A convenient method for the preparation of mono- and bis-substituted photochromic bis(benzothienyl)perfluorocyclopentenes via regioselective Friedel-Crafts acylation

Article abstract of DOI:10.1016/j.tetlet.2012.08.111

The regioselective Friedel-Crafts acylation of 1,2-bis(2-methylbenzo[b] thien-3-yl)hexafluorocyclopentene was developed. Depending on the reaction conditions, mono- or bis(bromoacetyl) derivatives are formed as single products in good yields. Further heterocyclizations involving α-bromoketone moieties gave a series of new photochromic compounds.

Full text of DOI:10.1016/j.tetlet.2012.08.111

Tetrahedron Letters 53 (2012) 5948–5951
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A convenient method for the preparation of mono- and bis-substituted
photochromic bis(benzothienyl)perfluorocyclopentenes via regioselective
Friedel–Crafts acylation
A. M. Bogacheva a, , V. N. Yarovenko b, K. S. Levchenko c, O. I. Kobeleva d, T. M. Valova d, V. A. Barachevsky d,
⇑
M. I. Struchkova b, P. S. Shmelin c, M. M. Krayushkin b, V. N. Charushin a
a I.Ya. Postovsky Institute of Organic Synthesis, Russian Academy of Sciences, 20 S. Kovalevskoy, Yekaterinburg 620990, Russia
b N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Pr., Moscow 119991, Russia
c Central Science Research Institute of Technology ‘Technomash’, 4 Ivana Franko St., Moscow 121108, Russia
d Photochemistry Center of RAS, 7a, bld. 1, Novatorov, Moscow 119421, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 July 2012
Revised 10 August 2012
Accepted 24 August 2012
Available online 1 September 2012
The regioselective Friedel–Crafts acylation of 1,2-bis(2-methylbenzo[b]thien-3-yl)hexafluorocyclopen-
tene was developed. Depending on the reaction conditions, mono- or bis(bromoacetyl) derivatives are
formed as single products in good yields. Further heterocyclizations involving
gave a series of new photochromic compounds.
a-bromoketone moieties
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Regioselective Friedel–Crafts acylation
Bis(benzothienyl)hexafluorocyclopentenes
Photochromes
Thiazoles
Benzofurans
Photochromic compounds containing perfluorocyclopentene-
bridged benzothiophene moieties attract considerable interest
because of their potential use as materials for photonics and
molecular electronics,1 in particular, for the design of light-sensi-
tive recording media for ultra high-density three-dimensional
optical memory systems, polymers with photo- and electrically
controlled conductivity, and optical switches.2–5
The design of new diarylethene skeletons with different aryl
moieties has become an active area of research.6 Moreover unsym-
metrical photochromic bis(benzothienyl)perfluorocyclopentenes
attract interest for fluorescence resonance energy transfer (FRET)
systems.7 Their photochemical properties and performance charac-
teristics are greatly influenced by substituents on the benzene
rings of the benzothiophene moieties.
Generally, these substituents are introduced into the starting
benzothiophenes, which are then lithiated and treated with octa-
fluorocyclopentene to give photochromic bis(benzothienyl)hexa-
fluorocyclopentenes 1. This method has limitations because of
problems encountered when functional groups on the substrates
are incompatible with organolithium species.
Electrophilic substitution reactions could provide a convenient
route for functionalization of the benzene ring in benzothiophenes.
