4-{3-(Dimethylamino)-1-[2-(dimethylamino)vinyl]prop-2-enylidene} -2-phenyl-1,3-oxazol-5(4H)-one and 5-{3-(dimethylamino)-1-[2-(dimethylamino)vinyl]prop-2-enylidene} -3-methyl-2-thioxo-1,3-thiazolidin-4-one in the synthesis of 1,4-dihydropyridine derivatives

Article abstract of DOI:10.3987/com-02-9433

4-{3-Dimethylamino-1-[2-(dimethylamino)vinyl]prop-2-enylidene] -2-phenyl-1,3-oxazol-5(4H)-one (3) and 5-{3-dimethylamino-1-[2-(dimethyl-amino)vinyl]prop-2-enylidene] -3-methyl-2-thioxo-1,3-thiazolidin-4-one (15) were prepared from 4-(1-methylethylidene)-2-phenyl-1,3-oxazol-5(4H)-one (2) and 5-(1-methylethylidene)-2-thioxo-1,3-thiazolidin-4-one (11), respectively. Treatment of compounds (3) and (15) with primary amines afforded 1,4-dihydropyridine derivatives (5) and (16) in 19-94percent yields. Reactions of oxazolones (5) with hydrazine hydrate gave the corresponding imidazolones (6), while upon base- or acid-catalysed methanolysis of 5 methyl (benzoylamino)(1-substituted pyridin-4(1H)-ylidene)acetates (7) were obtained. Catalytic hydrogenation of 7a furnished α-(piperidin-4-yl)glycine derivative (8) and/or α-(pyridin-2-yl)glycine derivative (9).

Full text of DOI:10.3987/com-02-9433

HETEROCYCLES, Vol. 57, No. 5, 2002, pp. 791 - 809, Received, 7th January, 2002
4-{3-DIMETHYLAMINO-1-(2-DIMETHYLAMINOVINYL)PROP-2-
ENYLIDENE}-2-PHENYL-1,3-OXAZOL-5(4H)-ONE AND 5-{3-DIMETH-
YLAMINO-1-[2-DIMETHYLAMINOVINYL)PROP-2-ENYLIDENE}-3-
METHYL-2-THIOXO-1,3-THIAZOLIDIN-4-ONE IN THE SYNTHESIS
OF 1,4-DIHYDROPYRIDINE DERIVATIVES
Aleš Hvala, Lucija Jukić Soršak, Gorazd Soršak, Urška Bratušek, Jurij Svete*,
Nina Lah, Ivan Leban, and Branko Stanovnik*
Faculty of Chemistry and Chemical Technology, University of Ljubljana,
Aškerčeva 5, 1000 Ljubljana, Slovenia
Dedicated to Emeritus Professor Miha Tišler, University of Ljubljana, on the
occasion of his 75th birthday
Abstract – 4-{3-Dimethylamino-1-[2-(dimethylamino)vinyl]prop-2-enylidene}-2-
phenyl-1,3-oxazol-5(4H)-one (3) and 5-{3-dimethylamino-1-[2-(dimethyl-
amino)vinyl]prop-2-enylidene}-3-methyl-2-thioxo-1,3-thiazolidin-4-one (15) were
prepared from 4-(1-methylethylidene)-2-phenyl-1,3-oxazol-5(4H)-one (2) and 5-
(1-methylethylidene)-2-thioxo-1,3-thiazolidin-4-one (11), respectively. Treatment
of compounds (3) and (15) with primary amines afforded 1,4-dihydropyridine
derivatives (5) and (16) in 19–94% yields. Reactions of oxazolones (5) with
hydrazine hydrate gave the corresponding imidazolones (6), while upon base- or
acid-catalysed methanolysis of 5 methyl (benzoylamino)(1-substituted pyridin-
4(1H)-ylidene)acetates (7) were obtained. Catalytic hydrogenation of 7a furnished
α-(piperidin-4-yl)glycine derivative (8) and/or α-(pyridin-2-yl)glycine derivative
(9).
The interest in dihydropyridines is due to the unique ability of these compounds to act as NAD(P)H
analogues of 1,4-dihydronicotinamide.1 They are most extensively studied as calcium antagonists,2
however, they also exhibit hepatoprotective,3 antitumor,4 antidiabetic,5 bronchodilating,6 and other pharma-

cological activities7–9 (Figure 1).
Figure 1.
Me
Examples of Pharmacologically Important 1,4-Dihydropyridine Derivatives.
H
N
Me
HN
H
N
N
F
N
O
Me
Cl
Me
Cl
MeOOC
COOMe
NO2
COOH
O
Nifedipine
(calcium channel blocker)
Clopidol
Ciprofloxacin
(antiparasitic)
(antibiotic)
There are several methods for the preparation of 1,4-dihydropyridine derivatives described in the
literature.10–13 The most widely used method is Hantzsch-type cyclocondensation reaction11,12 (Scheme 1).
Scheme 1.
Hantzch Three-Component Synthesis of 1,4-Dihydropyridines.
NH3
H
N
R1
R1
R1
R2OOC
O
R1
O
+
R2OOC
COOR2
COOR2
R3
CHO
R3
Various modifications of this reaction have also been described in the literature. For example, 1,4-
dihydropyridines can be formed from diaminoacrylates,14 by the condensation of aldehydes with
amidines15 or β-aminocrotonates,16 and from acetoacetate or aminocrotonate by condensation with
aldehydes forming the unsymmetrical 1,4-dihydropyridines.17 The other methods for preparation of 1,4-
dihydropyridines are various reductions of pyridines and pyridinium salts18 and nucleophilic additions to
pyridines and pyridinium salts.19 Some N-substituted 1,4-dihydropyridines have been prepared by
reaction of 2-amino-5-formyl-4H-pyran with primary amines.20 In recent years, interest has also been
focused on the aza-analogues, such as 1,4-dihydropyrimidines.21
Recently, alkyl 2-acylamino-3-dimethylaminopropenoates and their analogues, as masked α-formyl-α-
amino, and α-formyl-α-hydroxy acids, and their derivatives have been used as reagents for the
preparation of a variety of heterocyclic systems.22 Among them, dialkyl 4-oxo-1,4-dihydropyridin-3,5-
dicarboxylates
have
been
prepared
from
dialkyl
2,4-bis[(dimethylamino)methylene]-3-
oxopentanedioates.23 As an extension of this research, we report here the synthesis of the two bifunctional

