A new synthetic method for the 2H-[1,2,3]thiadiazolo[5,4-b]indoles

Article abstract of DOI:10.1016/j.tet.2007.01.059

The systematic study of oxidative cyclization of 3-hydrazono-1,3-dihydroindole-2-thiones has been carried out and a series of new?2H-[1,2,3]thiadiazolo[5,4-b]indoles has been prepared. The elaborated reaction represents an efficient method for the synthes

Full text of DOI:10.1016/j.tet.2007.01.059

Tetrahedron 63 (2007) 3042–3048
A new synthetic method for the 2H-[1,2,3]thiadiazolo[5,4-b]indoles
a
Maria L. Kondratieva,a Anna V. Pepeleva,a Natalia P. Belskaia,a, Alexandr V. Koksharov,
*
Paul V. Groundwater,b Koen Robeyns,c Luc Van Meervelt,c Wim Dehaen,c Zhi-Jin Fand
and Vasiliy A. Bakuleva
aDepartment of Chemistry, Urals State Technical University, 620002 Ekaterinburg, Mira Str. 19, Russia
bUniversity of Sunderland, Warncliffe Street, Sunderland SR1 3SD, UK
cDepartment of Chemistry, K.U. Leuven, Celestijnenlaan 200F, B-3001, Leuven, Belgium
dState Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, People’s Republic of China
Received 21 October 2006; revised 19 January 2007; accepted 25 January 2007
Available online 30 January 2007
Abstract—The systematic study of oxidative cyclization of 3-hydrazono-1,3-dihydroindole-2-thiones has been carried out and a series of
new 2H-[1,2,3]thiadiazolo[5,4-b]indoles has been prepared. The elaborated reaction represents an efficient method for the synthesis of fused
1,2,3-thiadiazoles.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
diazo group transfer with tosyl azide in indole-2-thiones.9
But this method has not found wider application because
of the formation of a by-product—bi-indoline-2,20-thione,
taking a different course of reaction and because of a rather
moderate yield of the parent compounds.
Synthetic methods for preparation of 1,2,3-thiadiazoles an-
nelated to other ring systems continue to attract considerable
attention because of their importance in medicinal chemis-
try, and especially due to the fact that the first chemical plant
activator was found to be a derivative of benzo-[1,2,3]-
thiadiazole.1–3 The known methods leading to fused 1,2,3-
thiadiazoles include reactions of hydrazones of cyclic
ketones with thionyl chloride (Hurd–Mori synthesis),4 gen-
eration and concomitant cyclization of a-diazothiocarbonyl
compounds (Wolff synthesis),4,5 ring transformation of other
sulfur-containing heterocyclic compounds and inter- and
intramolecular cyclization of preformed 1,2,3-thiadiazoles.4
Indeed, the purpose of our work was synthesis of the 3-
hydrazono-2,3-dihydroindolthionesandinvestigationoftheir
oxidative cyclization leading to 1,2,3-thiadiazoloindoles.
2. Results and discussion
The starting hydrazones 1a–g were prepared either by con-
densation of isatin with hydrazines10,11 or azocoupling of
aryldiazonium salts with indole-2-one.12 3-[(Thiazol-2-yl)-
hydrazono]-1,3-dihydroindole-2-ones 3a–c were prepared
by reacting thiosemicarbazone 2g with bromoacetophenones
2a–c in ethanol in 90% yield (Scheme 1).
Previously, we reported that oxidative cyclization of 2-hydra-
zonothiocarbonyl compounds with halogens proceeded
smoothly to afford corresponding monocyclic 1,2,3-thiadia-
zoles, namely, 2-aryl-2,5-dihydro-1,2,3-thiadiazol-5-imines.6
We decided to extend this method to prepare 1,2,3-thiadiazole
fused with heterocycle system. A convenient heterocycle
model for this type of investigation is indole as the starting
3-hydrazono-1,3-dihydro-indol-2-ones are readily available
and due to the interesting biological property of indoles.7–9
Transformation of the amide group into thioamide function
was carried out by reacting indoles 1a–f and 3a–c with Law-
esson’s reagent in boiling xylene (Scheme 1). 1H NMR spec-
tra of isatin hydrazones 1,3 and corresponding thiones 4a–j
show that they exist predominantly as the Z (cis) conforma-
tion in DMSO-d6 solution, presumably due to intramolecular
hydrogen bond between the NH of the hydrazone moiety and
the carbonyl (or thiocarbonyl) group of the indolinone. It
should be noted that in some analogues where a heteroatom
(O or N)-containing functionality was substituted at the
4-position of the oxoindole, allowing formation of the
It should be noted that only two derivatives of 4H-[1,2,3]thia-
diazolo[5,4-b]indole are known and they were prepared by
Keywords: Thioamide; Indole; 1,2,3-Thiadiazole; Hydrazone; Oxidative
cyclization; 1,2,3-Thiadiazolo[5,4-b]indoles.
* Corresponding author. E-mail: belska@htf.ustu.ru
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.01.059

M. L. Kondratieva et al. / Tetrahedron 63 (2007) 3042–3048
3043
Ar
R
O
N
N
Br
N
Ar
H
N
O
2
S
N
H
O
R=CSNH2
N
N
H
H
3
1
1a: R= Me
L.R.
2,3a : Ar=4-MeOC6H4
2, 3b: Ar=Ph,
L.R
1b: R=Bn
xylene
xylene
1c: R=4-EtOC6H4
1d: R=4-MeOC6H4
1e: R=4-BnOC6H4
1f: R=Ph
1g: R=4-ClC6H4
1h: R=CSNH2
2, 3c:Ar=4-ClC6H4
R
H
N
R
N
H
N
N
S
S
N
N
H
H
4 Z-isomer
4 E-isomer
e
g
4-ClC6H4
60
4
a
b
c
d
f
C6H4,
77
R
Me
51
Bn 4-EtOC6H4 4-MeOC6H4
4-BnOC6H4
75
48
87
74
Yield, %
j
4
R
h
i
4-(4-MeOC6H4)-thiazolyl 4-Ph-thiazolyl 4-(4-ClC6H4)-thiazolyl
99
70
96
Yield, %
L.R. = Lawesson's reagent
Scheme 1.
alternative hydrogen bond with NH function in E (trans)
conformation, H NMR spectra revealed the mixture of Z
(cis) conformation. The weak hydrogen bond between the
sulfur atom and the NH proton of the hydrazone group
(NH/S) practically forms a third six-membered ring, in
1
and E isomers.11
˚
the same plane as the indole group (d(NH)¼0.86 A, d(H/
ꢀ
˚
Of particular significance is the low field resonance for the
NH proton of the hydrazone group (at d 2.5 ppm) in arylhy-
drazono-1,3-dihydroindole-2-thiones 4 in comparison with
the parent hydrazones 1,3. The substituent in the aryl group
has the strongest effect on the NH-resonance of the hydra-
zone fragment and less on the NH-resonance of the indole.
Electron-withdrawing groups lead to significant deshielding
of the former signal (to 2.09 ppm) and less deshielding of the
latter one (to 0.5 ppm). The same influence was observed in
the 13C spectra for the signals of the thiocarbonyl and C3
indole atoms. Electron-withdrawing groups increase the
polarization of the thiocarbonyl and C3 atom, thereby caus-
ing deshielding of the carbon atom (CS for 2.5 ppm, C3 for
1.3 ppm).
S)¼2.37 A, ang(NH/S)¼140.6 ).
Thus, a series of 3-hydrazono-1,3-dihydroindole-2-thiones
4a–j, containing alkyl-, aryl- and heteroarylhydrazono
groups were successfully prepared. It should be noted
that conformation of Z-isomer is more suitable for the fol-
lowing interaction between sulfur atom and NH-hydrazone
fragment.
We have investigated the following protocols for oxidative
cyclization of hydrazonothiocarbonyl compounds 4a–j: (a)
bromine in acetic acid, (b) N-chlorosuccinimides in ethyl
acetate at 0–5 ꢀC, (c) iodine in ethanol. One can conclude
from the experimental data that the oxidation with bromine
in acetic acid (a) and with N-chlorosuccinimide (b) are the
methods of choice (Scheme 2).
The X-ray analysis (Fig. 1) of compound 4a confirms that
the hydrazono-1,3-dihydroindole-2-thiones adopt the Z
Based on what is known on the formation of corresponding
monocyclic 1,2,3-thiadiazoles6 we propose that the mecha-
nism of the reaction leading to thiadiazoloindoles 5 involves
the formation of intermediate adduct A followed by cycliza-
tion with the participation of a nitrogen atom of the hydra-
zono group to give the final products 5 (Scheme 2).
In a similar way to the monocyclic 1,2,3-thiadiazol-5-
imines, 5 are unstable and therefore they were characterized
as their salts with hydrogen halides.
In contrast to the starting thioamides 4, NMR spectra of 5 do
not contain proton signals of hydrazone. The signals of the
aromatic protons are shifted downfield by about 0.5 ppm.
Moreover, the proton signals by the methyl and benzyl
groups in compounds 5a,g,h,n, are also shifted downfield
by 0.5–1 ppm. These signals are displayed as doublets in
Figure 1. X-ray crystal structure of 4a.

3044
M. L. Kondratieva et al. / Tetrahedron 63 (2007) 3042–3048
1. NCS
2. NBS
3. I2
R
NNHR
S
N
N
N
R
H
N
S
S
-HHal
Hal
N
H
N
HHal
N
4 a-n
A
5 a-n
5
HHal
R
a
b
c
d
e
f
HCl
HCl
HCl
HCl
HCl
HCl
Me 4-EtOC6H4 4-BnOC6H4 4-ClC6H4 4-(4-MeOC6H4)-thiazolyl 4-(4-ClC6H4)-thiazolyl
Yield, % 85
60
69
51
42
33
g
j
5
h
i
k
l
m
HI
n
HBr
Me
93
HBr
Bn
60
HBr
Ph
99
HBr
4-Ph-thiazolyl
86
HI
Ph
57
HBr
4-MeOC6H4
HBr
4-EtOC6H4
HHal
R
Me
Yield, %
60
57
55
Scheme 2.
the thioamides 4 and as singlets in thiadiazoles 5. The 13C
NMR spectra show that annelation of the thiadiazole ring
to the indole leads to a downfield shift of the C-2 and C-3
indole signals by 30–40 ppm. It is remarkable that almost
all signals of thiadiazoloindoles 5 are downfield shifted by
2–5 ppm in comparison with those for the starting 3-arylhy-
drazono-1,3-dihydroindole-2-thiones 4. Most significantly,
the signals corresponding to the carbons at 2 and 4 positions
are shifted by 17–18 ppm and by 8–10 ppm, respectively. It
is worth noting that signals of C-2 are displayed as doublets
with J¼2.3–3.2 Hz for starting hydrazonothioamides 4 and
as singlets for thiadiazoloindoles 5.
were monitored by TLC, which was performed on Sorbfil
UV-254.
The hydrazones 1a–h were prepared by a standard proce-
dure12 through coupling of diazotized arylamines with
oxoindole or condensation of hydrazines with isatin.11
4.1.1. 3-{[4-(4-Methoxyphenyl)-thiazol-2-yl]-hydra-
zono}-1,3-dihydroindol-2-one (3a). A solution of the 2-
bromoacetophenone 2a (320 mg, 1.4 mmol) and thiosemi-
carbazide 1h (308 mg, 1.4 mmol) in 50 mL ethanol was
heated at reflux for 5 h. After cooling, the precipitated solid
was collected. Recrystallization from ethanol afforded
436 mg, 89% 3a as orange crystals. Mp 269–270 ꢀC. IR n:
3440, 3060, 3020 (NH), 2990, 2960, 2940, 2900, 2820
(CH), 1680 (CO) cmꢁ1. 1H NMR (DMSO-d6, 400 MHz) d:
13.34 (s, 1H, NH), 11.25 (s, 1H, NH), 7.83 (d, J¼8.8 Hz,
1H, Ar-H), 7.55 (d, J¼7.5 Hz, 1H, Ar-H), 7.46 (s, 1H,
CH), 7.35 (ddd, J¼7.7, 7.5, 1.2 Hz, 1H, Ar-H), 7.10 (ddd,
J¼7.6, 7.8, 0.9 Hz, 1H, Ar-H), 7.0–6.96 (m, 3H, Ar-H),
3.8 (s, 3H, OCH3). MS m/z (I, %): 350 (M+, 100%). Anal.
Calcd for C18H14N4O2S: C, 61.70, H, 4.03, N, 15.99%.
Found: C, 61.44, H, 3.81, N, 16.30%.
The mass spectra of 1,2,3-thiadiazoles 5a–n show the
molecular ion in 10–100% intensity of the base peak. The
fragmentation is very similar to that observed for 2-aryl-
2,5-dihydro-[1,2,3]-thiadiazoles.3 The most typical for
the mass spectra of 5 are the peaks corresponding to
[MꢁC6H4N2S]+ (3–100%) and [MꢁC8H4N2]+ (17–84%).
In contrast to monocyclic 1,2,3-thiadiazoles, mass spectra
of compounds 5 do not have the peak corresponding to
[MꢁS]+.
3. Conclusion
4.1.2. 3-[(4-Phenylthiazol-2-yl)-hydrazono]-1,3-dihy-
droindol-2-one (3b). According to the preparation of 3a,
compound 3b was obtained from 2-bromoacetophenone 2b
(279 mg, 1.4 mmol) and thiosemicarbazide 1h (308 mg,
1.4 mmol) as yellow needles. Yield: 421 mg, 94%. Mp
169–170 ꢀC. IR n: 3440, 3190, 3060, 3020 (NH), 2810
(CH), 1695 (CO) cmꢁ1. 1H NMR (DMSO-d6, 400 MHz) d:
13.37 (s, 1H, NH), 11.26 (s, 1H, NH), 7.92 (d, J¼9.0 Hz,
2H, Ar-H), 7.64 (s, 1H, CH), 7.56 (d, J¼7.6 Hz, 1H, Ar-H),
7.46–7.42 (m, 2H, Ar-H), 7.38–7.32 (m, 2H, Ar-H). MS m/z
(I, %): 320 (M+, 100%). Anal. Calcd for C17H12N4OS: C,
63.73, H, 3.78, N, 17.49%. Found: C, 63.54, H, 3.94, N,
17.70%.
This successful synthesis of 2H-[1,2,3]thiadiazolo[5,4-b]-
indoles demonstrated that oxidative cyclization of hydr-
azonothiocarbonyl compounds is a feasible method for the
synthesis of fused 1,2,3-thiadiazoles. This protocol can be
used for the synthesis of thiadiazoloindoles involving other
derivatives of isatin and by involving other ring systems
bearing an a-hydrazonothiocarbonyl fragment.
4. Experimental
4.1. General methods
4.1.3. 3-{[4-(4-Chlorophenyl)-thiazol-2-yl]-hydrazono}-
1,3-dihydroindol-2-one (3c). According to the preparation
of 3a, compound 3c was obtained from 2-bromoaceto-
phenone 2c (326 mg, 1.4 mmol) and thiosemicarbazide 1h
(308 mg, 1.4 mmol) as yellow crystals. Yield: 475 mg,
96%. Mp 289–290 ꢀC. IR n: 3500, 3260, 3180, 3140, 3120
Melting points are uncorrected. The IR data (potassium bro-
mide) were obtained using UR-20 spectrometer. H NMR
spectra were recorded on 400 MHz for H and 100 MHz
1
1
for 13C. Chemical shifts and coupling constants are
expressed in parts per million (d) and J (Hz) with respect
to tetramethylsilane. The mass spectra were obtained using
a Varian MATT 311A spectrometer using the electron
impact ionization technique (40–200 ꢀC, 70 eV). Reactions
(NH), 3070, 2820 (CH), 1700 (CO) cmꢁ1 1H NMR
.
(DMSO-d6, 400 MHz) d: 13.35 (s, 1H, NH), 11.26 (s, 1H,
NH), 7.93 and 7.48 (AA0BB0, J¼8.6 Hz, 4H, Ar-H), 7.7 (s,

M. L. Kondratieva et al. / Tetrahedron 63 (2007) 3042–3048
3045
1H, CH), 7.54 (d, J¼7.5 Hz, 1H, Ar-H), 7.34 (dd, J¼7.7,
7.6 Hz, 1H, Ar-H), 7.1 (dd, J¼7.7, 7.6 Hz, 1H, Ar-H), 6.97
(d, J¼7.8 Hz, 1H, Ar-H). MS m/z (I, %): 354 (M+, 100%).
Anal. Calcd for C17H11ClN4OS: C, 57.55, H, 3.12, Cl, 9.99,
N, 15.79%. Found: C, 57.76, H, 3.33, Cl, 10.37, N, 15.51%.
Ar-H), 4.89 (d, J¼4.0 Hz, 2H, CH2). 13C NMR (DMSO-
d6, 100 MHz) d: 172.7 (d, J¼2.6 Hz, C-2), 139.6 (dd, C-
3), 137.3 (m, C-Ar), 129.5 (m, C-3), 128.7 (dd, J¼162.0,
8.3 Hz, 2CH, HC-Ar), 127.8 (d, J¼162.0 Hz, 2C, HC-Ar),
127.7 (d, J¼162.0 Hz, HC-Ar), 126.4 (d, J¼161.7 Hz,
HC-Indole), 125.1 (m, C-4), 122.4 (dd, J¼159.5, 7.1 Hz,
HC-Indole), 117.2 (dd, J¼160.3, 8.2 Hz, HC-Indole), 110.2
(dd, J¼162.8, 8.1 Hz, HC-Indole), 55.6 (q, J¼136.4 Hz,
CH2). MS m/z (I, %): 267 (M+, 29%). Anal. Calcd for
C15H13N3S: C, 67.39, H, 4.90, N, 15.72, S, 11.99. Found:
C, 67.64, H, 5.11, N, 15.57, S, 11.99%.
4.2. General procedure (GP) for the synthesis
of the 3-hydrazono-1,3-dihydroindole-2-thiones 4a–j
A mixture of 3-hydrazono-1,3-dihydroindol-2-one 1a–g,
3a–c (2 mmol) and Lawesson’s reagent (570 mg, 1.4 mmol)
was heated at reflux in xylenes (50 mL) for 1–3 h. The solu-
tion was evaporated and the thiones 4 were recrystallized
from ethanol.
4.2.3. 3-[(4-Ethoxyphenyl)-hydrazono]-1,3-dihydroin-
dole-2-thione (4c). According to the GP 4c was obtained
as brown crystals. Yield: 517 mg, 87%. Mp 174–175 ꢀC.
4.2.1. 3-(Methylhydrazono)-1,3-dihydroindole-2-thione
(4a). According to the GP 4a was obtained as bright yellow
crystals. Yield: 194 mg, 51%. Mp 127–128 ꢀC. IR n: 3450,
IR n: 3450, 3200 (NH), 2910 (CH) cmꢁ1 1H NMR
.
(DMSO-d6, 400 MHz) d: 12.68 (s, 1H, NH), 11.3 (s, 1H,
NH), 7.68 (d, J¼7.6 Hz, 1H, Ar-H), 7.49 and 7.02 (AA0BB0,
J¼8.8 Hz, 4H, Ar-H), 7.28 (dd, J¼7.6, 7.5 Hz, 1H, Ar-H),
7.17 (dd, J¼7.6, 7.5 Hz, 1H, Ar-H), 7.11 (d, J¼7.8 Hz,
1H, Ar-H), 4.04 (q, J¼6.9 Hz, 2H, OCH2), 1.34 (t, J¼
6.9 Hz, 3H, CH3). MS m/z (I, %): 297 (M+, 100%). Anal.
Calcd for C16H15N3OS: C, 64.62, H, 5.08, N, 14.13, S,
10.78%. Found: C, 64.89, H, 5.17, N, 14.54, S, 10.55%.
3260, 3180 (NH), 2920, 2840 (CH) cmꢁ1 1H NMR
.
