Synthesis of new thiazolidine and imidazolidine derivatives of pharmacological interest

Article abstract of DOI:10.1002/jhet.5570450302

(Chemical Equation Presented) The hitherto unknown 5-(2-aryl-2-oxoethyl)-4- oxo-1,3-thiazolidines 1a-l have been synthesized via cycloaddition process between thiourea and/or its derivatives with 3-aroylpropenoic acids. ¹H NMR spectra revealed the presence of 1a-c as a tautmeric mixture. The presence of the thiazoline tautmers (1a-c)′ was confirmed by methylating the tautmeric mixture, to the respective methylated derivatives 2-N-methylanilino-5-(2-aryl-2-oxoethyl)-4-oxo-1,3-thiazolines 2a-c and 1g-i. Acidic treatment of 1 provided the respective 2-oxo homologues 3a-i. When 1a-d, k were refluxed with DMF, molecular rearrangement was achieved, providing the 4-oxo-2-thioxoimidazolidine isomers 4a-d, k. Bromination of 4a and 4d in hot acetic acid afforded the respective (E,Z)-5-benzoylmethylene derivatives 5a, d which were prepared authentically. Thiation of 1a-c and 4a-c gave 5-aryl-2,3-dihydro-2-phenyliminothieno[2,3-d]thiazoles 6a-c and 1-phenyl-5-aryl-2,3-dihydro-2-thioxothieno[2,3-d]imidazoles 7a-c, respectively. The proposed structures have been confirmed by elemental analysis and spectroscopic data. The selected products showed different antimicrobial effect.

Full text of DOI:10.1002/jhet.5570450302

May-Jun 2008
645
Synthesis of New Thiazolidine and Imidazolidine
Derivatives of Pharmacological Interest
Nadia K. El-Aasar*, Khaled F. Saied
Chemistry Department, Faculty of Science, Ain Shams University,
Abbassia, Cairo, Egypt, E-mail: nadia.alaasar@yahoo.com
Received September 24, 2006
S
R'HN
S
S
R'N
NR
NR
NR
NHR
AcOH
Br2 /AcOH/
O
Ar = Ph
DMF/
R'N
R'N
S
+
O
O
CH2COAr
4
CHCOPh
5
CH2COAr
O
C
C
O
1
Ar
HO
thiation
R, R'= H,Ph
DMS
thiation
AcOH/
H
O
Ph
S
AcONa
R'N
S
N
Me
S
NR
NR
NR
N
O
NR
R'N
S
O
S
S
R'N
S
+
1g-i
O
+
CH2COAr
CH2COAr
2
Ar
Ar
PhCO-CHO
3
6
7
The hitherto unknown 5-(2-aryl-2-oxoethyl)-4-oxo-1,3-thiazolidines 1a-l have been synthesized via
cycloaddition process between thiourea and/or its derivatives with 3-aroylpropenoic acids. 1H NMR
spectra revealed the presence of 1a-c as a tautmeric mixture. The presence of the thiazoline tautmers
(1a-c)' was confirmed by methylating the tautmeric mixture, to the respective methylated derivatives 2-N-
methylanilino-5-(2-aryl-2-oxoethyl)-4-oxo-1,3-thiazolines 2a-c and 1g-i. Acidic treatment of 1 provided
the respective 2-oxo homologues 3a-i. When 1a-d, k were refluxed with DMF, molecular rearrangement
was achieved, providing the 4-oxo-2-thioxoimidazolidine isomers 4a-d, k. Bromination of 4a and 4d in hot
acetic acid afforded the respective (E,Z)-5-benzoylmethylene derivatives 5a, d which were prepared
authentically. Thiation of 1a-c and 4a-c gave 5-aryl-2,3-dihydro-2-phenyliminothieno[2,3-d]thiazoles 6a-c
and 1-phenyl-5-aryl-2,3-dihydro-2-thioxothieno[2,3-d]imidazoles 7a-c, respectively. The proposed
structures have been confirmed by elemental analysis and spectroscopic data. The selected products
showed different antimicrobial effect.
J. Heterocyclic Chem., 45, 645 (2008).
propenoic acids [11], cycloaddition process was achieved
providing 5-(2-aryl-2-oxoethyl)-4-oxo-1,3-thiazolidines
1a-l in a good yield (Scheme 1).
INTRODUCTION
The reported biological activity for many thiazolidine
derivatives [1] such as antifungal [2], antiviral [3],
anticonvulsant [4] and antitubercular [5] as well as those
reported for imidazolidines [6-9] stimulated the authors to
prepare new derivatives of these classes.
Un-substituted thiourea has been reported to react with
maleic anhydride, maleic acid, fumaric acid and methyl
hydrogen fumarate, to afford 4-oxo-1,3-thiazolidines [10].
Similar to these methods, the thiazolidinone derivatives 1
were synthesized from thioureas and 3-aroylpropenoic
acids [11]. The study provides also a mild and facile route
to the 4-oxo-2-thioxoimidazolidines 4, compared with
previous methods for similar synthesis [12]. Moreover,
the reported biological activity for different thiophenes
[13] encouraged us to synthesize thiazole 6 and imidazole
7 derivatives containing this moiety, easily by thiation of
1 and 4, respectively with Lawesson's reagent [14].
IR spectrum of 1a exhibited absorption bands for aroyl
CO group at 1684 cm-1, νCO for cyclic amide at 1614 cm-1
besides two absorption bands for νNH at 3179, 3141 cm-1
.
The mass spectrum of 1a exhibited an intense molecular
ion peak m/e 310 (80 %) and a base peak m/e 205 (100%)
for the ionic radical [M- PhCO]+, besides other pattern of
intense peaks corresponding to the fragments,
[PhCOCH2]+. m/e 119 (31 %), [PhCO]+ m/e 105 (65 %)
1
and [Ph]+ m/e 77 (77 %). The H NMR spectra of 1a-c
exhibited patterns of successive doublets in the aromatic
H region at δ 7- 8 ppm, besides complicated multiplet for
the thiazolidinone proton at ~ 4.6 ppm and deformed
multiplet ~ 4.0- 4.2 ppm for the (CH2) protons (-CO-CH2).
These complicated spectra were interpreted due to the
existence of 1a-c as a tautmeric mixture.
The presence of the thiazoline tautmers (1a-c)' has been
confirmed by treating 1a-c with ethanolic KOH solution,
providing the respective potassium salts. Alkylating [15]
the hypothetically formed salts with dimethyl sulphate,
afforded the expected methyl derivatives Ph-N-CH3; 2-N-
RESULTS AND DISCUSSION
When thiourea, phenyl-, 1-methyl-3-phenyl- and/or 1,3-
diphenylthiourea was conducted to react with 3-aroyl-

646
K. Nadia and F. Khaled
Vol 45
Scheme 1
R'N
O
NHR
NR
R'N
NR
OH
OH
S
O
S
S
O
O
AcOH/
H2O
AcOH \
H
R'N
O
O
O
SH
+
O
O
-
RHN
R'HN
S
Y
Y
Y
Y
RHN
1a-l
3a-i
R,R',Y = 1a;H, Ph, H, e;Ph, Ph, Br
i;Me,Ph,Cl
R,Y = 3a;H, H,
b;H, Br, c;H, Cl,
d;Ph, H, e;Ph, Br, f;Ph,Cl
g;Me, H h;Me, Br, i;Me, Cl,
f;Ph, Ph, Cl
g;Me, Ph, H
h;Me, Ph, Br
b;H, Ph, Br
c;H, Ph, Cl
d;Ph,Ph, H,
j;H, H, H
k;H, H, Br
l;H, H, Cl
Synthesis of 1, 3
Scheme 2
Ph
N
PhHN
Ph
CH3
NH
Ph
N
N
S
N
CH3
O
S
N
N
O
O
S
S
i) EtOH\ KOH
10 oC
O
O
O
O
O
+
ii) (CH3)2SO4
Y
Y
Y
Y
1a-c
(1a-c)'
1g-i
2a-c
Y = 1, 2a; H, b; Br, c; Cl
Synthesis of 1g-i, 2a-c
methylanilino-5-(2-aryl-2-oxoethyl)-4-oxo-1,3-thiazolines
2a-c and CO-N-CH3; 2-phenylimino-3-methyl-5-(2-aryl-
2-oxoethyl)-4-oxo-1,3-thiazolidines 1g-i (Scheme 2).
The structure of the methylated products 1g-i has been
supported by elemental analysis and spectroscopic data.
Methylation was further confirmed by m.p matching with
the previous samples, the appearance of N-CH3 signal in
the H NMR spectra δ ~ 3.3 s 3H, (CH3), rather than the
disappearance of the NH signal. Besides the IR spectra
which were devoid of any NH absorption bands.
3a-i (Scheme 1). The structure for compound 3 was
confirmed by correct elemental analysis, 1H NMR and the
IR spectra which recorded the appearance of thiolactone
absorption bands ~1735-1760 cm-1. Moreover, the
structure was further supported by mass spectra, which
1
showed the correct molecular ion peaks. The H NMR
spectrum of 3a showed at δ 7.96 d, 2H; 7.64, 7.06 two
deformed t, 1H, 2H (Ph), at δ 7.26, 1H (NH), at δ 4.68,
dd, 1H (H-5), δ 4.69, 3.59 ppm 2dd, each1H (PhCO-CH2)
and the EI-MS exhibited [M+.] m/e 235 (21.9 %).
1
The structure of 2 has been proven via authentic samples
were prepared from 1-phenyl-1-methylthiourea [16] and
3-aroylpropenoic acids. Moreover, the structure of 2 was
also confirmed by the appearance of Ph-N-CH3 singlet in
their H NMR at δ ~ 3.6, besides the mass spectra which
displayed the expected molecular ion peaks.
When the 2-phenyl/imino 1a-l was treated with HCl in
boiled acetic acid solution, hydrolysis was achieved
[15,17], providing the corresponding 2-oxy derivatives
Upon reflux with dimethylformamide, the derivatives
under investigation 1a-c, d and k were found to undergo
molecular rearrangement into the respective 1-phenyl-,
1,3-diphenyl-, and 5-(2-aryl-2-oxoethyl)-4-oxo-2-thioxo-
imidazolidines 4a-c, d and k, respectively (Scheme 3).
The 2-imino 1k was refluxed for longer hours to undergo
this rearrangement, though in a poor yield of 4k.
1
Under the acidic conditions, Edman reaction described
a previous conversion for similar thiazolidinones [18].

May-Jun 2008
Rearrangement of Novel 4-Thiazolidinones
647
Accordingly, rearrangement of 1 with boiled DMF, in the
absence of any acidic conditions, could not be rationalized
in terms of Edman's mechanism. Moreover, the acidic
conditions were previously found to effect the conversion
of 1 into 3 [15,17].
Conversion of 1 into the imidazolidines 4 has occurred
most likely, via the suggested ionic intermediate [E],
which was believed to be generated through the dipolar
form II, by heterolytic cleavage along the 1, 5; S–C bond
(Scheme 4). The charges of the ionic resonance forms I,
II and the intermediate have stabilized by the polar DMF
solvent [19,20], while further stabilization was provided
by the phenyl group present at position-2. Therefore, the
2-phenylimino 1a-d were sufficiently supported to under-
go this rearrangement, in a good yield of 4a-d. Whilst,
the 2-imino 1k, which is devoid of this stabilizing phenyl
group, was unable to endure the transformation, providing
poor yield of 4k.
In spite of the disappointing yield of 4k, nevertheless it
was the result that supported the proposed mechanism.
The structures of 4 were proved by elemental analysis
and mass spectra, which exhibited the same [M+.] peak
1
values as their parent isomers 1. The H NMR and IR
spectra supported the structural nature between 1 and 4.
Moreover, treatment of 4a, d with bromine in hot acetic
acid solution [21], was carried out affording the expected
(E,Z) 5-benzoylmethylene analogues 5a, d. Then, it was
verified that compound 4 acquires the imidazolidinone
conformation when 5a, d were authentically prepared, by
condensing 1-phenyl and 1,3-diphenyl-4-oxo-2-thioxo-
imidazolidine [22,23], respectively with phenylglyoxal
(Scheme 3).
Scheme 3
S
R
R'N
R
S
N
N
S
R
NR
N
O
S
R'
O
N
O
N
O
R'
N
O
R'
O
O
AcOH/
Br2 /AcOH/
+
DMF
Fused
AcONa
i) Bromination
ii) - HBr
O
O
Ph
Y
Y
Lawesson's
reagent
4a-d,k
1a-d,k
Lawesson's
reagent
(E,Z)-5a,d
R
R
N
S
N
R'N
S
S
N
S
R'
Y
Y
7a-c
6a-c
R
R' Y
1-7a; H, Ph H,
b; H Ph Br,
c; H Ph Cl,
d; Ph Ph H,
k; H
H
Br
Synthesis of 4- 7
Scheme 4
S
R
N
N
N
R
O
R
N
R
N
N
R
N
O
Ph
N
N
N
S
S
O
S
O
S
O
O
O
O
O
O
Y
4a-d
Y
Y
Y
Y
I
E
II
1a-d
Isomerisation of 1 into 4

648
K. Nadia and F. Khaled
Vol 45
Table 1
Antimicrobial activity of tested products
Inhibition zone diameter (mm/ mg Sample)
Sample No. (20 mg/ mL)
Micro organism
Bacillus subtilis
T*
30
A** 1e
1g
1h
1j
1l
3c
3d
3i
3j
4a
4b
4k
6b
7c
-
13
14
14
15
14
17
14
13
15
14
14
13
14
13
Staphylococcus aureus
Escherichia coli
34
32
35
-
-
-
-
-
12
12
12
0.0
11
11
12
11
14
14
0.0
0.0
11
12
13
14
14
0.0
0.0
12
12
12
14
11
13
13
0.0
0.0
12
11
15
16
16
11
14
14
15
13
13
13
0.0
13
12
13
12
13
12
0.0
12
12
12
14
14
15
0.0
0.0
13
13
13
13
13
0.0
0.0
12
12
11
14
13
0.0
0.0
12
11
12
13
13
0.0
0.0
12
13
12
13
13
0.0
0.0
12
12
0.0
12
11
0.0
11
11
12
Pseudomonas aeruginosa
Aspergillus flavus
Aspergillus niger
Candida albicans
Candida Parapsilosis
-
14
17
16
18
20
0.0
0.0
0.0
12
-
* Tetracycline; standared antibacterial agent. ** Amphotricine-B; standared antifungal agent
compared with Tetracycline and Amphotricine-B,
respectively as standared antibacterial and antifungal
agents. All the tested samples showed activity against the
four bacterial strains, in 25-55% and activity against
Candida albicans and Candida Parapsilosis, in (60-75%).
Whilst, the activity against Aspergillus niger was only
shown by the samples having the 2,4-dioxy- structure
(class 3), besides 1e and 7c of other classes, in (68-87%).
In general, compound 3c was the most effective sample
and it was the only one that displayed activity against
Aspergillus flavus in 64%.
On the other hand, the structure of compound 5 was
also supported by elemental analysis and spectroscopic
1
data. The H NMR spectrum of 5a displayed at δ 6.2 (s,
42%, olefinic H) for isomer (E) and 6.84 (s, 58%, olefinic
H) for isomer (Z), 7.0- 7.63 m, 6H (aromatic H), 7.9, 7.07
each d, 2H (aromatic H), 9.45 s, 1H (NH). The config-
uration assignment of these isomers is based on the
accepted assumption that the olefinic proton in isomer (Z)
is more deshielded by the 4-oxo group, compared with the
(E) counterpart [24].
According to our previous studies [25], thiation of 1a-c
and 4a-c with Lawesson's reagent [14] was carried out
(Scheme 3), affording 5-aryl-2,3-dihydro-2-phenylimino-
thieno[2,3-d]thiazole derivatives 6a-c and 1-phenyl-5-
EXPERIMENTAL
aryl-2,3-dihydro-2-thioxothieno[2,3-d]imidazoles
7a-c,
All melting points are uncorrected. IR spectra were recorded
on Perkin Elmer 1600 FT.IR spectrophotometer. 1H-NMR
spectra were measured on Varian Gemini 200 MHz instrument;
chemical shifts (δ) are reported in ppm downfield from (TMS).
Mass spectra were recorded on a Shimadzu GC-MS-QP 1000X
spectrometer operating at 70 eV. Chromatography was carried
out with Silica gel S 0.63 - 0.1 mm Riedel-de-Haen on a column
with l = 17 cm, φ = 1.7 cm. dimensions. Thin layer chromatog-
raphy was performed on Merck Kieselgel 60 F254 aluminum
packed plates. Light petroleum is referred to the fraction b.p:
(60-80 °C).
