E-Z-izomerization of 2-methylenethiazolidin-4-ones

Article abstract of DOI:10.1023/A:1020912932335

The equilibrium concentrations of E- and Z-isomers of thiazolidin-4-ones containing exocyclic double bonds in positions 2 and 5 of the cycle were determined in DMSO-d₆. The influence of the nature of the substituents on the equilibrium position was found. Electron-releasing substituents stabilize the E,Z-configuration and electron-withdrawing substituents stabilize the Z,Z-configuration. The association constants of E- and Z-2-ethoxycarbonylmethylenethiazolidin-4-ones with the sodium cation were determined by ¹H NMR spectroscopy.

Full text of DOI:10.1023/A:1020912932335

1292
Russian Chemical Bulletin, International Edition, Vol. 51, No. 7, pp. 1292—1297, July, 2002
E—ZꢀIzomerization of 2ꢀmethylenethiazolidinꢀ4ꢀones
a
a
b
a
Yu. Yu. Morzherin,a M. F. Kosterina, V. S. Berseneva, W. Dehaen, and V. A. Bakulev
ꢀ
aThe Urals State Technical University,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation.
Fax: +7 (343 2) 74 5483. Eꢀmail: morjerine@htf.ustu.ru
bDepartment of Chemistry, University of Leuven,
Celestijnenlaan 200F, 3001 Heverlee (Leuven), Belgium
The equilibrium concentrations of Eꢀ and Zꢀisomers of thiazolidinꢀ4ꢀones containing
exocyclic double bonds in positions 2 and 5 of the cycle were determined in DMSOꢀd6. The
influence of the nature of the substituents on the equilibrium position was found. Electronꢀ
releasing substituents stabilize the E,Zꢀconfiguration and electronꢀwithdrawing substituents
stabilize the Z,Zꢀconfiguration. The association constants of Eꢀ and Zꢀ2ꢀethoxycarbonylꢀ
methylenethiazolidinꢀ4ꢀones with the sodium cation were determined by 1H NMR specꢀ
troscopy.
Key words: sulfurꢀcontaining heterocycles, nitrogenꢀcontaining heterocycles, exocyclic
double bond, complex formation, E—Zꢀizomerization.
Scheme 1
Thiazolidinꢀ4ꢀones containing exocyclic trisubstituted
double bonds attract attention due to their geometry.
The presence of carbonyl groups in the neighbor posiꢀ
tion to the cyclic sulfur and nitrogen atoms assumes the
use of these compounds as ligands for binding complexes
of various metal ions. We have previously developed a
convenient method for the synthesis of 5ꢀmethyleneꢀ
thiazolidinꢀ4ꢀones by the reaction of malonothioamides
with dimethyl acetylenedicarboxylate (DMAD).1 The
exocyclic double bond in position 5 of the cycle was
shown to have the Zꢀconfiguration. The compounds conꢀ
taining the exocyclic double bond in position 2 of the
thiazolidinone cycle can be considered as cyclic enamꢀ
ines2 and exhibit E—Zꢀisomerism.1,3
R = CN (a), CONMe2 (b), COOEt (c), CON(CH2CH2)2O (d),
CON(CH2CH2)2CH2 (e), CONHMe (f),
(g), CONHC6H11ꢀcyclo (h),
The purpose of this work is to study isomerization
about the exocyclic double bond of thiazolidines and
their complex formation with the sodium cation.
CONHCH2Ph (i), CONHPh (j), CONHC6H4OMeꢀ4 (k),
CONHC6H4OMeꢀ3 (l), CONHC6H5Meꢀ4 (m), CONHC6H4Meꢀ3 (n),
CONHC6H4Fꢀ4 (o), CONHC6H4Fꢀ2 (p), CONHC6H3Cl2ꢀ2,6 (q),
CONHC6H2Cl3ꢀ2,4,6 (r), CONHC6H4COOEtꢀ4 (s).
Results and Discussion
We have found that the mutual transformations of
compounds Z,Zꢀ1a—s and E,Zꢀ1a—s occur in various
solvents (Scheme 1). The condensation of thioamides of
malonic acid with dimethyl acetylenedicarboxylate alꢀ
most always affords mixtures of isomers 1, whose comꢀ
position depends on the nature of the solvent, namely,
the fraction of the E,Zꢀisomer increases in chloroform,
and that of the Z,Zꢀisomer increases in DMSO. Note
that isomerization occurs only about the exocyclic bond
in position 2 of the cycle. This fact is easily explained if
the RCH=C—NH fragment in these compounds is conꢀ
sidered as enaminic.
Individual isomers Z,Zꢀ1a—f,h,m,p—s and
E,Zꢀ1a—g,m,p—s were isolated by fractional crystallizaꢀ
tion from chloroform (isomers E,Zꢀ1a,m,p, unlike
Z,Zꢀ1a,m,p, are poorly soluble in chloroform). Other
compounds were used as mixtures of two isomers. The
equilibrium concentration of both isomers, which reꢀ
mains unchanged in time within a measurement error
characteristic of NMR spectroscopy, is established durꢀ
ing 2—3 days in DMSO solutions of compounds 1a—s
(Table 1). We failed to achieve the equilibrium concenꢀ
tration of the isomers in such solvents as acetoneꢀd6 and
CDCl3 even when solutions were stored for 10—15 days.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1194—1198, July, 2002.
1066ꢀ5285/02/5107ꢀ1292 $27.00 © 2002 Plenum Publishing Corporation

E—ZꢀIzomerization of 2ꢀmethylenethiazolidinꢀ4ꢀones Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1293
Table 1. Ratio of E,Zꢀ to Z,Zꢀisomers of compound 1 in
Table 2. Ratio of Eꢀ to Zꢀisomers of compound 2 in DMSOꢀd6
DMSOꢀd6 solutions
solutions
Comꢀ
pound
Content of isomers (%)
Equilibrium constant
Comꢀ
pound
Content of isomers (%)
Equilibrium constant
E,Z/Z,Z
Z/E
E,Z
Z,Z
E
Z
1a
1b
1c
1d
1e
1f
1g
1h
1I
1j
26
>99
81
80
75
55
61
6
49
86
92
37
88
82
42
10
0
74
<1
19
20
25
45
39
94
51
14
8
63
12
18
58
90
100
98
99
0.351
2a
2b
2c
2d
2e
90
85
60
93
98
10
15
40
7
9.00
5.67
1.50
13.3
49
4.26
4.00
3.00
1.22
1.56
0.064
0.960
6.14
3.34
0.587
7.33
4.55
0.538
0.111
0
2
5—15% (Table 2), except for orthoꢀsubstituted anilide
2c. Note that the reduction5 of compounds 1 always proꢀ
duces only the Eꢀisomer of 2. This is related, most likely,
to a higher thermodynamic stability of the Еꢀisomer.
1k
1l
1m
1n
1o
1p
1q
1r
1s
2
1
0.020
0.010
Scheme 2
Based on the position of the carboxyl substituents in
compounds 1 and 2, we can assume that the latter can be
used as ligands for various cations. We obtained the
1Н NMR spectra of compounds Z,Zꢀ1с and E,Zꢀ1c in
acetoneꢀd6 in the presence of NaI in different concenꢀ
trations. The E,Zꢀisomer of 2c exhibits the shift of the
signal from the methine proton at the double bond in
position 2 of the cycle by 0.2—0.8 ppm, whereas the
position of the signal from the methine proton at the
exocyclic double bond in position 5 remains virtually
unchanged (Fig. 1). The intensity of signals from the
The data obtained show that the introduction of elecꢀ
tronꢀwithdrawing substituents into the aryl residue
(R1 = NHAr) stabilizes the Z,Zꢀisomers of compound 1.
For example, Z,Zꢀisomers predominate for compounds
1p,s containing fluorine and the ethoxycarbonyl group in
the orthoꢀ and paraꢀpositions of the aryl substituent, reꢀ
spectively. This can be explained by the stabilizing S...O
interaction1,4 (Scheme 2). An increase in the stability of
the E,Zꢀisomer of compound 1 can be explained by the
stabilizing effect of the hydrogen bond, whose formation
is favored by the electronꢀreleasing substituents in the
carbamoyl groups. The steric factor substantially affects
the ratio of Z,Zꢀ and E,Zꢀisomers. For example, for comꢀ
pounds containing the cyclohexyl, 2,6ꢀdichlorophenyl,
2ꢀfluorophenyl, and 2,4,6ꢀtrichlorophenyl substituents in
the carboxamoyl fragment, the equilibrium is almost comꢀ
pletely shifted toward Z,Zꢀisomer 1h,q,p,r.
δ
1
6.6
6.4
2
6.2
6.0
5.8
5
10
15
C/mmol L–1
Fig. 1. Dependence of chemical shifts of methine protons in
compound E,Zꢀ1c on the concentration of NaI in acetoneꢀd6:
1, for the proton at the exocyclic bond in position 5 of the
cycle; and 2, for the proton at the exocyclic bond in position 2
of the cycle.
Unlike compounds 1, in thiazolidines 2a—e containꢀ
ing only one C=C bond the equilibrium is shifted toward
the Eꢀisomer. The content of the Zꢀisomer is at most

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Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
Morzherin et al.
NH protons also decreases strongly. For the Z,Zꢀisomer
of 1с the addition of NaI does not result in any substanꢀ
tial changes in the NMR spectra. We can conclude that
the effects observed in the case of the E,Zꢀisomer of 1c
1
Table 3. Н NMR spectra of compounds Z,Zꢀ1f—s and E,Zꢀ1f—s
Comꢀ
pound
δ (J/Hz)
Z,Zꢀ1f 10.23 (t, 1 H, NH); 6.52 (s, 1 H, CH=C(5)); 5.87 (s, 1 H, CH=C(2)); 3.77 (s, 3 H, OMe); 2.51 (d+s, 3 H, NMe)
Z,Zꢀ1g 12.16 (br.s, 1 H, NH); 7.80—7.90 (m, 4 H, ArH); 6.52 (s, 1 H, CH=C(5)); 5.46 (t, 1 H, CH=C(5), J = 7.6);
4.28 (d, 2 H, CH2, J = 7.6); 3.73 (s, 3 H, OMe)
Z,Zꢀ1h 12.18 (s, 1 H, NH); 7.99 (d, 1 H, NH, J = 7.6); 6.48 (s, 1 H, CH=C(5)); 5.87 (s, 1 H, CH=C(2)); 3.76 (s, 3 H,
OMe); 3.40—3.50 (m, 1 H, NCH); 1.00—2.00 (m, 10 H, C5H10)
Z,Zꢀ1i 12.16 (br.s, 1 H, NH); 8.62 (t, 1 H, NH, J = 6.2); 7.20—7.36 (m, 5 H, Ph); 6.50 (s, 1 H, CH=C(5)); 5.94 (s, 1 H,
CH=C(2)); 4.36 (d, 2 H, CH2, J = 6.2); 3.77 (s, 3 H, OMe)
Z,Zꢀ1j 12.29 (s, 1 H, NH); 10.05 (s, 1 H, NH); 7.60 (d, 2 H, ArH, J = 7.4); 7.25 (dd, 2 H, ArH, J = 7.4, J = 8.0); 7.00 (t,
1 H, ArH, J = 8.0); 6.54 (s, 1 H, CH=C(5)); 6.06 (s, 1 H, CH=C(2)); 3.80 (s, 3 H, OMe)
Z,Zꢀ1k 12.36 (br.s, 1 H, NН); 10.05 (s, 1 H, NН); 7.53 (d, 2 H, ArH, J = 9.2); 6.97 (d, 2 H, ArH, J = 9.2); 6.54 (s, 1 H,
СН=С(5)); 6.05 (s, 1 H, СН=С(2)); 3.78 (s, 3 H, OMe); 3.73 (s, 3 H, OMe)
Z,Zꢀ1l 12.4 (br.s, 1 H, NН); 10.15 (s, 1 H, NН); 7.10—7.36 (m, 3 H, ArН); 6.30—6.33 (m, 1 H, ArН); 6.56 (s, 1 H,
СН=С(5)); 6.07 (s, 1 H, СН=С(2)); 3.75 (s, 3 H, OMe); 3.74 (s, 3 H, OMe)
Z,Zꢀ1m 11.6 (br.s, 1 H, NН); 10.09 (s, 1 H, NН); 7.48 (d, 2 H, ArH, J = 8.2); 7.10 (d, 2 H, ArH, J = 8.2); 6.54 (s, 1 H,
СН=С(5)); 6.06 (s, 1 H, СН=С(2)); 3.78 (s, 3 H, OMe); 2.25 (s, 3 H, Me)
Z,Zꢀ1n 12.40 (s, 1 H, NH); 10.10 (s, 1 H, NH); 7.51 (s, 1 H, ArH); 7.38 (d, 1 H, ArH, J = 7.9); 7.18 (dd, 1 H, ArH,
