General
All chemicals were purchased from Aldrich and Merck with high-grade quality and used without any purification. All products were obtained by reaction at reflux in ethanol as solvent. The reactions were monitored by TLC and all yields refer to isolated products. All melting points were obtained by Barnstead Electro thermal 9200 apparatus and are uncorrected. IR spectra were recorded on a Bruker FT-IR Equinax-55 spectrophotometer in KBr with absorption in cm-1. The NMR spectra were recorded on a Varian model UNITY Inova 500 MHz spectrometer (1H: 500 MHz, 13C: 125 MHz) in DMSO-d6 using TMS as an internal standard. Elemental analysis were performed using a Carlo Erba EA 1108 instrument.
Synthesis of compounds 4 and 5 in catalyst-free conditions.
A mixture of aryl glyoxal (1, 1.0 mmol), aryl amine (2, 1.0 mmol), and 2-aminobenzothiazole (3, 1.0 mmol) was stirred in the presence of 5 mL ethanol under reflux conditions for 4-8 hours. The completion of the reaction was monitored by TLC, the solvent was removed under reduced pressure. The crude product was purified by recrystallization from ethanol to yield the highly pure compounds 4 (70-86%), and 5 (68-82%).
N,3-Bis(4-chlorophenyl)benzo[d]imidazo[2,1-b]thiazol-2-amine (4a).
Yellow solid; m.p. 238-239 °C. FT-IR (KBr) ʋ: 3433, 1665, 1585, 1476 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm): 6.60 (s, 1H, CH), 7.02 (d, J = 8.5 Hz, 1H, ArH), 7.26 (d, J = 8.5 Hz, 1H, ArH), 7.40-7.49 (m, 9H, ArH), 7.53-7.60 (m, 5H, ArH), 7.75 (d, J = 8.4 Hz, 3H, ArH), 7.94- 8.00 (m, 5H, ArH), 9.89 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6) δ (ppm): 124.06, 124.88, 129.00, 129.18, 129.22, 129.47, 129.60, 129.68, 129.71, 129.80, 129.84, 129.97, 130.32, 130.50, 131.74, 131.82, 132.35, 132.70, 134.08, 134.13, 134.48, 135.72, 137.26, 138.23, 138.59, 139.59, 140.05, 140.34, 141.53, 141.70, 142.66, 144.63, 153.79, 157.07. Anal. Calcd for C21H13Cl2N3S (410.32): C, 61.47; H, 3.19; N, 10.24. Found: C, 61.08; H, 3.14; N, 10.40.
3-(4-Bromophenyl)-N-(4-chlorophenyl)benzo[d]imidazo[2,1-b]thiazol-2-amine (4b).
Yellow solid; m.p. 233-234 °C. FT-IR (KBr) ʋ: 3449, 1665, 1584, 1475 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm): 6.59 (s, 1H, CH), 7.02 (d, J = 8.6 Hz, 1H, ArH), 7.26 (d, J = 8.5 Hz, 1H, ArH), 7.41 (d, J = 8.5 Hz, 2H, ArH), 7.48 (d, J = 8.5 Hz, 3H, ArH), 7.60 (d, J = 8.2 Hz, 3H, ArH), 7.68 (d, J = 8.8 Hz, 3H, ArH), 7.73 (d, J = 8.2 Hz, 4H, ArH), 7.80- 7.92 (m, 7H, ArH), 9.88 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6) δ (ppm): 124.06, 124.87, 126.31, 127.75, 129.62, 129.68, 129.97, 130.16, 130.21, 130.41, 131.27, 131.84, 131.95, 132.17, 132.43, 132.76, 133.06, 133.27, 133.67, 134.63, 134.80, 135.76, 137.55, 137.96, 138.22, 140.18, 140.75, 141.08, 142.13, 142.43, 145.32, 148.12, 153.69, 157.05. Anal. Calcd for C21H13BrClN3S (454.77): C, 55.46; H, 2.88; N, 9.24. Found: C, 55.94; H, 2.94; N, 9.11.
N-(4-Bromophenyl)-3-(4-chlorophenyl)benzo[d]imidazo[2,1-b]thiazol-2-amine (4c).
