Synthesis of heterocycles from arylation products of unsaturated compounds: XIII. 5-R1-benzyl-2-(R2-2-pyridylimino)thiazolidin-4-ones

Article abstract of DOI:10.1007/s11178-005-0292-x

Meerwein reactions of arenediazonium bromides with methyl and ethyl acrylates gave 3-aryl-2-bromopropionic acid esters which were subjected to cyclocondensation with N-(2-pyridyl)- and N-(6-methyl-2-pyridyl) thioureas to obtain 5-R¹-benzyl-2-(R

Full text of DOI:10.1007/s11178-005-0292-x

Russian Journal of Organic Chemistry, Vol. 41, No. 7, 2005, pp. 1050–1054. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 7, 2005,
pp. 1071–1075.
Original Russian Text Copyright © 2005 by Matiichuk, Obushak, Tsyalkovskii.
Synthesis of Heterocycles from Arylation Products of
Unsaturated Compounds: XIII.* 5-R1-Benzyl-2-(R2-2-
pyridylimino)thiazolidin-4-ones
V. S. Matiichuk, N. D. Obushak, and V. M. Tsyalkovskii
Ivan Franko L’viv National University, ul. Kirilla i Mefodiya 6, L’viv, 79005 Ukraine
e-mail: obushak@in.lviv.ua
Received November 16, 2004
Abstract—Meerwein reactions of arenediazonium bromides with methyl and ethyl acrylates gave 3-aryl-2-
bromopropionic acid esters which were subjected to cyclocondensation with N-(2-pyridyl)- and N-(6-methyl-2-
pyridyl)thioureas to obtain 5-R1-benzyl-2-(R2-2-pyridylimino)thiazolidin-4-ones. The latter were shown to
exist in solution as E isomers of the imino form.
found that methyl and ethyl 3-aryl-2-bromopropionates
IIa–IIr react with N-(2-pyridyl)thioureas IIIa and IIIb
to give the corresponding 5-R1-benzyl-2-(R2-2-pyri-
dylimino)thiazolidin-4-ones IVa–IVp and Va–Ve
(Scheme 1). The reactions were carried out by heating
the reactants for a short time in alcohol in the presence
of a base. No elimination of hydrogen bromide from
esters IIa–IIr (with formation of cinnamic acid deriva-
tives) occurred under these conditions. Compounds
IVa–IVp and Va–Ve were isolated in high yields as
colorless crystalline substances which were sparingly
soluble in alcohol, dioxane, and DMF. It should be
noted that some 2-(2-pyridylimino)thiazolidin-4-ones
were found to exhibit antibacterial activity [13].
The thiazolidine ring is a promising and effective
structural fragment for the design of biologically active
compounds [2–4]. Methods of synthesis of combina-
torial libraries of 4-thiazolidinone derivatives have
been developed [5–7]. In the recent time, 5-R-benzyl-
thiazolidine-2,4-diones attract increased interest, and
some compounds of this series have already been
introduced into medical practice as antidiabetic agents
[8–11]. By contrast, 2-imino derivatives of 4-thiazo-
lidinone have been studied to a lesser extent, despite
the possibility for introducing an additional pharmaco-
phoric fragment into the 2-position. A probable reason
is the limited set of convenient methods for the syn-
thesis of such compounds with various substituents
in both the thiazolidine ring and the imino fragment.
A general procedure for the synthesis of 2-iminothia-
zolidin-4-ones is based on cyclocondensation of mono-
and disubstituted thioureas with α-halo acids and their
esters [2, 12]. However, the application of this proce-
dure is limited due to the fact that the cyclization is
selective only when the nitrogen atoms in thioureas are
characterized by considerably different nucleophilic-
ities [13] or when other structural factors are favorable
(e.g., hydrogen bond formation) [14].
Esters IIa–IIr were prepared by reaction of arene-
diazonium bromides Ia–Ir with methyl or ethyl ac-
rylate according to Meerwein [17]. The reactions were
exothermic, and they were carried out at room tem-
perature or on slight heating. Compounds IIa–IIr can
be distilled under reduced pressure; they were isolated
as light yellow liquids or crystalline substances.
N-(2-Pyridyl)thioureas IIIa and IIIb were synthesized
by the known method [18] from benzoyl isothiocya-
nate (VI) and 2-aminopyridines VIIa and VIIb.
2-Aryliminothiazolidin-4-ones, which are struc-
turally related to compounds IVa–IVp and Va–Ve, are
known to exist in solution as mixtures of amino and
imino tautomers, and the imino form gives rise to Z,E
isomerism [16, 19–21]. According to the H NMR
data, thiazolidinones IVa–IVp and Va–Ve exist in
5-Benzyl-2-iminothiazolidin-4-ones can be prepar-
ed by reaction of 3-aryl-2-bromopropionic acid esters
with thiourea [15, 16]. In the present work we made
an attempt to synthesize 5-benzylthiazolidin-4-ones
containing a 2-pyridylimino group in position 2. We
1
* For communication XII, see [1].
solution as one isomer of the imino form. This conclu-
1070-4280/05/4107-1050 © 2005 Pleiades Publishing, Inc.

SYNTHESIS OF HETEROCYCLES FROM ARYLATION PRODUCTS ...: XIII.
1051
Scheme 1.
O
CuBr, Me2CO
N2+ Br–
OR2
H2O
CH2=CHCOOR2
R1
R1
+
Br
N
Ia–Ir
IIa–IIr
S
R1
Pyridine, EtOH
S
N
IIa–IIr
+
NH
R3
O
R3
N
N
NH2
H
IIIa, IIIb
IVa–IVp, Va–Ve
S
O
NaOH
PhCONCS
+
IIIa, IIIb
R3
N
NH2
R3
N
N
N
H
Ph
H
VI
VIIa, VIIb
I, R1 = 2-Me (a), 4-F (b), 2-Cl (c), 3-CF3 (d), 3-NO2 (e), 2,4-Cl2 (f), 2,5-Cl2 (g), 4-Me-3-Cl (h), H (i), 3-Me (j), 4-Me (k), 4-MeO (l),
3-Cl (m), 4-Cl (n), 4-Br (o), 4-EtO (p), 2,3-Cl2 (q), 3,4-Cl2 (r); II, R2 = Me, R1 = 2-Me (a), 4-F (b), 2-Cl (c), 3-CF3 (d), 3-NO2 (e),
2,4-Cl2 (f), 2,5-Cl2 (g), 4-Me-3-Cl (h); R2 = Et, R1 = H (i), 3-Me (j), 4-Me (k), 4-MeO (l), 3-Cl (m), 4-Cl (n), 4-Br (o), 4-EtO (p),
2,3-Cl2 (q), 3,4-Cl2 (r); III, VII, R3 = H (a), 6-Me (b); IV, R3 = H, R1 = H (a), 2-Me (b), 3-Me (c), 4-Me (d), 4-MeO (e), 4-EtO (f),
4-F (g), 2-Cl (h), 3-Cl (i), 4-Cl (j), 4-Br (k), 3-CF3 (l), 3-NO2 (m), 2,3-Cl2 (n), 2,5-Cl2 (o), 3,4-Cl2 (p); V, R3 = Me, R1 = H (a),
3-CF3 (b), 2,4-Cl2 (c), 3,4-Cl2 (d), 3-Cl-4-Me (e).
sion is confirmed by comparison of the spectral data of
these compounds with those of 2-aryliminothiazolidin-
4-ones [16]. Presumably, compounds IVa–IVp and
Va–Ve are the corresponding E isomers, for spatial
arrangement of the sulfur atom and nitrogen atom in
the pyridine ring (as well as of the methyl group in
the pyridine ring of Va–Ve) in the Z isomers is less
favorable.
the corresponding aromatic amine) was cooled to 0–
5°C and added dropwise under stirring to a solution of
0.22 mol of methyl or ethyl acrylate and 3 g of CuBr
in 150 ml of acetone. The temperature was maintained
in the range from 20 to 40°C so that nitrogen evolved
at a rate of 2–3 bubbles per second. When nitrogen no
longer evolved, the mixture was diluted with 200 ml of
water, and the organic phase was separated and dried
over MgSO4. The solvent was evaporated, and the
residue was distilled under reduced pressure. Com-
pounds IIi and IIn were described previously [15, 22].
