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CAS No. : | 716-79-0 | MDL No. : | MFCD00005592 |
Formula : | C13H10N2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | DWYHDSLIWMUSOO-UHFFFAOYSA-N |
M.W : | 194.23 | Pubchem ID : | 12855 |
Synonyms : |
|
Num. heavy atoms : | 15 |
Num. arom. heavy atoms : | 15 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 61.53 |
TPSA : | 28.68 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | Yes |
Log Kp (skin permeation) : | -5.18 cm/s |
Log Po/w (iLOGP) : | 1.83 |
Log Po/w (XLOGP3) : | 3.24 |
Log Po/w (WLOGP) : | 3.23 |
Log Po/w (MLOGP) : | 2.81 |
Log Po/w (SILICOS-IT) : | 3.6 |
Consensus Log Po/w : | 2.94 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.76 |
Solubility : | 0.0338 mg/ml ; 0.000174 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.52 |
Solubility : | 0.0593 mg/ml ; 0.000305 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -5.43 |
Solubility : | 0.00072 mg/ml ; 0.00000371 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.55 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With sulfuric acid; dihydrogen peroxide In water at 100 - 130℃; | General procedure: A solution of 10.0 mmol of compound 1a–1d in 14 mL of concentrated sulfuric acid was heated to 100–105°C, 14 mL (0.26 mol) of 30percent aqueous hydrogen peroxide was added dropwise with stirring,and the mixture was stirred for 1 h at 130°C. After cooling, the mixture was poured into water and adjusted to pH 4, and the precipitate was filtered off. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With gadolinium(III) chloride hexahydrate; at 80℃; for 5.5h; | General procedure: To a mixture of o-aromatic diamines (200 mg, 1.85 mmol) and 1,3-dicarbonyl compound (722 mg, 5.55 mmol), GdCl3*6H2O (25 mg, 0.09 mmol) was added and the mixture was stirred at 80°C for 3.0 hr. After completion of the reaction (TLC), the reaction mixture was poured into ice cold water and extracted with ethyl acetate. The organic layer was dried over sodium sulphate and concentrated under reduced pressure to afford the corresponding 2-methyl benzimidazole. The crude material was further purified by through column chromatography by using 10percent ethyl acetate in hexane. |
60% | With sodium iodide dichloride; In tetrahydrofuran; water; for 10h;Reflux; Sealed tube; | General procedure: To a mixture of o-substituted (?NH2 or ?SH or ?OH) anilines(1.0 mmol) and appropriate 1,3-diketones (1.1 mmol) in THF(5 mL) was added 30percentw/w aqueous NaICl2 (0.2 mmol, 20molpercent). The reaction was allowed to remain stirred at refluxtemperature for 2?3 h. After the reaction was complete, asindicated by TLC, the mixture was cooled to room temperature.The volatiles were removed under reduced pressureand treated successively with aqueous sodium thiosulphatesolution and saturated solution of NaHCO3, and extractedby ethylacetate (2×10 mL). The combined organic phaseswere washed with brine and dried over Na2SO4 and evaporatedunder vacuum. The crude reaction mixture was purifiedby column chromatography on silica gel using petroleumether/ethyl acetate as eluents. |
45% | With benzoic acid; In ethanol; at 70℃; for 36h;Schlenk technique; | O-phenylenediamine (54.0 mg, 0.5 mmol), 1, 3-diphenyl-1,3-diacetone (134. 5 mg, 0. 6 mmol) and benzoic acid (6.1 mg, 0. 05 mmol) were added sequentially to a 25 mL Schlenk flask, In ethanol (6.OmL), placed in oil bath at 70 ° C for 36h. After completion of the reaction, the solvent was removed under reduced pressure, and petroleum ether / B was used Ethyl acetate as eluant. The yield of 2-phenylbenzimidazole was 45percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | In neat (no solvent); for 1h;Milling; Green chemistry; | General procedure: A mixture of 1,2-phenylenediamine (2.5 g, 23.1 mmol) and 27.2 mmol of the appropriate carboxylicacid or aldehyde were introduced into stainless steel vials with appropriate weight of stainlesssteel balls for the mentioned time. The reaction was poured into water and neutralized with solidsodium carbonate. The formed precipitate was filtered, washed with water and recrystallizedfrom ethanol-water. |
95% | With diphosphorus tetraiodide; In acetonitrile; at 80℃; for 3h;Sealed tube; Inert atmosphere;Catalytic behavior; | General procedure: To amixture of ortho-substituted (-NH 2 or -SH or -OH) anilines(1 mmol) and aryl acids (1 mmol) in acetonitrile (2 mL) in asealed tube (10 mL) was added diphosphorus tetraiodide (0.2mmol) under nitrogen atmosphere. Then, the tube was cappedand the mixture heated in an oil bath at 80 C with stirringuntil the reaction was complete as monitored by TLC. Afterbeing cooled to room temperature, the reaction was quenchedwith aqueous NaHCO 3 solution and extracted with ethyl acetatethree times. The combined organic layer was washed withwater and brine and then dried over anhydrous Na 2 SO 4 . Thesolvent was removed under reduced pressure and the residuewas purified by chromatography on silica gel, eluting withpetroleum ether/ethyl acetate, to afford the correspondingproduct. The products obtained were known compounds andwere identified by melting point and 1 H NMR spectroscopy.The spectral data were compared with the literature values.2-Phenyl-1H-benzimidazole (Table-2, entry 1): m.p.:290-293 C (Lit. [21] 292-294 C); IR (KBr, nu max , cm -1 ): 3450,3045, 1620, 1580, 1458; 1 H NMR (400 MHz, DMSO-d 6 ): delta7.08-7.14 (m, 2H), 7.31-7.5 (m, 5H), 7.96 (d, 2H), 12.80 (s,1H); 13 C NMR (DMSO-d 6 , TMS): delta 116.5, 123.1, 127.4, 128.6,129.5, 130.7, 139.0, 152.7; MS (ESI) m/z: [M+H] + 195.1. |
94% | With 1,1'-carbonyldiimidazole; In 1-methyl-pyrrolidin-2-one; water; at 445℃; under 337534.0 Torr; for 0.00277778h;Supercritical conditions; | As a raw material, o-phenylenediamine (manufactured by Wako Pure Chemical Industries, Ltd., Wako first class), N, N'-carbonyldiimidazole (manufactured by Wako Pure Chemical Industries, Ltd. for peptide synthesis) and benzoic acid (manufactured by Wako Pure Chemical Industries, A chemical reaction represented by the following chemical reaction formula (12) was carried out in supercritical water in the same manner as in Example 1. The results are shown in Table 6. The objective compound was synthesized in supercritical water having a temperature of 400 to 445 C. and a pressure of 25 to 45 MPa |