(DMSO-d6, 400 MHz) d: 13.81 (q, J¼4.1 Hz, 1H, NH),
12.43 (s, 1H, NH), 7.49 (d, J¼7.6 Hz, 1H, Ar-H), 7.21 (dd,
J¼8.0, 7.6 Hz, 1H, Ar-H), 7.10 (dd, J¼8.0, 7.6 Hz, 1H,
Ar-H), 7.06 (d, J¼8.0 Hz, 1H, Ar-H), 3.47 (d, J¼4.1 Hz,
3H, NHCH3). 13C NMR (DMSO-d6, 100 MHz) d: 172.0
(d, J¼3.1 Hz, C-2,), 139.3 (m, C-3), 129.0 (m, C-9), 125.9
(dd, J¼160.4, 7.8 Hz, HC-Indole), 125.1 (m, C-4), 122.3
(dd, J¼159.7, 7.1 Hz, HC-Indole), 116.9 (dd, J¼160.1,
9.2 Hz, HC-Indole), 110.1 (dd, J¼162.3, 9.2 Hz, HC-
Indole), 40.2 (q, J¼143.4 Hz, CH3). MS m/z (I, %): 191 (M+,
100%). Anal. Calcd for C9H9N3S: C, 56.52, H, 4.74, N,
21.97, S, 16.75%. Found: C, 56.74, H, 4.61, N, 22.17, S,
16.75%.
4.2.4. 3-[(4-Methoxyphenyl)-hydrazono]-1,3-dihydroin-
dole-2-thione (4d). According to the GP 4d was obtained
as red-brown crystals. Yield: 419 mg, 74%. Mp 189–
190 ꢀC. IR n: 3200, 3190 (NH), 2920, 2960 (CH) cmꢁ1
.
1H NMR (DMSO-d6, 400 MHz) d: 15.81 (s, 1H, NH), 12.7
(s, 1H, NH), 7.68 (d, 1H, J¼7.6 Hz, Ar-H), 7.5 and 7.04
(AA0BB0, 4H, J¼9 Hz, Ar-H), 7.29 (dd, 1H, J¼7.6,
7.2 Hz, Ar-H), 7.18 (dd, 1H, J¼7.6, 7.2 Hz, Ar-H), 7.11
(d, 1H, J¼7.6 Hz, Ar-H), 3.80 (s, 3H, OCH3). MS m/z (I,
%): 283 (M+, 100%). Anal. Calcd for C15H13N3S: C,
63.58, H, 4.62, N, 14.83, S, 11.32%. Found: C, 63.74, H,
4.75, N, 14.65, S, 11.63%.
4.2.1.1. X-ray structure analysis. Crystal data:
C9H9N3S1 was crystallized from ethanol. Crystal dimen-
sions 0.16ꢂ0.20ꢂ0.50 mm, monoclinic, P21/n, a¼
˚
˚
˚
9.04880(10) A, b¼10.82860(10) A, c¼9.12250(10) A, b¼
91.9490(10) , V¼893.36(2) A ; Z¼4, rcalcd ¼1.422 g cmꢁ3
,
3
ꢀ
˚
2qmax¼142ꢀ, m(Cu Ka)¼2.823 cmꢁ1, Bruker SMART 6000
4.2.5. 3-[(4-Benzyloxyphenyl)-hydrazono]-1,3-dihy-
droindole-2-thione (4e). According to the GP 4e was ob-
tained as red-brown needles. Yield: 531 mg, 74%. Mp
188–189 ꢀC. IR n: 3440, 3190 (NH), 3060, 3020, 2920
˚
€
detector, Cu Ka (l¼1.54178 A), crossed Gobel mirrors,
T¼100 K, 9077 measured reflections, 1675 independent
reflections. The data were corrected for Lorentz absorption
and polarization effects. Structure was solved by direct
methods. Full matrix least-squares refinement based on
jF2j, 127 parameters, hydrogen atoms placed at calculated
positions with temperature factors 20% higher than parent
atom and the hydrogen bond distances were free to refine,
R1¼0.0300 (for 1639 with I>2s(I)), uR2¼0.0823, max/min
1
(CH) cmꢁ1. H NMR (DMSO-d6, 400 MHz) d: 15.77 (s,
1H, NH), 12.48 (s, 1H, NH), 7.64–6.95 (m, 13H, Ar-H), 5.1
(s, 2H, CH2). MS m/z (I, %): 359 (M+, 37%). Anal. Calcd for
C21H17N3OS: C, 70.17, H, 4.77, N, 11.69, S, 8.92%. Found:
C, 70.35, H, 4.86, N, 11.52, S, 8.77%.
ꢁ3
˚
residual electron density 0.26/ꢁ0.28 eA
.
4.2.6. 3-(Phenylhydrazono)-1,3-dihydroindole-2-thione
(4f). According to the GP 4f was obtained as red-brown crys-
tals. Yield: 390 mg, 77%. Mp 219–220 ꢀC. IR n: 3440, 3170
(NH), 2920 (CH) cmꢁ1. 1H NMR (DMSO-d6, 400 MHz) d:
15.67 (s, 1H, NH), 12.81 (s, 1H, NH), 7.71 (d, J¼7.6 Hz, 1H,
Ar-H), 7.49–7.35 (m, 4H, Ar-H), 7.27–7.21 (m, 1H, Ar-H),
7.20–7.14 (m, 3H, Ar-H). 13C NMR (DMSO-d6,
100 MHz) d: 174.5 (d, J¼3.2 Hz, C-2), 141.6 (m, C-Ar),
140.6 (m, C-3), 130.7 (m, C-9), 129.8 (dd, J¼160.0,
8.3 Hz, 2C, C-Ar), 127.7 (dd, J¼160.7, 8.0 Hz, HC-Indole),
124.7 (dt, J¼162.9, 6.9 Hz, HC-Ar), 124.5 (m, C-4), 122.9
(dd, J¼160.7, 7.2 Hz, HC-Indole), 118.4 (dd, J¼161.1,
8.0 Hz, HC-Indole), 115.7 (2C, d, J¼160.6 Hz, HC-Ar),
110.6 (dd, J¼163.5, 8.2 Hz, HC-Indole). MS m/z (I, %):
253 (M+, 100%). Anal. Calcd for C14H11N3S: C, 66.38, H,
Crystallographic data (excluding structure factors) for the
structure reported in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplemen-
tary publication no. CCDC-616795. Copies of the data can
be obtained free of charge on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK (fax: +44(0) 1223
336033 or e-mail: deposit@ccdc.cam.ac.uk).
4.2.2. 3-(Benzylhydrazono)-1,3-dihydroindole-2-thione
(4b). Compound 4b was obtained as orange crystals. Yield:
160 mg, 48%. Mp 84–85 ꢀC. 1H NMR (DMSO-d6,
400 MHz) d: 14.4 (t, J¼4.0 Hz, 1H, NH), 12.31 (s, 1H,
NH), 7.51 (d, J¼7.6 Hz, 1H, Ar-H), 7.05–7.5 (m, 8H,

3046
M. L. Kondratieva et al. / Tetrahedron 63 (2007) 3042–3048
4.38, N, 16.59, S, 12.66%. Found: C, 66.54, H, 4.21, N,
16.40, S, 12.85%.