Thus accessible bromoarylation products IIa–IIr
obtained from acrylic acid esters are convenient re-
agents for the synthesis of 4-thiazolidinone derivatives
containing a substituted benzyl group in position 5 and
a 2-pyridylimino substituent in position 2.
Methyl 2-bromo-3-(2-methylphenyl)propionate
(IIa). Yield 33%, bp 128°C (2 mm), nD20 = 1.5416.
Found, %: Br 31.01. C11H13BrO2. Calculated, %:
Br 31.08.
EXPERIMENTAL
Methyl 2-bromo-3-(4-fluorophenyl)propionate
(IIb). Yield 40%, bp 113–114°C (2 mm), nD20 = 1.5223.
Found, %: C 46.25; H 3.90. C10H10BrFO2. Calculated,
%: C 46.00; H 3.86.
1
The H NMR spectra were recorded on Bruker
DRX 500 (500 MHz; compounds IIg, Va, Vb), Bruker
AM-300 (300 MHz; IIe, IIj–IIm, IIq, IIr, IVa, IVk,
IVm), and Bruker WM-250 instruments (250 MHz;
IVc–IVe, IVh) using DMSO-d6 or DMSO-d6–CCl4
(1:3) (IIg, Va, Vb) as solvent; the chemical shifts
were measured relative to the residual proton signal of
the solvent (DMSO, δ 2.50 ppm).
Methyl 2-bromo-3-(2-chlorophenyl)propionate
(IIc). Yield 47%, bp 128–130°C (2 mm), nD20 = 1.5548.
Found, %: Br+Cl 41.50. C10H10BrClO2. Calculated,
%: Br+Cl 41.56.
Methyl 2-bromo-3-(3-trifluoromethylphenyl)-
propionate (IId). Yield 42%, bp 118–120°C (2 mm),
n2D0 = 1.4922. Found, %: C 42.34; H 3.08. C11H10BrF3O2.
Calculated, %: C 42.47; H 3.24.
3-Aryl-2-bromopropionic acid esters IIa–IIr
(general procedure). A solution of arenediazonium
bromide Ia–Ir (prepared by diazotization of 0.2 mol of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 7 2005

MATIICHUK et al.
1052
Methyl 2-bromo-3-(3-nitrophenyl)propionate
Ethyl 2-bromo-3-(4-bromophenyl)propionate
(IIo). Yield 53%, bp 162–165°C (2 mm), nD20 = 1.5574.
Found, %: Br 47.27. C11H12Br2O2. Calculated, %:
Br 47.56.
(IIe). Yield 46%, mp 101–102°C (from ethanol) [16].
1H NMR spectrum, δ, ppm: 3.33 d.d (1H, CH2, J =
14.0, 8.1 Hz), 3.57 d.d (1H, CH2, J = 14.0, 6.6 Hz),
3.73 s (3H, OMe), 4.80 t (1H, CH), 7.59 t (1H, Harom),
7.73 d (1H, Harom), 8.11 d (1H, Harom), 8.20 s
(1H, Harom).
Methyl 2-bromo-3-(2,4-dichlorophenyl)propio-
nate (IIf). Yield 59%, bp 168–171°C (2 mm), mp 74–
75°C (from ethanol). Found, %: Br + Cl 48.20.
C10H9BrCl2O2. Calculated, %: Br+Cl 48.34.
Ethyl 2-bromo-3-(4-ethoxyphenyl)propionate
(IIp). Yield 45%, bp 151–153°C (2 mm), mp 28–30°C
(from ethanol). Found, %: C 51.72; H 5.63.
C13H17BrO3. Calculated, %: C 51.84; H 5.69.
Ethyl 2-bromo-3-(2,3-dichlorophenyl)propionate
(IIq). Yield 56%, bp 178–180°C (2 mm), nD20 = 1.5542.
1H NMR spectrum, δ, ppm: 1.23 t (3H, Me), 3.40 d.d
(1H, CH2, J = 14.6, 8.1 Hz), 3.57 d.d (1H, CH2, J =
14.6, 7.8 Hz), 4.17 d.q (2H, OCH2), 4.65 t (1H, CH),
7.24– 7.35 m (2H, Harom), 7.48 d.d (1H, Harom, 4J = 1.5,
3J = 7.5 Hz). Found, %: Br+Cl 46.08. C11H11BrCl2O2.
Calculated, %: Br+Cl 46.26.
Methyl 2-bromo-3-(2,5-dichlorophenyl)propio-
nate (IIg). Yield 48%, bp 172–174°C (2 mm),
1
mp 61°C (from ethanol). H NMR spectrum, δ, ppm:
3.35 d.d (1H, CH2, J = 14.4, 8.2 Hz), 3.51 d.d (1H,
CH2, J = 14.4, 7.2 Hz), 3.75 s (3H, OMe), 4.63 t
4
3
(1H, CH), 7.29 d.d (1H, Harom, J = 2.6, J = 8.6 Hz),
7.36–7.40 m (2H, Harom). Found, %: Br+Cl 48.27.
C10H9BrCl2O2. Calculated, %: Br+Cl 48.34.
Ethyl 2-bromo-3-(3,4-dichlorophenyl)propionate
(IIr). Yield 53%, bp 175–177°C (2 mm), nD20 = 1.5530.
1H NMR spectrum, δ, ppm: 1.23 t (3H, Me), 3.17 d.d
(1H, CH2, J = 13.8, 6.9 Hz), 3.39 d.d (1H, CH2, J =
13.8, 7.2 Hz), 4.16 d.q (2H, OCH2), 4.68 t (1H, CH),
7.24 d (1H, Harom, J = 8.1 Hz), 7.46 d (1H, Harom, J =
8.1 Hz), 7.51 s (1H, Harom). Found, %: Br+Cl 46.12.
C11H11BrCl2O2. Calculated, %: Br+Cl 46.26.
Methyl 2-bromo-3-(3-chloro-4-methylphenyl)-
propionate (IIh). Yield 29%, bp 144–146°C (2 mm),
nD20 = 1.5521. Found, %: Br+Cl 39.41. C11H12BrClO2.
Calculated, %: Br+Cl 39.56.
Ethyl 2-bromo-3-(3-methylphenyl)propionate
(IIj). Yield 41%, bp 138°C (2 mm), nD20 = 1.5333 [15].
1H NMR spectrum, δ, ppm: 1.21 t (3H, Me), 2.30 s
(3H, Me), 3.14 d.d (1H, CH2, J = 14.1, 7.8 Hz),
3.35 d.d (1H, CH2, J = 14.1, 8.7 Hz), 4.13 q (2H,
OCH2), 4.54 t (1H, CH), 6.98–7.20 m (4H, Harom).
Ethyl 2-bromo-3-(4-methylphenyl)propionate
(IIk). Yield 37%, bp 149°C (2 mm), nD20 = 1.5343 [15].
1H NMR spectrum, δ, ppm: 1.21 t (3H, Me), 2.30 s
(3H, Me), 3.14 d.d (1H, CH2, J = 13.8, 6.6 Hz),
3.34 d.d (1H, CH2, J = 13.8, 9.0 Hz), 4.12 d.q
(2H, OCH2), 4.52 t (1H, CH), 7.07 d (2H, Harom, J =
7.8 Hz), 7.11 d (2H, Harom).
5-R-Benzyl-2-(2-pyridylimino)thiazolidin-4-ones
IVa–IVp (general procedure). Ester II, 0.01 mol, and
pyridine, 1 ml, were added to a solution of 0.01 mol
(1.53 g) of N-(2-pyridyl)thiourea (IIIa) in 10 ml of
ethanol. The mixture was heated for 0.5 h under reflux
and cooled, and the precipitate was filtered off and
recrystallized from DMF–ethanol. Compounds Va–Ve
were synthesized in a similar way using N-(6-methyl-
2-pyridyl)thiourea (IIIb).
5-Benzyl-2-(2-pyridylimino)thiazolidin-4-one
(IVa). Yield 73%, mp 217–218°C. 1H NMR spectrum,
δ, ppm: 3.00 d.d (1H, CH2, J = 14.1, 10.2 Hz), 3.43 d.d
(1H, CH2, J = 14.1, 4.0 Hz), 4.54 d.d (1H, CH), 7.10 t
(2H, 3-H, 5-H, pyridine), 7.22–7.34 m (5H, Harom),
7.78 t (1H, 4-H, pyridine), 8.34 d (1H, 6-H, pyridine),
11.92 br.s (1H, NH). Found, %: C 63.44; H 4.55;
N 15.02. C15H13N3OS. Calculated, %: C 63.58; H 4.62;
N 14.83.
Ethyl 2-bromo-3-(4-methoxyphenyl)propionate
(IIl). Yield 47%, bp 136–138°C (2 mm), nD20 = 1.5335
1
[16]. H NMR spectrum, δ, ppm: 1.21 t (3H, Me),
3.12 d.d (1H, CH2, J = 13.8, 8.1 Hz), 3.31 d.d (1H,
CH2, J = 13.8, 9.3 Hz), 3.75 s (3H, MeO), 4.12 d.q
(2H, OCH2), 4.51 t (1H, CH), 6.80 d (2H, Harom, J =
9.0 Hz), 7.14 d (2H, Harom).
5-(2-Methylbenzyl)-2-(2-pyridylimino)thiazoli-
din-4-one (IVb). Yield 70%, mp 222.5–223.5°C.
Found, %: C 64.86; H 4.79; N 14.12. C16H15N3OS.
Calculated, %: C 64.62; H 5.08; N 14.13.
Ethyl 2-bromo-3-(3-chlorophenyl)propionate
(IIm). Yield 43%, bp 141–143°C (2 mm), nD20
=
1
1.5391. H NMR spectrum, δ, ppm: 1.22 t (3H, Me),
3.19 d.d (1H, CH2, J = 14.1, 7.2 Hz), 3.40 d.d (1H,
CH2, J = 14.1, 8.1 Hz), 4.15 d.q (2H, OCH2), 4.65 t
(1H, CH), 7.18–7.35 m (4H, Harom). Found, %: Br+Cl
39.61. C11H12BrClO2. Calculated, %: Br+Cl 39.56.
5-(3-Methylbenzyl)-2-(2-pyridylimino)thiazoli-
din-4-one (IVc). Yield 69%, mp 176–177°C. 1H NMR
spectrum, δ, ppm: 2.32 s (1H, Me), 2.88 d.d (1H, CH2,
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SYNTHESIS OF HETEROCYCLES FROM ARYLATION PRODUCTS ...: XIII.
1053
J = 14.5, 10.1 Hz), 3.42 d.d (1H, CH2, J = 14.5,
3.5 Hz), 4.34 d.d (1H, CH), 7.00–7.12 m (4H, Harom),
7.18 t (2H, 3-H, 5-H, pyridine), 7.73 t (1H, 4-H, pyr-
idine), 8.31 d (1H, 6-H, pyridine), 11.90 br.s (1H, NH).
Found, %: C 64.88; H 5.01; N 13.95. C16H15N3OS.
Calculated, %: C 64.62; H 5.08; N 14.13.
