Subsequent chemical reactions of photochromic 4,5-dibenzothienylthiazoles

Article abstract of DOI:10.1002/ejoc.201200465

4,5-Dibenzothienylthiazole derivatives having leaving groups at the reactive 2-positions of benzothiophene rings have been synthesized, and their photochromic ring-closing reaction followed by spontaneous elimination and substitution reactions have been studied. A 4,5-dibenzothienylthiazole having an ethoxy group and a hydrogen atom at each 2-position of the benzothienyl ring underwent elimination to generate a condensed aromatic structure upon the addition of acid. 4,5-Dibenzothienylthiazoles having an ethoxy or methyl groups at the 2-position of the benzothienyl rings showed photochromism both in hexane and in methanol solutions with photocyclization quantum yields as high as 60 %. Upon the addition of acid to the methanol solutions of closed-ring isomers of dibenzothienylthiazoles, the substitution of the ethoxy group with a methoxy group occurred. The generation and rearrangement of the carbocation intermediate formed by elimination of the ethoxy group from the closed-ring isomers were apparent from the chemical structure of methoxy-substituted products. Subsequent chemical reactions are demonstrated for photoproducts of 4,5- dibenzothienylthiazoles possessing leaving groups at the 2-position of benzothienyl rings. Closed-ring isomers of 4,5-dibenzothienylthiazoles having an ethoxy group underwent an alcoholysis reaction under acidic conditions accompanying rearrangement of carbocation intermediates. Copyright

Full text of DOI:10.1002/ejoc.201200465

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DOI: 10.1002/ejoc.201200465
Subsequent Chemical Reactions of Photochromic 4,5-Dibenzothienylthiazoles
Hisako Nakagawa,[a] Takuya Nakashima,[a] and Tsuyoshi Kawai*[a]
Keywords: Terarylene / Photochromic compound / Elimination / Heterocycles / Photochromism / Dibenzothienylthiazoles /
Alcoholysis
4,5-Dibenzothienylthiazole derivatives having leaving
groups at the reactive 2-positions of benzothiophene rings
have been synthesized, and their photochromic ring-closing
reaction followed by spontaneous elimination and substitu-
tion reactions have been studied. A 4,5-dibenzothienyl-
thiazole having an ethoxy group and a hydrogen atom at
each 2-position of the benzothienyl ring underwent elimi-
nation to generate a condensed aromatic structure upon the
addition of acid. 4,5-Dibenzothienylthiazoles having an
ethoxy or methyl groups at the 2-position of the benzothienyl
rings showed photochromism both in hexane and in meth-
anol solutions with photocyclization quantum yields as high
as 60%. Upon the addition of acid to the methanol solutions
of closed-ring isomers of dibenzothienylthiazoles, the substi-
tution of the ethoxy group with a methoxy group occurred.
The generation and rearrangement of the carbocation inter-
mediate formed by elimination of the ethoxy group from the
closed-ring isomers were apparent from the chemical struc-
ture of methoxy-substituted products.
bio-probing and bio-controlling caged compounds,[8] and
so on. In an early report by Lehn and co-workers, substitu-
tion reactions specific for the ring-closed isomer of diary-
lethenes were demonstrated.[9] Other forms of selective
chemical reactivity for the ring-closed forms of diaryleth-
enes and terarylenes have been reported as photo-gated re-
actions.[10] It should be noted that the ring-closing reaction
of diarylethenes and terarylenes involves conversion of the
orbital of the reacting carbon atoms from sp2 to sp3 with
steric distortion, bringing about the specific reactivity of
closed-ring isomers. Recently, the authors have reported the
elimination of methanol from the ring-closed form of a ter-
arylene derivative to form condensed fluorescent aromatics
which never returned to the original open-ring isomer with
visible light irradiation (Scheme 1).[11] This elimination re-
action quantitatively proceeded either in highly polar sol-
vents such as acetone or in the presence of acid. Thus, the
set of reactions including photocyclization and subsequent
spontaneous dark reactions provides efficient routes not
only to polycyclic aromatics for which oxidative dehydroge-
Introduction
Electrocyclizations of a hexatriene moiety to form a cy-
clohexadiene structure, which is categorized as a pericycli-
zation reaction, has been widely studied as a typical photo-
chromic reaction.[1] Since the discovery of diarylethenes,
which undergo cyclization and cycloreversion reactions un-
der photo-irradiation, extensive studies have focused on the
synthetic organic chemistry of their derivatives and related
compounds. One of the typical features of diarylethene de-
rivatives is their relatively high photochromic sensitivity
even in single-crystalline and amorphous states.[2,3] Some
diarylethenes show photochemical quantum yields as high
as 100% in the crystalline state.[2d] Recent development of
terarylenes,[4] which are composed of three heteroaromatic
units to form a hexatriene backbone with photochromic re-
activity, has led to efficient photocyclization reaction sys-
tems by means of the control of molecular folding by supra-
molecular interactions with the aid of heteroaromatics.[5]
Among these systems, a 2,3-dithiazolylbenzothiophene with
the controlled photochromically active conformation,
which is tethered by multiple intramolecular interactions,
has been reported to show a photon-quantitative ring-clos-
ing reaction.[5c] This motivated us to explore the specific
chemical reactivity in ring-closed cyclohexadienes as a way
to enable efficient photochemical processes such as, photo-
acid generators[6] for efficient optical photolithography,[7]
[a] Graduate School of Materials Science, Nara Institute of Science
and Technology, NAIST,
8916-5 Takayama, Ikoma, Nara, Japan
Fax: +81-743-72-6179
Scheme 1. Photochromism and elimination reaction of the closed-
ring isomer of a terarylene with leaving groups at the photoreactive
carbon atoms.[11]
E-mail: tkawai@ms.naist.jp
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200465.
