2-Acetylbenzimidazole

To a solution of 1 (1.62 g, 0.01 mol), 2, 2, 6, 6-tetramethylpiperidin(0.016 g, 0.1 mmol) and potassium bromide(0.12 g, 1 mmol) in 40 mL acetonitrile/water (1:1), 8percent aqueoussodium hypochlorite (13.96 g, 0.015 mol) was added over a 15–20 min period, keeping the temperature of the reaction mixturebetween 10 and 15 C. The mixture was stirred for 30 min andwas extracted with ethyl acetate (50 mL 3). The combinedextracts were washed with 60 mL of 10percent aqueous sodium thiosul-fate and 60 mL of saturated sodium chloride solution. The organicphase was separated, dried over anhydrous MgSO4 and evaporatedto afford compound 2 with 85percent yield, MS (ESI) m/z: 161 (M+H)+. 1HNMR (400 MHz, DMSO) d 13.31 (s, 1H), 7.84 (d, J = 8.1 Hz, 1H), 7.57(d, J = 8.1 Hz, 1H), 7.39 (t, J = 7.1 Hz, 1H), 7.31 (d, J = 7.2 Hz, 1H), 2.72 (s, 3H).To a solution of 1-(1H-benzimidazol-2-yl)ethanol 1 (8.1 g, 0.05 mol) in dilute sulphuric acid (40 ml), a solution ofpotassiumdichromate (9.8 g, 0.05 mol) in water (60 ml) wasadded at room temperature. To this mixture, concentratedsulphuric acid (20 ml) was added in a dropwise fashion, over a period of 20 min. The reaction mixture was stirredvigorously during addition. The separated solid was filteredand wash with water (30 ml). The precipitate obtained wasre-suspended in water (50 ml) and treated very carefullywith aqueous ammonia to obtain a pH 6.0–6.5. The suspensionwas stirred for 0.5 h and filtered. The residue 2 waswashed with water (3 × 10 ml) and dried. Yield = 70percent, m.p. 189–191 °C. IR (KBr) cm−1: 3358 (NH), 3024 (Ar-CH), 2971 (CH3-CH), 1740 (C=O), 1647 (C=N), 1601 (C=C).1H-NMR (CDCl3, 500 MHz) δ ppm: 2.31 (s, 3H, CH3), 5.19(s, 1H, NH), 7.342–7.86 (m, 4H, Ar-CH). 13C-NMR(CDCl3, 500 MHz) δ ppm: 195.4 (C=O), 154.8 (C-2), 140.5 (C-8 & C-9), 129.6 (C-5 & C-6), 117.2 (C-4 & C-7), 29.7 (CH3). EI-MS m/z: 160 (M+). Anal. calcd forC9H8N2O: C, 67.49; H, 5.03; N, 17.49. Found: C, 67.68; H, 5.04; N, 17.44.The method for synthesizing 2-acetylbenzimidazole in this example is as follows:2-Hydroxyethylbenzimidazole (0.1 mol, 16.2 g)The ruthenium complex Ru(bpbp)(pydic) (10-4 mol, 0.0730 g) in Example 3 was added to the reaction vessel.Hydrogen peroxide (30percent, 0.3 mol, 9.1 ml) was slowly added to the reaction vessel with stirring.Control the reaction temperature below 80 °C for several hours.The reaction solution was concentrated under reduced pressure, Obtain a solid product, The solid product was dissolved in dichloromethane and subjected to silica gel column chromatography.Pure product 2-acetylbenzimidazole 11.0g was obtained. Yield 69percent.A 50 mL round bottom flask was added 5.4 g (0.05 mol) of o-phenylenediamine, 4.5 g (0.05 mol) of lactic acid and 20 ml of 4 mol / L hydrochloric acid, Heating reflux 1.5h, Cool to room temperature.With concentrated ammonia and purple purple litmus paper turned red, Filter out the solid, Recrystallization from water (63percent).To a 50 mL three-necked flask, 2.24 g (0.02 mol) of 2- (α-hydroxy) ethylbenzimidazole and 15 mL of glacial acetic acid were added, After heating to 90 ° C, an aqueous solution of CrO3 was added dropwise to the three-necked flask, After dripping, The reaction was stirred at 105 ° C for 10 min, The reaction was then poured into a beaker containing 200 mL of water, Stirring for a moment, Filter, The filtrate was extracted three times with chloroform, The chloroform layers were combined, Dried over anhydrous magnesium sulfate, The filtrate was evaporated to dryness to give a yellow solid, Recrystallization from toluene, Yield: 64percent.To a 50 mL three-necked flask was added 1.6 g of 2-acetylbenzimidazole, 15 mL of 2 mol / L NaOH solution, and 1.3 mL of bromoethane was added to the flask, After the dropwise addition, the three-necked flask was quickly placed in an ice bath and cooled to 0 ° C, 5min after precipitation of a large number of solid, Filter, Washed, Dried to obtain a yellow solid, Yield: 79percentTo a 50 ml round bottom flask was added 20 ml of 95percent ethanol and 3.20 g (0.02 mol) of 1- (1-ethyl-1H-benzimidazol-2-ethyl)Stir for about 10 min to completely dissolve the solid, Further, 8 ml of a 10percent aqueous solution of sodium hydroxide was added, 0.02 mol of 2-pyridinecarbaldehyde was added with stirring, After a period of time the system precipitates a lot of solid, The reaction end point was detected by TLC, After the reaction, the filtrate was filtered to obtain a solid, yield: 86percent(1H-benzo[d]imidazol-2-yl)ethanol (0.1 mol, 14.8 g) and Ru(bpbp)(pbb)Cl(0.001mmol, 7.32 × 10−3 g) were added into a reactor. Thereactor containing this mixture was heated to 50 °C in an oilbath under vigorous stirring, and then 30percent H2O2 (30 mL, 0.3mol) was slowly dropped into the reactor in 30min. Themixture was stirred for 5h. After filter, the solution wasevaporated under reduced pressure at 50 °C. After extractionwith CH2Cl2, the crude product was chromatographed onsilica gel (eluent: CH2Cl2). Pure 1-(1H-benzo[d]imidazol-2-yl)ethanone (0.07mmol, 10.2 g) was obtained with the isolated yield of 57percent by removing the solvent. The productwas identified by 1HNMR spectrum (400MHz, CDCl3)(Figure 5) and IR spectrum (Figure 6), which are all inagreement with the assumed structure. IR is also same withthe standard Bio-Rad/Sadtler IR Data.To a stirred solution of compound 190 (15 g, 73.13 mmol) in anhydrous THF (200 mL) under inert atmosphere was added methyl magnesium bromide (48.75 mL, 146.3 mmol, 3 M sol. in diethyl ether) dropwise for 15 min at 0 Preparation of 1-(1H-Benzimidazol-2-yl)-ethanone:

Molecular Weight:160.17
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:160.063662883
Monoisotopic Mass:160.063662883
Topological Polar Surface Area:45.8
Heavy Atom Count:12
Complexity:193
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes