New Azole Antifungals
imidazole H-4, imidazole H-5, H-6¢ and H-4), 7.86 (dd, 1H, J = 7.75
and 1.75 Hz, H-6), 9.01 (s, 1H, imidazole H-2).
J = 8.5 Hz, H-6¢), 7.89 (dd, 1H, J = 8.0 and 2.0 Hz, H-6), 9.00 (br s,
1H, imidazole H-2). 13C NMR (125 MHz, DMSO-d6) d 58.22, 67.42,
114.01, 119.47, 121.53, 123.40, 123.59, 127.76, 129.20, 130.73,
131.94, 132.61, 133.78, 134.00, 136.01, 136.70, 158.28, 190.99.
1-[2-(3-Fluorobenzyloxy)phenyl]-2-(1H-imidazol-
1-yl)ethanone hydrochloride (2c)
Yield 20%; mp 195–196 ꢀC; IR (KBr, 1 ⁄ cm): 3413, 3034, 2802, 1677,
1596, 1574, 1479, 1452, 1374, 1346, 1225, 1205, 1112, 1006, 757,
692. H NMR (500 MHz, DMSO-d6) d 5.43 (s, 2H, OCH2), 5.83 (s, 2H,
NCH2), 7.14 (dt, 1H, J = 7.5 and 0.5 Hz, H-5), 7.17–7.22 (m, 1H, H-4¢),
7.32 (d, 1H, J = 8.5 Hz, and H-3), 7.43–7.51 (m, 3H, H-2¢, H-5¢, and H-
6¢), 7.64–7.72 (m, 3H, imidazole H-4, imidazole H-5, and H-4), 7.88
(dd, 1H, J = 7.5 and 1.5 Hz, H-6), 9.03 (br s, 1H, imidazole H-2).
1-[2-(3,4-Dichlorobenzyloxy)phenyl]-2-(1H-
imidazol-1-yl)ethanone hydrochloride (2h)
Yield 23%; mp 235–236 ꢀC; IR (KBr, 1 ⁄ cm): 3423, 3017, 2653, 1667,
1599, 1574, 1477, 1451, 1367, 1345, 1294, 1219, 1199, 1160, 1029,
1
1
1007, 868, 759, 642, 630. H NMR (500 MHz, DMSO-d6) d 5.41 (s,
2H, OCH2), 5.82 (s, 2H, NCH2), 7.15 (t, 1H, J = 7.5 Hz, H-5), 7.31 (d,
1H, J = 8.5 Hz, H-3), 7.62 (dd, 1H, J = 8.0 and 2.0 Hz, H-6¢), 7.65–
7.73 (m, 4H, H-4, H-5¢, imidazole H-4, and imidazole H-5), 7.89 (dd,
1H, J = 7.75 and 1.75 Hz, H-6), 7.90 (d, 1H, J = 1.5 Hz, H-2), 9.03
(br s, 1H, imidazole H-2).
1-[2-(4-Fluorobenzyloxy)phenyl]-2-(1H-imidazol-
1-yl)ethanone hydrochloride (2d)
Yield 10%; mp 188–189 ꢀC; IR (KBr, 1 ⁄ cm): 3405, 3031, 1677, 1602,
1574, 1511, 1479, 1454, 1346, 1281, 1227, 1200, 1163, 1000, 840,
757, 647. 1H NMR (500 MHz, DMSO-d6) d 5.37 (s, 2H, OCH2), 5.76 (s,
2H, NCH2), 7.12 (dt, 1H, J = 7.75 and 0.5 Hz, H-5), 7.24 (dd, 2H,
J = 7.0 and 2.0 Hz, H-2¢ and H-6¢), 7.35 (d, 1H, J = 8.0 Hz, H-3), 7.61–
7.69 (m, 5H, imidazole H-4, imidazole H-5, H-4, H-3¢, and H-5¢), 7.86
(dd, 1H, J = 7.75 and 1.75 Hz, H-6), 8.99 (br s, 1H, imidazole H-2).
General procedure for the synthesis of triazole
derivatives (3a–h)
To a mixture of compound 8 (1.5 mmol, 305 mg) and K2CO3 (1.5 mmol,
207 mg) in acetone (15 mL), appropriate benzyl halide (1.5 mmol) was
added and refluxed for 24–44 h. After the completion of the reaction,
the solvent was evaporated under reduced pressure and the residue
was washed with water. The crude product was dissolved in the least
amount of absolute ethanol (2 mL) and treated with 37% aqueous HCl
(0.2 mL). The solution was cooled at a freezer prior to gradual addition
of diethyl ether to complete the precipitation of the hydrochloride salts
3b–h, which were collected by filtration and washed with diethyl
ether. In the case of compound 3a, the crude product was dissolved in
absolute ethanol (1.5 mL) and treated with 65% aqueous HNO3
(0.2 mL). After the addition of diethyl ether (2 mL), the mixture was
refrigerated to complete the precipitation of the nitrate salt 3a, which
was collected by filtration and washed with diethyl ether.
1-[2-(3-Chlorobenzyloxy)phenyl]-2-(1H-imidazol-
1-yl)ethanone hydrochloride (2e)
Yield 10%; mp 215–216 ꢀC; IR (KBr, 1 ⁄ cm): 3417, 3037, 2957, 1675,
1665, 1598, 1573, 1480, 1454, 1346, 1255, 1225, 1205, 1165, 1005,
758. 1H NMR (500 MHz, DMSO-d6) d 5.42 (s, 2H, OCH2), 5.82 (s,
2H, NCH2), 7.14 (t, 1H, J = 7.75 Hz, H-5), 7.31 (d, 1H, J = 8.0 Hz,
H-3), 7.4 (dt, 1H, J = 8.0 and 1.5 Hz, H-4¢), 7.46 (t, 1H, J = 7.5 Hz,
H-5¢), 7.59 (d, 1H, J = 7.5 Hz, H-6¢), 7.63–7.71 (m, 4H, H-4, H-2¢,
imidazole H-4, and imidazole H-5), 7.88 (dd, 1H, J = 8.0 and 2.0 Hz,
H-6), 9.00 (br s, 1H, imidazole H-2).
1-[2-(Benzyloxy)phenyl]-2-(1H-1,2,4-triazol-1-
yl)ethanone nitrate (3a)
1-[2-(4-Chlorobenzyloxy)phenyl]-2-(1H-imidazol-
1-yl)ethanone hydrochloride (2f)
Yield 7%; mp 116–119 ꢀC; IR (KBr, 1 ⁄ cm): 3427, 3121, 3049, 1686,
1597, 1447, 1419, 1403, 1384, 1307, 1229, 1116, 1010, 761, 647.
1H NMR (500 MHz, DMSO-d6) d 5.35 (s, 2H, OCH2), 5.74 (s, 2H,
NCH2), 7.10 (t, 1H, J = 7.5 Hz, H-5), 7.27–7.47 (m, 4H, H-3, and
phenyl H), 7.59 (dd, 2H, J = 7.5 and 0.5 Hz, phenyl H), 7.64 (dt, 1H,
J = 7.0 and 0.5 Hz, H-4¢), 7.78 (dd, 1H, J = 7.5 and 0.5 Hz, H-6),
8.13 (s, 1H, triazole H-5), 8.67 (s, 1H, triazole H-3).
Yield 16%; mp 210–211 ꢀC; IR (KBr, 1 ⁄ cm): 3124, 3023, 1670, 1599,
1478, 1454, 1344, 1223, 1198, 1161, 1089, 994, 758. 1H NMR
(500 MHz, DMSO-d6) d 5.39 (s, 2H, OCH2), 5.79 (s, 2H, NCH2), 7.12
(dt, 1H, J = 7.62 and 0.75 Hz, H-5), 7.33 (d, 1H, J = 8.0 Hz, H-3),
7.47 (d, 2H, J = 8.5 Hz, H-2¢, and H-6¢), 7.62–7.69 (m, 5H, imidazole
H-4, imidazole H-5, H-3¢, H-5¢, and H-4), 7.87 (dd, 1H, J = 8.0 and
2.0 Hz, H-6), 9.04 (br s, 1H, imidazole H-2).
1-[2-(4-Bromobenzyloxy)phenyl]-2-(1H-1,2,4-
triazol-1-yl)ethanone hydrochloride (3b)
1-[2-(2,4-Dichlorobenzyloxy)phenyl]-2-(1H-
imidazol-1-yl)ethanone hydrochloride (2g)
Yield 21%; mp 209–210 ꢀC; IR (KBr, 1 ⁄ cm): 3425, 3006, 1671, 1598,
1480, 1429, 1308, 1289, 1229, 1206, 1167, 1012, 755, 633. H NMR
1
Yield 20%; mp 215–216 ꢀC; IR (KBr, 1 ⁄ cm): 3433, 3031, 2821, 1673,
1598, 1574, 1480, 1454, 1370, 1346, 1306, 1226, 1200, 1164, 1013,
836, 760. 1H NMR (500 MHz, DMSO-d6) d 5.43 (s, 2H, OCH2), 5.74 (s,
2H, NCH2), 7.18 (dt, 1H, J = 7.5 and 0.7 Hz, H-5), 7.38 (dd, 1H,
J = 8.5 and 0.5 Hz, H-3), 7.52 (dd, 1H, J = 8.0 and 2.0 Hz, H-5¢), 7.64
(br s, 1H, imidazole H-5), 7.68 (br s, 1H, imidazole H-4), 7.71 (dt, 1H,
J = 7.8 and 1.8 Hz, H-4), 7.75 (d, 1H, J = 2.5 Hz, H-3¢), 7.77 (d, 1H,
(500 MHz, DMSO-d6) d 5.34 (s, 2H, OCH2), 5.73 (s, 2H, NCH2), 7.10
(dt, 1H, J = 7.5 and 1.0 Hz, H-5), 7.31 (dd, 1H, J = 8.0 and 0.5 Hz,
H-3), 7.47 (d, 2H, J = 8.5 Hz, H-2¢, and H-6¢), 7.62 (d, 2H,
J = 8.5 Hz, H-3¢, and H-5¢), 7.63 (m, 1H, H-4), 7.76 (dd, 1H, J = 8.0
and 1.5 Hz, H-6), 8.11 (br s, 1H, triazole H-5), 8.66 (br s, 1H, triazole
H-3). 13C NMR (125 MHz, DMSO-d6) d 59.02, 69.44, 113.96, 121.12,
124.38, 128.62, 130.16, 132.79, 135.33, 158.20, 192.47.
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