Ketene dithioacetals - Source for different heterocycles

Article abstract of DOI:10.1002/jhet.5570450422

(Chemical Equation Presented) Some pyrazoline, isoxazoline and pyrimidine derivatives were synthesized from ketene dithioacetals using appropriate nucleophiles.

Full text of DOI:10.1002/jhet.5570450422

Jul-Aug 2008
1089
Ketene Dithioacetals – Source for Different Heterocycles
Venkatapuram Padmavathi,* Gali Sudhakar Reddy, Duvvuru Deepti
and Adivireddy Padmaja
Department of Chemistry, Sri Venkateswara University, Tirupati-517502, India
(Phone: +91-877-2249666-303: Fax: +91-877-2248499:
E mail: vkpuram2001@yahoo.com)
Received August 30, 2007
NH2
NH2
CN
S
S
Ar
Ar
S
S
Ar
Ar
N
S
S
Ar
Ar
N
S/O
O/HN
EtOOC
HN
O
O
1
2/3
4/5
O
O
O
O
S
Ar
Ar
S
Ar
Ar
EtO
EtO
HN
S
S
Ar
Ar
HN
HN
S/O
O/
S
S
HN
O
O
6
7/8
9/10
Some pyrazoline, isoxazoline and pyrimidine derivatives were synthesized from ketene dithioacetals
using appropriate nucleophiles.
J. Heterocyclic Chem., 45, 1089 (2008).
INTRODUCTION
wide variety of heterocyclic compounds because the
double bond present in them is amenable for both
nucleophilic and electrophilic attack [8]. The
alkylsulfonyl group is substituted by different
nucleophiles to prepare oxazolidine [9], pyrazole [10],
benzodiazepine [11], imidazolidine [12] etc. However, to
our knowledge functionalization of gem cyanoester and
diester functionalities in ketene dithiolates for the
synthesis of heterocycles is hitherto not reported. The
present communication deals with the synthesis of
pyrazoline, isoxazoline and pyrimidine derivatives from
ketene dithioacetals exploiting gem diester and gem cyano
ester moieties.
Among different heterocyclic systems the chemistry of
five and six membered heterocycles viz., pyrazoles,
isoxazoles and pyrimidines has gained importance. The
pyrazole and isoxazole derivatives find applications as
pharmaceutical agents. In fact, celecoxib and valdecoxib
possess COX-1/ COX-2 inhibitory activity [1]. Apart
from these, many barbiturates were assayed as therapeutic
agents. Some barbituric and thiobarbituric acids were
found to be hypnotics, convulsants, muscle relaxants,
plant growth regulators [2] etc. The pyrazole, isoxazole
and pyrimidine derivatives can be generated in a facile
manner by cyclocondensation of Michael adducts with
hydrazine, hydroxylamine, urea and thiourea. In fact, we
have reported the synthesis of these heterocycles by the
reaction of Michael adducts with different nucleophiles
[3]. This methodology has also been used to develop spiro
heterocycles [4].
RESULTS AND DISCUSSION
The ethyl 3,3-bis(benzylthio)-2-cyanoacrylate (1) is
prepared by the reaction of ethyl cyanoacetate with carbon
disulfide in the presence of sodium ethoxide followed by
in situ bis thioalkylation of the resultant ketene dithiolate
anion with benzyl chloride. Similarly, condensation of
diethyl malonate with carbon disulfide followed by bis
thioalkylation resulted in diethyl 2-(bis(benzylthio)-
methylene)malonate (6). The IR spectra of 1 and 6
showed absorption bands at 1730-1735 and 1620-1628
cm-1 for ester and olefinic moieties. An additional
absorption band is observed in the IR spectrum of 1 at
2205-2208 cm-1 for the nitrile group. The 1H NMR
spectrum of 1a displayed two singlets at ꢀ 4.19 and 4.36
for benzylic protons indicating that they are in different
chemical environments. However, 6a exhibited a singlet
at ꢀ 4.21 for benzylic protons. Apart from this, a triplet
Ketene dithioacetals synthesized by Freund [5] are
versatile synthons for the development of a wide variety
of heterocyclic systems [6]. The preparation of ketene
dithioacetals is based on the condensation with carbon
disulfide followed by in situ bis thioalkyation of the
resultant ketene dithiolate anions. A number of reagents
viz., potassium hydroxide, sodium hydride, potassium
tert-butoxide, sodium tert-amylate, n-butyllithium,
lithium diisopropylamide, lithium dicyclohexylamide,
lithium hexamethyl disilazide, phase transfer catalysts etc.