However, these reactions, unlike substitution on the thiophene
rings of benzothiophenes, are limited,8,9 besides, they might pro-
duce mixtures of regioisomers which are difficult to separate.10,11
Another serious problem encountered when modifying benzothio-
phene photochromes is the lack of methods for the preparation of
monosubstituted derivatives in good yield. These derivatives, for
example, mononitro, monoaldehyde, and mono
a-bromoketone,
are very promising compounds, which are subjected to further mod-
ifications, thus making it possible to vary their photochemical
properties.12
To the best of our knowledge, the only reported example is the
synthesis of a mononitrate of the bis(benzothienyl) perfluorocycl-
opentene photochrome.12
Apparently, these difficulties are associated with the fact that the
benzothiophene moieties in compound 1 are not coplanar13 with
the plane of the double bond of the bridge, which, on the one hand,
does not provide efficient transfer of the effects of the electron-
withdrawing substituent on the benzothiophene moiety to another
one and, consequently, favors the formation of disubstituted prod-
ucts, and, on the other hand, interferes with the preparation of mon-
osubstituted compounds. The introduction of a
functionality into bis(benzothienyl) perfluorocyclopentene has
a-bromoketone
⇑
Corresponding author. Tel.: +7 916 528 2823; fax: +7 499 135 5328.
E-mail address: anna-bogacheva86@yandex.ru (A.M. Bogacheva).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.08.111

A. M. Bogacheva et al. / Tetrahedron Letters 53 (2012) 5948–5951
5949
Scheme 1. Reagents and conditions: (i) AlCl3 (4 equiv), pyridine (2 equiv), BrCH2COCl (2 equiv), CH2Cl2, 4 h, À5–0 °C, 56%; (ii): AlCl3 (2.5 equiv), BrCH2COCl (3 equiv), CH2Cl2,
4 h, À5–0 °C, 60%.
F
F
F
F
F
F
F
F
F
F
F
F
F
(i) or (ii)
2
N
R
N
S
(iii)
N
O
S
S
S
R1
S
S
4
7
R1= a) furan-2-yl;
b) thien-2-yl;
c) phenyl
R= a) NH2
b) Ph
H
N
H
N
R1
S
O
F
6
R1= a) furan-2-yl;
b) thien-2-yl;
c) phenyl
F
F
F
F
F
F
F
F
F
F
F
(iii)
F
F
N
N
S
N
R1
N
R1
O
O
F
S
(i) or (ii)
N
S
S
N
R
R
8
3
R1= a) furan-2-yl;
b) thien-2-yl;
c) phenyl
S
S
S
S
5
R= a) NH2
b) Ph
Scheme 2. Reagents and conditions: (i) EtOH, thiourea, reflux, 4 h, 50–56%; (ii) EtOH, PhC(S)NH2, K2CO3, reflux, 4 h, 50–60%; (iii) DMF, rt, 24 h, 30–60%.
R
F
F
F
F
F
F
F
F
F
F
F
F
R
(i)
O
OH
O
O
+
S
S
S
S
O
Br
2
9
10
R= a) Cl
b) NO2
R = a) Cl
b) NO2
Scheme 3. Reagents and conditions: (i) DMF, K2CO3, rt., 24 h, 40–42%.
wide synthetic potential for further transformations and the syn-
thesis of diverse heterocyclic structures.14–17
The problem of the regioselective introduction of a substituent
to one of the two benzene rings of dihetarylethenes was solved by
using 2 equiv of pyridine in the acylation reaction performed at
low temperature in dichloromethane in the presence of AlCl3
(Scheme 1).19 Under these conditions, the reaction gives only mon-
osubstituted product 2 in 56% yield; the use of even an excess of
the acylating agent did not lead to the formation of a disubstituted
product in a substantial amount. In the absence of pyridine, the
yield of the monosubstituted product was not higher than 18%
(the ratio of the components and the temperature varied). Disub-
stituted dihetarylethene 3 is always present as the major product
in the mixture.
In the present study, we have developed a simple method for
the synthesis of perfluorocyclopentene photochromes containing
both symmetrical and unsymmetrical benzothiophene moieties
based on the acylation of 1,2-bis(2-methylbenzo[b]thien-3-yl)
hexafluorocyclopentene (1) with bromoacetyl chloride, followed
by transformations of the thus obtained mono- and bis(bromoace-
tyl) derivatives.