92% | With Amberlyst-15; In water; at 90℃; for 1.33333h;Irradiation; | General procedure: To a solution of o-phenylenediamine 1a, o-amino phenol 1b or o-amino thiophenol 1c (1.0 mmol) and aromatic acid (2, 1.2 mmol) in water (5 mL) was added Amberlyst-15 (10%, w/w) and the mixture was irradiated with ultrasound (40 KHz) continuously at 90 C till the completion of the reaction(monitored by TLC) as indicated in Table 3. The solid separated was filtered, washed with diethyl ether (2 x 5 mL), dried and treated with EtOAc (15 mL). After stirring for 10 min the mixture was filtered to remove the insoluble catalyst. The filtrate was collected and concentrated under vacuum. The solid obtained was purified by recrystallization (column chromatography infew cases) to afford the desired products 3, 4 or 5. |
77% | With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In ethyl acetate; at 160℃; for 0.5h;Microwave irradiation; Sealed tube; | General procedure: A mixture of o-phenylenediamine (1 mmol), carboxylic acid (1 mmol), N,N-diisopropylethylamine (1.5 mmol) and propylphosphonic anhydride (1 mmol, 50% w/w in AcOEt) was irradiated for 30 min under microwave at 160 C in a sealed tube. It was diluted with H2O, followed by alkalinization with saturated aqueous NaHCO3 solution. The precipitate was collected by filtration and washed thoroughly with H2O to afford the respective benzimidazole. If necessary, simple recrystallization was carried out in EtOH/H2O. |
75% | In neat (no solvent); at 140℃;Green chemistry; | General procedure: A mixture of organic acid (40 mmol) and o-phenylenediamine(40 mmol), thoroughly grounded with a pestle in a mortar at roomtemperature until liquefied, was subsequently heated at 140 C for1.5e2 h. The progress of the reaction was monitored by thin-layerchromatography (TLC). After cooling, the resulting mass waswashed with water, filtered, and the final product was recrystallized.The synthesized 2-benzimidazoles were then characterizedand confirmed by comparing their physical data with thoseof literature known compounds, as follows. |
60% | With boric acid; In 5,5-dimethyl-1,3-cyclohexadiene; for 16h;Reflux; | 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 5.6.2.1 2-Phenyl-1H-benzo[d]imidazole (3a) Yield 60%; Light yellow solid; mp 286-287 C; IR (KBr) 2950, 2747, 1445, 1421, 1275, 1085, 748 cm-1; 1H NMR (400 MHz, DMSO-d6) delta 12.92 (br s, 1H), 8.15-8.22 (m, 2H), 7.64-7.71 (m, 1H), 7.46-7.59 (m, 4H), 7.16-7.27 (m, 2H); 13C NMR (100 MHz, DMSO-d6) delta 151.3, 143.9, 135.1, 130.3, 129.9, 129.0, 126.6, 126.5, 126.5, 122.6, 121.8, 119.0, 111.4; HRMS calcd for C13H10N2 m/z 194.0825, found 194.0823. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78.08% | With sulfuric acid; HNO3 at 20℃; for 3h; | Nitration of benzimidazole Compound General procedure: Take above synthesized compound (1 g) and mixture of H2SO4 (5 mL) and HNO3 (5 mL) were taken in a beaker and stirred for 3 h at room temperature. Yellow color solid was filtered and recrystallized by ethanol with the yield of 85.00%. All the compounds (XY-1, XY-2 & XY-3) were synthesized by following the said method by using different substituted aromatic acids (XY-(a-c) respectively as given in Table 1. Thin layer chromatography was performed to assess the progression of the reaction. |
38% | With sulfuric acid; HNO3 at 35℃; for 13.25h; | |
With HNO3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With benzaldehyde; 1,2-diamino-benzene In ethanol for 7h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With oxygen; acetic acid; In acetonitrile; at 80.0℃; for 7.0h;Green chemistry;Catalytic behavior; | General procedure: A mixture of benzamidine (1 mmol), HOAc (3 eq.) and alpha-ZrP/Uracil/Cu2+ (20 mg: 1.3 mol%) in CH3CN(3 mL) wasrefluxed at 80 C under the direct flow of O2(followed up byTLC). After consumption of benzamidine, the catalyst wasseparated by centrifugation and the reaction mixture wascooled to room temperature. The catalyst was thoroughlywashed with ethyl acetate, and then, the extraction with ethylacetate (3 × 10 ml) was performed on the reaction mixture.The organic extract was dried over anhydrous CaCl2,and thesolvent was vaporized under reduced pressure. The remainingsolid was purified by recrystallization from ethanol.Product specifications are provided in the supplementaryinformation. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; | EXAMPLE 4 Preparation of 1-Methyl-2-Phenylbenzimidazole Using DBU To a mixture of 2-phenylbenzimidazole (1.02 g, 5.25 mmol) in DMC (10 mL), DBU (0.80 g, 5.25 mmol) was added and the resulting mixture was heated to reflux (90° C.) for 6 hours. The solvent was evaporated under vacuum and the resulting oil was dissolved in methylene chloride (2 mL) and filtered through silica gel (2:1 EtOAc/hexane). The solvent was evaporated under vacuum to afford 1-methyl-2-phenylbenzimidazole as a solid. The yield of 1-methyl-2-phenylbenzimidazole as determined by HPLC analysis was 98percent conversion. | |
EXAMPLE 5 Preparation of 1-methyl-2-phenylbenzimidazole Using Dabco.(TM). To a mixture of 2-phenylbenzimidazole (2.02 g, 10.4 mmol) in DMC (10 mL), Dabco.(TM). (1.17 g, 10.4 mmol) was added and the resulting mixture was heated to reflux (90° C.) for 3 hours. The yield of 1-methyl-2-phenylbenzimidazole as determined by HPLC analysis was 99percent conversion. | ||