have been used for the condensation reaction [7]. Ketene
dithioacetals are key intermediates for the preparation of a

1090
V. Padmavathi, G. S. Reddy, D. Deepti and A. Padmaja
Vol 45
Scheme-1
NH2
NH2
S
S
Ar
Ar
CN
EtOOC
S
S
Ar
Ar
S
S
Ar
Ar
N
O
N
(ii)
(i)
HN
O
1
O
2
3
(iii)
NH2
N
S
S
Ar
Ar
X
HN
O
4 X = O
5 X = S
.
i. NH2NH2 H2O / Piperidine / EtOH
ii. NH2OH .HCl / Piperidine / EtOH
iii. NH2CXNH2 / Piperidine / EtOH
a Ar = C6H5
b Ar = p-CH3C6H4
c Ar = p-ClC6H4
Scheme-2
O
O
O
S
S
Ar
Ar
EtO
EtO
S
Ar
Ar
S
S
Ar
Ar
HN
(i)
HN
O
(ii)
HN
S
O
O
O
6
7
8
(iii)
O
HN
S
S
Ar
Ar
X
HN
O
9
X = O
10 X = S
(v)
O
O
HN
HN
HN
HN
S-Na+
(iv)
X
X
S-
+
Na
O
O
.
a Ar = C6H5
b Ar = p-CH3C6H4
c Ar = p-ClC6H4
i. NH2NH2 H2O / NaOEt / EtOH
ii. NH2OH .HCl / NaOEt / EtOH
iii. NH2CXNH2 / NaOEt / EtOH
iv. CS2 / NaOH / H2O
v. ArCH2Cl / EtOH
and a quartet are observed at ꢀ 1.35 and 4.22 due to
carboethoxy group. Treatment of 3,3-bis(benzylthio)-2-
cyanoacrylate (1) and diethyl 2-(bis(benzylthio)methyl-
ene)malonate (6) with hydrazine hydrate resulted in
3-amino-4-(bis(benzylthio)methylene)-pyrazol-5-one (2)
and 4-bis(benzylthio)methylene) pyrazolidine-3,5-dione
(7). The cyclocondensation of 1 and 6 with hydroxyl-
amine produced 3-amino-4-(bis(benzylthio)methylene)-
isoxazol-5-one (3) and 4-(bis(benzylthio)methylene)
compounds, 2-5 and 7-10 are obtained in moderate yields
(52-58 %). Compounds 9 and 10 are also obtained in good
yield (66-68 %) using the one pot method by the
treatment of barbituric acid and thiobarbituric acid with
carbon disulfide followed by bis thioalkylation with
benzyl chloride (Method B) (Schemes 1 and 2 and Table
1). The IR spectra of 2-5 displayed absorption bands at
1616-1628 (C=C), 1598-1614 (C=N) and 3320-3475 cm-1
(NH2). Apart from these, absorption bands are observed at
1736-1748 cm-1 (CO-O) in compound 3, 1654-1666 (CO-
NH), 3200-3232 cm-1 (NH) in compounds 2, 4 and 5, and
1490-1497 cm-1 (C=S) in compound 5. On the other hand,
compounds 7-10 showed absorption bands at 1621-1629
(C=C), 1656-1668 (CONH) and 3207-3236 cm-1 (NH).
Besides, compound 8 exhibited a band at 1731-1738 cm-1
(CO-O) and compound 10 exhibited bands at 1491-1495
cm-1 (C=S) (Table 2). The 1H NMR spectra of 2-5 showed
isoxazolidine-3,5-dione
(8).