215–217 ꢀC. IR n: 3450, 3180 (NH), 3060, 3020, 2980,
1
2920 (CH) cmꢁ1. H NMR (DMSO-d6, 400 MHz) d: 8.2
(d, J¼7.6 Hz, 1H, Ar-H), 7.93 (d, J¼8.0 Hz, 1H, Ar-H),
7.64 (ddd, J¼7.2, 7.2, 1.2 Hz, 1H, Ar-H), 7.46 (dd, J¼8.0,
7.2 Hz, 1H, Ar-H), 4.05 (s, 3H, NCH3). 13C NMR
(DMSO-d6, 100 MHz) d: 154.2 (s, C-2), 143.8 (dd,
J¼10.5, 8.1 Hz, C-3), 142.3 (dd, J¼2.3, 1.1 Hz, C-9),
127.9 (dd, J¼161.3, 7.5 Hz, HC-Indole), 122.9 (dd, J¼
162.2, 7.8 Hz, HC-Indole), 120.2 (dd, J¼163.9, 7.3 Hz,
HC-Indole), 117.2 (dd, J¼8.9, 5.6 Hz, C-4), 114.6 (dd,
J¼165.8, 8.0 Hz, HC-Indole), 43.2 (q, J¼143.4 Hz, NCH3).
MS m/z (I, %): 189 (M+ꢁHCl, 100%), 160 (C8H4N2S, 32),
102 (C7H4N, 31), 61 (CH3NS, 20). Anal. Calcd for
C9H8ClN3S: C, 47.90, H, 3.54, Cl, 15.74, N, 18.62, S
14.19%. Found: C, 47.75, H, 3.66, Cl, 16.13, N, 18.37%.
4.2.7. 3-[(4-Chlorophenyl)-hydrazono]-1,3-dihydro-
indole-2-thione (4g). According to the GP 4g was obtained
as orange crystals. Yield: 344 mg, 60%. Mp 259–260 ꢀC.
IR n: 3400, 3190, 3100, 2970 (NH), 2920, 2840 (CH) cmꢁ1
.
1H NMR (DMSO-d6, 400 MHz) d: 15.61 (s, 1H, NH), 12.61
(s, 1H, NH), 7.64 (d, 1H, J¼7.6 Hz, Ar-H), 7.47 and 7.3
(AA0BB0, J¼8.5 Hz, 4H, Ar-H), 7.27–7.21 (m, 1H, Ar-H),
7.15–7.04 (m, 2H, Ar-H). MS m/z (I, %): 287 (M+, 100%).
Anal. Calcd for C14H10ClN3S: C, 58.43, H, 3.50, Cl,
12.32, N, 14.60, S, 11.14%. Found: C, 58.64, H, 3.78, Cl,
12.17, N, 14.69, S, 11.35%.
4.2.8. 3-{[4-(4-Methoxyphenyl)-thiazol-2-yl]-hydra-
zono}-1,3-dihydroindole-2-thione (4h). According to the
GP 4h was obtained as red-brown crystals. Yield: 725 mg,
4.3.1.2. Hydrochloride of 2-(4-ethoxyphenyl)-2H-
[1,2,3]thiadiazolo[5,4-b]indole (5b). According to the
Method A 5b was obtained as an orange solid. Yield: 60 mg,
60%. Mp 219–220 ꢀC. IR n: 3440 (NH), 3200, 2960
99%. Mp 229–230 ꢀC. IR n: 3450, 3200, 3100 (NH) cmꢁ1
.
1H NMR (DMSO-d6, 400 MHz) d: 15.89 (s, 1H, NH), 12.9
(s, 1H, NH), 7.8 and 6.91 (AA0BB0, J¼8.8 Hz, 4H, Ar-H),
7.65–7.6 (m, 1H, Ar-H), 7.35 (s, 1H, HC-Thiazole), 7.3 (d,
J¼7.6 Hz, 1H, Ar-H), 7.18–7.08 (2H, m, Ar-H), 3.83 (3H,
s, OCH3). MS m/z (I, %): 366 (M+, 63%). Anal. Calcd for
C18H14N4OS2: C, 59.00, H, 3.85, N, 15.29, S, 17.50%.
Found: C, 59.24, H, 3.97, N, 15.40, S, 17.75%.
1
(CH) cmꢁ1. H NMR (DMSO-d6, 400 MHz) d: 12.53 (s,
1H, NH), 8.13 (d, J¼7.6 Hz, 1H, Ar-H), 7.99 (d, J¼8.2 Hz,
1H, Ar-H), 7.81 and 7.01 (AA0BB0, J¼8.9 Hz, 4H, Ar-H),
7.56 (dd, J¼8.0, 7.6 Hz, 1H, Ar-H), 7.41 (dd, J¼8.0, 7.2 Hz,
1H, Ar-H), 4.1 (q, J¼7.2 Hz, 2H, CH2), 1.42 (t, J¼6.9 Hz,
3H, CH3). 13C NMR (DMSO-d6, 100 MHz) d: 160.4 (m, C-
Arpara), 155.6 (s, C-2), 144.7 (C-3), 143.7 (C-9), 134.6 (C-
Aripso), 129.2 (HC-Indole), 124.2 (HC-Indole), 123.9 (2C,
HC-Arortho), 121.5 (HC-Indole), 118.6 (C-4), 116.6 (2C,
C-Armeta), 115.6 (HC-Indole), 64.6 (CH2), 15.4 (CH3). MS
m/z (I, %): 295 (M+ꢁHCl, 37%), 167 (EtOC6H5NS, 18),
160 (C8H4N2S, 6), 135 (EtOC6H5N, 72), 102 (C7H4N, 10),
(C10H8N2OS2, 22), 204 (C10H8N2OS, 56), 160 (C8H4N2S,
86), 102 (C7H4N, 2). Anal. Calcd for C16H14ClN3OS: C,
57.91, H, 4.22, Cl, 10.71, N, 12.66, S, 9.65%. Found: C,
58.26, H, 4.17, Cl, 10.49, N, 12.96, S, 9.95%.
4.2.9. 3-[(4-Phenylthiazol-2-yl)-hydrazono]-1,3-dihy-
droindole-2-thione (4i). According to the GP 4i was ob-
tained as red-brown crystals. Yield: 470 mg, 70%. Mp
1
119–120 ꢀC. IR n: 3440, 3200, 3100, 3090 (NH) cmꢁ1. H
NMR (DMSO-d6, 400 MHz) d: 15.9 (s, 1H, NH), 12.91 (s,
1H, NH), 7.89 (d, J¼7.3 Hz, 2H, Ar-H), 7.63 (d, J¼
7.3 Hz, 1H, Ar-H), 7.52 (s, 1H, HC-Thiazole), 7.42–7.22
(m, 4H, Ar-H), 7.19–7.08 (m, 2H, Ar-H). MS m/z (I, %):
336 (M+, 100%). Anal. Calcd for C17H12N4S2: C, 60.69,
H, 3.60, N, 16.65, S, 19.06%. Found: C, 60.43, H, 3.41, N,
16.31, S, 18.85%.