The disubstituted compound 3 was obtained in 60% yield by
conventional Friedel–Crafts acylation in the presence of 2.5 equiv
of AlCl3 and a threefold excess of the acylating agent (Scheme 1).18
Obviously, to prevent the introduction of a second electrophile
into mono-substituted 1,2-bis(2-methylbenzo[b]thien-3-yl)hexa-
fluorocyclopentene (1), it was necessary that the first substituent
had significant acceptor properties. Unfortunately, the keto group
is not able to provide such a strong effect. Another route involves
reduction of the strength of the acylating agent or Lewis acid. How-
ever, it was found that the use of Lewis acids such as TiCl4, SnCl4,
ZnCl2 instead of AlCl3 did not have any effect on the regioselectivity
of the process (TiCl4) or did not lead to acyl derivatives 2 or 3
(SnCl4, ZnCl2). We suggest that the addition of an organic base to
the AlCl3 should contribute to a softer and regioselective catalyst.
An analysis of the 1H and 13C NMR spectra of acylation products
2 and 3 showed that the acyl groups were located at position 6 of
the benzene rings.
Both the mono- and dibromoketone moieties in compounds 2
and 3 undergo easily further transformations to form photochro-
mic products containing heterocyclic moieties (Schemes 2 and 3).
Photochromic compounds 4a and 5a were prepared as shown in
Scheme 2 by refluxing
a-bromoketones 2 and 3 with thiourea in
ethanol. Compounds 4b and 5b were prepared using the same ap-
proach with thiobenzamide and K2CO3 was added as the base. The
yields of the thiazoles in both cases were 50–80%.

5950
A. M. Bogacheva et al. / Tetrahedron Letters 53 (2012) 5948–5951
Table 1
Results of the spectral-kinetic study for synthesized diarylethenes
e
e
kA
eA 10À4
kB
D
D
phot/DAd
kA–B/kB–A
kA
eA 10À4
kB
max
(nm)c
D
D
phot/DAd
kA–B/kB–A
max
(nm)a
max
(nm)c
max
(nm)a
b
b
(MÀ1 cmÀ1
)
(MÀ1 cmÀ1
)
2
3
322
325
308
303
309
305
343
1.00
1.25
1.75
3.75
2.25
3.77
3.32
550
562
546
562
566
564
547
0.2
0.3
0.2
0.2
0.2
0.2
0.1
8.4
8.2
14
11
19
16
2.4
7b
7c
8a
8b
8c
10a
10b
348
340
343
346
341
317
295
3.35
5.38
4.95
3.50
4.08
3.08
2.48
548
550
560
566
565
555
562
0.2
0.1
0.2
0.2
0.2
0.1
0.2
2.9
2.2
3.2
6.6
3.3
6.0
6.2
4a
4b
5a
5b
7a
a
b
c
Absorption maxima of the open-ring isomers in the UV region.
Absorption coefficients of the open-ring isomers at the absorption maxima in the UV region.
Absorption maxima of the closed-ring isomers in the visible region.
d
Value of a photo induced change of optical density at the maximum of the absorption band for the closed-ring isomers that normalized the amount of optical density at
the maximum of open-ring isomers.
e
The ratio of rate constants for photo coloration (a transformation from (A) into (B) form under UV irradiation) and photo bleaching (a transformation from (B) into (A)
form under visible irradiation).
1.4
UV irradiated
Visible irradiated
1
Before UV irradiation
After UV irradiation
1.2
1
hv
hv'
After irradiation with visible
light
0.8
0.6
0.4
0.2
0
1
10a 8a
1
10a 8a
F
F
F
F
F
F
F
F
hv
F
F
F
F
hv'
R
R'
R
R'
2
S
S
S
S
3
A
B
R, R'=H, C(O)CH2Br, C(O)Het, Het
300
350
400
450
500
550
600
650
700
Waveleight, (nm)
Figure 1. Absorption spectra of photochromic compound 10a in toluene (2.10À4 M) before (1) and after UV irradiation with a UFS-1 light filter for 15 s (2) followed by
irradiation with visible light (k > 450 nm) for 30 s (3).