Adopting
similar
methodology, 6-amino-5-bis(benzylthio)methylene)-
pyrimidine-2,4-dione (4), 6-amino-5-(bis(benzylthio)-
methylene)-2,3-dihydro-2-thioxopyrimidine-4-one (5), 5-
(bis(benzylthio)methylene) pyrimidine-2,4,6-trione (9)
and 5-(bis(benzylthio)methylene)-2,3-dihydro-2-thioxo-
pyrimidine-4,6-dione (10) are prepared by the reaction of
1 and 6 with urea and thiourea, respectively. However, the

Jul-Aug 2008
Ketene Dithioacetals – Source for Different Heterocycles
1091
1
two singlets for benzylic protons at ꢀ 4.06-4.21 and 4.18-
4.33, and a broad singlet at ꢀ 5.58-5.69 for NH2. The
compounds 2,4 and 5 also exhibited a broad singlet at ꢀ
10.81-10.98 for NH. The signals due to NH and NH2
disappeared on deuteration. The 13C NMR spectra of 2-5
displayed six signals in the regions ꢀ 39.4-42.2, 41.3-43.4
(CH2-S), 102.9-104.7 (=C-CO), 154.5-156.0 (=C-S),
154.2-159.2 (C=N), 173.6-176.1 (C=O). Besides
compound 4 showed another signal at ꢀ 170.5-171.6
(C=O) whereas 5 at ꢀ 164-7-166.3 (C=S). The H NMR
spectra of 7-10 exhibited a singlet at ꢀ 4.15-4.31 for
benzylic protons and a broad singlet at ꢀ 10.44-10.91 for
NH, which disappeared on deuteration. The 13C NMR
spectra of 7-10 exhibited four signals at ꢀ 40.9-43.8 (CH2-
S), 102.7-104-9 (=C-CO), 154.4-157.3 (=C-S), 164.8-
174.7 (C=O). Apart from these, compound 8 showed
another signal at ꢀ 171.4-171.9, 9 at ꢀ 157.9-159.6 (C=O)
and 10 at ꢀ 172.2-174.1 (C=S) (Table 3).
Table 1
Physical and Analytical Data of Compounds 2-10
Compound
Mp
(°C)
Ar
Yield
%
Molecular Formula
Analysis %
Calcd. /Found
C
H
N
2a
2b
2c
122-124
137-139
132-134
146-148
153-155
164-166
182-184
169-171
195-197
169-171
144-146
182-184
133-135
140-142
146-148
154-156
149-151
160-162
216-218
198-200
214-216
201-203
196-198
214-216
C6H5
58
55
57
52
57
56
55
58
54
56
57
55
58
57
55
53
54
58
C18H17N3OS2
60.82
60.64
62.63
62.71
50.94
50.84
60.65
60.75
62.47
62.53
50.83
50.76
59.51
59.60
61.29
61.18
50.45
50.52
57.11
57.20
58.99
59.04
48.72
48.79
60.65
60.69
62.47
62.41
50.83
50.92
60.48
60.53
62.31
62.34
50.71
50.79
59.35
59.42
61.14
61.10
50.34
50.39
56.97
56.92
58.85
58.89
48.61
48.64
4.82
4.87
5.52
5.50
3.56
3.58
4.52
4.49
5.24
5.28
3.32
3.30
4.47
4.52
5.14
5.17
3.34
3.32
4.29
4.33
4.95
4.90
3.23
3.20
4.52
4.55
5.24
5.28
3.32
3.30
4.23
4.26
4.97
5.00
3.07
3.12
4.19
4.15
4.89
4.91
3.11
3.10
4.03
4.08
4.70
4.67
3.01
3.00
11.82
11.91
10.96
10.90
9.90
9.98
7.86
7.93
7.29
7.34
6.59
6.52
10.96
10.90
10.21
10.28
9.29
9.37
10.52
10.60
9.83
9.90
8.97
8.93
7.86
7.82
7.29
7.23
6.59
6.65
3.92
3.88
3.63
3.67
3.29
3.33
7.29
7.25
6.79
6.83
6.18
6.23
6.99
7.04
6.54
6.59
5.97
6.03
p-CH3C6H4
p-ClC6H4
C6H5
C20H21N3OS2
C18H15N3 Cl2OS2
C18H16N2O2S2
C20H20N2O2S2
C18H14N2 Cl2O2S2
C19H17N3O2S2
C21H21N3O2S2
C19H15N3 Cl2O2S2
C19H17N3OS3
3a
3b
3c
p-CH3C6H4
p-ClC6H4
C6H5
4a
4b
4c
p-CH3C6H4
p-ClC6H4
C6H5
5a
5b
5c
p-CH3C6H4
p-ClC6H4
C6H5
C21H21N3OS3
C19H15N3 Cl2OS3
C18H16N2O2S2
C20H20N2O2S2
C18H14N2 Cl2O2S2
C18H15NO3S2
7a
7b
7c
p-CH3C6H4
p-ClC6H4
C6H5
8a
8b
8c
p-CH3C6H4
p-ClC6H4
C6H5
C20H19NO3S2
C18H13N Cl2O3S2
C19H16N2O3S2
C21H20N2O3S2
C19H14Cl2N2O3S2
C19H16N2O2S3
C21H20N2O2S3
C19H14Cl2N2O2S3
9a
9b
9c
57
65*
56
68*
55
67*
56
68*
55
66*
58
p-CH3C6H4
p-ClC6H4
C6H5
10a
10b
10c
p-CH3C6H4
p-ClC6H4
65*
* Yield obtained in method B.

