Synthesis of a new class of bisheterocycles from phenacylsulfonylacetic acid methyl ester

Article abstract of DOI:10.1002/jhet.5570450430

(Chemical Equation Presented) Novel bisheterocycles, 1,2,3-selenadiazoles, thiadiazoles and 2H-diazaphospholes in combination with oxadiazoles, thiadiazoles and triazoles were prepared from phenacylsulfonylacetic acid methyl ester.

Full text of DOI:10.1002/jhet.5570450430

Jul-Aug 2008
1131
Synthesis of a New Class of Bisheterocycles from
Phenacylsulfonylacetic Acid Methyl Ester
Venkatapuram Padmavathi,* Annaji Venkata Nagendra Mohan and Konda Mahesh
Department of Chemistry, Sri Venkateswara University, Tirupati-517502, India
Phone: +91-877-2249666-303: Fax: +91-877-2248499:
E mail: vkpuram2001@yahoo.com
N
N
N
N
O
O
O
O
O
O
O
Ar
Ar
O
S
S
S
Y
Y
OMe
Ar
N
X
N
P
N
N
4
Ph
11,13,15 X = Se
12,14,16 X = S
11,12 Y = S
19 Y = S
20 Y = N-NH2
21 Y = O
Y = N-NH2
13,14
15,16 Y = O
Novel bisheterocycles, 1,2,3-selenadiazoles, thiadiazoles and 2H-diazaphospholes in combination with
oxadiazoles, thiadiazoles and triazoles were prepared from phenacylsulfonylacetic acid methyl ester.
J. Heterocyclic Chem., 45, 1131 (2008).
INTRODUCTION
acid methyl ester (6) was used to develop oxadiazoles,
thiadiazoles and triazoles. Treatment of 3, 4 and 6 with
hydrazine hydrate produced the corresponding acid
hydrazide, (4-aryl[1,2,3]selenadiazole-5-sulfonyl)acetic
acid hydrazide (7), (4-aryl[1,2,3]thiadiazole-5-sulfonyl)-
acetic acid hydrazide (8) and (2-phenyl-5-aryl-2H-
[1,2,3]diazaphosphole-4-sulfonyl)acetic acid hydrazide
(17) (Table 1). The IR spectra of these compounds
displayed absorption bands around 1670 cm-1 for CONH,
1325-1342 and 1122-1152 cm-1 for SO2 and in the regions
3312-3322 and 3220-3230 cm-1 for NH and NH2,
respectively. Besides these, the compounds 7 and 8
displayed an absorption band at 1626-1638 cm-1 for C=C
and compound 17 at 1565-1600 cm-1 for CN (Table 2).
Among different heterocyclic systems oxadiazoles,
thiadiazoles and triazoles gained importance in both
chemical and pharmaceutical purposes. A number of these
compounds show analgesic, antidepressive, anticonvul-
sive and bactericidal activity [1]. Molecules having 1,3,4-
thiadiazole unit attached to the nitrogen of a lactam type
heterocycle possess phytosanitary activity [2-5]. Besides
1,2,3-selenadiazoles, thiadiazoles and 2H-diazaphos-
pholes possess varied physiological properties [6-10]. In
fact, the exploitation of a simple molecule with different
functionalities for the synthesis of heterocycles is a
worthwhile contribution in the field of organic syntheses.
Phenacylsulfonylacetic acid methyl esters are valuable
1
The H NMR spectra of 7a, 8a and 17a displayed broad
synthetic intermediates in
a
variety of synthetic
signals in the regions 9.41-9.47 and 5.16-5.24 ppm for
NH and NH2, which disappeared on deuteration. In
addition, a singlet was observed at 4.72, 4.70 and 4.64
ppm in 7a, 8a and 17a, respectively, for methylene
protons (Table 3). The potassium dithiocarbazate of the
acid hydrazide, 9, 10 and 18 were prepared from 7, 8 and
17 on treatment with carbon disulfide in the presence of
KOH under ultrasonic conditions. The carbodithioates on
heating in the presence of acetic acid produced 5ꢁ-(4-
aryl[1,2,3]selenadiazole-5-sulfonylmethyl)-[1ꢁ,3ꢁ,4ꢁ]thia-
diazole-2ꢁ-thiol (11), 5ꢁ-(4-aryl[1,2,3]thiadiazole-5-
sulfonylmethyl)-[1ꢁ,3ꢁ,4ꢁ]thiadiazole-2ꢁ-thiol (12) and
5ꢁ-(2-phenyl-5-aryl-2H-[1,2,3]diazaphosphole-4-sulfonyl-
methyl)thiadiazole-2ꢁ-thiol (19). Treatment of 9, 10 and
18 with hydrazine hydrate gave 4ꢁ-amino-5ꢁ-(4-aryl-
[1,2,3]selenadiazole-5-sulfonylmethyl)-4ꢁH-[1ꢁ,2ꢁ,4ꢁ]-
triazole-3ꢁ-thiol (13), 4ꢁ-amino-5ꢁ-(4-aryl[1,2,3]-thiadiazole-
5-sulfonylmethyl)-4ꢁH-[1ꢁ,2ꢁ,4ꢁ]triazole-3ꢁ-thiol (14) and
transformations and useful as building blocks to construct
vulnerable heterocycles [11-12]. In continuation of our
studies in the synthesis of biologically potent
heterocycles, herein we wish to report novel bis
heterocycles viz., selenadiazoles, thiadiazoles and 2H-
diazaphospholes in combination with oxadiazoles,
thiadiazoles and triazoles.