With dmap; In N,N-dimethyl-formamide; | EXAMPLE 6 Preparation of 1-Methyl-2-phenylbenzimidazole Using DMAP To a mixture of 2-phenylbenzimidazole (2.02 g, 10.4 mmol) in DMC (10 mL) and DMF (5 mL), DMAP (1.27 g, 10.4 mmol) was added and the resulting mixture was heated to reflux (90° C.) for 4 hours. The yield of 1-methyl-2-phenylbenzimidazole as determined by HPLC analysis was 99percent conversion. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 1-n-butyl-3-methylimidazolim bromide; In neat (no solvent); at 120℃; for 0.75h; | General procedure: A stirred mixture of aromatic diamine (1mmol) and beta-ketoester or beta-ketoamide (1mmol) was heated under inert condition at 120°C in the presence of 10molpercent of ionic liquid III. After completion of reaction as revealed by TLC, product was crystallized from ethyl acetate?hexane or passes through short pad silica-gel to remove any colour impurities from the product to obtain analytically pure benzimidazoles. |
92% | With iron(III) chloride adsorbed on silica gel; In ethanol; for 3h;Reflux; | General procedure: To a solution of aromatic diamine (1.0 mmol), beta-ketoester/amide (1 mmol) in ethanol (5 mL) SiO2-FeCl3 (40 mg) was added followed by reflux for appropriate time indicated in Table 1 and Table 2. After completion of reaction (TLC), the catalyst was filtered through Whatmann 42 filter paper; residue was washed several times with dichloromethane. The combined filtrate was evaporated to dryness to obtain crude product which was re-crystalized or passing through short pad silica-gel column to get analytically pure product. Residue can be re-used after washing with ethyl acetate or methanol. |
83% | With gadolinium(III) chloride hexahydrate; at 80℃; for 6.5h; | General procedure: To a mixture of o-aromatic diamines (200 mg, 1.85 mmol) and 1,3-dicarbonyl compound (722 mg, 5.55 mmol), GdCl3*6H2O (25 mg, 0.09 mmol) was added and the mixture was stirred at 80°C for 3.0 hr. After completion of the reaction (TLC), the reaction mixture was poured into ice cold water and extracted with ethyl acetate. The organic layer was dried over sodium sulphate and concentrated under reduced pressure to afford the corresponding 2-methyl benzimidazole. The crude material was further purified by through column chromatography by using 10percent ethyl acetate in hexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Powdered potassium hydroxide (2.24 g, 39.9 mmol) was added to a 250 mL round-bottom flask and vigorously stirred in DMSO (65 mL) for 30 min. A solution of 2- phenylbenzimidazole (4.11 g, 21.2 mmol) in DMSO (65 mL) was added to the basic DMSO solution and the mixture stirred for 45 min closed at room temperature. Iodomethane (1.4 mL, 22.5 mmol) was then added and the mixture stirred for 45 min. The mixture was then poured into a stirring solution of water (1.0 L) containing potassium hydroxide (5.0 g). Diethyl ether (300 mL) was then added and stirred until both layers were transparent. The organic layer was decanted and the same process was repeated with additional diethyl ether (2 x 200 mL). The combined organics were washed with water, brine, water, dried over magnesium sulfate, filtered, and evaporated at 44 °C under dynamic vacuum to yield 7 (3.74 g, 85percent) as a pale brown powder.1HNMR (500MHz, DMSO-d6, delta 7.86 (dd, J= 7.8, 1.7Hz, 2H), 7.69 (d, J= 7.9Hz,1H), 7.64-7.52 (m, 4H), 7.33-7.22 (m, 2H), 3.88 (s, 3H). 13C NMR (125 MHz, DMSOd 6, delta): 152.98, 142.47, 136.57, 130.15, 129.60, 129.28, 128.63, 122.32, 121.90, 118.98, 110.53, 31.64. | |
62% | Under an atmospheric nitrogen gas flow, sodium hydride in an amount of 12.8 mmol (containing 438 mg of 30 percent liquid paraffin) was placed into a three neck flask having a capacity of 100 milliliter, and adding n-pentane in an amount of 10 milliliter, the resultant solution was stirred at room temperature for 15 minutes. Subsequently, n-pentane was removed and then, after adding n-pentane again, the resultant solution was stirred. Repeating the above operation 4 times totally, the liquid paraffin was removed. Afterwards, the refined sodium hydride was vacume dried among the flask. Then, adding N,N-dimethylformamide in an amount of 15 milliliter and hpbi in an amount of 7.7 mmol (1.5 g), the resultant solution was stirred at a temperature of 35 °C for 1 hour and, further adding methyl iodide in an amount of 9.6 mmol (1.36 g), the resultant solution was further stirred at a temperature of 40 °C for 3 hours. After the resultant solution was cooled by leaving it standing, the solvent was removed by pressure reduction, and adding pure water, the resultant solution was stirred. Further, after adding dichloromethane, the resultant solution was divided by extraction. Gathering an organic layer, and after dehydration with the use of sodium sulfate, the solvent was concentrated by pressure reduction. A white precipitate generated by adding n-hexane was separated by filtration and 0.99 g of the aimed substance was obtained (yield: 62 percent). | |
49% | In acetone; at 20℃; for 6h; | The synthesis of 1-methyl-2-phenyl-1H-benzoimidazole (Mpb) is accomplished by referring to methods disclosed in Popov, 1. I., Chem. Heterocycl. Compd. (EN), 1996, 32, 6, p.672-681. The synthetic method is outlined in Scheme 1. To 20 mL acetone was added 2-phenyl-1H-benzoimidazole (1.94 g, 10 mmol), followed by the injection of iodomethane (1.42 mL, 12 mmol). The mixture was stirred at room temperature for 6 h, sodium hydroxide solution was then added, and the mixture reacted for an additional 5 min. The reaction mixture was extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography using n-hexanes/EA (v/v=80/20) as eluent. After the product was completely isolated, 1.03 mg (0.49 mmol) of the title compound was obtained (49percent yield). 1H NMR (CDCl3, delta): 3.87 (s, 3 H), 7.32-7.41 (m, 3 H), 7.51-7.56 (m, 3 H), 7.83-7.86 (m, 3 H). |