3-dimethylaminopropenoate analogues, 4-{3-(dimethylamino)-1-[2-(dimethylamino)-vinyl]prop-2-en-
ylidene}-2-phenyl-1,3-oxazol-5(4H)-one (3) and 5-{3-(dimethylamino)-1-[2-(dimethylamino)vinyl]-
prop-2-enylidene}-3-methyl-2-thioxo-1,3-thiazolidin-4-one (15), and their utilisation in the synthesis of
1,4-dihydropyridine derivatives.
The first starting compound, (3), was prepared in two steps from hippuric acid (1) as shown in Scheme 2.
The acid (1) was first transformed into 4-(1-methylethylidene)-2-phenyl-1,3-oxazol-5(4H)-one (2)
according to the procedure described in the literature.24 Both methyl groups of 2 reacted with N,N-
dimethylformamide dimethyl acetal (DMFDMA) by heating in DMF to give 3 in 80% yield. Treatment of
3 with hydrochlorides of various aliphatic and aromatic primary amines (4a–f) afforded the corresponding
4-[1-substituted pyridin-4(1H)-ylidene]-2-phenyl-1,3-oxazol-5(4H)-ones (5a–f) in 53–75% yield.
Similarly, the reaction of 3 with 1 equivalent of hydrazine hydrate furnished the corresponding 4-(1-
aminopyridin-4(1H)-ylidene)-2-phenyl-1,3-oxazol-5(4H)-one (5g) in 19% yield.
In the reaction of compounds (5a,b,f) with hydrazine hydrate, the oxazolone ring was transformed into 3-
amino-3,5-dihydro-4H-imidazol-4-one derivatives (6a,b,f) in 31–75% yield. When compounds (5a,b,d–f)
were treated with methanol in the presence of sodium methoxide or sulfuric acid at reflux, the oxazolone
ring was cleaved to give methyl (benzoylamino)(1-substituted pyridin-4(1H)-ylidene)acetates (7a,b,d–f)
in good yields.
Catalytic hydrogenation of 7a in formic acid in the presence of 10% Pd–C afforded methyl
(benzoylamino)(1-benzylpiperidin-4-yl)acetate (8) in 48% yield and methyl (benzoylamino)(pyridin-4-
yl)acetate (9) in 11% yield, while by catalytic hydrogenation in methanol in the presence of ammonium
formate and 10% Pd–C only the debenzylation took place and methyl (benzoylamino)(pyridin-4-
yl)acetate (9) was obtained in 99% yield (Scheme 2).
5-(1-Methylethylidene)-2-thioxo-1,3-thiazolidin-4-one (11), prepared from 2-thioxo-1,3-thiazolidin-4-one
(10) and acetone according to the procedure described in the literature,25 was treated with
bis(dimethylamino)-tert-butoxymethane (Bredereck's reagent) in toluene in an inert atmosphere at room
temperature to give 5-[3-dimethylamino-1-methylprop-2-enylidene]-2-thioxo-1,3-thiazolidin-4-one (12)
in 66% yield. Upon treatment of 11 with DMFDMA, also the methylation at the ring nitrogen atom took
place to give the corresponding N-methylated derivative (13) in 65% yield. Attempts to convert
compound (12) by heating with Bredereck's reagent at 100–120°C into bis(dimethylamino) compound
(14) failed, while the reaction of compound (13) with Bredereck's reagent gave 5-{3-dimethylamino-1-[2-
(dimethylamino)vinyl]prop-2-enylidene}-3-methyl-2-thioxo-1,3-thiazolidin-4-one (15) in 94% yield.
Compound (15) was transformed with various aliphatic (4a–c), aromatic (4e,h,i), and heteroaromatic
primary amines (4j–n) and with α-amino acid derivatives (4o,p) into 3-methyl-5-(1-substituted pyridin-
4(1H)-ylidene)-2-thioxo-1,3-thiazolidin-4-ones (16a–c,e,h–p) in 22–94% yields. (Scheme 3).

Scheme 2
O
O
COOH
O
O
Ph
O
Ph
O
Ph
i
ii
iii
N
N
N
NHCOPh
Me
1
Me2N
Me
N
2
R
NMe2
5a-g
3
NH2
N
O
O
Ph
O
N
Ph
MeOOC
iv
v
N
N
NHCOPh
N
N
R
R
R
6a,b,f
5a-f
7a,b,d-f
MeOOC
MeOOC
MeOOC
N
vi
vii
NHCOPh
NHCOPh
NHCOPh
9 +
N
N
Ph
Ph
9
8
7a
Compound
4a–7a
R
benzyl
4b–7b
methyl
4c,5c
2-hydroxyethyl
cyclohexyl
phenyl
4d, 5d, 7d
4e, 5e, 7e
4f–7f
4-methylphenyl
amino
4g, 5g
Reagents and conditions: i) acetone, Ac2O, AcONa, reflux; ii) DMFDMA, DMF, reflux; iii) RNH2 (4a–
g), EtOH, HCl, reflux; iv) N2H4 x H2O, reflux; v) MeOH, MeONa, rt or MeOH, H2SO4, reflux; vi) H2,
10% Pd–C, HCOOH, rt; vii) HCOONH4, 10% Pd–C, MeOH, reflux.

Scheme 3
Me2N
Me
Me
iv
S
S
S
S
Me2N
Me2N
NH
12
ii
NH
O
O
O
14
Me
S
S
S
S
S
S
iv
iii
i
Me
Me2N
NH
10
NH
11
N
Me
O
O
S
13
Me2N
R
N
S
S
S
v
Me2N
N
N
Me
Me
O
O
15
16a-c,e,h-p
Compound
4a, 16a
4b, 16b
4c, 16c
4e, 16e
4h, 16h
4i, 16i
R
benzyl
methyl
2-hydroxyethyl
phenyl
4-fluorophenyl
3-nitrophenyl
pyridin-2-yl
4j, 16j
4k, 16k
4l, 16l
5-chloropyridin-2-yl
isoxazol-3-yl
4m, 16m
4n, 16n
4o, 16o
4p, 16p
thiazol-2-yl
benzothiazol-2-yl
methoxycarbonylmethyl
ethoxycarbonylmethyl
Reagents and conditions: i) acetone, NH3(aq.), NH4Cl, reflux; ii) t-BuOCH(NMe2)2, toluene, rt; iii)
DMFDMA, toluene, rt; iv) t-BuOCH(NMe2)2, toluene, reflux; v) RNH2 (4a–c,e,h–p), EtOH, HCl, reflux.

1
The structure determination of the products is based on H NMR spectra, MS spectra, and X-Ray
analysis. The DMFDMA methylation of heterocyclic compounds with a thioamide structural element
gives in most cases the S-methylated product.26 In the reaction of 11 with DMFDMA the compound (13)
was formed. The chemical shift for the methyl group, δ = 3.47 ppm, clearly indicates that methylation
occurred at ring nitrogen atom. Also the chemical shifts for the methyl group in compounds (16) in the
range δ = 3.34–3.77 ppm indicate that the methyl group is attached at the thiazolidine ring nitrogen atom,
since the typical chemical shift of the S-methyl groups in azole series is usually within the range δ = 2.5–
3.0 ppm. Finally, the N-methylation was unambiguously confirmed by X-Ray analysis of compound
(16a) (Figure 2, Table 1).
Both, 12 and 13, exist in DMSO–d6 solution as mixtures of isomers in a ratio of 53:47 and 59:41,
respectively. On the other hand, 13 exists in CDCl3 solution as a single isomer, since only one set of
signals was observed by 1H NMR spectrum. A more detailed structural study has not yet been carried out,
however, according to previous studies in some related 3-(dimethylamino)propenoates,22a isomerization
around the exocyclic C=C double bond in compounds (12) and (13) is feasible via the mesomeric
structures (12') and (13') (Scheme 4).
Scheme 4
Isomerisation of compounds (12) and (13) in DMSO–d6 solution.
Me2N
Me
S
12 (R = H)
S
S
S
S
S
S
13 (R = Me)
Me
Me2N
Me2N
N
N
R
O
O
R
R
O
O
Me2N
Me
S
12' (R = H)
13' (R = Me)
Me
N
N
R
X-Ray Crystallography. A thin orange plate-like crystal with approximate dimensions of 0.22 x 0.11 x
0.06 mm was mounted on a glass fibre. Diffraction data were collected on a Nonius Kappa CCD
diffractometer27,28 with graphite monochromated MoKα radiation (λ=0.71073 Å). Crystal data:
C16H14N2OS2, Mr=314.41, monoclinic space group P21/n, a=4.159(2), b=28.7708(11), c=9612(6) Å,
β=93.908(2)˚, V=1428.0(1) Å3, Z=4, T=200 K. Structure was solved by direct methods (SHELXS-9729)

