2-(3,4-Dichlorobenzyl)-1H-benzimidazole

White crystals

General procedure: To a stirred solution of N-(2-iodophenyl)benzamide 4a (50 mg, 0.15 mmol), CuI (2.9 mg, 0.02 mmol), L-proline (3 mg, 0.03 mmol), and NaOH (9 mg, 0.22 mmol) in DMSO (1 mL) was added 30percent aqueous NHGeneral procedure: To a stirred solution of benzene-1, 2-diamine 1 (1.85 mmol)in xylenes (10 mL) were added carboxylic acid 2 (2.77 mmol)and boric acid (0.185 mmol). The resulting solution wasrefluxed for 16 h. After cooling to room temperature, the reactionwas concentrated under reduced pressure and diluted withEtOAc (50 mL). The organic phase was washed with saturatedNaHCO3 solution (2 50 mL), dried over anhydrous Na2SO4and then concentrated under reduced pressure. The residuewas purified by silica gel flash column chromatography (elutingwith 10–15percent Ethyl acetate in hexanes) to afford the title compounds3a–y and 5.6.2.8 General procedure: Solution ofbenzimidazole (0.1 mmol) in TfOH (1 mL) and arene (0.1 mL) was magnetically stirred at 140 Cin glass high pressure tube for 2.5 h, then poured into water (50 mL). After extraction with CH2Cl2(3 × 30 mL), the combined extracts were consequently washed with water (50 mL), saturatedaqueous solution of Na2CO3 (30 mL), water (50 mL), dried with anhydrous Na2SO4 and evaporatedin vacuo to give crude products, which were subjected to chromatographic separation on silica gelusing petroleum ether/diethyl ether as an eluent.General procedure: To a stirred solution of N-(2-iodophenyl)benzamide 4a (50 mg, 0.15 mmol), CuI (2.9 mg, 0.02 mmol), L-proline (3 mg, 0.03 mmol), and NaOH (9 mg, 0.22 mmol) in DMSO (1 mL) was added 30% aqueous NH4OH (14.3 muL, 0.22 mmol) dropwise. After stirring at room temperature for 3 h, acetic acid (1 mL) was added dropwise. Then, the reaction mixture was heated to 80 C for 7 h. After cooling to room temperature, the reaction mixture was extracted with EtOAc (3 ~ 20 mL) and washed with 5% aqueous solution of NaHCO3 (~ 20 mL). The organic layer was dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, n-hexane/EtOAc 2/1) to yield the title product 7a (18 mg, 60%).10.8 g of o-phenylenediamine and 24.6 g of 3, 4-chlorophenylacetic acid were placed in a 250 ml three-neck round bottom flask.Add 100 ml of xylene and stir for 5 minutes.Add 1.2 g of Zn/Al2O3 catalyst and connect the water separator.The mixture was heated to reflux at 130 C for 6 hours, and the solvent was recovered by using a distillation recovery device. When about 80 ml of xylene was recovered, the mixture was distilled under reduced pressure.Stop the vacuum distillation when the xylene recovery is 90 ml.Add 150 ml of ethanol and add 10 ml of ammonia water.0.5 g of activated carbon, stirred and dissolved for 30 minutes, Filter the activated carbon and slowly add 50 ml of pure water to the filtrate.Stir while stirring, product precipitation, filtration, hot water wash twice, Filtration and drying gave 22.2 g of 2-(3, 4-chlorobenzyl)benzimidazole, the yield was 80%, and the product color was good.General procedure: To a stirred solution of benzene-1, 2-diamine 1 (1.85 mmol)in xylenes (10 mL) were added carboxylic acid 2 (2.77 mmol)and boric acid (0.185 mmol). The resulting solution wasrefluxed for 16 h. After cooling to room temperature, the reactionwas concentrated under reduced pressure and diluted withEtOAc (50 mL). The organic phase was washed with saturatedNaHCO3 solution (2 50 mL), dried over anhydrous Na2SO4and then concentrated under reduced pressure. The residuewas purified by silica gel flash column chromatography (elutingwith 10-15% Ethyl acetate in hexanes) to afford the title compounds3a-y and 5.6.2.8 2-(3, 4-Dichlorobenzyl)-1H-benzo[d]imidazole (3h) Yield 65%; Off white solid; mp 189-191 C; IR (KBr) 2851, 2758, 1508, 1451, 1410, 1241, 1183, 1027, 754 cm-1; 1H NMR (400 MHz, DMSO-d6) delta 12.30 (br s, 1H), 7.64 (d, J = 2.20 Hz, 1H), 7.59 (d, J = 8.05 Hz, 1H), 7.48-7.56 (m, 1H), 7.39-7.48 (m, 1H), 7.33 (dd, J = 2.19, 8.29 Hz, 1H), 7.08-7.18 (m, 2H), 4.21 (s, 2H); 13C NMR (100 MHz, DMSO-d6) delta 152.7, 138.8, 131.0, 130.7, 129.5, 129.4, 121.5, 33.7; HRMS calcd for C14H10Cl2N2 m/z 276.0225, found 276.0221.General procedure: 2-phenyl-1H-benzo[d]imidazole To a round-bottom flask, N-(2-iodophenyl)benzamide (50 mg, 0.15 mmol), copper iodide (2.86 mg, 0.015 mmol), L-proline (3.45 mg, 0.03 mmol) and sodium hydroxide (9 mg, 0.225 mmol) are introduced and purging is carried out with nitrogen. Then, dimethyl sulfoxide (1 mL) is added thereto to dissolve the reaction mixture and 30% aqueous ammonia (14.3 muL, 0.225 mmol) is added dropwise thereto. The reaction mixture is agitated for 2-3 hours. The reaction progress and result are checked by TLC. Then, acetic acid (1 mL) is added dropwise thereto at room temperature and the reaction mixture is refluxed at 80 C. for 7 hours. The reaction progress and result are checked by TLC. After completing the reaction, the reaction mixture is extracted with ethyl acetate and water and aqueous solution of potassium carbonate is added dropwise thereto to perform neutralization, followed by extraction with ethyl acetate. The organic layer is dried with dry sodium sulfate, followed by filtering. The filtrate is concentrated under reduced pressure and the concentrate is purified by column chromatography (EA:n-hHex=1:2) to obtain 18 mg of the target compound (yield: 60%). 1H NMR (300 MHz, DMSO-d6) delta ppm 12.92 (br s, 1H) 8.18 (m, 2H) 7.52 (m, 5H) 7.21 (m, 2H)General procedure: To a stirred solution of 2-phenyl-1H-benzo[d]imidazole 7a (50 mg, 0.26 mmol) and NaH (7 mg, 0.31 mmol) in DMF (0.5 mL) was added methyl bromoacetate (29 muL, 0.31 mmol) dropwise. After stirring at room temperature for 16 h, the reaction mixture was extracted with EtOAc (3 ~ 20 mL) and washed with H2O (~ 20 mL). The organic layer was dried over anhydrous MgSO4, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, n-hexane/EtOAc 2/1) to yield the title product 8a (35 mg, 50%).

Molecular Weight:277.1
XLogP3:4.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:2
Exact Mass:276.0221037
Monoisotopic Mass:276.0221037
Topological Polar Surface Area:28.7
Heavy Atom Count:18
Complexity:287
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes