Synthesis and complexing properties of alkyl (3-oxo-2,3-dihydrothiophen-2- ylidene)- and (4-oxothiazolidin-5-ylidene)acetate derivatives

Article abstract of DOI:10.1023/B:RUJO.0000044550.62124.94

Condensation of dimethyl and diethyl acetylenedicarboxylate with thioacetamides gave the corresponding alkyl (3-oxo-2,3-dihydrothiophen-2- ylidene)- and (4-oxothiazolidin-5-ylidene)acetates. Treatment of these compounds with zinc in acetic acid resulted in reduction of the exocyclic double bonds. The products can be used in membrane processes as sodium cation carriers.

Full text of DOI:10.1023/B:RUJO.0000044550.62124.94

Russian Journal of Organic Chemistry, Vol. 40, No. 6, 2004, pp. 866–869. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 6, 2004,
pp. 904–907.
Original Russian Text Copyright © 2004 by Kosterina, Morzherin, Kramarenko, Berseneva, Matern, Tkachev, Bakulev.
Dedicated to Full Member of the Russian Academy of Sciences
O.N. Chupakhin on his 70th Anniversary
Synthesis and Complexing Properties
of Alkyl (3-Oxo-2,3-dihydrothiophen-2-ylidene)-
and (4-Oxothiazolidin-5-ylidene)acetate Derivatives
M. F. Kosterina1, Yu. Yu. Morzherin1, O. A. Kramarenko1, V. S. Berseneva1, A. I. Matern1,
A. V. Tkachev2, and V. A. Bakulev2
1 Ural State Technical University, ul. Mira 19, Yekaterinburg, 620002 Russia
e-mail: morjerine@htf.ustu.ru
2 Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: atkachev@nioch.nsc.ru
Received January 12, 2004
Abstract—Condensation of dimethyl and diethyl acetylenedicarboxylate with thioacetamides gave the corre-
sponding alkyl (3-oxo-2,3-dihydrothiophen-2-ylidene)- and (4-oxothiazolidin-5-ylidene)acetates. Treatment of
these compounds with zinc in acetic acid resulted in reduction of the exocyclic double bonds. The products can
be used in membrane processes as sodium cation carriers.
Extensive studies in the field of membrane transfer
processes, which play an important role in biological
systems, have started at the end of the 20th century [1].
The synthesis of first receptor molecules capable of
selectively binding organic and inorganic substrates
gave an impetus to development of a new interdis-
ciplinary field of chemistry, namely supramolecular
chemistry [2]. Apart from recognition and catalysis,
transport is an integral feature of supramolecules and is
a fundamental process in supramolecular chemistry.
ortho position with respect to the endocyclic hetero-
atom implies that such compounds can be used as
ligands for complex formation with various metal ions.
We previously developed a new convenient procedure
for the synthesis of 2,5-dimethylenethiazolidin-4-ones
and 2-methylenethiophenes via reaction of thioacet-
amides with dimethyl acetylenedicarboxylate (DMAD)
[5, 6]. The goal of the present work was to obtain
new thiophene and thiazole derivatives containing
an ethoxycarbonylmethylene group in the 2-position
and examine the possibility of using such heterocyclic
compounds as ligands for membrane transfer of
sodium salts.
Selective membrane permeability is ensured by
carrier molecules which are present in a liquid mem-
brane and are capable of selectively reacting with
a compound to be transferred [3]. Carrier molecules
determine the nature of substrates transferred through
a membrane and such physical parameters of mass
transfer as rate, selectivity, and type of the process.
Variation of the receptor structure makes it possible to
control the transfer process and analyze effects of
structural factors on the thermodynamic and kinetic
parameters [4].
We have found that, depending on the initial thio-
acetamide, the reaction with acetylenedicarboxylic
acid esters leads to formation of thiophenes IIa and
IIb or 2,5-dimethylenethiazolidin-4-ones IIIa and IIIb.
The latter were obtained from thioamide Ic which has
no substituents at the nitrogen atom (Scheme 1).
Treatment of compound IIIa with metallic zinc in
acetic acid at room temperature afforded a mixture of
products, and the conversion of IIIa was not complete.
When the reaction was carried out at 60–70°C, a single
Heterocycles possessing exocyclic trisubstituted
double bonds attract attention due to their specific
geometry. The presence of a carbonyl group in the
1
product was formed. Its H NMR spectrum contained
1070-4280/04/4006-0866 © 2004 MAIK “Nauka/Interperiodica”