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H. Nakagawa, T. Nakashima, T. Kawai
FULL PAPER
nation is often employed,[12,13] but also to sequential photo-
releasing systems[10b] that trigger further chemical reactions
in a remote manner.
Results and Discussion
Compounds 1–4 were synthesized by conventional cross-
coupling reactions of 4,5-dibromo-2-phenylthiazole and
various pinacolboranes of benzothiophene, and their chem-
ical structures were confirmed by 1H NMR, 13C NMR,
mass spectra, and elemental analysis.
In this study, we investigated subsequent reactions which
follow the efficient photochromic ring-closing reaction of
terarylenes using a series of 4,5-dibenzothienylthiazoles
with various substituents at the 2-position of a benzothienyl
ring. The chemical reactivity of the substituents was investi-
gated in association with the photocyclization reaction in
the presence of acid; new stereospecific reactions giving
complex polycyclic structures are also demonstrated. Com-
pounds 1–4 have a similar basic terarylene structure of 2-
phenyl-4,5-dibenzothienylthiazole, which has been demon-
strated to show relatively high photocyclization reaction
efficiency above 60%,[5a] with different substituents at the
2-position of benzothienyl rings (Scheme 2). Compound 1
has an ethoxy group and a hydrogen atom at the respective
2-positions of each benzothienyl ring and was expected to
undergo ethanol elimination in a manner similar to that
shown in Scheme 1. Unlike 1, compounds 2 and 3 had
methyl groups at each 2-position opposite to the ethoxy
group; in each case the methyl group was anticipated to
suppress the concerted elimination reaction. Given that the
elimination reaction from the ring-closed intermediate pro-
ceeds through the agency of a carbocation intermediate, 2
and 3 were expected to give alcoholysis products with an
alkoxy substituent corresponding to the alcohols used as
solvents in the presence of acid. The subsequent chemical
reaction is discussed in terms of the chemical structure of
products determined by 1H NMR, mass spectra, and X-ray
crystal structures.
As shown in Figure 1, compound 1 showed both photo-
induced coloration and de-coloration reactions in hexane.
We observed a colorless solution of the open-ring isomer
1a turn orange upon irradiation with UV light (λ = 313 nm)
and showing an absorption maximum at 530 nm. The col-
ored solution was bleached by visible light irradiation (λ Ͼ
400 nm) and returned to the original colorless solution of
1a. However, the closed-ring isomer 1b was difficult to iso-
late from the colored solution since the subsequent elimi-
nation reaction occurred in the reverse-phase HPLC col-
umn when using polar solvents as eluent. The hexane solu-
tion containing the ring-closed 1b became yellow immedi-
ately following addition of a small amount of trifluoroacetic
acid (TFA), and the absorption band at 530 nm completely
disappeared. The absorption profile of the product was
found to be clearly different from that of 1a, indicating the
formation of a new compound. Neither UV nor visible irra-
diation to the yellowish solution caused further spectral
change. The single yellow component was isolated by
HPLC and identified as condensed structure 1c in Scheme 3
1
on the basis of H NMR and mass spectra, which corre-
sponds well with the previous result (Scheme 1). Gradual
Figure 1. Absorption spectrum change of 1 in hexane: open form
(dotted line), photostationary state under irradiation with 313 nm
light (solid line) and after the addition of TFA (dashed line).
Scheme 2. Photochemical interconversion of 4,5-dibenzothienylthi-
azoles.
Scheme 3. Photoreaction and subsequent elimination reaction of 1.
2
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Photochromic 4,5-Dibenzothienylthiazoles
formation of 1c from 1b was also observed in methanol in
the absence of both acid and light.
Photochromic properties of 4,5-dibenzothienylthiazoles
2a and 3a with opposing ethoxy and methyl groups at each
benzothienyl 2-position and 4a with two opposing ethoxy
groups were then investigated. The values for λmax and ε of
2, 3 and 4 are summarized in Table 1 with photochromic
cyclization quantum yields evaluated by the standard pro-
cedure with 3,3,4,4,5,5-hexafluoro-1,2-bis(2-methylbenzo-
[b]thiophene-3-yl)cyclopentene[14] in hexane as a standard.
Relatively high quantum yields were obtained for com-
pounds 2–4 in their cyclization reactions, which were almost
comparable with those reported for 4,5-dibenzothienylthi-
azoles.[5a] The colorless solutions of 2a–4a turned to red-
purple, bluish-purple and blue upon irradiation at 313 nm.
These colors are due to the formation of closed-ring iso-
mers 2b–4b. The conversion ratios between 2a and 2b, be-
tween 3a and 3b and between 4a and 4b at their photo-
stationary states, achieved by irradiation with UV light (λ
= 313 nm) were estimated to be 86, 81 and 90%, respec-
tively. Upon irradiation with visible light, the closed-ring
isomers reverted to 2a–4a with a decrease of absorption
band in the visible region. 4,5-Dibenzothiazoles 2–4 showed
the photochromic reactions in methanol as well as in hex-
ane. Since isosbestic points were clearly observed in both
hexane and methanol, the well-defined two-component re-
action schemes between the open-ring and the closed-ring
isomers are apparent under these conditions. Unlike 1, the
ring-closed forms 2b–4b were successfully isolated by re-
verse-phase HPLC using methanol as an eluent, and their
structures were elucidated by 1H NMR spectroscopy. These
ring-closed forms seemed to be stable in methanol. The
existence of clear isosbestic points in the absorption spectral
change (Figure 2) in methanol solutions also supports the
stability of the ring-closed form in methanol.
Figure 2. Absorption spectra for 2 (a), 3 (b) and 4 (c) in methanol:
open-form a (dotted lines), closed-form b (solid lines) and photo-
stationary state under irradiation with 313 nm light (broken lines).
The concentrations of 2, 3 and 4 were 1.0ϫ10–5, 1.44ϫ10–5 and
1.29ϫ10–5 m, respectively.
Table 1. Absorption maxima (λmax) and coefficients (ε) of the open-
and closed-ring isomers of 1–4, together with the ring-closing
quantum yields (Φa–b) in hexane solution.
Entry
Compound
λmax [nm] (ε [104 m–1 cm–1])
Φa–b
addition of TFA, and a new absorption band appeared at
253 nm (Figure 3b). These acid-induced spectral changes
were observed in the dark. The absorption profiles of final
products were different from those of starting materials 2a
and 3a, indicating the formation of new components. The
isosbestic points at 400 nm (for 2) and 280 nm (for 3) were
clearly found, supporting the involvement of two-compo-
nent chemical reactions with the addition of TFA. The final
products no longer showed photochromic changes upon ir-
radiation with either UV or visible light. The reaction mix-
tures were characterized by a reverse-phase HPLC with a
flow rate of 3 mL/min. The fact that no closed-form mole-
[a]
1
2
1a
1b
310 (1.1)
–
530[b] (–)[a]
–
3
4
2a
2b
340 (1.2)
0.53
–
545[b] (0.94)
5
6
3a
3b
336 (1.0)
0.64
–
554[b] (0.98)
7
8
4a
4b
344 (0.90)
566[b] (1.1)
0.62
–
[a] Not determined because 1b could not be isolated. [b] Absorp-
tion maximum in the visible region.
In order to evaluate the mechanism of ethoxy group eli- cules 2b (66 min) or 3b (65 min) were observed (Supporting
mination from the benzothiophene 2-position, TFA was Information, Figure S1) indicates a conversion ratio of al-
added to methanolic solutions of 2b and 3b. The absorption most 100%, which is consistent with the observed changes
band at 545 nm derived from the closed-ring isomer 2b de- in absorption spectra (Figure 3). Each reaction mixture of
creased following addition of TFA, and a new absorption 2b and 3b with TFA gave single HPLC peaks at 57 and
band appeared at 368 nm (Figure 3a). Similarly, the absorp- 71 min, respectively; these are different from the retention
tion band for 3b observed at 554 nm decreased following times of 2a (46 min) and 3a (51 min), respectively. Mean-
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while, addition of TFA to methanol solutions of open-ring
isomers 2a and 3a did not induce any observable changes
1
in absorption or H NMR spectra, demonstrating a ring-
closed form-selective reaction. Although 4b with two
ethoxy groups at the reactive benzothiophene carbon atoms
showed a similar spectral change to those observed for 2b
and 3b with an isosbestic point by the addition of TFA
(Supporting Information, Figure S3), the reaction mixture
gave a complicated HPLC chromatogram with multiple
peaks.
1
Figure 4. H NMR spectra for 2b (a), 2c (b), 3b (c) and 3c (d) in
CD2Cl2. For clarity, only parts of the aliphatic region (δ = 0.5–
4.0 ppm) are shown.
Fortunately, 2c and 3c crystallized from their hexane
solutions as colorless crystals enabling us to identify the
absolute structures of 2c and 3c by single-crystal X-ray
analysis (Figure 5).[15] Although 2c and 3c are indeed meth-
oxy-substituted products, the methoxy group regiochemis-
try was found to be different from that of the ethoxy groups
in 2a and 3a, respectively. The methoxy group in 2c was
introduced at C10 (Figure 5a), and the methoxy group in
3c was found to reside at C20 (Figure 5b). This suggests the
generation of intermediates (2b–OEt)+ and (3b–OEt)+ by
the elimination of the ethoxy group as ethanol from 2b and
3b, respectively, and subsequent carbocation rearrange-
ments. According to the resonance structures depicted in
Scheme 4, the positive charge seems to be mainly localized
on the C3, C10 and C19 positions for (2b–OEt)+ and C2,
C17 and C20 positions for (3b–OEt)+. Considering the rela-
tive stability of the three possible resonance structures X, Y
and Z for carbocation intermediates in Scheme 4 in terms
of the number of aromatic rings involved, canonical struc-
tures Z seem to be the most stable ones for both
(2b–OEt)+ and (3b–OEt)+.
Figure 3. Absorption spectral changes of 2b (a) and 3b (b) after
the addition of TFA. Spectra were recorded every 5 min after the
addition of TFA.
The reaction products derived from 2b and 3b by the
addition of TFA in methanol were isolated by HPLC as 2c
and 3c, respectively, and were characterized with the aid of
1
1H NMR and mass spectra. Figure 4 shows the H NMR
spectral change in the aliphatic region in going from 2b to
2c and from 3b to 3c. Signals at δ = 3.72, 3.39 and 1.08 ppm
assigned to an ethoxy group in 2b disappeared in 2c,
whereas the methyl group proton signals on another reac-
tive carbon atom at δ = 2.1 ppm remained, and a new sing-
let signal appeared at δ = 3.00 ppm (3 H). A similar result
1
was also observed in the H NMR spectral change from 3b
to 3c. The new singlet at δ = 3 ppm was assigned as the
methoxy group, which takes the place of the ethoxy group
of 2b and 3b by alcoholysis in methanol. The change in
molecular mass with the decrease of 14 observed by mass
measurement also supported the replacement of an ethoxy
group with a methoxy group. The possibility of simple sub-
stitution reactions has been excluded since 2c and 3c failed
to show any photochromic capability.
Figure 5. ORTEP drawings (showing 50% probability displacement
ellipsoids) of the crystals of 2c (a) and 3c (b).
4
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Photochromic 4,5-Dibenzothienylthiazoles
anol from 1b under neutral conditions; such a scenario
clearly warrants further study.
Scheme 4. Resonance structures of carbocation intermediates (2b–
OEt)+ and (3b–OEt)+.
Scheme 5. Suggested reaction mechanism for the elimination of
ethanol followed by the introduction of a methoxy group in 2.
The distribution of the positive charge in (2b–OEt)+ and
(3b–OEt)+ was also simulated using density function theory
(DFT) calculations at the B3LYP/6-31++G* level. The pos-
itive charges were found to be more localized at C10 for
(2b–OEt)+ and at C20 for (3b–OEt)+ (Supporting Infor-
mation, Figure S4) than for other possible carbon atoms.
This finding was consistent with structures elucidated for
products 2c and 3c. It also should be noted that X-ray crys-
tallographic data revealed only cis-substituted compounds,
although trans-compounds could be generated according to
the reaction mechanism. However, 1H NMR and HPLC
results never suggested the formation of diastereomeric
products. In order to compare the stability of cis and trans
forms of 2c, Merck Molecular Force Field (MMFF94) cal-
culations were performed. The cis structure was calculated
based on the X-ray single-crystal structure. According to
the MMFF calculations, the cis structure is much more
stable than the trans structure by 22 kcal/mol. CH/O inter-
actions between methyl and methoxy groups in the cis form
may stabilize the cis form. Moreover, substantial strain in
the fused aromatic rings may destabilize the trans form. The
methoxy group, once attached to the trans position, might
be readily eliminated under acidic conditions to bias the
chemical equilibrium towards the more stable cis form.
On the basis of these results we consider that a plausible
mechanism for the elimination reaction in acidic conditions
is as shown in Scheme 5. The ethoxy group on the 2-posi-
tion of benzothiophene leaves as ethanol in the presence
of TFA. The carbocation, which can assume a number of
different resonance structures, then selectively reacts with
methanol at the most positively charged carbon atom. This
SN1-like reaction mechanism seems to be dominant under
the acidic conditions because of the poor leaving group
ability of the methoxylate anion under neutral conditions.
However, it should also be mentioned that the contribution
of a concerted reaction, where the elimination of ethanol
and the addition of the methoxy group occur simulta-
neously, cannot be ruled out completely. Although 2b and
3b were stable in neutral methanol, 1b spontaneously
formed 1c. This specific reactivity of 1b may originate from
a particularly facile deprotonation due to a unique H-bond-
Conclusions
We synthesized 4,5-dibenzothienylthiazoles with leaving
groups at the 2-position of each benzothienyl ring and
studied the elimination and substitution reactions under
alcoholysis conditions. All compounds underwent photo-
chromic reactions in hexane and subsequent reactions spe-
cific for ring-closed forms under acidic conditions. Com-
pound 1 having a hydrogen atom and an ethoxy group at
reacting carbon atoms underwent an irreversible elimi-
nation reaction following the addition of acid as we have
already reported.[11] On the other hand, closed isomers 2b
and 3b having a methyl group on the side opposite to the
ethoxy group underwent substitution of the ethoxy group
with a methoxy group in methanol. The crystal structures
of 2c and 3c along with DFT calculations suggest the gener-
ation of carbocationic intermediates and the rearrangement
of these carbocations to give the most stable cis-substituted
products.
Experimental Section
General: 1H NMR spectra were recorded with a JEOL AL-300
spectrometer (300 MHz). Preparative and analytical HPLC was
performed with a HITACHI LaChrom ELITE HPLC system and
a JASCO LC-2000 Plus Series. Mass spectra were measured with
a JEOL JMS-T100LC AccuTOF mass spectrometer. Absorption
spectra in solution were studied with JASCO V-550 and V-660 spec-
trophotometers. Irradiations were carried out with a USHIO
500 W ultra-high-pressure mercury lamp as the excitory light
source. Monochromic light was obtained by passing the light
through a monochromator (Shimadzu SPG-120S, 120 mm, f = 3.5).
X-ray crystallographic analyses were carried out with a Rigaku R-
AXIS RAPID/s imaging-plate diffractometer with Mo-Kα radia-
tion at 296 K.
Synthesis of 1a–4a: Dibenzothienylthiazoles 1a–4a were prepared
by cross-coupling reactions as illustrated in Scheme 6.
4-Bromo-5-(2-ethoxybenzo[b]thiophen-3-yl)-2-phenylthiazole (7): A
500 mL four-necked flask was charged with 2-(2-ethoxybenzo[b]-
ing network, which enables concerted elimination of eth- thiophen-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5, 2.2 g,
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Scheme 6. Syntheses of compounds 1a–4a. Reagents and conditions: triphenylphosphane, Pd(PPh3)4, K3PO4 (2 m)/H2O, 1,4-dioxane.
7.2 mmol), 4,5-dibromo-2-phenylthiazole (6, 2.3 g, 7.2 mmol), tri-
phenylphosphane (940 mg, 3.6 mmol), Pd(PPh3)4 (410 mg,
0.36 mmol), and K3PO4 (2 m) in water/1,4-dioxane (100 mL/
and K3PO4 (2 m) in water/1,4-dioxane (100 mL/200 mL) solution.
