These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(Trifluoromethyl)-1H-benzo[d]imidazole, its application will become more common.
Application of 312-73-2,Some common heterocyclic compound, 312-73-2, name is 2-(Trifluoromethyl)-1H-benzo[d]imidazole, molecular formula is C8H5F3N2, 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.
A stirred mixture of 2-Trifluoromethyl-1 H-benzoimidazole (4.92g, 26.4 mmol), 4-fluorobenaldehyde (3.1 mL, 29.1 mmol), and K2CO3 (4.37g, 31.7 mmol) in DMF (50 mL) was heated to 150 0C for 16 h. After being cooled to room temperature, the reaction mixture was partitioned between H2O and EtOAC. After usual workup, the crude product was purified by silica gel chromatography (20% Hexane/EtOAc to 30% Hexane/EtOAc) to afford a yellow oil which was subjected to a second silica gel chromatography (DMC) to provide the aldehyde intermediate 4-(2-Trifluoromethyl-benzoimidazol-1-yl)- benzaldehyde as a white solid (4.0 g).To a solution of the above 4-(2-Trifluoromethyl-benzoimidazol-1-yl)- benzaldehyde (0.155g, 0.53 mmol) and (2,3-Difluoro-phenyl)-acetonttrile (83 mg, 0.54 mmol) in EtOH (5 mL) was added a solution of KOH (0.2g) in H2O (0.5 mL). The mixture was then stirred at rt for 1h, partitioned between EtOAc/H2theta. The organic layer was dried and concentrated followed by silica gel chromatography (20% Hexane/EtOAc) to afford the product Compound 47 as a colorless oil.To a stirred solution of 4-(2-Trifluoromethyl-benzoimidazol-1-yl)-benzaldehyde (0.58 g, 2 mmol) in acetone (25 mL) was added Jone’s reagent (1.0 mL, 2.0 M) at O0C. After stirring at room temperature for 2h, the mixture was partitioned between EtOAc and saturated NaHCO3 solution. After usual workup, the crude material was separated by silica gel chromatography (50% Hexane/EtOAc to EtOAc) to afford the intermediate acid 4-(2-Trifluoromethyl- benzoimidazol-1-yl)-benzoic acid as a while solid (490 mg).To a stirred solution of 4-(2-Trifluoromethyl-benzoirnidazol-1-yl)-benzoic acid (102 mg, 0.33 mmol) in dry CHCI3 (15 mL) was added oxalyl chloride (0.09 mL) followed by one drop of DMF at room temperature. After 1h, the reaction pot was concentrated and vacuum dried. Dry chloroform (15 mL) and pyridine (0.1 mL) was then added followed by the addition of 2,3-difluoroaniHine (36 mg, 0.28 mmol). The reaction was monitored by TLC, after completion, the mixture was partitioned between 1 N HCI and DCM. Organic layer was separated and dried (Na2SO4). Removal of solvents followed silica gel chromatography (20% hexane/EtOAc) afforded the product Compound 46 as a white solid.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-(Trifluoromethyl)-1H-benzo[d]imidazole, its application will become more common.