J = 7.9, J = 7.5); 6.86 (d, 1 H, ArH, J = 7.5); 6.55 (s, 1 H, CH=C(5)); 6.08 (s, 1 H, CH=C(2)); 3.79 (s, 1 H,
OMe); 2.28 (s, 3 H, Me)
Z,Zꢀ1o 12.8 (s, 1 H, NH); 10.1 (s, 1 H, NH); 7.62—7.69 (m, 2 H, ArH); 7.08—7.19 (m, 2 H, ArH); 6.56 (s, 1 H, CH=C(5));
6.06 (s, 1 H, CH=C(2)); 3.79 (s, 3 H, OMe)
Z,Zꢀ1p 12.44 (s, 1 H, NH); 10.00 (s, 1 H, NH); 7.95—8.10 (m, 1 H, ArH); 7.10—7.30 (m, 3 H, ArH); 6.56 (s, 1 H,
CH=C(5)); 6.30 (s, 1 H, CH=C(2)); 3.78 (s, 3 H, OMe)
Z,Zꢀ1r 12.70 (s, 1 H, NH); 9.70 (s, 1 H, NH); 8.52 (s, 1 H, ArH); 7.62 (s, 1 H, ArH); 6.55 (s, 1 H, CH=C(5));
6.32 (s, 1 H, CH=C(2)); 3.81 (s, 3 H, OMe)
Z,Zꢀ1s 12.48 (s, 1 H, NH); 10.50 (s, 1 H, NH); 7.90 (d, 9.2, 2 H, ArH); 7.75 (d, 9.2, 2 H, ArH); 6.58 (s, 1 H, CH=C(5));
6.10 (s, 1 H, CH=C(2)); 4.28 (q, 2 H, OMe, J = 7.1); 3.79 (s, 3 H, OMe); 1.31 (t, 3 H, Me, J = 7.1)
E,Zꢀ1f 9.65 (t, 1 H, NH); 6.85 (s, 1 H, CH=C(5)); 5.46 (s, 1 H, CH=C(2)); 3.78 (s, 3 H, OMe); 2.53 (d+s, 3 H, NMe)
E,Zꢀ1g 11.88 (br.s, 1 H, NH); 7.80—7.90 (m, 4 H, ArH); 6.53 (s, 1 H, CH=C(5)); 5.00 (t, 1 H, CH=C(5), J = 7.3);
4.50 (d, 2 H, CH2, J = 7.3); 3.72 (s, 3 H, OMe)
E,Zꢀ1h 12.10 (s, 1 H, NH); 8.02 (d, 7.5, 1 H, NH); 6.72 (s, 1 H, CH=C(5)); 5.45 (s, 1 H, CH=C(2)); 3.77 (s, 3 H, OMe);
3.40—3.50 (m, 1 H, NCH); 1.00—2.00 (m, 10 H, C5H10)
E,Zꢀ1i 12.6 (br.s, 1 H, NH); 8.65 (t, 1 H, NH, J = 6.2); 7.20—7.36 (m, 5 H, Ph); 6.77 (s, 1 H, CH=C(5)); 5.73 (s, 1 H,
CH=C(2)); 4.37 (d, 2 H, CH2, J = 6.2); 3.76 (s, 3 H, OMe)
E,Zꢀ1j 11.79 (s, 1 H, NH); 9.51 (s, 1 H, NH); 7.58 (d, 2 H, ArH, J = 7.6); 7.28 (dd, 2 H, ArH, J = 7.6, J = 7.9); 7.09 (t,
1 H, ArH, J = 7.9); 6.84 (s, 1 H, CH=C(5)); 5.86 (s, 1 H, CH=C(2)); 3.77 (s, 3 H, OMe)
E,Zꢀ1k 12.33 (br.s, 1 H, NН); 9.85 (s, 1 H, NН); 7.52 (d, 2 H, ArH, J = 9.2); 6.87 (d, 2 H, ArH, J = 9.2); 6.69 (s, 1 H,
СН=С(5)); 5.85 (s, 1 H, СН=С(2)); 3.77 (s, 3 H, OMe); 3.72 (s, 3 H, OMe)
E,Zꢀ1l 11.9 (br.s, 1 H, NН); 10.15 (s, 1 H, NН); 7.10—7.36 (m, 3 H, ArН); 6.70 (s, 1 H, СН=С(5)); 6.30—6.35 (m, 1 H,
ArН); 5.70 (s, 1 H, СН=С(2)); 3.79 (s, 3 H, OMe); 3.78 (s, 3 H, OMe)
E,Zꢀ1m 12.38 (br.s, 1 H, NН); 10.08 (s, 1 H, NН); 7.50 (d, 8.2, 2 H, ArH); 7.11 (d, 8.2, 2 H, ArH); 6.70 (s, 1 H,
СН=С(5)); 5.70 (s, 1 H, СН=С(2)); 3.78 (s, 3 H, OMe); 2.25 (s, 3 H, Me)
E,Zꢀ1n 12.00 (s, 1 H, NH); 10.05 (s, 1 H, NH); 7.51 (s, 1 H, ArH); 7.37 (d, 1 H, ArH, J = 7.9); 7.17 (dd, 1 H, ArH,
J = 7.9, J = 7.5); 6.85 (d, 1 H, ArH, J = 7.5); 6.85 (s, 1 H, CH=C(5)); 5.68 (s, 1 H, CH=C(2)); 3.77 (s, 3 H,
OMe); 2.29 (s, 3 H, Me)
E,Zꢀ1o 12.68 (s, 1 H, NH); 10.21 (s, 1 H, NH); 7.62—7.69 (m, 2 H, ArH); 7.08—7.19 (m, 2 H, ArH); 6.71 (s, 1 H,
CH=C(5)); 5.70 (s, 1 H, CH=C(2)); 3.78 (s, 3 H, OMe)
E,Zꢀ1p 12.48 (s, 1 H, NH); 10.00 (s, 1 H, NH); 7.95—8.10 (m, 1 H, ArH); 7.10—7.30 (m, 3 H, ArH); 6.76 (s, 1 H,
CH=C(5)); 5.80 (s, 1 H, CH=C(2)); 3.79 (s, 3 H, OMe)
E,Zꢀ1r 12.57 (s, 1 H, NH); 9.74 (s, 1 H, NH); 8.52 (s, 1 H, ArH); 7.62 (s, 1 H, ArH); 6.78 (s, 1 H, CH=C(5));
5.82 (s, 1 H, CH=C(2)); 3.81 (s, 3 H, OMe)
E,Zꢀ1s 12.00 (s, 1 H, NH); 10.46 (s, 1 H, NH); 7.91 (d, 2 H, ArH, J = 9.2); 7.74 (d, 2 H, ArH, J = 9.2); 6.85 (s, 1 H,
CH=C(5)); 5.95 (s, 1 H, CH=C(2)); 4.27 (q, 2 H, OCH2, J = 7.1); 3.77 (s, 3 H, OMe); 1.25 (t, 3 H, Me, J = 7.1)

E—ZꢀIzomerization of 2ꢀmethylenethiazolidinꢀ4ꢀones Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1295
are caused by the coordination of the sodium cation to
the ester group at the exocyclic bond in position 2 of the
cycle and to the nitrogen atom of the cycle. No coordiꢀ
nation involves the ester group at the double exocyclic
bond in position 5 of the cycle, as well as the ester group
in position 2 of the cycle for the Z,Zꢀisomer, and to the
sulfur atom. We calculated the association constant
(105 12 L mol–1) from the chemical shift of the methine
bond in position 2 of the heterocycle. The influence of
substituents on the position of equilibrium was found,
and electronꢀdonating substituents were shown to stabiꢀ
lize the E,Zꢀisomer. It was revealed that the E,Zꢀisomer
of 1c and the Еꢀisomer of 2a form complexes with NaI
in acetone, whereas Z,Zꢀ1c and Zꢀ2a cannot form
complexes.
1
Experimental
proton in the Н NMR spectrum at different concentraꢀ
tions of NaI using the method proposed previously.6 The
Eꢀisomer of 2 exhibits the downfield shift of the signals
from the methine proton depending on the concentraꢀ
tion of NaI, while no shift of the signal from the methine
proton is observed for the Zꢀisomer of 1a. The associaꢀ
NMR spectra were recorded on Bruker 250 (250 MHz
1
1
for Н) and Bruker DRXꢀ500 (500 MHz for Н and 125 MHz
for 13С) instruments using HMDS as internal standard. IR
spectra were recorded on an IRꢀ75 spectrometer in KBr pelꢀ
lets. The reaction course and purity of compounds were moniꢀ
tored by TLC on the Silufol UVꢀ254 plates in chloroform or
ethyl acetate—hexane (1 : 1) and chloroform—ethanol (9 : 1)
systems. Corrections for melting points were not introduced.
