A one-pot synthesis and 1,3-dipolar cycloaddition of [1,2]dithiolo[4,3-b]indole-3(4H)-thiones

Article abstract of DOI:10.1016/j.tet.2009.01.069

Treatment of N-substituted 2-methyl-1H-indoles 1 with S₂Cl₂ and DABCO in chloroform gave the corresponding [1,2]dithiolo[4,3-b]indole-3(4H)-thiones 5 by the addition of triethylamine in high yield. 1,2-Dithiole-3-thiones 5 underwent

Full text of DOI:10.1016/j.tet.2009.01.069

Tetrahedron 65 (2009) 2178–2183
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A one-pot synthesis and 1,3-dipolar cycloaddition of [1,2]dithiolo[4,3-b]indole-
3(4H)-thiones
*
Lidia S. Konstantinova, Kirill A. Lysov, Stanislav A. Amelichev, Natalia V. Obruchnikova, Oleg A. Rakitin
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect, 47, 119991 Moscow, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Treatment of N-substituted 2-methyl-1H-indoles 1 with S2Cl2 and DABCO in chloroform gave the
corresponding [1,2]dithiolo[4,3-b]indole-3(4H)-thiones 5 by the addition of triethylamine in high yield.
1,2-Dithiole-3-thiones 5 underwent cycloaddition with one or two DMAD equivalents to afford either
2-(3-thioxo-1,3-dihydro-2H-indol-2-ylidene)-1,3-dithioles 10 or fused 4,5-dihydrothiopyrano[3,2-b]in-
doles 9.
Received 18 November 2008
Received in revised form 23 December 2008
Accepted 15 January 2009
Available online 21 January 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Sulfur–nitrogen heterocycles
Fused 3H-1,2-dithiole-3-thiones
Cycloaddition
DMAD
1,3-Dipoles
1. Introduction
chemistry of dithioloindole thiones has not practically been
investigated.
Despite the continuous interest in indoles,1 only a limited
number of polysulfur-containing derivatives of compounds that
belong to this class have been reported. One of the examples is 5,10-
dihydro-[1,2,3,4]tetrathiocino[5,6-b;8,7-b]diindole, which is a po-
tent antifungal agent with particularly strong activity against
Botrytis cinerea.2 2-Thioindole derivatives have been demonstrated
to be useful intermediates in the synthesis of 2,20-dithiobisindole
tyrosine kinase inhibitors.3 Indoles fused with sulfur heterocycles
have attracted much attention; e.g., 6-chloro-8H-thieno[2,3-b]in-
dole-2-carboxamide was isolated from the Streptomyces albogri-
seolus culture broth and was shown to have both growth promoting
and inhibition activities in rice seedlings.4 6-Methyl-
pentathiepino[6,7-b]indole have been proposed as a cathode ma-
terial for storage batteries.5
We have recently shown that N-isopropyl groups can be
converted by S2Cl2 into N-(1,2-dithiole-3-thiones).10 Nitrogen
heterocycles containing methyl and C–H groups in ortho-posi-
tions, such as the easily available and even commercial 2- and
3-methylindole, are structurally similar to the isopropyl group
and may be considered as potential intermediates in the syn-
thesis of dithioloindole thiones. Fused 1,2-dithole-3-thiones
have never been generated from methyl heterocycles bearing
C–H groups in ortho-positions. In this paper we report a one-
pot synthesis of [1,2]dithiolo[4,3-b]indole-3(4H)-thiones from
N-substituted 2-methylindoles and their 1,3-dipolar cycload-
dition to DMAD.
2. Results and discussion
Indoles fused with the 1,2-dithiole-3-thione ring could be of
interest as condensed 3H-1,2-dithiole-3-thiones, which have
a broad spectrum of biological activity and may be useful
synthons for many sulfur heterocycles.6 Few 1,2-dithio-
loindoles, including non-substituted [1,2]dithiolo[4,3-b]indole-
3(4H)-thione7 and [1,2]dithiolo[3,4-b]indole-3(8H)-thione8 and
its N-methyl derivative,9 are known, and their syntheses are
not of general character and the yields are low. Also the
Treatment of 1,2-dimethylindole 1 with S2Cl2 in chloroform for
48 h at room temperature gave
a
mixture of bis-indoles 2
Me
Me
N
S
Me + S2Cl2
N
Me
N
n
Me
Me
1a
2
n = 2-4
Scheme 1. Reaction of 1,2-dimethylindole with S2Cl2.
* Corresponding author. Tel.: þ7 499 135 53 27; fax: þ7 499 135 53 28.
E-mail address: orakitin@ioc.ac.ru (O.A. Rakitin).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.069

L.S. Konstantinova et al. / Tetrahedron 65 (2009) 2178–2183
2179
+
Further on, we extended this reaction to other N-substituted 2-
methylindoles 1. Fused dithioloindoles 5 were obtained in a re-
action with N-alkyl- and N-benzyl-2-methylindoles 1 in moderate
to high yields. N-Acetyl- and N-benzoyl-2-methylindole did not
react with S2Cl2 and their complexes 3 and 4 even under forcing
conditions (refluxing for 5 h in chloroform); the starting indoles
were isolated from the reaction mixtures in high yields. Apparently
electron-withdrawing substituents at nitrogen in indole (acetyl or
benzoyl groups) suppress the reaction with S2Cl2 even under more
vigorous conditions.