1092
V. Padmavathi, G. S. Reddy, D. Deepti and A. Padmaja
Vol 45
Table 2
IR Data of Compounds 2-10
Compound
IR (cm-1)
C=C
C=S
C=N
CONH
CO-O
NH
NH2
2a
2b
2c
1622
1628
1619
1623
1626
1628
1616
1627
1624
1620
1625
1622
1624
1627
1625
1622
1628
1624
1629
1623
1620
1623
1621
1623
-
1602
1661
1654
1659
-
-
3209
3200
3204
-
3369
3475
-
1611
-
3355
3449
-
1605
-
3364
3471
3a
3b
3c
-
1599
1736
3325
3468
-
1607
-
1742
-
3320
3465
-
1611
-
1748
-
3326
3470
4a
4b
4c
-
1614
1661
1664
1656
1662
1666
1658
1659
1666
1662
1664
1658
1661
1656
1663
1657
1664
1656
1661
-
3212
3217
3232
3208
3225
3213
3219
3207
3222
3225
3231
3218
3234
3226
3229
3224
3236
3230
3331
3472
-
1609
-
3329
3469
-
1598
-
3323
3467
5a
5b
5c
1493
1613
-
3332
3470
1497
1611
-
3334
3473
1490
1609
-
3336
3471
7a
7b
7c
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
8a
8b
8c
-
1738
-
1731
-
1736
9a
9b
9c
-
-
-
-
-
-
-
-
-
10a
10b
10c
1495
1493
1491
7-10 hours. The solution was cooled and poured into crushed ice
containing conc. HCl. The solid obtained was collected by
filtration, dried, and recrystallized from ethanol.
CONCLUSION
The functionalization of gem diester and gem cyano
ester functionalities in ketene dithioacetals with different
nucleophiles led to a new class of biologically potent
heterocycles pyrazoline, isoxazoline pyrimidine and their
derivatives.
6-Amino-5-(bis(benzylthio)methylene)pyrimidine-2,4-
dione (4)
/
6-amino-5-(bis(benzylthio)methylene)-2,3-
dihydro-2-thioxopyrimidine-4-one (5): General Procedure.
The compound 1 (1 mmol) was dissolved in ethanol (10 mL). To
this, urea / thiourea (1.5 mmol) in ethanol (10 mL) and
piperidine (3 mL) was added and refluxed for 10-12 hours. The
contents were cooled and poured into crushed ice containing
conc. HCl. The separated solid was collected by filtration, dried
and recrystallized from ethanol.
4-(Bis(benzylthio)-methylene) pyrazolidine-3,5-dione (7) /
4-(bis(benzylthio) methylene) isoxazolidine-3,5-dione (8):
General Procedure. To a solution of 6 (1 mmol) in ethanol,
hydrazine hydrate (1.5 mmol) / hydroxylamine hydrochloride
(1.2 mmol) and sodium ethoxide (3 mL) were added and
refluxed for 6-8 hours. The solution was cooled and poured into
crushed ice containing conc. HCl. The solid obtained was
collected by filtration, dried, and recrystallized from ethanol.
5-(bis(benzylthio)methylene)pyrimidine-2,4,6-trione (9) /
EXPERIMENTAL
Melting points were determined in open capillaries on a Mel-
Temp apparatus and are uncorrected. The purity of the
compounds was checked by TLC (silica gel H, BDH, ethyl
acetate/hexane, 1:3). The IR spectra were recorded on a Thermo
Nicolet IR 200 FT-IR spectrometer as KBr pellets and the wave
numbers were given in cm-1. The 1H NMR spectra were recorded
in CDCl3 / DMSO-d6 on a Varian EM-360 spectrometer (300
MHz). The 13C NMR spectra were recorded in CDCl3 / DMSO-
d6 on a Varian VXR spectrometer operating at 75.5 MHz. All
chemical shifts are reported in ꢀ (ppm) using TMS as an internal
standard. The microanalyses were performed on a Perkin-Elmer
240C elemental analyzer. The starting compounds ethyl 3,3-
bis(benzylthio)-2-cyanoacrylate (1) and diethyl 2-(bis(benzyl-
thio)methylene)malonate (6) were prepared by the literature
procedure [13].
