Synthesis and Activity of Kojic Acid Derivatives
13
J = 7.5 Hz, 2H, CH
2
), 4.26 (s, 2H, CH
2
), 5.88 (s, 2H,
6
OH); C NMR (DMSO-d , 125 MHz) d: 19.86, 32.29,
NH
2
), 6.37 (s, 1H, CH), 8.02 (s, 1H, CH), 9.11 (s, 1H, OH);
112.94, 125.55, 126.35, 129.86, 130.30, 130.39, 138.02,
139.92, 145.86, 150.40, 155.22, 163.33, 173.71; IR(KBr)
m: 3412, 3208, 3028, 2962, 2816, 1640, 1580, 1470,
1
3
6
C NMR (DMSO-d , 125 MHz) d: 13.68, 19.60, 25.56,
3
1
1
1
2.08, 112.71, 139.77, 145.79, 149.14, 156.56, 163.43,
73.66; IR(KBr) m: 3317, 3189, 2965, 2932, 2873, 1636,
606, 1582, 1527, 1459, 1421, 1384, 1322, 1286, 1206,
ꢁ1
+
1380, 1241, 1200 cm ; MS (ESI, m/z): 331 (M + H)
.
+
+
HRMS (ESI, m/z) calcd for [C H N O S] (M + H)
15 15 4 3
ꢁ
1
155, 1132, 942 cm ; MS (ESI, m/z): MS (ESI, m/z): 305
331.0859, found 331.0855.
+
+
(M + Na) . HRMS (ESI, m/z) calcd for [C11
H
14
N
4
NaO
3
S]
+
(M + Na) 305.0684, found 305.0675.
5-(4-methoxylphenyl)-3-[5-hydroxy-4-pyrone-2-yl-meth-
ymercapto]-4-amino-1,2,4-triazole (6h). Brown powder;
1
5
4
5
-phenyl-3-[5-hydroxy-4-pyrone-2-yl-methymercapto]-
-amino-1,2,4-triazole (6d). White powder; yield
1.2%; mp. 205–206 °C; H NMR (DMSO-d , 500 MHz)
yield 36.5%; mp. 223–224 °C;
500 MHz) d: 3.81 (s, 3H, CH
H
NMR (DMSO-d6,
), 6.16 (s,
3
), 4.34 (s, 2H, CH
2
1
2H, NH ), 6.44 (s, 1H, CH), 7.07 (d, J = 9.0 Hz, 2H, PhH),
6
2
d: 4.36 (s, 2H, CH
2
), 6.20 (s, 2H, NH
2
), 6.46 (s, 1H, CH),
7.94 (d, J = 8.5 Hz, 2H, PhH), 8.06 (s, 1H, CH), 9.16 (s, 1H,
OH); C NMR (DMSO-d , 125 MHz) d: 32.11, 55.32,
6
13
7
1
1
1
.51–7.53 (m, 3H, PhH), 7.98–8.00 (m, 2H, PhH), 8.06 (s,
H, CH), 9.15 (s, 1H, OH);
25 MHz) d: 32.06, 112.84, 126.73, 127.78, 128.53,
29.78, 139.85, 145.82, 151.85, 154.43, 163.36, 173.69;
13
C
NMR (DMSO-d6,
112.83, 113.98, 119.12, 129.31, 139.85, 145.82, 151.23,
154.28, 160.39, 163.40, 173.69; IR(KBr) m: 3448,3244,
3091, 2938, 2836, 1648, 1589, 1480, 1379, 1249,
ꢁ
1
+
IR(KBr) m: 3318, 3179, 3035, 1649, 1583, 1508, 1475,
1213 cm ; MS (ESI, m/z): 347 (M + H) . HRMS (ESI, m/z)
+
+
1
455, 1436, 1413, 1339, 1285, 1236, 1214, 1169, 1158,
calcd for [C H N O S] (M + H) 347.0809, found
15 15 4 4
ꢁ
1
+
1135 cm ; MS (ESI, m/z): 317 (M+H) . HRMS (ESI, m/z)
347.0802.
+
+
calcd for [C14
H
13
N
4
O
3
S]
(M+H)
317.0703, found
3
17.0712.
5-(2-methoxylphenyl)-3-[5-hydroxy-4-pyrone-2-yl-meth-
ymercapto]-4-amino-1,2,4-triazole (6i). Brown powder;
1
5-(4-methylphenyl)-3-[5-hydroxy-4-pyrone-2-yl-methym-
yield 40.8%; mp. 116–117 °C;
500 MHz) d: 3.82 (s, 3H, CH
H
NMR (DMSO-d6,
), 5.74 (s,
ercapto]-4-amino-1,2,4-triazole (6e). Gray powder; yield
3
), 4.35 (s, 2H, CH
2
1
4
2
2.6%; mp. 201–202 °C; H NMR (DMSO-d , 500 MHz) d:
.37 (s, 3H, CH
2H, NH ), 6.45 (s, 1H, CH), 7.09 (t, J = 8.5 Hz, 1H, PhH),
6
2
3
), 4.35 (s, 2H, CH
2
), 6.18 (s, 2H, NH
2
), 6.45
7.19 (d, J = 8.5 Hz, 1H, PhH), 7.41–7.56 (m, 2H, PhH),
13
(s, 1H, CH), 7.32 (d, J = 8.0 Hz, 2H, PhH), 7.88 (d,
6
8.06 (s, 1H, CH), 9.19 (s, 1H, OH); C NMR (DMSO-d ,
J = 8.5 Hz, 2H, PhH), 8.06 (s, 1H, CH), 9.16 (s, 1H, OH);
C NMR (DMSO-d , 125 MHz) d: 20.99, 32.07, 112.85,
6
125 MHz) d: 31.85, 55.85, 112.88, 115.52, 120.59, 131.51,
132.05, 139.86, 145.83, 150.52, 154.44, 156.96, 162.37,
163.42, 173.71; IR(KBr) m: 3542, 3316, 3070, 2945, 2774,
1
3
1
1
2
23.93, 127.69, 129.11, 139.50, 139.87, 145.84, 151.60,
ꢁ
1
54.47, 163.48, 173.71; IR(KBr) m: 3437, 3168, 3031,
1646, 1581, 1471, 1449, 1408, 1295, 1224 cm ; MS (ESI,
ꢁ
1
+
968, 2753, 1632, 1582, 1460, 1383, 1247, 1217 cm
;
m/z): 347 (M + H)
. HRMS (ESI, m/z) calcd for
+
+
+
MS (ESI, m/z): 331 (M + H) . HRMS (ESI, m/z) calcd for
[C H N O S] (M + H) 331.0859, found 331.0857.