To prepare isomers of indolodithioles 5d[1,2]dithiolo[3,4-
b]indole-3(8H)-thiones 6dthe reaction of 1,3-dimethylindole with
S2Cl2 and its complexes with DABCO was investigated in detail.
Treatment of 1,3-dimethylindole with complex 4 in chloroform at
room temperature for 3 days led to a mixture of polysulfides 7
analogous to 2 prepared from 1,2-dimethylindole and S2Cl2. Com-
plex 3 and S2Cl2 also did not give dithioloindole 6. Only traces of
2,5-dichloro-1,3-dimethyl-1H-indole 8 were detected in the re-
action mixture. A reaction with a more powerful mixture of S2Cl2
and N-ethyldiisopropylamine13 in chloroform at 0 ꢀC for 3 days
gave this product 8 in moderate yield (Scheme 4). Disulfur
dichloride chlorinated both pyrrole and benzene rings in the indole
molecules under these conditions but not react with the 3-methyl
group.
+
DABCO
N
N
S
+
N
N
N + S2Cl2
N
N
S
S
N
S
Cl
Cl_
2Cl_
4
DABCO
3
Scheme 2. Complexes 3 and 4.
S
1. 4, 48 h, rt
2. Et3N
Me
S
S
N
R
N
R
1
5a R = Me, 94%
5b R = Et, 56%
5c R = Pri, 66%
5d R = Bn, 70%
Scheme 3. Synthesis of N-substituted [1,2]dithiolo[4,3-b]indole-3(4H)-thiones 5.
Me
Me
Me
Me
Cl
S2Cl2, EtNPri2
4
S
Cl
n
N
N
N
N
Me
Me
Me
Me
The 3-methyl group in 1,3-dimethylindole was found to be non-
reactive toward S2Cl2 and its mixtures in contrast to the 2-methyl
group in 1,2-dimethylindole. The ready reactivity of the 2-methyl
group can be explained by the low acidity of the 2-methyl hydro-
gens.14 The most plausible mechanism for the formation of 1,2-
dithole-3-thiones 5 is given in Scheme 5. The key steps are assumed
to be similar to those to produce 1,2-dithiole-3-thiones from ter-
tiary N-isopropylamines15 and involve the addition of the S2Cl2
molecule with the formation of 1,2-dithiole ring 14 and further
oxidation to dithiolium salt 15, and chlorination to 3-chlor-
odithiolium salt 16. Sulfur nucleophiles generated from sulfur and
triethylamine are likely to produce thione 5 (Scheme 5).
7
8, 34%
n = 2-4
S
S
S
N
Me
6
Scheme 4. Reaction of 1,3-dimethylindole with S2Cl2.
connected by two, three, and four sulfur atoms in low yields (NMR
and mass spectral data) and the 2-methyl group in indole remains
intact under the action of S2Cl2 (Scheme 1).
In an attempt to increase the sulfurating ability of S2Cl2 we
used in this reaction complexes 3 and 4 formed from S2Cl2 and 1,4-
diazabicyclooctane (DABCO) in ratios 1:1 and 1:2, respectively
(Scheme 2).11 Recently we have shown that these complexes can
convert N-alkylpyrroles into N-alkylpentathiepinopyrroles11 or
bis(dithiolo)pyrroles12 in high yield.
Reaction of 1,2-dimethylindole 1a with a fivefold excess of
complex 3 in chloroform for 48 h at room temperature led after
treatment with Et3N to dithiole thione 5a in moderate yield (34%).
Unsurprisingly, complex 4, a more selective sulfurating agent,
reacted with 1a in the same conditions more cleanly to afford
thione 5a in high yield (Scheme 3).
Depending on the reactivity, fused 1,2-dithiole-3-thiones un-
dergo cycloaddition to one or two molecules of activated acetylenes
bearing two electron-withdrawing groups,16 however, it is hard to
predict that. We wished to compare the reactivity of N-substituted
[1,2]dithiolo[4,3-b]indole-3(4H)-thiones
5
and 8-methyl[1,2]
dithiolo[3,4-b]indole-3(8H)-thione 6.9 Thione 5a was the first to be
subjected to a reaction with a typical acetylene with two electron-
withdrawing groups, i.e., dimethyl acetylenedicarboxylate (DMAD).
Thus, the reaction of 5a (1 equiv) and DMAD (2.4 equiv) in benzene
refluxing for 1 h gave product 9a, a yellow solid, in quantitative
yield. The mass spectrometry and microanalysis showed 9a to be
a 1:2 adduct with the composition C22H21NO8S3. Its 13C and 1H NMR
spectra confirmed the structure. By analogy, reactions of other
Y
S
S
S
S
S
S
4
4
S
Me
Y
S
Cl _
- DABCO,
- HCl
H
N
R
- DABCO,
- HCl
- HCl
N
R
H
N
R
N
Cl _
R
+
N
1
14
N
Y =
S+
S+
S
S
S
S
S2Cl2
S8, Et3N
Cl _
S
Cl
- DABCO,
- S2, - H+
- 1/4 S8, - HCl
Cl _
N
R
N
R
N
R
15
16
5
Scheme 5. A plausible mechanism for the formation of [1,2]dithiolo[4,3-b]indole-3(4H)-thiones 5.