8 g | With potassium tert-butylate; In tetrahydrofuran; at 20℃; | 2-Phenyl-1H-benzo [d] imidazole (10 g, Tokyo Chemical Industry) was dissolved in dehydrated tetrahydrofuran (200 ml, Wako Pure Chemical Industries), potassium t-butoxide (6.07 g, Wako Junyaku), iodinated Methyl (3.85 ml, Wako Pure Chemical Industries, Ltd.) was added and the mixture was stirred overnight at room temperature. After the reaction, the reaction mixture was extracted with chloroform (Wako Pure Chemical Industries, Ltd.), washed twice with water, and the organic layer was recovered. The organic layer was dried with anhydrous sodium sulfate (Wako Pure Chemical Industries, Ltd.) and concentrated. The residue was purified by silica gel column chromatography to obtain 8 g of 1-methyl-2-phenyl-1H-benzo [d] imidazole. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate 1) DMF, 25 deg C, 20 min, 2) DMF, 18 h; Yield given; Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With iron(III) sulfate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; In neat (no solvent); at 110℃; for 12h;Green chemistry; | General procedure: A mixture of 6 mmol of the alcohol or the amine and5 mmol o-phenylenediamine, o-aminophenol or o-aminothiophenol,10 mol % Fe2(SO4)3, 10 mol % TEMPO wasprepared in a 10 ml three-necked flask, and then stirred inopen air at 110 C for several hours, The reaction progresswas monitored by TLC. When the final reaction mixturecooled to room temperature, the crude products was directlypurified by column chromatography on silica gel using hexane/ethyl acetate (7:3) as eluent to afford the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 120℃; for 3h;Inert atmosphere; | Step3: Under nitrogen protection,2-Chlorobenzimidazole (1.41 g, 9.2 mmol) was added to the reaction vessel.Phenylboronic acid (1.02 g, 8.4 mmol),Tetrakistriphenylphosphine palladium (0.09g, 0.08mmol),Potassium carbonate (3.48g, 25.2mmol),Toluene 60mL, ethanol 20mL and distilled water 20mL,Stir at 120 ° C for 3 h.After the end of the reaction, the reaction was quenched with distilled water, ethyl acetate was extracted, and the organic layer was dried over MgSO..The solvent was removed by distillation under reduced pressure.After purification by silica gel column chromatography, Intermediate 75-3 (1.22 g, 75percent) was obtained. |
75% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 120℃; for 3h;Inert atmosphere; | Step 3: Under the protection of nitrogen, 2-chlorobenzimidazole (1.41 g, 9.2 mmol) and phenylboronic acid were added to the reaction vessel. (1.02 g, 8.4 mmol), tetrakistriphenylphosphine palladium (0.09 g, 0.08 mmol), potassium carbonate (3.48 g, 25.2 mmol), toluene 60 mL, ethanol 20 mL, and distilled water 20 mL, and stirred at 120 ° C for 3 h. After the end of the reaction, the reaction was quenched with distilled water, extracted with ethyl acetate, and the organic layer was dried over MgSO 4 After purification by silica gel column chromatography, Intermediate 73-3 (1.22 g, 75percent). |
75% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 120℃; for 3h;Inert atmosphere; | Under nitrogen protection,2-Chlorobenzimidazole (1.41 g, 9.2 mmol) was added to the reaction vessel.Phenylboronic acid (1.02 g, 8.4 mmol),Tetrakistriphenylphosphine palladium (0.09g, 0.08mmol),Potassium carbonate (3.48g, 25.2mmol),Toluene 60mL, ethanol 20mL and distilled water 20mL,Stir at 120 ° C for 3 h.After the reaction is over, the distilled water stops the reaction.Extracted with ethyl acetate,The organic layer was dried over MgSO 4The solvent was removed by distillation under reduced pressure.After purification by silica gel column chromatography, Intermediate 7-7 (1.22 g, 75percent) was obtained. |
75% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 120℃; for 3h;Inert atmosphere; | Step3: Under nitrogen protection,Add to the reaction vessel2-chlorobenzimidazole (1.41 g, 9.2 mmol),Phenylboronic acid (1.02 g, 8.4 mmol),Tetrakistriphenylphosphine palladium (0.09g, 0.08mmol),Potassium carbonate (3.48g, 25.2mmol),Toluene 60mL,20mL of ethanol and 20mL of distilled water,Stir at 120 ° C for 3 h.After the reaction is over, the distilled water stops the reaction.Extracted with ethyl acetate,The organic layer was dried over MgSO 4The solvent was removed by distillation under reduced pressure.After purification by silica gel column chromatography, Intermediate 77-3 (1.22 g, 75percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With potassium iodide; potassium hydroxide; In dimethyl sulfoxide; at 20℃; for 4h;Cooling; | To 28 mL of dimethyl sulfoxide was added 2.8 g (14 mmol, 1 equivalent) of 2-phenyl-1H-1,3-benzodiazole, 1.6 g (28 mmol, 2 eq.) Of potassium hydroxide, 0.12 g (0.72 mmol, 5 molpercent) of potassium iodide were sequentially added thereto, followed by cooling and stirring, 3.0 mL (28 mmol, 2 equivalents) of butane bromide was slowly added thereto, and the mixture was heated to room temperature and agitated for 4 hours. After completion of the reaction, 60 mL of water and 60 mL of ethyl acetate were added to the reaction mixture, After further washing with 60 mL of water, the solution was concentrated and purified by silica column chromatography to obtain 3.3 g (91percent) of 1-butyl-2-phenyl-1H-1,3-benzodiazole. |
87% | With sodium hydroxide; In water; at 20℃; for 0.5h;Micellar solution; | General procedure: To the reaction vessel containing benzimidazole or imidazole (1mmol), alkyl halide (1mmol), 50percent NaOH (0.5mL) and anionic surfactant sodium dodecyl sulfate (5molpercent) was added and the reaction mixture was vigorously stirred at room temperature or 60°C. After the completion of reaction (TLC) followed by standard workup using ethyl acetate as extracting solvent the crude product was purified over silica-gel (60?120 mesh) using ethyl acetate?hexane (3:7) as eluent to afford pure products. Identities of the products were judged by the comparison of melting point, IR data, 1H NMR, 13C NMR and HRMS analyses. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With carbon monoxide; 1,10-phenanthroline hydrate In N,N-dimethyl-formamide at 120℃; for 139.75h; | |