5-(bis(benzylthio)
methylene)-2,3-dihydro-2-thioxopyrim-
idine-4,6-dione (10): General Procedure. The compound 6 (1
mmol) was dissolved in ethanol (10 mL). To this, urea / thiourea
(1.5 mmol) in ethanol (10 mL) and sodium ethoxide (3 mL) was
added and refluxed for 8-10 hours. The contents were cooled
and poured into crushed ice containing conc. HCl. The separated
solid was filtered, dried and recrystallized from ethanol.
3-Amino-4-(bis(benzylthio)methylene)-pyrazol-5-one (2) /
3-amino-4-(bis(benzylthio)methylene) isoxazol-5-one (3):
General Procedure. To a solution of 1
hydrazine hydrate (1.5 mmol) / hydroxylamine hydrochloride
(1.2 mmol) and piperidine (3 mL) were added and refluxed for
(1 mmol) in ethanol,
Method B. A mixture of barbituric acid / thiobarbituric acid
(1 mmol), 30% sodium hydroxide solution (10 mL) and carbon
disulfide (1.5 mmol) was stirred for 20-24 hours. To this, 1 N

Jul-Aug 2008
Ketene Dithioacetals – Source for Different Heterocycles
1093
Table 3
1H and 13C NMR Data of Compounds 2-5 and 6-10
Compound
1H NMR (ꢀ, ppm)
13C NMR (ꢀ, ppm)
2a
4.19 (s, 2H, CH2), 4.33 (s, 2H, CH2), 5.62 (s, 2H, NH2), 40.3 (CH2-S), 41.3 (CH2-S), 104.7 (=C-CO), 155.2 (=C-S),
7.12-7.76 (m, 10H, Ar-H), 10.91 (bs, 1H, NH)
157.4 (C=N), 174.3 (C=O), 128.2, 129.2, 130.4, 131.6, 131.9,
132.4 (aromatic carbons)
2b
2c
3a
3b
3c
4a
4b
4c
5a
5b
5c
2.32 (s, 3H, Ar-CH3), 4.13 (s, 2H, CH2), 4.28 (s, 2H, 24.5 (Ar-CH3), 41.1 (CH2-S), 42.5 (CH2-S), 103.9 (=C-CO),
CH2), 5.69 (s, 2H, NH2), 7.15-7.72 (m, 8H, Ar-H), 155.0 (=C-S), 159.2 (C=N), 173.6 (C=O), 128.4, 130.0, 130.6
10.98 (bs, 1H, NH)
131.4, 132.7, 133.6. (aromatic carbons)
4.09 (s, 2H, CH2), 4.22 (s, 2H, CH2), 5.64 (s, 2H, NH2), 40.6 (CH2-S), 42.1 (CH2-S), 104.2 (=C-CO), 155.5 (=C-S),
7.11-7.79 (m, 8H, Ar-H), 10.94 (bs, 1H, NH)
156.7 (C=N), 174.0 (C=O), 129.6, 129.9, 130.4, 133.4, 134.6,
135.8 (aromatic carbons)
4.21 (s, 2H, CH2), 4.30 (s, 2H, CH2), 5.58 (s, 2H, NH2), 40.2 (CH2-S), 42.4 (CH2-S), 104.1 (=C-CO), 155.5 (=C-S),
7.03-7.27 (m, 10H, Ar-H)
154.2 (C=N), 174.8 (C=O), 128.4, 129.4, 129.7, 131.8, 134.2,
135.2 (aromatic carbons)
2.35 (s, 3H, Ar-CH3), 4.16 (s, 2H, CH2), 4.27 (s, 2H, 23.9 (Ar-CH3), 42.2 (CH2-S), 43.4 (CH2-S), 103.6 (=C-CO),
CH2), 5.63 (s, 2H, NH2), 7.08-7.36 (m, 8H, Ar-H)