Synthesis of 2-(Phenyl)/imino-3-(un)/substituted-5-(2-aryl-
2-oxoethyl)-4-oxo-1,3-thiazolidines 1a-l (1g-i Method I); An
acetic acid (50 mL) solution containing (5.0 mmol) of each of
phenyl- (0.67 g), 1,3-diphenyl- (1.14 g), 1-methyl-3-phenyl-
(0.88 g) and/or thiourea (0.38 g), was added to (5.0 mmol) of
the required 3-benzoyl- (0.88 g), 3-(4-bromobenzoyl)- (1.27 g) or
3-(4-chlorobenzoyl)-2-propenoic acid (1.0 g). The whole
mixture was refluxed either for an hour or till a sudden
precipitation of the crude 1j-l. The solution of 1a-i was
concentrated (20 mL) and left to cool. The solid precipitated was
filtered off, dried and recrystallized from the proper solvent to
afford 1a-l.
respectively. The IR spectra of either 6 or 7 were devoid
of any CO absorption bands. The mass spectra of 6a-c as
well as 7a-c displayed the same molecular ion peak
values, showing the isomeric relationship between these
compounds. The spectra showed also pattern of other
fragments supporting the construction of these molecules.
Antimicrobial activity (Table 1) was measured in Micro
Analytical Center, Cairo University, Giza, Egypt. The
method was performed by saturating a sterilized filter
paper disc with the selected sample with concentration of
20 mg/mL. Then, it was placed on a plate containing
solid bacterial medium (nutrient agar both) or fungal
medium (Dox's medium) to be seeded with the spore
suspension of the tested organism. After inoculation, the
diameter of the clear zone of inhibition surrounding the
sample was taken as a measure of the inhabitation power
against the particular tested organism [26-29]. The
selected samples were screened against 2 bacterial Gram-
positive; Bacillus subtilis and Staphylococcus aureus; and
2 bacterial Gram-negative; Pseudomonas aeruginosa and
Escherichia coli. Antifungal activity was tested against
Aspergillus flavus, Aspergillus niger, Candida albicans
and Candida Parapsilosis. The recorded results were
2-Phenylimino-5-(2-phenyl-2-oxoethyl)-4-oxo-1,3-thiazoli-
dine (1a). 2.8 g (85.3%); mp 215-217° (acetic acid). ir: ν 3179,
3141 (N-H, hetero, exo), 3035, 3006 (=CH), 2904 (C-H), 1684,
1660 (C=O, aroyl and hetero ring), 1617 (C=N), 760, 690 cm-1.

May-Jun 2008
Rearrangement of Novel 4-Thiazolidinones
649
1H nmr: δ 11.32 (brs, 1H, NH.), 7.08- 8.11 (four deformed m,
10Harom), 4.65-4.63 (complicated m, 1HA), 4.18- 4.01 (deformed
m, 2H, HM, HX) ; ms: m/z 310 (79.0), 205 (100), 119 (31), 105
(54.8),77 (77.1). Anal. Calcd for C17H14N2O2S (310): C, 65.8; H,
4.51; N, 9.03. Found: C, 65.82; H, 4.48; N, 9.1.
2-Phenylimino-5-[2-(4-bromophenyl)-2-oxoethyl]-4-oxo-1,3-
thiazolidine (1b). 3.5 g (87.5%); mp 241-243° (acetic acid).
ir: ν 3266, 3207, 3412 (N-H), 3080, 3000 (=CH), 2924, 2860
(C-H), 1668 br (C=O, aroyl and hetero ring), 1638 (C=N), 818,
750, 690 cm-1. 1H nmr: δ 11.99, 11.25 (brs, 2H, CONH, PhNH),
7.0-7.93 (four deformed m. 9Harom), 4.56– 4.53 (complicated m.
1HA), 4.08- 3.97, 3.75- 3.53 (two deformed m. 2H, HM, HX); ms:
m/z 388 (20.4), 205 (100), 183 (28.1), 77(33.1). Anal. Calcd for
C17H13BrN2O2S (388): C, 52.72; H, 3.35; N, 7.21. Found: C,
52.70; H, 3.33; N, 7.11.
2-Phenylimino-5-[2-(4-chlorophenyl)-2-oxoethyl]-4-oxo-
1,3-thiazolidine (1c). 3.2 g (80.4%); mp 233-235° (acetic acid).
ir: ν 3262, 3205,3142 (N-H), 3030-3000 (=CH), 2913-2858 (C-
H), 1676 br (C=O, aroyl and hetero ring), 1629 (C=N), 820, 750,
700 cm-1. 1H nmr: δ 11.90, 11.15 (brs, 2H, CONH, PhNH), 6.98-
8.01 (five deformed m, 9Harom), 4.53- 4.50 (complicated m,
1HA), 4.05-3.94, 3.71-3.62 (two deformed m. 2H, HM, HX); ms:
m/z 344 (54.7), 205 (100) 139 (39.3), 118 (16.6), 77(22.6).
.Anal. Calcd for C17H13ClN2O2S (344.5): C, 59.21; H, 3.77; N,
8.13. Found: C, 59.19; H, 3.78; N, 8.14.
2-Phenylimino-3-methyl-5-(2-phenyl-2-oxoethyl)-4-oxo-
1,3-thiazolidine (1g). 1.43 g (87.7%); mp 67-70° (light
petroleum/chloroform). ir: ν 3058,3027 (=CH), 2924 (C-H),
1716, 1674 (C=O, aroyl and hetero ring), 1639 (C=N), 761, 688
cm-1. 1H nmr: δ 7.92 (d, 2H, Harom, J = 8.0 Hz), 7.39-7.60 (m, 3H,
Harom), 7.33 (apt., 2H, Harom, J = 7.4 Hz), 7.116 (apt., 1H, Harom, J
= 7.4 Hz), 6.96 (d, 2H, Harom, J = 7.4 Hz), 4.49 (dd, 1HA, JAX
=
11.0, JAM = 3.0 Hz), 4.11 (dd, 1HM, JMX = 18.7, JAM = 3.0 Hz),
3.44 (dd, 1HX, JMX = 18.7, JAM = 11.0 Hz), 3.37 (s, 3H, CH3) ;
ms: m/z. 324 (100), 105 (2.48), 219 (40.6), 77 (6.83). Anal.
Calcd for C18H16N2O2S (324): C, 66.66; H, 4.93; N, 8.64. Found:
C, 66.63; H, 4.91; N, 8.71.
2-Phenylimino-3-methyl-5-[2-(4-bromophenyl)-2-oxoethyl]-
4-oxo-1,3-thiazoildine (1h). 1.77 g (88.0%); mp 141-143° (light
petroleum/chloroform). ir: ν 3070, 3025 (=CH), 2923 (C-H),
1715, 1674 (C=O, aroyl and hetero ring), 1639 (C=N), 826 cm-1.
1H nmr: δ 7.79, 7.61 each (d, 2H, Harom, J = 8.0 Hz), 7.32 (apt.,
2H, Harom, J = 8.2 Hz ), 7.14 (apt., 1H, Harom, J = 8.2 Hz), 6.957
(d, 2H, Harom, J = 8.2 Hz), 4.47 (dd, 1HA, JAX = 11.0, JAM = 2.6
Hz), 4.05 (dd, 1HM, JMX = 18.6, JAM = 2.6 Hz), 3.39 (dd, 1HX,
JMX = 18.6, JAX = 11.0 Hz), 3.362 (s, 3H, CH3) ; ms: m/z. 402
(28.9) 219 (100)183 (3.27). Anal. Calcd for C18H15BrN2O2S
(402): C, 53.73; H, 3.73; N, 6.96. Found: C, 53.69; H, 3.72; N,
6.98.
2-Phenylimino-3-methyl-5-[2-(4-chlorophenyl)-2-oxoethyl]-
4-oxo-1,3-thiazolidine (1i). 1.6 g (89.1% Method І) , 0.26 g
(26.1% Method ІІ); mp 128-130° (light petroleum/ chloroform).
ir: ν 3065, 3024 (=CH), 2924 (C-H), 1716, 1674 (C=O, aroyl
2-Phenylimino-3-phenyl-5-(2-phenyl-2-oxoethyl)-4-oxo-1,3-
thiazolidine (1d). 1.62 g (84.0%); mp 138-140° (light petroleum
/chloroform). ir: ν 3054, 3031 (=CH), 2919 (C-H), 1723, 1672
1
1
(C=O, aroyl and hetero ring), 1634 (C=N), 768, 691 cm-1. H
and hetero ring), 1642 (C=N), 831, 765, 694 cm-1. H nmr: δ
nmr: δ 7.96 (d, 2H, Harom, J = 7.8 Hz), 7.45-7.62 (m, 8H, Harom),
7.29 (apt., 2H, Harom, J = 7.6 Hz), 7.68 (apt., 1H, Harom, J = 7.6
Hz), 6.92 (d, 2H, Harom, J = 7.8 Hz), 4.64 (dd, 1HA, JAX = 10.6,
JAM = 2.8 Hz), 4.14 (dd, 1HM, JMX = 18.4, JAM = 2.8 Hz), 3.62
(dd, 1HX, JMX = 18.4, JAX = 10.6 Hz); ms: m/z. 386 (56.7), 105
(40), 281 (100), 77 (75.7). Anal. Calcd for C23H18N2O2S (386):
C, 71.5; H, 4.66; N, 7.25. Found: C, 71.48; H, 4.62; N, 7.31.
2-Phenylimino-3-phenyl-5-[2-(4-bromophenyl)-2-oxoethyl]-
4-oxo-1,3-thiazolidine (1e). 2.07 g (89.6%); mp 169-171° (light
petroleum/chloroform). ir: ν 3059 (=CH), 2917 (C-H), 1718,
1685 (C=O, aroyl and hetero ring), 1631 (C=N), 817, 766, 693
cm-1. 1H nmr: δ 7.81, 7.63 each (d, 2H, Harom, J = 8.8 Hz), 7.54
(d, 2H, Harom, J = 7.8 Hz), 7.43-7.48 (m, 3H, Harom), 7.29 (apt.,
2H, Harom, J = 7.8 Hz), 7.1 (apt., 1H, Harom, J = 7.4 Hz), 6.92 (dd,
7.86 (d, 2H, Harom, J = 8.8 Hz), 7.45 (d, 2H, Harom, J = 8.6 Hz),
7.11 (apt., 2H, Harom, J = 7.2 Hz), 6.95 (d, 2H, Harom, J = 7..2 Hz),
6.84 (apt., 1H, Harom, J = 7.2 Hz), 4.47 (dd, 1HA, JAX = 10.8, JAM
= 2.8 Hz), 4.05 (dd, 1HM, JMX = 18.6, JAM = 2.8 Hz), 3.39 (dd,
1HX, JMX = 18.6, JAX = 10.8 Hz), 3.36 (s, 3H, CH3) ; ms: m/z.
358 (46.00), 219 (100),111 (18.2), 139 (20.10). Anal. Calcd for
C18H15ClN2O2S (358.5): C, 60.25; H, 4.81; N, 7.81. Found: C,
60.23; H, 4.79; N, 7.8.
2-Imino-5-(2-phenyl-2-oxoethyl)-4-oxo-1,3-thiazolidine (1j).
1.03 g (87.4%); m.p. > 300°C (DMF/ EtOH). ir: ν 3194 br (N-
H), 3060-2940 br (=CH, C-H), 1677 br (C=O, aroyl and hetero
ring), 761, 684 cm-1. 1H nmr: δ 9.10 (brs., 1H, NHhetero), 8.91 (s,
1H, NHimino), 8.08 (d, 2H, Haroyl, J = 7.6 Hz), 7.77 (apt., 1H,
Harom, J = 7.2 Hz), 7.64 (apt., 2H, Harom, J = 7.2 Hz), 4.52 (dd,
1HA, JAX = 10.6, JAM = 2.8 Hz), 4.06 (dd, 1HM, JMX = 18.6, JAM
=
2H, Harom, J = 8.2, 1.4 Hz), 4.62 (dd, 1H, HA, JAX = 10.2, JAM
=
2.8 Hz), 3.56 (dd, 1HX, JMX = 18.6, JAX = 10.6 Hz) ; ms: m/z. 234
(18.9), 129 (100),105 (74.8), 77 (80.8). Anal. Calcd for
C11H10N2O2S (234): C, 56.41; H, 4.27; N, 11.96. Found: C,
56.38; H, 4.21; N, 11.93.
2.8 Hz), 4.09 (dd, 1H, HM, JMX = 18.7, JAM = 2.8 Hz), 3.58 (dd,
1H, HX, JMX = 18.7, JAX = 10.2 Hz; ); ms: m/z. 464 (25.3), 282
(100), 183 (15.9), 77 (33.1). Anal. Calcd for C23H17BrN2O2S
(464): C, 59.48; H, 3.66; N, 6.03. Found: C, 59.42; H, 3.68; N,
6.02.
2-Phenylimino-3-phenyl-5-[2-(4-chlorophenyl)-2-oxoethyl]-
4-oxo-1,3-thiazolidine (1f ). 1.85 g (88.4%); mp 168-169°
(light petroleum/chloroform). ir: ν 3059 (=CH), 2954, 2919
(C-H), 1719, 1686 (C=O, aroyl and hetero ring), 1634
(C=N), 818, 766, 693 cm-1. 1H nmr: δ 7.88 (d, 2H, Harom, J =
8.6 Hz), 7.56 (d, 2H, Harom, J = 8.6 Hz), 7.41- 7.52 (m, 5H,
2-Imino-5-[2-(4-bromophenyl)-2-oxoethyl]-4-oxo-1,3-thia-
zolidine (1k). 1.44 g (92.3%); mp > 300° (DMF/ EtOH). ir: ν
3230 br (N-H), 3023 br (=CH), 2930 br (C-H), 1671 br (C=O,
1
aroyl and hetero ring), 821 cm-1. H nmr: δ 9.09 (brs., 1H,
NHhetero), 8.78 (brs, 1H, NHimino), 7.93 (d, 2H, Harom, J = 8.6 Hz),
7.76 (d, 2H, Harom, J = 8.4 Hz), 4.42 (dd, 1HA, JAX = 10.6, JAM
2.6 Hz), 3.95 (dd, 1HM, JMX = 18.4, JAM = 2.6 Hz), 3.49 (dd, 1HX,
JMX = 18.4, JAX 10.6 Hz); ms: m/z. 312 (8.30), 129 (100),183
=
=
Harom), 7.27 (apt., 2H, Harom, J = 7.8 Hz), 7.09 (apt., 1H, Harom
J = 7.6 Hz), 6.91 (d, 2H, Harom, J = 7.6 Hz), 4.62 (dd, 1HA,
JAX = 10.0, JAM = 2.8 Hz), 4.09 (dd, 1HM, JMX = 18.4, JAM
,
(21.60). Anal. Calcd for C11H9BrN2O2S (312): C, 42.3; H, 2.88;
N, 8.97. Found: C, 42.23; H, 2.81; N, 8.98.
=
2.8 Hz), 3.58 (dd, 1HX, JMX = 18.4, JAX = 10.0 Hz); ms: m/z.
420 (45.4),281 (100) 139 (29.8), 77 (25.1). Anal. Calcd for
C23H17ClN2O2S (420.5): C, 65.63; H, 4.04; N, 6.66. Found:
C, 65.66; H, 4.11; N, 6.71.
2-Imino-5-[2-(4-chlorophenyl)-2-oxoethyl]-4-oxo-1,3-thiaz-
olidine (1l). 1.23 g (92.7%); mp > 300° (DMF/ EtOH). ir: ν
3217 br (N-H), 3060-2940 br (=CH, C-H), 1672 br (C=O, aroyl
and hetero ring), 826 cm-1. 1H nmr: δ 9.95 (s, 1H, NHhetero.), 9.10

650
K. Nadia and F. Khaled
Vol 45
(brs., 1H, NHimino), 8.08 (d, 2H, Harom, J = 8.4 Hz), 7.69 (d, 2H,
Harom, J = 8.4 Hz), 4.510 (dd, 1HA, JAX = 10.6, JAM = 3.0 Hz),
(25 mL) containing 1a-k or l 0.5 g (1.0- 2.5 mmol) was refluxed
with conc. HCl (2 mL) for 10 hours (5 hours for 1j-l). The
solution was concentrated and poured into ice-cold water (30
mL). The solid separated was collected by filtration, washed,
dried and crystallized from the proper solvent to give:
5-(2-Phenyl-2-oxoethyl)-2,4-dioxo-1,3-thiazolidine (3a).