and refined by full-matrix least squares on F2 using SHELXL-97.30 Non-hydrogen atoms were refined
anisotropically, hydrogen atoms were placed at calculated positions with appropriate thermal parameters
and allowed to ride on their parent atoms. Final refinement cycle was based on 5595 measured reflections
[3095 independent, 1688 observed with I>2σ(I)]. Final agreement factors on observed reflections are
R1=0.061 and wR2=0.144 for 191 refined parameters. Relevant crystal data and data collection summary
are quoted in Table 1. Crystallographic data have been deposited at the CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK. A copy can be obtained on request, free of charge, by quoting the publication
citation and the deposition number CCDC 167052.
Figure 2.
ORTEP view of compound (16a) with atomic numbering scheme. Thermal ellipsoids are
drawn at 50% probability level.
O4
C3
C22
C62
C33
C23
C13
C32
C41
C1
N12
C51
N31
C21
C42
C52
C35
C34
C36
S2
S11
Figure 3.
Crystal packing of compound (16a) viewed along a axis.
c
b
O

Description of the structure. The molecular geometry31 and crystal packing32 are depicted in Figures 2
and 3, respectively. Bond lengths and angles are normal and in agreement with related compounds. The
distances S11-C21 and S11-C51 of 1.720(5) and 1.767(4) Å suggest a single C-S bond, whereas the
distance S2-C21 of 1.675(5) indicates a double bond character. The torsion angles S11-C51-C42-C52 and
C41-C51-C42-C32 are -1.2(5) and -3.8(7)˚, respectively. There are no significant intermolecular contacts.
Table 1.
Relevant crystal data and data collection summary for compound (16a).
Formula
Formula weight
Colour
C16H14N2OS2
314.41
Orange
Size (mm)
Crystal system
Space group
a (Å)
0.22 x 0.11 x 0.06
Monoclinic
P21/n
4.1592(2)
28.7708(11)
11.9612(6)
93.9084(16)
1427.99(11)
4
b (Å)
c (Å)
β (°)
V (Å3)
Z
D
calc. (g·cm-3)
1.462
µ (mm-1)
0.372
Diffractometer
Temperature (K)
θmin,θmax (˚)
Scan type
Nonius Kappa CCD
200
2.22, 28.81
1.5˚ φ and ω scans
5595
Total data
Unique data
Observed data [I>2(σI)]
Rint.
3095
1688
0.076
R1 [I>2(σI)]
wR2 [I>2(σI)]
0.061
0.144

EXPERIMENTAL
Melting points were taken on a Kofler micro hot stage. The 1H NMR spectra were obtained on a Varian
EM360L (60 MHz) spectrometer and Bruker Avance DPX 300 (300 MHz) spectrometer with TMS as
the internal standard, MS spectra on an AutoSpecQ spectrometer, IR spectra on a Perkin-Elmer 1310
infrared spectrophotometer and microanalyses for C, H and N on a Perkin-Elmer CHN Analyser 2400.
4-(1-Methylethylidene)-2-phenyl-1,3-oxazol-5(4H)-one (2)24 and 5-(1-methylethylidene)-2-thioxo-1,3-
thiazolidin-4-one (11)25 were prepared according to the procedures described in the literature.
4-{3-Dimethylamino-1-[2-(dimethylamino)vinyl]prop-2-enylidene}-2-phenyl-1,3-oxazol-5(4H)-one (3).
Procedure A. A mixture of 2 (0.378 g, 2 mmol), DMFDMA (1.2 mL, 8 mmol), and DMF (3 mL) was
heated under reflux for 3 h. The volatile components were evaporated in vacuo, a mixture of water and
ethanol (4 mL, 3:1) was added, and the precipitate was collected by filtration to give 3. Yield: 0.498 g
(80%); mp 57–60°C (from ethanol/water). MS: (EI) m/z = 311 (M+). 1H NMR (60 MHz, CDCl3) δ: 3.05
(12H, s, 2 NMe2), 6.04 (2H, d, J = 13 Hz, 2 CHNMe2), 7.31–7.59 (3H, m, 3H of Ph), 7.58 (2H, d, J = 13
Hz, 2 CH=CH–NMe2), 7.92–8.20 (2H, m, 2H of Ph). Anal. Calcd for C18H21N3O2 x 1.5 H2O: C, 63.89; H,
7.15; N, 12.42. Found: C, 64.30; H, 7.02; N, 12.59.
Procedure B. A mixture of 2 (0.402 g, 2 mmol), DMFDMA (0.9 mL, 6 mmol), and DMF (2 mL) was
heated under reflux for 2 h. The volatile components were evaporated in vacuo, the residue was
suspended in water (3 mL) and extracted with chloroform (3 x 10 mL). Organic phases were combined,
dried over anhydrous sodium sulphate, filtered, and evaporated in vacuo to give the crude compound (3)
which was used for further transformations without purification.
General Procedure for the Preparation of 4-(1-Substituted Pyridin-4(1H)-ylidene)-2-phenyl-1,3-
oxazol-5(4H)-ones (5a–g). A mixture of compound (3) (0.622 g, 2 mmol), ethanol (3 mL) and amine
hydrochloride (4a–g) (2 mmol) was heated under reflux for 2–6 h, cooled, and the precipitate was
collected by filtration to give dihydropyridine derivatives (5a–g). (Compounds (5d) and (5f) were not
prepared in analytically pure form, however, further transformations led to analytically pure compounds
(7d) and (6f), respectively.)
The following compounds were prepared in this manner:
4-(1-Benzylpyridin-4(1H)-ylidene)-2-phenyl-1,3-oxazol-5(4H)-one (5a). This compound was prepared
from benzylamine hydrochloride (4a); reflux for 5.5 h. Yield: 0.464 g (71%), mp 178–179°C (from
ethanol), MS: (EI) m/z = 328 (M+), 1H NMR (60 MHz, CDCl3) δ: 4.95 (2H, s, CH2), 7.08–7.59 (11H, m,