5-(4-Methylbenzyl)-2-(2-pyridylimino)thiazoli-
din-4-one (IVd). Yield 81%, mp 242–243°C. 1H NMR
spectrum, δ, ppm: 2.30 s (3H, Me), 2.90 d.d (1H, CH2,
J = 14.0, 10.2 Hz), 3.39 d.d (1H, CH2, J = 14.0,
3.8 Hz), 4.32 d.d (1H, CH), 7.05 t (2H, 3-H, 5-H,
pyridine), 7.09 d (2H, Harom, J = 8.0 Hz), 7.15 d (2H,
Harom), 7.73 t (1H, 4-H, pyridine), 8.30 d (1H, 6-H,
pyridine), 11.87 br.s (1H, NH). Found, %: C 64.83;
H 5.34; N 14.20. C16H15N3OS. Calculated, %: C 64.62;
H 5.08; N 14.13.
%: C 56.46; H 3.93; N 13.32. C15H12ClN3OS. Calculat-
ed, %: C 56.69; H 3.81; N 13.22.
5-(4-Bromobenzyl)-2-(2-pyridylimino)thiazoli-
din-4-one (IVk). Yield 63%, mp 252–253°C. 1H NMR
spectrum, δ, ppm: 3.02 d.d (1H, CH2, J = 14.2,
10.1 Hz), 3.38 d.d (1H, CH2, J = 14.2, 4.3 Hz),
4.53 d.d (1H, CH), 7.05–7.11 m (2H, 3-H, 5-H,
pyridine), 7.25 d (2H, Harom, J = 8.0 Hz), 7.51 d (2H,
Harom), 7.79 t (1H, 4-H, pyridine), 8.33 d (1H, 6-H,
pyridine), 11.98 br.s (1H, NH). Found, %: C 49.89;
H 3.21; N 11.60. C15H12BrN3OS. Calculated, %:
C 49.74; H 3.34; N 11.60.
2-(2-Pyridylimino)-5-(3-trifluoromethylbenzyl)-
thiazolidin-4-one (IVl). Yield 79%, mp 204–205°C.
Found, %: C 54.98; H 3.40; N 11.94. C16H12F3N3OS.
Calculated, %: C 54.70; H 3.44; N 11.96.
5-(4-Methoxybenzyl)-2-(2-pyridylimino)thiazoli-
din-4-one (IVe). Yield 77%, mp 208–210°C. 1H NMR
spectrum, δ, ppm: 2.89 d.d (1H, CH2, J = 14.3,
10.1 Hz), 3.36 d.d (1H, CH2, J = 14.3, 3.6 Hz), 3.75 s
(1H, MeO), 4.31 m (1H, CH), 6.83 d (2H, Harom, J =
8.2 Hz), 7.06 t (2H, 3-H, 5-H, pyridine), 7.18 d (2H,
Harom), 7.73 t (1H, 4-H, pyridine), 8.31 d (1H, 6-H,
pyridine), 11.87 br.s (1H, NH). Found, %: C 61.19;
H 5.08; N 13.13. C16H15N3O2S. Calculated, %:
C 61.32; H 4.82; N 13.41.
5-(4-Ethoxybenzyl)-2-(2-pyridylimino)thiazoli-
din-4-one (IVf). Yield 67%, mp 207–208°C. Found,
%: C 62.48; H 5.08; N 12.63. C17H17N3O2S. Calculat-
ed, %: C 62.37; H 5.23; N 12.83.
5-(4-Fluorobenzyl)-2-(2-pyridylimino)thiazoli-
din-4-one (IVg). Yield 72%, mp 234–235°C. Found,
%: C 59.69; H 4.17; N 14.20. C15H12FN3OS. Calculat-
ed, %: C 59.79; H 4.01; N 13.94.