(from 1a or 1j) 0.46 g (90%); mp 153-155° (toluene); ir: ν 3167
(N-H), 3053 (=CH), 2789, 2959 (C-H), 1753 (C=O), 1677 br
(C=O, aroyl and hetero ring), 772, 685 cm-1. 1H nmr: δ 7.96 (d,
2H, Harom, J = 7.8 Hz), 7.64 (ap.t., 1H, Harom, J = 7.6 Hz), 7.506
(apt., 2H, Harom, J = 7.6 Hz), 7.26 (s, 1H, NH), 4.68 (dd, 1H, HA,
4.04 (dd, 1HM, JMX = 18.8, JAM = 3.0 Hz), 3.57 (dd, 1HX, JMX
=
18.8, JAX = 10.6 Hz) ; ms: m/z. 268 (12.10), 219 (100),139
(38.50). Anal. Calcd for C11H9ClN2O2S (268.5): C, 49.16; H,
3.35; N, 10.43. Found: C, 49.22; H, 3.31; N, 10.46.
Synthesis of 2-N-methylanilino-5-(2-aryl-2-oxoethyl)-4-
oxo-1,3-thiazolines 2a-c (Method Ӏ): A solution of acetic acid
(50 mL) containing 1-methyl-1-phenylthiourea (0.83 gm, 5.0
mmol) was refluxed for 1h with (5.0 mmol) of 3-benzoyl- (0.88
gm), 3-(4-bromobenzoyl)- (1.27 gm) or 3-(4-chlorobenzoyl)-2-
propenoic acid (1.0 gm). The solution was concentrated (20 mL)
and worked out as above to give 2a-c.
Synthesis of 1g-i and 2a-c (Method ӀӀ): To a cold solution
of ethanol (15 mL) containing KOH (0.17 g, 3 mmol), 1a, b
and/or c (3 mmol) was added. The mixture was stirred (20 min)
in an ice bath, then treated with (CH3)2SO4 (0.5 mL). The
stirring was continued (20 min). The reaction mixture was
poured into cold water (25 mL), extracted with two portions of
chloroform (50 mL). The organic layers were combined
together, dried (CaCl2 anhydrous) and concentrated (1 mL). The
residue was chromatographed on a column silica gel with light
petroleum/ ethylacetate mixture first by (80/ 20 v/v) to afford
1g-i then with (50/50 v/v) to give 2a-c.
JAX = 10.4, JAM = 3.0 Hz), 4.69 (dd, 1H, HM, JMX = 18.6, JAM
=
3.0 Hz), 3.594 (dd, 1H, HX, JMX = 18.6, JAX = 10.4 Hz); ms: m/z.
235 (21.9), 130 (8.20), 105 (100), 77 (59.2). .Anal. Calcd for
C11H9NO3S (235): C, 56.17; H, 3.84; N, 5.95. Found: C, 56.13;
H, 3.79; N, 5.96.
5-[2-(4-Bromophenyl)-2-oxoethyl]-2,4-dioxo-1,3-thiazolid-
ine (3b) (from 1b or 1k). 0.47 g (95.5%); mp 184-185°
(toluene); ir: ν 3173 (N-H), 3066 (=CH), 2950, 2799 (C-H),
1760 (C=O), 1689 br (C=O, aroyl and hetero ring), 816 cm-1. 1H
nmr: δ 7.82, 7.65 each (d, 2H, Harom, J = 8.6 Hz), 7.36 (s, 1H,
NH). 4.67 (dd, 1H, HA, JAX = 10.4, JAM = 3.0 Hz), 4.04 (dd, 1H,
HM, JMX = 18.6, JAM = 3.0 Hz), 3.54 (dd, 1H, HX, JMX = 18.6, JAX
= 10.4 Hz); ms: m/z. 313 (29.40)130 (45), 183 (100)155 (17.50).
Anal. Calcd for C11H8BrNO3S (313): C, 42.17; H, 2.55; N, 4.47.
Found: C, 42.14; H, 2.55; N, 4.46.
Compounds 1g-i were matched (mp, admixing mp) with the
respective sample previously obtained by (Method Ӏ).
2-N-Methylanilino-5-(2-phenyl-2-oxoethyl)-4-oxo-1,3-thia-
zoline (2a) 1.1 gm (67.5% Method І); 0.50 gm (51.3 % Method
ІІ); mp 180-182° (Light petroleum/ chloroform). ir: ν 3070 br
(=CH), 2918 br (C-H), 1695 (C=O, aroyl and hetero ring), 750
cm-1. 1H nmr: δ 7.92 (dd, 2H, Harom, J = 3.5, 1.6 Hz), 7.29-7.62
(m, 8H, Harom), 4.49 (dd, 1HA, JAX = 11.8, JAM = 2.8 Hz), 4.19
(dd, 1HM, JMX = 18.6, JAM = 2.8 Hz), 3.66 (s, 3H, CH3), 3.31 (dd,
1HX, JMX = 18.6, JAX= 11.8 Hz) ; ms: m/z. 324 (3), 219 (18), 133
(50.75), 155 (35.5) 77 (100). Anal. Calcd for C18H16N2O2S
(324): C, 66.66; H, 4.93; N, 8.64. Found: C, 66.64; H, 4.91; N,
8.66.
2-N-Methylanilino-5-[2-(4-bromophenyl)-2-oxoethyl]-4-oxo-
1,3-thiazoline (2b). 1.4 g (69.6% Method І), 0.63 g (52.6%
Method ІІ); mp 140-142° (Light petroleum/ chloroform). ir: ν
3060 (=CH), 2918 (C-H), 1705, 1676 (C=O, aryl and hetero
ring), 1620 (C=N), 816 cm-1. 1H nmr: δ 7.78 (d, 2H, Harom, J =
8.6 Hz), 7.59 (d, 2H, Harom, J = 8.6 Hz), 7.44- 7.48 (m, 3H,
5-[2-(4-Chlorophenyl)-2-oxoethyl]-2,4-dioxo-1,3-thiazolid-
ine (3c) (from 1c or 1l). 0.46 g (92%); mp 161-163° (toluene);
ir: ν 3168 (N-H), 3067 (=CH), 2950, 2799 (C-H), 1756 (C=O),
1690 br (C=O, aroyl and hetero ring), 822 cm-1. 1H nmr: δ 8.6
(br, NH), 7.9, 7.48 each (d, 2H, Harom, J = 8.4 Hz), 4.66 (dd, 1H,
HA, JAX = 10.2, JAM = 3.0 Hz), 4.04 (dd, 1H, HM, JMX = 18.8, JAM
= 3.0 Hz), 3.55 (dd, 1H, HX, JMX = 18.4, JAX = 10.2 Hz); ms: m/z.
269 (27),130 (21), 139 (100), 111 (41). Anal. Calcd for
C11H8ClNO3S (269.5): C, 48.97; H, 2.97; N, 5.19. Found: C,
48.93; H, 2.96; N, 5.18
3-Phenyl-5-(2-phenyl-2-oxoethyl)-2,4-dioxo-1,3-thiazolid-
ine (3d) (from 1d). 9.1 g (91%); mp 117- 118° (EtOH); ir: ν
3067 (=CH), 2917 (C-H), 1735 (C=O), 1674 br (C=O, aroyl and
hetero ring), 754, 688 cm-1. 1H nmr: δ 7.98 (d, 2H, H, J = 7.8
Hz), 7.64 (apt., 1H, Harom, J = 7.2 Hz), 7.45-7.57 (m, 5H, Harom),
7.336 (dd, 2Harom, J = 6.7, 2.0 Hz), 4.742 (dd, 1H, HA, JAX = 9.9,
JAM = 3.0 Hz), 4.15 (dd, 1H, HM, JMX = 18.7, JAM = 3.0 Hz), 3.70
(dd, 1H, HX, JMX = 18.7, JAX = 9.8 Hz); ms: m/z. 311 (34), 206
(59), 105 (100), 77 (67). Anal. Calcd for C17H13NO3S (311): C,
65.59; H, 4.18; N, 4.50. Found: C, 65.61; H, 4.20; N, 4.53.
3-Phenyl-5-[2-(4-bromophenyl)-2-oxoethyl]-2,4-dioxo-1,3-
thiazolidine (3e) (from 1e). 1.0 g (93.0%); mp 182-184°
(EtOH); ir: ν 3064 (=CH), 2943, 2909 (C-H), 1751 (C=O), 1678
br (C=O, aroyl and hetero ring), 816, 750, 689 cm-1. 1H nmr: δ
7.85, 7.66 each (d, 2H, Harom, J = 8.6 Hz), 7.45-7.57 (m, 3H,
Harom), 7.30 (dd, 2H, Harom, J = 5.0, 2.0 Hz), 4.47 (dd, 1HA, JAX
=
11.6, JAM = 3.0 Hz), 4.13 (dd, 1HM, JMX = 18.8, JAM = 3.0 Hz),
3.659 (s, 3H, CH3), 3.26 (dd, 1HX, JMX = 18.8, JAX = 11.6 Hz);
ms: m/z. 402 (31), 219 (100).183 (31.95)77 (67.16). Anal. Calcd
for C18H15BrN2O2S (402): C, 53.73; H, 3.73; N, 6.96. Found: C,
53.72; H, 3.63; N, 6.99.
2-N-Methylanilino-5-[2-(4-chlorophenyl)-2-oxoethyl]-4-oxo-
1,3-thiazoline (2c). 1.4 g (61.3% Method І), 0.61 g (57.0%
Method ІІ); mp 151-153° (Light petroleum/ chloroform); ir: ν
3063 (=CH), 2924 (C-H), 1687 br (C=O, aryl and hetero ring),
813 cm-1. 1H nmr: δ 7.86 (d, 2H, J = 8.6 Hz), 7.413-7.484 (m,
5H, Harom), 3.32 (dd, 2H, Harom, J = 5.40, 2.4 Hz), 4.48 (dd, 1HA,
JAX = 11.6, JAM = 2.8 Hz), 4.15 (dd, 1HM, JMX = 18.8, JMX = 2.8
Hz), 3.66 (s, 3H, Me), 3.27 (dd, 1HX, JMX = 18.8, JAX = 11.6 Hz);
ms: m/z. 358 (5.17), 219 (91.87), 139 (82), 111 (100). Anal.
Calcd for C18H15ClN2O2S (358.5): C, 60.25; H, 4.2; N, 7.81.
Found: C, 60.26; H, 4.21; N, 7.83.
Harom), 7.33 (d, 2H, Harom, J = 8.6 Hz), 4.73 (dd, 1H, 1HA, JAX
=
9.8, JAM = 3.0 Hz), 4.10 (dd, 1H, HM, JMX = 18.6, JAM = 3.0 Hz),
3.67 (dd, 1H, HX, JMX = 18.6, JAX = 9.8 Hz); ms: m/z. 389 (24),
206 (100), 183 (52), 155 (21). Anal. Calcd for C17H12BrNO3S
(389): C, 52.44; H, 3.08; N, 3.59. Found: C, 52.50; H, 3.11; N,
3.62.
3-Phenyl-5-[4-(chlorophenyl)-2-oxoethyl]-2,4-dioxo-1,3-thi-
azolidine (3f) (from 1f). Yield: 1.8 g (92.0%); mp 180-182°
(EtOH); ir: ν 3098, 3065 (=CH), 2943, 2911 (C-H), 1749
(C=O), 1680 br (C=O, aroyl and hetero ring), 825, 751, 691
cm-1. 1H nmr: δ 7.8, 7.64 each (d, 2H, Harom, J = 8.8 Hz), 7.30-
Synthesis of 3-un/substituted-5-(2-aryl-2-oxoethyl)-2,4-
dioxo-1,3-thiazolidines 3a-i. A solution of glacial acetic acid

May-Jun 2008
Rearrangement of Novel 4-Thiazolidinones
651
7.44 (m, 5H, Harom), 4.58 (dd, 1H, HA, JAX = 10.6, JAM = 3.0 Hz),
4.05 (dd, 1H, HM, JMX = 18.6, JAM = 3.0 Hz), 3.42 (dd, 1H, HX,
JMX = 18.6, JAX = 10.6 Hz) ; ms: m/z. 345 (35), 206 (97) 139
(100) 111 (46.80). Anal. Calcd for C17H12ClNO3S (345.5): C,
59.04; H, 3.47; N, 4.05. Found: C, 59.10; H, 3.46; N, 4.12.
3-Methyl-5-(2-phenyl-2-oxoethyl)-2,4-dioxo-1,3-thiazolid-
ine (3g) (from 1g). 0.41 g (82.0%); mp 85-87° (EtOH); ir: ν
3065 (=CH), 2961, 2920 (C-H), 1740 (C=O), 1678 br (C=O,
1H, HM, JMX = 18.2, JAM = 4.4 Hz), 3.30 (dd, 1H, HX, JMX = 18.2,
JAX = 4.4 Hz); ms: m/z. 388 (27), 205 (100), 77 (39). Anal. Calcd
for C17H13BrN2O2S (388): C, 52.57; H, 3.35; N, 7.21. Found: C,
52.50; H, 3.32; N, 7.18
1-Phenyl-5-[2-(4-chlorophenyl)-2-oxoethyl]-4-oxo-2-thiox-
oimidazolidine (4c). 0.95 g (93.0%); mp 238-240°; ir: 3229-
3040 br (N-H, =CH), 2928 (C-H), 1740, 1681 (C=O, aroyl and
hetero ring), 1205 (C=S), 809, 760, 695 cm-1. 1H nmr: δ 12.23
(1H, NH), 7.84, 7.55 each (d, 2H, Harom, J = 8.6 Hz), 7.39-7.28
(m, 5H, C6H5), 5.314 (apt., 1HA, JAM = JAX = 4.2 Hz), 3.66 (dd,
1
aroyl and hetero ring), 686, 745 cm-1. H nmr: δ 7.95 (d, 2H,
Harom, J = 7.2 Hz), 4.63 (apt., 1H, Harom, J = 7.2 Hz), 7.46 (apt.,
2H, Harom, J = 7.2 Hz), 4.59 (dd, 1HA, JAX = 10.6, JAM = 2.8 Hz),
1HM, JMX = 18.8, JAM = 4.2 Hz), 3.40 (dd, 1HX, JMX = 18.8, JAX
=
4.2 Hz); ms: m/z. 344 (7), 205 (100), 77 (48). Anal. Calcd for
C17H13ClN2O2S (344.5): C, 59.21; H, 3.77; N, 8.12. Found: C,
59.22; H, 3.70; N, 8.15.
1,3-Diphenyl-5-(2-phenyl-2-oxoethyl)-4-oxo-2-thioxoimida-
zolidine (4d). 1.1 g (90 %); mp 152-154°; ir: ν 3062 (=CH),
2918 (C-H), 1759, 1669 (C=O, aroyl and hetero ring), 1220
(C=S), 753, 691 cm-1. 1H nmr: δ 7.82 (d, 2H, Harom, J = 8.4 Hz),
7.37 – 7.61 (m, 13H, Harom) 4.98 – 5.02 (m,1H, HA), 3.68 (dd,
4.12 (dd, 1HM, JMX = 18.6, JAM = 2.8 Hz), 3.51 (dd, 1HX, JMX
=
18.6, JAX = 10.6 Hz), 3.16 (s, 3H, CH3) ; ms: m/z. 249 (100), 144
(77.23),105 (65.00), 77 (84.68). 235 (21.9)130 (8.20),105
(100),77 (59.2). Anal. Calcd for C12H11NO3S (249): C, 57.83; H,
4.41; N, 5.62. Found: C, 57.81; H, 4.43; N, 5.61.
3-Methyl-5-[2-(4-bromophenyl)-2-oxoethyl]-2,4-dioxo-1,3-
thiazolidine (3h) (from 1h). 0.46 g (92.0%); mp 148-150°
(EtOH); ir: ν 3072, 3040 (=CH), 2983, 2906 (C-H), 1752
(C=O), 1675 br (C=O, aroyl and hetero ring), 818 cm-1. 1H nmr:
δ 7.87 (d, 2H, Harom, J = 8.0 Hz), 7.46 (d, 2H, Harom, J = 8.2 Hz),
1H, HM, JMX = 18.6, JAM = 3.9 Hz), 3.54 (dd, 1H, HX, JMX
=
18.6, JAX = 3.6 Hz); ms: m/z 386 (39), 281 (100), 77 (69). .Anal.
Calcd for C23H18N2O2S (386): C, 71.5; H, 4.66; N, 7.25. Found:
C, 71.35; H, 4.60; N, 7.33.
5-[2-(4-Bromophenyl)-2-oxoethyl]-4-oxo-2-thioxoimidazol-
idine (4k). 0.10 g (10%); mp 206- 208° (EtOH); ir: 3190 (br, N-
H), 3089 (=CH), 2574 (S-H), 1734, (C=O, aroyl and hetero
ring), 1680 (C=N), 819 cm-1; ms: m/z 312 (28), 129 (100), 183
(24). Anal. Calcd for C11H9BrN2O2S (312): C, 42.3; H, 2.88; N,
8.97. Found: C, 42.53; H, 2.80; N, 8.93.
Synthesis of 1-phenyl and 1,3-diphenyl-5-(benzoyl-
methylene)-4-oxo-2-thioxoimidazolidines 5a and 5d: (Method
A): A solution of glacial acetic acid (10 mL) containing 1-
phenyl [18] (0.38 g, 2 mmol) and/or 1,3-diphenyl-4-oxo-2-
thioxoimidazolidine [19] (0.53 g, 2 mmol) was refluxed for 20
min with phenylglyoxal (0.27 g, 2 mmol) and fused CH3COONa
(0.5 g, 6 mmol). The reaction mixtures were concentrated (3
mL), poured onto water (50 mL) and extracted twice with CHCl3
(50 mL). The organic solutions were combined, dried (CaCl2
anhydrous) and evaporated. The residue was chromatographed
silica gel- (diethyl ether/light petroleum 5:1 v/v) to give 5a, b.
(Method B): A solution of glacial acetic acid (15 mL)
containing 4a (0.3 g, 1mmol) and/or 4d (0.38 g, 1mmol) was
treated with bromine (0.5 mL, 1 mmol). The mixture was stirred
for 10 min, and then warmed till HBr ceased to evolve. The
reaction mixture of 4a was concentrated and the precipitated
solid was collected by filtration dried, and reystallized from
acetic acid to give 5a. The reaction mixture of 4d was worked
out as described in method A to afford 5b.
4.57 (dd, 1HA, JAX = 10.6, JAM = 3.0 Hz), 3.97 (dd, 1HM, JMX
=
18.4, JAM = 3.0 Hz), 3.46 (dd, 1HX, JMX = 18.4, JAX= 10.6 Hz),
3.14 (s, 3H, CH3); ms: m/z. 327 (24.7), 206(100), 155 (21.2),
183 (52.50). Anal. Calcd for C12H10BrNO3S (328): C, 43.93; H,
3.08; N, 4.27. Found: C, 43.96; H, 3.05; N, 4.31.
3-Methyl-5-[2-(4-chlorophenyl)-2-oxoethyl]-2,4-dioxo-1,3-
thiazolidine (3i) (from 1i). 0.43 g (86.0%); mp 128-130°
(EtOH). ir: ν 3072, 3033 (=CH), 2946, 2906 (C-H), 1748 (C=O),
1678 br (C=O, aroyl and hetero ring), 821 cm-1. 1H nmr: δ 7.80
(d, 2H, Harom, J = 8.6 Hz), 7.64 (d, 2H, Harom, J = 8.6 Hz), 4.57
(dd, 1HA, JAX = 10.6, JAM = 2.8 Hz), 4.06 (dd, 1HM, JMX = 18.4,
JAM = 2.8 Hz), 3.46 (dd, 1HX, JMX = 18.4, JAX = 10.6 Hz), 3.16 (s,
3H, CH3); ms: m/z. 283 (31), 144 (87), 139 (100), 111(49.20).
Anal. Calcd for C12H10ClNO3S (283.5): C, 50.79; H, 3.53; N,
4.94. Found: C, 50.77; H, 3.56; N, 4.93.
Rearrangement of 1a-c, d and k into 1-phenyl-, 1,3-
diphenyl-, and 5-(2-aryl-2-oxoethyl)-4-oxo-2-thioxoimidaz-
olidines 4a-c, d and k. A solution of DMF (50 mL) containing
1a, b, c, d or k (1.0 g) was refluxed for 4h (10 h for 1k). The
solution was concentrated (5 mL) under vacuum and treated
with 20 mL of ethanol (ethyl acetate for 1d). The separated solid
from 1a-d was collected by filtration and recrystallized
(toluene/light petroleum) to give 4a-d. The unchanged 1k was
removed by filtration and the mother liquor was evaporated and
diluted with ethanol. The crud product was collected by
filtration and recrystallized (chloroform/light petroleum) to
afford 4k.
1-Phenyl-5-(2-phenyl-2-oxoethyl)-4-oxo-2-thioxoimidazoli-
dine (4a). 0.28 g (93%); mp 226-228°; ir: ν 3237-3040 br (N-H,
=CH), 2964 (C-H), 1739, 1681 (C=O, aroyl and hetero ring),
1248(C=S), 760, 690 cm-1. 1H nmr (DMSO-d6): δ 11.72 (s, 1H,
NH), 7.60 (d, 2Harom, J = 8.0 Hz), 7.07 - 7.44 (m, 8Harom ) , 4.84 -
4.88 (m, 1H, HA), 3.21 – 3.44 (m, 2H , HM, HX); ms: m/z. 310
(35), 205 (59), 77 (100). Anal. Calcd for C17H14N2O2S (310): C,
65.80; H, 4.51; N, 9.03. Found: C, 65.78; H, 4.50; N, 9.00.
1-Phenyl-5-[2-(4-bromophenyl)-2-oxoethyl]-4-oxo-2-thiox-
oimidazolidine (4b). 1.10 g (95.0%); mp 247-249°; ir: ν 3226-
3040 br (N-H, =CH), 2980 (C-H), 1741, 1681 (C=O, aroyl and
hetero ring), 1225 (C=S), 807, 762, 695 cm-1. 1H-NMR: δ = 12.0
(1H, NH), 7.56, 7.48 each (d, 2H, Harom, J = 6.6 Hz), 7.20-7.33
(m, 5H, C6H5), 4.94 (apt., 1H, HA, JAM = JAX = 4.4 Hz), 343 (dd,
1-Phenyl-5-(benzoylmethylene)-4-oxo-2-thioxoimidazol-
idine (5a). 0.28 g (36 %, method A), 0.20 g (56 %, method B);
mp 154-156°C (light petroleum/ chloroform); ir: ν 3238-3030 br
(N-H, =CH), 1739, 1681 (C=O, aroyl and hetero ring), 1222
(C=S), 750, 690 cm-1. 1H nmr: δ 9.45 (s, 1 H, NH) 7.05 – 7.628
(m,6 H, Harom ), E-isomer (42 %): 7.9 (d, 2H, Harom , J = 7.8 Hz),
6.2 (s, 1 H, =CH), Z-isomer (58 %), 7.07 (d, 2H, Harom, J = 7.8
Hz), 6.835 (s, 1H, =CH); ms: m/z. 308 (47.2),105 (80.9) 77
(100). Anal. Calcd for C17H12N2O2S (308): C, 66.22; H, 3.92; N,
9.08. Found: C, 66.26; H, 3.93; N, 9.12.
1,3-Diphenyl-5-(benzoylmethylene)-4-oxo-2-thioxoimida-
zolidine (5d). 0.28 g (36 %, method A) , 0.20 g (56%, method
B); mp 155-157° (light petroleum/ chloroform); ir: ν 3058
(=CH), 1749, 1666 (C=O, aroyl and hetero ring), 1230(C=S),

652
K. Nadia and F. Khaled
Vol 45
760, 690 cm-1. 1H nmr: δ 7.14- 7.61 (m, 13H, Harom ), E-isomer
(29%): 7.93 (d, 2H, Harom, J = 7.0 Hz), 6.12 (s, 1 H, =CH), Z-
isomer (71%) , 7,66 (d, 2H, Harom, J = 8.0 Hz), 6.85 (s,1H,
=CH); ms: m/z. 384 (11), 105 (100), 77 (91). Anal. Calcd for
C23H16N2O2S (384): C, 71.87; H, 4.16; N, 7.29. Found: C, 71.82;
H, 4.11; N, 7.33.
Synthesis of 5-aryl-2,3-dihydro-2-phenyliminothieno[2,3-d]-
thiazoles 6a-c. A mixture 1a, b and/or c (0.5 g; 1.5 mmol) and
Lawesson’s reagent [18] (0.7 g; 1.7 mmol) was refluxed in
xylene/ dioxane solution (50 mL; 5/2 v/v) for 4 h. The mixture
was concentrated (15 mL), treated with light petroleum and left
to cool. The product was collected by filtration, washed with hot
water, dried and recrystallized from toluene – dioxane to afford
6a-c.
(2.3), 265 (3). Anal. Calcd for C17H11ClN2S2 (342.5): C, 59.65;
H, 3.21; N, 8.18. Found: C, 59.67; H, 3.20; N, 8.27.
REFERENCES AND NOTES
[1] Singh, S. P.; Parmar, S. S.; Raman, K.; Stenberg, V. I., Chem.
Rev. 1981, 175.
[2] Sharma, S. C., Bull. Chem. Soc. Jpn., 1967, 40, 2422.
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Path. Microbiol., 1965, 28, 382.
[4] Shyam, R.; Tiwari, I. C., Bull. Chem. Soc. Jpn., 1977, 50,
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[5] Litvinchuk, M. D., Farmakol. Toksikol., 1963, 26; Chem.