Multi-step reaction with 2 steps 1: ammonium chloride; zinc / methanol; water / 0.25 h / 0 °C 2: potassium carbonate; copper(I) bromide / dimethyl sulfoxide / 14 h / 120 °C / 760.05 Torr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 2: sulfuric acid / Diazotization.anschliessend Behandeln der Diazoverbindung mit Alkohol 3: hydriodic acid; red phosphorus / 170 - 180 °C / im Rohr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetonitrile; | EXAMPLE 11 Preparation of 1-Methyl-2-Phenylbenzimidazole Using DBU and Microwave Heating A solution of 2-phenylbenzimidazole (5 g, 25.7 mmmol) in DMC (50 mL), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (3.9 g, 25.7 mmol), and acetonitrile (50 mL), was passed through a Milestone ETHOS-CFR continuous-flow reactor preheated to 160° C. at 20 bar. The reaction products were analyzed by HPLC after each pass (6 min). The yield of 1-methyl-2-phenylbenzimidazole after 12 minutes as determined by HPLC was 97percent conversion. The results in Example 11 show that the relative rate of reaction was about 30 times faster to achieve essentially the same conversion using microwave heating at 160° C., as compared to using thermal heating to prepare 1-methyl-2-phenylbenzimidazole in Example 4 which was conducted at 90° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With copper(l) iodide; caesium carbonate; 9,10-phenanthroline; In N,N-dimethyl-formamide; for 48h;Heating / reflux; | 5.1g(10mmol) of <strong>[474688-76-1]2-bromo-9,10-di(2-naphthyl)anthracene</strong>,2.3 g (12 mmol) of 2-phenyl-1H-benzimidazole, 0.19 g (1.0 mmol) of copper iodide, and 3. 6 g (2.0 mmol) of 9, 10-phenanthroline were dissolved into a 2 M solution of cesium carbonate in dimethylformamide (DMF), and the whole was refluxed under heating for 48 hours in an argon atmosphere. After the completion of the reaction, the resultant was filtered. The filtrate was poured into 1L of 10-mass% hydrochloric acid, and the whole was extracted with methylene chloride. An organic layer was taken out and dried with magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resultant solid was purified by means of silica gel column chromatography to obtain 2.2 g of a pale yellow solid (35% yield). Mass spectral analysis confirmed that the solid was a target product. The solid had an m/e of 622 with respect to a molecular weight of 622.24. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 10h; | General procedure: 2.5 g (12.88 mmol) of 2-phenyl-benzimidazole was dissolved in 30 ml of N,N-dimethylformamide, and 5.3 g (38.6 mmol) of K2CO3 and 2.0 ml (16.7 mmol) of 1-chloro-4-iodobutane were added to the resulting solution, followed by mixing the mixture at a room temperature for 10 hours. The reactant was combined with 100 ml of water and extracted with ethylacetate (70 ml X 5) being washed with water and a sodium hydroxide solution, and then the combined organic layer was dried over anhydrous sodium sulfate and filtered. The solvent was removed from the filtrate under a reduced pressure, and the resulting residue was refined by silica gel column chromatography (n-hexane/ethylacetate=2/1) to obtain 3.5 g (yield 96%) of the title compound.1H NMR (300MHz, CDCl3) delta 1.69(m, 2H), 2.00(m, 2H), 3.43(t, 2H), 4.29(t, 2H), 7.30-7.50(m, 3H), 7.55(m, 3H), 7.72(m, 2H), 7.83(m, 1H); MS(m/e, M+): 285 |
96% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 10h; | Preparation Example 7; Preparation of l-f4-chlorobuM)-2-phenyl-lH-benzimidazole (formula (IV); n=3. X=H) 2.5 g (12.88 mmol) of 2-rhohenyl-benzimidazole was dissolved in 30 ml of N,N-dimethylformamide, and 5.3 g (38.6 mmol) Of K2CO3 and 2.0 ml (16.7 mmol) of l-chloro-4-iodobutane were added to the resulting solution, followed by mixing the mixture at a room temperature for 10 hours. The reactant was combined with 100 ml of water and extracted with ethylacetate (70 ml X 5) being washed with water and a sodium hydroxide solution, and <n="30"/>then the combined organic layer was dried over anhydrous sodium sulfate and filtered. The solvent was removed from the filtrate under a reduced pressure, and the resulting residue was refined by silica gel column chromatography (n-hexane/ethylacetate=2/l) to obtain 3.5 g (yield 96%) of the title compound.1H NMR (300MHz, CDCl3) delta 1.69(m, 2H), 2.00(m, 2H), 3.43(t, 2H), 4.29(t, 2H), 7.30-7.50(m, 3H), 7.55(m, 3H), 7.72(m, 2H), 7.83(m, IH); MS(m/e, M+): 285 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 10h; | 9 Preparation Example 9; Preparation of l-f5-cMoroρentyl)-2-phenvϖNo.-benzimidazole fformula (IV); n=4, X=H)2.5 g (12.88 mmol) of 2-ρhenyl-benzimidazole was dissolved in 30 ml of N,N-dimethylformamide, and 5.3 g (38.6 mmol) Of K2CO3 and 2.3 ml (16.7 mmol) of l-chloro-5-iodopetane were added to the resulting solution, followed by mixing the solution at a room temperature for 10 hours. The reaction mixture was combined with 100 ml of water and extracted with ethylacetate (70 ml X 5) being washed with water and a sodium hydroxide solution, and then the combined organic layer was dried over anhydrous sodium sulfate, and filtered. The solvent was removed under a reduced pressure, and the resulting residue was refined by silica gel column chromatography (n-hexane/ethylacetate=3/l) to obtain 3.16 g (yield 82%) of the title compound. 1H NMR (SOOMHZ5 CDCl3) δ 1.35(m, 2H), 1.67-1.87(m, 4H)5 3.41 (t, 2H)5 4.25(t, 2H)5 7.31(m3 2H), 7.39(m5 IH)5 7.51-7.55(m5 3H), 7.70(m, 2H)5 7.81(m, IH); MS(m/e5 M+): 298 |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 10h; | 1-(4-chlorobutyl)-2-phenyl-1H-benzimidazole (2) General procedure: 2.5 g (12.88 mmol) of 2-phenyl-benzimidazole was dissolved in 30 ml of N,N-dimethylformamide, and 5.3 g (38.6 mmol) of K2CO3 and 2.0 ml (16.7 mmol) of 1-chloro-4-iodobutane were added to the resulting solution, followed by mixing the mixture at a room temperature for 10 hours. The reactant was combined with 100 ml of water and extracted with ethylacetate (70 ml X 5) being washed with water and a sodium hydroxide solution, and then the combined organic layer was dried over anhydrous sodium sulfate and filtered. The solvent was removed from the filtrate under a reduced pressure, and the resulting residue was refined by silica gel column chromatography (n-hexane/ethylacetate=2/1) to obtain 3.5 g (yield 96%) of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium hydroxide In acetone Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 10h; | 1-(4-chlorobutyl)-2-phenyl-1H-benzimidazole (2) General procedure: 2.5 g (12.88 mmol) of 2-phenyl-benzimidazole