Solvents were purified and dried using standard procedures.
tion constant of the Eꢀisomer of 1a is 112 8 L mol–1
.
Thus, it was shown that isomerization in solutions of
2,5ꢀdimethylenethiazolidinꢀ4ꢀones in DMSOꢀd6, СDCl3,
and acetoneꢀd6 occurs only about the double exocyclic
Table 4. Physicochemical data for compounds E,Zꢀ1f—s and Eꢀ2c—e
Comꢀ
pound
Yield
(%)
M.p./°C
Found
Calculated
Molecular
formula
IR
(%)
ν(С=О)/cm–1
N
S
1f
45
28
44
55
47
62
42
55
60
56
57
62
58
47
49
52
285—287
205—206
213—215
140—141
195—196
240—242
249—252
245—248
222—225
200—204
239—242
268—269
254—255
170
10.23
10.42
8.56
8.31
9.12
8.91
8.75
8.76
9.12
9.03
8.65
8.48
8.53
8.48
9.02
8.76
8.77
8.76
8.99
8.69
8.78
8.69
7.58
7.39
7.45
7.40
8.55
8.45
8.95
9.11
9.45
9.14
8.12
7.95
6.02
6.34
7.00
6.80
6.53
6.69
7.02
6.89
6.50
6.47
6.48
6.47
6.88
6.69
6.45
6.69
6.53
6.63
6.78
6.63
5.55
5.64
5.77
5.65
6.27
6.44
6.67
6.95
6.77
6.98
C9H10N2O4S
C16H12N2O5S
C14H18N2O4S
C15H14N2O4S
C14H12N2O4S
C15H14N2O5S
C15H14N2O5S
C15H14N2O4S
C15H14N2O4S
C14H11FN2O4S
C14H11FN2O4S
C14H9Cl3N2O4S
C17H16N2O6S
C15H16N2O5S
C12H16N2O5S
C13H18N2O4S
1705, 1685
1710, 1690
1705, 1685
1705, 1695
1710, 1680
1710, 1685
1705, 1685
1710, 1690
1710, 1680
1705, 1685
1705, 1690
1710, 1695
1710, 1700, 1680
1700, 1680
1700, 1690
1700, 1680
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1r
1s
2c
2d
2e
185
178

1296
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
Morzherin et al.
1
Table 5. Н NMR spectra (DMSOꢀd6) for compounds Zꢀ2c—e and Eꢀ2c—e
Comꢀ
pound
δ (J/Hz)
Zꢀ2c
11.20 (s, 1 H, NH); 8.77 (s, 1 H, NH); 8.00—8.08 (m, 1 H, ArH); 6.83—7.00 (m, 3 H, ArH); 5.65 (s, 1 H, CH=);
4.27 (dd, 1 H, CH, J = 4.8, J = 7.9); 3.84 (s, 3 H, OMe); 3.67 (s, 3 H, OMe); 3.11 (dd, 1 H, CH, J = 4.8,
J = 17.8); 2.84 (dd, 1 H, CH, J = 7.9, J = 17.8)
Zꢀ2d
Zꢀ2e
11.58 (s, 1 H, NH); 5.62 (s, 1 H, CH=); 4.124 (dd, 1 H, CH, J = 4.6, J = 7.6); 3.65 (s, 3 H, OMe); 3.40—3.60
(m, 8 H, 4 CH2); 3.12 (dd, 1 H, CH, J = 4.6, J = 17.2); 2.86 (dd, 1 H, CH, J = 7.6, J = 17.2)
11.00 (s, 1 H, NH); 5.68 (s, 1 H, CH=); 4.09 (dd, 1 H, CH, J = 4.6, J = 7.7); 3.66 (s, 3 H, OMe); 3.40—3.60
(m, 4 H, 2 NCH2); 3.00 (dd, 1 H, CH, J = 4.6, J = 17.5); 2.72 (dd, 1 H, CH, J = 7.7, J = 17.5); 1.40—1.70
(m, 6 H, 3 CH2)
Eꢀ2c
11.42 (s, 1 H, NH); 8.87 (s, 1 H, NH); 8.00—8.08 (m, 1 H, ArH); 6.83—7.00 (m, 3 H, ArH); 5.97 (s, 1 H, CH=);
4.04 (dd, 1 H, CH, J = 4.7, J = 7.9); 3.84 (s, 3 H, OMe); 3.67 (c, 3 H, OMe); 3.08 (dd, 1 H, CH, J = 4.7,
J = 17.8); 2.85 (dd, 1 H, CH, J = 7.9, J = 17.8)
Eꢀ2d
Eꢀ2e
11.29 (s, 1 H, NH); 5.84 (s, 1 H, CH=); 4.04 (dd, 1 H, CH, J = 4.6, J = 7.6); 3.66 (s, 3 H, OMe); 3.40—3.60
(m, 8 H, 4 CH2); 3.08 (dd, 1 H, CH, J = 4.6, J = 17.2); 2.85 (dd, 1 H, CH, J = 7.6, J = 17.2)
11.18 (s, 1 H, NH); 5.88 (s, 1 H, CH=); 4.01 (dd, 1 H, CH, J = 4.8, J = 7.7); 3.66 (s, 3 H, OMe); 3.40—3.60
(m, 4 H, 2 NCH2); 2.98 (dd, 1 H, CH, J = 4.8, J = 17.5); 2.75 (dd, 1 H, CH, J = 7.7, J =17.5); 1.40—1.70
(m, 6 H, 3 CH2)
The thioacetamides RCH2—C(S)NH2 (3a—c) were synꢀ
was cooled, and the precipitate of thioamide RCH2CSNH2
(3d—s) was filtered off. The product was recrystallized from
ethanol.
thesized by a previously described procedure.7 Compounds 1a—s
were synthesized from dimethyl acetylenedicarboxylate and corꢀ
responding substituted thioacetamides 3a—s according to a deꢀ
scribed procedure.1 Compounds 2a,b were synthesized by the
reduction of corresponding thiazolidinones 1 with Zn(AcOH)
as described in Ref. 5. Compounds 2c—d were prepared simiꢀ
larly. The physicochemical characteristics of the compounds
are presented in Tables 3—6.
Preparation of 2,5ꢀdimethylenethiazolidinꢀ4ꢀones (1a—s)
(general procedure). Dimethyl acetylenedicarboxylate (0.4 mL,
3.17 mmol) was added to a suspension of the corresponding
thioacetamide 3 (3 mmol) in 30 mL of ethanol (40 mL of
chloroform or 2 mL of DMSO) at ∼20 °C. The reaction mixꢀ
ture was stirred for 2 h and cooled. The precipitate was filtered
off, and the product was recrystallized from ethanol.
Preparation of 5ꢀmethylenethiazolidinꢀ4ꢀones (2a—e) (genꢀ
eral procedure). Zinc dust (1 g) was added to a suspension of
compound 1 (0.5 g) in glacial acetic acid (4 mL). The mixture
was stirred for 24 h at 30—35 °C, 100 mL of water were added,
Preparation of thioacetamides 3d—s (general procedure).
A suspension of the corresponding acetonitrile RCH2CN
(0.1 mol) and triethylamine (1.4 mL, 0.01 mol) in ethanol
(100 mL) saturated with H2S (5.1 g, 0.15 mol) was placed in an
autoclave and heated for 1.5 h at 70 °C. The reaction mixture
Table 6. Physicochemical data for thioacetamides Z,Zꢀ3d—s
Comꢀ Yield M.p. Found
pound (%) /°C Calculated
Molecular
formula
MS,
m/z
Comꢀ Yield M.p. Found
pound (%) /°C Calculated
Molecular
formula
MS,
m/z
(%)
(%)
(Irel (%))
(Irel (%))
N
S
N
S
3d
3e
3f
85
73
92
68
71
93
96
87
120
140
105
158
15.28 16.65 C7H12N2O2S
14.88 17.03
15.23 16.89 C8H14N2OS
15.04 17.21
21.00 24.62 C4H8N2OS
21.19 24.26
11.68 14.03 C11H10N2O2S 234 (8)
11.96 13.69
188 (52)
186 (17)
132 (35)
3l
89
142
12.59 14.12 C10H12N2O2S 224 (26)
12.49 14.30
3m
3n
3o
3p
3q
3r
3s
76 106— 12.89 14.92 C10H12N2OS
208 (12)
208 (53)
212 (56)
212 (32)
108
114
13.45 15.39
13.69 15.65 C10H12N2OS
13.45 15.39
86
53
48
75
68
55
3g
3h
3i
125
(decomp.)