4.3.1.3. Hydrochloride of 2-(4-benzyloxyphenyl)-2H-
[1,2,3]thiadiazolo[5,4-b]indole (5c). According to the
Method A 5c was obtained as an orange solid. Yield: 81 mg,
4.2.10. 3-{[4-(4-Chlorophenyl)-thiazol-2-yl]-hydrazono}-
1,3-dihydroindole-2-thione (4j). According to the GP 4j
was obtained as red-brown crystals. Yield: 710 mg, 96%.
Mp 264–265 ꢀC. IR n: 3400, 3200, 3100 (NH), 2920
1
69%. Mp 227–228 ꢀC. H NMR (DMSO-d6, 400 MHz) d:
12.57 (br s, 1H, NH), 8.14 (d, J¼7.5 Hz, 1H, Ar-H), 7.98
(d, J¼8.3 Hz, 1H, Ar-H), 7.86 and 7.07 (AA0BB0,
J¼9.2 Hz, 4H, Ar-H), 7.57 (dd, J¼7.8, 7.7 Hz, 1H, Ar-H),
7.51–7.21 (m, 6H, Ar-H), 5.2 (s, 2H, OCH2). MS m/z (I,
%): 357 (M+, 9%), 102 (C7H4N, 4), 91 (C6H5CH2, 100).
Anal. Calcd for C21H16ClN3OS: C, 64.00, H, 4.07, Cl,
9.02, N, 10.67, S, 8.13%. Found: C, 64.30, H, 3.83, Cl,
9.39, N, 11.01, S, 8.31%.
1
(CH) cmꢁ1. H NMR (DMSO-d6, 400 MHz) d: 15.89 (s,
1H, NH), 12.93 (s, 1H, NH), 7.91 and 7.39 (AA0BB0, J¼
8.5 Hz, 4H, Ar-H), 7.63 (d, J¼7.5 Hz, 1H, Ar-H), 7.61 (s,
1H, HC-Thiazole), 7.3 (d, J¼7.5 Hz, 1H, Ar-H), 7.19–7.09
(m, 2H, Ar-H). MS m/z (I, %): 370 (M+, 100%). Anal. Calcd
for C17H11ClN4S2: C, 55.05, H, 2.99, Cl, 9.56, N, 15.11, S,
17.29%. Found: C, 55.34, H, 3.16, Cl, 9.35, N, 15.34, S,
17.45%.
4.3.1.4. Hydrochloride of 2-(4-chlorophenyl)-2H-
[1,2,3]thiadiazolo[5,4-b]indole (5d). According to the
Method A 5d was obtained as an orange solid. Yield: 50 mg,
4.3. Procedure for oxidation of 3-hydrazono-1,3-dihydro-
indole-2-thiones 4a–j
1
51%. Mp 282–283 ꢀC. H NMR (DMSO-d6, 400 MHz) d:
8.12 (d, J¼7.6 Hz, 1H, Ar-H), 8.0–7.8 (m, 3H, Ar-H), 7.4–
7.7 (m, 3H, Ar-H), 7.59 (dd, J¼7.6, 7.4 Hz, 1H, Ar-H).
13C NMR (DMSO-d6, 100 MHz) d: 157.7 (s, C-2), 145.3
(C-3), 143.8 (s, C-9), 140.8 (C-Aripso), 134.8 (C-Arpara),
131.0 (dd, J¼168.0, 5.6 Hz, 2C, C-Armeta), 129.4 (dd,
J¼160.8, 8.0 Hz, HC-Indole), 124.3 (dd, J¼162.5, 7.4 Hz,
HC-Indole), 123.1 (dd, J¼165.5, 5.6 Hz, 2C, HC-Arortho),
121.6 (dd, J¼163.4, 8.6 Hz, HC-Indole), 119.2 (dd, C-4),
115.5 (dd, J¼166.7, 7.6 Hz, HC-Indole). MS m/z (I, %):
4.3.1. Method A. NCS or NBS (0.6 mmol) was added to
a solution of 3-hydrazono-1,3-dihydroindole-2-thione 4
(0.3 mmol) in 50 mL EtOAc and the reaction mixture was
stirred at 0 ꢀC for 2 h. The precipitate was filtered off.
4.3.1.1. Hydrochloride of 2-methyl-2H-[1,2,3]thiadi-
azolo[5,4-b]indole (5a). According to the Method A 5a
was obtained as a greenish solid. Yield: 58 mg, 85%. Mp

M. L. Kondratieva et al. / Tetrahedron 63 (2007) 3042–3048
3047
285.5 (M+ꢁHCl, 8%), 160 (C8H4N2S, 8), 157.5 (ClC6H4NS,
72), 125.5 (ClC6H4N, 100), 102 (C7H4N, 2). Anal. Calcd for
C14H9Cl2N3S: C, 52.17, H, 2.80, Cl, 22.05, N, 13.04, S,
9.94%. Found: C, 52.30, H, 2.58, Cl, 22.35, N, 12.78, S,
9.60%.
(HC-Indole), 124.2 (HC-Indole), 121.6 (HC-Indole), 117.9
(C-4), 115.6 (HC-Indole), 60.54 (CH2). MS m/z (I, %):
265 (M+ꢁHBr, 29%), 105 (C6H5CH2, 3), 102 (C7H4N,
10), 91 (C6H4CH2, 100). Anal. Calcd for C15H12BrN3S: C,
52.02, H, 3.47, Br, 23.12, N, 12.14, S, 9.25%. Found: C,
52.28, H, 3.23, Br, 23.25, N, 12.31, S, 9.37%.
4.3.1.5. Hydrochloride of 2-[4-(4-methoxyphenyl)-
thiazol-2-yl]-2H-[1,2,3]thiadiazolo[5,4-b]indole (5e). Ac-
cording to the Method A 5e was obtained as a dark-red solid.
4.3.2.3. Hydrobromide of 2-(4-ethoxyphenyl)-2H-
[1,2,3]thiadiazolo[5,4-b]indole (5i). According to Method
B 5i was obtained as a brown solid. Yield: 45 mg, 60ꢁ%1.
Mp 219–220 ꢀC. IR n: 3440 (NH), 3200, 2960 (CH) cm
.
