Fischer synthesis of 1H- and 3H-[1]benzothieno[3,2-b]pyrroles

Article abstract of DOI:10.1055/s-2007-983821

The reaction of 1-benzothiophen-3(2H)-one hydrazone with various ketones under different conditions has been studied and a convenient method has been proposed for the synthesis of thienopyrrole derivatives. The method is applicable to the preparation of 1H- and 3H-benzothienopyrroles with a range of substituents. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-983821

2706
PAPER
Fischer Synthesis of 1H- and 3H-[1]Benzothieno[3,2-b]pyrroles
Fischer Synthesis
l
1
H
-
e
and
3
H
-[1]
x
e
[3,2-
b
]pyrro
y
les A. Shimkin, Arthur K. Mailian, Valerii Z. Shirinian,* Mikhail M. Krayushkin
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp. 47, 119991 Moscow, Russian Federation
Fax +7(495)1355328; E-mail: shir@ioc.ac.ru
Received 16 February 2007; revised 7 June 2007
We have studied the reaction of hydrazone 1 with a num-
Abstract: The reaction of 1-benzothiophen-3(2H)-one hydrazone
ber of different ketones in the presence of an acid catalyst
(Scheme 1).
In previous studies,6 thienopyrroles were prepared using
hydrochloric acid as catalyst and either methanol or acetic
acid as solvent. Under these conditions, however, the re-
action of compound 1 with ketones 2 gave the thienopyr-
roles 3 in only low to moderate yields (Table 1, method
with various ketones under different conditions has been studied
and a convenient method has been proposed for the synthesis of
thienopyrrole derivatives. The method is applicable to the prepara-
tion of 1H- and 3H-benzothienopyrroles with a range of substitu-
ents.
Key words: Fischer reaction, thieno[3,2-b]pyrroles, hydrazones,
ketones, [3,3]-sigmatropic rearrangements
A), with significant amounts of bithiophene 4 also isolat-
ed; results which are analogous to those obtained by
Shvedov et al.7
The synthesis and reactivity of thienopyrrole derivatives
has generated great interest because of the potent biologi-
cal activity exhibited by these compounds.1 Thienopyr-
roles, which are indole isosters, have been extensively
studied as synthons for dyes and optoelectronic materi-
als.2 The main methods for their synthesis are the reduc-
tion and cyclization of nitrothiophene derivatives3 and the
thermal decomposition of azide derivatives of thiophene.4
The Fischer method, which is widely applied in indole
syntheses has, however, been used only once for the prep-
aration of thienopyrrole derivatives5 because thienylhy-
drazines are difficult to prepare and much less stable then
phenylhydrazines.
Table 1 Synthesis of 1-Benzothieno[3,2-b]pyrroles 3
Product
R1
R2
Yield (%)a
A
B
C
3a
3b
3c
3d
3e
3f
Me
Me
Et
40
38
39
57
19
48
24
15
28
87
70
90
82
65
51
Me
(CH2)4
Me
CH2CO2Et 46
Me
Ph
26
3
Recently, we synthesized the first thienopyrrolenines by
the reaction of alkyl 4-(2-hydrazino)-2-methyl-3-
thiophenecarboxylates with 3-methyl-2-butanone under
Fischer reaction conditions.6 Here, we are pleased to re-
port an efficient and convenient method for the synthesis
of a range of benzothienopyrrole derivatives from very
simple starting materials.
Me
COOEt
a Methods: from hydrazone 1 in MeOH (A) and benzene (B); from
hydrazone hydrochloride in benzene (C).
O
NH2
H
R2
8
N
7
R1
NH2
N
R1
S
1
2
2a–f
H+
+
6
S
3
R2
5
S
4
S
H2N
3a–f
1
4
a R1 = R2 = Me
b R1 = Me, R2 = Et
c R1R2 = (CH2)4
d R1 = Me, R2 = CH2COOEt
e R1 = Me, R2 = Ph
f R1 = Me, R2 = COOEt
Scheme 1
SYNTHESIS 2007, No. 17, pp 2706–2710
x
x.
x
x
.
2
0
0
7
Advanced online publication: 30.07.2007
DOI: 10.1055/s-2007-983821; Art ID: Z04107SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Fischer Synthesis of 1H- and 3H-[1]Benzothieno[3,2-b]pyrroles
2707
N
Proposed pathways for the formation of the target
thienopyrroles and the minor product are shown in
Scheme 2. The formation of both the thienopyrroles and
bisthiophene is due to the [3,3]-sigmatropic rearrange-
ment of intermediates 5 and 6, correspondingly. Since the
latter is presumably formed as a result of nucleophilic
substitution in hydrazone 1, this undesirable nucleophilic
process could be prevented by changing the solvent from
methanol to the less polar benzene (Table 1, method B).
To this end, solutions of hydrazone 1 and ketones 2 in
benzene were refluxed in order to obtain the non-symmet-
ric azines 5; gaseous hydrogen chloride was then passed
into the boiling mixtures. However, during the reaction of
the hydrazone with the ketones, a great number of side
products were formed in addition to the undesired
bisthiophene 4. Therefore, in order to minimize side reac-
tions, the procedure was reversed: the benzene solution of
hydrazone 1 was saturated with hydrogen chloride and,
after the ketone was added, the mixture was refluxed for
2–6 hours (Table 1, Method C). In this case the target
compounds were obtained in 51–90% yields.
R1
R2
N
NH2
1) HCl
O
R2
R3
S
R3
S
2)
R1
7a–c
8a–c
1
a R1 = R2 = R3 = Me
b R1 = Me, R2 = R3 = Ph
c R1R2 = (CH2)4, R3 = Me
Scheme 3
O2N
O2N
N
N
Ph
S
S
Ph
9
10
N
N
S
11
This method allowed us to prepare the more complex
1-benzothieno[3,2-b]pyrroles 3g and 3h in yields of 56–
80% (Figure 1). The starting ketones for these thienopyr-
roles were synthesized by alkylation of 3-hydroxy-
thiophene as previously described.8
Figure 2
Hydrazones 1, 14 and 15 were prepared by reaction of
benzothiophen-3-ones 12a–c or acetates 13a and 13b with
hydrazine hydrate in ethanol, in the presence of 4-methyl-
benzenesulfonic acid (Scheme 4). Acetates 13 were pre-
ferred because of their stability to oxidation in air.
H
N
R
S
S
R
O
HO
COOEt
X
S
3g R = Me
3h R = 4-BrC6H4
R
N
NH2
12a–c
N2H4·H2O
TsOH
R
Figure 1
X
OAc
S
1, 14, 15
Method C was also used for the preparation of thienopyr-
rolenine derivatives, which are analogues of indolenines
and can be used as intermediates for the preparation of
dyes and photochromic spiro compounds.9 The reaction of
hydrazone 1 with branched ketones 7a–c by procedure C
led to pyrrolenines 8a–c in 27–61% yield (Scheme 3).
X
S
13a,b
12a, 13a, 1 X = CH, R = H
12b, 13b, 14 X = CH, R = NO2
12c, 15 X = N, R = H
Scheme 4
The optimized reaction conditions could also be extended
to the synthesis of other thienopyrrolenine derivatives
such as 7-nitrobenzothienopyrrolenines 9, 10 and the
thieno[2,3-b]pyridine derivative 11 (Figure 2). It should
be noted that, in the latter case, the presence of the basic
pyridine fragment did not hinder the reaction.
The molecular structures of all compounds obtained were
confirmed by 1H NMR, mass-spectra and elemental anal-
ysis. The signals of the four aromatic protons of ben-
1
zothienopyrrole appear in their H NMR spectra at d =
R1
O
R2
R2
S
R1
1
N
N
N
3
1
4
H+
N
– NH2NH2
S
S
6
5
Scheme 2
Synthesis 2007, No. 17, 2706–2710 © Thieme Stuttgart · New York

2708
A. A. Shimkin et al.
PAPER
Anal. Calcd for C12H11NS: C, 71.60; H, 5.51; N, 6.96; S, 15.93.
Found: C, 71.26; H, 5.63; N, 6.76; S, 15.72.
7.1–7.9 ppm as an ABCD system with coupling constants
3JAB = 7.9 Hz, 3JBC = 7.2 Hz and 3JCD = 7.9 Hz.10 The 3H-
pyrroles were also characterized by 13C NMR spectrosco-
py, the main features of which were the signals arising
from C-3 at d = 54–73 ppm.
2-Ethyl-3-methyl-1H[1]benzothieno[3,2-b]pyrrole (3b)
Yield: 1.84 g (70%); yellow solid; mp 52–53 °C (PE).
1H NMR (250 MHz, CDCl3): d = 1.33 (t, J = 7.3 Hz, 3 H, CH2CH3),
2.37 (q, J = 7.3 Hz, 2 H, CH2CH3), 2.38 (s, 3 H, CH3), 7.18 (dd,
J = 7.9, 7.2 Hz, 1 H, H-Ar), 7.32 (dd, J = 7.9, 7.2 Hz, 1 H, H-Ar),
7.59 (d, J = 7.9 Hz, 1 H, H-Ar), 7.80 (d, J = 7.9 Hz, 1 H, H-Ar),
8.15 (br s, 1 H, NH).
In conclusion, an easy and convenient method has been
developed for the synthesis of a range of thienopyrrole de-
rivatives from very simple starting materials under Fis-
cher reaction conditions. This method permits the use of
various ketones and thienylhydrazines and the synthesis
of thienopyrroles with alkyl, aryl and heteroaryl substitu-
ents.
MS (EI, 70 eV): m/z (%) = 215 (75) [M]+, 200 (100) [M – CH3]+.
Anal. Calcd for C13H13NS: C, 72.52; H, 6.09; N, 6.51; S, 14.89.
Found: C, 72.64; H, 6.15; N, 6.27; S, 14.75.
2,3,4,10-Tetrahydro-1H-[1]benzothieno[3,2-b]indole (3c)
Yield: 2.49 g (90%); red-brown monoclinic crystals; mp 123–
126 °C (i-PrOH).
1H NMR (250 MHz, CDCl3): d = 1.80–2.00 (m, 4 H, 2 × CH2),
2.63–2.71 (m, 2 H, CH2), 2.73–2.81 (m, 2 H, CH2), 7.20 (dd,
J = 7.9, 7.2 Hz, 1 H, H-Ar), 7.35 (dd, J = 7.9, 7.2 Hz, 1 H, H-Ar),
7.60 (d, J = 7.9 Hz, 1 H, H-Ar), 7.80 (d, J = 7.9 Hz, 1 H, H-Ar),
8.15 (br s, 1 H, NH).
1H NMR spectra were recorded in CDCl3 on Bruker WM-250 and
Bruker AM-300 instruments. Mass spectra were obtained on a Kra-
tos spectrometer (70 eV) with direct sample injection into the ion
source. Melting points were measured on a Boetius hot stage appa-
ratus and are uncorrected. All reactions were monitored by TLC us-
ing silica gel 60 F254 Merck plates [petroleum ether (PE; bp 60–80
°C)–EtOAc, 6:1]. Column chromatography was performed with sil-
ica gel 60 (70–230 mesh) purchased from Merck. 1-Benzothiophen-
2-yl acetate (13a),11 5-nitro-1-benzothiophen-2-yl acetate (13b)12
and thieno[2,3-b]pyridin-3-ol (12c)13 were prepared by known pro-
cedures. Ethyl 4-hydroxy-2-methyl-5-(2-oxopropyl)-3-thiophene-
carboxylate (2g), ethyl 5-[2-(4-bromophenyl)-2-oxoethyl]-4-
hydroxy-2-methyl-3-thiophenecarboxylate (2h)8 and 1-benzo-
thiophen-3(2H)-one hydrazone (1)6 were prepared according the
procedures described earlier.
MS (EI, 70 eV): m/z (%) = 227 (57) [M]+, 199 (77) [M – C2H4]+, 55
(100).
Anal. Calcd for C14H13NS: C, 73.97; H, 5.76; N, 6.16; S, 14.11.
Found: C, 74.03; H, 6.14; N, 6.19; S, 13.85.
Ethyl 2-(2-Methyl-1H-[1]benzothieno[3,2-b]pyrrol-3-yl)acetate
(3d)
Yield: 2.73 g (82%); light red prismatic crystals; mp 151–153 °C
(EtOH).