RESULTS AND DISCUSSION
In our earlier communication, we have reported the
synthesis of 1,2,3-selenadiazoles, thiadiazoles and 2H-
diazaphospholes by exploiting ꢀ-ketomethylene group in
phenacylsulfonylacetic acid methyl ester [13] (Scheme 1).
In continuation of our efforts to develop bis heterocycles
the ester functionality in (4-aryl[1,2,3]selenadiazole-5-
sulfonyl)acetic acid methyl ester (3), (4-aryl[1,2,3]thia-
diazole-5-sulfonyl)acetic acid methyl ester (4) and (2-
phenyl-5-aryl-2H-[1,2,3]diazaphosphole-4-sulfonyl)acetic

1132
V. Padmavathi, A. V. N. Mohan and K. Mahesh
Vol 45
Table 1
Physical and Analytical Data of Compounds 7-21
Compound.
Mp
Ar
Yield
%
Molecular Formula
Analysis %
(°C)
Calcd. /Found
C
-
H
-
N
-
7a
135-137
126-128
140-142
149-151
143-145
158-160
164-166
158-160
171-173
180-182
176-178
191-193
168-170
155-157
177-179
180-182
171-173
186-188
154-156
147-149
161-163
166-167
159-161
175-177
165-167
161-163
177-179
195-197
188-190
212-213
210-212
Ph
76
78
72
75
70
73
71
68
66
72
67
69
68
65
64
66
63
68
70
65
68
74
69
67
72
74
76
69
71
67
70
C10H10N4O3SSe
(345.24)
C11H12N4O3SSe
(359.26)
C10H9ClN4O3SSe
(379.68)
C10H10N4O3S2
(298.34)
C11H12N4O3S2
(312.37)
C10H9ClN4O3S2
(332.79)
C11H8N4O2S3Se
(403.36)
C12H10N4O2S3Se
(417.39)
C11H7ClN4O2S3Se
(437.81)
C11H8N4O2S4
(356.47)
C12H10N4O2S4
(370.49)
C11H7ClN4O2S4
(390.91)
C11H10N6O2S2Se
(401.33)
C12H12N6O2S2Se
(415.35)
C11H9ClN6O2S2Se
(435.77)
C11H10N6O2S3
(354.43)
C12H12N6O2S3
(368.46)
C11H9ClN6O2S3
(388.88)
C11H8N4O3S2Se
(387.3)
C12H10N4O3S2Se
(401.32)
C11H7ClN4O3S2Se
(421.74)
C11H8N4O3S3
(340.4)
C12H10N4O3S3
(354.43)
C11H7ClN4O3S3
(374.85)
C16H15N4O3PS
(374.35)
C17H17N4O3PS
(388.38)
C16H14ClN4O3PS
(408.8)
C17H13N4O2PS3
(466.92)
C18H15N4O2PS3
446.51
C17H12ClN4O2PS3
432.48
C17H15N6O2PS2
430.44
7b
4-MePh
4-ClPh
Ph
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
7c
8a
8b
4-MePh
4-ClPh
Ph
8c
11a
11b
11c
12a
12b
12c
13a
13b
13c
14a
14b
14c
15a
15b
15c
16a
16b
16c
17a
17b
17c
19a
19b
19c
20a
32.75
(32.82)
34.53
(34.60)
30.18
(30.13)
37.06
(37.14)
38.90
(38.99)
33.80
(33.72)
32.92
(32.99)
34.70
(34.76)
30.32
(30.36)
37.28
(37.25)
39.12
(39.21)
33.97
(33.90)
34.11
(34.07)
35.91
(36.00)
31.33
(31.37)
38.81
(38.90)
40.67
2.00
(1.98)
2.41
(2.44)
1.61
(1.60)
2.26
(2.29)
2.72
(2.70)
1.80
(1.83)
2.51
(2.50)
2.91
(2.94)
2.08
(2.10)
2.84
(2.88)
3.28
(3.25)
2.33
(2.37)
2.08
(2.06)
2.51
(2.49)
1.67
(1.70)
2.37
(2.35)
2.84
13.89
(13.95)
13.42
(13.47)
12.80
(12.86)
15.72
(15.68)
15.12
(15.19)
14.33
(14.37)
20.94
(21.02)
20.23
(20.32)
19.29
(19.38)
23.71
(23.76)
22.81
(22.89)
21.61
(21.68)
14.47
(14.52)
13.96
(14.02)
13.28
(13.35)
16.46
(16.52)
15.81
4-MePh
4-ClPh
Ph
4-MePh
4-ClPh
Ph
4-MePh
4-ClPh
Ph
4-MePh
4-ClPh
Ph
4-MePh
4-ClPh
Ph
4-MePh
4-ClPh
Ph
(40.72)
35.25
(35.21)
-
(2.80)
1.88
(1.90)
-
(15.85)
14.95
(14.99)
-
4-MePh
4-ClPh
Ph
-
-
-
-
-
-
43.73
(43.79)
48.42
(48.38)
47.21
(47.27)
47.44
(47.51)
2.59
(2.63)
3.39
(3.37)
3.03
(3.07)
3.51
(3.48)
12.00
(12.08)
12.55
(12.50)
12.95
(12.99)
19.52
(19.60)
4-MePh
4-ClPh
Ph

Jul-Aug 2008
Synthesis of a New Class of Bisheterocycles from Phenacylsulfonylacetic Acid Methyl Ester
1133
Table 1 (continued)
Compound.