1
Yield: 50 mg, 42%. Mp 204–205 ꢀC. H NMR (DMSO-d6,
400 MHz) d: 10.92 (br s, 1H, NH), 8.15 (d, J¼8.3 Hz, 1H,
HC-Indole), 7.96–7.89 (3H, m, HC-Indole+Ar-H), 7.8 (s,
1H, HC-Thiazole), 7.6 (dd, J¼8.0, 7.3 Hz, 3H, HC-Indole),
7.45 (dd, J¼8.3, 7.0 Hz, 3H, HC-Indole), 7.0 (d, J¼8.9 Hz,
2H, Ar-H), 3.81 (s, 3H, CH3). MS m/z (I, %): 364 (M+ꢁHCl,
100%). Anal. Calcd for C18H13ClN4OS2: C, 53.93, H, 3.25,
Cl, 8.86, N, 13.98, S, 8.0%. Found: C, 53.71, H, 3.12, Cl,
8.52, N, 14.21, S, 8.23%.
1H NMR (DMSO-d6, 400 MHz) d: 12.53 (s, 1H, NH), 8.13
(d, J¼7.6 Hz, 1H, Ar-H), 7.99 (d, J¼8.2 Hz, 1H, Ar-H),
7.81 and 7.01 (AA0BB0, J¼8.9 Hz, 4H, Ar-H), 7.56 (dd, J¼
8.0, 7.6 Hz, 1H, Ar-H), 7.41 (dd, J¼8.0, 7.2 Hz, 1H, Ar-H),
4.1 (q, J¼7.2 Hz, 2H, CH2), 1.42 (t, J¼6.9 Hz, 3H, CH3).
13C NMR (DMSO-d6, 100 MHz) d: 160.4 (m, C-Arpara),
155.6 (s, C-2), 144.7 (C-3), 143.7 (C-9), 134.6 (C-Aripso),
129.2 (HC-Indole), 124.2 (HC-Indole), 123.9 (2C, HC-
Arortho), 121.5 (HC-Indole), 118.6 (C-4), 116.6 (2C,
C-Armeta), 115.6 (HC-Indole), 64.6 (CH2), 15.4 (CH3). MS
m/z (I, %): 295 (M+ꢁHBr, 37%), 167 (EtOC6H5NS, 18),
160 (C8H4N2S, 6), 135 (EtOC6H5N, 72), 102 (C7H4N, 10).
Anal. Calcd for C16H14BrN3OS: C, 51.06, H, 3.72, Br,
21.28, N, 11.17%. Found: C, 51.28, H, 3.92, N, 10.96%.
4.3.1.6. Hydrochloride of 2-[4-(4-chlorophenyl)-thi-
azol-2-yl]-2H-[1,2,3]thiadiazolo[5,4-b]indole (5f). Accord-
ing to the Method A 5f was obtained as an orange solid.
1
Yield: 40 mg, 33%. Mp 244–245 ꢀC. H NMR (DMSO-d6,
400 MHz) d: 12.9 (br s, 1H, NH), 8.13 (d, J¼8.0 Hz, 1H,
Ar-H), 8.02–7.86 (m, 4H, Ar-H+H-Thiazole), 7.60 (dd,
J¼8.0, 7.5 Hz, 1H, Ar-H), 7.3 (d, J¼8.5 Hz, 3H, Ar-H).
13C NMR (DMSO-d6, 100 MHz) d: 160.6 (C-Thiazole),
159.9 (s, C-2), 152.1 (C-3), 145.9 (s, C-9), 144.5 (C-Thi-
azole), 134.4 (C-Arpara), 132.9 (C-Aripso), 130.3 (HC-Indole),
129.8 (d, J¼165.9 Hz, 2C, HC-Armeta), 128.5 (d, J¼
162.0 Hz, 2C, C-Arortho), 124.9 (HC-Indole), 122.2 (HC-
Indole), 119.2 (C-4), 115.8 (d, J¼165.0 Hz, HC-Indole),
114.5 (d, J¼190.4 Hz, HC-Thiazole). MS m/z (I, %): 368
(M+ꢁHCl, 53%), 240 (C9H5ClN2S2, 20), 208 (C9H5ClN2S,
27), 160 (C8H4N2S, 100), 102 (C7H4N, 27). Anal. Calcd
for C17H10Cl2N4S2: C, 50.43, H, 2.47, Cl, 17.55, N, 13.84,
S, 7.91%. Found: C, 50.65, H, 2.70, Cl, 17.68, N, 13.70, S,
8.20%.
4.3.2.4. Hydrobromide of 2-(4-methoxyphenyl)-2H-
[1,2,3]thiadiazolo[5,4-b]indole (5j). According to Method
B 5j was obtained as brown solid. Yield: 41 mg, 57%. Mp
1
254–255 ꢀC. IR n: 3190 (CH), 2960 (CH3) cmꢁ1. H NMR
(DMSO-d6, 400 MHz) d: 12.58 (br s, 1H, NH), 8.13 (d,
J¼7.6 Hz, 1H, Ar-H), 7.99 (d, J¼8.2 Hz, 1H, Ar-H), 7.84
and 7.14 (AA0BB0, J¼8.6 Hz, 4H, Ar-H), 7.56 (dd, J¼7.5,
7.3 Hz, 1H, Ar-H), 7.43 (dd, J¼7.7, 7.4 Hz, 1H, Ar-H),
3.88 (s, 3H, OCH3). 13C NMR (DMSO-d6, 100 MHz) d:
160.2 (m, C-Ar), 154.8 (s, C-2), 143.8 (dd, J¼10.3,
9.9 Hz, C-3), 142.7 (d, J¼2.8 Hz, C-9), 133.8 (tt, J¼9.3,
2.4 Hz, C-Ar), 128.3 (dd, J¼160.7, 7.3 Hz, HC-Indole),
123.3 (dd, J¼164.1, 10.1 Hz, HC-Indole), 123.0 (dd,
J¼163.9, 5.9 Hz, 2C, C-Ar), 120.6 (dd, J¼164.1, 8.5 Hz,
HC-Indole), 117.7 (dd, J¼5.6, 9.0 Hz, C-4), 115.4 (dd,
J¼162.2, 5.1 Hz, 2C, HC-Ar), 114.7 (dd, J¼163.2, 8.2 Hz,
HC-Indole), 55.7 (q, J¼144.2 Hz, OCH3). MS m/z (I, %):
281 (M+ꢁHBr, 35%), 160 (C8H4N2S, 3), 153
(MeOC6H4NS, 22), 121 (MeOC6H5N, 100), 102 (C7H4N,
5). Anal. Calcd for C15H12BrN3OS: C, 49.72, H, 3.31, Br,
22.10, N, 11.60, S, 8.84%. Found: C, 49.46, H, 3.57, Br,
22.35, N, 11.86, S, 8.61%.
4.3.2. Method B. A solution of bromine (1.3 g, 8 mmol) in
5 mL AcOH was added to a solution of 3-hydrazono-1,3-
dihydroindole-2-thione 4 (2 mmol) in 100 mL AcOH
at room temperature and the reaction mixture was stirred
at ambient temperature for 5 h. The precipitate was filtered
off.