The mixture was then stirred at 110 °C under N2. After stirring for
12 h, the reaction mixture was extracted with EtOAc, and the or-
200 mL) solution. The mixture was then stirred at 110 °C under ganic layer was dried with anhydrous magnesium sulfate, filtered,
N2. After stirring for 20 h, the reaction mixture was extracted with
EtOAc, and the organic layer was dried with anhydrous magnesium
sulfate, filtered, and concentrated. Silica gel column chromatog-
raphy (hexane/EtOAc, 20:1) followed by recrystallization from hex-
ane afforded 7 (2.0 g, 67%) as a colorless solid. 1H NMR
(300 MHz, [D6]acetone): δ = 1.42–1.47 (t, J = 7 Hz, 3 H), 4.42–
and concentrated. Silica gel column chromatography (hexane/
EtOAc, 20:1) followed by recrystallization from hexane afforded 2a
(1.2 g, 69 %) as a colorless solid. 1H NMR (300 MHz, CD2Cl2/
TMS): δ = 0.85–0.89 (t, J = 7 Hz, 3 H), 2.1 (s, 3 H), 3.81 (s, 2 H),
7.12–7.18 (m, 2 H), 7.25–7.28 (m, 2 H), 7.48–7.52 (m, 4 H), 7.62–
7.65 (m, 1 H), 7.72–7.75 (m, 2 H), 8.06–8.09 (m, 2 H) ppm. 13C
4.43 (q, J = 7 Hz, 2 H), 7.34–7.40 (m, 2 H), 7.54–7.57 (m, 4 H), NMR (75 MHz, CD2Cl2/TMS): δ = 14.40, 14.93, 71.32, 105.82,
7.84–7.86 (d, J = 8 Hz, 1 H), 8.01–8.04 (m, 2 H) ppm.
121.21, 121.98, 122.57, 123.39, 123.59, 124.07, 124.44, 125.41,
126.79, 127.15, 128.42, 129.41, 130.45, 131.14, 134.30, 137.59,
138.35, 139.36, 140.49, 148.62, 161.78, 167.14 ppm. ESI-HRMS:
4-(Benzo[b]thiophen-3-yl)-5-(2-ethoxybenzo[b]thiophen-3-yl)-2-
phenylthiazole (1a): A 200 mL four-necked flask was charged with
4,4,5,5-tetramethyl-2-(2-methylbenzo[b]thiophen-3-yl)-1,3,2-di-
oxaborolane (8, 170 mg, 0.64 mmol), 4-bromo-5-(2-ethoxybenzo[b]-
thiophen-3-yl)-2-phenylthiazole (7, 270 mg, 0.64 mmol), tri-
phenylphosphane (83 mg, 0.32 mmol), Pd(PPh3)4 (36 mg,
calcd. for C28H22NOS3 [M + H]+ 484.0858; found 484.0856.
+
C28H21NOS3 (483.66): calcd. C 69.53, H 4.38, N 2.90; found C
69.55, H 4.18, N 3.08.
4-Bromo-5-(2-methylbenzo[b]thiophen-3-yl)-2-phenylthiazole (10): A
0.032 mmol), and K3PO4 (2 m) in water/1,4-dioxane (25 mL/50 mL) 300 mL four-necked flask was charged with 4,4,5,5-tetramethyl-2-
solution. The mixture was then stirred at 110 °C under N2. After
stirring for 2 d, the reaction mixture was extracted with EtOAc,
and the organic layer was dried with anhydrous magnesium sulfate,
filtered, and concentrated. Silica gel column chromatography (hex-
ane/EtOAc, 20:1) and reverse-phase HPLC (MeOH) afforded 1a
(52 mg, 17%) as a colorless solid. 1H NMR (300 MHz, [D6]ace-
tone/TMS): δ = 1.02–1.28 (t, J = 7 Hz, 3 H), 4.02–4.04 (q, J =
(2-methylbenzo[b]thiophen-3-yl)-1,3,2-dioxaborolane (9, 570 mg,
2.1 mmol), 4,5-dibromo-2-phenylthiazole (6, 660 mg, 2.1 mmol),
triphenylphosphane (270 mg, 1.0 mmol), Pd(PPh3)4 (120 mg,
0.1 mmol), and K3PO4 (2 m) in water/1,4-dioxane (70 mL/150 mL)
solution. The mixture was then stirred at 110 °C under N2. After
stirring for 12 h, the reaction mixture was extracted with EtOAc,
and the organic layer was dried with anhydrous magnesium sulfate,
7 Hz, 2 H), 7.23–7.26 (m, 2 H), 7.37–7.45 (m, 4 H), 7.55–7.60 (m, filtered, and concentrated. Recrystallization from hexane afforded
3 H), 7.78–7.79 (m, 1 H), 7.92–7.93 (m, 1 H), 8.13–8.14 (m, 2 H),
10 (570 mg, 71 %) as a colorless solid. 1H NMR (300 MHz,
[D6]acetone/TMS): δ = 2.58 (s, 3 H), 7.42–7.57 (m, 6 H), 7.96–8.06
(m, 3 H) ppm.
+
8.32–8.33 (m, 1 H) ppm. EI-HRMS: calcd. for C27H19NOS3
[M]+ 469.6409; found 469.0630.