112
(decomp.)
89
—
14.92 C9H9FN2OS
15.11
98— 14.19 15.42 C9H16N2OS
100
110
200 (53)
208 (65)
194 (56)
—
14.74 C9H9FN2OS
15.11
13.99 16.01
13.05 14.98 C10H12N2OS
13.45 15.39
14.02 16.08 C9H10N2OS
14.42 16.51
12.12 13.95 C10H12N2O2S 224 (18)
12.49 14.30
10.69 12.25 C9H8Cl2N2OS 264 (32),
10.65 12.18 262 (55)
9.63 10.54 C9H7Cl3N2OS 298 (22),
9.41 10.77 296 (23)
10.86 11.86 C12H14N2O3S 266 (8)
10.52 12.04
3j
106
128
86
3k
108

E—ZꢀIzomerization of 2ꢀmethylenethiazolidinꢀ4ꢀones Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1297
and the resulting mixture was stirred for 30 min. The precipiꢀ
tate was filtered off and recrystallized from ethanol.
References
Methyl E,Zꢀ(2ꢀ[2ꢀ(1,3ꢀdioxoꢀ1,3ꢀdihydroisoindolꢀ2ꢀyl)ethylꢀ
idene]ꢀ4ꢀoxothiazolꢀ5ꢀylidene)acetate (E,Zꢀ1g). 13C NMR
(DMSOꢀd6), δ: 167.3 (CON); 166.3 (COOMe); 164.2 (C(3));
144.1 (C(2)); 134.5, 123.1, 131.6 (Ar); 135.1 (C(5)); 110.7
(CH=C(5)); 99.6 (CH=C(2)); 52.1 (OCH3), 34.7 (CH2).
Methyl Z,Zꢀ{2ꢀ[2ꢀ(1,3ꢀdioxoꢀ1,3ꢀdihydroisoindolꢀ2ꢀyl)ethylꢀ
idene]ꢀ4ꢀoxothiazolidinꢀ5ꢀylidene}acetate (Z,Zꢀ1g). 13C NMR
(DMSOꢀd6), δ: 167.2 (CON); 166.4 (COOMe); 165.3 (C(3));
144.1 (C(2)); 134.4, 123.0, 131.7 (Ar); 132.4 (C(5)); 110.5
(CH=C(5)); 100.3 (CH=C(2)); 52.1 (OCH3); 34.3 (CH2).
Determination of association constant. To determine assoꢀ
1. V. S. Berseneva, A. V. Tkachev, Yu. Yu. Morzherin,
W. Dehaen, I. Luyten, S. Toppet, and V. A. Bakulev, J. Chem.
Soc., Perkin Trans. 1, 1998, 2133.
2. J. A. M. Guard and P. J. Steel, Heterocycles, 1994, 37, 1711.
3. R. Markovic and M. Baranac, J. Serb. Chem. Soc., 1998,
63(3), 165.
4. B. D´hooge and W. Dehaen, Bull. Soc. Chim. Belg., 1997,
106, 729.
5. Yu. Yu. Morzherin, M. F. Kosterina, A. S. Bezborodov,
V. S. Berseneva, I. Luyten, W. Dehaen, and V. A. Bakulev,
Khim. Geterotsikl. Soed., 2000, 119 [Khim. Geterocycl. Soed.,
2000 (Engl. Transl.)].
6. J. A. A. De Boer, D. N. Reinhoudt, S. Harkema, G. J.
van Hummel, and F. de Jong, J. Am. Chem. Soc., 1982,
104, 4073.
7. V. A. Bakulev, A. T. Lebedev, E. F. Dankova,
V. S. Mokrushin, and V. S. Petrosyan, Tetrahedron, 1989,
45, 7329.
1
ciation constants, we used Н NMR spectroscopy in a solution
of acetoneꢀd6 at 298 К at constant concentrations of comꢀ
pounds 1с and 2a (3 mmol L–1) and varied concentrations of
NaI (0.8, 1.8, 4.5, 7.5, 11.8, and 21.7 mmol L–1). The chemiꢀ
cal shift of the signal from the methine proton of the exocyclic
double bond in position 2 was used for measurements. The
association constant was calculated from the nonlinear regresꢀ
sion as described in Ref. 6.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 01ꢀ03ꢀ96431ꢀ
r2001Ural).
Received July 20, 2001;
in revised form December 5, 2001