Abstr., 1964, 60, 13671e.
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H. I., Bioorg. Med. Chem., 2006, 7324.
[7] Jordan, A. D.;Vaidya, A. H.; Rosenthal, D. I.; Dubinsky, B.;
Kordik, C. P.; Sanfilippo, P. J.; Wu, W.; Ritz, A. B., Bioorg. Med.
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[8] Bosford, F. R.; Curd, F. H. S.; Rose, F. L., Imperial Chemical
Industries Ld; British Patent 593, 499; Chem. Abstr., 1948, 42, 2291.
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Chem. 1997, 40, 586.
[10] Zawisza, T.; Wagner, E., Pol. J. Chem. 1985, 59, 149;
Balasubramaniyan, V.; Balasubramaniyan, P.; Wani, M. J., Indian J.
Chem. Sect. B, 1990 , 1092.
[11] Papa, D.; Schwenk, E.; Villani, F.; Klingsberg, E., J. Am.
Chem. Soc., 1948, 70, 3356.
[12] Vasu, Nirmala, K. A., Chopra, D., Mohan, S., Saravanan, J.,
Acta Cryst. C, 2004, 60, o636; Bradley, D. A., Godfrey, A. G., Schmid,
C. R., Tetrahedron Lett., 1999, 40, 5155.
[13] Baltrusis, R.; Beresnevicius, Z.; Vizgaitis, I.; Gatilov, Y. V.,
Khim. Geterotsikl. Soedin., 1981, 1669; Chem. Abstr., 1982, 96, 85477.
[14] Scheibye, S.; Kristensen, J.; Lawesson, S. O., Tetrahedron,
1979, 35, 1339.
[15] David, J. A.; Davis, F. B., J. Am. Chem. Soc., 1935, 57, 2627.
[16] Hartmann, V. H.; Reuther, I., J. Prakt. Chem., 1973, 315,
144.
5-Phenyl-2,3-dihydro-2-phenyliminothieno[2,3-d]thiazole
(6a) 0.4 g (80 %); mp 200- 202°; ir: ν 3176 (=NH), 1565 (C=N),
1269 (C-N), 3055 (=CH), 693, 750 cm-1. 1H nmr: δ 10.57 (s, 1H,
NH) 7.62-7.74 (m, 4H, Harom), 7.69 (s, 1H, H-6) 7.2565-7.469
(m,5H, Harom), 7.02 (apt., 1 H, Harom, J = 8.0 Hz); ms: m/z. 308
(100), 204 (6), 146 (2). Anal. Calcd for C17H12N2S2 (308): C,
66.23; H, 3.89; N, 9.09. Found: C, 66.26; H, 3.91; N, 9.12
5-(4-Bromophenyl)-2,3-dihydro-2-phenyliminothieno[2,3-d]-
thiazole (6b). 0.42 g (84 %); mp 259- 261°C; ir: ν 3176 (=NH),
1
3044 (=CH), 1563 (C=N), 1267 (C-N),698, 752, 811 cm-1. H
nmr: δ 10.558 (s, 1H, NH), 7.70 (s, 1H, H-6), 7.67 (d, 2H, Harom
,
J = 7.2 Hz), 7.57- 7.58 (m, 4H, Harom), 7.36 (apt., 2H, Harom , J =
7.2 Hz), 7.11 (apt., 1 H, Harom , J =7.2 Hz); ms: m/z. 387 (100),
386 (76), 282 (11), 224 (9). Anal. Calcd for C17H11BrN2S2 (386):
C, 52.85; H, 2.85; N, 7.25. Found: C, 52.84; H, 2.80; N, 7.29.
5-(4-Chlorophenyl)-2,3-dihydro-2-phenyliminothieno[2,3-d]-
thiazole (6c). 0.42 g (84 %); mp 216- 218°; ir: ν 3188 (=NH),
3044 (=CH), 1569 (C=N), 1272 (C-N), 693, 748, 810 cm-1; ms:
m/z. 342 (100), 238 (12.9), 180 (3.62). Anal. Calcd for
C17H11ClN2S2 (342.5): C, 59.65; H, 3.21; N, 8.18. Found: C,
59.65; H, 3.22; N, 8.26.
Synthesis of 1-phenyl-5-aryl-2,3-dihydro-2-thioxothieno-
[2,3-d]imidazoles 7a-c. A mixture 4a, b and/or c (0.5 gm; 1.5
mmol) and Lawesson’s reagent (0.7 gm; 1.7 mmol) was refluxed
in xylene solution (50 mL) for 4h. The reaction mixture was
concentrated (30 mL). After cooling, the crude precipitate was
collected by filtration, washed with water then with dilute
methanol, dried and recrystallized from the proper solvent with
charcoalization to give 7a-c.
1,5-Diphenyl-2,3-dihydro-2-thioxothieno[2,3-d]imidazole
(7a). 0.41 g (82 %); mp 236-238°; ir: ν 3065 (=CH), 2668 (S-
H), 682, 743 cm-1 1H nmr: δ 11.65 (brs, 1H, NH), 7.68 (d, 2H,
Harom, J = 8.0Hz), 7.58 (apt., 2H, Harom, J = 8.0 Hz), 7.46- 7.54,
7.26- 7.37 each (m, 3H, Harom), 6.89 (s, 1H, H-6); ms:m/z. 308
(100), 307 (25), 121 (28). Anal. Calcd for C17H12N2S2 (308): C,
66.23; H,3.89; N,9.09. Found:C,66.30;H,3.91; N, 9.10.
[17] Klare, S. M.; Emmet, E. R., J. Am. Chem. Soc., 1930, 52,
2137.
[18] Edman, P., Acta Chem. Scand., 1950, 4, 283.
[19] Markovic, R.; Shirazi, A.; Dzambaski, Z.; Baranac, M.;
Minic, D., J. Serb. Chem. Soc., 2003, 68, 1.
[20] Dietze, P. E., J. Org. Chem., 1992, 57, 1042.
[21] Omar, M. T.; Fouli, A.; El-Garhi, M. Z., Bull. Chem. Soc.
Jpn., 1991, 64, 750.
[22] Henry, L.W.; Chrles, A. B., Am. Chem. J., 1911, 45, 446;
Chem. Abstr., 1911, 5, 26464.
[23] Shirai, H; Yashiro, T., Nagoya Shiritsu Daigaku Yakugakubu
Kiyo, 1963, 50, 11; Chem. Abstr., 1964, 61, 13302e.
[24] Baumann, N., Sung, M., Ullman E. F., J. Am. Chem. Soc.
1968, 90, 4157; Brockmann, H.; Knobloch, G., Tetrahedron Lett., 1970,
11, 267; Desmoni, G.; Gamba, A.; Righetti, P. P.; Tacconi G., Gazz.
Chim. Ital., 1972, 102, 491.
[25] Omar, M. T.; EL-Aasar, N. K.; Saied, K. F., Synthesis, 2001,
413.
[26] Jawetz, E.; Melnick, J. L.; Adelberg, E. A., Review of
Medical Microbiology. Lang Medical Publication, Los Altos, California,
1974.
[27] Grayer, R. J.; Harbone, J. B., Phytochemistry, 1994, 37, 19.
[28] Muanza, D. N.; Kim, B.W.; Euler, K. L.; Williams, L., Int. J.
Pharmacogn. 1994, 32, 337.
[29] Irob, O. N.; Moo-Young, M.; Anderson, W. A., Int. J.
Pharmacogn., 1996, 34, 87.
1-Phenyl-5-(4-bromophenyl)-2,3-dihydro-2-thioxothieno-
[2,3-d]imidazole (7b). 0.37 g (74 %); mp 279- 281°; ir: ν 3065
(=CH), 2668 (S-H), 686, 733, 799 cm-1. 1H nmr: δ 7.95 (brs, 1H,
NH), 7.42-7.68 (m, 9H, Harom), 7.36 (s, 1H, H-6); ms: m/z. 386
(93.6), 307 (5.4), 308 (2.5). .Anal. Calcd for C17H11BrN2S2 (386):
C, 52.85; H, 2.85; N, 7.25. Found: C, 52.86; H, 2.80; N, 7.31.
1-Phenyl-5-(4-chlorophenyl)-2,3-dihydro-2-thioxothieno-
[2,3-d]imidazole (7c). 0.4 g (80 %); mp 222-224°; ir: ν 3065
(=CH), 2668 (S-H), 686, 799 cm-1; ms: m/z. 342 (100) 307