2180
L.S. Konstantinova et al. / Tetrahedron 65 (2009) 2178–2183
CO2Me
CO2Me
Compounds similar to 10 and 11 readily react as heterodienes
S
with activated alkynes to give fused 4H-thiopyranes.16d,e In our
case, only 1,3-dithioles 10 formed 1:2 adducts 9 by treatment with
DMAD. On the contrary, adduct 11, which is a regio isomer of 10a,
did not react with the second DMAD molecule as a dienophile.
Apparently, the reason for this is a different reactivity of the two
thione groups in 11 and 10a. The thione group in 11 structurally is
a thioamide group neutral to 1,3-dipolar cycloaddition. Also iso-
mers 10a and 11 have a striking difference in color and electronic
S
2 DMAD, benzene,
boiling for 1 h
S
S
S
N
R
S
N
R
CO2Me
CO2Me
9a-d, 100%
5
DMAD
DMAD
a R = Me
b R = Et
c R = Pri
d R = Bn
S
S
CO2Me
CO2Me
spectra: 10a is crystallized as violet plates with h
n
578 nm
+ 9a-d
(lg 450 nm (lg
3
¼3.79) and 11 as red prisms (h
n
3
¼3.92)). This dif-
N
S
ference can be explained by an additional opportunity of electronic
delocalization for 11 and its low possibility for 10a due to a loss of
the indole ring aromaticity (Scheme 8).
R
48-55%
10a-d, 25-35%
Scheme 6. Reaction of 1,2-dithiole-3-thiones 5 with DMAD.
S
S_
CO2Me
CO2Me
CO2Me
CO2Me
S
S
S
S
+
N
Me
N
Me
N-substituted [1,2]dithiolo[4,3-b]indole-3(4H)-thiones
5
and
DMAD in the same ratio and in the same conditions gave, re-
spectively, products 9 in the form of yellow solids, all in practically
quantitative yields. It was observed (TLC) that in each reaction
a blue spot initially appeared, which then disappeared as the re-
actants were consumed. We concluded that under thermal condi-
tions the first cycloaddition reaction of 5 with DMAD was more
energy demanding than the corresponding reaction of the expected
highly reactive 1:1 cycloadduct 10 and DMAD. In search of the in-
termediate 1:1 adduct 10 we performed a reaction of 5 (1 equiv)
and DMAD (1 equiv) in benzene at lower temperature. During 3
days, both at 5 ꢀC and at room temperature, we managed to isolate
monoadducts 10 (25–35%) and bisadducts 9 (48–55%) after chro-
matography (Scheme 6). Monoadducts 10 reacted with 1 equiv of
DMAD in benzene refluxing for a few minutes to give 9 in quanti-
tative yield.
10a
MeO2C
S
MeO2C
S
CO2Me
CO2Me
S
S
S_
S
+
N
Me
N
Me
11
Scheme 8. Resonance structures for 10a and 11.
3. Conclusion
Treatment of thione 6 (1 equiv) with a DMAD excess (2.4 equiv)
in benzene under reflux (1 h) gave monoadduct 11 (18%)8 along
with ketone 12 (23%) (Scheme 7). No traces of the expected 1:2
adduct 13 were observed. Only product 11 was obtained in high
yield (72%) in the reaction of 6 (1 equiv) and DMAD (1.2 equiv) in
benzene at room temperature. The generation of ketone 12 in the
reactions of 1,2-dithiole-3-thione 6 with DMAD was unexpected,
and we investigated this process further. Thione 6 was found to be
perfectly stable in benzene solutions under reflux for 10 h, yet the
reaction with DMAD (a fivefold excess) in refluxing benzene gave
ketone 12 in moderate yield (65%).
The reaction of N-substituted 2-methylindoles with S2Cl2 pro-
vides a new route to [1,2]dithiolo[4,3-b]indole-3(4H)-thiones 5,
which are of special interest as biologically active compounds. The
novelty of the reaction is the formation of condensed 1,2-dithiole-
3-thiones from methyl-substituted heterocycles (in our case 2-
methylindoles). The described experimental procedures may serve
as an efficient basis for a new synthesis of fused 1,2-dithiole-3-
thiones from methyl-substituted heterocycles and their further
cycloaddition to highly branched sulfur heterocycles.
4. Experimental
4.1. General
DMAD
MeO2C
S
MeO2C
S
Melting points were determined on a Kofler hot-stage apparatus
and are uncorrected. IR spectra were recorded on a Specord M-80
instrument in KBr pellets. 1H NMR spectra were recorded on
a Bruker WM 250 spectrometer (250 MHz) and 13C NMR spectra
were recorded on a Bruker AM 300 (75.5 MHz) in CDCl3 or pyri-
dine-d5 solutions with TMS as an internal standard. J values are
given in hertz. Mass spectra were recorded on a Finnigan MAT
INCOS 50 instrument using electron impact ionization. UV spectra
were recorded on a Specord UV–VIS. Elemental analyses were
performed on Perkin Elmer 2400 Elemental Analyser.
