Synthesis of 4-ethyl-5-ethylimino-[1,2,4]-dithiazolidin-3-trithione through ethyl-(4-ethyl-5-thioxo-[1,2,4]-dithiazolidin-3-ylidene)ammonium oxopentachlorotungstate(VI) hydrolysis and the dimroth rearrangement in it on heating

Article abstract of DOI:10.1134/S0020168513090112

We demonstrate that the previously synthesized product of ethyl isothiocyanate insertion into tungsten hexachloride, WCl₅{N(Et)C(S) N(Et)C(S)Cl}, whose partial hydrolysis yields {N(Et)C(S)-S-S-C=NH(Et)}[WOCl ₅] (I), can be used as a source of biologically active heterocyclic compounds. ¹H and ¹³C NMR and gas chromatography-mass spectrometry data show that reaction of I with a saturated aqueous Na ₂CO₃ solution yields a number of thiazolidine heterocycles, mostly 4-ethyl-5-ethylimino-[1,2,4]-dithiazolidin-3-trithione. The thermal Dimroth rearrangement leads to the formation of 2,4-diethyl-[1,2,4]- dithiazolidin-3,5-dithione and the products of partial hydrolysis of both heterocycles: 4-ethyl-5-ethylimino-[1,2,4]-dithiazolidin-3-on and 2,4-diethyl-3-thioxo-[1,2,4]-dithiazolidin-5-on.

Full text of DOI:10.1134/S0020168513090112

ISSN 0020ꢀ1685, Inorganic Materials, 2013, Vol. 49, No. 9, pp. 943–946. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © N.A. Ovchinnikova, A.E. Sinyakov, S.G. Sakharov, A.E. Gekhman, Yu.N. Mikhailov, A.S. Kanishcheva, 2013, published in Neorganicheskie Materialy,
2013, Vol. 49, No. 9, pp. 1012–1015.
Synthesis of 4ꢀEthylꢀ5ꢀEthyliminoꢀ[1,2,4]ꢀDithiazolidinꢀ3ꢀ
Trithione through Ethylꢀ(4ꢀEthylꢀ5ꢀThioxoꢀ[1,2,4]ꢀDithiazolidinꢀ
3ꢀylidene)ammonium Oxopentachlorotungstate(VI) Hydrolysis
and the Dimroth Rearrangement in It on Heating
N. A. Ovchinnikova, A. E. Sinyakov, S. G. Sakharov, A. E. Gekhman,
†
Yu. N. Mikhailov, and A. S. Kanishcheva
Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences,
Leninskii pr. 31, Moscow, 119991 Russia
eꢀmail: talan@igic.ras.ru
Received December 27, 2012
Abstract—We demonstrate that the previously synthesized product of ethyl isothiocyanate insertion into
tungsten hexachloride, WCl5{N(Et)C(S)N(Et)C(S)Cl}, whose partial hydrolysis yields {N(Et)C(S)–S–S–
C=NH(Et)}[WOCl5] (
NMR and gas chromatography–mass spectrometry data show that reaction of
I C
), can be used as a source of biologically active heterocyclic compounds. 1H and 13
I
with a saturated aqueous
Na2CO3 solution yields a number of thiazolidine heterocycles, mostly 4ꢀethylꢀ5ꢀethyliminoꢀ[1,2,4]ꢀdithiaꢀ
zolidinꢀ3ꢀtrithione. The thermal Dimroth rearrangement leads to the formation of 2,4ꢀdiethylꢀ[1,2,4]ꢀdithiꢀ
azolidinꢀ3,5ꢀdithione and the products of partial hydrolysis of both heterocycles: 4ꢀethylꢀ5ꢀethyliminoꢀ
[1,2,4]ꢀdithiazolidinꢀ3ꢀon and 2,4ꢀdiethylꢀ3ꢀthioxoꢀ[1,2,4]ꢀdithiazolidinꢀ5ꢀon.
DOI: 10.1134/S0020168513090112
INTRODUCTION
EXPERIMENTAL
Hydrolysis of I. To carry out the reaction, we used
The synthesis and properties of thiazolidine comꢀ
pounds have attracted considerable attention because
they possess high reactivity in various chemical transꢀ
formations. These derivatives were shown to offer a
wide range of biological activities. In particular, penicilꢀ
lin compounds are known to contain thiazolidine as a
component, and the healing power of this type of drug
substance is due to this ring.
earlier prepared, structurally characterized crystals of
I
[1], Na2CO3 (analytical grade), absolute ether, and hexꢀ
ane (analytical grade).
To a weighed amount of I (1.05 g, 20 mL) was added
a saturated aqueous Na2CO3 solution. As a result, the
solution took on a turquoise color, a yellow oily product
was formed on the bottom of the flask, and HCl gas
evolved. The oil was extracted with 10 mL of ethyl ether,
boiled down to 10 mL under vacuum, and left to stand
until complete ether vaporization. Next, the isolated
compound was recrystallized from hexane and characꢀ
terized by 1H and 13C NMR and gas chromatography–
mass spectrometry.
As shown earlier, the reaction of WCl6 with EtNCS
in dichloroethane leads to the insertion of two isothioꢀ
cyanate molecules into one tungsten–chlorine bond,
yielding WCl5{N(Et)C(S)N(Et)C(S)Cl}[1]. It is
shown as well that holding the addition product in an
excess of EtNCS in the presence of trace levels of
atmospheric moisture causes its partial hydrolysis,
which, according to Xꢀray diffraction results [1], leads
to partial cyclization of the hydrolyzed ligand, yielding
1H and 13C NMR spectra were taken on a Bruker
AC 200 spectrometer at working frequencies of 200.13
and 50.3 MHz, respectively, using a deuterium lock.
1
The H and 13C chemical shifts were determined relaꢀ
{N(Et)C(S)–S–S–C=NH(Et)} [WOCl5] (I), conꢀ
taining a dithiazolidin derivative as a cation.
tive to tetramethylsilane. The signals from the СН2 and
СН3 groups in the 13C NMR spectra were assigned by
the DEPT method using a 135° editing pulse [2]. The
In this paper, we report NMR and gas chromatograꢀ
phy–mass spectrometry studies of the hydrolysis of
and describe counter synthesis necessary to identify the
signals in the proton and carbon NMR spectra were
correlated using a twoꢀdimensional heterocorrelated
I
1
experiment: 13C, HꢀCORR [3]. Signals from tertiary
organic products of the hydrolysis of I.
carbon atoms were accumulated and assigned using
selective polarization transfer from protons having scaꢀ
†
Deceased.
943

944
OVCHINNIKOVA et al.
1
lar spin–spin interaction with a 13C nucleus through product by H and 13C NMR (table) and gas chromaꢀ
several bonds (INEPT LR) [4].
tography–mass spectrometry. In addition, when the
reaction was left to stand, yellow crystals precipitated
from the solution. The crystals were also characterized
by NMR spectroscopy (table, V).
Since the sample to be analyzed by mass spectromeꢀ
try was passed through a highꢀtemperature zone (above
Gas chromatography–mass spectrometry experiꢀ
ments were carried out on an Automass 150 spectromeꢀ
ter (DelsiꢀNermag, France) in electron impact mode
(ionization energy of 70 eV). Chromatographic separaꢀ
tion was performed with an OVꢀ1 capillary column
(inner diameter, 0.25 mm; length, 25 m; He carrier gas,
0.75 atm). Chromatographic modes: injector with a
150
ization of a solution of II in CDCl3 after holding II at
160 for 55 min, which indicated the formation of a
mixture of four compounds (table, II ).
°С), we performed an additional NMR characterꢀ
°С
split ratio of 1 : 40; tinj
0.5 L; initial column temperature, 100
temperature program, 10 C/min to 270
=
300
°
С
; injected sample volume,
–V
µ
°С
.
(2 min);
°
°С
It is remarkable that the addition of Na2CO3 led not
only to the formation of dark yellow oil (II) but also to
the precipitation of yellow crystals (VI), in contrast to
what was reported by Freund [5]. According to Xꢀray
diffraction data, which agreed well with earlier results
Counter synthesis. 4ꢀEthylꢀ5ꢀethyliminoꢀ[1,2,4]ꢀ
dithiazolidinꢀ3ꢀthione (II) was prepared as described
by Freund [5]. We used ethyl isothiocyanate (Fluka),
Na2CO3 (analytical grade), bromine dried over concenꢀ
trated H2SO4, nꢀoctane distilled twice over CaH2, chloꢀ
roform (analytical grade), and absolute ether.
[6], the crystals consisted of crystalline sulfur, S8
.
The structure of VI was determined by Xꢀray diffracꢀ
tion on an EnrafꢀNonius CADꢀ4 singleꢀcrystal autoꢀ
matic diffractometer (4 (λ MoKα, graphite monochroꢀ
mator).