SYNTHESIS AND COMPLEXING PROPERTIES
867
Scheme 1.
R2
R3
S
N
R4OCO
COOR4
+
R1
Ia–Ic
O
O
MeO
H
R1
OR4
OMe
Zn/AcOH
S
S
O
O
R2
N
N
R3
O
IIa, IIb
V
O
O
H
OR4
OMe
HN
Zn/AcOH
HN
O
S
S
R1
O
O
MeO
NH
IIIa, IIIb
IV
I, II, R1 = 4-MeOC6H4, R2R3N = morpholino, R4 = Me (a); R1 = 4-BrC6H4, R2R3N = morpholino, R4 = Et (b);
Ic, R1 = 4-MeOC6H4NHCO, R2 = R3 = H; III, R1 = 4-MeOC6H4NHCO, R4 = Me (a), Et (b).
signals from two NH protons at δ 9.76 and 8.58 ppm,
two two-proton doublets from aromatic protons at
δ 7.43 and 6.78 ppm, two three-proton singlets from
two methoxy groups at δ 3.89 and 3.66 ppm, and
six one-proton doublets of doublets at δ 4.93 (J = 8.5,
4.6 Hz), 3.97 (J = 4.2, 9.6 Hz), 3.01 (J = 16.8, 4.2 Hz),
2.94 (J = 14.9, 4.6 Hz), 2.70 (J = 16.8, 9.6 Hz), and
2.62 ppm (J = 14.9, 8.5 Hz). The latter were assigned
to two CHCH2 groups. Taking into account these data
and also the presence of the molecular ion peak with
m/z 338 (47%) in the mass spectrum, the product was
assigned the structure of thiazolidine IV.
3.7 Hz), and 2.62 ppm (J = 17.1, 10.7 Hz) which were
assigned to 2-H and 2-CH2.
Using the NMR titration technique, we previously
[7] found that thiazolidinones structurally related to
III are capable of forming complexes with sodium
cation. In the present work we examined complexing
properties of compounds IIa, IIb, and IV by the mem-
brane transfer technique. The ion fluxes of sodium
salts through an impregnated liquid membrane are
given in table together with the results of blank
experiment in which the membrane contained no
carrier. It is seen that thiophene derivatives IIa and IIb
insignificantly increase the rate of ion transport and
that the latter weakly depends on the anion nature.
Our attempts to reduce the exocyclic double bond
in thiophene derivatives IIa and IIb under analogous
conditions resulted in decomposition of the thiophene
ring. The reaction with thiophene IIa at reduced
temperature was complete in less than 30 min, and
we isolated 20% of 2,3-dihydrothiophene V. In the
1H NMR spectrum of the product we observed signals
from aromatic protons as two two-proton doublets at
δ 7.06 and 6.90 ppm (J = 8.5 Hz), two methoxy groups
as two three-proton singlets at δ 3.75 and 3.64 ppm,
protons of the morpholine fragment as a multiplet at
δ 3.20–3.35 ppm, and three one-proton doublets of
doublets at δ 4.05 (J = 10.7, 3.7 Hz), 3.15 (J = 17.1,
Initial ion fluxes through impregnated liquid membranes
(temperature 20°C)
Ion flux, (mol s–1 m–2)×10–6
Compound no.
Na2Cr2O7
9.6000
0.1460
0.1460
0.0750
Na2SO4
6.7200
0.1720
0.1620
0.0735
NaCl
15.5000
00.4370
00.4750
00.0644
IVa
IIa
IIb
Blank experiment
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 6 2004

KOSTERINA et al.
868
Thiazolidine derivative IV ensures a higher transfer
rate. These data may be interpreted in terms of
formation of dative bonds involving the ester carbonyl
oxygen atom and sulfur atom in thiophenes II or
carbamoyl oxygen atom and ring nitrogen atom in IV,
as shown in Scheme 2 [7].
CH), 6.93 d (2H, Harom, J = 6.8 Hz), 7.16 d (2H, Harom,
J = 6.8 Hz). Found, %: N 4.12; S 8.97. C18H19NO5S.
Calculated, %: N 3.88; S 8.86.
Ethyl 2-[(Z)-4-(4-bromophenyl)-5-morpholino-
3-oxo-2,3-dihydrothiophen-2-ylidene]acetate (IIb)
was synthesized in a similar way using diethyl ace-
1
tylenedicarboxylate. Yield 65%, mp 184°C. H NMR
spectrum (DMSO-d6), δ, ppm: 1.30 t (3H, CH3, J =
7.1 Hz), 3.44–3.46 m (4H, 2CH2), 3.60–3.64 m (4H,
2CH2), 4.25 q (2H, OCH2, J = 7.1 Hz), 6.61 s (1H,
Scheme 2.
O
O
H
Na
O
R1
CH), 7.25 d (2H, Harom, J = 6.8 Hz), 7.60 d (2H, Harom
,
OMe
N
OMe
J = 7.0 Hz). Mass spectrum, m/z (Irel, %): 425 (29), 423
(30). Found, %: N 3.64; S 8.01. C18H18BrNO4S. Cal-
culated, %: N 3.30; S 7.56.
S
S
O
R2
O
N
R3
Ar
NH
Na
Methyl 2-[(2E,5Z)-2-(4-methoxyphenylcarba-
moylmethylene)-4-oxothiazolidin-5-ylidene]acetate
(IIIa). Dimethyl acetylenedicarboxylate, 0.4 ml
(3.17 mmol), was added at room temperature to
a suspension of 3 mmol of thioacetamide Ic in 30 ml
of ethanol (or 40 ml of chloroform, or 2 ml of DMSO).
The mixture was stirred for 2 h and cooled, and the
precipitate was filtered off and recrystallized from
alcohol. Yield 85%, mp 128–129°C; published data
Thus we have developed a procedure for the syn-
thesis of hydrogenated sulfur-containing heterocycles
having methylene and alkoxycarbonylmethylene sub-
stituents and demonstrated the possibility of using the
products as carriers for transfer of sodium cations
through an impregnated liquid membrane.
EXPERIMENTAL
1
[7]: mp 128°C. H NMR spectrum (DMSO-d6), δ,
ppm: 3.72 s (3H, OMe), 3.77 s (3H, OMe), 5.85 s (1H,
CH=C2), 6.69 s (1H, CH=C5), 6.87 d (2H, Harom, J =
9.2 Hz), 7.52 d (2H, Harom, J = 9.2 Hz), 9.85 s (1H,
NH), 12.33 br.s (1H, NH). Found, %: N 8.38; S 9.95.
C15H14N2O5S. Calculated, %: N 8.38; S 9.59.
The progress of reactions and the purity of products
were monitored by TLC on Silufol UV-254 plates
using the following solvent systems: chloroform,
chloroform–ethanol (9:1, 15:1, 20:1), and ethyl
acetate–hexane (1.5:2, 1:2). The NMR spectra were
1
recorded on Bruker WM-250 (250 MHz for H) and
Ethyl 2-[(2E,5Z)-2-(2-methoxyphenylcarbamoyl-
methylene)-4-oxothiazolidin-5-ylidene]acetate (IIIb)
was synthesized as described above for compound
IIIa using diethyl acetylenedicarboxylate. Yield 80%,
1
Bruker DRX-400 spectrometers (400 MHz for H and
100 MHz for 13C) using tetramethylsilane as internal
reference. The mass spectra (electron impact, 70 eV)
were obtained on Varian MAT 311A and Finnigan
MAT 8200 instruments with direct sample admission
into the ion source. The solvents were dried and
purified by standard procedures.
1
mp 128–129°C. H NMR spectrum (DMSO-d6), δ,
ppm: 1.12 t (3H, Me, J = 7.0 Hz), 4.12 q (2H, OCH2,
J = 7.0 Hz), 5.82 s (1H, CH=C2), 6.68 s (1H, CH=C5),
7.0–7.2 m (4H, Harom), 9.85 s (1H, NH), 12.33 br.s
(1H, NH). Mass spectrum, m/z (Irel, %): 398 (47), 396
(46). Found, %: N 7.22; S 7.95. C15H13BrN2O4S. Cal-
culated, %: N 7.05; S 8.07.
Methyl 2-[(Z)-4-(4-methoxyphenyl)-5-morpho-
lino-3-oxo-2,3-dihydrothiophen-2-ylidene]acetate
(IIa). Dimethyl acetylenedicarboxylate, 0.1 mol, was
added to a solution of 0.1 mol of 1-morpholino-2-(4-
methoxyphenyl)ethanethione (Ia) in 10 ml of anhy-
drous ethanol, and the mixture was heated for 2 h
under reflux. The solvent was distilled off, the residue
was ground with alcohol, and the precipitate was
filtered off and recrystallized from chloroform–hexane.
Yield 50%, mp 159–161°C; published data [6]:
Methyl 2-[2-(4-methoxyphenylcarbamoyl-
methyl)-4-oxothiazolidin-5-yl]acetate (IV). Metallic
zinc, 6 mmol, was added at room temperature to
a suspension of 3 mmol of thiazolidinone IIIa in 10 ml
of glacial acetic acid. The mixture was heated for 2 h
under reflux, an additional 6 mmol of zinc was added,
and the mixture was heated for 6 h under reflux,
cooled, and filtered from the undissolved material. The
filtrate was extracted with chloroform (3×100 ml),
the extract was washed with water and evaporated, and
1
mp 160°C. H NMR spectrum (DMSO-d6), δ, ppm:
3.44–3.48 m (4H, 2CH2), 3.60–3.64 m (4H, 2CH2),
3.76 s (3H, OCH3), 3.77 s (3H, OCH3), 6.63 s (1H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 6 2004

SYNTHESIS AND COMPLEXING PROPERTIES
869
the residue was recrystallized from chloroform–
hexane. Yield 75%, mp 190°C. 13C NMR spectrum
(DMSO-d6), δC, ppm: 38.97 (CH2), 42.11 (C5), 45.16
(CH2), 51.69 (C2), 51.77 (OCH3), 55.14 (OCH3),
113.82 (CHarom), 120.71 (CHarom), 131.95 (NCarom),
155.22 (OCarom), 166.97 (CONH), 171.12 (COOMe),
173.47 (C4). Mass spectrum, m/z (Irel, %): 338 (47).
Found, %: N 7.92; S 9.35. C15H18N2O5S. Calculated,
%: N 8.28; S 9.48.
a 1 M solution of the corresponding salt. The substrate
concentration in the receiving phase (distilled water,
V = 400 ml) was determined by measuring the
conductivity.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 04-03-96143a URAL) and by the American Civil
Research and Development Foundation for Inde-
pendent States of the Former Soviet Union (CRDF)
(grant no. REC-005).
Methyl 2-[4-(4-methoxyphenyl)-5-morpholino-3-
oxo-2,3-dihydro-2-thienyl]acetate (V). Metallic zinc,
6 mmol, was added to a suspension of 3 mmol of
thiophene IIa in 10 ml of glacial acetic acid at 15–
18°C. The mixture was stirred for 30 min, 50 ml of
water was added, and the product was extracted into
methylene chloride (3×30 ml). The extract was dried
and evaporated, and the residue was purified by flash
chromatography using CH2Cl2 as eluent. Yield 20%,
oily substance. Mass spectrum, m/z (Irel, %): 363 (17).
Found, %: N 3.92; S 8.53. C18H21NO5S. Calculated, %:
N 3.85; S 8.82.
REFERENCES
1. Mulder, M., Basic Principles of Membrane Technology,
Dordrecht: Kluwer Academic, 1996, 2nd ed.
2. Lehn, J.-M., Supramolecular Chemistry: Concepts and
Perspectives, Weinheim: VCH, 1995. Translated under
the title Supramolekulyarnaya khimiya, Novosibirsk:
Nauka, Sib. Predpr. Ross. Akad. Nauk, 1998, p. 334.
3. Pedersen, C.J., J. Am. Chem. Soc., 1967, vol. 89, p. 2495.
4. Antipin, I.S., Stoikov, I.I., Khrustalev, A.A., and Kono-
valov, A.I., Izv. Ross. Akad. Nauk, Ser. Khim., 2001,
p. 2038.
Ion transport through a liquid membrane. The
electric conductivity of solutions was measured with
a Radelkis OK-102 conductometer. The ion fluxes
through impregnated liquid membranes were measured
in a glass beaker using a platinum electrode. Liquid
membranes were prepared by impregnation of a poly-
(tetrafluoroethylene) membrane (Sigma–Aldrich;
diameter 25 mm, pore diameter 0.2 µm) with
a solution of 0.02 mmol of carrier in 0.02 ml of
o-nitrophenyl octyl ether. The exhaustible phase was
5. Berseneva, V.S., Tkachev, A.V., Morzherin, Yu.Yu.,
Dehaen, W., Luyten, I., Toppet, S., and Bakulev, V.A.,
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Ross. Akad. Nauk, Ser. Khim., 2002, p. 604.
7. Morzherin, Yu.Yu., Kosterina, M.F., Berseneva, V.S.,
Dehaen, W., and Bakulev, V.A., Izv. Ross. Akad. Nauk,
Ser. Khim., 2002, p. 1194.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 6 2004