CO2Me
CO2Me
S
S
S
S
S
DMAD
+
S
O
N
Me
N
N
Me
Me
11, 18%
CO2Me
CO2Me
6
12, 23%
MeO2C
Compounds 117 and 69 were prepared as previously reported.
S
S
CO2Me
4.1.1. General procedure for the preparation of N-substituted
[1,2]dithiolo[4,3-b]indole-3(4H)-thiones 5
Disulfur dichloride (0.4 mL, 5 mmol) was added dropwise at
ꢁ25 to ꢁ35 ꢀC to a stirred solution of DABCO (1.12 g, 10 mmol) in
chloroform (25 mL) under argon. The mixture was stirred at room
S
N
Me
13
Scheme 7. Reaction of 1,2-dithiole-3-thione 6 with DMAD.

L.S. Konstantinova et al. / Tetrahedron 65 (2009) 2178–2183
2181
temperature for 1 h. The corresponding N-substituted 2-methyl-
1H-indole 1 (1 mmol) in chloroform (5 mL) was added and the
mixture was stirred at room temperature for 48 h under argon.
Then Et3N (1.4 mL, 10 mmol) was added at 0 ꢀC, the mixture was
stirred at room temperature for 2 h, refluxed for 3 h, filtered, and
the solvents were evaporated. The residue was separated by col-
umn chromatography (Silica gel Merck 60, light petroleum and
then light petroleum–CH2Cl2 mixtures).
4.1.3. 2,5-Dichloro-1,3-dimethyl-1H-indole (8)
Disulfur dichloride (1 mL, 12.5 mmol) was added dropwise at
ꢁ35 to ꢁ25 ꢀC to
a stirred solution of anhydrous N-ethyl-
diisopropylamine (1.6 g, 12.5 mmol) in chloroform (100 mL) under
argon. The mixture was stirred at this temperature for 1 h. 1,3-
Dimethylindole (0.36 g, 2.5 mmol) in chloroform (10 mL) was
added, the mixture was stirred for 72 h at 0 ꢀC, filtered, and the
solvents were evaporated. The residue was separated by column
chromatography (Silica gel Merck 60, light petroleum and then
light petroleum–CH2Cl2 mixtures), yield 180 mg (34%). Yellow oil,
Rf¼0.65 (CH2Cl2/light petroleum, 1:1). Anal. Calcd for C10H9Cl2N:
C, 56.10; H, 4.24; N, 6.54. Found: C, 56. 01; H, 4.18; N, 6.72. 1H
4.1.1.1. 4-Methyl[1,2]dithiolo[4,3-b]indole-3(4H)-thione (5a). Yield
94%. Orange crystalline solid, mp 165–167 ꢀC; Rf¼0.69 (CH2Cl2).
Anal. Calcd for C10H7NS3: C, 50.60; H, 2.97; N, 5.90. Found: C, 50.42;
H, 2.87; N, 6.02. C10H7NS3 requires M, 236.9741. Found Mþ,
NMR (250 MHz, CDCl3)
d: 2.29 (3H, s, C–CH3), 3.63 (3H, s, N–CH3),
236.9741. 1H NMR (250 MHz, CDCl3)
d
: 4.30 (3H, s, CH3), 7.25 (1H, m,
7.12 (1H, d, J 10.4, Ar), 7.22 (1H, s, Ar), 7.38 (1H, d, J 7.9, Ar). 13C
Ar), 7.44 (1H, d, J 8.5, Ar), 7.57 (1H, m, Ar), 7.77 (1H, d, J 7.9, Ar). 13C
NMR (75.5 MHz, CDCl3) d: 8.7 (C–CH3), 29.8 (N–CH3), 109.0, 119.2,
NMR (75.5 MHz, CDCl3)
d
: 28.9 (CH3), 111.5, 121.0, 121.2, and 129.1
and 120.1 (3CH), 107.7, 124.1, 125.8, 127.8, and 135.9 (five sp2
tertiary C). MS (EI, 70 eV), m/z (%): 213 (Mþ, 88), 178 (100), 162
(25), 128 (23).
(4 CH), 120.4, 141.0, 141.1, and 146.3 (four sp2 tertiary C), 195.3
(C]S). MS (EI, 70 eV), m/z (%): 237 (Mþ, 100), 204 (48), 191 (40), 145
(36). UV lmax (CHCl3) 256 (lg
(3.95). IR (KBr):
¼1612, 1436, 1336, 1228, 1132, 1040, 900,
736 cmꢁ1
3
¼3.93), 340 (4.14), 381 (3.85), 463
n
4.1.4. General procedure for the reaction of N-substituted
dithioloindole thiones 5 and 6 with DMAD
.
DMAD (1.2 or 2.4 mmol) was added to a solution of appropriate
dithioloindolethione (1 mmol) in benzene (7 mL) at room tem-
perature. The reaction mixture was stirred for 24 h at room tem-
perature or refluxed for 1 h and solvent was evaporated under
reduced pressure. The residue was separated by column chroma-
tography (Silica gel Merck 60, light petroleum, then light petro-
leum–CH2Cl2 mixtures, then CH2Cl2). Quantity of reagents is given
in the text.