5-(2-Ethoxybenzo[b]thiophen-3-yl)-4-(2-methylbenzo[b]thiophen-3-
yl)-2-phenylthiazole (2a): A 300 mL four-necked flask was charged
with 4,4,5,5-tetramethyl-2-(2-methylbenzo[b]thiophen-3-yl)-1,3,2-
dioxaborolane (9, 990 mg, 3.6 mmol), 4-bromo-5-(2-ethoxybenzo-
[b]thiophen-3-yl)-2-phenylthiazole (7, 1.5 g, 3.6 mmol), triphenyl-
phosphane (940 mg, 3.6 mmol), Pd(PPh3)4 (939 mg, 3.6 mmol),
4-(2-Ethoxybenzo[b]thiophen-3-yl)-5-(2-methylbenzo[b]thiophen-3-
yl)-2-phenylthiazole (3a): A 200 mL four-necked flask was charged
with 2-(2-ethoxybenzo[b]thiophen-3-yl)-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (5, 360 mg, 1.2 mmol), 4-bromo-5-(2-meth-
ylbenzo[b]thiophen-3-yl)-2-phenylthiazole (10, 570 mg, 1.2 mmol),
triphenylphosphane (150 mg, 0.59 mmol), Pd(PPh3)4 (69 mg,
6
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Photochromic 4,5-Dibenzothienylthiazoles
0.060 mmol), and K3PO4 (2 m) in water/1,4-dioxane (70 mL/
150 mL) solution. The mixture was then stirred at 110 °C under
N2. After stirring for 12 h, the reaction mixture was extracted with
EtOAc, and the organic layer was dried with anhydrous magnesium
sulfate, filtered, and concentrated. Silica gel column chromatog-
raphy (hexane/EtOAc, 20:1) and recrystallization from hexane af-
forded 3a (320 mg, 57%) as a colorless solid. 1H NMR (300 MHz,
CD2Cl2/TMS): δ = 0.59–0.64 (t, J = 7 Hz, 3 H), 2.10 (s, 3 H), 3.43–
3.48 (dq, J = 9, 6 Hz, 1 H), 3.70–3.75 (dq, J = 9, 6 Hz, 1 H), 7.21–
7.37 (m, 4 H), 7.48–7.53 (m, 3 H), 7.64–7.69 (m, 2 H), 7.75–7.78
(m, 1 H), 7.87–7.90 (d, J = 8 Hz, 1 H), 8.07–8.10 (m, 2 H) ppm.
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[3]
[4]
ESI-HRMS: calcd. for C28H21NNaOS3 [M + Na]+ 506.0683;
+
found: 506.0709. C28H21NOS3 (483.66): calcd. C 69.53, H 4.38, N
2.90; found C 69.41, H 4.19, N 2.86.
4,5-Bis(2-ethoxybenzo[b]thiophen-3-yl)-2-phenylthiazole (4a):
A
500 mL four-necked flask was charged with 2-(2-ethoxybenzo[b]-
thiophen-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5, 0.94 g,
3.1 mmol), 4,5-dibromo-2-phenylthiazole (6, 0.45 g, 1.4 mmol), tri-
phenylphosphane (0.39 g, 1.5 mmol), Pd(PPh3)4 (0.17 g,
0.15 mmol), and K3PO4 (2 m) in water/1,4-dioxane (150 mL/
300 mL) solution. The mixture was then stirred at 110 °C under
N2. After stirring for 20 h, the reaction mixture was extracted with
EtOAc, and the organic layer was dried with anhydrous magnesium
sulfate, filtered, and concentrated. Silica gel column chromatog-
raphy (hexane/EtOAc, 20:1) and recrystallization from hexane af-
[5]
[6]
1
forded 4a (0.44 g, 61%) as a colorless solid. H NMR (300 MHz,
[D6]acetone): δ = 0.54–0.59 (t, J = 7 Hz, 3 H), 0.68–0.75 (t, J =
7 Hz, 3 H), 3.49–3.56 (q, J = 7 Hz, 2 H), 3.72–3.79 (q, J = 7 Hz, 2
H), 7.11–7.16 (m, 3 H), 7.21–7.26 (m, 1 H), 7.40–7.47 (m, 4 H),
7.61–7.68 (m, 2 H), 7.77–7.80 (d, J = 8 Hz, 1 H), 7.97–8.00 (m, 2
H) ppm. C29H23NO2S3 (513.69): calcd. C 67.81, H 4.51, N 2.73;
found C 67.73, H 4.32, N 2.70.
1c: 1H NMR (300 MHz, [D6]acetone): δ = 7.39–7.45 (m, 3 H),
7.49–7.70 (m, 4 H), 8.11–8.47 (m, 4 H), 8.47 (d, J = 8 Hz, 2 H)
ppm. EI-HRMS: calcd. for C25H13NS3 [M]+ 423.0210; found
423.0208.