Reactions of bis(benzothienyl)perfluorocyclopentenes 2 and 3
with N-acylthioureas 6a–c proceeded under mild conditions (DMF,
rt) to afford thiazoles 7–8 in good to excellent yields (Scheme 2).20
Scheme 3 illustrates another example of successful modification
cyclic form practically does not change but the absorption
band of the open form moves as compared with absorption
bands for compounds 2–5. As for nonsymmetrical and symmet-
rical diarylethene derivatives changing the phenyl substituent to
furan or thienyl leads to a small hypsochromic shift of the
absorption band for the cyclic form. These compounds are char-
acterized by the same UV sensitivity as for the previously men-
tioned diarylethenes but their sensitivity to visible irradiation
increases dramatically as evidenced by the decreasing kA–B/kB–A
ratio.
The photoinduced spectral changes for diarylethene 10a in
toluene are shown in Figure 1. The open form of this compound
is characterized by an absorption band at 310 nm
Upon UV irradiation, an absorption band due to the cyclic form
appeared in the visible region of the spectrum at 550 nm. This band
disappeared upon irradiation with visible light. Compound 10b
exhibited virtually the same properties. The only difference was
that the absorption band of the open form was shifted to a shorter
wavelength by 10 nm.
of mono a-bromoketone 2 under mild conditions (DMF, K2CO3, rt)
using salicylaldehydes.21 All compounds 1–10 exhibited good pho-
tochromic properties and can be switched between their colorless
ring-open (A) and colored ring-closed (B) forms by alternate irradi-
ation with ultraviolet and visible light. We present the results of
the spectral-kinetic studies of compounds 2–5, 7–8, and 10. It
was found that these compounds were thermally stable and under-
went transformations only in the presence of light (Table 1). The
comparison of results shows that compounds 2 and 3 have close
characteristics of the open form, UV sensitivity was defined by
the parameter
coloration and photo bleaching by kA–B/kB–A
DD
phot/DA, and the ratio of rate constants for photo
.
An exception is the bathochromic shift of the maximum of the
absorption band for the cyclic form of the symmetrical derivative
3 because of increased conjugation bonds in a molecule as com-
pared with compound 2.
Compared with diarylethenes 2 and 3, compounds 4–5 are char-
acterized by shortwave but of more intense absorption bands of the
open form, comparable sensitivity to UV irradiation as well as sub-
stantial reduction of the efficiency of photobleaching under visible
light as evidenced by the increasing ratio of kA–B/kB–A. As in the case
of compounds 2 and 3, symmetric derivatives are characterized by a
more long-wave absorption maximum of the cyclic form.
A similar effect is observed for nonsymmetrical and symmet-
rical compounds 7–8. The position of absorption bands for the
The results of the spectral-kinetic study provide the basis for
designing improved diarylethenes with characteristics which meet
the requirements for their applications as recording media of
three-dimensional bitwise working optical memory.
Acknowledgment
The authors thank the Russian Foundation for Basic Research for
financial support (Grant # 11-03-90736) and Dr. A. Y. Bochkov for
helpful suggestions.

A. M. Bogacheva et al. / Tetrahedron Letters 53 (2012) 5948–5951
5951
131.46; 138.86; 142.15; 189.46 (C@O). 19F NMR (280 MHz, CDCl3, d, ppm):
À110.10–(À111.60) (m, 4F, CF2); À133.31–(À133.62) (m, 2F, CF2). HRMS (ESI)
m/z [MH+] Calcd for C27H16Br2F6O2S2: 710.8916. Found 710.8913.
Supplementary data
Supplementary data (experimental procedures and character-
ization data of synthesized compounds) associated with this article
can be found, in the online version, at http://dx.doi.org/10.1016/
j.tetlet.2012.08.111.