4.1.1.2. 4-Ethyl[1,2]dithiolo[4,3-b]indole-3(4H)-thione
(5b). Yield
56%. Orange crystalline solid, mp 90–91 ꢀC; Rf¼0.71 (CH2Cl2).
Anal. Calcd for C11H9NS3: C, 52.55; H, 3.61; N, 5.57. Found: C,
52.53; H, 3.78; N, 5.58. 1H NMR (250 MHz, CDCl3)
d: 1.37 (3H, t, J
7.2, CH3), 4.83 (2H, q, J 7.2, CH2), 7.18 (1H, m, Ar), 7.38 (1H, d, J 8.5,
Ar), 7.50 (1H, m, Ar), 7.70 (1H, d, J 7.9, Ar). 13C NMR (75.5 MHz,
CDCl3)
d: 16.0 (CH3), 37.7 (CH2), 111.6, 121.1, 121.4, and 129.1
(4CH), 120.7, 140.7, 141.3 and 145.4 (four sp2 tertiary C), 194.8
(C]S). MS (EI, 70 eV), m/z (%): 251 (Mþ, 100), 236 (75), 223 (42),
4.1.4.1. Tetramethyl
50-methyl-50H-spiro[1,3-dithiole-2,40-thiopyr-
218 (20), 191 (39). IR (KBr):
n
¼1612, 1480, 1340, 1208, 1050, 908,
ano[3,2-b]indole]-20,30,4,5-tetracarboxylate (9a). Yield 100%. Yellow
crystalline solid, mp 201–203 ꢀC; Rf¼0.47 (CH2Cl2). Anal. Calcd for
C22H19NO8S3: C, 50.66; H, 3.67; N, 2.69. Found: C, 50.40; H, 3.84; N,
752 cmꢁ1
.
4.1.1.3. 4-Isopropyl[1,2]dithiolo[4,3-b]indole-3(4H)-thione (5c). Yield
66%. Orange crystalline solid, mp 104–107 ꢀC; Rf¼0.73 (CH2Cl2). Anal.
Calcd for C12H11NS3: C, 54.30; H, 4.18; N, 5.28. Found: C, 54.58; H,
2.68. 1H NMR (250 MHz, CDCl3)
d: 3.77 (6H, s, CH3), 3.80 (3H, s,
CH3), 3.87 (3H, s, CH3), 4.13 (3H, s, N–CH3), 7.24 (1H, m, Ar), 7.44
(1H, m, Ar), 7.62 (1H, d, J 8.1, Ar), 7.74 (1H, d, J 8.6, Ar). 13C NMR
4.34; N, 5.26. 1H NMR (250 MHz, CDCl3)
d
: 1.70 (6H, d, J 7.4, CH3), 4.74
(1H, septet, J 7.4, CH), 7.23 (1H, m, Ar), 7.51 (1H, d, J 7.4, Ar), 7.71 (1H,
m, Ar), 7.78 (1H, d, J 8.1, Ar). 13C NMR (75.5 MHz, CDCl3)
: 21.3 (CH3),
(75.5 MHz, CDCl3) d: 33.2 (N–CH3), 53.2, 53.3, and 53.8 (3CH3), 65.7
(sp3 tertiary), 102.1, 122.0, 122.6, 125.2, 128.0, and 139.4 (six sp2
tertiary C), 110.1, 118.9, and 127.3 (3CH), 160.8, 164.0, and 165.8
(3C]O). MS (EI, 70 eV), m/z (%): 521 (Mþ, 9), 462 (31), 430 (7), 346
d
44.0 (CH), 114.6, 120.7, 121.6, and 128.6 (4CH), 121.0, 139.8, 142.1, and
144.2 (four sp2 tertiary C), 195.2 (C]S). MS (EI, 70 eV), m/z (%): 265
(Mþ, 100), 250 (97), 232 (17), 223 (98), 191 (57), 146 (75). IR (KBr):
(27). UV lmax (CHCl3) 284 (lg
3
¼4.21), 396 (3.63). IR (KBr): ¼1736
n
(C]O), 1560, 1432, 1248, 1020, 936, 744 cmꢁ1
.
n
¼1608, 1464, 1332, 1228, 1140, 1028, 912, 736 cmꢁ1
.
4.1.4.2. Tetramethyl
50-ethyl-50H-spiro[1,3-dithiole-2,40-thiopyr-
4.1.1.4. 4-Benzyl[1,2]dithiolo[4,3-b]indole-3(4H)-thione (5d). Yield
70%. Orange crystalline solid, mp 120–123 ꢀC; Rf¼0.62 (CH2Cl2).