[7]
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a) G. M. Wallraff, W. D. Hinsberg, Chem. Rev. 1999, 99, 1801–
1822; b) A. Sundaramurthy, P. J. Schuck, N. R. Conley, D. P.
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1
2c: H NMR (300 MHz, CD2Cl2/TMS): δ = 2.10 (s, 3 H), 3.01 (s,
3 H), 7.14–7.31 (m, 3 H), 7.44–7.50 (m, 4 H), 7.55–7.58 (m, 1 H),
7.83 (m, 1 H), 7.96–7.99 (m, 3 H), 8.16–8.19 (d, J = 8 Hz, 1 H)
ppm. EI-HRMS: calcd. for C27H19NOS3 [M]+ 469.063; found
469.063.
[9]
S. H. Kawai, S. L. Gilat, J.-M. Lehn, Eur. J. Org. Chem. 1999,
1
3c: H NMR (300 MHz, CD2Cl2/TMS): δ = 2.07 (s, 3 H), 3.05 (s,
9, 2359–2366.
3 H), 7.15–7.18 (m, 1 H), 7.23–7.33 (m, 2 H), 7.42–7.62 (m, 7 H),
7.92–7.95 (d, J = 8 Hz, 1 H), 8.07–8.10 (m, 2 H) ppm. ESI-HRMS:
calcd. for C27H19NOS3 [M + H]+ 470.071; found 470.070.
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J. Am. Chem. Soc. 2008, 130, 14570–14575.
Supporting Information (see footnote on the first page of this arti-
cle): Analytical HPLC details, full-range 1H NMR spectra of 2b,
2c, 3b, and DFT calculations of carbocation intermediates.
[11]
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Acknowledgments
This study was partly supported by the Nara Institute of Science
and Technology (NAIST), under the NAIST advanced collabora-
tion project for “Bio-oriented Photoreactive Molecule” as well as
by the Ministry of Education, Culture, Sports, Science and Tech-
nology (MEXT) of Japan with Grants-in-Aid for Scientific Re-
search on a Priority Area, “New frontiers in Photochromism”. The
authors thank Y. Nishikawa, M. Yamamura and Y. Nishiyama for
mass spectrometric measurements, S. Katao for X-ray crystallogra-
phy and F. Asanoma for elemental analysis measurements.
[13]
[14]
[15]
Crystallographic data for 2c: C17H19NOS3, a = 10.3731(2), b =
15.0793(3), c = 14.9232(4) Å, β = 107.8331(7)°, monoclinic,
space group P21/n (#14), Z = 4, V = 2222.17(8) Å3, ρcalcd.
=
1.404 gcm–3. Of 21818 reflections measured up to 2θ = 55.0°,
5090 were independent (Rint = 0.018). The structure was solved
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Date: 04-07-12 16:12:39
Pages: 9
H. Nakagawa, T. Nakashima, T. Kawai
FULL PAPER
by direct methods and refined with a full matrix against all F2
data. Hydrogen atoms were calculated in riding positions. wR
fined with a full matrix against all F2 data. Hydrogen atoms
were calculated in riding positions. wR = 0.0931, R = 0.0480.
CCDC-875531 (for 2c) and -875532 (for 3c) contain the supple-
mentary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Received: April 12, 2012
=
0.0882, R = 0.0334. Crystallographic data for 3c:
C17H19NOS3, a = 9.7515(3), b = 10.8079(4), c = 20.4930(7) Å,
β = 95.7083(9)°, monoclinic, space group P21/n (#14), Z = 4,
V = 2149.1(2) Å3, ρcalcd. = 1.451 gcm–3. Of 20613 reflections
measured up to 2θ = 54.9°, 4903 were independent (Rint
=
0.0143). The structure was solved by direct methods and re-
Published Online: ᭿
8
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Job/Unit: O20465
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Date: 04-07-12 16:12:39
Pages: 9
Photochromic 4,5-Dibenzothienylthiazoles
Photochromism
H. Nakagawa, T. Nakashima,
T. Kawai* .......................................... 1–9
Subsequent Chemical Reactions of Pho-
tochromic 4,5-Dibenzothienylthiazoles
Subsequent chemical reactions are demon-
strated for photoproducts of 4,5-dibenzo-
thienylthiazoles possessing leaving groups
at the 2-position of benzothienyl rings.
Closed-ring isomers of 4,5-dibenzothienyl-
thiazoles having an ethoxy group under-
went an alcoholysis reaction under acidic
conditions accompanying rearrangement
of carbocation intermediates.
Keywords: Terarylene / Photochromic com-
pound
/ Elimination / Heterocycles /
Photochromism / Dibenzothienylthiazoles /
Alcoholysis
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