5-(3-Nitrobenzyl)-2-(2-pyridylimino)thiazolidin-
4-one (IVm). Yield 75%, mp 231–232°C. H NMR
1
spectrum, δ, ppm: 3.26 d.d (1H, CH2, J = 14.1, 9.0 Hz),
3.51 d.d (1H, CH2, J = 14.1, 4.5 Hz), 4.63 d.d (1H,
CH), 7.11 t (2H, 3-H, 5-H, pyridine), 7.61 t (1H, 5-H,
C6H4), 7.72–7.81 m (2H, 4-H, pyridine, and 6-H,
C6H4), 8.10 d (1H, 4-H, C6H4), 8.17 s (1H, 2-H, C6H4),
8.33 d (1H, 6-H, pyridine), 12.05 br.s (1H, NH).
Found, %: C 54.83; H 3.83; N 16.99. C15H12N4O3S.
Calculated, %: C 54.87; H 3.68; N 17.06.
5-(2,3-Dichlorobenzyl)-2-(2-pyridylimino)thiazo-
lidin-4-one (IVn). Yield 81%, mp 264–265°C. Found,
%: C 51.38; H 2.97; N 12.09. C15H11Cl2N3OS. Calcu-
lated, %: C 51.15; H 3.15; N 11.93.
5-(2,5-Dichlorobenzyl)-2-(2-pyridylimino)thiazo-
lidin-4-one (IVo). Yield 83%, mp 222–223°C. Found,
%: C 51.01; H 3.11; N 12.11. C15H11Cl2N3OS. Calcu-
lated, %: C 51.15; H 3.15; N 11.93.
5-(2-Chlorobenzyl)-2-(2-pyridylimino)thiazoli-
din-4-one (IVh). Yield 65%, mp 217–218°C. 1H NMR
spectrum, δ, ppm: 3.03 d.d (1H, CH2, J = 14.5,
10.2 Hz), 3.63 d.d (1H, CH2, J = 14.5, 4.5 Hz), 4.39 m
(1H, CH), 7.02–7.14 m (2H, 3-H, 5-H, pyridine), 7.25–
7.35 m (2H, Harom), 7.36–7.44 m (2H, Harom), 7.74 t
(1H, 4-H, pyridine), 8.31 d (1H, 6-H, pyridine),
12.03 br.s (1H, NH). Found, %: C 56.62; H 4.05;
N 13.40. C15H12ClN3OS. Calculated, %: C 56.69;
H 3.81; N 13.22.
5-(3,4-Dichlorobenzyl)-2-(2-pyridylimino)thiazo-
lidin-4-one (IVp). Yield 78%, mp 232–233°C. Found,
%: C 51.22; H 2.98; N 11.81. C15H11Cl2N3OS. Calcu-
lated, %: C 51.15; H 3.15; N 11.93.
5-Benzyl-2-(6-methyl-2-pyridylimino)thiazoli-
1
din-4-one (Va). Yield 75%, mp 236–237°C. H NMR
spectrum, δ, ppm: 2.44 s (3H, Me), 2.97 d.d (1H, CH2,
J = 13.4, 10.4 Hz), 3.45 d.d (1H, CH2), 4.16 m (1H,
CH), 6.83–6.90 m (2H, 3-H, 5-H, pyridine), 7.19–
7.23 m (1H, Harom), 7.25–7.30 m (4H, Harom), 7.53–
7.59 m (1H, 4-H, pyridine). Found, %: C 64.35;
H 5.30; N 14.21. C16H15N3OS. Calculated, %: C 64.62;
H 5.08; N 14.13.
5-(3-Chlorobenzyl)-2-(2-pyridylimino)thiazoli-
din-4-one (IVi). Yield 69%, mp 192–193°C. Found,
%: C 56.65; H 3.96; N 13.12. C15H12ClN3OS. Calculat-
ed, %: C 56.69; H 3.81; N 13.22.
5-(4-Chlorobenzyl)-2-(2-pyridylimino)thiazoli-
2-(6-Methyl-2-pyridylimino)-5-(3-trifluorometh-
din-4-one (IVj). Yield 75%, mp 239–240°C. Found,
ylbenzyl)thiazolidin-4-one (Vb). Yield 72%, mp 242–
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 7 2005

MATIICHUK et al.