To a bromine solution (5 mL) in octane (100 mL)
was added in small portions with constant stirring an
ethyl isothiocyanate solution (9 mL) in octane (9 mL).
The reaction was highly exothermic and yielded a dark
vinous oil, which was separated from the solution by filꢀ
tration, washed with octane, and dried to constant
weight.
RESULTS AND DISCUSSION
1
The present 13C and H NMR spectroscopy results
(table) demonstrate that the organic product resulting
The oily product was decomposed by water
(200 mL) over a period of three days. To the resultant
pale yellow solution was added Na2CO3 until CO2 evoꢀ
lution ceased. The dark yellow oil resulting from the
hydrolysis was extracted with ethyl ether (150 mL), and
the extract was dried using a roughing pump.
from the hydrolysis of
ring: 4ꢀethylꢀ5ꢀethyliminoꢀ[1,2,4]ꢀdithiazolidinꢀ3ꢀ
thione (II).
What is surprising at first sight is that the mass specꢀ
trum of the reaction product shows two mass 190 peaks
and two mass 260 peaks, indicating that the sample conꢀ
I is a fiveꢀmembered dithiazole
The product, having the form of yellow oil, was tains, in addition to II (dithiazole derivative) and III (its
treated with water. As a result, light yellow oil (II) was bond isomer), two isomeric compounds formed
formed on the flask wall. It was filtered off, dissolved in through partial hydrolysis of the above compounds: the
chloroform on the filter, and used to identify the organic oxo derivatives IV and V:
–
+
S
S
S
O
W
Cl
S
Cl
Cl
Cl
Cl
H O/Na CO
2
S
C
S
C
2
3
C
C
Et
N
N
NEt
N
Et
II
H
I
I
S
S
S
C
C
S
t
> 150°C
+
+
O C
.
EtN NEt
EtN NEt
C
N
C
S
C S
NEt
Et
S
O
III
IV
V
Additional studies showed that the observed distincꢀ same four compounds (table) as after passing II through
tions between NMR and mass spectrometry results were a highꢀtemperature zone in gas chromatography–mass
due to the difference in temperature programs.
spectrometry characterization.
In particular, the NMR spectrum of the solution of
These transformations, resulting in bond isomerizaꢀ
II after heat treatment indicated the presence of the tion of II followed by the hydrolysis of both isomers,
INORGANIC MATERIALS Vol. 49
No. 9
2013

SYNTHESIS OF 4ꢀETHYLꢀ5ꢀETHYLIMINOꢀ[1,2,4]ꢀDITHIAZOLIDINꢀ3ꢀTRITHIONE
Parameters of the 1H and 13C NMR spectra of the organic compounds isolated in CDCl3 at 298 K
945
3J, Hz
δ
, ppm
δ
, ppm
13C
Compound
Position
Group
proton NMR
CH3
CH2
CH3
CH2
C
4
4
5
5
5
3
1.167
t
6.95
6.95
7.18
7.18
–
10.76
45.51
15.3
4.21
1.25
3.36
–
q
S
1S
5C
2
t
S
C3
4
N
NEt
q
47.5
(II)
Et
152.03
192.45
C
–
–
CH3
CH2
CH3
CH2
C
4
4
2
2
3
5
1.25
4.39
1.31
4.03
–
t
7.24
7.24
7.22
7.22
–
10.89
44.19
12.79
44.06
175.7
187.63
S
q
t
C
3
EtN
4
2
NEt
1
C5
S
q
(III)
S
C
–
–
CH3
CH2
CH3
CH2
C
4
4
5
5
5
3
1.21
4.01
1.23
3.65
–
t
7.16
7.16
7.27
7.27
–
11.77
39.93
13.81
39.75
153.4
187.3
q
t
S
1S
2
O C 3 4
5
C
N
q
Et
NEt
(IV)
C
–
–
CH3
CH2
CH3
CH2
C
4
4
2
2
5
3
1.23
4.06
1.29
4.03
–
t
7.1
7.1
7.1
7.1
–
12.1
44.1
S
q
t
C
12.7
3
4
5
EtN 2NEt
1
q
41.7
C S
(V)
O
166.9
174.9
C
–
–
constitute an example of the thermal Dimroth rearꢀ the structure of the heterocycles in the thermolysis
rangement, often encountered in heteroaromatic comꢀ products are linked to one another only through CN
bonds, in contrast to their analogs synthesized without
heating.
pounds [7]. They are accompanied by preliminary ring
opening in the hydrolysis of II, followed by the formaꢀ
tion of its bond isomer (III) and oxo derivatives correꢀ
sponding to II and III (IV and V, respectively).