155.2 (=C-S), 155.8 (C=N), 175.2 (C=O), 129.4, 129.8, 130.7,
131.4, 134.3, 134.7 (aromatic carbons)
4.11 (s, 2H, CH2), 4.23 (s, 2H, CH2), 5.67 (s, 2H, NH2), 40.9 (CH2-S), 42.9 (CH2-S), 104.0 (=C-CO), 155.7 (=C-S),
7.02-7.31 (m, 8H, Ar-H)
159.2 (C=N), 174.0 (C=O), 128.7, 130.4, 132.3, 133.6, 134.0,
136.9 (aromatic carbons)
4.07 (s, 2H, CH2), 4.20 (s, 2H, CH2), 5.64 (s, 2H, NH2), 40.1 (CH2-S), 42.0 (CH2-S), 102.9 (=C-CO), 154.7 (=C-S),
7.10-7.39 (m, 10H, Ar-H), 10.89 (bs, 1H, NH)
159.2 (C=N), 170.5, 176.1 (C=O), 128.2, 129.4, 130.2, 130.8,
131.4, 131.9 (aromatic carbons)
2.29 (s, 3H, Ar-CH3), 4.14 (s, 2H, CH2), 4.27 (s, 2H, 24.7 (ArCH3), 39.4 (CH2-S), 41.9 (CH2-S), 103.7 (=C-CO),
CH2), 5.61 (s, 2H, NH2), 7.11-7.42 (m, 8H, Ar-H), 154.5 (=C-S), 158.7 (C=N), 170.5, 174.8 (C=O), 128.6, 129.1,
10.86 (bs, 1H, NH)
129.7, 130.9, 131.2, 132.4 (aromatic carbons)
4.18 (s, 2H, CH2), 4.26 (s, 2H, CH2), 5.64 (s, 2H, NH2), 41.3 (CH2-S), 42.8 (CH2-S), 104.1 (=C-CO), 154.9 (=C-S),
7.08-7.66 (m, 8H, Ar-H), 10.82 (bs, 1H, NH)
159.2 (C=N), 171.6, 174.1 (C=O), 128.8, 129.4, 131.4, 131.8,
132.4, 132.8 (aromatic carbons)
4.06 (s, 2H, CH2), 4.18 (s, 2H, CH2), 5.68 (s, 2H, NH2), 39.5 (CH2-S), 41.6 (CH2-S), 103.2 (=C-CO), 155.4 (=C-S),
7.10-7.64 (m, 10H, Ar-H), 10.85 (bs, 1H, NH)
157.4 (C=N), 164.7 (C=S), 173.9 (C=O), 128.5, 129.8, 130.6,
131.7, 132.1, 132.5 (aromatic carbons)
2.34 (s, 3H, Ar-CH3), 4.17 (s, 2H, CH2), 4.22 (s, 2H, 25.5 (Ar-CH3), 40.6 (CH2-S), 42.5 (CH2-S), 103.7 (=C-CO),
CH2), 5.63 (s, 2H, NH2), 7.15-7.68 (m, 8H, Ar-H), 154.9 (=C-S), 158.2 (C=N), 165.3 (C=S), 174.6 (C=O), 128.8,
10.81 (bs, 1H, NH)
129.6, 130.8, 131.6, 132.7, 133.2 (aromatic carbons)
4.13 (s, 2H, CH2), 4.21 (s, 2H, CH2), 5.61 (s, 2H, NH2), 41.4 (CH2-S), 43.3 (CH2-S), 104.1 (=C-CO), 156.0 (=C-S),
7.08-7.62 (m, 8H, Ar-H), 10.88 (bs, 1H, NH)
157.9 (C=N), 166.3 (C=S), 174.3 (C=O), 128.6, 129.1, 129.5,
129.8, 131.1, 132.4, 134.7, 134.9 (aromatic carbons)
7a
7b
4.15 (s, 4H, CH2), 7.11-7.67 (m, 10H, Ar-H), 10.85 41.9 (CH2-S), 102.9 (=C-CO), 155.5 (=C-S), 172.7 (C=O),
(bs, 2H, NH) 128.2, 129.2, 131.4, 132.7, 132.9 (aromatic carbons)
2.32 (s, 3H, Ar-CH3), 4.23 (s, 4H, CH2), 7.12-7.69 (m, 23.9 (Ar-CH3), 42.4 (CH2-S), 103.7 (=C-CO), 155.1 (=C-S),
8H, Ar-H), 10.79 (bs, 2H, NH)
172.1 (C=O), 128.4, 129.5, 131.5, 132.6, 133.4 (aromatic
carbons)
7c
8a
8b
4.21 (s, 4H, CH2), 7.08-7.72 (m, 8H, Ar-H), 10.81 (bs, 43.1 (CH2-S), 104.2 (=C-CO), 154.7 (=C-S), 173.7 (C=O),
2H, NH) 128.1, 129.4, 131.4, 131.9, 132.6 (aromatic carbons)
4.20 (s, 4H, CH2), 7.14-7.70 (m, 10H, Ar-H), 10.84 42.1 (CH2-S), 103.5 (=C-CO), 155.2 (=C-S), 171.4, 174.4
(bs, 1H, NH) (C=O), 129.4, 129.6, 130.5, 131.1, 132.0 (aromatic carbons)
2.30 (s, 3H, Ar-CH3), 4.28 (s, 4H, CH2), 7.11-7.71 (m, 25.1 (Ar-CH3), 43.7 (CH2-S), 104.2 (=C-CO), 155.6 (=C-S),
8H, Ar-H), 10.81 (bs, 1H, NH)
171.6, 174.0 (C=O), 128.2, 129.2, 131.4, 131.8, 132.0
(aromatic carbons)
8c
9a
9b
4.31 (s, 4H, CH2), 7.19-7.70 (m, 8H, Ar-H), 10.83 (bs, 43.0 (CH2-S), 104.4 (=C-CO), 154.4 (=C-S), 171.9, 174.7
1H, NH) (C=O), 129.3, 129.9, 132.3, 134.6, 137.3 (aromatic carbons)
4.23 (s, 4H, CH2), 7.12-7.74 (m, 10H, Ar-H), 10.86 42.1 (CH2-S), 103.9 (=C-CO), 155.8 (=C-S), 159.6, 166.6
(bs, 2H, NH) (C=O), 128.9, 129.2, 132.6, 133.9 (aromatic carbons)
2.33 (s, 3H, Ar-CH3), 4.28 (s, 4H, CH2), 7.09-7.81 (m, 24.3 (Ar-CH3), 43.3 (CH2-S), 104.2 (=C-CO), 156.0 (=C-S),
8H, Ar-H), 10.84 (bs, 2H, NH)
158.4, 165.2 (C=O), 128.9, 129.1, 129.6, 131.6, 135.5
(aromatic carbons)
9c
4.25 (s, 4H, CH2), 7.11-7.69 (m, 8H, Ar-H), 10.91 (bs, 43.8 (CH2-S), 104.9 (=C-CO), 155.3 (=C-S), 157.9, 164.8
2H, NH) (C=O), 128.5, 129.4, 129.8, 130.4, 134.7 (aromatic carbons)
4.19 (s, 4H, CH2), 7.10-7.77 (m, 10H, Ar-H), 10.89 40.9 (CH2-S), 102.7 (=C-CO), 154.9 (=C-S), 165.9 (C=O),
10a
(bs, 2H, NH)
172.2 (C=S), 128.2, 129.0, 131.4, 132.3, 133.6 (aromatic
carbons)
10b
10c
2.35 (s, 3H, Ar-CH3), 4.27 (s, 4H, CH2), 7.08-7.49 (m, 23.8 (Ar-CH3), 42.3 (CH2-S), 103.2 (=C-CO), 167.3 (=C-S),
8H, Ar-H), 10.85 (bs, 2H, NH)
168.2 (C=O), 173.5 (C=S), 127.4, 128.4, 129.6, 130.1, 132.4
(aromatic carbons)
4.29 (s, 4H, CH2), 7.12-7.48 (m, 8H, Ar-H), 10.44 (bs, 43.2 (CH2-S), 103.5 (=C-CO), 156.2 (=C-S), 166.1 (C=O),
2H, NH)
174.1 (C=S), 129.1, 129.5, 129.8, 131.1, 133.6 (aromatic
carbons)

1094
V. Padmavathi, G. S. Reddy, D. Deepti and A. Padmaja
Vol 45
Heteroatom. Chem. 2001, 12, 131; [b] Padmavathi, V.; Balaiah, A.;
Bhaskar Reddy, D. J. Heterocycl. Chem. 2002, 39, 649; [c] Padmavathi,
V.; Balaiah, A.; Venugopal Reddy, K.; Padmaja, A.; Bhaskar Reddy, D.