was dissolved in 30 ml of N,N-dimethylformamide, and 5.3 g (38.6 mmol) of K2CO3 and 2.0 ml (16.7 mmol) of 1-chloro-4-iodobutane were added to the resulting solution, followed by mixing the mixture at a room temperature for 10 hours. The reactant was combined with 100 ml of water and extracted with ethylacetate (70 ml X 5) being washed with water and a sodium hydroxide solution, and then the combined organic layer was dried over anhydrous sodium sulfate and filtered. The solvent was removed from the filtrate under a reduced pressure, and the resulting residue was refined by silica gel column chromatography (n-hexane/ethylacetate=2/1) to obtain 3.5 g (yield 96%) of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With indium; acetic acid; In ethyl acetate; for 3h;Reflux; Inert atmosphere; | General procedure: 2-Nitroaniline derivative (1 mmol) was added to a mixture of indium powder (574 mg, 5.0 mmol for 2-nitroaniline, 918 mg 8.0 mmol for 1,2-dinitroarene), and acetic acid (0.572 mL, 10 mmol) in ethyl acetate (2 mL), followed by the addition of trimethyl orthoester (2.0 mmol) in ethyl acetate (3 mL for 2-nitroaniline; 8 mL for 1,2-dinitroarene). The reaction mixture was stirred at reflux under a nitrogen atmosphere. After the reaction was completed, the reaction mixture was diluted with ethyl acetate (30 mL), filtered through Celite, poured into 10% NaHCO3 (30 mL), and then extracted with ethyl acetate (30 mL×3). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The residue was eluted with ethyl acetate/hexane (v/v=10/90) for 2-phenylbenzimidazole derivatives or methanol/dichloromethane (v/v=1/99) for 2-methylbenzimidazole derivatives through a silica gel column to give the corresponding benzimidazoles. The structures of the benzimidazoles were characterized by 1H NMR, 13C NMR, FTIR, and GC-MS, and were mostly known compounds. HRMS data were reported in addition for unknown compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With indium; acetic acid; In ethyl acetate; for 1.5h;Reflux; Inert atmosphere; | General procedure: 2-Nitroaniline derivative (1 mmol) was added to a mixture of indium powder (574 mg, 5.0 mmol for 2-nitroaniline, 918 mg 8.0 mmol for 1,2-dinitroarene), and acetic acid (0.572 mL, 10 mmol) in ethyl acetate (2 mL), followed by the addition of trimethyl orthoester (2.0 mmol) in ethyl acetate (3 mL for 2-nitroaniline; 8 mL for 1,2-dinitroarene). The reaction mixture was stirred at reflux under a nitrogen atmosphere. After the reaction was completed, the reaction mixture was diluted with ethyl acetate (30 mL), filtered through Celite, poured into 10% NaHCO3 (30 mL), and then extracted with ethyl acetate (30 mL×3). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The residue was eluted with ethyl acetate/hexane (v/v=10/90) for 2-phenylbenzimidazole derivatives or methanol/dichloromethane (v/v=1/99) for 2-methylbenzimidazole derivatives through a silica gel column to give the corresponding benzimidazoles. The structures of the benzimidazoles were characterized by 1H NMR, 13C NMR, FTIR, and GC-MS, and were mostly known compounds. HRMS data were reported in addition for unknown compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With indium; acetic acid; In ethyl acetate; for 1h;Reflux; Inert atmosphere; | General procedure: 2-Nitroaniline derivative (1 mmol) was added to a mixture of indium powder (574 mg, 5.0 mmol for 2-nitroaniline, 918 mg 8.0 mmol for 1,2-dinitroarene), and acetic acid (0.572 mL, 10 mmol) in ethyl acetate (2 mL), followed by the addition of trimethyl orthoester (2.0 mmol) in ethyl acetate (3 mL for 2-nitroaniline; 8 mL for 1,2-dinitroarene). The reaction mixture was stirred at reflux under a nitrogen atmosphere. After the reaction was completed, the reaction mixture was diluted with ethyl acetate (30 mL), filtered through Celite, poured into 10% NaHCO3 (30 mL), and then extracted with ethyl acetate (30 mL×3). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The residue was eluted with ethyl acetate/hexane (v/v=10/90) for 2-phenylbenzimidazole derivatives or methanol/dichloromethane (v/v=1/99) for 2-methylbenzimidazole derivatives through a silica gel column to give the corresponding benzimidazoles. The structures of the benzimidazoles were characterized by 1H NMR, 13C NMR, FTIR, and GC-MS, and were mostly known compounds. HRMS data were reported in addition for unknown compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With indium; acetic acid; In ethyl acetate; for 2.5h;Reflux; Inert atmosphere; | General procedure: 2-Nitroaniline derivative (1 mmol) was added to a mixture of indium powder (574 mg, 5.0 mmol for 2-nitroaniline, 918 mg 8.0 mmol for 1,2-dinitroarene), and acetic acid (0.572 mL, 10 mmol) in ethyl acetate (2 mL), followed by the addition of trimethyl orthoester (2.0 mmol) in ethyl acetate (3 mL for 2-nitroaniline; 8 mL for 1,2-dinitroarene). The reaction mixture was stirred at reflux under a nitrogen atmosphere. After the reaction was completed, the reaction mixture was diluted with ethyl acetate (30 mL), filtered through Celite, poured into 10% NaHCO3 (30 mL), and then extracted with ethyl acetate (30 mL×3). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The residue was eluted with ethyl acetate/hexane (v/v=10/90) for 2-phenylbenzimidazole derivatives or methanol/dichloromethane (v/v=1/99) for 2-methylbenzimidazole derivatives through a silica gel column to give the corresponding benzimidazoles. The structures of the benzimidazoles were characterized by 1H NMR, 13C NMR, FTIR, and GC-MS, and were mostly known compounds. HRMS data were reported in addition for unknown compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With dipotassium peroxodisulfate; potassium iodide at 80℃; for 6h; Schlenk technique; | (16) N-(1H-1,2,3-benzotriazol-1-ylmethyl)-N-methylacetamide(3a); typical procedure General procedure: A 50 mL Schlenk tube equipped with a stirrer bar was charged with KI (16.6 mg, 0.1 mmol), benzotriazole (59.5 mg, 0.5 mmol), DMA (2 mL), and K2S2O8 (270 mg, 1 mmol) under air. The mixture was then stirred at 80 °C for 6 h (TLC monitoring), poured into H2O (20 mL), and extracted with EtOAc (3 ×). Then the organic phase was evaporated under vacuum, and the crude product was purified by column chromatography [silica gel, PE-EtOAc (10:1 to 2:1)] to give a colorless oil; yield: 98 mg (96%); |