Yellow solid m.p. 239-241 °C. FT-IR (KBr) ʋ: 3449, 1665, 1583, 1400 cm-1.1H NMR (500 MHz, DMSO-d6) δ (ppm): 6.62 (s, 1H, CH), 6.96 (d, J = 9.0 Hz, 1H, ArH), 7.35-7.40 (m, 4H, ArH), 7.46 (d, J = 8.5 Hz, 3H, ArH), 7.53-7.62 (m, 8H, ArH), 7.76 (d, J = 8.8 Hz, 3H, ArH), 7.94- 8.00 (m, 5H, ArH), 9.90 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6) δ (ppm): 117.70, 124.31, 125,14, 129.00, 129.22, 129.47, 129.80, 129.85, 130.31, 131.83, 132.59, 132.88, 134.40, 134.47, 134.87, 135.73, 137.20, 137.28, 137.33, 138.39, 138.60, 138.69, 140.28, 140.87, 141.94, 143.39, 144.58, 145.69, 146.45, 148.43, 148.91, 149.14, 155.78, 156.90. Anal. Calcd for C21H13BrClN3S (454.77): C, 55.46; H, 2.88; N, 9.24. Found: C, 55.09; H, 2.80; N, 9.81.
N,3-Bis(4-bromophenyl)benzo[d]imidazo[2,1-b]thiazol-2-amine (4d).
Yellow solid; m.p. 233-235 °C. FT-IR (KBr) ʋ: 3435, 1668, 1585, 1458 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm): 6.60 (s, 1H, CH), 7.35 (d, J = 8.8 Hz, 4H, ArH), 7.40 (d, J = 8.9 Hz, 1H, ArH), 7.60 (d, J = 3.5 Hz, 3H, ArH), 7.62 (d, J = 3.6 Hz, 3H, ArH), 7.67-7.70 (m, 5H, ArH), 7.73- 7.75 (m, 4H, ArH), 7.86-7.88 (m, 3H, ArH), 7.92 (d, J = 8.6 Hz, 1H, ArH), 9.90 (s, 1H, NH).13C NMR (125 MHz, DMSO-d6) δ (ppm): 124.02, 124.32, 125.11, 126.81, 127.33, 129.93, 130.01, 130.37, 130.40, 131.20, 131.34, 131.96, 132.00, 132.11, 132.40, 132.44, 132.68, 132.88, 136.38, 136.76, 137.51, 137.83, 138.48, 140.68, 141.49, 145.24, 145.75, 145.93, 146.29, 147.00, 154.59, 155.76, 156.01, 158.96. Anal. Calcd for C21H13Br2N3S (499.22): C, 50.52; H, 2.62; N, 8.42. Found: C, 49.37; H, 2.51; N, 8.11.
N-(4-Chlorophenyl)-3-(4-nitrophenyl)benzo[d]imidazo[2,1-b]thiazol-2-amine (4e).
Yellow solid; m.p. 245-248 °C. FT-IR (KBr) ʋ: 3449, 1672, 1585, 1407 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm): 6.68 (s, 1H, CH), 7.48 (d, J = 8.9 Hz, 3H, ArH), 7.53 (d, J = 6.6 Hz, 4H, ArH), 7.99 (d, J = 8.05 Hz, 4H, ArH), 8.20-8.37 (m, 13H, ArH), 10.26 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6) δ (ppm): 124.10, 124.62, 125.18, 129.30, 129.37, 129.68, 129.76, 130.09, 130.19, 131.42, 132.94, 134.19, 134.97, 137.05, 137.86, 137.95, 138.62, 138.80, 139.64, 140.11, 140.25, 141.96, 142.55, 143.36, 144.92, 148.68, 149.10, 149.73, 150.51, 152.48, 153.75, 155.99, 156.67, 157.76. Anal. Calcd for C21H13ClN4O2S (420.87): C, 59.93; H, 3.11; N, 13.31. Found: C, 59.47; H, 3.04; N, 13.51.
N-(4-Bromophenyl)-3-(4-nitrophenyl)benzo[d]imidazo[2,1-b]thiazol-2-amine (4f).
Yellow solid; m.p. 255-258 °C. FT-IR (KBr) ʋ: 3450, 1672, 1593, 1488 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm): 6.71 (s, 1H, CH), 7.43 (d, J = 7.4 Hz, 3H, ArH), 7.66 (d, J = 8.2 Hz, 4H, ArH), 8.00 (d, J = 8.4 Hz, 3H, ArH), 8.21-8.37 (m, 14H, ArH), 10.26 (s, 1H, NH).13C NMR (125 MHz, DMSO-d6) δ (ppm): 124.11, 124.61, 125.43, 129.38, 129.67, 131.43, 132.14, 132.68, 132.99, 133.90, 134.44, 135.70, 135.73, 136.28, 136.68, 137.99, 138.28, 139.91, 140.07, 140.76, 141.57, 142.75, 143.25, 144.62, 146.72, 147.12, 147.73, 147.90, 149.70, 150.43, 151.73, 152.94, 155.09, 156.10. Anal. Calcd for C21H13BrN4O2S (465.33): C, 54.21; H, 2.82; N, 12.04. Found: C, 53.71; H, 2.77; N, 12.17.
N-(4-Chlorophenyl)-3-(4-fluorophenyl)benzo[d]imidazo[2,1-b]thiazol-2-amine (4g).
Yellow solid; m.p. 222-224 °C. FT-IR (KBr) ʋ: 3434, 1665, 1587, 1412 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm): 6.63 (s, 1H, CH), 7.03 (d, J = 8.05 Hz, 1H, ArH), 7.21-7.28 (m, 5H, ArH), 7.31-7.38 (m, 5H, ArH), 7.43 (d, J = 8.4 Hz, 2H, ArH), 7.49 (d, J = 8.5 Hz, 3H, ArH), 7.82- 7.85 (m, 3H, ArH), 8.03- 8.09 (m, 5H, ArH), 9.83 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6) δ (ppm): 116.30, 123.93, 124.82, 129.46, 129.59, 129.65, 129.94, 130.49, 130.69, 130.76, 130.94, 131.42, 131.49, 131.57, 131.98, 132.13, 132.58, 133.14, 133.22, 133.28, 133.39, 134.33, 135.25, 135.29, 136.18 137.87, 138.06, 138.37, 145.72, 146.82, 147.81, 149.64, 155.95, 156.90. Anal. Calcd for C21H13ClFN3S (393.86): C, 64.04; H, 3.33; N, 10.67. Found: C, 63.24; H, 3.27; N, 10.52.
N-(4-Bromophenyl)-3-(4-fluorophenyl)benzo[d]imidazo[2,1-b]thiazol-2-amine (4h).
Yellow solid; m.p. 220-222 °C. FT-IR (KBr) ʋ: 3449, 1664, 1592, 1412 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm):6.64 (s, 1H, CH), 6.97 (d, J = 8.0 Hz, 1H, ArH), 7.21-7.24 (m, 2H, ArH), 7.29- 7.41 (m, 11H, ArH), 7.62 (d, J = 8.1 Hz, 2H, ArH), 7.82-7.85 (m, 2H, ArH), 8.01-8.07 (m, 6H, ArH), 9.83 (s, 1H, NH). 13C NMR (125 MHz, DMSO-d6) δ (ppm): 116.31, 124.19, 125.08, 126.76, 127.67, 128.94, 129.16, 129.22, 130.71, 130.78, 131.42, 131.49, 131.60, 132.57, 132.86, 133.16, 133.24, 133.92, 134.47, 135.20, 135.27, 136.29, 137.21, 138.48, 138.82, 142.49, 142.87, 144.44, 145.63, 148.27, 149.73, 151.05, 155.81, 156.74. Anal. Calcd for C21H13BrFN3S (438.32): C, 57.55; H, 2.99; N, 9.59. Found: C, 57.70; H, 3.11; N, 9.36.
2,2'-Oxybis(2-(4-chlorophenyl)amino)-1-(p-tolyl)ethan-1-one) (5a).
Yellow solid; m.p. 195-197 °C. FT-IR (KBr) ʋ: 3336, 1663, 1600, 1492 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm):2.33 (s, 3H, CH3), 2.35 (s, 3H, CH3), 5.52 (d, J = 9.75 Hz, 1H, CH), 5.58 (d, J = 7.7 Hz, 1H, CH), 6.18 (s, 1H, NH), 6.26 (s, 1H, NH), 6.58-6.61 (m, 4H, ArH), 6.95 (d, J = 8.3 Hz, 2H, ArH), 6.99 (d, J = 8.6 Hz, 2H, ArH), 7.25 (d, J = 8.0 Hz, 2H, ArH), 7.31 (d, J = 7.9 Hz, 2H, ArH), 7.78 (d, J = 10.0 Hz, 2H, ArH), 7.82 (d, J = 12.5 Hz, 2H, ArH). 13C NMR (125 MHz, DMSO-d6) δ (ppm): 21.58, 21.61, 57.41, 58.98, 114.57, 114.72, 120.34, 120.75, 123.84, 128.64, 128.80, 128.90, 128.99, 129.68, 129.86, 133.27, 134.29, 144.38, 146.13, 146.82, 197.22, 197.99. Anal. Calcd for C30H26Cl2N2O3 (533.45): C, 67.55; H, 4.91; N, 5.25. Found: C, 67.37; H, 4.73; N, 5.63.