Mp
Ar
Yield
%
Molecular Formula
Analysis %
(°C)
Calcd. /Found
C
H
N
20b
20c
21a
21b
21c
198-200
218-220
187-189
183-185
206-208
4-MePh
4-ClPh
Ph
73
75
67
63
65
C18H17N6O2PS2
444.47
C17H14ClN6O2PS2
(464.89)
C17H13N4O3PS2
(416.41)
C18H15N4O3PS2
(430.44)
48.64
(48.60)
43.92
(43.97)
49.03
(48.96)
50.23
(50.30)
45.29
3.86
(3.90)
3.04
(3.02)
3.15
(3.14)
3.51
(3.55)
2.68
18.91
(18.88)
18.08
(18.14)
13.45
(13.50)
13.02
(13.08)
12.43
4-MePh
4-ClPh
C17H12ClN4O3PS2
(450.86)
(45.22)
(2.72)
(12.40)
Scheme 1
O
O
O
S
O
OMe
Ar
1
i
O
O
O
O
O
O
H
N
Ar
Ar
S
S
H2N
5
4
3
4
5
OMe
OMe
iii
ii
N
O
O
O
3
1
1 Se
O
N
N
S
2
2
S
N
N
OMe
Ar
3
4
2
O
O
O
H
N
Ar
S
4
5
Ph
N
O
O
OMe
iv
v
O
1
1
3
S
N
P
2
OMe
Ar
N
Ph
6
5
Ar = a) Ph
b) 4-MePh
c) 4-ClPh
(i) NH2NHCONH2 / AcONa/EtOH
(ii) SeO2/AcOH
(iii) SOCl2/CH2Cl2
(iv) PhNHNH2/EtOH
(v) PCl3/Et3N/Et2O
Table 2
IR Data of Compounds 7-21
Comp.
No.
7a
IR (cm-1)
C-Se/S
722
C=C
1638
SO2
N=N
1443
C=O
1664
C=N
-
SH
-
NH
NH2
3224
1329
1127
1325
1130
1333
1122
1326
1138
1332
1143
3316
3314
3318
3320
3315
7b
7c
8a
8b
724
729
714
722
1635
1632
1626
1628
1435
1446
1452
1437
1668
1670
1662
1665
-
-
-
-
-
-
-
-
3222
3227
3226
3223

1134
V. Padmavathi, A. V. N. Mohan and K. Mahesh
Vol 45
Table 2 (continued)
Comp.
IR (cm-1)
No.
C-Se/S
725
C=C
1636
SO2
1342
N=N
1449
C=O
1669
C=N
-
SH
-
NH
NH2
8c
3322
3229
1139
11a
11b
11c
12a
12b
12c
13a
13b
13c
14a
14b
14c
15a
15b
15c
16a
16b
16c
723
726
728
715
720
724
721
727
730
711
716
720
723
726
728
715
724
727
1631
1624
1637
1635
1638
1633
1628
1632
1637
1632
1629
1635
1625
1630
1636
1634
1628
1639
1337
1445
1433
1448
1451
1439
1444
1433
1443
1438
1450
1437
1446
1448
1437
1452
1445
1436
1447
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1568
1563
1572
1564
1561
1573
1566
1575
1578
1567
1573
1582
1568
1565
1575
1566
1563
1577
2556
2553
2560
2558
2554
2562
2555
2552
2557
2554
2556
2562
2557
2553
2561
2555
2552
2557
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1144
1331
-
1142
1346
-
1150
1336
-
1148
1334
-
1135
1334
-
1150
1328
3243
1139
1337
3245
1141
1349
3249
1146
1326
3244
1143
1335
3247
1148
1342
3252
1150
1337
-
-
-
-
-
-
1144
1336
1129
1334
1152
1330
1139
1331
1154
1338
1149
17a
17b
17c
19a
19b
19c
20a
20b
20c
21a
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1325 1126
1332 1134
1328 1152
1335 1151
1338 1137
1343 1132
1337 1143
1329 1146
1344 1135
1327
-
-
-
-
-
-
-
-
-
-
1665
1600
1565
1574
1568
1567
1572
1560
1558
1567
1570
-
3314
3220
3224
3227
-
1668
-
3312
1672
-
3318
-
-
-
-
-
-
-
2558
2555
2565
2552
2555
2566
2557
-
-
-
-
-
-
-
-
-
3240
3245
3248
-
1133
21b
21c
-
-
-
-
1332
-
-
-
-
1574
1577
2554
2562
-
-
-
-
1139
1339
1125

Jul-Aug 2008
Synthesis of a New Class of Bisheterocycles from Phenacylsulfonylacetic Acid Methyl Ester
1135
Scheme 2
O
O
O
O
O
O
S
S
Ar
Ar
i
4
5
NHNH2
OMe
3
1
X
N
X
N
2
N
N
7
8
X = Se
X = S
X = Se
X = S
3
4
O
O
O
S
Ar
-
+
NHNHCS K
ii
X
S
N
N
X = Se
X = S
9
10
iii
v
iv
N
N
4' 3'
N
4' 3'
N
N
1'
5'
N
2'
O
O
O
O
O
O
Ar
Ar
Ar
5'
5'
S
S
S
2'
3'
2'
1'
S
1'
O
4'
4
5
4
3
5
SH
4
5
SH
SH
N
3
3
1
1
X
1
X
N
X
N
N
2
N
NH2
2
2
N
N
X = Se
X = S
X = Se
X = S
X = Se
X = S
13
14
15
16
11
12
(i) N2H4.H2O / Pyridine / EtOH
(ii) CS2 / KOH / EtOH / US
(iii) AcOH
Ar = a) Ph
b) 4-Me.Ph
c) 4-Cl.Ph
(iv) N2H4.H2O / H2O
(v) HCl / H2O
1
4ꢀ-amino-5ꢀ-(2-phenyl-5-aryl-2H-[1,2,3]diazaphosphole-
4-sulfonylmethyl)-4ꢀH-[1ꢀ,2ꢀ,4ꢀ]triazole-3ꢀ-thiol (20).