19. General procedure for the preparation of 2: Py (76 mg, 0.961 mmol) was added to
a suspension of AlCl3 (256 mg, 1.921 mmol) in CH2Cl2 (15 mL) at À5–0 °C. After
20 min, compound 1 (200 mg, 0.427 mmol) and bromoacetyl chloride (202 mg,
1.281 mmol) were added. The mixture was stirred for 4 h at À5–0 °C. After
completion of the reaction, the solution was poured into 10% aq HCl solution.
The mixture was extracted with CH2Cl2 (4 Â 50 mL). The organic layer was
washed with H2O (3 Â 150 mL), dried over MgSO4, and filtered. The solvent
was distilled, and the residue was purified on a chromatographic column
(petroleum ether–EtOAc, 10:1). Yield 56%, m.p. 80–83 °C (EtOH). 1H NMR
(300 MHz, CDCl3, d, ppm): 2.29 (s, 3H, CH3); 2.62 (s, 3H, CH3); 4.49 (s, 2H, CH2);
7.60–8.00 (m, 6H, ArH); 8.26 (s, 1H, ArH). 13C NMR (50 MHz, CDCl3, d, ppm):
24.76 (CH3); 30.65 (CH2Br); 101.94; 121.91; 122.21; 123.68; 123.84; 124.17;
124.37; 124.60; 124.81; 125.01; 138.35; 190.60 (C@O). 19F NMR (280 MHz,
CDCl3, d, ppm): À110.46–(À111.72) (m, 4F, CF2); À133.36–(À133.54) (m, 2F,
CF2). HRMS (ESI) m/z [MH+] Calcd for C25H15BrF6OS2: 588.9725. Found
588.9724.
References and notes
1. Irie, M. Chem. Rev. 2000, 100, 1685–1716.
2. Matsuda, K.; Irie, M. Chem. Lett. 2006, 35, 1204–1209.
3. Krayushkin, M. M.; Kalik, M. A. Adv. Heterocycl. Chem. 2011, 103, 1–5.
4. Barachevsky, V. A.; Krayushkin, M. M. Russ. Chem. Bull. 2008, 57, 867–875.
5. Yamaguchi, T.; Irie, M. J. Photochem. Photobiol., A 2006, 178, 162–169.
6. Pu, S.; Yan, P.; Liu, G.; Miao, W.; Liu, W. Tetrahedron Lett. 2011, 52, 143–147.
7. Fukaminato, T. J. Photochem. Photobiol., C 2011, 12, 177–208.
8. Rayner, C. M.; Graham, N. A. In Science of Synthesis: Houben–Weyl Methods of
Molecular Transformations; Georg Thieme: Stuttgart, 2000; 10, 155–184.
9. Pal, S.; Khan, M. A.; Bindu, P.; Dubey, P. K. Beilstein J. Org. Chem. 2007, 3, 35.
10. Yarovenko, V. N.; Khristoforova, L. V.; Belen’kii, L. I.; Shashkov, A. S.;
Baryshnikova, T. K.; Rrayushkin, M. M. Chem. Heterocycl. Compd. 2011, 47,
166–172.
11. Yarovenko, V. N.; Khristoforova, L. V.; Belenkii, L. I.; Chuvylkin, N. D.;
Krayushkin, M. M. Russ. Chem. Bull. 2011, 11, 2270–2274.
12. Kim, E.; Kim, M.; Kim, K. Tetrahedron 2006, 62, 6814–6821.
13. Kobatake, S.; Yamada, M.; Yamada, T.; Irie, M. J. Am. Chem. Soc. 1999, 121,
8450–8456.