CONCLUSIONS
It is remarkable that a similar thermal rearrangeꢀ
ment was identified previously in Xꢀray diffraction
characterization of complete [8] or partial [9] hydrolysis
products: symmetric and asymmetric triazine rings
obtained through EtNCO insertion into WCl6 under
various temperature conditions. In particular, in the
case of an ethyl isocyanate derivative, raising the synꢀ
The present results suggest that ethyl isothiocyanate
insertion into tungsten hexachloride and subsequent
hydrolysis of the reaction product can be used for modꢀ
eling and creating drugs based on complexes containing
dithiazole rings. Moreover, these reactions can be
thought of as a direct path to the preparation of 4ꢀethylꢀ
5ꢀethyliminoꢀ[1,2,4]ꢀdithiazolidinꢀ3ꢀthione (II), its
thesis temperature from 20°C to the boiling point of the
reaction mixture leads to bond isomerization, like in bond isomer (III), and their oxo derivatives (IV and
V),
this study. In both cases, all of the isocyanate groups in which may exhibit biological activity.
INORGANIC MATERIALS Vol. 49
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946
OVCHINNIKOVA et al.
6. Gallacher, A.C. and Pinkerton, A.A., Redetermination
REFERENCES
of monoclinic Yꢀsulfur, Acta Crystallogr., Sect. C: Cryst.
Struct. Commun., 1993, vol. 49, pp. 125–126.
1. Ovchinnikova, N.A., Sinyakov, A.E., Sergienko, V.S.,
and Aleksandrov, G.G., Insertion of ethyl isothiocyanate
into tungsten hexachloride: Crystal structure of ethylꢀ
(4ꢀethylꢀ5ꢀthioxo[1.2.4]dithiazolidinꢀ3ꢀylidene)ammoꢀ
7. Obshchaya organicheskaya khimiya (General Organic
Chemistry), Kochetkova, N.K., Ed., Moscow: Khimiya,
1985, vol. 8, p. 462.
nium oxopentachlorotungstate(VI), Crystallogr. Rep.
,
2003, vol. 48, no. 4, pp. 602–605.
8. Ovchinnikova, N.A., Sinyakov, A.E., Reznik, A.M.,
et al., Insertion of ethyl isocyanate at the tungsten–chloꢀ
rine bond. Crystal structure of 1,3,5ꢀtriethylꢀ1,3,5ꢀtriazꢀ
2. Pegg, D.T. and Bendall, M.R., Selfꢀcompensation of
pulse error effect in editing 13C spectra with a modified
DEPT sequence, J. Magn. Reson., 1984, vol. 60,
pp. 347–351.
3. Sarkar, S.K. and Bax, A., A simple and sensitive oneꢀ
dimensional NMR technique for correlation of proton
and carbon chemical shifts, J. Magn. Reson., 1985,
vol. 62, pp. 109–112.
ineꢀ2,4,6ꢀ(1H,3H,5H)ꢀtrione, Russ. J. Coord. Chem.
,
2002, vol. 28, no. 9, pp. 673–677.
9. Ovchinnikova, N.A., Sinyakov, A.E., Sergienko, V.S.,
et al., Triple insertion of the ethylisocyanate into a W–Cl
bond and its innerꢀsphere cyclization. Crystal structure
of tetraꢀchlorooxo(3,5ꢀdiethylꢀ2ꢀmethylaminoꢀ[1,3,5]ꢀ
4. Bax, A., Niu, C.ꢀH., and Live, D., Sensitivityꢀenhanced
NMR detection of nonprotonated nitrogenꢀ15 nuclei, J.
Am. Chem. Soc., 1984, vol. 106, p. 1150.
oxadiazineꢀ2,4ꢀdione)tungsten(VI), J. Coord. Chem.
,
2003, vol. 56, pp. 995–1002.
5. Freund, M., Über die Einwirking von Brom und Aethylꢀ
und Phenylsenfol, J. Liebigs Ann. Chem., 1895, vol. 285,
pp. 184–185.
Translated by O. Tsarev
INORGANIC MATERIALS Vol. 49
No. 9
2013