4.3.2.1. Hydrobromide of 2-methyl-2H-[1,2,3]thiadi-
azolo[5,4-b]indole (5g). According to the Method B 5g
was obtained as a yellowish solid. Yield: 50 mg, 93%. Mp
246–247 ꢀC. MS m/z (I, %): 189 (M+ꢁHBr, 91%). Anal.
Calcd for C9H8BrN3S: C, 40.00, H, 2.96, Br, 29.63, N,
15.56, S, 11.85%. Found: C, 40.25, H, 2.76, Br, 29.85, N,
15.37, S, 12.02%.
4.3.2.5. Hydrobromide of 2-phenyl-2H-[1,2,3]thiadi-
azolo[5,4-b]indole (5k). According to Method B 5k was
obtained as a yellow solid. Yield: 66 g, 99%. Mp 244–
245 ꢀC. IR n: 3190 (NH), 2920 (CH) cmꢁ1 1H NMR
.
(DMSO-d6, 100 MHz) d: 12.81 (br s, 1H, NH), 8.28 (d, J¼
7.6 Hz, 1H, Ar-H), 8.02–7.99 (m, 2H, Ar-H), 7.96 (dd,
J¼7.6 Hz, 1H, Ar-H), 7.72–7.67 (m, 3H, Ar-H), 7.61 (dd,
J¼7.6, 7.2 Hz, 1H, Ar-H), 7.52 (dd, J¼7.6, 7.2 Hz, 1H,
Ar-H). 13C NMR (DMSO-d6, 100 MHz) d: 155.9 (C-2),
145.4 (C-3), 145.3 (C-9), 141.2 (C-Aripso), 131.3 (2C, HC-
Armeta), 130.8 (HC-Indole), 129.9 (HC-Indole), 124.6
(HC-Arpara), 122.0 (3C, HC-Indole and HC-Arortho), 118.4
(C-4), 115.8 (HC-Indole). MS m/z (I, %): 251 (M+ꢁHBr,
65%), 160 (C9H6N2S2, 5), 123 (C9H6N2S, 8), 91 (C6H5N,
4.3.2.2. Hydrobromide of 2-benzyl-2H-[1,2,3]thiadi-
azolo[5,4-b]indole (5h). According to the Method B 5h
was obtained as a light brown solid. Yield: 40 mg, 60%. Mp
124–125 ꢀC. IR n: 3420, 3240 (NH), 3020, 2920 (CH) cmꢁ1
.
1H NMR (DMSO-d6, 400 MHz) d: 12.41 (br s, 1H, NH),
8.06 (d, J¼7.8 Hz, 1H, Ar-H), 7.93 (d, J¼8.2 Hz, 1H,
Ar-H), 7.55–7.32 (m, 7H, Ar-H), 5.91 (s, 2H, CH2). 13C
NMR (DMSO-d6, 100 MHz) d: 154.7 (C-2), 145.2 (C-3),
145.0 (C-9), 135.8 (C-Aripso), 129.9 (5C, HC-Ar), 129.4

3048
M. L. Kondratieva et al. / Tetrahedron 63 (2007) 3042–3048
100), 102 (C7H4N, 10). Anal. Calcd for C14H10BrN3S: C,
50.60, H, 3.01, Br, 24.10, N, 12.65, S, 9.64%. Found: C,
50.36, H, 2.85, Br, 24.35, N, 12.40, S, 9.78%.
for C14H10IN3S: C, 44.33, H, 2.64, N, 11.08, S, 8.44%.
Found: C, 44.36, H, 2.31, N, 10.90, S, 8.26%.
4.3.2.6. Hydrobromide of 2-(4-phenylthiazol-2-yl)-
2H-[1,2,3]thiadiazolo[5,4-b]indole (5l). According to
Method B 5l was obtained as a light brown solid. Yield:
71 mg, 86%. Mp 234–235 ꢀC. IR n: 3150 (NH), 1620
(CH) cmꢁ1. 1H NMR (DMSO-d6, 400 MHz) d: 12.91 (br s,
1H, NH), 8.14 (d, J¼8.0 Hz, 1H, HC-Indole), 7.99–7.96
(m, 3H, HC-Indole+Ar-H), 7.8 (s, 1H, HC-Thiazole), 7.59
(dd, J¼7.6, 7.0 Hz, 1H, HC-Indole), 7.49–7.33 (m, 4H,
HC-Indole+Ar-H). 13C NMR (DMSO-d6, 100 MHz) d:
159.9 (C-Thiazole), 153.5 (C-2), 146.1 (C-3), 144.6 (C-9),
134.2 (C-Thiazole), 130.4 (d, J¼156.0 Hz, HC-Ph), 129.8
(d, J¼159.1 Hz, 2C, HC-Ph), 129.6 (d, J¼160.0 Hz, HC-
Indole), 126.9 (d, J¼159.3 Hz, 2C, HC-Ph), 125.1 (d, J¼
163.6 Hz, HC-Indole), 122.4 (d, J¼163.9 Hz, HC-Indole),
119.3 (C-4), 115.9 (d, HC-Indole), 113.9 (d, J¼191.3 Hz,
HC-Thiazole). MS m/z (I, %): 334 (M+ꢁHBr, 100%), 206
(C9H6N2S2, 33), 174 (C9H6N2S, 93), 160 (C8H4N2S, 81),
102 (C7H4N, 34). Anal. Calcd for C17H11BrN4S2: C,
49.16, H, 2.65, Br, 19.27, N, 13.49, S, 7.71%. Found: C,
49.44, H, 2.88, Br, 19.55, N, 13.71, S, 7.45%.
Acknowledgements
This research was supported by Russian fund for basic
research (grant N 04-03-32926a), F.W.O.-Vlaanderen and
K.U. Leuven.
References and notes
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4.3.3. Method C. A saturated solution of iodine in ethanol
was added to a solution of hydrazone (0.5 mmol) in 10 mL
of ethanol until the iodine colour persisted. The reaction
mixture was stirred at 0 ꢀC for 2 h. The precipitate was
filtered off.
4.3.3.1. Hydroiodide of 2-methyl-2H-[1,2,3]thiadi-
azolo[5,4-b]indole (5m). According to Method C 5m was
obtained as a yellow-green solid. Yield: 87 mg, 55%. Mp
227–228 ꢀC. MS m/z (I, %): 189 (M+ꢁHI, 95%). Anal.
Calcd for C9H8IN3S: C, 33.96, H, 2.52, N, 13.21, S,
10.06%. Found: C, 34.36, H, 2.21, N, 12.90, S, 10.31%.
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4.3.3.2. Hydroiodide of 2-phenyl-2H-[1,2,3]thiadi-
azolo[5,4-b]indole (5n). According to Method C 5n was
obtained as a brown solid. Yield: 108 mg, 57%. Mp 186–
187 ꢀC. MS m/z (I, %): 251 (M+ꢁHI, 63%). Anal. Calcd