2,2'-Oxybis(2-(4-chlorophenyl)amino)-1-(4-methoxyphenyl)ethan-1-one) (5b).
Yellow solid; m.p. 198-199 °C. FT-IR (KBr) ʋ: 3418, 1658, 1550, 1447 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm):3.81 (s, 3H, OCH3), 5.55 (d, J = 9.8 Hz, 1H, CH), 6.31 (d, J = 9.7 Hz, 1H, NH), 6.57 (d, J = 8.9 Hz, 2H, ArH), 6.97 (d, J = 8.6 Hz, 2H, ArH), 7.00 (d, J = 3.2 Hz, 2H, ArH), 7.88 (d, J = 8.9 Hz, 2H, ArH). 13C NMR (125 MHz, DMSO-d6) δ (ppm): 56.03, 57.25, 114.41, 114.71, 120.67, 128.97, 129.69, 131.07, 146.20, 163.85, 196.83. Anal. Calcd for C30H26Cl2N2O5 (565.45): C, 63.72; H, 4.63; N, 4.95. Found: C, 63.14; H, 4.82; N, 5.11.
2,2'-Oxybis(2-(4-chlorophenyl)amino)-1-phenylethan-1-one) (5c)
Yellow solid; m.p. 200-202°C. FT-IR (KBr) ʋ: 3361, 1664, 1594, 1447 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm):5.65 (d, J = 9.8 Hz, 1H, CH), 6.39 (d, J = 7.3 Hz, 1H, NH), 6.59 (d, J = 8.9 Hz, 2H, ArH), 7.00 (d, J = 8.8 Hz, 2H, ArH), 7.45 (t, J = 7.8 Hz, 2H, ArH), 7.58 (t, J = 7.3 Hz, 1H, ArH),7.90 (d, J = 7.8 Hz, 2H, ArH). 13C NMR (125 MHz, DMSO-d6) δ (ppm): 57.58, 114.72, 120.85, 128.65, 129.02, 129.10, 133.85, 136.75, 146.05, 198.45. Anal. Calcd for C28H22Cl2N2O3 (505.40): C, 66.54; H, 4.39; N, 5.54. Found: C, 65.70; H, 4.17; N, 5.61.
2,2'-Oxybis(2-(4-bromophenyl)amino)-1-phenylethan-1-one) (5d).
Yellow solid; m.p. 199-200 °C. FT-IR (KBr) ʋ: 3372, 1665, 1589, 1447 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm):5.64 (d, J = 8.1 Hz, 1H, CH), 6.42 (d, J = 8.1 Hz, 1H, NH), 6.54 (d, J = 8.5 Hz, 2H, ArH), 7.11 (d, J = 8.5 Hz, 2H, ArH), 7.45 (t, J = 7.7 Hz, 2H, ArH), 7.57 (t, J = 7.4 Hz, 1H, ArH), 7.89 (d, J = 7.8 Hz, 2H, ArH). 13C NMR (125 MHz, DMSO-d6) δ (ppm): 57.45, 108.26, 115.24, 128.64, 129.10, 131.84, 133.86, 136.72, 146.42, 198.38. Anal. Calcd for C28H22Br2N2O3 (594.30): C, 56.59; H, 3.73; N, 4.71. Found: C, 56.66; H, 3.75; N, 4.63.
2,2'-Oxybis(2-(4-bromophenyl)amino)-1-(4-methoxyphenyl)ethan-1-one) (5e).
Yellow solid; m.p. 209-210 °C. FT-IR (KBr) ʋ: 3365, 1654, 1599, 1462 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm):3.80 (s, 3H, OCH3) 5.55 (d, J = 7.1 Hz, 1H, CH), 6.32 (d, J = 8.3 Hz, 1H, NH), 6.53 (d, J = 8.6 Hz, 2H, ArH), 6.97 (d, J = 8.9 Hz, 2H, ArH), 7.10 (d, J = 8.4 Hz, 2H, ArH), 7.88 (d, J = 8.7 Hz, 2H, ArH). 13C NMR (125 MHz, DMSO-d6) δ (ppm): 56.03, 57.05, 108.06, 114.41, 115.21, 129.63, 131.08, 131.81, 146.55, 163.85, 196.75. Anal. Calcd for C30H26Br2N2O5 (654.36): C, 55.07; H, 4.01; N, 4.28. Found: C, 55.47; H, 4.13; N, 4.32.
