7
70
Biol. Pharm. Bull.
Vol. 38, No. 5 (2015)
Anal. Calcd for C H N O S: C, 53.25; H, 2.98; N, 24.84. aldehyde (0.001mol) in absolute ethanol (15mL) was heated
15
10
6
2
Found: C, 53.47; H, 3.10; N, 25.19%.
-(2-Chloroethylsulphanyl)-5-(pyridin-4-yl)-1,3,4-oxadi- was filtered, dried then crystallized from acetic acid to give
azole (6) A mixture of 1 (0.89g, 0.005mol), 1-bromo- 12–19.
-chloroethane (3.58g, 0.025mol) and anhydrous potassium (Z/E) N′-Benzilidene-2-[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-
carbonate (3.45g, 0.025mol) in dry N,N-dimethylformamide ylsulphanyl]acetohydrazide (12) Yield, 56%; mp 201–202°C;
under reflux for 3h. After cooling, the formed solid product
2
2
1
(
DMF) (15mL) was stirred 12h at room temperature then
H-NMR (DMSO-d , 500MHz) δ: 4.27, 4.69 (2H, 2s),
6
poured onto ice-cold water (20mL). The precipitate so formed 7.42–8.81 (9H, m), 8.05, 8.22 (1H, 2s), 11.84 (1H, s). IR
−1
was filtered, dried and crystallized from benzene in Yield, (KBr) cm : 3170, 3074, 2947, 2858, 1681, 1616. ESI-MS m/z:
1
6
7%; mp 96–97°C; H-NMR (DMSO-d , 500MHz) δ: 3.71 339.00, 179.00, 146.10, 106.05, 78.05, 51.00. Anal. Calcd for
6
(
2H, t, J=6.9, 6.9Hz), 4.01 (2H, t, J=6.9, 6.9Hz), 7.91 (2H, d, C H N O S: C, 56.63; H, 3.86; N, 20.64. Found: C, 56.74; H,
16 13 5 2
1
−
J=4.5Hz), 8.82 (2H, d, J=4.5Hz). IR (KBr) cm : 3039, 2997, 3.91; N, 20.92%.
1
1
4
+
·
+·
608. ESI-MS m/z: 243.35 (M+2 ), 241.45 (M ), 179.35,
N′-[(Z/E)-(4-Bromophenyl)methylidene]-2-{[5-(pyridin-
46.65, 79.35, 51.35. Anal. Calcd for C H ClN OS: Calcd, C, 4-yl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetohydrazide (13) Yield,
9
8
3
1
4.72; H, 3.34; N, 17.39, Found, C, 44.79; H, 3.38; N, 17.43.
65%; mp 196–197°C; H-NMR (DMSO-d , 300MHz) δ: 4.27,
6
General Procedure for the Preparation of 2-[2-(4-Aryl- 4.70 (2H, 2s), 7.64–8.81 (8H, m), 8.01, 8.18 (1H, 2s), 11.89,
−1
piperazin-1-yl)ethylsulphanyl]-5-(pyridin-4-yl)-1,3,4-oxa- 11.91 (1H, 2s). IR (KBr) cm : 3205, 3051, 2935, 2816, 1689,
+
·
diazoles (7–9) To a solution of 6 (0.24g, 0.001mol) in dry 1608. ESI-MS m/z: 417.00 (M ), 77.00, 51.00. Anal. Calcd for
acetonitrile (20mL), anhydrous potassium carbonate (0.69g, C H BrN O S: C, 45.94; H, 2.89; N, 16.74. Found: C, 45.95;
16
12
5
2
0
.005mol) and few specs of potassium iodide (0.05g) were H, 2.89; N, 16.98%.
added. The reaction mixture was heated under reflux for 0.5h,
N′-[(Z/E)-(4-Fluorophenyl)methylidene]-2-{[5-(pyridin-
then an appropriate phenylpiperazine (0.003mol) was added, 4-yl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetohydrazide (14) Yield,
and the heating was continued for 20h. After cooling, the 93%; mp 200–201°C; H-NMR (DMSO-d , 300MHz) δ: 4.27,
1
6
reaction mixture was poured onto ice-cold water with continu- 4.70 (2H, s), 7.25–8.80 (8H, m), 8.03, 8.21 (1H, 2s), 11.84,
−1
ous stirring. The precipitate formed was filtered, washed with 11.86 (1H, 2s). IR (KBr) cm : 3421, 3055, 2939, 2827, 1690,
+
·
cold ether, dried then crystallized from isopropanol to give 1612. ESI-MS m/z: 357.00 (M ), 179.00, 96.00, 70.00. Anal.
compounds 7–9.
Calcd for C H FN O S: C, 53.77; H, 3.38; N, 19.60. Found: C,
16
12
5
2
2
-[2-(4-Phenyl-piperazin-1-yl)ethylsulphanyl]-5-(pyridin- 53.91; H, 3.42; N, 19.79%.
4
-yl)-1,3,4-oxadiazole (7) Yield, 50%; mp 112–113°C.
N′-[(Z/E)-(3-Hydroxyphenyl)methylidene]-2-{[5-(pyridin-
1
H-NMR (DMSO-d , 500MHz) δ: 2.50–2.56 (4H, m), 2.75 4-yl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetohydrazide (15) Yield,
(
6
7
6
1
2H, t, J=6.1, 6.1Hz), 2.90–3.02 (4H, m), 3.51 (2H, t, J=6.1, 59%; mp 220–221°C; H-NMR (DMSO-d , 500MHz) δ: 4.26,
6
.1Hz), 6.72 (1H, t, J=8.4, 8.4Hz), 6.85 (2H, d, J=8.4Hz), 4.69 (2H, 2s), 6.80–8.81 (8H, m), 7.95, 8.11 (1H, 2s), 9.64 (1H,
13
.15 (2H, t, J=8.4, 8.4Hz), 7.86 (2H, d, J=5.4Hz), 8.77 (2H, s), 11.78, 11.82 (1H, 2s). C-NMR (DMSO-d ): 34.87, 112.61,
6
13
d, J=5.4Hz). C-NMR (DMSO-d ): 30.2, 48.1, 52.2, 56.3, 117.37, 118.8, 119.9, 121.3, 129.8, 135.1, 144.4, 150.2, 157.7,
6
−1
1
(
1
15.3, 118.8, 119.8, 128.8, 130.0, 130.1, 150.8, 163.3, 165.7, IR 163.5, 164.9, 167.7. IR (KBr) cm : 3400 (OH), 3186, 3070,
−1
+·
+·
KBr) cm :3035, 2951, 2819, 1600. ESI-MS m/z: 367.00 (M ), 2978, 2870, 1670, 1612. ESI-MS m/z: 355.00 (M ), 106.05,
89.05, 175.05, 78.00. Anal. Calcd for C H N OS: C, 62.10; 78.00, 50.95. Anal. Calcd for C H N O S: C, 54.08; H, 3.69;
19
21
5
16 13
5
3
H, 5.76; N, 19.06. Found: C, 62.17; H, 5.82; N, 19.12.
-[2-(4-(4-Chlorophenyl)-piperazin-1-yl)ethylsulphanyl]-
N, 19.71. Found: C, 54.12; H, 3.58; N, 19.84%.
2
N′-[(Z/E)-(2-Methoxyphenyl)methylidene]-2-{[5-(pyridin-
5
1
-(pyridin-4-yl)-1,3,4-oxadiazole (8) Yield, 60%; mp 4-yl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetohydrazide (16) Yield,
1
1
20–121°C; H-NMR (DMSO-d , 300MHz) δ: 2.50–2.54 (4H, 82% (150mg); mp 180–181°C; H-NMR (DMSO-d , 300MHz)
6
6
m), 2.75 (2H, t, J=6.1, 6.1Hz), 2.90–3.02 (4H, m), 3.51 (2H, t, δ: 3.85 (3H, s), 4.23, 4.68 (2H, 2s), 6.96–8.79 (8H, m), 8.37,
−1
J=6.1, 6.1Hz), 6.87 (2H, d, J=9.2Hz), 7.17 (2H, d, J=9.2Hz), 8.55 (1H, 2s), 11.78, 11.87 (1H, 2s). IR (KBr) cm : 3201, 3066,
−
1
+·
7
3
(
.86 (2H, d, J=5.4Hz), 8.77 (2H, d, J=5.4Hz). IR (KBr) cm : 2935, 2839, 1685, 1608. ESI-MS m/z: 369.00 (M ), 107.00,
+
·
039, 2924, 2816, 1593. ESI-MS m/z: 403.20 (M+2 ), 401.20 106.05, 78.00, 51.00. Anal. Calcd for C H N O S: C, 55.27;
M ), 225.10, 223.10, 211.10, 209.10, 78.05. Anal. Calcd for H, 4.09; N, 18.96. Found: C, 55.33; H, 4.19; N, 19.32%.
1
7
15
5
3
+
·
C H ClN OS: C, 56.78; H, 5.02; N, 17.43. Found: C, 56.74; H,
N′-[(Z/E)-(4-Nitrophenyl)methylidene]-2-{[5-(pyridin-4-yl)-
19
20
5
5.12; N, 17.67.
1,3,4-oxadiazol-2-yl]sulfanyl}acetohydrazide (17) Yield, 66%;
1
2
-[2-(4-(4-Methoxyphenyl)-piperazin-1-yl)ethylsulphanyl]- mp 216–217°C; H-NMR (DMSO-d , 500MHz) δ: 4.31, 4.76
6
5
1
-(pyridin-4-yl)-1,3,4-oxadiazole (9) Yield, 49%; mp (2H, 2s), 7.70–8.80 (8H, m), 8.35, 8.53 (1H, 2s), 12.06, 12.13
1
−1
25–126°C; H-NMR (DMSO-d6, 300MHz) δ: 2.50–2.58 (4H, (1H, 2s). IR (KBr) cm : 3421, 3074, 2939, 2823, 1685, 1608.
+
·
m), 2.79 (2H, t, J=6.3, 6.3Hz), 2.83–2.93 (4H, m), 3.54 (2H, ESI-MS m/z: 384.00 (M ), 179.00, 106.00, 78.00, 51.00. Anal.
t, J=6.3, 6.3Hz), 3.67 (3H, s), 6.75–6.95 (4H, m), 7.89 (2H, d, Calcd for C H N O S: C, 50.00; H, 3.15; N, 21.86. Found: C,
16
12
6
4
−1
J=5.8Hz), 8.80 (2H, d, J=5.8Hz). IR (KBr) cm : 3050, 2816, 50.11; H, 3.23; N, 22.14%.
+
·
1600. ESI-MS m/z: 397.20 (M ), 219.15, 205.15, 78.05, 70.10.
N′-[(Z/E)-(3-Indolyl)methylidene]-2-{[5-(pyridin-4-yl)-1,3,4-
Anal. Calcd for C H N O S: C, 60.43; H, 5.83; N, 17.62. oxadiazol-2-yl]sulfanyl}acetohydrazide (18) Yield, 80%; mp
Found: C, 60.52; H, 5.94; N, 17.93.
2
0
23
5
2
1
242–243°C. H-NMR (DMSO-d , 500MHz) δ: 4.25, 4.77 (2H,
6
General Procedure for the Preparation of (Z/E) N′- 2s), 7.11–8.80 (9H, m), 8.22, 8.37 (1H, 2s), 11.50, 11.59 (2H,
−1
Arylidene-2-[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-ylsulphan- 2s). IR (KBr) cm : 3263, 3104, 2863, 1671, 1617. ESI-MS m/z:
+
·
yl]acetohydrazides (12–19)
A
solution of equimolar 377.95 (M ), 142.05, 129.05, 116.05, 78.00, 50.95. Anal. Calcd
amounts of 11 (0.25g, 0.001mol) and the appropriate aromatic for C H N O S: C, 57.13; H, 3.73; N, 22.21. Found: C, 57.17;
18
14
6
2