8H of Ph, 3H of pyridine), 7.58–8.16 (3H, m, 2H of Ph, 1H of pyridine). Anal. Calcd for C21H16N2O2: C,
76.81; H, 4.91; N, 8.53. Found: C, 76.61; H, 4.82; N, 8.74.
4-(1-Methylpyridin-4(1H)-ylidene)-2-phenyl-1,3-oxazol-5(4H)-one (5b). This compound was prepared
from methylamine hydrochloride (4b); reflux for 2.5 h. Yield: 0.283 g (56%); mp 220–222°C (from
1
ethanol). H NMR (60 MHz, DMSO–d6) δ: 3.81 (3H, s, Me), 7.18–7.60 (4H, m, 2H of Ph and 2H of
pyridine), 7.60–8.01 (5H, m, 3H of Ph and 2H of pyridine). Anal. Calcd for C15H12N2O2: C, 71.42; H,
4.79; N, 11.10. Found: C, 71.19; H, 4.58; N, 11.21.
4-[1-(2-Hydroxyethyl)pyridin-4(1H)-ylidene]-2-phenyl-1,3-oxazol-5(4H)-one (5c). This compound
was prepared from 2-aminoethanol hydrochloride (4c); reflux for 2 h. Yield: 0.425 g (75%); mp 198–
200°C (from ethanol), 1H NMR (60 MHz, DMSO–d6) δ: 3.78 (2H, m, NCH2), 4.11 (2H, m, OCH2), 5.11
(1H, br s, OH), 7,26–7.63 (4H, m, 3H of Ph and 1H of pyridine), 7.67–8.06 (5H, m, 2H of Ph and 3H of
pyridine). Anal. Calcd for C16H14N2O3: C, 68.07; H, 5.00; N, 9.92. Found: C, 67.80; H, 4.68; N, 10.01.
4-(1-Cyclohexylpyridin-4(1H)-ylidene)-2-phenyl-1,3-oxazol-5(4H)-one (5d). This compound was
prepared from cyclohexylamine hydrochloride (4d); reflux for 6 h. Yield: 0.460 g (72%); mp 228–230°C
(from ethanol), 1H NMR (60 MHz, CDCl3) δ: 0.98–2.20 (10H, m, 10H of cyclohexyl), 3.32–3.88 (1H, m,
1H of cyclohexyl), 7.20–7.56 (6H, m, 3H of Ph and 3H of pyridine), 7.82–8.15 (3H, m, 2H of Ph and 1H
of pyridine). Anal. Calcd for C20H20N2O2: C, 74.98; H, 6.29; N, 8.74. Found: C, 75.45; H, 6.22; N, 8.30.
4-(1-Phenylpyridin-4(1H)-ylidene)-2-phenyl-1,3-oxazol-5(4H)-one (5e). This compound was prepared
from aniline hydrochloride (4e); reflux for 5 h. Yield: 0.334 g (53%); mp 194–196°C (from methanol), 1H
NMR (60 MHz, CDCl3) δ: 7.30–7.70 (11H, m, 8H of Ph and 3H of pyridine), 7.84–8.19 (3H, m, 2H of Ph
and 1H of pyridine). Anal. Calcd for C20H14N2O2: C, 76.42; H, 4.49; N, 8.91. Found: C, 76.10; H, 4.15;
N, 9.17.
4-[1-(4-Methylphenyl)pyridin-4(1H)-ylidene]-2-phenyl-1,3-oxazol-5(4H)-one (5f). This compound
was prepared from 4-methylaniline hydrochloride (4f); reflux for 2.5 h. Yield: 0.490 g (75%); mp 267–
269°C (from DMF). MS: m/z = 328 (M+). 1H NMR (60 MHz, CF3COOD) δ: 1.57 (3H, s, Me), 6.55 (4H,
br s, C6H4), 6.67–6.96 (3H, m, 3H of Ph), 7.05–7.63 (6H, m, 2H of Ph and 4H of pyridine). Anal. Calcd
for C21H16N2O2: C, 76.81; H, 4.91; N, 8.53. Found: C, 76.19; H, 4.76; N, 8.26.
4-[1-Aminopyridin-4(1H)-ylidene]-2-phenyl-1,3-oxazol-5(4H)-one (5g). This compound was prepared

from hydrazine hydrochloride (4g), reflux for 5 h. Yield: 0.098 g (19%); mp 233–234°C (from ethanol),
1H NMR (60 MHz, DMSO–d6) δ: 6.88 (2H, s, NH2), 7.18–8.00 (9H, m, 5H of Ph and 4H of pyridine).
Anal. Calcd for C14H11N3O2: C, 66.40; H, 4.38; N, 16.59. Found: C, 66.76; H, 4.05; N, 16.88.
General Procedure for the Preparation of 3-Amino-5-(1-substituted pyridin-4(1H)-ylidene)-2-
phenyl-3,5-dihydro-4H-imidazol-4-ones (6a,b,f). A mixture of oxazolone (5a,b,f) (1 mmol) and
hydrazine hydrate (99%, 3 mL, 59 mmol) was heated under reflux for 1–16 h, cooled, and the precipitate
was collected by filtration to give 6a,b,f.
The following compounds were prepared in this manner:
3-Amino-5-(1-benzylpyridin-4(1H)-ylidene)-2-phenyl-3,5-dihydro-4H-imidazol-4-one (6a). This
compound was prepared from 5a, reflux for 12.5 h. Yield: 0.182 g (53%); mp 213–216°C (from
1
ethanol/water). H NMR (60 MHz, DMSO–d6) δ: 5.13 and 5.20 (4H, 2s, 1:1, CH2 and NH2), 7.21–7.67
(9H, m, 8H of Ph and 1H of pyridine), 7.83–8.47 (5H, m, 2H of Ph and 3H of pyridine). Anal. Calcd for
C21H18N4O: C, 73.67; H, 5.30; N, 16.36. Found: C, 73.47; H, 5.24; N, 16.55.
3-Amino-5-(1-methylpyridin-4(1H)-ylidene)-2-phenyl-3,5-dihydro-4H-imidazol-4-one (6b). This
compound was prepared from 5b; reflux for 8 h. Yield: 0.199 g (75%); mp 273–278°C (decomp) (from
ethanol), 1H NMR (60 MHz, DMSO–d6) δ: 3.70 (3H, s, Me), 5.08 (2H, s, NH2), 7.12–7.50 (4H, m, 3H of
Ph and 1H of pyridine), 7.55–8.39 (5H, m, 2H of Ph and 3H of pyridine). Anal. Calcd for C15H14N4O: C,
67.65; H, 5.30; N, 21.04. Found: C, 67.43; H, 5.01; N, 21.43.
3-Amino-5-[1-(4-methylphenyl)pyridin-4(1H)-ylidene]-2-phenyl-3,5-dihydro-4H-imidazol-4-one
(6f). This compound was prepared from 5f; reflux for 16 h. Yield: 0.105 g (31%); mp 246–249°C (from
methanol), 1H NMR (60 MHz, CDCl3) δ: 2.40 (3H, s, Me), 4.40 (2H, s, NH2), 7.08–7.62 (10H, m, C6H4,
3H of Ph, and 3H of pyridine), 7.89–8.37 (3H, m, 2H of Ph and 1H of pyridine). Anal. Calcd for
C21H18N4O: C, 73.67; H, 5.30; N, 16.36. Found: C, 73.61; H, 5.34; N, 16.22.
General Procedures for the Preparation of Methyl (Benzoylamino)[1-Substituted Pyridin-4(1H)-
ylidene]acetates (7a,b,d–f).
Procedure A. A mixture of compound (5) (1 mmol) and a solution of sodium (92 mg, 4 mmol) in
methanol (5 mL) was heated under reflux for 0.25–2 h, cooled, and the precipitate was collected by
filtration to give 7.
Procedure B. A mixture of compound (5) (1 mmol) and a solution of sulfuric acid (96%, 0.3 mL) in