15 15 4 3
[C15
H
15
N
4
O
4
S] (M + H) 347.0809, found 347.0806.
+
+
5-(4-chlorophenyl)-3-[5-hydroxy-4-pyrone-2-yl-methymer-
5
-(3-methylphenyl)-3-[5-hydroxy-4-pyrone-2-yl-methy-
capto]-4-amino-1,2,4-triazole (6j). Brown powder; yield
1
mercapto]-4-amino-1,2,4-triazole (6f). Brown powder;
yield 39.5%; mp. 170–171 °C;
43.5%; mp. 206–207 °C; H NMR (DMSO-d , 500 MHz) d:
6
1
H
NMR (DMSO-d
), 4.35 (s, 2H, CH ), 6.19 (s,
), 6.45 (s, 1H, CH), 7.31–7.41 (m, 2H, PhH), 7.77–
6
,
4.52 (s, 2H, CH
2 2
), 5.74(s, 2H, NH ), 6.51 (s, 1H, CH), 7.66 (d,
500 MHz) d: 2.37 (s, 3H, CH
2H, NH
7.80 (m, 2H, PhH), 8.08 (s, 1H, CH), 9.17 (s, 1H, OH);
3
2
J = 9.0 Hz, 2H, PhH), 7.97 (d, J = 8.5 Hz, 2H, PhH), 8.09 (s,
13
2
6
1H, CH), 9.25 (s, 1H, OH); C NMR (DMSO-d , 125 MHz) d:
13
C
33.11, 113.33, 121.84, 128.31, 129.64, 136.90, 140.09,
145.95, 162.22, 162.50, 164.90, 173.62; IR(KBr) m: 3438,
3058, 2969, 2940, 2891, 2671, 1640, 1481, 1429, 1390,
NMR (DMSO-d , 125 MHz) d: 21.02, 32.03, 112.84,
6
1
1
3
24.94, 126.64, 128.28, 128.44, 130.39, 137.79, 139.86,
45.84, 151.74, 154.52, 163.37, 173.70; IR(KBr) m: 3432,
168, 3028, 2960, 2812, 1638, 1580, 1459, 1386, 1241,
ꢁ
1
+
1388, 1151 cm ; MS (ESI, m/z): 351 (M + H) . HRMS (ESI,
+
+
4 3
m/z) calcd for [C14H12ClN O S] (M + H) 351.0313, found
ꢁ
1
+
1221 cm ; MS (ESI, m/z): 331 (M + H) . HRMS (ESI, m/z)
351.0321.
+
+
15 4 3
calcd for [C15H N O S] (M + H) 331.0859, found
3
31.0855.
5-(2-chlorophenyl)-3-[5-hydroxy-4-pyrone-2-yl-methym-
ercapto]-4-amino-1,2,4-triazole (6k). Yellow powder;
1
5-(2-methylphenyl)-3-[5-hydroxy-4-pyrone-2-yl-methy-
yield 49.5%; mp. 147–148 °C;
6
H NMR (DMSO-d ,
mercapto]-4-amino-1,2,4-triazole (6g). Brown powder;
500 MHz) d: 4.37 (s, 2H, CH ), 5.96 (s, 2H, NH ), 6.44 (s,
2 2
1
yield 38.2%; mp. 173–174 °C;
H
NMR (DMSO-d
), 4.35 (s, 2H, CH ), 5.95 (s,
H, NH ), 6.43 (s, 1H, CH), 7.29–7.32 (m, 1H, PhH), 7.36
6
,
1H, CH), 7.47–7.51 (m, 1H, PhH), 7.56–7.59 (m, 2H, PhH),
7.63–7.65 (m, 1H, PhH), 8.07 (s, 1H, CH), 9.22 (s, 1H, OH);
500 MHz) d: 2.24 (s, 3H, CH
3
2
13
2
C NMR (DMSO-d , 125 MHz) d: 32.34, 113.03, 126.21,
2
6
(
(
d, J = 7.5 Hz, 1H, PhH), 7.40–7.43 (m, 1H, PhH), 7.47
d, J = 7.5 Hz, 1H, PhH), 8.07 (s, 1H, CH), 9.20 (s, 1H,
127.19, 129.73, 131.96, 132.50, 133.50, 139.95, 145.89,
150.91, 153.88, 163.24, 173.73; IR(KBr) m: 3420, 3078,
Chem Biol Drug Des 2015; 86: 1087–1092
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