1054
1
6. Maclean, D., Holden, F., Davis, A.M., Scheuer-
man, R.A., Yanofsky, S., Holmes, C.P., Fitch, W.L.,
Tsutsui, K., Barrett, R.W., and Gallop, M.A., J. Comb.
Chem., 2004, vol. 6, p. 196.
243°C. H NMR spectrum, δ, ppm: 2.43 s (3H, Me),
3.09 d.d (1H, CH2, J = 14.0, 9.2 Hz), 3.50 d.d (1H,
CH2, J = 14.0, 3.4 Hz), 4.21 m (1H, CH), 6.84–6.91 m
(2H, 3-H, 5-H, pyridine), 7.47–7.54 m (2H, Harom),
7.54–7.59 m (2H, 4-H, pyridine, Harom), 7.60 s
(1H, Harom), 11.90 br.s (1H, NH). Found, %: C 56.06;
H 3.70; N 11.68. C17H14F3N3OS. Calculated, %:
C 55.88; H 3.86; N 11.50.
7. Fraga-Dubreuil, J. and Bazureau, J.P., Tetrahedron,
2003, vol. 59, p. 6121.
8. Lee, H.W., Kim, B.Y., Ahn, J.B., Son, H.J., Lee, J.W.,
Ahn, S.K., and Hong, C.I., Heterocycles, 2002, vol. 57,
p. 2163.
5-(2,4-Dichlorobenzyl)-2-(6-methyl-2-pyridyl-
imino)thiazolidin-4-one (Vc). Yield 80%, mp 273–
274°C. Found, %: C 52.21; H 3.50; N 11.64.
C16H13Cl2N3OS. Calculated, %: C 52.47; H 3.58;
N 11.47.
9. Lohray, B.B., Bhushan, V., Reddy, A.S., Rao, P.B.,
Reddy, N.J., Harikishore, P., Haritha, N., Vikrama-
dityan, R.K., Chakrabarti, R., Rajagopalan, R., and
Katneni, K., J. Med. Chem., 1999, vol. 42, p. 2569.
10. Urban, F.J. and Moore, B.S., J. Heterocycl. Chem.,
1992, vol. 29, p. 431.
11. Hulin, B., McCarthy, P.A., and Gibbs, E.M., Curr.
Pharm. Design, 1996, vol. 2, p. 85.
5-(3,4-Dichlorobenzyl)-2-(6-methyl-2-pyridyl-
imino)thiazolidin-4-one (Vd). Yield 79%, mp 258–
259°C. Found, %: C 52.32; H 3.59; N 11.23.
C16H13Cl2N3OS. Calculated, %: C 52.47; H 3.58;
N 11.47.
12. Brown, F.C., Chem. Rev., 1961, vol. 61, p. 463.
13. Fujikawa, F., Hirai, K., Hirayama, T., Yoshikawa, T.,
Nakagawa, T., Naito, M., Tsukuma, S., Kamada, M.,
and Ohta, Y., Yakugaku Zasshi, 1969, vol. 89, p. 1099.
14. Laurent, D.R.St., Qi Gao, Dedong Wu, and Serrano-
Wu, M.H., Tetrahedron Lett., 2004, vol. 45, p. 1907.
15. Obushak, N.D., Matiichuk, V.S., and Ganushchak, N.I.,
5-(3-Chloro-4-methylbenzyl)-2-(6-methyl-2-
pyridylimino)thiazolidin-4-one (Ve). Yield 76%,
mp 262–263°C. Found, %: C 59.03; H 4.48; N 12.25.
C17H16ClN3OS. Calculated, %: C 59.04; H 4.66;
N 12.15.
Russ. J. Org. Chem., 1998, vol. 34, p. 239.
16. Obushak, N.D., Matiichuk, V.S., Ganushchak, N.I., and
Burlak, Yu.E., Khim. Geterotsikl. Soedin., 1998, p. 555.
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