6) (40%). For carvacrol compound, 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 4-methyl benzenesulfonate (6.2
mM, 2.01 g) and K2CO3 (15 mM, 2.1 g) were dissolved in DMF (20 mL). Add carvacrol (6.5 mM, 1.0 g) in
DMF (10 mL) and the reaction mixture was stirred at 70–80 °C for 14–16 h. The crushed ice was added and the
compound (11) obtained was extracted by addition of ethyl acetate. The target product was separated by column
chromatography (ethyl acetate: hexane, 3: 7 to 4: 6) to get pure compound (51%).
Synthesis of metronidazole menthol ether (8)
Yellow Solid, Melting point: 135-136 °C; IR (KBr, cm-1) υ: 1449, 1368 (NO2); 1226, 1173 (C-O, ether); 1H
NMR (CDCl3): δ 8.05 (s, 1H, imidazole), 5.0 (t, 2H, N-CH2), 4.7 (t, 2H, CH2-O), 2.7 (t, 1H, O-CH, ring), 2.42
(s, 3H, CH3-imidazole), 2.0 (m, 1H, HC-CH(CH3)2), 1.01 (m, 6 H, CH3-CH-CH3). 13C NMR: δ 155.0 (N-C=N),
130.41 (CH=C-NO2), 127.70 (N-CH=C), 71.59 (-CH-O-C), 50.16 (-CH-CH, ring), 46.86 (CH2-ring), 45.05
(CH2-ring), 40.16 (CH-N), 34.55 (CH2-CH-), 31.65 (CH3-CH), 25.88 (CH3-CH-CH3), 23.16 (CH2-CH2-CH,
menthol), 22.22 (CH2-ring), 21.74 (3 CH3 group of menthol), 16.12 (CH3, imidazole); DEPT-135; 46.76 (N-
CH2), 45.03 (CH2-ring), 34.55 (CH2-CH-), 23.16 (CH2-CH2-CH, menthol) (negative). ESI-MS (m/z): (M+H)
310.2337 Calculated: 310.2125.
Synthesis of metronidazole thymol ether (9)
Brown solid, Melting point: 116-118 °C with decomposition; IR (KBr, cm-1) υ: 1536, 1367 (NO2); 1235, 1188
(C-O, ether); 1H NMR (CDCl3): δ 7.98 (s, 1H, imidazole), 7.02 (d, 1H, aromatic), 6.72 (d, 1H, aromatic), 6.52
(s, 1H, aromatic), 4.72 (t, 2H, O-CH2), 4.23 (t, 2H, N-CH2), 2.87 (m, 1H, CH3-CH-CH3), 2.69 (s, 3H, CH3-
imidazole), 2.23 (s, 3H, H3C-O-aromatic), 1.03 (m, 6H, HC(CH3)2). 13C NMR: δ, 154.58 (C=C-O), 150.76
(CH=C-NO2), 138.09 (O2N-C=C), 136 (CH, aromatic), 133.79 (CH, aromatic), 129.40 (N-CH=C), 126 (CH Ar),
126.79 (CH aromatic), 122.65 (=CH-CH=, aromatic), 112.43 (CH=CH, aromatic), 66.89 (O-CH2), 46.76 (N-
CH2), 26.43 (CH3-CH-CH3), 22.77 (2 CH3 group -CH), 21.24 (CH3-aromatic), 13.78 (CH3, imidazole). DEPT-
135; 66.89 (O-CH2), 46.76 (N-CH2) negative. ESI-MS (m/z): (M+H) 304.1660, calculated: 304.1655.
Synthesis of metronidazole eugenol ether (10)
Yellow solid, Melting point: 96-98°C; IR (KBr, cm-1) υ: 1593, 1366 (NO2); 1260, 1191 (C-O, ether); 1H NMR
(CDCl3): δ 8.06 (s, 1H, imidazole), 6.75 (dd, 3H aromatic), 5.9 (m, 1H, CH=CH2), 5.08 (m, 2H, CH=CH2), 4.77
(m, 2H, O-CH2), 4.32 (m, 2H, N-CH2), 3.78 (s, 3H, OCH3), 3.39 (d, 2H, CH2- aromatic), 2.85 (s, 3H, CH3-
imidazole). 13C NMR: δ 151.91 (N-C=N), 149.45 (C=C-OCH3, aromatic), 146.45 (CH=C-NO2), 145 (O-C=C,
aromatic), 137 (CH2=CH, aliphatic), 136 (CH, aromatic), 134.44 (O2N-C=C), 120.40 (=CH-CH=, aromatic),
115.90 (CH2=CH, aliphatic), 113.88 (CH=CH, aromatic), 112.0 (CH=CH, aromatic), 67.85 (CH2-CH2-O), 55.58
(O-CH3), 47.10 (aromatic-CH2), 39.80 (N-CH2), 13.45 (CH3, imidazole), DEPT-135; 115.90 (CH2=CH,
aliphatic), 67.65 (CH2-CH2-O), 47.10 (aromatic-CH2), 39.80 (N-CH2) all are negative. ESI-MS (m/z): (M+H)
318.1444 calculated: 318.1449.
Synthesis of metronidazole carvacrol ether (11)
Yellow solid, Melting point: 87-89°C with decomposition; IR (KBr, cm-1) υ: 1578, 1360 (NO2); 1254, 1187 (C-
O, ether); 1H NMR (CDCl3): δ 7.98 (s, 1H, imidazole), 6.95 (d, 1H, aromatic), 6.72 (d, 1H, aromatic), 6.50 (s,
1H, aromatic), 4.6 (t, 2H, O-CH2), 4.23 (t, 2H, N-CH2), 2.85 (m, 1H, CH3-CH-CH3), 2.60 (s, 3H, CH3-
imidazole), 1.98 (s, 3H, H3C-O-aromatic), 1.10 (m, 6H, HC(CH3)2). 13C NMR: δ 155.32 (N-C=N), 147.5
(CH=C-NO2), 131.94 (aromatic, CH2), 130 (N-CH=C), 129.80 (CH, aromatic), 122.35 (CH, aromatic), 117.0
(CH, aromatic), 116.39 (CH, aromatic), 110.76 (CH, aromatic), 109.0 (CH, aromatic), 67.1 (CH2-CH2-O), 34.5
(N-CH2), 27.13 (CH3-CH-CH3), 23.50 (2 CH3, carvacrol), 15.0 (CH3, carvacrol), 13.90 (CH3, imidazole). DEPT-
135; 39.80 (N-CH2), 47.10 (aromatic-CH2), 67.65 (CH2-CH2-O), 115.90 (CH2=CH, aliphatic) all are negative.
ESI-MS (m/z): (M+H) 304.1660, calculated: 304.1655.
2.2 Biology
2.2.1 MTT based Anti H. pylori activity
Two strains of H. pylori the ATCC 26695 and H. pylori P12 were screened. Antibacterial activity of the eight
compounds were evaluated by MTT assay as previously described in literature with some modifications[28][29]
Each of the two strains was cultured in heart infusion broth (BHI). Final working solution (optical density 0.2)
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