10
T.J. Rashamuse et al. / European Journal of Medicinal Chemistry 190 (2020) 112111
4.2.5.4. 2-[5-(3,4-Dimethoxyphenyl)-1H-imidazol-1-yl]acetic
19c. Physical characteristics: yellow solid; Yield: 179 mg, 71%; Mp:
124e127 ꢀC; 1H NMR (DMSO‑d6)
7.77 (1H, s, 2-CH), 6.88e67.02
(4H, overlapping signals, m, ArH and 4-CH), 4.74 (2H, s, NCH2), 3.77
and 3.74 (6H, 2 x s, 2 x ArOCH3); 13C NMR (DMSO‑d6)
170.3 (C]O),
acid
solvent was removed and DCM was added to generate a precipitate
which was then filtered and dried under high vacuum to afford
pure 2-(5-aryl-1H-imidazol-1-yl)acetohydrazides.
(NB: 1H and 13C NMR spectra reported below are for major
rotamer only).
d
d
148.7 and 148.7 (2 x ArCOCH3), 139.4 (2-C), 132.8 (5-C), 125.9, 127.8
(ArC), 120.7 (4-C), 112.0, 111.9 (ArC), 55.5 and 55.4 (2 x ArCOCH3),
4.2.6.2. 2-[5-(4-Fluorophenyl)-1H-imidazol-1-yl]acetohydrazide
46.9 (NCH2); FTIR
n
max/cm-1 (KBr): 3126, 3050, 2970, 2841, 2604,
20a. Physical characteristics: white solid; Yields: 194 mg, 92%; Mp:
1612, 1512, 1471, 1447, 1380, 1324, 1256, 1224, 1181, 1146, 1021, 826,
806, 695, 676; HRMS (ESI-TOF) m/z: [MþH]þ Calcd for C13H15N2O4
263.1040, Found 263.1017.
178e180 ꢀC; 1H NMR (DMSO‑d6)
d
9.31 (1H, s, NHNH2), 7.69 (1H, s,
2-CH), 7.25e7.45 (4H, m, ArH), 6.99 (1H, s, 4-CH), 4.59 (2H, s, NCH2),
4.29 (2H, s, NHNH2); 13C NMR (DMSO‑d6)
d 166.4 (C]O), 160.6 (d,
1JC,F ¼ 245 Hz, para-CF),140.0 (2-C),131.8 (5-C),130.5 (d, 3JC,F ¼ 8 Hz,
4
4.2.5.5. 2-(5-(Benzo[d][1,3]dioxol-6-yl)-1H-imidazol-1-yl)acetic acid
ortho-C), 127.3 (4-C), 126.0 (d, JC,F ¼ 3 Hz, 10-C), 115.6 (d,
19d. Physical characteristics: yellow solid; Yield: 161 mg, 68%; Mp:
2JC,F ¼ 22 Hz, meta-C), 45.8 (NCH2); FTIR
nmax/cm-1 (KBr): 3104,
233e236 ꢀC; 1H NMR (DMSO‑d6)
d
7.79(1H, s, 2-CH),6.82e6.99 (4H,
overlapping signals, m, ArH and 4-CH), 6.05 (2H, s, ArOCH2O), 4.77
(2H, s, NCH2); 13C NMR (DMSO‑d6)
170.0 (C]O), 147.6 and 147.1
(ArCOCH2O), 139.4 (2-C), 132.6 (5-C), 126.2, 123.0, 122.1, 108.7 (ArC),
101.4 (ArCOCH2O), 46.7 (NCH2); FTIR max/cm-1 (KBr): 3435, 3152,
3026, 2417, 1747, 1495, 1380, 1223, 1163, 1110, 928, 824, 698, 674,
544, HRMS (ESI-TOF) m/z: [MþH]þ Calcd for C11H12FN4O 235.0990,
found 235.0995.
d
n
4.2.6.3. 2-(5-Phenyl-1H-imidazol-1-yl)acetohydrazide 20b. 2 Phys-
3096, 2500, 1652, 1604, 1504, 1474, 1388, 1313, 1257, 1226, 1035,
882, 691; HRMS (ESI-TOF) m/z: [MþH]þ Calcd for C12H11N2O4
247.0713, found 247.0702.
ical characteristics: pale yellow solid; Yields: 176 mg, 90%; Mp:
172e174 ꢀC; 1H NMR (DMSO‑d6)
d
9.32 (1H, s, NHNH2), 7.36 (1H, s,
2-CH), 7.35e7.45 (5H, m, ArH), 7.00 (1H, s, 4-CH), 4.62 (2H, s, NCH2),
4.30 (2H, s, NHNH2); 13C NMR (DMSO‑d6)
167.5 (C]O), 141.1 (2-C),
133.2 (5-C), 130.5, 129.7, 129.1, 128.7, 128.1 (ArC), 128.1 (4-C), 46.8
(NCH2); FTIR max/cm-1 (KBr): 3321, 3197, 3119, 3026, 2950, 1676,
d
4.2.5.6. 2-(5-(4-tert-Butylphenyl)-1H-imidazol-1-yl)acetic acid 19e.
Physical characteristics: yellow solid; Yield: 333 mg, 56%; Mp:
n
170e173 ꢀC; 1H NMR (DMSO‑d6)
d
7.82 (1H, s, 2-CH), 7.45 (2H, d,
J ¼ 7.6 Hz, ArH), 7.30 (2H, d, J ¼ 7.6 Hz, ArH), 7.04 (1H, s, 4-CH), 4.81
(2H, s, NCH2), 1.29 [9H, s, C(CH3)3]; 13C NMR (DMSO‑d6)
169.9 (C]
1638, 1608, 1553, 1489, 1425, 1298, 1285, 1229, 1112, 1006, 927, 909,
820, 767, 718, 703, 678, 647, 581, 534; HRMS (ESI (ESI-TOF) m/z:
[MþH]þ Calcd for C11H13N4O 217.1084, found 217.1082.
d
O), 150.4 [ArCC(CH3)3], 139.7 (2-C), 132.7, 127.7, 126.5, 126.3, 125.7
(ArC and 4-C), 46.7 (NCH2), 34.4 [ArCC(CH3)3], 31.1 [ArCC(CH3)3];
4.2.6.4. 2-[5-(3,5-Dimethoxyphenyl)-1H-imidazol-1-yl]acetohy-
FTIR
n
max/cm-1 (KBr): 3132, 3035, 2961, 2905, 2868, 2509, 1722,
drazide 20c. Physical characteristics: yellow solid; Yields:
1678, 1625, 1463, 1378, 1335, 1269, 1233, 1112, 1035, 1010, 841, 677;
HRMS (ESI-TOF) m/z: [MþH]þ Calcd for C15H19N2O2 259.1441,
Found 259.1440.
259 mg,94%; Mp: 89e91 ꢀC; 1H NMR (DMSO‑d6)
d 9.37 (1H, s,
NHNH2), 7.66 (1H, s, 2-CH), 6.88e7.01 (4H, overlapping multiplets,
ArH and 4-CH), 4.59 (2H, s, NCH2), 4.33 (2H, s, NHNH2), 3.78 and
3.76 (6H, 2 x s, 2 x ArOCH3); 13C NMR (DMSO‑d6)
d 166.7 (C]O),
4.2.5.7. 2-(5-(3-Hydroxy-4-methoxyphenyl)-1H-imidazol-1-yl)acetic
148.7 & 148.6 (2 x ArCOCH3), 139.6 (2-C), 132.8 (5-C), 126.5 (4-C),
121.9, 121.9, 111.9, 112.9 (ArC), 55.5 and 55.4 (2 x ArCOCH3), 45.8
(NCH2); FTIR nmax/cm-1 (KBr): 3565, 3209, 2938, 2838, 1693, 1586,
acid 19f. Physical characteristics: yellow solid; Yield: 138 mg, 58%;
Mp: 211e214 ꢀC; 1H (DMSO‑d6)
d
7.85 (1H, s, 2-CH), 7.00 (1H, s, 4-
CH), 6.89 (1H, s, 4-CH), 6.82 (1H, d, J ¼ 8.0 Hz, ArH), 6.75 (2H, d,
1557, 1511, 1463, 1418, 1321, 1254, 1168, 1142, 1112, 1024, 868, 815,
J ¼ 8.0, ArH), 5.57 (1H, br, ArOH), 4.75 (2H, s, NCH2), 3.76 (3H, s,
766, 656, 628, 601, 534; HRMS (ESI-TOF) m/z: [MþH]þ Calcd for
ArOCH3); 13C NMR (NMR (DMSO‑d6)
d
166.7 (C]O), 147.6 and 146.5
C13H17N4O3 277.1295, found 277.1260.
(ArCOCH3 and ArCOH), 139.3 (2-C), 133.1 (5-C), 126.2 (ArC), 121.2 (4-
C), 120.4, 115.7, 112.4 (ArC), 55.6 (ArCOCH3), 45.7 (NCH2); FTIR
4.2.6.5. 2-(5-(Benzo[d][1,3]dioxol-6-yl)-1H-imidazol-1-yl)acetohy-
n
max/cm-1 (KBr): 2973, 2930, 2600, 1748, 1604, 1552, 1514, 1358,
drazide 20d. Physical characteristics: pale yellow solid; Yields:
1312, 1280, 1214, 1139, 1109, 1026, 865, 822; HRMS (ESI-TOF) m/z:
211 mg, 90%; Mp: 169e171 ꢀC; 1H NMR (DMSO‑d6)
d 9.33 (1H, s,
[MþH]þ Calcd for C12H13N2O4 249.2421, found 249.2438.
NHNH2), 7.65 (1H, s, 2-CH), 6.84e6.97 (4H, overlapping signals, ArH
and 4-CH), 6.06 (2H, s, ArOCH2O), 4.58 (2H, s, NCH2), 3.42 (2H, s,
4.2.5.8. 2-[5-(3-Methoxyphenyl)-1H-imidazol-1-yl]acetic acid 19g.
NHNH2); 13C NMR (DMSO‑d6)
d
170.9 (C]O), 147.5 and 147.1 (2 x
ArCOCH2O), 139.6 (2-C), 132.7 (5-C), 127.2 (4-C), 126.7, 123.2, 122.0,
108.8 (ArC), 101.3 (ArCOCH2O), 45.7 (NCH2); FTIR max/cm-1 (KBr):
Physical characteristics: yellow solid; Yield: 125 mg, 56%; 1H NMR
(DMSO‑d6)
4-CH), 6.93e6.96 (3H, m, ArH), 4.81 (2H, s, NCH2), 3.76 (3H, s,
ArOCH3);13C NMR (DMSO‑d6)
170.1 (C]O),159.5 (ArCOCH3),140.0
(2-C), 132.7 (5-C), 130.7, 130.0, 126.6 (ArC), 120.3 (4-C), 113.6, 113.4
(ArC), 55.1 (ArCOCH3), 46.9 (NCH2); FTIR max/cm-1 (KBr): 3126,
d
7.83 (1H, s, 2-CH), 7.33e7.37 (1H, m, ArH), 7.09 (1H, s,
n
3318, 3210, 3104, 2994, 2929, 1655, 1619, 1561, 1500, 1428, 1344,
1321, 1292, 1231, 1121, 1142, 1040, 968, 934, 918, 880, 874, 841, 833,
809, 759, 665, 642, 579; HRMS (ESI-TOF) m/z: [MþH]þ Calcd. for
d
n
C12H13N4O3 261.0982, found 261.0992.
2946, 2450, 1696, 1609, 1578, 1487, 1394, 1300, 1207, 1168, 1028,
854, 777, 693; HRMS (ESI-TOF) m/z: [MþH]þ Calcd for C12H13N2O3
233.0921, found 233.0922.
4.2.6.6. 2-[5-(4-tert-Butylphenyl)-1H-imidazol-1-yl]acetohydrazide
20e. Physical characteristics: pale yellow solid; Yields: 228 mg,
93%; Mp: 178e180 ꢀC; 1H NMR (DMSO‑d6)
d 9.36 (1H, s, NHNH2),
4.2.6. Synthesis of 2-(5-aryl-1H-imidazol-1-yl)acetohydrazide
4.2.6.1. General synthetic procedure. Ethyl 2-(5-aryl-1H-imidazol-
1-yl)acylate (0.90 mmol) and hydrazine monohydrate (2.70 mmol)
and MeOH (5 ml) were placed in a 10 ml microwave vessel
equipped with a magnetic stirrer bar. The cap was then fitted and
the resulting mixture was microwave irradiated at a set tempera-
ture of 75 ꢀC for 30 min. After completion of the reaction, the
7.69 (1H, s, 2-CH), 7.44 (2H, d, J ¼ 8.0 Hz, ArH), 7.31 (2H, d, J ¼ 8.0 Hz,
ArH), 6.97 (1H, s, 4-CH), 4.61 (2H, s, NCH2), 4.45 (2H, brs, NHNH2),
1.30 [9H, s, C(CH3)3]; 13C NMR (DMSO‑d6)
d
166.6 (C]O), 150.2
[ArCC(CH3)3], 139.9 (2-C), 132.7, 127.9, 127.0, 126.7, 125.6 (ArC), 45.8
(NCH2), 34.4 [ArCC(CH3)3], 31.1 [ArCC(CH3)3]; FTIR max/cm-1
n
(KBr): 3335, 3220, 3062, 2957, 2865, 1663, 1603, 1589, 1501, 1478,
1382, 1362, 1296, 1274, 1228, 1116, 992, 964, 913, 842, 828, 783, 740,