A convenient synthesis of benzo[b]chalcogenophenes from 4-(2-chloro-5-nitrophenyl)-1,2,3-chalcogenadiazoles

Article abstract of DOI:10.1016/j.tetlet.2013.04.077

An unusual base-promoted transformation of readily available 4-(2-chloro-5-nitrophenyl)-1,2,3-thia- and selenadiazoles affords a convenient approach toward benzo[b]thiophenes and benzo[b]selenophenes.

Full text of DOI:10.1016/j.tetlet.2013.04.077

Accepted Manuscript
A convenient synthesis of benzo[b]chalcogenophenes from 4-(2-chloro-5-ni‐
trophenyl)-1,2,3-chalcogenadiazoles
Anna G. Lyapunova, Dmitry A. Androsov, Mikhail L. Petrov
PII:
S0040-4039(13)00672-2
DOI:
http://dx.doi.org/10.1016/j.tetlet.2013.04.077
TETL 42845
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
9 January 2013
28 March 2013
19 April 2013
Please cite this article as: Lyapunova, A.G., Androsov, D.A., Petrov, M.L., A convenient synthesis of
benzo[b]chalcogenophenes from 4-(2-chloro-5-nitrophenyl)-1,2,3-chalcogenadiazoles, Tetrahedron Letters (2013),
doi: http://dx.doi.org/10.1016/j.tetlet.2013.04.077
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benzo[b]chalcogenophenes from 4-(2-chloro-
5-nitrophenyl)-1,2,3-chalcogenadiazoles
Anna G. Lyapunova, Dmitry A. Androsov*, Mikhail L. Petrov

1
Tetrahedron Letters
journal homepage: www.elsevier.com
A convenient synthesis of benzo[b]chalcogenophenes from 4-(2-chloro-5-
nitrophenyl)-1,2,3-chalcogenadiazoles
Anna G. Lyapunova, Dmitry A. Androsov, Mikhail L. Petrov
Department of Organic Chemistry, Saint-Petersburg State Institute of Technology, Moskovskii prospekt 26, Saint-Petersburg 190013, Russia
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An unusual base-promoted transformation of readily available 4-(2-chloro-5-nitrophenyl)-1,2,3-
thia- and selenadiazoles affords a convenient approach toward benzo[b]thiophenes and
benzo[b]selenophenes.
2009 Elsevier Ltd. All rights reserved.
Available online
Keywords:
benzo[b]thiophene
benzo[b]selenophene
1,2,3-thiadiazole
1,2,3-selenadiazoles
cyclization
Benzo[b]thiophene and related derivatives represent an
important class of fused thiophene compounds in the field of
bioactive and optoelectronic materials. In particular,
polythiophene fused aromatic compounds are attracting current
interest as promising electronic materials for organic conductors,
organic light-emitting diodes, photovoltaic cells, and field-effect
transistors.1
ethynylchalcogenols (III) and tautomeric chalcogenoketenes7
(IV) (Scheme 1).
The synthesis and characterization of benzo[b]selenophenes
are of current interest owing to their potential applications as
organic semiconductors for various optoelectronic devices.2
Benzo[b]selenophenes have received little attention as potential
drugs, although their potent biological activity and synthetic
utility have been discussed in the literature.3
Our previous research and that of W. Dehaen8 has shown the
5-exo-dig cyclization reaction of the in situ generated ortho-
hydroxy- and -aminochalcogenoketenes to be a facile and
efficient approach toward benzo[b]furans and indoles. These
results prompted us to examine the possible synthesis of
benzo[b]chalcogenophenes by 5-exo-trig cyclization reaction of
the in situ generated ortho-halo chalcogenoketenes with
nucleophiles (Nu = RO¯, R2NH, Scheme 2).
One of the most versatile and efficient routes to
benzo[b]thiophenes and benzo[b]selenophenes involves metal-
catalyzed cyclization reactions of ortho-ethynylthiophenols4 and
ortho-ethynylselenophenols.2b,5 These precursors are typically
obtained by nucleophilic displacement of halogen atom at the
ortho position relative to the ethynyl group by the corresponding
chalcogenide.2b
5-Unsubstituted 1,2,3-thiadiazoles and 1,2,3-selenadiazoles (I)
are usually easily cleaved with liberation of nitrogen to form
alkynethiolates and alkyneselenolates6 (II) under the action of
strong bases, such as organolithium reagents or potassium
ethoxide. The acetylenic thiolates and selenolates have been
widely used in organic chemistry for the synthesis of acetylenic
sulfides and selenides, in cycloaddition reactions leading to new
heterocycles or, after protonation, as a source of highly reactive
———
 Corresponding authors. Tel.: +7-812-494-9354; fax: +7-812-494-9354; e-mail: da_androsov@hotmail.com

2
Tetrahedron
compared to that of the thiadiazole ring of 3b, providing a higher
yield (79%) of the cyclization product 4g.
A similar reaction of thiadiazole 3b with MeONa in MeOH
under
an
inert
atmosphere
led
to
2-methoxy-5-
nitrobenzo[b]thiophene (4j) (23%, Scheme 4, Table 1).
Treatment of compounds 3a and 3c, having no nitro group on
the phenyl ring, with amines in the presence of a base afforded
amides 6a and 6b. Formation of cyclic products was not
observed even at a temperature of 130 °C (Scheme 6).
The Hurd-Mori reaction gives 4-substituted 1,2,3-thiadiazoles
from methyl ketones under the action of thionyl chloride on their
ethylcarbazones or tosylhydrazones.6a,9 This procedure was used
for the synthesis of 4-(2-chloroaryl)-1,2,3-thiadiazoles 3a and 3b
from 2-chloroacetophenones 1a and 1b by treatment of their
ethoxycarbonylhydrazones 2a and 2b with thionyl chloride. The
reaction of 2-chloroacetophenones 1a and 1b with semicarbazide
hydrochloride gave semicarbazones 2c and 2d, which were
converted into 4-(2-chloroaryl)-1,2,3-selenadiazoles 3c and 3d
under the action of selenium dioxide in acetic acid (Scheme 3).
We next attempted the base-promoted (K2CO3, KOH)
alkylamination of chalcogenadiazoles 3 with a variety of primary
and secondary amines at room temperature in DMF or aliphatic
amine. The products of the reaction were unexpected 2-
aminobenzo[b]chalcogenophenes 4a-4i (Scheme 4, Table 1). It
was found, that the reaction was tolerant to the nature of the
solvent and MeCN, Me2CO or MeOH could be used as the
reaction medium. The use of DMF allowed the reaction to
proceed at room temperature (20-25 °C).
Compound 4e was obtained in a low yield (7%) due to the
relatively high nucleophilicity of pyrrolidine which displaces the
chlorine atom on the benzene ring faster than cyclization into 4e
occurs, affording thioamide 5 (62%) as major product (Scheme
5). Similar decomposition of the more labile selenadiazole ring of
compound 3d under the action of pyrrolidine occurs faster
a Me2NH was obtained from K2CO3, NH4OAc and DMF.

3
The progress of the reaction was followed by 1H NMR
monitoring of a reaction mixture containing compound 3b, n-
butylamine, and K2CO3 in DMF at 25 °C (Scheme 7, Figures 1
and 2).
dithiafulvene 13, which further rearranged into the more stable
trans-dithiafulvene 14, after heating in boiling water (Scheme 8).
Initially, the thiadiazole ring-opening was indicated by the
disappearance of the thiadiazole hydrogen atom H5Het at δH 9.19
ppm (the formation of an 1,2,3-thiadiazol-5-yl intermediate anion
7 was not observed in our experiment, but is supported by data
reported in literature. For example, the 4-phenyl-1,2,3-thiadiazol-
5-yl anion was generated on treatment of 4-phenyl-1,2,3-
thiadiazole with methyllithium in THF at –78 °C. Subsequent
quenching of the reaction mixture with 38% deuterium chloride
in deuterium oxide resulted in 5-deutero-4-phenyl-1,2,3-
thiadiazole.6h Similarly, the 4-phenyl-1,2,3-thiadiazol-5-yl anion
was generated on treatment with lithium diisopropylamide in
THF at –78 °C. This anion was successfully trapped as 5-
trimethylsilyl-4-phenyl-1,2,3-thiadiazole (55%) on addition of
chlorotrimethylsilane.6h In addition, it was shown that the H5Het
atom of 4-(2-hydroxyphenyl)-1,2,3-thiadiazole was partially
deuterated when treated with tetrabutylammonium hydroxide in
CD3CN at room temperature, proving the intermediacy of the
1,2,3-thiadiazol-5-yl anion8a). Decomposition of the thiadiazole
ring was accompanied by nitrogen evolution and formation of
enthiolate 11, which can be trapped as thioamide 12 on addition
of acid [signals at δH (ppm) 7.44 (NH) 7.57 (H3Ph), 8.11 (H4Ph)
and 8.32 (H6Ph), Figure 1 (b)]. The progress of the reaction was
also followed by GC-MS. The observation of an intermediate
with m/z = 286 (compound 12) supported the formation of 11.
After 22 hours the transformation was complete and the NMR
spectrum showed a clean absorption pattern for N-butyl-5-
Figure 1. Transformation of thiadiazole 3b into benzothiophene 4a
(DMF, 25 °C) as monitored by 1H-NMR spectroscopy. 1H NMR
spectra of the aromatic region after selected reaction intervals.
nitrobenzo[b]thiophen-2-amine
(4a)
[δH
(ppm):
0.97
(CH3CH2CH2CH2-NH), 1.46 (CH3CH2CH2CH2-NH), 1.67
(CH3CH2CH2CH2-NH), 3.24 (CH3CH2CH2CH2-NH), 4.28
(CH3CH2CH2CH2-NH), 6.12 (H3Het), 7.59 (H7Ph), 7.87 (H6Ph),
8.21 (H4Ph)]. There were no detectable impurities present.
(a) beginning of the reaction (0 hours elapsed)
(b) progress of the reaction (3 hours elapsed)
(c) end of the reaction (22 hours elapsed)
An experiment with addition of weakly nucleophilic proton
donors, such as water, supported the formation of presumed
intermediates 8-10.6b,c,h Thus, the potassium carbonate promoted
decomposition of thiadiazole 3b in boiling acetonitrile gave
alkynylthiolate 8. Addition of water resulted in immediate
protonation and dimerization of intermediates 8 and 10 into cis-

4
Tetrahedron
39333940. (d) Abramov, M. A.; Dehaen, W. Synthesis 2000,
15291531. (e) Petrov, M. L.; Abramov, M. A.; Androsov, D. A.;
Dehaen, W. Russ. J. Gen. Chem. 2000, 70, 16521653. (f) Petrov,
M. L.; Abramov, M. A.; Abramova, I. P., Dehaen, W.,
Lyakhovetskii, Yu. I. Russ. J. Org. Chem. 2001, 37, 16431648.
(g) Petrov, M. L.; Abramov, M. A.; Androsov, D. A.; Dehaen, W.;
Lyakhovetskii, Yu. I. Russ. J. Gen. Chem. 2002, 72, 12821285.
(h) Petrov, M. L.; Dehaen, W.; Abramov, M. A.; Abramova, I. P.;
Androsov, D. A. Russ. J. Org. Chem. 2002, 38, 15101518. (i)
Petrov, M. L.; Androsov, D. A.; Abramov, M. A.; Dehaen, W.
Russ. J. Org. Chem. 2003, 39, 284286. (j) Petrov, M. L.;
Androsov, D. A.; Lyakhovetskii, Yu. I. Russ. J. Org. Chem. 2004,
40, 16911693. (k) Petrov, M. L.; Androsov, D. A.; Abramov, M.
A.; Abramova, I. P.; Dehaen, W.; Lyakhovetskii, Yu.I. Russ. J.
Org. Chem. 2006, 42, 15211527. (l) Petrov, M. L.; Teplyakov, F.
S.; Androsov, D. A.; Yekhlef, M. Russ. J. Org. Chem. 2009, 45,
17271729. (m) Petrov, M. L.; Yekhlef, M.; Teplyakov, F. S.;
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In conclusion, we have reported a simple and convenient
synthetic approach toward benzo[b]chalcogenophenes from
readily accessible 4-(2-chloroaryl)-1,2,3-chalcogenadiazoles.
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