All the solvents and reagents for the preparation of extracts, chemical synthesis and biological assays were obtained from Sigma Aldrich. The chemical reactions were monitored by using F254 silica gel TLC plates (E. Merck) using ceric ammonium sulphate and UV torch for the detection of spots. All the compounds were purified by column chromatography on silica gel (60–120 mesh). 1H NMR and 13C NMR spectra (with chemical shifts expressed in δ and coupling constants in Hertz) were recorded on Bruker DPX 400 instrument using CDCl3 as the solvent with TMS as internal standard. High resolution mass spectra (HRMS) were recorded on Agilent Technologies 6540 instrument and IR recorded on an FT-IR Bruker (270–30) spectrophotometer. Melting points of compounds were recorded on Buchi melting point apparatus.
General procedure for synthesis triazolyl derivatives (15a to 20a)
Compound 2 (3 mmol) and different freshly prepared organic azides (3 mmol) were sonicated in 10 ml of a 2:1 water:t-butanol mixture with sodium ascorbate (0.3 mmol, 300 μL of freshly prepared 1 M solution in water) followed by copper (II) sulfate pentahydrate (0.03 mmol, in 100 μl of water). The reaction mixture was extracted with ethyl acetate (30x3 ml) and the combined organic layer was dried over sodium sulphate and purified through column chromatography to give pure products in excellent yields of 85–90 %.
5-((1-(2-Nitrophenyl)-1H-1,2,3-triazol-4-yl)methoxy)juglone 15a
Yellow liquid; Yield: 87 %; 1H NMR (400 MHz, CDCl3) δ: 1H NMR (CDCl3, 400 MHz) δ: 8.07 (d, J = 8.0 Hz, 1H), 7.96 (s, 1H), 7.80 (t, J = 8.0 Hz, 1H), 7.75 (m, 2H), 7.69 (m, 2H), 7.25 (d, J = 8.0 Hz, 1H), 6.92 (2H, m), 4.40 (s, 2H). 13C NMR (126 MHz, CDCl3) δ: 191.02, 185.10, 160.77, 146.47, 144.41, 139.84, 138.89, 136.80, 133.80, 132.01, 130.63, 130.37, 127.62, 125.45, 124.74, 124.21, 119.40, 115.22, 65.25. HR-ESIMS m/z: calculated for C19H12N4O5 [M + H]+ 377.0816, found 377.0859.
5-((1-(3-Nitrophenyl)-1H-1,2,3-triazol-4-yl)methoxy)juglone 15b
Yellowish liquid; Yield: 88 %; 1H NMR (400 MHz, CDCl3) δ: 8.60 (s, 1H), 8.30 (m, 1H), 8.26 (s, 1H), 8.18 (m, 1H), 7.75 (m, 3H), 7.30 (d, J = 8.0 Hz, 1H), 6.98 (m, 2H), 4.24 (s, 2H). 13C NMR (126 MHz, CDCl3) δ: 190.88, 185.21, 161.72, 148.99, 140.11, 138.92, 137.86, 136.97, 132.33, 131.01, 125.84, 124.74, 123.08, 120.59, 120.59, 120.11, 115.62, 115.01, 65.44. HR-ESIMS m/z: calculated for C19H12N4O5 [M + H]+ 377.0816, found 377.0863.
5-((1-(4-Nitrophenyl)-1H-1,2,3-triazol-4-yl)methoxy)juglone 15c
Yellow liquid; Yield: 88 %; 1H NMR (400 MHz, CDCl3) δ: 8.44 (d, J = 9.0 Hz, 2H), 8.29 (s, 1H), 7.98 (d, J = 9.0 Hz, 2H), 7.81 (m, 2H), 7.29 (d, J = 8.0 Hz, 1H), 6.97 (2H, m), 4.29 (s, 2H). 13C NMR (126 MHz, CDCl3) δ: 190.60, 184.34, 161.65, 147.61, 147.12, 141.24, 139.91, 138.88, 136.80, 132.05, 125.58, 125.58, 124.04, 120.56, 120.30, 120.30, 119.41, 115.02, 59.81. HR-ESIMS m/z: calculated for C19H12N4O5 [M + H]+ 377.0816, found 377.0861.
5-((1-(2-Cyanophenyl)-1H-1,2,3-triazol-4-yl)methoxy)juglone 16a
Yellowish liquid; Yield: 89 %; 1H NMR (400 MHz, CDCl3) δ: 8.35 (s, 1H), 7.86 (m, 3H), 7.80 (m, 2H), 7.63 (m, 1H), 7.30 (d, J = 8.0 Hz, 1H), 6.97 (2H, m), 4.23 (s, 2H). 13C NMR (126 MHz, CDCl3) δ: 190.62, 184.44, 161.68, 146.69, 140.10, 138.92, 138.68, 136.82, 134.39, 134.39, 132.06, 129.46, 124.66, 125.37, 123.15, 119.49, 115.70, 115.20, 65.12. HR-ESIMS m/z: calculated for C20H12N4O3 [M + H]+ 357.0917, found 357.1002.
5-((1-(3-Cyanophenyl)-1H-1,2,3-triazol-4-yl)methoxy)juglone 16b
Yellow liquid; Yield: 85 %; 1H NMR (400 MHz, CDCl3) δ: 8.35 (m, 1H), 8.25 (s, 1H), 8.16 (m, 1H), 7.80 (m, 2H), 7.65 (m, 1H), 7.68 (t, J = 8.2 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 6.92 (m, 2H), 4.25 (s, 2H). 13C NMR (126 MHz, CDCl3) δ: 190.65, 184.64, 162.04, 147.10, 146.61, 141.20, 139.92, 138.87, 136.57, 132.00, 125.51, 125.51, 124.77, 120.55, 120.25, 119.99, 114.82, 120.25, 65.31. HR-ESIMS m/z: calculated for C20H12N4O3 [M + H]+ 357.0917, found 357.0989.
5-((1-(4-Cyanophenyl)-1H-1,2,3-triazol-4-yl)methoxy)juglone 16c
Yellow liquid; Yield: 95 %; 1H NMR (400 MHz, CDCl3) δ: 8.20 (s, 1H), 7.92 (d, J = 8.8 Hz, 2H), 7.86 (d, J = 8.8 Hz, 2H), 7.82 (m, 2H), 7.34 (d, J = 8.0 Hz, 1H), 6.99 (m, 2H), 4.23 (s, 2H). 13C NMR (126 MHz, CDCl3) δ: 191.09, 185.21, 161.88, 147.48, 140.47, 139.95, 133.95, 138.99, 136.97, 133.95, 131.88, 124.52, 120.43, 120.43, 120.40, 120.02, 117.71, 115.77, 65.36. HR-ESIMS m/z: calculated for C20H12N4O3 [M + H]+ 357.0917, found 357.1003.
5-((1-(2-Methoxyphenyl)-1H-1,2,3-triazol-4-yl)methoxy)juglone 17a
Yellow liquid; Yield: 89 %; 1H NMR (400 MHz, CDCl3) δ: 8.2 (s, 1H), 7.80 (m, 2H), 7.77 (d, J = 8.0 Hz, 1H), 7.42 (m, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.10 (m, 2H), 6.93 (m, 2H), 4.22 (s, 2H), 3.60 (s, 3H). 13C NMR (126 MHz, CDCl3) δ: 191.08, 184.82, 162.34, 151.10, 139.98, 138.73, 136.49, 131.71, 130.05, 126.33, 125.68, 125.52, 125.42, 121.35, 121.21, 119.88, 115.38, 112.18, 65.32, 55.60. HR-ESIMS m/z: calculated for C20H15N3O4 [M + H]+ 362.1071, found 362.1133.
5-((1-(3-Methoxyphenyl)-1H-1,2,3-triazol-4-yl)methoxy)juglone 17b
Yellow liquid; Yield: 90 %; 1H NMR (400 MHz, CDCl3) δ: 8.10 (s, 1H), 7.74 (m, 2H), 7.38 (m, 2H), 7.25 (m, 1H), 7.22 (d, J = 8.0 Hz, 1H), 6.93 (m, 2H), 6.97 (m, 1H), 4.23 (s, 2H), 3.62 (s, 3H). 13C NMR (126 MHz, CDCl3) δ: 189.92, 183.80, 161.34, 145.96, 139.25, 137.91, 137.12, 136.22, 132.05, 130.49, 124.44, 120.91, 119.76, 119.04, 115.18, 114.49, 112.29, 106.21, 65.41, 55.62. HR-ESIMS m/z: calculated for C20H15N3O4 [M + H]+ 362.1071, found 362.1129.
5-((1-(4-Methoxyphenyl)-1H-1,2,3-triazol-4-yl)methoxy)juglone 17c
Yellow liquid; Yield: 88 %; 1H NMR (400 MHz, CDCl3) δ: 8.05 (s, 1H), 7.79 (m, 2H), 7.66 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 8.0 Hz, 1H), 7.05 (d, J = 8.8 Hz, 2H), 6.97 (m, 2H), 4.59 (s, 2H), 3.88 (s, 3H). 13C NMR (126 MHz, CDCl3) δ: 190.75, 184.88, 161.37, 159.77, 146.19, 139.83, 138.19, 136.77, 132.14, 130.53, 124.91, 122.21, 122.21, 121.18, 119.53, 115.31, 114.74, 114.74, 65.42, 55.62. HR-ESIMS m/z: calculated for C20H15N3O4 [M + H]+ 362.1071, found 362.1131.
5-((1-(2-Bromophenyl)-1H-1,2,3-triazol-4-yl)methoxy)juglone 18a
Yellowish liquid; Yield: 88 %; 1H NMR (400 MHz, CDCl3) δ: 8.07 (s, 1H), 7.77 (m, 3H), 7.56 (m, 1H), 7.49 (m, 1H), 7.39 (m, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.03 (m, 2H), 4.25 (s, 2H). 13C NMR (126 MHz, CDCl3) δ: 190.88, 184.72, 161.70, 145.28, 140.20, 138.92, 136.83, 136.71, 133.94, 132.19, 131.07, 128.48, 128.20, 124.73, 124.74, 119.40, 118.48, 115.22, 65.35. HR-ESIMS m/z: calculated for C19H12BrN3O3 [M + H]+ 410.0070; [M + 2]+ 411.0042, found 410.0182, 411.0138.
5-((1-(3-Bromophenyl)-1H-1,2,3-triazol-4-yl)methoxy)juglone 18b
Yellow liquid; Yield: 88 %; 1H NMR (400 MHz, CDCl3) δ: 8.06 (s, 1H), 7.81 (m, 2H), 7.42 (m, 2H), 7.30 (m, 1H), 7.18 (d, J = 8.0 Hz, 1H), 6.95 (m, 2H), 7.01 (m, 1H), 4.30 (s, 2H). 13C NMR (126 MHz, CDCl3) δ: 190.12, 183.38, 161.52, 145.10, 138.71, 137.08, 137.15, 136.25, 132.12, 130.55, 125.02, 120.18, 119.55, 118.82, 115.51, 114.76, 112.30, 106.15, 65.77. HR-ESIMS m/z: calculated for C19H12BrN3O3 [M + H]+ 410.0070, [M + 2]+ 411.0042, found 410.0179, 411.0134.
5-((1-(3-Bromophenyl)-1H-1,2,3-triazol-4-yl)methoxy)juglone 18c
Yellow liquid; Yield: 89 %; 1H NMR (400 MHz, CDCl3) δ: 8.09 (s, 1H), 7.82 (m, 2H), 7.67 (d, J = 9.1 Hz, 2H), 7.63 (d, J = 9.1 Hz, 2H), 7.31 (d, J = 8.0 Hz, 1H), 6.92 (m, 2H), 4.23 (s, 2H). 13C NMR (126 MHz, CDCl3) δ: 190.89, 184.65, 161.70, 146.15, 139.92, 138.98, 137.15, 135.12, 132.02, 131.91, 131.91, 124.25, 121.28, 120.80, 120.80, 119.59, 119.53, 115.22, 64.40. HR-ESIMS m/z: calculated for C19H12BrN3O3 [M + H]+ 410.0070, [M + 2]+ 411.0042, found 410.0180, 411.0140.
5-((1-Phenyl-1H-1,2,3-triazol-4-yl)methoxy)juglone 19a
Yellow liquid; Yield: 90 %; 1H NMR (400 MHz, CDCl3) δ: 8.10 (s, 1H), 7.76 (m, 4H), 7.54 (m, 2H), 7.44 (m, 1H), 7.29 (d, J = 8.0 Hz, 1H), 6.99 (m, 2H), 4.24 (s, 2H). 13C NMR (126 MHz, CDCl3) δ: 190.90, 184.45, 161.79, 146.50, 139.98, 138.92, 137.19, 136.86, 132.35, 129.75, 129.75, 128.68, 124.74, 120.83, 120.48, 120.48, 119.40, 115.27, 65.55. HR-ESIMS m/z: calculated for C19H13N3O3 [M + H]+ 332.0965, found 332.1018.
5-((2-Chlorophenyl-1H-1,2,3-triazol-4-yl)methoxy)juglone 20a
Yellow liquid; Yield: 89 %; 1H NMR (400 MHz, CDCl3) δ: 8.10 (s, 1H), 7.76 (m, 3H), 7.42 (m, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.12 (m, 2H), 6.95 (m, 2H), 4.22 (s, 2H). 13C NMR (126 MHz, CDCl3) δ: 190.98, 185.04, 161.68, 145.48, 140.04, 138.92, 136.90, 134.98, 132.12, 130.79, 130.67, 128.46, 127.94, 127.75, 124.69, 124.38, 119.14, 115.18, 65.32. HR-ESIMS m/z: calculated for C19H12ClN3O3 [M + H]+ 366.0575, found 366.0638.