methanol (2 mL) was heated under reflux for 1–1.5 h, cooled, neutralised with 5% aqueous solution of
sodium hydrogen carbonate, and the product was extracted with chloroform (5 mL). The organic phase
was dried over anhydrous sodium sulphate, filtered, and the filtrate was evaporated in vacuo. The oily
residue was triturated with an appropriate solvent and the precipitate was collected by filtration to give 7.
The following compounds were prepared in this manner:
Methyl (Benzoylamino)[1-Benzylpyridin-4(1H)-ylidene]acetate (7a). This compound was prepared
from 5a; Procedure A, reflux for 2 h. Yield: 0.356 g (99%); mp 230–232°C (from acetonitrile), 1H NMR
(60 MHz, DMSO–d6) δ: 3.49 (3H, s, OMe), 4.93 (2H, s, CH2), 6.00–6.18 (1H, m, 1H of pyridine), 7.12–
7.63 (10H, m, 8H of Ph and 2H of pyridine), 7.69–8.00 (3H, m, 2H of Ph and 1H of pyridine), 8.91 (1H,
s, NH). Anal. Calcd for C22H20N2O3: C, 73.32; H, 5.59; N, 7.77. Found: C, 73.12; H, 5.43; N, 7.81.
Methyl (Benzoylamino)[1-Methylpyridin-4(1H)-ylidene]acetate (7b). This compound was prepared
from 5b; Procedure B, reflux for 1 h, trituration with acetone. Yield: 0.189 (66%); mp 210°C (from
1
methanol). H NMR (60 MHz, DMSO–d6) δ: 3.25 (6H, br s, OMe and NMe), 6.02–6.20 (1H, m, 1H of
pyridine), 7.14–7.40 (2H, m, 2H of pyridine), 7.45–7.66 (3H, m, 3H of Ph), 7.77–8.09 (3H, m: 2H of Ph
and 1H of pyridine), 8.95 (1H, s, NH). Anal. Calcd for C16H16N2O3: C, 67.59; H, 5.67; N, 9.85. Found: C,
67.57; H, 5.54; N, 9.79.
Methyl (Benzoylamino)[1-Cyclohexylpyridin-4(1H)-ylidene]acetate (7d). This compound was
prepared from 5d; Procedure B, reflux for 1.5 h, trituration with acetone. Yield: 0.260 g (74%); mp 229–
231°C (from methanol), 1H NMR (60 MHz, DMSO–d6) δ: 0.95–2.03 (10H, m, 10H of cyclohexyl), 3.28–
3.94 (1H, m, 1H of cyclohexyl), 3.59 (3H, s, OMe), 6.02–6.19 (1H, m, 1H of pyridine), 7.28–7.65 (5H,
m, 3H of Ph and 2H of pyridine), 7.78–8.09 (3H, m, 2H of Ph and 1H of pyridine), 8.95 (1H, s, NH).
Anal. Calcd for C21H24N2O3: C, 71.57; H, 6.86; N, 7.95. Found: C, 71.46; H, 6.68; N, 7.99.
Methyl (Benzoylamino)[1-Phenylpyridin-4(1H)-ylidene]acetate (7e). This compound was prepared
from 5e; Procedure A, reflux for 15 min. Yield: 0.314 g (91%); mp 244–247°C (from
1
methanol/acetonitrile). H NMR (60 MHz, DMSO–d6) δ: 3.56 (3H, s, OMe), 6.14–6.31 (1H, m, 1H of
pyridine), 7.18–7.70 (10H, m, 8H of Ph and 2H of pyridine), 7.81–8.10 (3H, m, 2H of Ph and 1H of
pyridine), 9.09 (1H, s, NH). Anal. Calcd for C21H18N2O3: C, 72.82; H, 5.24; N, 8.09. Found: C, 72.67; H,
4.90; N, 8.40.
Methyl (Benzoylamino)[1-(4-Methylphenyl)pyridin-4(1H)-ylidene]acetate (7f). This compound was

prepared from 5f; Procedure B, reflux for 1.5 h, trituration with water/methanol (2:1). Yield: 0.138 g
1
(38%); mp 237–240°C (from methanol), H NMR (60 MHz, DMSO–d6) δ: 2.34 (3H, s, Ar–Me), 3.56
(3H, s, COOMe), 6.17–6.33 (1H, m, 1H of pyridine), 7.22–7.77 (9H, m, C6H4, 3H of Ph, and 2H of
pyridine), 7.87–8.11 (3H, m, 2H of Ph and 1H of pyridine), 9.13 (1H, s, NH). Anal. Calcd for
C22H20N2O3: C, 73.32; H, 5.59; N, 7.77. Found: C, 73.51; H, 5.68; N, 8.05.
Methyl (Benzoylamino)(1-Benzylpiperidin-4-yl)acetate (8) and Methyl (Benzoylamino)(Pyridin-4-
yl)acetate (9). A mixture of compound (7a) (720 mg, 2 mmol), formic acid (6 mL), and 10% Pd–C (150
mg) was hydrogenated at rt for 48 h at 340 kPa pressure of hydrogen. The mixture was filtered through
Vulkasil®, washed with formic acid (2 x 5 mL), and the filtrate was evaporated in vacuo. The oily residue
was triturated with methanol/water and the precipitate was collected by filtration to give 9; yield: 0.065 g
(12%). The filtrate was evaporated in vacuo, the residue was triturated with diisopropyl ether/methanol,
and the precipitate was collected by filtration to give 8. Yield: 0.352 g (48%); mp 122–125°C (from
acetone), 1H NMR (60 MHz, CDCl3) δ: 1.25–2.18 (7H, m, 7H of piperidine), 2.86 and 3.04 (2H, 2m, 1:1,
2H of piperidine), 3.48 (2H, s, CH2Ph), 3.68 (3H, s, COOMe), 4.37 (1H, dd, J = 4.0, 8.0 Hz, CHNH),
7.35 (5H, s, Ph), 7.46–7.68 (3H, m, 3H of Ph), 7.73–8.08 (2H, m, 2H of Ph), 8.71 (1H, br d, J = 8.0 Hz,
NH). Anal. Calcd for C22H26N2O3: C, 72.11; H, 7.15; N, 7.64. Found: C, 71.96; H, 7.05; N, 7.56.
Methyl (Benzoylamino)(Pyridin-4-yl)acetate (9). A mixture of compound (7a) (2.090 g, 5.93 mmol),
methanol (20 mL), ammonium formate (1.096 g, 17.4 mmol), and 10% Pd–C (1.450 g) was heated under
reflux for 30 min. The mixture was filtered through Vulkasil®, washed with hot methanol, and the filtrate
was evaporated in vacuo. The oily residue was triturated with methanol/water (1:3, 4 mL) and the
precipitate was collected by filtration to give 9. Yield: 1.586 g (99%); mp 117–119°C (from diisopropyl
ether/methanol), 1H NMR (60 MHz, DMSO–d6) δ: 3.72 (3H, s, OMe), 5.82 (1H, d, J = 8.0 Hz, CHNH),
7.30–7.69 (5H, m, 3H of Ph, 3'–H, and 5'–H), 7.72–8.12 (2H, m, 2H of Ph), 8.61 (2H, m, 2'–H, 6'–H),
9.36 (1H, d, J = 8.0 Hz, NH). Anal. Calcd for C15H14N2O3: C, 66.66; H, 5.22; N, 10.36. Found: C, 66.35;
H, 4.86; N, 10.74.
5-[3-Dimethylamino-1-methylprop-2-enylidene]-2-thioxo-1,3-thiazolidin-4-one (12). A solution of
compound (11) (1.733 g, 10 mmol) and Bredereck's reagent (8.3 mL, 40 mmol) in anhydrous toluene (20
mL) was stirred at rt under argon atmosphere for 84 h. The volatile components were evaporated in
vacuo, ethanol (10 mL) was added to the residue, and the precipitate was collected by filtration to give 12.
Yield: 1.516 g (66%); mp 257–259°C (from ethanol/toluene), MS: (EI) m/z = 228 (M+), (FAB) m/z = 229
1
(MH+). IR (KBr) 3110, 2998, 2837, 1651, 1592, 1518 cm-1. H NMR (300 MHz, DMSO–d6) Major