Anal. Calcd for C16H11NS3: C, 61.31; H, 3.54; N, 4.47. Found: C, 61.56;
ano[3,2-b]indole]-20,30,4,5-tetracarboxylate (9b). Yield 100%. Yellow
crystalline solid, mp 205–206 ꢀC; Rf¼0.49 (CH2Cl2). Anal. Calcd for
C23H21NO8S3: C, 51.58; H, 3.95; N, 2.62. Found: C, 51.73; H, 4.23; N,
H, 3.69; N, 4.46. 1H NMR (250 MHz, CDCl3)
d
: 6.20 (2H, s, CH2), 7.25
(6H, m, Ar), 7.38 (1H, d, J 8.5, Ar), 7.47 (1H, m, Ar), 7.80 (1H, d, J 7.9,
Ar). 13C NMR (75.5 MHz, CDCl3)
: 44.2 (CH2), 112.4, 121.3, 121.4,
2.52. 1H NMR (250 MHz, CDCl3)
d: 1.61 (3H, t, J 7.3, CH3), 3.83 (6H, s,
CH3), 3.90 (3H, s, CH3), 3.93 (3H, s, CH3), 4.78 (2H, q, J 7.3, CH2), 7.24
d
(1H, m, Ar), 7.46 (3H, m, Ar). 13C NMR (75.5 MHz, CDCl3)
d: 13.8
127.0, 127.5, 128.7, and 129.2 (7CH), 120.7, 137.2, 140.4, 141.8, and
(CH2CH3), 41.0 (CH2CH3), 53.2, 53.3, 53.5, and 53.8 (4CH3), 66.1 (sp3
tertiary), 102.4, 121.8, 123.0, 127.3, 128.4, and 138.4 (six sp2 tertiary
C), 110.8, 119.0, 121.1, and 125.2 (4CH), 160.8, 163.9, and 165.8
(3C]O). MS (EI, 70 eV), m/z (%): 535 (Mþ, 1), 476 (2), 360 (3), 301
145.9 (five sp2 tertiary C), 194.7 (C]S). MS (EI, 70 eV), m/z (%): 313
(Mþ, 17), 280 (13), 264 (7), 249 (6), 191 (15). IR (KBr):
n
¼1608, 1472,
1436, 1332, 1252, 1060, 880, 744 cmꢁ1
.
(5). IR (KBr):
n
¼1732 (C]O), 1560, 1428, 1252, 1020, 940, 736 cmꢁ1
.
4.1.2. 8-Methyl[1,2]dithiolo[3,4-b]indole-3(8H)-thione (6)
Yellow crystalline solid, mp 232–233 ꢀC, lit.9 mp 234–236 ꢀC;
4.1.4.3. Tetramethyl 50-isopropyl-50H-spiro[1,3-dithiole-2,40-thiopyr-
ano[3,2-b]indole]-20,30,4,5-tetracarboxylate (9c). Yield 100%. Yellow
crystalline solid, mp 203–206 ꢀC; Rf¼0.51 (CH2Cl2). Anal. Calcd for
C24H23NO8S3: C, 52.44; H, 4.22; N, 2.55. Found: C, 52.44; H, 4.35; N,
Rf¼0.68 (CH2Cl2). 1H NMR (250 MHz, CDCl3)
d: 3.73 (3H, s, CH3),
7.30 (2H, m, Ar), 7.38 (1H, m, Ar), 8.55 (1H, d, J 7.9, Ar). 13C NMR
(75.5 MHz, CDCl3)
d: 32.3 (CH3), 110.9, 118.0, 122.7, and 124.8
(4CH), 122.1, 127.5, 143.8, and 162.6 (four sp2 tertiary C), 198.1
2.56. 1H NMR (250 MHz, CDCl3)
d: 1.77 (6H, d, J 6.6, CH3), 3.83 (6H, s,
(C]S). MS (EI, 70 eV), m/z (%): 237 (Mþ, 100), 204 (62), 191 (24),
2 CH3), 3.90 (3H, s, CH3), 3.92 (3H, s, CH3), 5.77 (1H, septet, J 6.6,
CH), 7.20 (1H, m, Ar), 7.33 (1H, m, Ar), 7.50 (1H, d, J 8.1, Ar), 7.69 (1H,
172 (17), 160 (37). UV lmax (CHCl3) 288 (lg
(3.85). IR (KBr):
¼1584, 1480, 1464, 1312, 1200, 1128, 1076, 980,
744 cmꢁ1
3¼4.23), 342 (4.05), 398
n
d, J 8.8, Ar). 13C NMR (75.5 MHz, CDCl3)
d
: 19.9 (CH(CH3)2), 49.9
.
(CH(CH3)2), 53.2, 53.3, and 53.8 (3 CH3), 66.3 (sp3 tertiary), 102.3,

2182
L.S. Konstantinova et al. / Tetrahedron 65 (2009) 2178–2183
123.9, 121.5, 127.0, 127.4, 128.5, 128.7, and 136.8 (eight sp2 tertiary
C), 113.7, 119.2, 120.6, and 124.6 (4CH), 160.8, 163.9, and 165.8
(3C]O). MS (EI, 70 eV), m/z (%): 549 (Mþ, 1), 490 (3), 416 (3), 374
C
22H17NO4S3: C, 58.00; H, 3.76; N, 3.07. Found: C, 58.20; H, 3.94; N,
3.06. 1H NMR (250 MHz, CDCl3)
: 3.90 (3H, s, CH3), 3.97 (3H, s,
CH3), 5.55 (2H, s, CH2), 7.13 (3H, m, Ar), 7.31 (4H, m, Ar), 7.49 (1H, m,
Ar), 8.03 (1H, d, J 8.1, Ar). 13C NMR (75.5 MHz, CDCl3)
: 49.6 (CH2),
d
(64), 301 (72). IR (KBr):
n
¼1732 (C]O), 1564, 1428, 1244, 1020, 988,
d
740 cmꢁ1
.
53.7 (CH3), 110.4, 120.8, 124.5, 126.0, 127.7, 129.0, and 132.9 (7CH),
114.1, 131.9, 133.2, 136.4, 136.7, 137.7 and 148.8 (seven sp2 tertiary
C), 159.3 and 160.4 (2C]O), 183.3 (C]S). MS (EI, 70 eV), m/z (%):
455 (Mþ, 10), 364 (85), 313 (4), 297 (5), 280 (5), 146 (42). IR (KBr):
4.1.4.4. Tetramethyl
50-benzyl-50H-spiro[1,3-dithiole-2,40-thiopyr-
ano[3,2-b]indole]-20,30,4,5-tetracarboxylate (9d). Yield 100%. Yellow
crystalline solid, mp 162–164 ꢀC; Rf¼0.41 (CH2Cl2). Anal. Calcd for
C28H23NO8S3: C, 56.27; H, 3.88; N, 2.34. Found: C, 56.39; H, 3.80; N,
n
¼1736 and 1724 (C]O), 1608, 1588, 1492, 1436, 1268, 1100, 1024,
736 cmꢁ1
.
2.31. 1H NMR (250 MHz, CDCl3)
d: 3.74 (6H, s, 2CH3), 3.90 (3H, s,
CH3), 3.92 (3H, s, CH3), 6.00 (2H, s, CH2), 7.02 (2H, m, Ar), 7.23 (6H,
4.1.4.9. Dimethyl 2-(1-methyl-2-thioxo-1,2-dihydro-3H-indol-3-yli-
dene)-1,3-dithiole-4,5-dicarboxylate (11). Yield 16%. Red crystalline
solid, mp 242–244 ꢀC, lit.8 mp 243–244 ꢀC; Rf¼0.24 (CH2Cl2). 1H
m, Ar), 7.56 (1H, d, J 7.9, Ar). 13C NMR (75.5 MHz, CDCl3)
d: 49.5
(CH2), 53.1 and 53.8 (2CH3), 65.9 (sp3 tertiary), 103.1, 122.5, 125.6,
127.2, 127.4, 128.3, 128.6, and 139.4 (eight sp2 tertiary C), 111.4,
119.0, 121.4, 122.8, 126.1, 127.0, and 136.6 (7CH), 160.5, 163.8, and
165.7 (3C]O). MS (EI, 70 eV), m/z (%): 598 (Mþ, 2), 538 (9), 504 (7),
NMR (250 MHz, CDCl3) d: 3.77 (3H, s, N–CH3), 3.99 (3H, s, CH3), 4.00
(3H, s, CH3), 7.32 (1H, m, Ar), 7.35 (2H, m, Ar), 7.77 (1H, d, J 7.9, Ar).
MS (EI, 70 eV), m/z (%): 379 (Mþ, 60), 320 (7), 237 (100), 204 (40),
191 (17), 172 (18), 160 (13), 146 (15). UV lmax (CHCl3) 304
478 (7), 422 (100). IR (KBr):
n
¼1748 (C]O), 1572, 1436, 1236, 1044,
920, 740 cmꢁ1
.
(lg
3
¼4.27), 310 (4.34), 398 (4.19), 450 (3.92). IR (KBr): ¼1756 and
n
1728 (C]O), 1576, 1520, 1428, 1356, 1216, 1072, 744 cmꢁ1
.
4.1.4.5. Dimethyl 2-(1-methyl-3-thioxo-1,3-dihydro-2H-indol-2-yli-
dene)-1,3-dithiole-4,5-dicarboxylate (10a). Yield 32%. Violet crys-
talline solid, mp 219–221 ꢀC; Rf¼0.26 (CH2Cl2). Anal. Calcd for
C16H13NO4S3: C, 50.64; H, 3.45; N, 3.69. Found: C, 50.52; H, 3.62; N,
4.1.4.10. Dimethyl
2-(1-methyl-2-oxo-1,2-dihydro-3H-indol-3-yli-
dene)-1,3-dithiole-4,5-dicarboxylate (12). Yield 23%. Yellow crys-
talline solid, mp 199–203 ꢀC; Rf¼0.15 (CH2Cl2). Anal. Calcd for
C16H13NO5S2: C, 52.88; H, 3.61; N, 3.85. Found: C, 52.62; H, 3.52; N,
3.66. 1H NMR (250 MHz, CDCl3)
d
: 3.93 (6H, s, CH3), 3.98 (3H, s, N–
CH3), 7.07 (1H, m, Ar), 7.21 (1H, d, J 7.8, Ar), 7.56 (1H, m, Ar), 7.98
(1H, d, J 7.6, Ar). 13C NMR (75.5 MHz, CDCl3)
: 34.0 (N–CH3), 53.8
3.98. 1H NMR (250 MHz, CDCl3)
d
: 3.35 (3H, s, N–CH3), 3.97 (6H, s,
CH3), 6.92 (1H, d, J 8.1, Ar), 7.15 (1H, m, Ar), 7.25 (1H, m, Ar), 7.40
(1H, d, J 6.6, Ar). 13C NMR (75.5 MHz, CDCl3)
: 29.7 (N–CH3), 53.7
d
(CH3), 110.0, 120.4, 124.5, and 128.0 (4CH), 129.1, 131.8, 133.5, 137.2,
143.8, and 149.1 (six sp2 tertiary C), 159.3 and 160.6 (2C]O), 182.9
(C]S). MS (EI, 70 eV), m/z (%): 379 (Mþ, 17), 237 (100), 204 (47), 191
d
(CH3), 108.0, 121.2, 121.9, and 126.8 (4CH), 114.0, 128.5, 128.9, 137.0,
139.3, and 140.6 (six sp2 tertiary C), 159.3 and 160.1 (2C]O), 165.5
(C]O). MS (EI, 70 eV), m/z (%): 363 (Mþ, 100), 304 (22), 276 (8), 246
(22), 146 (42). UV lmax (CHCl3) 254 (lg
(4.22), 578 (3.79). IR (KBr):
¼1740 and 1712 (C]O), 1608, 1584,
1496, 1432, 1260, 1100, 988, 740 cmꢁ1
3¼4.03), 283 (4.04), 408
n
(8), 189 (90), 160 (58), 146 (27). IR (KBr):
n
¼1716 and 1676 (C]O),
.
