Electronic Supplementary Data
Catalytic synthesis of benzimidazole derivatives over modified forms of zirconia
T E Mohan Kumara, b, S Z Mohamed Shamshuddina, b, *, Venkatesha, b & S Reena Sarithaa, b
aChemistry Research Laboratory, HMS Institute of Technology, NH4, Kyathsandra, Tumakuru 572 104, Karnataka, India
bResearch and Development Center, Bharathiar University, Coimbatore 572 104, India Email: mohamed.shamshuddin@gmail.com
No. Contents Pg No.
1 Table S1 – Synthesis of various benzimidazole derivatives over Mo(VI)/ZrO2 solid acid catalyst.
[React. cond.: Reaction temp. = 80 °C; solvent = 20 mL ethanol; molar ratio of aldehyde: diamine
= 1:1; weight of the MZ catalyst = 0.06 g]
2
2 Table S2 – Effect of reusability on the yield of benzimidazoles over ZrO2, Mo(VI)/ZrO2 and Pt-SO42-/ZrO2. [React. cond.: React. temp. = 80 °C; react. time = 3 h; solvent = 20 mL ethanol;
molar ratio of 3,5-dimethyl-benzaldehyde: 4,5-dimethyl-benzene-1,2-daimine = 1:1; weight of solid acid catalyst = 0.06 g]
5
3 Fig. S1 – PXRD pattern of pure zirconia calcined at 300 oC 5
4 Appendix S1 5
Table S1 – Synthesis of various benzimidazole derivatives over Mo(VI)/ZrO2 solid acid catalyst. [React. cond.: Reaction temp. = 80 °C; solvent = 20 mL ethanol; molar ratio of aldehyde: diamine = 1:1; weight of the MZ catalyst = 0.06 g]
Entry Aldehyde Diamine Product Time
(h)
Yield (%)
1
O H
NH2NH2
N H N
3.0 53.1
2
O H
NH2NH2
N N
3.0 22.2
3
O H
NH2NH2 O
N H N
O
N N H
O and
1.0 82.1
4
O H
NH2NH2 N
H
N 1.0 59.3
5
O H
NH2NH2 N
N 1.0 31.6
6
O H
NH2NH2 N
H N
N NH and
1.0 72.4
7
O H
O
NH2
NH2 N
H N
O
1.0 84.2
8 O H
Cl
Cl
NH2
NH2
NH N
Cl
Cl
N
NH Cl
and
1.0 98.1
9 O H Cl
Cl
NH2
NH2 O
NH N
Cl
Cl
O
N NH
Cl
Cl
O and
2.0 70.2
10
O H
F F F
F
NH2 NH2
F N
H N
F
F F F F
N NH
F
F F F F
and
2.0 82.6
11
O H
F F F
F
NH2
NH2 N
H N
F
F F F
1.0 93.7
12
O H
F F F
F
NH2
NH2
O N
H N
F F
F O F
NH
F and
2.0 91.1
Table S2 – Effect of reusability on the yield of benzimidazoles over ZrO2, Mo(VI)/ZrO2 and Pt-SO42-
/ZrO2. [React. cond.: React. temp. = 80 °C; react. time = 3 h; solvent = 20 mL ethanol; molar ratio of 3,5-dimethyl- benzaldehyde: 4,5-dimethyl-benzene-1,2-daimine = 1:1; weight of solid acid catalyst = 0.06 g]
Reaction cycle (no.)
Z MZ Pt-SZ
Yield (%) of Product-A
Yield (%) of Product-B
Yield (%) of Product-A
Yield (%) of Product-B
Yield (%) of Product-A
Yield (%) of Product-B
1 (Fresh) 24.1 11.3 53.1 22.2 61.6 26.2
2 23.9 11.2 52.6 22.0 60.1 25.6
3 23.6 11.0 52.1 21.7 58.2 25.1
4 23.2 10.8 51.7 21.5 56.4 24.2
5 23.0 10.5 51.2 21.2 53.1 23.1
Product-A = 2-(3,5-dimethylphenyl)-5,6-dimethyl-1H-benzo[d]imidazole.
Product-B = 1-(3,5-dimethylbenzyl)-2-(3,5-dimethylphenyl)-5,6-dimethyl-1H-benzo[d]imidazole.
Fig. S1 – PXRD pattern of pure zirconia calcined at 300 oC
Appendix S1 – 1H NMR, 13C NMR, LC-MS, HPLC data, physical state and melting point of the synthesized benzimidazole derivatives (Refer to Table 2).
Entry 1:
2-(3,5-dimethylphenyl)-5,6-dimethyl-1H-benzo[d]imidazole
1H NMR (DMSO-d6, 400 MHz): δ (ppm) 2.286 (s, 3H), 2.302 (s, 3H), 2.334 (s, 6H), 7.060 (s, 1H), 7.240 (s, 1H), 7.372 (s, 1H), 7.740 (s, 2H), 12.485 (s, 1H, D2O exchangeable). 13C NMR (DMSO-d6, 100 MHz):
δ (ppm) 20.434, 21.386, 111.697, 119.258, 124.449, 130.182, 130.786, 131.274, 131.391, 133.932, 138.309, 142.965, 150.999. Calculated for C17H18N2 [M+H]+: 251.15, found [M+H]+: 251.1; physical state: off-white solid; melting point: 303-305 °C.
Entry 2:
Calculated for C26H28N2 [M+H]+: 369.23, found [M+H]+: 369.2; physical state: off-white solid; melting point: 185-187 °C.
Entry 3:
2-(3,5-dimethylphenyl)-5-methoxy-1H-benzo[d]imidazole and 2-(3,5-dimethylphenyl)-6-methoxy-1H- benzo[d]imidazole
1H NMR (DMSO-d6, 400 MHz): δ (ppm) 2.339 (s, 6H), 3.775 (d, 3H, J = 7.6 Hz), 6.795 (t, 1H, J = 9.6 Hz), 6.937 (s, 0.5H), 7.073 (d, 1H, J = 4.4 Hz), 7.137 (s, 0.5H), 7.350 (d, 0.5H, J = 8.4 Hz), 7.483 (d, 0.5H, J = 8.8 Hz), 7.727 (d, 2H, J = 7.6 Hz), 12.602 (d, 1H, J = 7.2 Hz, D2O exchangeable). 13C NMR (DMSO-d6, 100 MHz): δ (ppm) 21.394, 55.916, 94.854, 101.866, 111.588, 119.638, 124.387, 130.678, 131.329, 136.085, 138.355, 145.127, 151.278, 156.275. Calculated for C16H16N2O [M+H]+: 253.13, found [M+H]+: 253.1; physical state: light brown solid; melting point: 176-178 °C.
Entry 4:
2-(4-isopropylphenyl)-5,6-dimethyl-1H-benzo[d]imidazole
1H NMR (DMSO-d6, 400 MHz): δ (ppm) 1.223 (d, 6H, J = 7.2 Hz), 2.283 (s, 3H), 2.305 (s, 3H), 2.914- 2.948 (m, 1H), 7.235 (s, 1H), 7.366 (d, 3H, J = 7.6 Hz), 8.023 (d, 2H, J = 8.0Hz), 12.474 (s, 1H, D2O exchangeable). 13C NMR (DMSO-d6, 100 MHz): δ (ppm) 20.441, 24.121, 33.759, 111.666, 119.266, 126.711, 127.199, 128.594, 130.166, 131.290, 133.939, 143.011, 150.356, 150.945. Calculated for C18H20N2 [M+H]+: 265.16, found [M+H]+:265.1; physical state: off-white solid; melting point: 223-225
°C.
Entry 5:
1-(4-isopropylbenzyl)-2-(4-isopropylphenyl)-5,6-dimethyl-1H-benzo[d]imidazole
1H NMR (DMSO-d6, 400 MHz): δ (ppm) 1.118 (d, 6H, J = 7.2 Hz), 1.203 (d, 6H, J = 7.2 Hz), 2.255 (s, 3H), 2.289 (s, 3H), 2.778-2.812 (m, 1H), 2.905-2.939 (m, 1H), 5.453 (s, 2H), 6.871 (d, 2H, J = 8.0 Hz), 7.133 (d, 2H, J = 7.6 Hz), 7.168 (s, 1H), 7.343 (d, 2H, J = 8.0 Hz), 7.599 (d, 2H, J = 8.0 Hz). 13C NMR (CDCl3, 100 MHz): δ (ppm) 20.225, 20.510, 23.803, 23.904, 33.712, 34.014, 48.091, 110.589, 119.893, 125.874, 126.726, 127.021, 127.827, 129.159, 131.282, 131.855, 134.156, 134.768, 141.872, 148.202, 150.511, 153.540. Calculated for C28H32N2 [M+H]+: 397.26, found [M+H]+:397.2; physical state: off- white solid; melting point: 174-176 °C.
Entry 6:
5-(tert-butyl)-2-(4-isopropylphenyl)-1H-benzo[d]imidazole and 6-(tert-butyl)-2-(4-isopropylphenyl)-1H- benzo[d]imidazole
1H NMR (DMSO-d6, 400 MHz): δ (ppm) 1.229 (d, 6H, J = 6.8 Hz), 1.332 (s, 9H), 2.922-2.939 (m, 1H), 7.246 (t, 1H, J = 8.8 Hz), 7.386 (d, 3H, J = 8.0 Hz), 7.526 (d, 0.5H, J = 8.4 Hz), 7.595 (s, 0.5H), 8.033 (d, 2H, J = 4.4 Hz), 12.605 (s, 1H, D2O exchangeable). 13C NMR (DMSO-d6, 100 MHz): δ (ppm) 24.121, 32.101, 33.782, 34.844, 34.960, 107.537, 110.899, 115.245, 118.545, 120.002, 120.660, 126.789, 127.269, 128.501, 133.265, 135.380, 142.283, 144.391, 144.685, 145.653, 150.565, 151.619, 151.812.
Calculated for C20H24N2 [M+H]+: 293.19, found [M+H]+: 293.2; physical state: off-white solid; melting point: 203-205 °C.
Entry 7:
2-(4-methoxy-2-methylphenyl)-5,6-dimethyl-1H-benzo[d]imidazole
1H NMR (DMSO-d6, 400 MHz): δ (ppm) 2.284 (s, 3H), 2.301 (s, 3H), 2.568 (s, 3H), 3.789 (s, 3H), 6.875
160.056. Calculated for C17H18N2O [M+H]+: 267.14, found [M+H]+: 267.1; physical state: off-white solid; melting point: 228-230 °C.
Entry 8:
5-(tert-butyl)-2-(2,5-dichlorophenyl)-1H-benzo[d]imidazole and 6-(tert-butyl)-2-(2,5-dichlorophenyl)- 1H-benzo[d]imidazole
1H NMR (DMSO-d6, 400 MHz): δ (ppm) 1.339 (s, 9H), 7.320 (t, 1H, J = 8.4 Hz), 7.477 (d, 1H, J = 12.8Hz), 7.584 (dd, 2H, J1 = 2.0 Hz, J2 = 8.4 Hz), 7.662 (d, 1H, J = 8.8 Hz), 7.934 (s, 1H), 12.597 (s, 1H, D2O exchangeable). 13C NMR (DMSO-d6, 100 MHz): δ (ppm) 32.062, 35.045, 108.149, 111.619, 115.578, 119.065, 120.552, 121.575, 130.701, 131.127, 131.607, 132.034, 132.382, 132.607, 132.979, 135.117, 141.563, 143.678, 145.157, 146.513, 147.892. Calculated for C17H16Cl2N2 [M+H]+: 319.07, found [M+H]+: 319.0; physical state: off-white solid; melting point: 171-173 °C.
Entry 9:
2-(2,5-dichlorophenyl)-5-methoxy-1H-benzo[d]imidazole and 2-(2,5-dichlorophenyl)-6-methoxy-1H- benzo[d]imidazole
1H NMR (DMSO-d6, 400 MHz): δ (ppm) 3.790 (s, 3H), 6.832-6.855 (m, 1H), 7.026 (s, 0.5H), 7.208 (s, 0.5H), 7.439 (d, 0.5H, J = 8.4 Hz), 7.566 (d, 1.5H, J = 8.8 Hz), 7.653 (d, 1H, J = 9.2 Hz), 7.947 (s, 1H), 12.595 (d, 1H, J = 14.4 Hz, D2O exchangeable). 13C NMR (DMSO-d6, 100 MHz): δ (ppm) 55.932, 94.978, 112.820, 118.135, 120.273, 128.059, 130.531, 130.980, 131.491, 131.855, 132.390, 132.646, 147.443, 156.608. Calculated for C14H10Cl2N2O [M+H]+: 293.02, found [M+H]+: 293.0; physical state:
yellow solid; melting point: 167-169 °C.
Entry 10:
5-fluoro-2-(4-fluoro-2-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole and 6-fluoro-2-(4-fluoro-2- (trifluoromethyl)phenyl)-1H-benzo[d]imidazole
1H NMR (DMSO-d6, 400 MHz): 7.061-7.105 (m, 1H), 7.327 (d, 0.5H, J = 7.6 Hz), 7.460-7.527 (m, 1H), 7.697-7.738 (m, 1.5H), 7.848 (d, 2H, J = 7.2 Hz), 12.882 (s, 1H, D2O exchangeable). 13C NMR (DMSO- d6, 100 MHz): δ (ppm) 98.379, 104.926, 109.985, 110.597, 111.279, 112.735, 114.804, 114.858, 115.059, 115.113, 119.088, 119.839, 120.048, 120.599, 121.815, 124.557, 126.874, 127.269, 129.911, 129.996, 130.228, 130.306, 130.546, 130.624, 130.864, 130.949, 131.894, 135.233, 135.318, 140.532, 144.112, 150.402, 157.886, 160.257, 161.466, 163.945. Calculated for C14H7F5N2 [M+H]+: 299.05, found [M+H]+: 299.3; physical state: off-white solid; melting point: 186-188 °C.
Entry 11:
2-(4-fluoro-2-(trifluoromethyl)phenyl)-5,6-dimethyl-1H-benzo[d]imidazole
1H NMR (DMSO-d6, 400 MHz): δ (ppm) 2.298 (s, 3H), 2.310 (s, 3H), 7.270 (s, 1H), 7.421 (s, 1H), 7.669- 7.710 (m, 1H), 7.797-7.820 (m, 2H), 12.451 (s, 1H, D2O exchangeable). 13C NMR (DMSO-d6, 100 MHz):
δ (ppm) 20.395, 111.852, 114.695, 114.749, 114.951, 115.005, 119.615, 119.715, 119.925, 121.869, 124.596, 127.556, 130.143, 130.228, 130.414, 130.538, 131.855, 133.529, 135.132, 135.218, 142.609, 147.877, 161.241, 163.720. Calculated for C16H12F4N2 [M+H]+: 309.09, found [M+H]+: 309.1; physical
(ppm) 55.932, 94.823, 101.881, 111.914, 113.200, 114.718, 114.765, 114.974, 115.020, 119.150, 119.762, 119.971, 121.877, 124.604, 127.385, 129.492, 129.779, 129.857, 130.097, 130.174, 130.414, 130.492, 130.732, 135.156, 135.241, 135.613, 138.433, 144.716, 147.776, 155.980, 156.662, 161.264, 163.751. Calculated for C15H10F4N2O [M+H]+: 311.07, found [M+H]+: 311.1; physical state: brown solid;
melting point: 80-82 °C.