However, acid catalysed hydrolysis of 9, 10 and 18
resulted in 5ꢀ-(4-aryl[1,2,3]selenadiazole-5-sulfonyl-
methyl)-[1ꢀ,3ꢀ,4ꢀ]oxadiazole-2ꢀ-thiol (15), 5ꢀ-(4-aryl-
[1,2,3]-thiadiazole-5-sulfonyl-methyl)-[1ꢀ,3ꢀ,4ꢀ]oxadiazole-
2ꢀ-thiol (16) and 5ꢀ-(2-phenyl-5-aryl-2H-[1,2,3]diaza-
phosphole-4-sulfonylmethyl)-[1ꢀ,3ꢀ,4ꢀ]oxadiazole-2ꢀ-thiol
(21) (Schemes 2, 3 and Table 1). The IR spectra of 11-16
and 19-21 displayed an absorption band at 1558-1582 for
C=N and at 1326-1349 and 1125-1154 cm-1 for SO2.
Apart from these the bands due to C=C were also
observed at 1624-1639 cm-1 for 11-16, whereas 13, 14 and
20 showed a broad band at 3240-3252 cm-1 for NH2 (Table
2). The H NMR spectra of these compounds displayed a
singlet at 10.12-10.61 for SH and another singlet at 4.62-
4.79 ppm for methylene protons besides signals due to
aromatic protons. Compounds 13, 14, and 20 also
displayed a broad singlet at 5.60-5.68 ppm for NH2, which
disappeared on deuteration. The structures of the
compounds 11-16 and 19-21 were further confirmed by
13C NMR spectra (Table 3).
EXPERIMENTAL
General. Melting points were determined in open capillaries
on a Mel-Temp apparatus and are uncorrected. The purity of
compounds was checked by TLC (silica gel H, BDH, ethyl

1136
V. Padmavathi, A. V. N. Mohan and K. Mahesh
Vol 45
Table 3
1H and 13C NMR Data of Compounds 7-21
Compd.
No.
1H NMR (ꢀ, ppm)
13C NMR (ꢀ, ppm)
7a
4.72 (s, 2H, SO2-CH2), 5.17 (bs, 2H, NH2), 7.46-7.95 (m, 57.2 (SO2-CH2), 156.5 (C-5), 157.4 (C-4), 170.8 (C=O), 127.6,
5H, Ar-H), 9.45 (bs, H, NH) 129.7, 131.2, 134.8 (aromatic carbons)
2.38 (s, 3H, Ar-CH3), 4.63 (s, 2H, SO2-CH2), 5.12 (bs, 20.8 (Ar-CH3), 56.7 (SO2-CH2), 156.1 (C-5), 157.8 (C-4), 168.5
2H, NH2), 7.38-7.92 (m, 4H, Ar-H), 9.37 (bs, H, NH) (C=O), 126.5, 128.3, 130.9, 134.4 (aromatic carbons)
4.76 (s, 2H, SO2-CH2), 5.21 (bs, 2H, NH2), 7.49-7.97 (m, 57.5 (SO2-CH2), 155.7 (C-5), 157.2 (C-4), 170.2 (C=O), 127.8,
4H, Ar-H), 9.52 (bs, H, NH) 129.9, 132.3, 135.2 (aromatic carbons)
4.70 (s, 2H, SO2-CH2), 5.24 (bs, 2H, NH2), 7.42-7.93 (m, 56.9 (SO2-CH2), 151.4 (C-5), 154.7 (C-4), 160.2 (C=O), 126.7,
5H, Ar-H), 9.41 (bs, H, NH) 127.4, 131.6, 134.8 (aromatic carbons)
2.34 (s, 3H, Ar-CH3), 4.67 (s, 2H, SO2-CH2), 5.26 (bs, 21.6 (Ar-CH3), 56.5 (SO2-CH2), 152.2 (C-5), 154.5 (C-4), 159.3
2H, NH2), 7.40-7.92 (m, 4H, Ar-H), 9.45 (bs, H, NH) (C=O), 125.8, 126.7, 130.9, 134.5 (aromatic carbons)
4.69 (s, 2H, SO2-CH2), 5.28 (bs, 2H, NH2), 7.45-7.89 (m, 57.6 (SO2-CH2), 151.9 (C-5), 153.2 (C-4), 160.7 (C=O), 126.4,
