Lewis Acid Catalyst Free Synthesis of Substituted Imidazoles in 2,2,2-Trifluoroethanol

Supporting Information

Lewis acid catalyst free synthesis of substituted imidazoles in 2,2,2-trifluoroethanol

Samad Khaksar ● Mandana Alipour

Chemistry Department, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran

Typical experimental procedure: Benzil (1 mmol), aldehyde (1 mmol) and ammonium acetate (2 mmol) were dissolved in TFE (2 mL) and was stirred at reflux until complete dissolution of the reagents was observed. After 10-15 min the precipitation of light-yellow crystals occurred gradually and precipitation continued for 5 h. The mixture was cooled to room temperature and the precipitate filtered and the crude product was purified by recrystallization from ethanol to yield the highly pure 2,4,5-trisubstituted imidazoles. The physical data (mp, IR, NMR) of known compounds were found to be identical with those reported in the literature [34]. Spectroscopic data for selected examples are shown below.

2,4,5-Triphenyl-1H-imidazole (Table 1, entry 1); mp 267–269 °C. FTIR (KBr): 3455, 2852, 1636, 1490 cm-1; 1H NMR (400 MHz, DMSO-d6): δ= 7.22–7.56 (m, 13H), 8.09 (d, J=7.8 Hz, 2H), 12.69 (s, 1H), 13C NMR(100 MHz, DMSO-d6): δ= 125.3, 126.5, 127.3, 127.8, 128.3, 128.5, 128.6, 128.7, 130.4, 131.4, 135.2, 137.2, 146.6.

2-(4-Chlorophenyl)-4,5-diphenyl-1H-imidazole (Table 1, entry 2); mp 262–264 °C. FTIR (KBr): 3452, 3065, 1635, 1323 cm-1; 1H NMR (400 MHz, DMSO-d6): δ= 7.23–7.56 (m, 12H), 8.12 (d, J=8.1 Hz, 2H), 12.78 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ= 116.3, 123.3, 125.2, 125.5, 126.4, 127.1, 127.4, 128.5, 129.2, 129.9, 130.3, 146.3.

2-(2-Chlorophenyl)-4,5-diphenyl-1H-imidazole (Table 1, entry 3); mp 191–193 °C. FTIR (KBr): 3440, 3065, 2955, 1610 cm-1; 1H NMR (400 MHz, DMSO-d6): δ= 7.03 (d, J=7.7 Hz, 2H), 7.20–7.50 (m, 10H), 8.01 (d, J=7.7 Hz, 2H), 12.40 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ= 114.1, 123.2, 126.5, 126.8, 127.1, 127.3, 127.8, 128.1, 128.2, 128.3, 128.4, 145.6.

2-(2,4-Dichlorophenyl)-4,5-diphenyl-1H-imidazole (Table 1, entry 4); mp 175–178 °C. FTIR (KBr): 3060, 2930, 1598, 1475 cm-1; 1H NMR (400 MHz, DMSO-d6): δ= 7.20–7.55 (m, 12H), 7.85 (s, 1H), 12.65 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ= 126.3, 127.2, 127.4, 127.9, 128.1, 128.7, 128.9, 129.8, 131.1, 132.3, 132.6, 133.7, 134.8, 136.9, 143.1.

2-(4-Bromophenyl)-4,5-diphenyl-1H-imidazole (Table 1, entry 5); mp 254–256 ◦C. FTIR (KBr): 3450, 3070, 1615, 1320 cm-1; 1H NMR (400 MHz, DMSO-d6): δ= 7.13–7.50(m, 12H), 8.15 (d, J=8.1 Hz, 2H), 12.68 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ=116.2, 123.2, 125.1, 125.5, 126.6, 127.1, 127.2, 128.4, 129.1, 129.6, 130.5, 146.1.

2-(4-Fluorophenyl)-4,5-dipheny-limidazole (Table 1, entry 6); mp 260–262 ◦C. FTIR (KBr): 3067, 3033, 1609,1494, 1454cm-1; 1H NMR (400 MHz, DMSO-d6): δ= 7.55–7.21(m, 12H), 8.12 (d, J = 2.1 Hz, 1H), 8.14 (d, J = 2.0 Hz, 1H), 12.69 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ= 116.3, 123.3, 125.2, 125.5, 126.4, 127.1, 127.4, 128.5, 129.2, 129.9, 130.3, 146.3.

2-(4-Nitrophenyl)-4,5-diphenyl-1H-imidazole (Table 1, entry 7); mp 199–201 °C. FTIR (KBr): 3402, 2928,1598,1519,1346 cm-1; 1H NMR(400 MHz, DMSO-d6): δ= 7.42-8.01(m, 14H), 12.82 (s, 1H); 13C NMR(100 MHz, DMSO-d6): δ= 118.5, 122.3, 125.2, 125.4, 126.1, 127.1, 127.4, 127.8, 128.5, 129.7, 130.6, 131.6, 143.6, 148.9.

2-(3-Nitrophenyl)-4,5-diphenyl-1H-imidazole (Table 1, entry 8); mp 264-266 оC; FT-IR (KBr): 1349, 1524, 1590, 1650, 3452 cm–1; 1H NMR(400 MHz, DMSO-d6): δ= 7.32–7.53 (m, 10H), 7.80 (d, J=7.8 Hz, 1H), 8.22 (d, J=7.8 Hz, 1H), 8.54 (d, J=7.5 Hz, 1H), 8.90 (s, 1H), 12.90 (s, 1H); 13C NMR(100 MHz, DMSO-d6): δ= 119.2, 123.6, 127.3, 128.4, 128.7, 130.4, 131.2, 132.8, 143.4, 148.5.

4,5-Diphenyl-2-p-tolyl-1H-imidazole (Table 1, entry 9); mp 233–235 °C. FTIR (KBr, cm-1): 3449, 3034, 1611, 1495, 1320 cm -1; 1H NMR (400 MHz, DMSO-d6): δ= 2.35 (s, 3H), 7.21–7.54 (m,12H), 7.98 (d, J=7.8 Hz, 2H), 12.59 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ=20.8, 125.1, 126.4, 127.1, 127.6, 127.9, 128.1, 128.3, 128.6, 129.2, 131.1, 135.2, 136.9, 137.6, 145.6.

2-(4-Methoxyphenyl)-4,5-diphenyl-1H-imidazole (Table 1, entry 10); mp 220–223 °C. FTIR (KBr): 3420, 3029, 2956, 1620, 1495 cm-1; 1HNMR(400 MHz, DMSO-d6): δ= 3.82 (s, 3H), 7.05 (d, J=8.4 Hz, 2H), 7.50–7.33(m, 10H), 8.03 (d, J=8.1 Hz, 2H), 12.50 (s, 1H); 13C NMR (100MHz, DMSO-d6): δ= 55.2, 114.1, 123.1, 125.1, 126.8, 127.7, 128.3, 128.4, 129.3, 131.1, 135.2, 136.9, 137.6, 145.7, 159.5.

2-(3,4-Dimethoxyphenyl)-4,5-diphenyl-1H-imidazole (Table 1, entry 11); mp 210-212 °C; FTIR (KBr): 3431, 2988, 2893, 2465, 1636, 1216 cm-1; 1HNMR(400 MHz, DMSO-d6): δ= 3.85 (s, 6H), 6.95 (d, 1H), 7.28 - 7.61 (m, 10H), 8.05 (d, 2H, J = 8.7 Hz), 12.48 (s, 1H); 13C NMR (100MHz, DMSO-d6): δ= 56.2, 112.3, 115.8, 120.8, 124.2, 133.1, 127.5, 127.5, 128.8, 128.9, 129.2, 129.3, 129.5, 144.8, 147.6, 150.3.

2-(2-furyl)-4,5-diphenyl-1H-imidazole (Table 1, entry 12); mp 235-237 °C; FTIR (KBr): 3316, 2993, 1660,1210 cm-1; 1HNMR(400 MHz, DMSO-d6): δ= 7.46-7.58 (m, 4 H), 7.15-7.6 (m,10 H), 11.21 (s, 1H); 13C NMR (100MHz, DMSO-d6): δ= 108.5, 112.3, 118.2, 123.4, 124.1, 127.1, 127.4, 127.8, 128.5, 129.7, 130.6, 138.6, 140.2, 143.6, 148.9.

2-(4-Bromo-phenyl)-4,5-di-p-tolyl-1H-imidazole (Table 1 entry 13); m p 213-215 °C; FTIR (KBr): 3432, 2978, 2465, 1638,1216 cm-1; 1HNMR(400 MHz, DMSO-d6): δ= 2.35 (s, 6H), 7.11-7.15 (m, 4H), 7.42-7.46 (m, 4H), 7.54-7.58 (d, 2H), 8.02-8.06 (d, 2H), 12.78 (s, 1H); 13C NMR (100MHz, DMSO-d6): δ= 19.4, 119.8, 125.4, 126.1, 127.3, 129.8, 134.7, 142.8.

2-Phenyl-4, 5-di-p-tolyl-1H-imidazole (Table 1, entry 14). mp. 252-254 °C; FTIR (KBr): 3430, 2990, 2460, 1638 cm-1; 1HNMR(400 MHz, DMSO-d6): δ= 2.34 (s, 6H), 7.12-7.18 (m, 8H), 7.33-7.38(m, 5H), 12.50 (s, 1H); 13C NMR (100MHz, DMSO-d6): δ= 19.5, 124.2, 126.5, 126.8, 127.2, 127.6, 128.8, 129.1, 128.1, 135.2.

4,5-Di(4-chlorophenyl)-2-phenyl-1H-imidazole(Table 1, entry 15): mp 175–178 °C. FTIR (KBr): 3060, 2930, 1598, 1475; 1HNMR(400 MHz, DMSO-d6): δ= 7.40 (d, J = 8.0 Hz, 1H), 7.45 -7.54 (m, 10H), 8.09 (d, J = 8.0 Hz, 2H), 12.74 (s, 1H); 13C NMR (100MHz, DMSO-d6): δ= 125.7,128.3, 129.1, 129.3, 130.5, 131.8, 132.3, 135.6, 146.5.

4,5-Di(furan-3-yl)-2-phenyl-1H-imidazole (Table 1, entry 16): mp 198–200 °C. FTIR (KBr): 3410, 3028, 2955, 1610, 1500 cm-1; 1HNMR(400 MHz, DMSO-d6): δ=6.30–6.32 (m, 2H), 6.80 (d, J = 3.3 Hz, 2H), 7.12–7.50 (m, 5H), 7.60–7.76 (m, 2H), 11.65 (s, 1H); 13C NMR (100MHz, DMSO-d6): δ= 107.5, 125.5, 128.1, 129.1, 142.3, 146.3, 150.1, 175.8.

2-(4-Phenyl)-1,4,5-triphenyl-1H-imidazole (Table 2, entry 1); mp, 220-222 °C; FTIR (KBr): 1595, 1572, 1495 cm-1; 1HNMR(400 MHz, DMSO-d6): δ= 7.24–7.47 (m, 20H); 13C NMR (100MHz, DMSO-d6): δ= 124.1, 124.5, 125.1, 126.9,128.3, 129.1, 130.3, 130.6, 132.9, 134.3, 136.8, 139.0, 139.2, 139.5, 139.8, 140.1, 144.6.

2-(4-Chlorophenyl)-1,4,5-triphenyl-1H-imidazole (Table 2, entry 2); mp 157–159 ◦C; FTIR (KBr): 3056, 1596, 1516, 1440 cm-1; 1HNMR(400 MHz, DMSO-d6): δ= 7.16–7.42 (m, 17H), 7.93-7.95 (m, 2H); 13C NMR (100MHz, DMSO-d6): δ= 122.2, 124.1, 124.5, 126.3, 127.2, 127.8, 128.3, 128.5, 128.6, 128.8, 128.9, 129.1, 129.2, 129.4, 129.5, 130.2, 131.1, 132.4, 134.1, 136.3, 136.1, 140.1, 144.2, 147.1.

1,4,5-Triphenyl-2-p-tolyl-1H-imidazole (Table 2, entry 3); mp 181–183 ◦C; FTIR (KBr): 3040, 2922, 1660, 1590 cm-1; 1HNMR(400 MHz, DMSO-d6): δ= 2.32 (s, 3H), 7.04–7.32 (m,17H), 7.62 (d, J=7.2 Hz, 2H); 13C NMR (100MHz, DMSO-d6): δ= 21.2, 126.1, 126.9, 127.6, 127.8, 128.1, 128.2, 128.5, 128.8, 129.1, 130.5, 130.7, 131.2, 133.9, 137.2, 138.3,147.4.

2-(4-Nitrophenyl)-1,4,5-triphenyl-1H-imidazole (Table 2, entry 4); mp 191–193 °C. FTIR (KBr): 3054, 1595, 1514, 1340 cm-1; 1HNMR(400 MHz, DMSO-d6): δ= 7.04–7.56 (m, 17H), 8.10 (d, J=8.7 Hz, 2H); 13C NMR (100MHz, DMSO-d6): δ= 123.5, 124.1, 124.2, 127.2, 127.9, 128.2, 128.3, 128.4, 128.5, 128.6, 128.8, 129.2, 129.3, 129.4, 129.6, 129.9, 131.2, 132.4, 133.5, 136.5, 137.1, 139.3, 143.3, 147.4.

1-Benzyl-2,4,5-triphenyl-1H-imidazole (Table 2, entry 5); mp 163–165 °C.FTIR (KBr): 3055, 2926, 1610 cm-1; 1HNMR(400 MHz, DMSO-d6): δ=5.10(s, 2H), 6.82 (d, J=7.5 Hz, 2H), 7.14–7.40 (m, 14H), 7.53–7.63 (m, 4H); 13C NMR (100MHz, DMSO-d6): δ=48.1, 126.2, 126.4, 126.8, 127.3, 128.3, 128.5, 128.6, 128.8, 128.9, 129.5, 130.5, 130.8, 131.6, 132.7, 135.1, 137.3, 138.5,148.2.

1-Benzyl-2-(4-chlorophenyl)-4,5-diphenyl-1H-imidazole (Table 2, entry 6); IR (KBr): 3095, 3015, 2980, 1595, 1450, 1350 cm-1; 1HNMR(400 MHz, DMSO-d6): δ= 5.13 (s, 2H), 6.84 (d, J= 6.0 Hz, 2H), 7.20-7.42 (m, 11H), 7.65 (t, J= 7.3 Hz, 4H); 13C NMR (100MHz, DMSO-d6): δ= 48.5, 126.5, 126.9, 127.4, 128.2, 128.5, 129.1, 129.2, 129.3, 129.8, 130.7, 130.9, 131.4, 134.8, 136.1, 137.8, 147.2.

1-Benzyl-2-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazole (Table 2, entry 7); mp 164–165 °C. FTIR (KBr): 3045, 1605, 1450, 1345 cm-1; 1HNMR(400 MHz, DMSO-d6): δ= 3.81 (s, 3H), 5.08 (s, 2H), 6.78–6.90 (m, 4H), 7.10–7.29 (m, 11H), 7.55 (d, J=7.8 Hz, 4H); 13C NMR (100MHz, DMSO-d6): δ= 48.2, 56.2, 113.5, 124.3, 125.9, 126.4, 126.7, 127.2, 127.8, 128.5, 128.7, 129.1, 130.1, 130.3, 130.9, 131.2, 134.5, 138.1, 147.7, 159.8.

1-Benzyl-2-(4-cyanophenyl)-4,5-diphenyl-1H-imidazole (Table 2, entry 8); mp 207–209 °C. FTIR (KBr): 3095, 3005, 2980, 2210, 1600, 1480, 1455cm-1; 1HNMR(400 MHz, DMSO-d6): δ= 5.15 (s, 2H), 6.86-6.88 (m, 2H), 7.19-7.45(m, 11H), 7.59-7.61 (m, 2H), 7.69 (d, 2H, J = 8.4 Hz), 7.84 (d, 2H, J = 8.4 Hz); 13C NMR (100MHz, DMSO-d6): δ= 48.8, 113.6, 119.0, 127.2, 127.5, 128.3, 128.6, 129.3, 129.4, 129.5, 129.7, 130.8, 131.4, 131.9, 133.1, 134.4, 135.8, 137.4, 139.8.