Month 2017
Antibacterial and Antifungal Activities of 2-(substituted ether)-5-(1-phenyl-5-
trifluoromethyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazole Derivatives
(
2
-allyloxy-5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-
119.4 (q, J = 270.3 Hz, CF ), 109.1, 49.3, 21.2; IR (KBr) ν:
3
1
,3,4-oxadiazole (6f). This compound was obtained as canary
3121, 3059, 3027, 2932, 2856, 1786, 1643, 1595, 1502, 1458,
1
À1
yellow solid; yield 81.0%, m. p. 77 ~ 78°C; H NMR
1428, 1410, 1302, 1191, 973, 936, 772, 750, 695 cm ; MS
+
(
500 MHz, DMSO-d
6
) δ 8.35 (s, 1H, pyrazole-H), 7.60–7.52
= 22.4, J = 10.6,
(ESI) m/z 401 [M + H] ; Anal. Calcd. for C20
H
15
F
3
N
4
O
2
: C,
(
m, 5H, benzene-H), 5.91 (ddd, J
1
2
60.00; H, 3.78; N, 13.99. Found: C, 59.90; H, 3.98; N, 14.24.
J = 5.4 Hz, 1H, CH=), 5.25 (d, J = 9.1 Hz, 2H, O-CH ), 4.37
2-((trifluoromethylbenzyl)oxy)-5-(1-phenyl-5-(trifluoromet-
3
2
1
3
(
d, J = 5.3 Hz, 2H, =CH2); C NMR (125 MHz, DMSO-d ) δ
hyl)-1H-pyrazol-4-yl)-1,3,4-oxadiazole (6k).
This compound
6
1
1
3
1
52.4, 146.3, 140.7, 138.9, 133.1, 130.9, 129.9, 126.6, 119.9,
was obtained as canary yellow solid; yield 78.1%, m. p.
1
19.4 (q, J = 270.6 Hz, CF ), 109.1, 48.2; IR (KBr) ν: 3106,
3
81 ~ 82°C; H NMR (500 MHz, DMSO-d ) δ 8.35 (s, 1H,
6
022, 2959, 2927, 2853, 1781, 1646, 1595, 1499, 1465, 1419,
pyrazole-H), 7.73 (d, J = 8.1 Hz, 2H, benzyl-H), 7.61–7.50 (m,
À1
13
405, 1303, 1183, 968, 928, 770, 696 cm ; MS(ESI) m/z 337
7H, benzene H & benzyl-H), 5.08 (s, 2H, CH2); C NMR
+
[
M + H] . Anal. Calcd. for C15
H
11
F
3
N
4
O
2
: C, 53.58; H, 3.30;
(125 MHz, DMSO-d ) δ 153.2, 146.8, 140.8, 140.6, 138.9,
6
N, 16.66. Found: C, 53.30; H, 3.72; N, 16.22.
-benyloxy-5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-
,3,4-oxadiazole (6g). This compound was obtained as white
130.9, 129.9, 128.9, 126.6, 126.1, 124.7 (q, J = 272.4 Hz,
benzyl-CF ), 119.4 (q, J = 270.7 Hz, pyrazole-CF ), 109.1,
3 3
48.9; IR (KBr) ν: 3067, 3048, 2953, 2927, 2854, 1792, 1653,
2
1
1
solid; yield 84.3%, m. p. 98 ~ 99°C; H NMR (500 MHz,
DMSO-d ) δ 8.35 (s, 1H, pyrazole-H), 7.59–7.52 (m, 5H,
benzene-H), 7.42–7.28 (m, 5H, benzyl-H), 4.96 (s, 2H, CH );
1599, 1559, 1501, 1472, 1419, 1325, 1169, 998, 969, 761, 747,
À1
+
684, 668 cm ; MS(ESI) m/z 455 [M + H] ; Anal. Calcd. for
: C, 52.87; H, 2.66; N, 12.33. Found: C, 52.77;
6
20 12 6 4 2
C H F N O
2
13
C NMR (125 MHz, DMSO-d ) δ 153.1, 146.5, 140.7, 138.9,
H, 3.07; N, 12.25.
6
1
35.8, 130.9, 129.9, 129.2, 128.5, 128.2, 126.6, 119.4 (q,
2-((3-fluorobenzyl)oxy)-5-(1-phenyl-5-(trifluoromethyl)-1H-
J = 270.1 Hz, CF
3
), 109.1, 49.5; IR (KBr) ν: 3116, 3031, 2962,
pyrazol-4-yl)-1,3,4-oxadiazole (6l).
A white solid, yield
79.7%, m. p. 96 ~ 98°C; H NMR (500 MHz, DMSO-d ) δ
8.35 (s, 1H), 7.60–7.51 (m, 5H), 7.40 (td, J = 8.3, J = 6.4 Hz,
1H), 7.19 (dd, J = 9.6, J = 4.4 Hz, 2H), 7.14 (td, J = 9.1,
= 2.6 Hz, 1H), 4.99 (s, 2H, CH ); C NMR (125 MHz,
DMSO-d ) δ 162.60 (d, J = 242.5 Hz, benzyl-C), 153.12,
1
2
927, 2852, 1781, 1642, 1596, 1501, 1465, 1452, 1419, 1305,
6
À1
1
189, 970, 959, 764, 747, 686 cm ; MS(ESI) m/z 387
1
2
+
[
M + H] . Anal. Calcd. for C19
N, 14.50. Found: C, 58.94; H, 3.75; N, 14.05.
-((4-chlorobenzyl)oxy)-5-(1-phenyl-5-(trifluoromethyl)-1H-
pyrazol-4-yl)-1,3,4-oxadiazole (6h). This compound was
obtained as canary yellow solid; yield 85.2%, m. p. 80 ~ 82°C;
H
13
F
3
N
4
O
2
: C, 59.07; H, 3.39;
1
2
1
13
J
2
2
2
6
146.71, 140.77, 139.83 (d, J = 7.9 Hz, benzyl-C), 138.95,
131.15 (d, J = 8.5 Hz, benzyl-C), 130.90, 129.95, 126.66,
125.80 (d, J = 2.2 Hz, benzyl-C), 119.43 (q, J = 270.0 Hz,
1
H NMR (500 MHz, DMSO-d
.63–7.50 (m, 5H, benzene-H), 7.43 (d, J = 8.4 Hz, 2H, 4-Cl-
benzyl-H), 7.37 (d, J = 8.4 Hz, 2H, 4-Cl-benzyl-H), 4.96 (s,
6
) δ 8.34 (s, 1H, pyrazole-H),
CF
3
), 116.59 (d, J = 22.3 Hz, benzyl-C), 115.36 (d,
7
J = 21.3 Hz, benzyl-C), 109.08, 48.89; IR (KBr) ν: 3118, 3081,
13
2
1
963, 2930, 2852, 1783, 1645, 1593, 1501, 1486, 1449, 1419,
2
1
1
3
1
4
2
2 6
H, CH ); C NMR (125 MHz, DMSO-d ) δ 153.1, 146.6,
À1
306, 1189, 971, 946, 763, 748, 681 cm ; MS(ESI) m/z 405
40.7, 138.9, 134.8, 133.2, 130.9, 130.1, 129.9, 129.2, 126.6,
19.4 (q, J = 270.6 Hz, CF ), 109.1, 48.7; IR (KBr) ν: 3086,
059, 3035, 2923, 2850, 1792, 1653, 1596, 1503, 1492, 1465,
+
[
M + H] ; Anal. Calcd. for C19
H
12
F
4
N
4
O
2
: C, 56.44; H, 2.99;
3
N, 13.86. Found: C, 56.82; H, 3.27; N, 13.84.
À1
437, 1302, 1181, 970, 925, 765, 747, 690 cm ; MS(ESI) m/z
General synthetic Procedures for the target compounds
+
21 [M + H] . Anal. Calcd. for C19
H
12ClF
3
N
4
O
2
: C, 54.23; H,
(7a–7b).
Intermediate 5 (1.01 mmol) was dissolved in a
.87; N, 13.32. Found: C, 54.62; H, 3.25; N, 12.87.
-((4-fluorobenzyl)oxy)-5-(1-phenyl-5-(trifluoromethyl)-1H-
pyrazol-4-yl)-1,3,4-oxadiazole (6i). A light yellow liquid,
yield 83.4%, H NMR (500 MHz, DMSO-d ) δ 8.17 (s, 1H,
mixture of DMF (10.0 mL), and NaOH (1.21 mmol). Then the
dibromo-substituted alkane (1.51 mmol) was added and stirred
at room temperature for 5 h. After that, 30 mL ethyl acetate was
added into the mixture. Later, the organic layer was washed by
2
1
6
pyrazole-H), 7.59–7.47 (m, 5H, benzene-H), 7.43 (dd, J = 8.6,
saturated NH Cl, water, dried with anhydrous sodium sulfate,
1
4
J = 5.3 Hz, 2H, 4-F-benzyl-H), 7.10 (t, J = 8.8 Hz, 2H, 4-F-
filtered, and followed by the removal of the solvent under
vacuum. The crude product was incubated in pyridine at 60°C
for 12 h. After that, the extra pyridine was removed under
reduced pressure. The crude residue was further purified by
flash column chromatography on a silica gel using CH Cl and
2
1
3
benzyl-H), 4.95 (s, 2H, CH
δ 160.19 (d, J = 243.8 Hz, benzyl C), 153.21, 146.65, 140.76,
38.95, 132.76 (d, J = 2.6 Hz, benzyl C), 131.89 (d,
2 6
); C NMR (125 MHz, DMSO-d )
1
J = 8.3 Hz, benzyl C), 130.87, 129.95, 126.65, 119.41 (q,
2
2
J = 270.1 Hz, CF ), 116.09 (d, J = 21.3 Hz, benzyl C), 109.11,
CH OH (6:1) as the eluant to afford the desired product (7a–7b).
3
3
4
1
6
8.71; IR (KBr) ν: 3072, 3046, 2947, 2923, 2852, 1784, 1653,
1-(6-((5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,3,
598, 1559, 1506, 1472, 1433, 1325, 1179, 989, 959, 771,
4-oxadiazol-2-yl)oxy)hexyl)pyridin-1-ium bromide (7a).
A
À1
+
1
94 cm ; MS(ESI) m/z 405 [M + H] ; Anal. Calcd. for
white liquid; yield 55.0%; H NMR (500 MHz, CDCl ) δ 9.27
3
C H F N O : C, 56.44; H, 2.99; N, 13.86. Found: C, 56.70;
(d, J = 10.0 Hz, 2H, pyridine-H), 8.55 (t, J = 7.5 Hz, 1H,
19 12 4 4 2
H, 2.92; N, 14.10.
-((4-methylbenzyl)oxy)-5-(1-phenyl-5-(trifluoromethyl)-1H-
pyrazol-4-yl)-1,3,4-oxadiazole (6j). This compound w1as
obtained as white solid; yield 83.1%, m. p. 71 ~ 72°C;
NMR (500 MHz, DMSO-d ) δ 8.34 (s, 1H, pyrazole-H), 7.60–
.50 (m, 5H, benzene-H), 7.22 (d, J = 7.9 Hz, 2H, 4-CH3-
benzyl-H), 7.15 (d, J = 7.9 Hz, 2H, 4-CH -benzyl-H), 4.90 (s,
pyridine-H), 8.12 (t, J = 5.0 Hz, 2H, pyridine-H), 7.98 (s, 1H,
pyrazole-H), 7.32–7.42 (m, 5H, phenyl-H), 4.85 (t, J = 7.5 Hz,
2
2H, CH
2
-N), 3.68 (t, J = 7.5 Hz, 2H, CH
), 1.67–1.73 (m, 2H, CH ), 1.35–1.38 (m, 4H, 2CH
C NMR (125 MHz, CDCl ) δ 153.3, 146.6, 145.8, 144.9,
2
-O), 1.97–2.02 (m,
H
2H, CH
2
2
2
);
13
6
3
7
140.0, 138.8, 130.1, 129.3, 128.8, 125.8, 120.1, 117.9, 109.0,
+
61.8, 45.8, 31.6, 27.8, 25.7, 25.3. MS(ESI): m/z 458 [M-Br] ;
3
13
2
H, CH
2
); C NMR (125 MHz, DMSO-d
6
) δ 153.2, 146.5,
Anal. Calcd. for C23
3 5 2
H23BrF N O : C, 51.31; H, 4.31; N, 13.01.
1
40.7, 138.9, 137.8, 132.8, 130.8, 129.9, 129.7, 128.2, 126.6,
Found: C, 50.92; H, 4.51; N, 12.65.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet