4597-21-1, These common heterocyclic compound, 4597-21-1, name is 1,2-Dimethyl-1H-benzo[d]imidazole-5-carbaldehyde, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
Grignard reagent was prepared in an oven-dried three necked flask outfitted with a reflux condenser, dropping funnel, and magnetic stirrer. 3,5-dimethoxy-bromobenzene (2.0 g, 9.0 mmol) in THF (10 mL) was added to a mixture of magnesium turning (0.2 g, 9.0 mmol) in THF (5 mL) with a small piece of iodine. The resulting mixture was refluxed for about 3 h then cooled to room temperature for about 30 min. The (3,5-dimethoxyphenyl)magnesium bromide was then added slowly to a stirred solution of 1,2-dimethoxy-1H-benzoimidazole-5-carbaldehyde (1.3 g, 7.5 mmol) in THF (10 mL) at 0 C. After complete addition, the solution was allowed to stir at room temperature for about 1 h. The mixture was cooled to 0 C. and quenched with saturated NH4Cl solution (40 mL). The aqueous layer was extracted with EtOAc (3¡Á20 mL). The combined organic layers were washed with water (2¡Á30 mL), brine (30 mL) and dried (MgSO4). Solvent was removed and the crude product was slurried in hexane to afford (3,5-dimethoxy-phenyl)-(1,2-dimethyl-1H-benzoimidazlo-5-yl)-methanol (2.1 g, 91%) as a off white solid: 1H NMR (CDCl3) delta 7.66 (s, 1H), 7.24-7.20 (dd, J=1, 8 Hz, 1H), 7.17 (d, J=8 Hz, 1H), 6.56 (d, J=2 Hz, 2H), 6.31 (t, J=2 Hz, 1H), 5.84 (s, 1H), 3.72 (s, 6H), 3.63 (s, 3H), 3.55 (b, 1H), 2.52 (s, 3H). A suspension of (3,5-dimethoxy-phenyl)-(1,2-dimethyl-1H-benzoimidazol-5-yl)-methanol (2.1 g, 6.7 mmol) and MnO2 (2.9 g, 33.6 mmol) in CH2Cl2 (300 mL) was stirred at room temperature for 17 h. The mixture was filtered through celite and solvent was removed. The crude product was slurried with ether to afford (3,5-dimethoxy-phenyl)-(1,2-dimethyl-1H-benzoimidazol-5-yl)-methanone (2.0 g, 99%) as an off white solid: 1H NMR (DMSO-d6) delta 7.90 (s, 1H), 7.71-7.62 (m, 2H), 6.80 (s, 3H), 3.80 (s, 3H), 3.35 (s, 3H), 2.58 (s, 3H); 13C NMR (DMSO-d6) delta 195.28, 160.17, 154.83, 141.54, 140.27, 139.15, 130.15, 123.50, 120.73, 109.70, 107.19, 103.62, 55.47, 29.96, 13.52. 3-(3,5-Dimethoxy-phenyl)-3-(1,2-dimethyl-1H-benzoimidazol-5-yl)-acrylonitrile (E and Z isomers) were prepared analogously to 3-(3-amino-4-methoxy-phenyl)-3-(3,4-dimethoxy-phenyl)-acrylonitrile (E and Z isomers) using (3,5-dimethoxy-phenyl)-(1,2-dimethyl-1H-benzoimidazol-5-yl)-methanone (2.0 g, 6.4 mmol), lithium bis (trimethylsilyl)amide (7.7 mL, 7.7 mmol) and diethyl cyanomethylphosphate (1.4 g, 7.7 mmol). The crude product was purified by flash chromatography (silica gel, CH2Cl2:CH3OH 95:5) to afford mixture of isomers of 3-(3,5-dimethoxy-phenyl)-3-(1,2-dimethyl-1H-benzoimidazol-5-yl)-acrylonitrile (1.1 g, 50%) as a white solid: mp 199-201 C.; 1H NMR (CDCl3) delta 7.69 (m, 3H), 6.56-6.42 (m, 3H), 5.70 (5.74) (s, 1H), 3.77 (s, 3H), 3.73 (3.74) (s, 6H), 2.61 (s, 3H); 13C NMR (CDCl3) delta 163.76 160.63 (160.60), 153.22 (153.54), 142.35 (142.57), 141.69 (139.43), 137.04 (137.38), 130.69 (132.54), 123.74 (122.64), 120.81 (119.54), 118.23 (118.09), 108.84 (108.80), 107.02 (107.72), 102.08 (102.02), 94.32 (93.47), 55.42 (55.41), 30.05 (30.00), 13.88; Anal Calcd for C20H19N3O2+0.2H2O: C, 71.28; H, 5.80; N, 12.47. Found: C, 71.18; H, 5.86; N, 12.42.
Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 4597-21-1.
Reference:
Patent; Muller, George W.; Man, Hon-Wah; US2006/52596; (2006); A1;,
Imidazole – Wikipedia,
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