4H, Ar-H), 9.47 (bs, H, NH) 127.9, 132.6, 135.2 (aromatic carbons)
4.70 (s, 2H, SO2-CH2), 7.42-7.93 (m, 5H, Ar-H) 10.26 (s, 58.1 (SO2-CH2), 155.5 (C-5), 158.3 (C-4), 163.2 (C-2'), 168.4 (C-
H, SH) 5'), 127.3, 129.8, 131.5, 134.7 (aromatic carbons)
2.29 (s, 3H, Ar-CH3), 4.65 (s, 2H, SO2-CH2), 7.34-7.89 21.9 (Ar-CH3), 56.9 (SO2-CH2), 154.7 (C-5), 158.1 (C-4), 162.8 (C-
(m, 4H, Ar-H) 10.12 (s, H, SH) 2'), 167.6 (C-5'), 126.2, 128.5, 131.3, 134.6 (aromatic carbons)
4.73 (s, 2H, SO2-CH2), 7.46-7.93 (m, 4H, Ar-H) 10.29 (s, 57.8 (SO2-CH2), 156.8 (C-5), 157.6 (C-4), 163.5 (C-2'), 168.7 (C-
H, SH) 5'), 127.6, 129.9, 132.4, 135.3 (aromatic carbons)
4.68 (s, 2H, SO2-CH2), 7.39-7.91 (m, 5H, Ar-H) 10.27 (s, 56.8 (SO2-CH2), 152.7 (C-5), 154.3 (C-4), 162.4 (C-2'), 168.2 (C-
H, SH) 5'), 127.1, 129.5, 131.6, 134.9 (aromatic carbons)
2.24 (s, 3H, Ar-CH3), 4.62 (s, 2H, SO2-CH2), 7.37-7.86 22.4 (Ar-CH3), 56.3 (SO2-CH2), 151.7 (C-5), 153.1 (C-4), 162.8 (C-
(m, 4H, Ar-H) 10.13 (s, H, SH) 2'), 167.6 (C-5'), 126.2, 128.5, 131.3, 134.6 (aromatic carbons)
4.75 (s, 2H, SO2-CH2), 7.46-7.96 (m, 4H, Ar-H) 10.32 (s, 57.5 (SO2-CH2), 152.6 (C-5), 154.8 (C-4), 163.3 (C-2'), 168.5 (C-
H, SH) 5'), 127.5, 129.7, 132.1, 134.9 (aromatic carbons)
4.73 (s, 2H, SO2-CH2), 5.64 (bs, 2H, NH2), 7.46-7.98 (m, 57.9 (SO2-CH2), 155.3 (C-5), 158.4 (C-4), 163.6 (C-5'), 145.8 (C-
5H, Ar-H), 10.34 (s, H, SH) 3'), 127.3, 129.8, 131.9, 134.8 (aromatic carbons)
2.27 (s, 3H, Ar-CH3), 4.71 (s, 2H, SO2-CH2), 5.60 (bs, 21.8 (Ar-CH3), 57.6 (SO2-CH2), 154.1 (C-5), 157.2 (C-4), 165.5 (C-
2H, NH2), 7.41-7.89 (m, 4H, Ar-H), 10.44 (s, H, SH) 5'), 147.5 (C-3'), 126.8, 128.8, 131.6, 134.4 (aromatic carbons)
4.79 (s, 2H, SO2-CH2), 5.66 (bs, 2H, NH2), 7.43-7.87 (m, 58.2 (SO2-CH2), 155.9 (C-5), 157.7 (C-4), 163.8 (C-5'), 146.4 (C-
4H, Ar-H), 10.61 (s, H, SH) 3'), 127.5, 130.6, 132.4, 135.2 (aromatic carbons)
4.65 (s, 2H, SO2-CH2), 5.65 (bs, 2H, NH2), 7.37-7.85 (m, 56.3 (SO2-CH2), 151.4 (C-5), 154.1 (C-4), 163.3 (C-5'), 145.9 (C-
5H, Ar-H), 9.43 (bs, 2H, NH2), 10.28 (s, H, SH) 3'), 126.1, 129.3, 131.7, 134.6 (aromatic carbons)
2.29 (s, 3H, Ar-CH3), 4.70 (s, 2H, SO2-CH2), 5.63 (bs, 22.5 (Ar-CH3), 58.4 (SO2-CH2), 152.3 (C-5), 154.5 (C-4), 166.7 (C-
2H, NH2), 7.43-7.91 (m, 4H, Ar-H), 10.36 (s, H, SH) 5'), 144.7 (C-3'), 127.8, 129.9, 132.6, 135.3 (aromatic carbons)
4.76 (s, 2H, SO2-CH2), 5.68 (bs, 2H, NH2), 7.33-7.89 (m, 57.9 (SO2-CH2), 152.6 (C-5), 154.9 (C-4), 164.7 (C-5'), 146.5 (C-
4H, Ar-H), 10.45 (s, H, SH) 3'), 127.6, 130.8, 132.7, 135.4 (aromatic carbons)
4.71 (s, 2H, SO2-CH2), 7.40-7.91 (m, 5H, Ar-H) 10.29 (s, 57.5 (SO2-CH2), 155.4 (C-5), 157.6 (C-4), 163.5 (C-2'), 168.7 (C-
H, SH) 5'), 127.5, 130.4, 132.3, 134.9 (aromatic carbons)
2.24 (s, 3H, Ar-CH3), 4.68 (s, 2H, SO2-CH2), 7.39-7.89 22.4 (Ar-CH3), 56.8 (SO2-CH2), 155.3 (C-5), 157.7 (C-4), 162.3 (C-
(m, 4H, Ar-H) 10.26 (s, H, SH) 2'), 167.5 (C-5'), 126.3, 128.1, 131.5, 134.4 (aromatic carbons)
4.75 (s, 2H, SO2-CH2), 7.41-7.92 (m, 4H, Ar-H) 10.32 (s, 57.8 (SO2-CH2), 156.7 (C-5), 157.9 (C-4), 164.1 (C-2'), 168.8 (C-
H, SH) 5'), 127.8, 130.3, 132.8, 135.5 (aromatic carbons)
4.73 (s, 2H, SO2-CH2), 7.45-7.96 (m, 5H, Ar-H) 10.34 (s, 57.4 (SO2-CH2), 152.6 (C-5), 155.9 (C-4), 163.3 (C-2'), 167.7 (C-
H, SH) 5'), 126.9, 130.2, 132.5, 135.3 (aromatic carbons)
2.28 (s, 3H, Ar-CH3), 4.71 (s, 2H, SO2-CH2), 7.41-7.88 21.9 (Ar-CH3), 56.6 (SO2-CH2), 153.1 (C-5), 154.5 (C-4), 161.7 (C-
(m, 4H, Ar-H) 10.28 (s, H, SH) 2'), 167.3 (C-5'), 126.4, 128.9, 131.8, 134.8 (aromatic carbons)
4.77 (s, 2H, SO2-CH2), 7.47-7.94 (m, 4H, Ar-H) 10.38 (s, 56.6 (SO2-CH2), 151.5 (C-5), 154.8 (C-4), 162.7 (C-2'), 168.5 (C-
H, SH) 5'), 127.5, 129.7, 132.9, 135.2 (aromatic carbons)
4.64 (s, 2H, SO2-CH2), 5.16 (bs, 2H, NH2), 7.60-7.83 (m, 61.3 (SO2-CH2), 146.5 (C-5), 158.9 (C-4), 164.6 (C=O), 128.8,
10H, Ar-H), 9.47 (bs, H, NH) 129.4, 129.7, 130.5, 132.7, 133.3, 134.7, 135.2 (aromatic carbons)
2.35 (s, 3H, Ar-CH3), 4.62 (s, 2H, SO2-CH2), 5.13 (bs, 22.3 (Ar-CH3), 58.7 (SO2-CH2), 148.5 (C-5), 159.2 (C-4), 164.9
7b
7c
8a
8b
8c
11a
11b
11c
12a
12b
12c
13a
13b
13c
14a
14b
14c
15a
15b
15c
16a
16b
16c
17a
17b
2H, NH2), 7.62-7.85 (m, 9H, Ar-H), 9.43 (bs, H, NH)
(C=O), 127.7, 128.5, 129.4, 130.1, 131.4, 131.6, 132.7, 133.5
(aromatic carbons)
17c
19a
4.67 (s, 2H, SO2-CH2), 5.19 (bs, 2H, NH2), 7.65-7.89 (m, 61.9 (SO2-CH2), 147.4 (C-5), 157.8 (C-4), 163.8 (C=O), 127.4,
9H, Ar-H), 9.43 (bs, H, NH) 128.1, 128.7, 129.8, 131.7, 132.8, 133.6, 135.3 (aromatic carbons)
4.72 (s, 2H, SO2-CH2), 7.62-7.86 (m, 10H, Ar-H), 10.29 61.5 (SO2-CH2), 146.7 (C-5), 159.2 (C-4), 161.4 (C-2'), 168.5 (C-
(s, H, SH)
5'), 128.5, 129.6, 129.9, 130.7, 132.7, 133.3, 134.7, 135.4 (aromatic
carbons)
19b
2.29 (s, 3H, Ar-CH3), 4.68 (s, 2H, SO2-CH2), 7.64-7.89 22.3 (Ar-CH3), 60.6 (SO2-CH2), 146.3 (C-5), 158.7 (C-4), 162.1 (C-
(m, 9H, Ar-H), 10.22 (s, H, SH)
2'), 168.3 (C-5'), 128.3, 129.4, 129.5, 130.4, 132.6, 133.5, 134.5,
134.9 (aromatic carbons)

Jul-Aug 2008
Synthesis of a New Class of Bisheterocycles from Phenacylsulfonylacetic Acid Methyl Ester
1137
Table 3 (continued)
Compd.
No.
1H NMR (ꢀ, ppm)
13C NMR (ꢀ, ppm)
19c
20a
20b
20c
21a
21b
21c
4.76 (s, 2H, SO2-CH2), 7.68-7.92 (m, 9H, Ar-H), 10.22 (s, 61.8 (SO2-CH2), 147.5 (C-5), 159.6 (C-4), 162.7 (C-2'), 168.8 (C-
H, SH)
5'), 128.9, 129.8, 130.3, 131.6, 132.9, 133.5, 134.8, 135.7 (aromatic
carbons)
4.75 (s, 2H, SO2-CH2), 5.64 (bs, 2H, NH2), 7.66-7.89 (m, 59.7 (SO2-CH2), 146.9 (C-5), 159.6 (C-4), 163.8 (C-5'), 146.2 (C-
10H, Ar-H), 10.24 (s, H, SH)
3'), 128.2, 129.7, 130.4, 130.9, 132.6, 133.8, 134.6, 135.2 (aromatic
carbons)
2.32 (s, 3H, Ar-CH3), 4.73 (s, 2H, SO2-CH2), 5.62 (bs, 21.9 (Ar-CH3), 59.2 (SO2-CH2), 146.4 (C-5), 159.3 (C-4), 163.5 (C-
2H, NH2), 7.61-7.84 (m, 9H, Ar-H), 10.18 (s, H, SH)
5'), 145.7 (C-3'), 128.4, 129.6, 130.6, 131.7, 132.8, 134.2, 134.7,
135.4 (aromatic carbons)
4.77 (s, 2H, SO2-CH2), 5.66 (bs, 2H, NH2), 7.69-7.92 (m, 60.6 (SO2-CH2), 147.4 (C-5), 159.3 (C-4), 162.5 (C-5'), 144.3 (C-
9H, Ar-H), 10.27 (s, H, SH)
3'), 128.4, 129.6, 130.6, 131.7, 132.8, 134.2, 134.7, 135.4 (aromatic
carbons)
4.67 (s, 2H, SO2-CH2), 7.60-7.85 (m, 10H, Ar-H), 10.16 59.7 (SO2-CH2), 146.3 (C-5), 159.4 (C-4), 162.8 (C-2'), 168.7 (C-
(s, H, SH)
5'), 127.3, 128.9, 129.8, 131.8, 132.6, 133.5, 134.4, 135.3 (aromatic
carbons)
2.26 (s, 3H, Ar-CH3), 4.63 (s, 2H, SO2-CH2), 7.66-7.93 22.5 (Ar-CH3), 60.4 (SO2-CH2), 147.1 (C-5), 159.5 (C-4), 161.7 (C-
(m, 9H, Ar-H), 10.25 (s, H, SH)
2'), 167.9 (C-5'), 126.8, 128.4, 129.3, 130.7, 131.9, 133.4, 134.8,
135.1 (aromatic carbons)
4.75 (s, 2H, SO2-CH2), 7.65-7.84 (m, 9H, Ar-H), 10.28 (s, 60.6 (SO2-CH2), 146.9 (C-5), 160.3 (C-4), 163.7 (C-2'), 169.5 (C-
H, SH)
5'), 128.2, 130.3, 131.7, 132.8, 133.2, 133.8, 134.7, 135.5 (aromatic
carbons)
Scheme 3
O
O
O
O
O
O
S
S
Ar
Ar
i
NHNH2
OMe
4
5
3
P
1
N
P
N
2
N
N
Ph
Ph
6
17
ii
O
O
O
S
Ar
-
+
NHNHCS K
S
P
N
N
Ph
18
iii
v
iv
N
N
N
N
N
N
1'
2'
3'
4'
4' 3'
5'
O
O
O
O
O
O
Ar
Ar
5'
Ar
5'
3'
2'
2'
S
S
S
4'
1'
1'
SH
SH
SH
N
O
S
5
4
5
4
5
4
3
3
1
1
P
P
1
N
3
P
N
N
NH2
2
2
2
N
N
N
Ph
Ph
Ph
19
20
21
(i) N2H4.H2O / Pyridine / EtOH
(ii) CS2 / KOH / EtOH / US
(iii) AcOH
Ar = a) Ph
b) 4-Me.Ph
c) 4-Cl.Ph
(iv) N2H4.H2O / H2O
(v) HCl / H2O

1138
V. Padmavathi, A. V. N. Mohan and K. Mahesh
Vol 45
mmol) in 6 mL of water, hydrazine hydrate (80%, 2 mmol) was
added and refluxed for 8-9 h. The contents of the flask were
cooled, diluted with water and acidified with 2 mL of acetic
acid. The separated solid was collected by filtration, dried and
recrystallized from 2-propanol.
5ꢀ-(4-Aryl[1,2,3]selenadiazole-5-sulfonylmethyl)-[1ꢀ,3ꢀ,4ꢀ]-
oxadiazole-2ꢀ-thiol (15), 5ꢀ-(4-Aryl[1,2,3]thiadiazole-5-
sulfonylmethyl)-[1ꢀ,3ꢀ,4ꢀ]oxadiazole-2ꢀ-thiol (16) and 5ꢀ-(2-
Phenyl-5-aryl-2H-[1,2,3]diazaphosphole-4-sulfonylmethyl)-
[1ꢀ,3ꢀ,4ꢀ]oxadiazole-2ꢀ-thiol (21). General Procedure. The
compound 9/10/18 (1 mmol) was dissolved in 6 mL of water and
acidified with 1-2 mL of conc. HCl. The regenerated solid was
collected by filtration, dried and recrystallized from 2-propanol.
acetate-hexane, 1:4). 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 and 13C NMR spectra were
recorded in CDCl3/DMSO-d6 on a Varian EM-360 spectrometer
at 300 and 75.5 MHz, respectively. All chemical shifts are
reported in ꢀ (ppm) using TMS as an internal standard. The
microanalyses were performed on Perkin-Elmer 240C elemental
analyzer. The starting compounds (4-aryl[1,2,3]selenadiazole-5-
sulfonyl)acetic acid methyl ester (3), (4-aryl[1,2,3]thiadiazole-5-
sulfonyl)acetic acid methyl ester (4), (2-phenyl-5-aryl-2H-
[1,2,3]diazaphosphole-4-sulfonyl)acetic acid methyl ester (6)
were prepared by the literature procedure [13].
(4-Aryl[1,2,3]selenadiazole-5-sulfonyl)acetic acid hydra-
zide (7), (4-Aryl[1,2,3]thiadiazole-5-sulfonyl)acetic acid
hydrazide (8) and (2-Phenyl-5-aryl-2H-[1,2,3]diazaphos-
phole-4-sulfonyl)acetic acid hydrazide (17). General
Procedure. To a solution of 3/4/6 (1 mmol) in absolute ethanol,
hydrazine hydrate (80%, 4.5 mmol) and pyridine (0.4 mL) were
added and stirred for 6 h at room temperature. The resultant
solid was collected by filtration and recrystallized from ethanol.
Potassium (4-aryl[1,2,3]selenadiazole-5-sulfonylacetyl)-
hydrazine-N'-carbodithio-ate (9), potassium (4-aryl[1,2,3]-
thiadiazole-5-sulfonylacetyl)-hydrazine-N'-carbodithioate (10)
and potassium (2-phenyl-5-aryl-2H-[1,2,3]diazaphosphole-4-
sulfonylacetyl)-hydrazine-N'-carbodithioate (18). General
Procedure. to a mixture of potassium hydroxide (2 mmol) and
7/8/17 (1 mmol) in absolute ethanol (5 mL), carbon disulfide (4
mmol) was added and sonicated for 12 h. the separated solid was
filtered and dried.
Acknowledgement. The authors are grateful to DST, New
Delhi for financial assistance under major research project.
REFERENCES
[1] Kleeman, A; Engel, J. Pharmazeutische Wirkstoffe, 2. Aufl.,
Georg Thieme Verlag, Stuttgart, 1982.
[2] Giri, S; Singh, H. J. Indian Chem. Soc., 1972, 49, 175.
[3] Velsicol Chemical Co., U.S. Patent 3,990,882 1976; Chem.
Abstr., 1977, 86, 89830s.
[4] Bayer, A. G.; German Patent 2,921,141, 1980; Chem. Abstr.,
1981, 94, 156939q.
[5] Bayer, A. G.; German Patent 2,415,056, 1975; Chem. Abstr.,
1976, 84, 17373f.
[6] Lalezari, I.; Shafiee, A.; Yalpani, M. Angew. Chem. Int. Ed
(Eng). 1970, 9, 464.
[7] Oteleanu, D.; Anges, M.D. Farmacia, 1979, 27, 151.
[8] Padmavathi, V.; Sumathi, R. P.; Ramana Reddy, M. V.;
Bhaskar Reddy, D. Org Prep. Proc. Intl. 1998, 30, 35.
[9] Bhaskar Reddy, D.; Chandrasekhar Babu, N.; Padmavathi,
V.; Padmaja, A. Tetrahedron. 1997, 53, 17351.
5ꢀ-(4-Aryl[1,2,3]selenadiazole-5-sulfonylmethyl)-[1ꢀ,3ꢀ,4ꢀ]-
thiadiazole-2ꢀ-thiol (11) / 5ꢀ-(4-Aryl[1,2,3]thiadiazole-5-
sulfonylmethyl)-[1ꢀ,3ꢀ,4ꢀ]thiadiazole-2ꢀ-thiol (12) / 5ꢀ-(2-
Phenyl-5-aryl-2H-[1,2,3]diazaphosphole-4-sulfonylmethyl)-
thiadiazole-2ꢀ-thiol (19). General Procedure. The compound 9
/ 10 / 18 (1 mmol) in acetic acid (4 mL) was refluxed for 24 h.
The contents of the flask were cooled and poured onto crushed
ice. The solid obtained was collected by filtration, dried and
recrystallized from 2-propanol.
[10] Jennings, L. D.; Foreman, K. W.; Rush, T.S.; III, Tsao, D. H.
H.; Mosyak, L.; Yuanhong Li; Sukhdeo, M. N.; Ding, W.; Dushin, E.
G.; Kenny, C. H.; Moghazeh, S. L.; Petersen, P. J.; Ruzin, A. V.;
Tuckman, M.; Sutherland, A. G. Bioorg. Med. Chem. Lett. 2004, 14,
1427.
4ꢀ-Amino-5ꢀ-(4-aryl[1,2,3]selenadiazole-5-sulfonylmethyl)-
4ꢀH-[1ꢀ,2ꢀ,4ꢀ]triazole-3ꢀ-thiol (13), 4ꢀ-Amino-5ꢀ-(4-aryl-[1,2,3]-
thiadiazole-5-sulfonylmethyl)-4ꢀH-[1ꢀ,2ꢀ,4ꢀ]triazole-3ꢀ-thiol
(14) and 4ꢀ-Amino-5ꢀ-(2-phenyl-5-aryl-2H-[1,2,3]diazaphos-
phole-4-sulfonylmethyl)-4ꢀH-[1ꢀ,2ꢀ,4ꢀ]triazole-3ꢀ-thiol (20).
[11] Padmavathi, V.; Obula Reddy, B. C.; Thriveni, P.; Nagendra
Mohan, A. V. Synth. Commun., 2007, 37, 3127.
[12] Padmavathi, V.; Thriveni, P.; Obula Reddy, B. C.; Mahesh,
K. J. Heterocycl. Chem., 2007, 44, 93.
[13] Padmavathi, V.; Mahesh, K.; Thriveni, P.; Ramana Reddy,
T.V. J. Heterocycl. Chem., 2007, 44, 1165.
General Procedure. To
a solution of 9/10/18 (1