isomer δ: 2.03 (3H, s, Me), 3.02 (6H, br s, NMe2), 6.97 (1H, d, J = 13.2 Hz, CH=CHNMe2), 7.64 (1H, d,
J = 13.2 Hz, CH=CHNMe2). 12.71 (1H, br s, NH); Minor isomer δ: 2.43 (3H, s, Me), 4.71 (1H, d, J =
12.4 Hz, CH=CHNMe2), 7.54 (1H, d, J = 12.4 Hz, CH=CHNMe2). Anal. Calcd for C9H12N2OS2: C,
47.34; H, 5.30; N, 12.27. Found: C, 47.50; H, 5.31; N, 12.19.
5-[3-Dimethylamino-1-methylprop-2-enylidene]-3-methyl-2-thioxo-1,3-thiazolidin-4-one (13).
A
solution of compound (11) (1.970 g, 11.4 mmol) and DMFDMA (9.1 mL, 68.4 mmol) in anhydrous
toluene (20 mL) was stirred at rt under argon atmosphere for 24 h. The volatile components were
evaporated in vacuo, ethanol (10 mL) was added to the residue, and the precipitate was collected by
filtration to give 13. Yield: 1.800 g (65%); mp 195–198°C (from ethanol/toluene). MS: (EI) m/z = 242
(M+), (FAB) m/z = 243 (MH+). IR (KBr) 2905, 1660, 1601, 1521, 1400, 1260 cm-1. 1H NMR (300 MHz,
CDCl3) δ: 2.09 (3H, s, Me), 3.06 (6H, s, NMe2), 3.47 (3H, s, Me–N(3)), 7.19 (2H, s, CH=CH). 1H NMR
(300 MHz, DMSO–d6) Major isomer δ: 2.10 (3H, s, Me), 3.18 (6H, br s, NMe2), 3.31 (3H, s, Me–N(3)),
7.09 (1H, d, J = 12.8 Hz, CH=CHNMe2), 7.75 (1H, d, J = 12.8 Hz, CH=CHNMe2); Minor isomer δ: 2.94
(6H, br s, NMe2), 3.29 (3H, s, Me–N(4)), 4.84 (1H, d, J = 12.1 Hz, CH=CHNMe2), 7.64 (1H, d, J = 12.1
Hz, CH=CHNMe2). Anal. Calcd for C10H14N2OS2: C, 49.56; H, 5.82; N, 11.56. Found: C, 49.49; H, 5.75;
N, 11.31.
5-{3-Dimethylamino-1-[2-(dimethylamino)vinyl]prop-2-enylidene}-3-methyl-2-thioxo-1,3-thiazoli-
din-4-one (15). A solution of compound (13) (0.528 g, 2.4 mmol) and Bredereck's reagent (1 mL, 4.8
mmol) in anhydrous toluene (10 mL) was stirred at 110–120°C under argon atmosphere for 1 h. The
volatile components were evaporated in vacuo, ethanol (5 mL) was added to the residue, and the
precipitate was collected by filtration to give 15. Yield: 0.670 g (94%); mp 198–199°C (from
ethanol/toluene). MS: (EI) m/z = 297 (M+), (FAB) m/z = 298 (MH+). HRMS: Calcd for C13H19N3OS2:
1
297.096956. Found: 297.098050. IR (KBr) 2905, 2808, 1649, 1586, 1503, 1259 cm-1. H NMR (300
MHz, CDCl3) δ: 2.98 (12H, s, 2 NMe2), 3.47 (3H, s, Me–N(3)), 5.72 (2H, br s, 2 CH=CHNMe2), 6.97
(2H, d, J = 12.8 Hz, 2 CH=CHNMe2). Anal. Calcd for C13H19N3OS2: C, 52.49; H, 6.44; N, 14.13. Found:
C, 52.46; H, 6.35; N, 14.02.
General Procedure for the Preparation of 3-Methyl-5-[1-Substituted Pyridin-4(1H)-ylidene]-2-
thioxo-1,3-thiazolidin-4-ones (16a–c,e,h–p). A mixture of compound (15) (0.149 g, 0.5 mmol), amine
hydrochloride (4) (0.5 mmol), and ethanol (1 mL) was stirred under reflux for 15 min–3 h. The volatile
components were evaporated in vacuo, ethanol (0.5 mL) was added to the residue, and the precipitate was
collected by filtration to give 16.

