
(2ϫCH), 141.8, 148.3, 152.8 (C=O), 168.0 (2ϫC=O) ppm. MS (CI/
the α-zink derivative in the first flask. The reaction mixture was
NH3): m/z (%) = 496 (100) [M + NH4+]. C20H19N2O4I (478.28): stirred at 38 °C for 16 h, until no spot of the starting iodide was
calcd. C 50.22, H 4.00, N 5.86; found C 50.10, H 4.34, N 5.60.
detected on TLC. Then it was diluted with EtOAc (40 mL), washed
with saturated aq. NH4Cl (40 mL) and dried. After evaporation of
the solvent, the residue was purified on silica gel (60 g) with hexane/
EtOAc mixture (1:2), and the title product was isolated as a light
yellow oil (40 mg, 47%). HPLC (see Supporting Information): tR
= 18.9 min (100%), A/B: from 50:50 to 0:100 in 25 min, 25 °C,
detection at 254 nm. 1H NMR (300.5 MHz, CDCl3, two rotamers):
δ = 1.40 (s, 9 H), 2.04 (s, 3 H), 2.08 (s, 1.5 H), 2.11 (s, 1.5 H), 2.29
4-[2-[2,4-Dimethyl-5-(pyridin-4-yl)thiophen-3-yl]-3,3,4,4,5,5-hexa-
fluorocyclopent-1-enyl]-3,5-dimethyl-2-(trimethylsilyl)thiophene (9-
SiMe3): To a solution of 3-bromo-2,4-dimethyl-5-trimethylsylilthio-
phene (8) (820 mg, 3.1 mmol) in anhydrous THF (4 mL), nBuLi
(2.5  in hexanes, 1.26 mL, 3.15 mmol) was added slowly at –78 °C,
and the mixture was stirred at this temperature for 30 min. A solu-
tion of compound 5 (980 mg, 2.57 mmol) in anhydrous THF
(4 mL) was added slowly at –78 °C. After stirring for 20 min at
–78 °C, the reaction mixture was warmed-up to room temperature,
stirred for 30 min, diluted with diethyl ether (100 mL), and washed
with water (50 mL). The organic solution was dried and concen-
trated in vacuo. The residue was purified on silica gel (100 g) with
hexane/EtOAc mixture (1:1), and the title compound was isolated
3
(s, 3 H), 2.31 (s, 1.5 H), 2.34 (s, 1.5 H), 3.09 (s, 3 H), 7.13 (d, J =
3
8.5 Hz, 2 H), 7.21 (m, 2 H), 7.29 (d, J = 8.5 Hz, 2 H), 7.49 (dd,
4
3
4
3J = 3.6, J = 1.9 Hz, 0.5 H), 7.52 (dd, J = 3.6, J = 1.9 Hz, 0.5
3
4
3
H), 7.57 (dd, J = 3.8, J = 1.9 Hz, 1 H), 7.69 (d, J = 8.1 Hz, 1
H), 8.53 (d, 3J = 4.7 Hz, 2 H) ppm. 13C NMR (75.5 MHz, CDCl3):
δ = 14.8 (4ϫMe), 24.0 (Me), 28.1 (3ϫMe), 82.7 (C-O), 107.9 (CH),
120.6 (CH), 123.1 (2ϫCH), 123.6 (2ϫCH), 125.8, 126.7, 127.6
(CH), 128.1, 130.9, 129.8 (2ϫCH), 132.2, 132.5, 133.1, 134.4, 135.4,
139.2, 139.4, 141.0, 141.8, 148.3, 149.8 (2ϫCH), 152.9 (CO), 167.8
(CO), 167.9 (CO) ppm. MS (ESI): m/z (%) = 824 (100) [M + H]+.
H R M S ( E S I ) : m / z = 8 2 4 . 2 0 4 6 8 [ M + H ] + , c a l c d . fo r
C42H36N3F6O4S2: 824.20514.
1
as a yellow-red oil (1.00 g, 71%). H NMR (300.5 MHz, CDCl3):
δ = 0.28 (s, 9 H), 2.09–2.16 (m, 6 H), 2.29–2.38 (m, 6 H), 7.24 (dd,
4
3
4
3J = 4.9, J = 1.6 Hz, 1 H), 7.26 (dd, J = 4.9, J = 1.6 Hz, 1 H),
8.6 (d, 3J = 4.9, 4J = 1.6 Hz, 2 H) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = –0.3 (3ϫCH3), 14.9 (2ϫMe), 16.3 (2ϫMe), 123.0
(2ϫCH), 126.8, 127.0, 132.2, 133.1, 134.4, 140.8, 141.0, 141.7,
143.0, 144.5, 144.7, 150.1 (2ϫCH) ppm. MS (ESI): m/z (%) = 546
(100) [M + H+]. C25H25NF6S2Si (545.65): calcd. C 55.03, H 4.62,
N 2.57; found C 55.35, H 4.64, N 2.49.
4-[4-(4-{2-[2,4-Dimethyl-5-(pyridin-4-yl)thiophen-3-yl]-3,3,4,4,5,5-
hexafluorocyclopenten-1-yl}-3,5-dimethylthiophen-2-yl)phenylamino]-
N-methylphthalimide (1-H): Compound 1-H was prepared as de-
scribed above for the substance 1-Boc from the iodide 6-H (40 mg,
0.106 mmol) and 4 mol-equiv. of the thiophene 9-H (200 mg,
0.423 mmol). The crude product was purified on silica gel (60 g)
with CH2Cl2/CH3OH mixture (50:1) as eluent. Yield 12 mg (16%)
of a yellow oil. HPLC (see Supporting Information): tR = 3.6 min
(95.6%), A/B: from 20:80 to 0:100 in 25 min, 25 °C, detection at
254 nm. 1H NMR (300.5 MHz, CDCl3): δ = 2.04 (m, 3 H), 2.11
(m, 3 H), 2.29 (s, 3 H), 2.34 (br. s, 3 H), 3.07 (s, 3 H), 6.40 (d, 3JH,H
4-{2-[2,4-Dimethyl-5-(pyridin-4-yl)thiophen-3-yl]-3,3,4,4,5,5-hexa-
fluorocyclopent-1-enyl}-3,5-dimethylthiophene (9-H): To a solution
of 9-SiMe3 (1.0 g, 1.83 mmol) in anhydrous THF (10.0 mL),
Bu4NF (1.0  in THF, 3.67 mL, 3.67 mmol) was added slowly at
room temperature, and stirring was continued for 20 min. The mix-
ture was diluted with diethyl ether (100 mL), washed with water
(50 mL), dried and filtered. The solvents were removed in vacuo,
and the residue was purified by filtration through silica gel (45 g)
with hexane/EtOAc mixture (1:1) as an eluent. After removing of
the solvent, an orange-red oil was obtained, which solidified in ca.
one week; yield 800 mg (92%). 1H NMR (300.5 MHz, CDCl3): δ
= 0.28 (s, 9 H), 2.00 (s, 3 H), 2.06 (s, 3 H), 2.25 (s, 3 H), 2.38 (s, 3
3
4
= 4.4 Hz, 1 H), 7.09 (dd, JH,H = 8.2, JH,H = 2.0 Hz, 1 H), 7.11
3
3
(d, JH,H = 8.6 Hz, 2 H), 7.22 (d, JH,H = 6.0 Hz, 2 H), 7.28 (d,
3JH,H = 8.6 Hz, 1 H), 7.36 (d, JH,H = 2.0 Hz, 1 H), 7.60 (d, JH,H
3
3
3
= 8.2 Hz, 1 H), 8.54 (d, JH,H = 5.1 Hz, 2 H) ppm. 13C NMR
(50.3 MHz, CDCl3): δ = 14.8 (4ϫMe), 23.7 (Me), 108.0, 109.2
(CH), 119.2 (CH), 120.8 (2ϫCH), 122.5, 123.2 (2ϫCH), 125.1
(CH), 129.5, 130.5 (2ϫCH), 133.4, 134.5, 135.1, 136.0, 139.5, 141.8,
149.3, 150.2 (2ϫCH), 168.5 (2ϫC=O) ppm. MS (ESI): m/z (%) =
724 (100) [M + H]+. HRMS (ESI): m/z = 724.15223 [M + H]+,
calcd. for C37H28N3F6O2S2: 724.15271.
3
4
H), 6.67 (s, 1 H), 7.19 (dd, J = 4.5, J = 1.7 Hz, 2 H), 8.53 (dd,
3J = 4.5, J = 1.6 Hz, 2 H) ppm. 13C NMR (50.3 MHz, CDCl3): δ
4
= 14.8 (2ϫMe), 17.0 (2ϫMe), 119.7 (CH), 123.1 (2ϫCH), 124.6,
127.0, 133.4, 134.5, 136.7, 141.0, 141.5, 150.2 (2ϫCH) ppm. MS
(EI): m/z (%) = 473 (100) [M+]. C22H17NF6S2 (473.50): calcd. C
55.80, H 3.62, N 2.96; found C 56.13, H 3.84, N 3.09.
Supporting Information (see also the footnote on the first page of
this article): HPLC traces (1-Boc and 1-H) and 13C NMR spectrum
of 1-H.
4-[4-(4-{2-[2,4-Dimethyl-5-(pyridin-4-yl)thiophen-3-yl]-3,3,4,4,5,5-
hexafluorocyclopent-1-enyl}-3,5-dimethylthiophen-2-yl)phenylamino]-
N-(tert-butyloxycarbonyl)-N-methylphthalimide (1-Boc): 2,2,6,6-
Tetramethylpiperidine (112.5 mg, 0.798 mmol) and anhydrous
THF (1 mL) were introduced through a septum into a flame-dried
flask (25 mL). tBuLi (1.48  in pentane, 0.532 mL, 0.785 mmol)
was added slowly to this solution at –78 °C, and stirring was con-
tinued for 10 min. Then a solution of the substance 9-H (171 mg,
0.361 mmol) in anhydrous THF (1 mL) was added carefully at
–78 °C, and the mixture was stirred for 30 min. After that, a solu-
tion of anhydrous ZnCl2 (1  in Et2O, 0.818 mL, 0.818 mmol) was
added carefully, and simultaneously 10 mL of cold dry THF were
added dropwise. Then a cooling bath was removed, and the reac-
tion mixture was warmed-up to 0 °C. In another dry flask, a mix-
Acknowledgments
This work was supported by the Max-Planck-Gesellschaft, Bundes-
ministerium für Bildung und Forschung (Biophotonics program),
European Union through a Marie Curie fellowship (grant to
M. B.), and a NEST/Adventure program (SPOTLITE) (project
grant to S. W. H.). The authors are very grateful to Mr. Machinek
and Dr. Frauendorf and coworkers for obtaining the NMR and
mass spectra, and to Mr. Hambloch for performing the elemental
analyses in Institut fuer Organische und Biomolekulare Chemie
ture of 6-Boc (50 mg, 0.105 mmol), [Pd(dba)2] (7 mg, 12 µmol) and (Georg-August-Universität, Göttingen). The authors are grateful
Ph3P (14 mg, 52 µmol) was prepared under nitrogen. Anhydrous
to B. Rankin for critical reading of the manuscript.
Eur. J. Org. Chem. 2008, 2531–2538
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2537

S. F. Yan, V. N. Belov, M. L. Bossi, S. W. Hell
FULL PAPER
Zelinskii, I. E. Obyknovennaya, Izv. Ross. Akad. Nauk. Ser.
Fiz. 1965, 29, 1363–1368.
Cf.: S. H. Kawai, S. L. Gilat, J.-M. Lehn, Eur. J. Org. Chem.
1999, 9, 2359–2366.
a) K. Yagi, C. F. Song, M. Irie, J. Org. Chem. 2001, 66, 5419–
5423; b) M. Bossi, V. Belov, S. Polyakova, S. W. Hell, Angew.
Chem. 2006, 118, 7623–7627; Angew. Chem. Int. Ed. 2006, 45,
7462–7465.
[1] Molecular Switches (Ed.: B. L. Feringa), Wiley-VCH,
Weinheim, 2001.
[2] a) H. Miyasaka, S. Arai, A. Tabata, T. Nobuto, N. Mataga,
M. Irie, Chem. Phys. Lett. 1994, 230, 249–254; b) N. Tamai, T.
Saika, T. Shimidzu, M. Irie, J. Phys. Chem. 1996, 100, 4689–
4692; c) M. Handschuh, M. Seibold, H. Port, H. C. Wolf, J.
Phys. Chem. A 1997, 101, 502–506.
[20]
[21]
[3] Y. Hirshberg, C. R. Chim. 1950, 231, 903–904.
[4] a) F. Ebisawa, M. Hoshino, K. Sukegawa, Appl. Phys. Lett.
1994, 65, 2919–2921; b) N. Tanio, M. Irie, Jpn. J. Appl. Phys.
1994, 33, 1550–1553.
[5] a) M. Seibold, H. Port, Chem. Phys. Lett. 1996, 252, 135–140;
b) M. Seibold, H. Port, H. C. Wolf, Mol. Cryst. Liq. Cryst.