1576, 1468, 1376, 1292, 1036, 736 cmꢁ1
.
4.1.4.6. Dimethyl
2-(1-ethyl-3-thioxo-1,3-dihydro-2H-indol-2-yli-
Acknowledgements
dene)-1,3-dithiole-4,5-dicarboxylate (10b). Yield 35%. Violet crys-
talline solid, mp 202–204 ꢀC; Rf¼0.25 (CH2Cl2). Anal. Calcd for
C17H15NO4S3: C, 51.89; H, 3.84; N, 3.56. Found: C, 51.81; H, 3.77;
We gratefully acknowledge financial support from the Russian
Foundation for Basic Research (grant no. 05-03-32032).
N, 3.69. 1H NMR (250 MHz, CDCl3)
d: 1.34 (3H, t, J 7.3, CH3), 3.97
(3H, s, CH3), 3.99 (3H, s, CH3), 4.35 (2H, q, J 7.3, CH2), 7.05 (1H, m,
Ar), 7.20 (1H, d, J 8.1, Ar), 7.52 (1H, m, Ar), 7.97 (1H, d, J 8.1, Ar).
References and notes
13C NMR (75.5 MHz, CDCl3)
d: 15.2 (CH3CH2), 41.1 (CH3CH2), 53.9
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Rees, C. W., Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996; Vol. 3; Chapter 3.11,
(CH3), 110.1, 120.5, 124.7, and 132.9 (4CH), 129.0, 132.3, 133.9,
136.1, 136.8, and 148.4 (six sp2 tertiary C), 159.5 and 160.7
(2C]O), 184.1 (C]S). MS (EI, 70 eV), m/z (%): 393 (Mþ, 12), 364
(8), 251 (61), 236 (34), 223 (19), 191 (49), 146 (100). IR (KBr):
n
¼1748 and 1712 (C]O), 1608, 1584, 1496, 1236, 1092, 992,
744 cmꢁ1
.
4.1.4.7. Dimethyl 2-(1-isopropyl-3-thioxo-1,3-dihydro-2H-indol-2-
ylidene)-1,3-dithiole-4,5-dicarboxylate (10c). Yield 31%. Violet
crystalline solid, mp 153–156 ꢀC; Rf¼0.23 (CH2Cl2). Anal. Calcd for
C18H17NO4S3: C, 53.05; H, 4.20; N, 3.44. Found: C, 53.09; H, 4.39; N,
3.44. 1H NMR (250 MHz, CDCl3)
d
: 1.59 (6H, d, J 7.4, CH3), 3.98 (6H, s,
CH3), 4.86 (2H, septet, J 7.4, CH), 7.09 (1H, m, Ar), 7.44 (2H, m, Ar),
7.99 (1H, d, J 8.1, Ar). 13C NMR (75.5 MHz, CDCl3)
: 21.5 ((CH3)2CH),
ˇ
´
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50.3 ((CH3)2CH), 53.8 and 53.9 (2CH3), 114.3, 121.0, 125.0, and 132.0
(4CH), 130.3, 133.8, 134.3, 138.4, 139.1, and 148.9 (six sp2 tertiary C),
159.6 and 160.5 (2C]O), 185.3 (C]S). MS (EI, 70 eV), m/z (%): 407
(Mþ, 25), 364 (67), 265 (20), 250 (14), 223 (30), 191 (21), 146 (100).
IR (KBr):
n
¼1720 (C]O), 1604, 1588, 1484, 1444, 1256, 1096,
748 cmꢁ1
.
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dene)-1,3-dithiole-4,5-dicarboxylate (10d). Yield 25%. Violet crys-
talline solid, mp 189–193 ꢀC; Rf¼0.19 (CH2Cl2). Anal. Calcd for

L.S. Konstantinova et al. / Tetrahedron 65 (2009) 2178–2183
2183
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