20. General procedure for the preparation of 8: Compound 3 (50 mg, 0.07 mmol) and
1-(4-fluorophenyl)-3-(furan-2-carbonyl)thiourea (6a) (21 mg, 0.084 mmol)
were dissolved in DMF (0.5 mL). The mixture was stirred for 24 h and poured
into H2O. The precipitate was filtered, and the residue purified on
a
chromatographic column (petroleum ether–EtOAc, 10:4). Compound 8a:
Yield 60%, mp 123–124 °C (EtOH). 1H NMR (300 MHz, CDCl3, d, ppm): 2.00 (s,
6H, CH3); 6.41 (m, 2H, furan); 6.73–6.67 (m, 2H, ArH); 6.93–7.23 (m, 11H,
ArH); 7.52–7.62 (m, 7H, ArH). 13C NMR (50 MHz, CDCl3, d, ppm): 24.50 (CH3);
102.76; 106.35; 110.48; 110.85; 110.93; 116.46; 117.53; 120.13; 121.47;
125.09; 125.25; 128.06; 133.16; 139.33; 140.38; 146.32; 154.36; 159.32;
169.70. 19F NMR (280 MHz, CDCl3, d, ppm): À109.92–(À111.25) (m, 4F, CF2);
À112.53 (s, 2F, CF); À133.12–(À133.58) (m, 2F, CF2). HRMS (ESI) m/z [MH+]
Calcd for C51H28F8N4O4S4: 1041.0938. Found 1041.0935.
14. Erian, A. W.; Sherif, S. M.; Gaber, H. M. Molecules 2003, 8, 793–865.
15. Moiseev, I. K.; Makarova, N. V.; Zemtsova, M. N. Russ. J. Org. Chem. 2003, 39,
1759–1773.
21. General procedure for the preparation of 10a,b: Compound
2 (50 mg,
16. Bora, U.; Saikia, A.; Boruah, R. C. Org. Lett. 2003, 5, 435–438.
17. Gan, S. F.; Wan, J. P.; Pan, Y. J.; Sun, C. R. Synlett 2010, 973–975.
18. General procedure for the preparation of 3: AlCl3 (142 mg, 1.067 mmol) was
added to a solution of compound 1 (200 mg, 0.427 mmol) in CH2Cl2 (15 mL) at
À5–0 °C. After 20 min, bromoacetyl chloride (202 mg, 1.281 mmol) was added.
The mixture was stirred for 4–5 h at À5–0 °C. After completion of the reaction,
the solution was poured into 10% aq HCl solution. The mixture was extracted
with CH2Cl2 (4 Â 50 mL). The organic layer was washed with H2O (3 Â 150 mL),
dried over MgSO4, and filtered. The solvent was distilled, and the residue
purified on a chromatographic column (petroleum ether–EtOAc, 10:2). Yield
60%, mp. 83–84 °C (EtOH). 1H NMR (300 MHz, CDCl3, d, ppm): 2.30 (s, 6H, CH3);
4.42 (s, 4H, CH2); 7.62–8.01 (m, 4H, ArH); 8.29 (s, 2H, ArH). 13C NMR (125 MHz,
353 K, toluene-d8, d, ppm): 15.33 (CH3); 30.28 (CH2Br); 122.32; 123.93;
0.085 mmol), salicylaldehyde (16 mg, 0.102 mmol), and K2CO3 (14 mg,
0.102 mmol) were dissolved in DMF (0.5 mL). The mixture was stirred for
24 h and poured into H2O. The precipitate was filtered, and the residue was
purified on
a chromatographic column (petroleum ether–EtOAc, 10:1).
Compound 10a: Yield 40%, mp. 85–86 °C (EtOH). 1H NMR (300 MHz, CDCl3, d,
ppm): 2.15 (s, 3H, CH3); 2.71 (s, 3H, CH3); 7.28–8.11 (m, 10H, ArH); 8.37–8.49
(m, 1H, ArH). 13C NMR (50 MHz, CDCl3, d, ppm): 24.77 (CH3); 113.71; 115.36;
122.20; 122.67; 123.62; 124.46; 124.81; 125.13; 125.78; 128.26; 128.76;
129.81; 132.89; 138.23; 154.29; 183.04. 19F NMR (280 MHz, CDCl3, d, ppm):
À109.66–(À112.65) (m, 4F, CF2); À133.34–(À133.50) (m, 2F, CF2). HRMS (ESI)
m/z [MH+] Calcd for C32H17ClF6O2S2: 647.0335. Found 647.0331.