Indian J. Chem. 2002, 41B, 1670; [d] Padmavathi, V.; Balaiah, A.;
Ramana Reddy, T. V.; Bhaskar Reddy, D. Heteroatom Chem. 2003, 14,
513; [e] Padmavathi, V.; Jagan Mohan Reddy, B.; Venkata Subbaiah, D.
R. C.; Padmaja, A. Indian J. Chem. 2006, 45B, 808-812; [f] Padmavathi,
V.; Bhasa, S. M.; Venkata Subbaiah, D.R.C.; Ramana Reddy, T.V.;
Padmaja, A. J. Heterocycl. Chem. 2001, 38, 769.
hydrochloric acid (10 mL) was added followed by benzyl
chloride (2 mmol) in ethanol (5 mL). Stirring was continued for
15-17 hours. The yellow precipitate that separated was collected
by filtration, dried and recrystallized from DMF.
Acknowledgements. The authors are grateful to CSIR, New
Delhi for financial assistance under major research project.
REFERENCES
[5] Kolb M. Synthesis 1990, 171.
[6] Mashraqui, Sabir H.; Hariharasubramanian, H. J. Chem.
Research (s) 1999, 492.
[1] Dannhardt, G.; Kiefer, W.; Kramer, G.; Maehrlein, S.; Nowe,
U.; Fiebich, B. Eur. J Med. Chem. 2000, 35, 499.
[7a] Kelber, C. Chem. Ber., 1910, 43, 1252; Thuillier, A.;. Vialle,
J. J. Bull. Soc. Chim. Fr. 1959, 1398; [b] Thuillier, A.; Vialle, J. J. Bull.
Soc. Chim. Fr. 1962, 2194; [c] Shahak, I.; Sasson, Y. Tetrahedron Lett.
1973, 14, 4207; [d] Dieter, R. K. Tetrahedron, 1981, 46, 5031; [e]
Junjappa, H.; Chauhan, S. M. S. Tetrahedron 1976, 32, 1779.
[8] Villemin, D.; Ben Alloum, A. Synthesis 1991, 301.
[9] Soliman, A. M. Synth. Commun. 2000, 30, 1269.
[10] Abdel-Ghany, H.; El-Saghier, A. M. M.; El-Sayed, A.M.
Synth. Commun. 1996, 26, 4289.
[11] Huang, Z. T.; Wang, M. X. Synthesis 1992, 12, 1273.
[12] El-Saghier, A. M. M.; Mahub, A. A.; Al-Shiryada, H. A.,
Synth. Commun. 1997, 27, 2433.
[13] Jensen, K. A.; Henriksen, L. Acta Chemica Scandinavica
1968, 22, 1107.
[2a] Lee, J.; Smith, F. A. US Patent, 2764585 (1956); Chem.
Abstr., 1957, 51, 4446d; [b] Fessenden, R. J.; Larsen, J. G.; Coon, M. D.;
Fessenden, J.S. J Med. Chem. 1964, 7, 695; [c] Friendlander, W.S.;
Mattson, J.R. US Patent, 3270019 (1966); Chem. Abstr. 1967, 66,
37944z; [d] Voronin, V.G.; Yu Polevaya, O.; Makhanova, V. G.;
Landau, M. A.; Kolbanov, V. M.; Privol’neva, T. P.; Chugunov, V. V.;
Lavertskaya E. F. Khim. Farm. Zh. 1976, 10, 43.
[3a] Padmavathi, V.; Rajagopala Sarma, M.; Padmaja, A.; Bhaskar
Reddy, D. Heterocycl. Commun. 2002, 8, 91; [b] Padmavathi, V.; Venkata
Subbaiah, D. R. C.; Rajagopala Sarma, M.; Balaiah, A. Heteroatom Chem.
2004, 15, 477; [c] Padmavathi, V.; Venkata Subbaiah, D. R. C.; Jagan
Mohan Reddy, B. J. Heterocycl. Chem. 2005, 42, 255.
[4a] Bhaskar Reddy, D.; Chandrasekhar Babu, N.; Padmavathi, V.