1996, 283, 75–80.
[6] a) G. M. Tsivgoulis, J.-M. Lehn, Angew. Chem. Int. Ed. Engl.
1995, 34, 1119–1122; b) T. Inada, S. Uchida, Y. Yokoyama,
Chem. Lett. 1997, 321–322; c) M. Takeshita, M. Irie, Chem.
Lett. 1998, 1123–1124; d) Y. C. Liang, A. S. Dvornikov, P. M.
Rentzepis, Res. Chem. Intermed. 1998, 24, 905–914; e) for a
review on fluorescence modulation, see: F. M. Raymo, M. To-
masulo, J. Phys. Chem. A 2005, 109, 7343–7352.
[7] a) S. L. Gilat, S. H. Kawai, J.-M. Lehn, J. Chem. Soc. Chem.
Commun. 1993, 1439–1442; b) S. L. Gilat, S. H. Kawai, J.-M.
Lehn, Chem. Eur. J. 1995, 1, 275–284.
[8] a) B. L. Feringa, W. F. Jager, B. De Lange, E. W. Meijer, J. Am.
Chem. Soc. 1991, 113, 5468–5470; b) Y. Yokoyama, S. Uchida,
Y. Yokoyama, Y. Sugawara, Y. Kurita, J. Am. Chem. Soc. 1996,
118, 3100–3107; c) B. L. Feringa, R. A. van Delden, N. Kou-
mura, E. M. Geertsema, Chem. Rev. 2000, 100, 1789–1816.
[9] a) K. Matsuda, M. Irie, J. Am. Chem. Soc. 2000, 122, 7195–
7201; b) K. Matsuda, M. Irie, J. Am. Chem. Soc. 2000, 122,
8309–8310.
[22]
[23]
T. Kawai, T. Sasaki, M. Irie, Chem. Commun. 2001, 711–712.
a) T. D. Nelsona, R. D. Crouch in Organic Reactions, 2004, 63,
265–555; b) B. S. Portnaya, N. F. Turitsyna, T. P. Bobkova, I. I.
Levkoev, Russ. J. Gen. Chem. 1960, 30, 2693–2698.
I. Sapountzis, P. Knochel, J. Am. Chem. Soc. 2002, 124, 9390–
9391. This “one-pot” synthesis of diarylamines from aryl ha-
lide and an (aromatic) nitro compound is a combination of
three processes: i. formation of ArMgX from ArX and
iPrMgCl; ii. reductive addition of ArMgX to ArЈNO2 to yield
ArN(OH)ArЈ; iii. reduction of the latter with NaBH4.
[24]
[25]
[26]
H. Karatani, Bull. Chem. Soc. Jpn. 1987, 60, 2023–2029.
We used the commercial PhMgCl in THF, and at the last step
added NaBH4 as a solution in DMF. These changes increased
the yield from 2.6% (as in the case of adding dry NaBH4) to
26%. Unfortunately, no solvent for NaBH4 was specified in the
ref.[24]
.
[27]
[28]
G. M. Tsivgoulis, J.-M. Lehn, Chem. Eur. J. 1996, 2, 1399–
1406.
For the method of the Boc-protection for diphenylamines, see:
J. P. Sadighi, R. A. Singer, S. L. Buchwald, J. Am. Chem. Soc.
1998, 120, 4960–4976.
A. F. Littke, G. C. Fu, Angew. Chem. 1998, 110, 3586–3587;
Angew. Chem. Int. Ed. 1998, 37, 3387–3388.
a) M. Irie, T. Fukaminato, T. Sasaki, N. Tamai, T. Kawai, Na-
ture 2002, 420, 759–760; b) T. Fukaminato, T. Sasaki, T. Kawai,
N. Tamai, M. Irie, J. Am. Chem. Soc. 2004, 126, 14843–14849.
G. L. Stahl, R. Walter, C. W. Smith, J. Org. Chem. 1978, 43,
2285–2286.
N. Fujii, A. Otaka, O. Ikemura, K. Akaji, S. Funakoshi, Y.
Hayashi, Y. Kuroda, H. Yajima, J. Chem. Soc. Chem. Commun.
1987, 274–275.
U. Jacquemard, V. Beneteau, M. Lefoix, S. Routier, J.-Y. Mer-
our, G. Coudert, Tetrahedron 2004, 60, 10039–10047.