2,2'-Oxybis(1-(p-tolyl)-2-(p-tolylamino)ethan-1-one) (5f).
Yellow solid; m.p. 188-189 °C. FT-IR (KBr) ʋ: 3419, 1655, 1518, 1453 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm):2.07 (s, 3H, CH3), 2.32 (s, 3H, CH3), 2.34 (s, 3H, CH3), 2.36 (s, 3H, CH3),5.45 (d, J = 9.0 Hz, 1H, CH), 5.54 (d, J = 7.9 Hz, 1H, CH), 5.69 (s, 2H, 2NH), 6.47 (d, J = 8.5 Hz, 2H, ArH), 6.51 (d, J = 7.3 Hz, 2H, ArH), 6.67-6.88 (m, 4H, ArH), 7.23-7.37 (m, 4H, ArH), 7.81 (d, J = 8.2 Hz, 4H, ArH).13C NMR (125 MHz, DMSO-d6) δ (ppm): 20.42, 21.15, 21.59, 21.72, 57.96, 59.84, 113.56, 113.66, 122.11, 125.93, 128.58, 128.81, 129.61, 129.69, 129.83, 130.38, 130.68, 133.61, 134.66, 144.99, 145.72, 157.28, 197.99, 198.30. Anal. Calcd for C32H32N2O3 (492.62): C, 78.02; H, 6.55; N, 5.69. Found: C, 77.54; H, 6.27; N, 5.77.
2,2'-Oxybis(1-(4-chlorophenyl)-2-(p-tolylamino)ethan-1-one) (5g).
Yellow solid; m.p. 175-177 °C. FT-IR (KBr) ʋ: 3344, 1672, 1614, 1399 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm):2.07 (s, 6H, 2CH3), 5.52 (d, J = 8.4 Hz, 1H, CH), 5.59 (d, J = 4.7 Hz, 1H, CH), 5.90 (d, J = 10.1 Hz, 1H, NH), 5.99 (d, J = 4.6 Hz, 1H, NH), 6.46-6.54 (m, 4H, ArH), 6.77-6.79 (m, 4H, ArH), 7.50 (d, J = 8.5 Hz, 2H, ArH), 7.57 (d, J = 8.5 Hz, 2H, ArH), 7.92 (d, J = 5.6 Hz, 2H, ArH), 7.94 (d, J = 5.5 Hz, 2H, ArH).13C NMR (125 MHz, DMSO-d6) δ (ppm): 20.44, 21.17, 58.20, 60.04, 113.59, 122.25, 125.99, 126.26, 129.15, 129.40, 129.74, 130.39, 130.51, 132.49, 134.84, 135.71, 138.68, 144.71, 145.49, 156.81, 197.62, 198.24.
2,2'-Oxybis(1-(4-bromophenyl)-2-(p-tolylamino)ethan-1-one) (5h).
Yellow solid; m.p. 180-181 °C. FT-IR (KBr) ʋ: 3350, 1672, 1614, 1396 cm-1. 1H NMR (500 MHz, DMSO-d6) δ (ppm):2.06 (s, 6H, 2CH3), 5.48 (d, J = 9.0 Hz, 1H, CH), 5.55 (d, J = 8.6 Hz, 1H, CH), 5.86 (d, J = 10.0 Hz, 1H, NH), 5.94 (d, J = 7.2 Hz, 1H, NH), 6.41-6.51 (m, 4H, ArH), 6.72-6.81 (m, 4H, ArH), 7.64 (d, J = 8.3 Hz, 2H, ArH), 7.71 (d, J = 8.3 Hz, 2H, ArH), 7.79-7.87 (m, 4H, ArH). 13C NMR (125 MHz, DMSO-d6) δ (ppm): 20.44, 21.18, 58.15, 59.99, 113.57, 122.26, 126.26, 127.85, 129.73, 129.76, 130.47, 130.59, 132.11, 132.36, 132.57, 135.16, 136.03, 144.69, 145.47, 156.80, 197.82, 198.43. Anal. Calcd for C30H26Br2N2O3 (622.36): C, 57.90; H, 4.21; N, 4.50. Found: C, 57.37; H, 4.14; N, 4.68.