1H-[1]Benzothieno[3,2-b]pyrroles (3); General Procedure
Method A. To a stirred suspension of 1-benzothiophen-3-one hy-
drazone (1; 2.0 g, 12 mmol) in MeOH (10 mL), ketone 2 (14 mmol)
was added. The mixture was refluxed for 15 min and concd HCl (1.5
mL, 15 mmol) was added. The dark solution was refluxed for 1 h
then cooled, poured into cold H2O (100 mL) and extracted with
EtOAc (3 × 30 mL). Evaporation of the solvent gave a brown tar
that was either recrystallized from a suitable solvent, or purified by
column chromatography (PE–EtOAc, 10:1).
1H NMR (250 MHz, CDCl3): d = 1.31 (t, J = 7.2 Hz, 3 H, CH2CH3),
2.34 (s, 3 H, CH3), 3.59 (s, 2 H, CH2), 4.21 (q, J = 7.2 Hz, 2 H,
CH2CH3), 7.17 (dd, J = 7.9, 7.2 Hz, 1 H, H-Ar), 7.28 (dd, J = 7.9,
7.2 Hz, 1 H, H-Ar), 7.57 (d, J = 7.9 Hz, 1 H, H-Ar), 7.76 (d, J = 7.9
Hz, 1 H, H-Ar), 8.55 (br s, 1 H, NH).
MS (EI, 70 eV): m/z (%) = 273 (76) [M]+, 200 (100) [M – CO2Et]+.
Anal. Calcd for C15H15NO2S: C, 65.91; H, 5.53; N, 5.12; S, 11.73.
Found: C, 65.68; H, 5.98; N, 5.08; S, 11.30.
Method B. To a suspension of hydrazone 1 (2.0 g, 12 mmol) in ben-
zene (15 mL), ketone 2 (14 mmol) was added. The mixture was re-
fluxed for 15 min during which the precipitate dissolved. HCl gas
was passed into the boiling solution and the brown-gray precipitate
that initially formed was gradually dissolved over 1 h. After cool-
ing, the reaction mixture was filtered and evaporated under reduced
pressure. The product was purified by either recrystallization or col-
umn chromatography.
2-Methyl-3-phenyl-1H-[1]benzothieno[3,2-b]pyrrole (3e)
Yield: 2.08 g (65%); yellow monoclinic crystals; mp 145–146 °C
(PE–EtOAc, 10:1).
1H NMR (250 MHz, CDCl3): d = 2.54 (s, 3 H, CH3), 7.20–7.40 (m,
3 H), 7.47–7.70 (m, 5 H), 7.85 (d, J = 7.9 Hz, 1 H, H-Ar), 8.41 (br
s, 1 H, NH).
Method C. HCl gas was passed into a stirred suspension of hydra-
zone 1 (2 g, 12 mmol) in benzene (30 mL) for 0.5 h. Ketone 2 (14
mmol) was added and the reaction mixture was refluxed until the
brown-gray precipitate initially formed dissolved. The solvent was
removed under reduced pressure to give either a dark tar or a solid
that was purified by either column chromatography or recrystalliza-
tion.
MS: m/z (%) = 263 (100) [M]+.
Anal. Calcd for C17H13NS: C, 77.53; H, 4.98; N, 5.32. Found: C,
77.12; H, 5.02; N, 5.43.
Ethyl2-Methyl-1H-[1]benzothieno[3,2-b]pyrrole-3-carboxylate
(3f)
Yield: 1.61 g (51%); light yellow solid; 200–202 °C (PE–EtOAc,
15:1).
2,3-Dimethyl-1H[1]benzothieno[3,2-b]pyrrole (3a)
Yield: 2.13 g (87%); light brown plates; mp 132–134 °C (PE–
EtOAc, 15:1).
1H NMR (250 MHz, CDCl3): d = 2.20 (s, 3 H, CH3), 2.37 (s, 3 H,
CH3), 7.18 (dd, J = 7.9, 7.2 Hz, 1 H, H-Ar), 7.32 (dd, J = 7.9, 7.2
Hz, 1 H, H-Ar), 7.59 (d, J = 7.9 Hz, 1 H, H-Ar), 7.80 (d, J = 7.9 Hz,
1 H, H-Ar), 8.16 (br s, 1 H, NH).
1H NMR (250 MHz, CDCl3): d = 1.44 (t, J = 7.1 Hz, 3 H, CH2CH3),
2.73 (s, 3 H, CH3), 4.39 (q, J = 7.1 Hz, 2 H, CH2CH3), 7.23 (dd,
J = 7.9, 7.2 Hz, 1 H, H-Ar), 7.33 (dd, J = 7.9, 7.2 Hz, 1 H, H-Ar),
7.65 (d, J = 7.9 Hz, 1 H, H-Ar), 7.81 (d, J = 7.9 Hz, 1 H, H-Ar),
8.96 (br s, 1 H, NH).
MS (EI, 70 eV): m/z (%) = 259 (98) [M]+, 230 (100) [M – Et]+.
MS (EI, 70 eV): m/z (%) = 201 (100) [M]+, 186 (13) [M – CH3]+.
Anal. Calcd for C14H13NO2S: C, 64.84; H, 5.05; N, 5.40; S, 12.37.
Found: C, 64.89; H, 5.34; N, 5.62; S, 11.97.
Synthesis 2007, No. 17, 2706–2710 © Thieme Stuttgart · New York

PAPER
Fischer Synthesis of 1H- and 3H-[1]Benzothieno[3,2-b]pyrroles
2709
Ethyl 4-Hydroxy-2-methyl-5-(2-methyl-1H-[1]benzothieno[3,2-
b]pyrrol-3-yl)thiophene-3-carboxylate (3g)
Yield: 3.62 g (80%); pale pink solid; 175–176 °C.
13C NMR (62.9 MHz, CDCl3): d = 18.51 (Me), 72.99 (3-C), 121.59,
123.91, 124.30, 125.01, 127.79, 127.99, 129.02, 130.30, 140.15,
144.08, 144.60, 151.87, 187.81 (2-C).
1H NMR (250 MHz, CDCl3): d = 1.44 (t, J = 7.2 Hz, 3 H, CH2CH3),
2.53 (s, 3 H, Me), 2.70 (s, 3 H, Me), 4.45 (q, J = 7.2 Hz, 2 H,
CH2CH3), 7.18 (dd, J = 7.9, 7.2 Hz, 1 H, H-Ar), 7.30 (dd, J = 7.9,
7.2 Hz, 1 H, H-Ar), 7.61 (d, J = 7.9 Hz, 1 H, H-Ar), 7.77 (d, J = 7.9
Hz, 1 H, H-Ar), 8.48 (br s, 1 H, NH), 9.39 (br s, 1 H, OH).
MS (EI, 70 eV): m/z (%) = 339 (100) [M]+, 297 (29), 221 (29).
Anal. Calcd for C23H17NS: C, 81.38; H, 5.05; N, 4.13. Found: C,
80.76; H, 5.04; N, 4.16.
4a-Methyl-2,3,4,4a-tetrahydro-1H-[1]benzothieno[3,2-b]indole
(8c)
Yield: 1.17 g (40%); pale brown solid; mp 103–104 °C (PE).
MS (EI, 70 eV): m/z (%) = 371 (48) [M]+, 325 (46) [M – EtOH]+,
297 (100) [M – EtOH – CO]+.
Anal. Calcd for C19H17NO3S2: C, 61.43; H, 4.61; N, 3.77. Found: C,
61.30; H, 4.64; N, 3.56.
1H NMR (250 MHz, CDCl3): d = 1.15–1.28 (m, 1 H, CH), 1.30 (s,
3 H, Me), 1.32–1.49 (m, 1 H, CH), 1.52–1.71 (m, 2 H, CH2), 2.02–
2.16 (m, 1 H, CH), 2.16–2.28 (m, 1 H, CH), 2.51 (td, 2J = 13.8 Hz,
3J = 5.9 Hz, 1 H, CH), 2.81–2.93 (m, 1 H, CH), 7.24 (dd, J = 7.3,
7.9 Hz, 1 H, H-Ar), 7.38 (dd, J = 7.3, 7.9 Hz, 1 H, H-Ar), 7.76 (d,
J = 7.9 Hz, 1 H, H-Ar), 8.08 (d, J = 7.9 Hz, 1 H, H-Ar).
Ethyl 5-{2-(4-Bromophenyl)-1H-[1]benzothieno[3,2-b]pyrrol-
3-yl}-4-hydroxy-2-methylthiophene-3-carboxylate (3h)
Yield: 3.49 g (56%); pale brown plates; mp 186–188 °C.