The following compounds were prepared in this manner:
5-[1-Benzylpyridin-4(1H)-ylidene]-3-methyl-2-thioxo-1,3-thiazolidin-4-one (16a). This compound
was prepared from benzylamine hydrochloride (4a), reflux for 2 h. Yield: 0.148 g (94%); mp 287–288°C
1
(from ethanol). IR (KBr) 3036, 1660, 1616, 1526, 1406, 1270 cm-1. H NMR (300 MHz, DMSO–d6) δ:
3.28 (3H, s, Me), 5.23 (2H, s, CH2), 6.46 (1H, dd, J = 2.5, 7.2 Hz, 5'–H), 7.33–7.45 (5H, m, Ph), 7.98–
8.02 (2H, m, 2'–H and 6'–H), 8.25 (1H, dd, J = 2.5, 7.5 Hz, 3'–H). Anal. Calcd for C16H14N2OS2: C,
61.12; H, 4.49; N, 8.91. Found: C, 61.29; H, 4.62; N, 8.64.
3-Methyl-5-[1-methylpyridin-4(1H)-ylidene]-2-thioxo-1,3-thiazolidin-4-one (16b). This compound
was prepared from methylamine hydrochloride (4b), reflux for 1 h. Yield: 0.093 g (78%); mp 315–316°C
1
(from ethanol/DMF). IR (KBr) 3046, 2936, 1663, 1618, 1530, 1263 cm-1. H NMR (300 MHz, DMSO–
d6) δ: 3.32 (3H, s, Me–N(3)), 3.77 (3H, s, Me–N(1')), 6.45 (1H, ddd, J = 0.6, 2.6, 7.1 Hz, 5'–H), 7.84–
7.87 (2H, m, 2'–H and 6'–H), 8.25 (1H, ddd, J = 0.6, 2.6, 7.3 Hz, 3'–H). Anal. Calcd for C10H10N2OS2: C,
50.39; H, 4.23; N, 11.75. Found: C, 50.43; H, 4.11; N, 11.59.
5-[1-(2-Hydroxyethyl)pyridin-4(1H)-ylidene]-3-methyl-2-thioxo-1,3-thiazolidin-4-one (16c). This
compound was prepared from 2-aminoethanol hydrochloride (4c), reflux for 1 h. Yield: 0.121 g (90%);
1
mp 290–294°C (from ethanol/DMF). IR (KBr) 3345, 1656, 1580, 1509, 1396, 1275 cm-1. H NMR (300
MHz, DMSO-d6) δ: 3.34 (3H, s, Me), 3.69 (2H, dt, J = 5.1, 5.2 Hz, CH2OH), 4.05 (2H, t, J = 5.1 Hz,
H2C–N(1')), 5.07 (1H, t, J = 5.2 Hz, OH), 6.46 (1H, dd, J = 2.5, 7.3 Hz, 5'–H), 7.85–7.89 (2H, m, 2'–H
and 6'–H), 8.26 (1H, dd, J = 2.5, 7.4 Hz, 3'–H). Anal. Calcd for C11H12N2O2S2: C, 49.23; H, 4.51; N,
10.44. Found: C, 49.09; H, 4.41; N, 10.15.
3-Methyl-5-[1-phenylpyridin-4(1H)-ylidene]-2-thioxo-1,3-thiazolidin-4-one (16e). This compound
was prepared from aniline hydrochloride (4e), reflux for 3 h. Yield: 0.125 g (83%); mp 312–314°C (from
1
ethanol/DMF). IR (KBr) 3051, 1657, 1620, 1532, 1489, 1265 cm-1. H NMR (300 MHz, CDCl3) δ: 3.51
(3H, s, Me), 6.29 (1H, dd, J = 2.5, 7.5 Hz, 5'–H), 7.34–7.37 (2H, m, 2H of Ph), 7.45–7.50 (3H, m, 3H of
Ph), 7.53–7.56 (2H, m, 2'–H, 6'–H), 8.44 (1H, dd, J = 2.5, 7.9 Hz, 3'–H). Anal. Calcd for C15H12N2OS2: C,
59.97; H, 4.03; N, 9.33. Found: C, 60.03; H, 3.98; N, 9.13.
5-[1-(4-Fluorophenyl)pyridin-4(1H)-ylidene]-3-methyl-2-thioxo-1,3-thiazolidin-4-one (16h). This
compound was prepared from 4-fluoroaniline hydrochloride (4h), reflux for 2 h. Yield: 0.148 g (93%);
1
mp 320–322°C (from ethanol/DMF). IR (KBr) 3051, 1663, 1622, 1509, 1277 cm-1. H NMR (300 MHz,

CDCl3) δ: 3.50 (3H, s, Me), 6.26 (1H, dd, J = 2.4, 7.3 Hz, 5'–H), 7.22–7.27 (2H, m, 2H of Ph), 7.32–7.37
(2H, m, 2H of Ph), 7.39–7.42 (2H, m, 2'–H and 6'–H), 8.42 (1H, dd, J = 7.7, 2.4 Hz, 3'–H). Anal. Calcd
for C15H11N2OFS2: C, 56.58; H, 3.48; N, 8.80. Found: C, 56.45; H, 3.51; N, 8.60.
3-Methyl-5-[1-(3-nitrophenyl)pyridin-4(1H)-ylidene]-2-thioxo-1,3-thiazolidin-4-one (16i). This
compound was prepared from 3-nitroaniline hydrochloride (4i), reflux for 1 h. Yield: 0.096 g (56%); mp
1
347–350°C (from ethanol/DMF). IR (KBr) 3063, 1665, 1626, 1528, 1352, 1271 cm-1. H NMR (300
MHz, DMSO–d6) δ: 3.35 (3H, s, Me), 6.50–6.55 (1H, m, 5'–H), 7.86–7.91 (1H, m, 1H of Ar), 8.10–8.14
(1H, m, 1H of Ar), 8.21–8.25 (2H, m, 2H of Ar), 8.29–8.35 (2H, m, 2'–H and 6'–H), 8.51–8.53 (1H, m,
3'–H). Anal. Calcd for C15H11N3O3S2: C, 52.16; H, 3.21; N, 12.17. Found: C, 52.42; H, 3.24; N, 11.97.
3-Methyl-5-[1-(pyridin-2-yl)pyridin-4(1H)-ylidene]-2-thioxo-1,3-thiazolidin-4-one
(16j).
This
compound was prepared from 2-aminopyridine hydrochloride (4j), reflux for 30 min. Yield: 0.073 g
(48%); mp 345–347°C (from ethanol/DMF). IR (KBr) 1663, 1619, 1528, 1431, 1267 cm-1. 1H NMR (300
MHz, DMSO–d6) δ: 3.35 (3H, s, Me), 6.53 (1H, ddd, J = 0.5, 2.6, 7.5 Hz, 5'–H), 7.52 (1H, ddd, J = 0.9,
4.8, 7.4 Hz, 5''–H), 7.88 (1H, deg dt, J = 0.9, 7.3 Hz, 3''–H), 8.11 (1H, ddd, J = 1.9, 7.3, 7.4 Hz, 4''–H),
8.30 (1H, ddd, J = 0.5, 2.6, 7.9 Hz, 3'–H), 8.53–8.57 (2H, m, 2'–H and 6'–H), 8.60 (1H, ddd, J = 0.9, 1.9,
4.8 Hz, 6''–H). Anal. Calcd for C14H11N3OS2: C, 55.79; H, 3.68; N, 13.94. Found: C, 56.04; H, 3.69; N,
13.64.
5-[1-(5-Chloropyridin-2-yl)pyridin-4(1H)-ylidene]-3-methyl-2-thioxo-1,3-thiazolidin-4-one
(16k).
This compound was prepared from 2-amino-5-chloropyridine hydrochloride (4k), reflux for 1 h. Yield:
1
0.053 g (32%); mp 339–341°C (from ethanol/DMF), IR (KBr) 3092, 1663, 1622, 1531, 1275 cm-1. H
NMR (300 MHz, DMSO–d6) δ: 3.35 (3H, s, Me), 6.52 (1H, dd, J = 2.5, 7.9 Hz, 5'–H), 7.93 (1H, dd, J =
0.8, 8.9 Hz, 3''–H), 8.25 (1H, dd, J = 2.5, 8.9 Hz, 4''–H), 8.27 (1H, dd, J = 2.5, 8.1 Hz, 3'-H), 8.47–8.52
(2H, m, 2'–H and 6'–H), 8.65 (1H, dd, J = 0.8, 2.5 Hz, 6''–H). Anal. Calcd for C14H10N3OClS2: C, 50.07;
H, 3.00; N, 12.51. Found: C, 50.13; H, 2.84; N, 12.41.
5-[1-(Isoxazol-3-yl)pyridin-4(1H)-ylidene]-3-methyl-2-thioxo-1,3-thiazolidin-4-one (16l). This
compound was prepared from 3-aminoisoxazole hydrochloride (4l), reflux for 1 h. Yield: 0.062 g (43%);
1
mp 224–226°C (from ethanol/DMF). IR (KBr) 3108, 2362, 1674, 1630, 1464, 1273 cm-1. H NMR (300
MHz, DMSO–d6) δ: 3.34 (3H, s, Me), 6.47 (1H, dd, J = 1.3, 7.9 Hz, 5'–H), 7.27 (1H, d, J = 1.8 Hz, 4''–
H), 8.18–8.21 (3H, m, 2'–H, 3'–H, and 6'–H), 9.12 (1H, d, J = 1.8 Hz, 5''–H). Anal. Calcd for
C12H9N3O2S2: C, 49.47; H, 3.11; N, 14.42. Found: C, 49.32; H, 2.89; N, 14.29.