E. Negishi, J. Organomet. Chem. 2002, 653, 34–40.
G. Saroja, A. Samanta, J. Chem. Soc. Faraday Trans. 1996, 92,
2697–2701.
a) C. Reichardt, Chem. Rev. 1994, 94, 2319–2358; b) C.
Reichardt, Solvents and Solvent Effects in Organic Chemistry,
3rd ed., Wiley-VCH, Weinheim, 2003.
[29]
[30]
[10] J. J. D. de Jong, L. N. Lucas, R. M. Kellogg, J. H. van Esch,
B. L. Feringa, Science 2004, 304, 278–281.
[11] M. Irie, Chem. Rev. 2000, 100, 1685–1716.
[31]
[32]
[12] a) J. Walz, K. Ulrich, H. Port, H. C. Wolf, Chem. Phys. Lett.
1993, 213, 321–324; b) L. Giordano, T. M. Jovin, M. Irie, E. A.
Jares-Erijman, J. Am. Chem. Soc. 2002, 124, 7481–7489; c) M.
Irie, T. Fukaminato, T. Sasaki, N. Tamai, T. Kawai, Nature
2002, 420, 759–760; d) T. Fukaminato, T. Umemoto, Y. Iwata,
S. Yokojima, M. Yoneyama, S. Nakamura, M. Irie, J. Am.
Chem. Soc. 2007, 129, 5932–5938; e) T. A. Golovkova, D. V.
Kozlov, D. C. Neckers, J. Org. Chem. 2005, 70, 5545–5549; f)
A. L. Myles, N. R. Branda, Adv. Funct. Mater. 2002, 12, 167–
173; g) M.-S. Kim, T. Kawai, M. Irie, Chem. Lett. 2001, 702–
703; h) R. T. F. Jukes, V. Adamo, F. Hartl, P. Besler, L.
De Cola, Inorg. Chem. 2004, 43, 2779–2792; i) A. de Meijere,
L. Zhao, V. N. Belov, M. Bossi, M. Noltemeyer, S. W. Hell,
Chem. Eur. J. 2007, 13, 2503–2516.
[13] In some cases it is difficult to identify the substructure of the
fluorophore, which may be a part of the photochromic diaryle-
thene.
[14] Y. C. Liang, A. S. Dvornikov, P. M. Rentzepis, Proc. Natl.
Acad. Sci. USA 2003, 100, 8109–8112.
[15] E. N. Viktorova, V. V. Zelinskii, N. F. Neznaiko, Russ. J. Phys.
Chem. 1966, 40, 47–50.
[33]
[34]
[35]
[36]
[37]
[38]
M. Irie, K. Sayo, J. Phys. Chem. 1992, 96, 7671–7674.
a) S. W. Hell, Opt. Commun. 1994, 106, 19–22; b) S. W. Hell,
Nat. Biotechnol. 2003, 21, 1347–1355; c) M. Bossi, J. Fölling,
M. Dyba, V. Westphal, S. W. Hell, New J. Phys. 2006, 8, 275;
J. Fölling, S. Polyakova, V. Belov, A. van Blaaderen, M. Bossi,
S. W. Hell, Small 2007, 4, 134–142.
M. H. Deniel, D. Lavabre, J. C. Micheau, in Organic Photo-
chromic and Thermochromic Compounds, vol. 2, Physicochemi-
cal Studies, Biological Applications, and Thermochromism (Eds.:
J. C. Crano, R. J. Guglielmetti), Kluwer Academic, Plenum
Publishers, New York, 1999, 167–209.
[39]
[40]
[16] T. Veselova, E. Viktorova, V. Klochkov, A. Makushenko, I.
Reznikova, O. Stolbova, Opt. Spectrosc. 1995, 79, 55–70.
[17] G. Saroja, T. Soujanya, B. Ramachandram, A. Samanta, J.
Fluoresc. 1998, 8, 405–410.
M. Irie, K. Sakemura, M. Okinaka, K. Uchida, J. Org. Chem.
1995, 60, 8305–8309.
[18] V. V. Zelinskii, V. P. Kolobkov, Dokl. Phys. Chem. 1955, 101,
241–244.
[19] a) T. V. Veselova, I. I. Reznikova, A. S. Cherkasov, V. I. Shiro-
kov, Izv. Ross. Akad. Nauk. Ser. Fiz. 1970, 34, 648–653; b) V. V.
Received: February 1, 2008
Published Online: March 13, 2008
2538
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2531–2538