Synthesis of Photochromic 1,2-Dihetarylethene Using Regioselective Acylation of Thienopyrroles

Article abstract of DOI:10.1021/ol026705i

(Matrix Presented) The influence of catalysts, acid chlorides, and solvents in the acylation of methyl 2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylate was studied. Conditions for the regioselective acylation processes were found. Thienopyrrole-based photoc

Full text of DOI:10.1021/ol026705i

ORGANIC
LETTERS
2
002
Vol. 4, No. 22
879-3881
Synthesis of Photochromic
,2-Dihetarylethene Using Regioselective
3
1
Acylation of Thienopyrroles
Michael M. Krayushkin,* Vladimir N. Yarovenko, Stanislav L. Semenov,
Igor V. Zavarzin, Anatoliy V. Ignatenko, Andrey Yu. Martynkin, and
Boris M. Uzhinov†
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky Prospect, 119991 Moscow, Russian Federation
mray@mail.ioc.ac.ru
Received August 9, 2002
ABSTRACT
The influence of catalysts, acid chlorides, and solvents in the acylation of methyl 2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylate was studied.
Conditions for the regioselective acylation processes were found. Thienopyrrole-based photochrome was synthesized for the first time.
Thermally stable photochromic 1,2-dihetarylethenes with
high cyclicity are of considerable interest as promising
elements for optical memory.1
activity and are intensely studied as promising drugs and
cosmetic makeup preparations.
2
,3
In this connection, it was of interest to synthesize
previously undescribed dihetarylethenes containing thieno-
pyrrole fragments, which are rather close heterocyclic
analogues of all three indicated types of substituents, and to
study their properties.
In this work, we studied the possibility of regioselective
acylation reactions of methyl 2-methyl-4H-thieno[3,2-b]-
4
pyrrole-5-carboxylate (1a) (Scheme 1). As we showed and
5
the authors described, the acyl moiety that formed is of
interest for subsequent transformation into the bridging
fragments of 1,2-dihetarylethenes.
It is known that high cyclicity is demonstrated by photo-
chromic products containing fused heterocycles: benzo-
thiophene, indole, and thieno[3,2-b]thiophene. Note that 1,2-
1
dihetarylethenes containing indole rings not only are photo-
chromes but also exhibit a wide spectrum of biological
(2) Tsujioka, T.; Irie, M.; Obara, S. Jpn Patent 06161024, 1994; Chem.
Abstr. 1995, 122, 68408g.
2
(3) Dhingra, U. H.; Huryn, D. M.; Keith, D. D.; Weber, G. U.S. Patent
F.5891901, 1999; Chem. Abstr. 1999, 130, 267343. Bergstrand, H.;
Karabelas, K.; Lepisto, M.; Linden, M.; Noori, C.; Stenvall, K. Br. Patent
9811105, 1998; Chem. Abstr. 1998, 128, 257664x.
(4) Krayushkin M. M.; Ivanov S. N.; Martynkin A. Yu.; Lichitsky B.
V.; Dudinov, A. A.; Uzhinov B. M. Russ. Chem. Bl. 2001, 50, 1, 116-
121.
†
Current address: Department of Chemistry, M. V. Lomonosov Moscow
State University, Leninskie Gory, Moscow, Russian Federation. E-mail:
uzhnov@mail.ru.
(
1) Irie, M. Chem. ReV. 2000, 100, 1685. Krayushkin, M. M. Chem.
Heterocycl. Compd. (NY) 2001, 37, 1, 15-36.
1
0.1021/ol026705i CCC: $22.00 © 2002 American Chemical Society
Published on Web 10/09/2002

Scheme 1
Table 1. Acylation Products of Thienopyrrole 1a
molar ratio of
product ratio yield,
entry reagent 1a :Lewis acid solvent
of 2a :4a :3
%
1
2
3
4
5
6
7
8
9
0
1
2
3
4
A
2.1A
B
C
D
E
F
1.1A
1.1C
A
1:2.1c
1:3.1c
1:2.1c
1:2.1c
1:2.1c
1:2.1c
1:2.1c
1:2c
a
a
a
a
a
a
a
c
c
a
b
a
b
a
100:0:0
100:0:0
100 (2b)
100 (2c)
100 (2d )
100 (2e)
100 (2f)
100:0:0
100:0:0
25:0:75
15:0:85
0:0:100
0:25:75
0:20:80
95
93
67
77
67
66
63
92
90
91
89
93
91
92
1:2c
1
1
1
1
1
1:1.1c
1:1.1c
1:2.1d
1:2.1d
1:2.1d
A
A
A
2.1A
a
Reagents: A, CH3COCl; B, CH3CH2COCl; C, ClCH2COCl; D,
b
Cl2CHCOCl; E, Cl3CCOCl; F, (CH3)2CHCOCl. Solvents: a, ClCH2CH2Cl;
We synthesized thienopyrroles (1a-c) by the condensation
b, CH3NO2; c, 1-butyl-3-methylimidazolium heptachlorodialuminate(III).
c
AlCl3. d SnCl4.
of the corresponding thiophenaldehydes with esters of
6
azidoacetic acid (Hemetsberger-Knittel reaction) (Scheme
2). Compounds 1b,c were synthesized for the unambiguous
pyrrole ring in the presence of AlCl
is a weaker Lewis acid than AlCl
3
. The use of SnCl
4
, which
3
, decreases the electron-
withdrawing character of the complexes formed with thieno-
pyrrole and allows the regioselective synthesis of ketone 3
Scheme 2
4
(entry 12). At the same time, in the presence of SnCl , the
acetyl group cannot be selectively introduced into the
thiophene ring (entries 13 and 14).
We also showed that the target synthesis of various mixed
diketones (4a-e) can be performed in nitromethane by the
successive selective introduction of one acyl group into the
3
thiophene ring in the presence of AlCl and then of another
4
into the pyrrole ring in the presence of SnCl (Scheme 3).
interpretation of the H and 13C NMR spectra of isomers 2
1
and 3.
It should be mentioned that the acylation of thieno[3,2-
b]pyrrole carboxylates was poorly studied, and only the
reaction of ethyl 4H-thieno[3,2-b]pyrrole-5-carboxylate with
acetyl chloride resulting in the insertion of the keto group
into position 2 of thienopyrrole was described.7
Scheme 3
We studied the influence of the nature of catalysts,
reactants, and solvents on thienopyrrole 1a acylation. The
results of compound 1a acylation in dichloroethane, nitro-
methane, and ionic liquid in the presence of different
equivalents of AlCl
It can be seen in Table 1 that when two or more AlCl
3 4
and SnCl are presented in Table 1.
When compound (3) was used as the substrate, the second
acylation did not occur.
We also investigated the possibility of acetylating the
pyrrole nitrogen atom. The reaction was performed in the
3
equivalents are used, acylation in dichloroethane occurs
regioselectively at the thiophene ring (entries 1 and 2). The
introduction of electron-withdrawing substituents into ali-
phatic acid chlorides has no effect on the position selectivity
of the process (entries 3-7). Acylation of thienopyrrole in
ionic liquid, 1-butyl-3-methylimidazolium heptachlorodi-
aluminate(III), led to introduction of one acyl group into the
thiophene ring (entries 8 and 9). The application of equimolar
Scheme 4
3
amounts of AlCl enhances the probability of the reaction
at the pyrrole ring because, in this case, complex-free
thienopyrrole can be attacked (entries 10 and 11). However,
it is impossible to perform the selective acetylation of the
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Org. Lett., Vol. 4, No. 22, 2002

Thus, we showed the possibility of the regioselective
introduction of acyl groups into different positions of
thienopyrrole 1a.
Scheme 5
For the first time, we synthesized photochromic 1,2-
dihetarylethene (8) in which thienopyrrole fragments are
linked by the tetrahydrothiophene. The transformations were
5
carried out by analogy to a described procedure (Scheme
5
).
The photochromic properties of compound 8 were studied
in an acetonitrile solution. Compound 8 (Figure 1) exhibits
presence of different bases, and the highest yield of the
corresponding amide (5) was achieved for potassium tert-
butylate. As should be expected, even trace amounts of this
compound are absent from the acylation products of thieno-
pyrrole 1a under the Friedel-Crafts conditions. However,
Figure 1. Absorption spectra of 8 and in the photostationary state
under irradiation with 254 nm light.
3
when amide 5 is acylated in the presence of AlCl , only
ketone 2a is formed instead of the corresponding diacyl
derivative.
typical photochromic properties and undergoes at least 20
cycles of the photoinduced transition from the open form
1
A to the cyclic form 1B and back. Without irradiation (in
The structure of the obtained compounds was proved from
the dark), the cyclic form of compound 8 is stable for at
least 200 h.
1
13
the H and C NMR spectra of compounds 1b,c and
acylation products of thienopyrrole and chemical transforma-
tions (Scheme 4).
Supporting Information Available: Procedures for
synthesis of acylthienopyrroles and photochromic 1,2-
dihetarylethene. This material is available free of charge via
the Internet at http://pubs.acs.org.
(
5) Huang, Z.-N.; Xu, B. A.; Jin, S.; Fan, M.-G. Synthesis 1998, 8, 1092-
1
094.
(
(
6) Hemetsberger, H.; Knittel, D. Monatsh. Chem. 1972, 103, 194.
7) Gale, W.; Scott, A.; Snyder, H. J. Org. Chem. 1964, 29, 2160.
OL026705I
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