3-Methyl-5-[1-(thiazol-2-yl)pyridin-4(1H)-ylidene]-2-thioxo-1,3-thiazolidin-4-one (16m). This
compound was prepared from 2-aminothiazole hydrochloride (4m), reflux for 1 h. Yield: 0.102 g (66%);
1
mp 228–229°C (from ethanol/DMF). IR (KBr) 3073, 1672, 1628, 1499, 1409, 1269 cm-1. H NMR (300
MHz, DMSO–d6) δ: 3.35 (3H, s, Me), 6.45 (1H, dd, J = 2.6, 7.9 Hz, 5'–H), 7.69 (1H, d, J = 3.4 Hz, 4''–
H), 7.72 (1H, d, J = 3.4 Hz, 5''–H), 8.21 (1H, dd, J = 2.6, 7.9 Hz, 3'–H), 8.29–8.34 (2H, m, 2'–H and 6'–
H). Anal. Calcd for C12H9N3OS3: C, 46.88; H, 2.95; N, 13.67. Found: C, 46.99; H, 2.73; N, 13.48.
5-[1-(Benzothiazol-2-yl)pyridin-4(1H)-ylidene]-3-methyl-2-thioxo-1,3-thiazolidin-4-one (16n). This
compound was prepared from 2-aminobenzothiazole hydrochloride (4n), reflux for 1 h. Yield: 0.076 g
1
(43%); mp >350°C (from ethanol/DMF). IR (KBr) 1675, 1618, 1501, 1404, 1259 cm-1. H NMR (300
MHz, DMSO–d6) δ: 3.36 (3H, s, Me), 6.50 (1H, dd, J = 2.5, 7.7 Hz, 5'–H), 7.48 (1H, ddd, J = 1.2, 6.5, 8.3
Hz, 6''–H), 7.58 (1H, ddd, J = 1.3, 6.5, 7.9 Hz, 5''–H), 7.96 (1H, ddd, J = 0.8, 1.2, 7.9 Hz, 4''–H), 8.18
(1H, dd, J = 1.3, 8.3 Hz, 7''–H), 8.23 (1H, dd, J = 2.5, 7.9 Hz, 3'–H), 8.37–8.41 (2H, m, 2'–H and 6'–H).
Anal. Calcd for C16H11N3OS3: C, 53.76; H, 3.10; N, 11.75. Found: C, 53.75; H, 2.87; N, 11.55.
5-[1-Methoxycarbonylmethylpyridin-4(1H)-ylidene]-3-methyl-2-thioxo-1,3-thiazolidin-4-one (16o).
This compound was prepared from methyl glycinate hydrochloride (4o), reflux for 15 min. Yield: 0.070 g
(47%); mp 223–225°C (from toluene). IR (KBr) 2949, 1744, 1670, 1618, 1530 cm-1. 1H NMR (300 MHz,
CDCl3) δ: 3.48 (3H, s, Me), 3.84 (3H, s, COOMe), 4.49 (2H, s, CH2), 6.17 (1H, dd, J = 2.5, 7.4 Hz, 5'–
H), 7.04–7.11 (2H, m, 2'–H and 6'–H), 8.33 (1H, dd, J = 2.5, 7.4 Hz, 3'–H). Anal. Calcd for
C12H12N2O3S2: C, 48.63; H, 4.08; N, 9.45. Found: C, 48.39; H, 3.90; N, 9.23.
5-[1-Ethoxycarbonylmethylpyridin-4(1H)-ylidene]-3-methyl-2-thioxo-1,3-thiazolidin-4-one
(16p).
This compound was prepared from ethyl glycinate hydrochloride (4p), reflux for 15 min. Yield: 0.078 g
(50%); mp 229–231°C (from toluene/DMF). MS: (EI) m/z = 310 (M+), (FAB) m/z = 311 (MH+). IR (KBr)
1
2986, 1738, 1660, 1617, 1532 cm-1. H NMR (300 MHz, CDCl3) δ: 1.32 (3H, t, J = 7.1 Hz, CH2CH3),
3.48 (3H, s, Me), 4.29 (2H, q, J = 7.1 Hz, CH2CH3), 4.48 (2H, s, CH2COOEt), 6.17 (1H, dd, J = 2.3, 7.2
Hz, 5'–H), 7.07–7.13 (2H, m, 2'–H and 6'–H), 8.33 (1H, dd, J = 2.3, 7.5 Hz, 3'–H). Anal. Calcd for
C13H14N2O3S2: C, 50.30; H, 4.55; N, 9.03. Found: C, 49.99; H, 4.51; N, 8.86.
ACKNOWLEDGEMENTS
Financial support from the Ministry of Science and Technology, Slovenia, is gratefully acknowledged.
The crystallographic data for three compounds were collected on the Kappa CCD Nonius diffractometer

in the Laboratory of Inorganic Chemistry, Faculty of Chemistry and Chemical Technology, University of
Ljubljana, Slovenia. We acknowledge with thanks the financial contribution of the Ministry of Science
and Technology, Republic of Slovenia through grants X-2000 and PS-511-103, which thus made the
purchase of the apparatus possible.
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