1H NMR (250 MHz, DMSO-d6): d = 1.36 (t, J = 7.3 Hz, 3 H, Me),
2.61 (s, 3 H, Me), 4.37 (q, J = 7.3 Hz, 2 H, CH2), 7.27 (dd, J = 7.9,
7.2 Hz, 1 H, H-Ar), 7.42 (dd, J = 7.9, 7.2 Hz, 1 H, H-Ar), 7.54 (d,
J = 8.5 Hz, 2 H, H-Ar), 7.62 (d, J = 8.5 Hz, 2 H, H-Ar), 7.87 (d,
J = 7.9 Hz, 1 H, H-Ar), 8.02 (d, J = 7.9 Hz, 1 H, H-Ar), 9.16 (br s,
1 H, NH), 12.44 (br s, 1 H, OH).
13C NMR (62.9 MHz, CDCl3): d = 20.23, 21.36, 29.70, 30.41,
39.66, 55.21 (3-C), 121.14, 123.85, 123.90, 124.79, 130.50, 143.51,
144.51, 151.42, 192.32 (2-C).
MS (EI, 70 eV): m/z (%) = 241 [M]+.
Anal. Calcd for C15H15NS: C, 74.65; H, 6.26; N, 5.80. Found: C,
74.29; H, 6.59; N, 5.88.
MS (EI, 70 eV): m/z (%) for 81Br = 513 (80) [M]+, 467 (64) [M –
EtOH]+, 372 (100).
2,3,3-Trimethyl-7-nitro-3H-[1]benzothieno[3,2-b]pyrrol (9)
Anal. Calcd for C24H18BrNO3S2: C, 56.25; H, 3.54; N, 2.73. Found:
C, 56.58; H, 4.01; N, 2.60.
Yield: 1.71 g (64%); brown solid; mp 125–128 °C (PE–EtOAc).
1H NMR (200 MHz, CDCl3): d = 1.45 (s, 6 H, CMe2), 2.37 (s, 3 H,
Me), 7.91 (d, J = 8.8 Hz, 1 H, H-Ar), 8.15 (d, J = 8.8 Hz, 1 H, H-
Ar), 8.94 (s, 1 H, H-Ar).
2,2¢-Bi-1-benzothiophen-3,3¢-diamine (4)
Yield: 0.27 g (15%); pale yellow needles; 237–239 °C (EtOH).
1H NMR (250 MHz, CDCl3): d = 4.17 (br s, 4 H, 2 × NH2), 7.35–
7.42 (m, 4 H, H-Ar), 7.60 (d, J = 6.6 Hz, 2 H, H-Ar), 7.77 (d, J = 6.6
Hz, 2 H, H-Ar).
MS (EI, 70 eV): m/z (%) = 260 (100) [M]+, 245 (22) [M – Me]+, 219
(80) [M – MeCN]+.
Anal. Calcd for C13H12N2O2S: C, 59.98; H, 4.65; N, 10.76. Found:
C, 59.80; H, 4.83; N, 10.66.
MS (EI, 70 eV): m/z (%) = 296 (100) [M]+.
Anal. Calcd for C16H12N2S2: C, 64.83; H, 4.08; N, 9.45; S, 21.64.
Found: C, 64.74; H, 3.97; N, 9.29; S, 21.53.
2-Methyl-7-nitro-3,3-diphenyl-3H-[1]benzothieno[3,2-b]pyr-
role (10)
Yield: 1.17 g (25%); brown solid; mp 181–183 °C (EtOH).
Thieno[3,2-b]pyrrolenines 8–11
1H NMR (250 MHz, CDCl3): d = 2.41 (s, 3 H, Me), 7.13–7.23 (m,
4 H, H-Ar), 7.30–7.39 (m, 6 H, H-Ar), 7.88 (d, J = 8.7 Hz, 1 H, H-
Ar), 8.17 (dd, J = 2.0, 8.7 Hz, 1 H, H-Ar), 9.01 (d, J = 2.0 Hz, 1 H,
H-Ar).
Compounds 8–11 were prepared by method C from hydrazones 1,
14 and 15 (12 mmol) and purified by column chromatography
(CHCl3–EtOAc, 3:1).
MS (EI, 70 eV): m/z (%) = 384 (100) [M]+, 354 (39), 338 (28) [M –
2,3,3-Dimethyl-3H-[1]benzothieno[3,2-b]pyrrole (8a)
Yield: 1.60 g (61%); pale yellow plates; mp 86–88 °C (PE).
NO2]+, 295 (58).
1H NMR (300 MHz, CDCl3): d = 1.40 (s, 6 H, CMe2), 2.33 (s, 3 H,
Me), 7.30 (dd, J = 7.4, 8.1 Hz, 1 H, H-Ar), 7.43 (dd, J = 7.4, 8.1 Hz,
1 H, H-Ar), 7.81 (d, J = 8.1 Hz, 1 H, H-Ar), 8.07 (d, J = 8.1 Hz,
1 H, H-Ar).
13C NMR (62.9 MHz, CDCl3): d = 15.68 (Me), 23.27 (CMe2), 54.68
(CMe2), 120.97, 123.74, 123.78, 124.73, 130.38, 143.40, 143.48,
150.44, 189.92 (C=N).
Anal. Calcd for C23H16N2O2S: C, 71.86; H, 4.19; N, 7.29. Found: C,
71.54; H, 4.28; N, 6.96.
2,3,3-Trimethy-3H-pyrrolo[2¢,3¢:4,5]thieno[3,2-b]pyridine (11)
Yield: 1.24 g (47%); yellow monoclinic crystals; mp 80–82 °C
(PE).
1H NMR (250 MHz, CDCl3): d = 1.15 (s, 6 H, CMe2), 2.07 (s, 3 H,
Me), 7.08 (dd, J = 3.3, 7.2 Hz, 1 H, H-Ar), 8.03 (d, J = 7.2 Hz, 1 H,
H-Ar), 8.24 (d, J = 3.3 Hz, 1 H, H-Ar).
MS (EI, 70 eV): m/z (%) = 215 (100) [M]+, 200 (48) [M – Me]+, 174
(70) [M – MeCN]+.
MS (EI, 70 eV): m/z (%) = 216 (100) [M]+, 201 (40) [M – Me]+, 175
Anal. Calcd for C13H13NS: C, 72.52; H, 6.09; N, 6.51. Found: C,
72.53; H, 6.38; N, 6.50.
(88) [M – MeCN]+.
Anal. Calcd for C12H12N2S: C, 66.67; H, 5.56; N, 12.96. Found: C,
66.40; H, 5.57; N, 13.24.
2-Methyl-3,3-diphenyl-3H-[1]benzothieno[3,2-b]pyrrole (8b)
Yield: 1.12 g (27%); orange solid; mp 181–183 °C (EtOH).
5-Nitro-1-benzothiophen-3(2H)-one Hydrazone (14)
Prepared from acetate 13b (0.1 mol).6
1H NMR (300 MHz, CDCl3): d = 2.41 (s, 3 H, Me), 7.18–7.25 (m,
4 H, 4 × H-Ar), 7.29–7.37 (m, 7 H, 7 × H-Ar), 7.47 (dd, J = 7.4, 8.1
Hz, 1 H, H-Ar), 7.79 (d, J = 8.1 Hz, 1 H, H-Ar), 8.14 (d, J = 8.1 Hz,
1 H, H-Ar).
Yield: 16.5 g (79%); brown needles; mp 160–165 °C (EtOH).
Synthesis 2007, No. 17, 2706–2710 © Thieme Stuttgart · New York

2710
A. A. Shimkin et al.
PAPER
1H NMR (250 MHz, CDCl3): d = 4.13 (s, 2 H, CH2), 6.88 (br s, 2 H,
NH2), 7.52 (d, J = 8.6 Hz, 1 H, H-Ar), 8.00 (dd, J = 2.4, 8.6 Hz, 1 H,
H-Ar), 8.08 (d, J = 2.4 Hz, 1 H, H-Ar).
(3) (a) Garsia, F.; Galvez, C. Synthesis 1985, 143.
(b) Abramovitch, R. A.; Chellathurai, T.; McMaster, I. T.;
Takaya, T.; Azogu, C. I.; Vanderpool, D. P. J. Org. Chem.
1977, 42, 2914. (c) Kaszynski, P.; Dougherty, D. A. J. Org.
Chem. 1993, 58, 5209. (d) Appukkuttan, P.; van der Eycken,
E.; Dehaen, W. Synlett 2005, 127. (e) Krayushkin, M. M.;
Stoyanovich, F. M.; Shorunov, S. V. Mendeleev Commun.
2004, 29.
MS (EI, 70 eV): m/z (%) = 209 (100) [M]+, 192 (88) [M – NH3]+.
Anal. Calcd for C8H7N3O2S: C, 45.92; H, 3.37; N, 20.08. Found: C,
46.17; H, 3.71; N, 19.70.
Thieno[2,3-b]pyridin-3(2H)-one Hydrazone (15)
Prepared from thiophen-3-one 12c (0.1 mol).6
(4) (a) Gairns, R. S.; Moody, C. J.; Rees, C. W. J. Chem. Soc.,
Perkin Trans. 1 1986, 501. (b) Degl’Innocenti, A.;
Funicello, M.; Scafato, P.; Spagnolo, P.; Zanirato, P. J.
Chem. Soc., Perkin Trans. 1 1995, 2141. (c) Eras, J.;
Galvez, C.; Garcia, F. J. Heterocycl. Chem. 1984, 21, 215.
(d) Chen, J.; Burghart, A.; Derecskei-Kovacs, A.; Burgess,
K. J. Org. Chem. 2000, 65, 2900. (e) Arad, O.; Morros, J.;
Batllori, X.; Teixido, J.; Nonell, S.; Borrell, J. I. Org. Lett.
2006, 8, 847.
(5) Shvedov, V. I.; Trofimkin, Yu. I.; Vasil’eva, V. K.; Grinev,
A. N. Chem. Heterocycl. Compd. 1975, 11, 1133; Khim.
Geterotsikl. Soedin. 1975, 1324.
(6) Shirinian, V. Z.; Krayushkin, M. M.; Nikalin, D. M.;
Shimkin, A. A. Russ. Chem. Bull. 2005, 54, 738; Izv. Akad.
Nauk, Ser. Khim. 2005, 725.
(7) Shvedov, V. I.; Trofimkin, Yu. I.; Vasil’eva, V. K.; Vlasova,
T. F.; Griniev, A. N. Chem. Heterocycl. Compd. 1975, 11,
802; Khim. Geterotsikl. Soedin. 1975, 914.
(8) Krayushkin, M. M.; Shirinian, V. Z.; Nikalin, D. M.;
Shimkin, A. A. Russ. Chem. Bull. 2004, 53, 631; Izv. Akad.
Nauk, Ser. Khim. 2004, 602.
(9) (a) Krayushkin, M. M.; Shirinian, V. Z.; Nikalin, D. M.
Russ. Chem. Bull. 2004, 53, 720; Izv. Akad. Nauk., Ser.
Khim. 2004, 687. (b) Shirinian, V. Z.; Krayushkin, M. M.;
Nikalin, D. M.; Shimkin, A. A.; Vorontsova, L. G.;
Starikova, Z. A. Arkivoc 2005, (vii), 72. (c) Shimkin, A. A.;
Shirinian, V. Z.; Nikalin, D. M.; Krayushkin, M. M.; Pivina,
T. S.; Troitsky, N. A.; Vorontsova, L. G.; Starikova, Z. A.
Eur. J. Org. Chem. 2006, 2087.
Yield: 10.9 g (66%); yellow prismatic crystals; mp 138–140 °C
(EtOH).
1H NMR (250 MHz, CDCl3): d = 3.92 (s, 2 H, CH2), 5.43 (br s, 2 H,
NH2), 6.97 (dd, J = 5.2, 7.4 Hz, 1 H, H-Ar), 7.77 (dd, J = 1.5, 7.4
Hz, 1 H, H-Ar), 8.28 (dd, J = 1.5, 5.2 Hz, 1 H, H-Ar).
MS (EI, 70 eV): m/z (%) = 165 (91) [M]+, 148 (65) [M – NH3]+, 136
(100) [M – N2H2]+.
Anal. Calcd for C7H7N3S: C, 50.89; H, 4.27; N, 25.43. Found: C,
49.77; H, 4.63; N, 25.63.
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Synthesis 2007, No. 17, 2706–2710 © Thieme Stuttgart · New York