80% | With di-tert-butyl peroxide; iron(II) chloride In chlorobenzene at 120℃; for 3h; Inert atmosphere; Schlenk technique; | |
62% | With tert.-butylhydroperoxide; iron(II) acetate In decane; 1,2-dichloro-ethane at 80℃; for 3h; Inert atmosphere; | General procedure for the iron catalyzed oxidative coupling of N-alky amide with azoles: General procedure: A tert-butyl hydroperoxide (1.5 mmol, 5-6 M decane) was dropped slowly for 5 minutes to a mixture of azole (0.5 mmol), Fe(OAc)2 (10 mol%) and N,N-dimethylacetamide (5.0 mmol) in 1,2-dichloroethane (DCE, 1.0 mL) in to the reaction mixture under nitrogen atmosphere. The resulting mixture was stirred at 80 °C for 3 hours. The reaction was monitored by thin layer chromatography. After completion of the reaction, the resulting solution was cooled to room temperature. The reaction mixture was then filtered through silica gel bed using ethyl acetate and the filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel using ethyl acetate/methanol as an eluent to afford the corresponding products. The products were confirmed by 1H, 13C NMR, IR and Mass spectroscopic analysis. |
15 %Chromat. | With tert.-butylhydroperoxide In decane at 110℃; for 24h; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With boron trifluoride diethyl etherate; In 1,4-dioxane; at 100℃; for 1h;Inert atmosphere; | General procedure: To a solution of o-diaminobenzene (5.0 mmol, 0.5405 g) and Weinreb amide (N-methoxy-Nmethylbenzamide, 5.0 mmol, 0.82595 g) in dioxane (10 mL), boron trifluoride diethyl etherate (5.0 mmol) was added at room temperature. The reaction mixture was stirred for the specified time (Table 3) at 100 C. TLC revealed the complete consumption of starting material. Subsequently hydrolysis was achieved by the addition of saturated NH4Cl solution (50 mL). The aqueous layer was extracted with ethyl acetate (3 X 25 mL), washed with water (2 X 25 mL), brine solution (2 X 25 mL), dried over anhydrous Na2SO4 and concentrated under vacuum to get crude product. This was purified by column chromatography over silica gel using hexane/ethyl acetate mixture in 1:1 ratios as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With 5%-palladium/activated carbon In water; toluene at 110℃; for 20h; Inert atmosphere; | Typical Experimental Procedure General procedure: A mixture of o-phenylenediamine (1) (0.108 g, 1 mmol), tributylamine (2a) (0.185g, 1 mmol), 5% Pd/C (0.106 g, 0.05 mmol) and toluene/H2O (10 mL/0.5 mL) was placed in 25 mL round bottom flask. After the system was flushed with Ar from an Ar balloon connected to the flask via a reflux condenser, the reaction mixture was allowed to react at 110 oC for 20 h. The reaction mixture was filtered through a short silica gel column (ethylacetate-hexane mixture) to eliminate catalyst residue. Removal of the solvent left a crude mixture, which was separated by thin layer chromatography (silica gel, ethyl acetate-hexanemixture = 1/1) to give 2-propylbenzimidazole (3a) (0.115 g,72%). All products are known and several selected spectroscopic data are shown below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; copper(II) acetate monohydrate; In acetonitrile; at 80℃; for 12h;Inert atmosphere; | General procedure: A mixture of bicyclic olefin 2a (0.2083 mmol, 1.75 equiv),2-phenylimidazole (0.1191 mmol, 1.0 equiv), [RhCl2Cp*]2(0.0029 mmol, 2.5 molpercent), and Cu(OAc)2·H2O (0.1338mmol, 1.5 equiv) were weighed in a Schlenk tube anddegassed for 10 min. Anhydrous MeCN (2 mL) was added,and the reaction mixture was purged with argon and allowedto stir at 80 °C for 12 h. The solvent was evaporated invacuo, and the residue was purified with columnchromatography (silica gel, 100?200 mesh) using anEtOAc?hexane mixture. Mono- and biscyclopentenylfunctionalizedaza heteroaromatics were obtained in 48percentand 39percent yields, respectively. |
52% | With [RhCl2(p-cymene)]2; copper(II) acetate monohydrate; In toluene; at 110℃; for 12h;Schlenk technique; Inert atmosphere; | General procedure: A mixture of diazabicyclic olefin (50 mg, 0.2083 mmol, 1.0 eqiuv), N-phenylpyrazole (30 mg, 0.2083 mmol, 1.0 eqiuv), [RuCl2(p-cymene)]2 (6 mg, 0.0104 mmol, 5.0 mol percent), and Cu(OAc)2·H2O (62.46 mg, 0.3123 mmol, 1.5 equiv) was weighed in a Schlenk tube and degassed for 10 min. Dry toluene (2 mL) was added and the reaction mixture was purged with argon and allowed to stir at 110 °C for 12 h. The reaction mixture on silica gel column chromatography using mixtures of EtOAc?hexane yielded functionalized cyclopentene 3a in 73percent yield (58 mg). |
52% | With [ruthenium(II)(eta6-1-methyl-4-isopropyl-benzene)(chloride)(mu-chloride)]2; copper(II) acetate monohydrate; In toluene; at 110℃;Schlenk technique; Inert atmosphere; | General procedure: A mixture of diazabicyclic olefin (50 mg, 0.2083 mmol,1.0 eqiuv), N-phenylpyrazole (30 mg, 0.2083 mmol, 1.0 eqiuv), [RuCl2(p-cymene)]2 (6 mg, 0.0104 mmol, 5.0 mol percent), and Cu(OAc)2H2O (62.46 mg,0.3123 mmol, 1.5 equiv) was weighed in a Schlenk tube and degassed for10 min. Dry toluene (2 mL) was added and the reaction mixture was purged with argon and allowed to stir at 110 °C for 12 h. The reaction mixture on silicagel column chromatography using mixtures of EtOAc?hexane yielded functionalized cyclopentene 3a in 73percent yield (58 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With caesium carbonate; In acetonitrile; at 20℃; for 3h; | Example 18 Preparation of Methyl 2-(2-phenyl-1H-benzo[d]imidazol-1-yl)acetate (S18) To a suspension of 2-phenyl benzimidazole (0.32 g, 1.6 mmol) in acetonitrile (5 mL) was added caesium carbonate (0.80 g, 2.5 mmol) and methyl bromoacetate (0.16 mL, 1.7 mmol). The reaction mixture was stirred at room temperature for 3 hours and concentrated in vacuo. The residue was suspended in a mixture of CH2Cl2 and sat. NaHCO3 (vol percent 50:50, 15 mL). The aqueous layer was reextracted with CH2Cl2 (2 x 20 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in in vacuo to afford the product (0.40 g, 1.5 mmol, 91 percent). 1H NMR (400 MHz, DMSO-d6) delta 7.77 - 7.63 (m, 3H), 7.63 - 7.44 (m, 4H), 7.33 - 7.09 (m, 2H), 5.21 (s, 2H), 3.64 (s, 3H). 13C NMR (101 MHz, DMSO-d6) delta 169.40, 153.91, 143.08, 136.91, 130.57, 130.51, 129.62, 129.53, 123.45, 123.00, 119.87, 111.36, 53.17, 46.57. LC-MS (ESI): calcd for C16H14N2O2: 267.11280 [M+H]+, found: 267.18 [M+H]+; HR-MS found 267.11311 [M+H]+. |
91% | With caesium carbonate; In acetonitrile; at 20℃; for 3h; | To a suspension of 2-phenyl benzimidazole (0.32 g, 1 .6 mmol) in acetonitrile (5 mL) was added caesium carbonate (0.80 g, 2.5 mmol) and methyl bromoacetate (0.16 mL, 1 .7 mmol). The reaction mixture was stirred at room temperature for 3 5 hours and concentrated in vacuo. The residue was suspended in a mixture of CH2CI2 and sat. NaHCO3 (vol percent 50:50, 15 mL). The aqueous layer was reextracted with CH2CI2 (2 x 20 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in in vacuo to afford the product (0.40 g, 1 .5 mmol, 91 percent). 1H NMR (400 MHz, DMSO-c/6) delta 7.77 - 7.63 (m, 3H), 7.63 - 7.44 (m, 4H), 7.33 - 7.09 (m, 2H), 5.21 (s, 2H), 3.64 (s, 3H). 13C NMR (101 MHz, DMSO-c/6) delta 169.40, 153.91 , 143.08, 136.91 , 130.57, 130.51 , 129.62, 129.53, 123.45, 123.00, 1 19.87, 1 1 1 .36, 53.17, 46.57. LC-MS (ESI): calcd for Ci6Hi4N2O2: 267.1 1280 [M+H]+, found: 267.18 [M+H]+; HR-MS found 267.1 131 1 [M+H]+. |
50% | Example 3 Methyl 2-(2-phenyl-1H-benzo[d]imidazol-1-yl)acetate 2-phenyl-1H-benzo[d]imidazole (50 mg, 0.26 mmol) and sodium hydride (7.5 mg, 0.31 mmol) are dissolved into dimethyl formamide (500 muL) under nitrogen. At room temperature, the reaction mixture is agitated for 1 hour. After adding methyl bromoacetate (28.6 muL, 0.31 mmol) is added thereto, the reaction mixture is agitated for 16 hours at room temperature. The reaction progress and result are checked by TLC. After completing the reaction, water is added to the reaction mixture and is extracted with ethyl acetate. The organic layer is dried with dry magnesium sulfate, followed by filtering. The filtrate is concentrated under reduced pressure and the concentrate is purified by column chromatography (EA:n-Hex=1:2) to obtain 35 mg of the target compound (yield: 50percent). 1H NMR (300 MHz, CDCl3-d) delta ppm 7.87 (m, 1H) 7.72 (m, 2H) 7.54 (m, 3H) 7.35 (m, 3H) 4.93 (s, 2H) 3.82 (s, 3H) |
50% | With sodium hydride; In N,N-dimethyl-formamide; at 20℃; for 16h;Inert atmosphere; | 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, 50percent). 1H NMR (300 MHz, CDCl3) delta ppm 7.87 (m, 1H) 7.72 (m, 2H) 7.54 (m, 3H) 7.35 (m, 3H) 4.93 (s, 2H) 3.82 (s, 3H); LC/MS (ESI+, MeCN/H2O): m/z: calcd for C15H13N2O2: 253.09 [M + H]+; found: 253.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In N,N-dimethyl-formamide at 110℃; for 5h; | |
79% | With iron(III) chloride hexahydrate In N,N-dimethyl-formamide at 100℃; for 24h; | |
67% | With triethylamine; copper(I) bromide In N,N-dimethyl-formamide at 20 - 100℃; chemoselective reaction; |
60% | With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In water; dimethyl sulfoxide at 100℃; for 2h; Sealed tube; | |
With potassium carbonate; copper(I) bromide In dimethyl sulfoxide at 120℃; for 14h; | General procedure for synthesis of benzimidazole derivatives 5a-h General procedure: A solutionof2-aminoaniline 4a-h (0.2 mmol), K2CO3 (0.6 mmol,83mg), andCuBr (0.02 mmol,2.8mg) in DMSO (2mL) was provided.Themixturewasallowedto stirunderair (1 atm) at 120 °C for14h.Aftercompletionofthereaction,theresulting solutionwascooledtoroomtemperatureandfiltered.Afterward,thefil-trate wasevaporatedusingarotaryevaporator.Thentheresiduewaspurifiedbycol-umn chromatographyonsilicagelusingpetroleumether / ethyl acetate (3:1 to2:1) aseluent toprovide 5a-h. Alltheproductswereidentifiedandcharacterizedbycom-parison ofmeltingpoint (mp), IR,and 1H NMRand 13CNMR spectroscopy.[35] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With triphenylphosphine(1,5-cyclooctadiene)[1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene]iridium(I) hexafluorophosphate; deuterium; In dichloromethane; at 25℃; under 760.051 Torr; for 1h;Sealed tube; | 4.3.1.8 2-Phenylbenzimidazole 13 Following general procedure A, exchange of <strong>[716-79-0]2-phenylbenzimidazole</strong> 13 (16.8 mg) in the presence of catalyst 1a (4.4 mg) gave [2',6'-2H2]-13 (14.8 mg, 88percent, 84percentD). Following general procedure A, exchange of <strong>[716-79-0]2-phenylbenzimidazole</strong> 13 (16.8 mg) in the presence of catalyst 1b (4.6 mg) gave [2',6'-2H2]-13 (14.9 mg, 89percent, 83percentD). Following general procedure A, exchange of <strong>[716-79-0]2-phenylbenzimidazole</strong> 13 (16.8 mg) in the presence of catalyst 1c (3.8 mg) gave [2',6'-2H2]-13 (13.8 mg, 82percent, 72percentD). Following general procedure A, exchange of <strong>[716-79-0]2-phenylbenzimidazole</strong> 13 (16.8 mg) in the presence of catalyst 5 (3.4 mg) gave [2',6'-2H2]-13 (15.3 mg, 91percent, 72percentD). deltaH (300 MHz, DMSO-d6) 12.90 (s, 1H), 8.19-8.17 (m, 2H), 7.60-7.47 (m, 5H), 7.23-7.18 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With tert.-butylhydroperoxide; trimethylsilylazide; copper(II) acetate monohydrate In decane; dimethyl sulfoxide at 80℃; for 12h; | |
77% | With tert.-butylhydroperoxide; sodium azide; copper diacetate; acetic acid In dimethyl sulfoxide at 80℃; for 10h; | |
163 mg | With tert.-butylhydroperoxide; copper(l) iodide; trimethylsilylazide at 20 - 90℃; regioselective reaction; |
Multi-step reaction with 2 steps 1.1: N-chloro-succinimide / N,N-dimethyl-formamide; dichloromethane / 20 - 22 °C 1.2: 0 - 22 °C 2.1: fac-tris(2-phenylpyridinato-N,C2')iridium(III) / N,N-dimethyl acetamide / 20 - 22 °C / Sealed tube; Irradiation; Inert atmosphere | ||
Multi-step reaction with 2 steps 1.1: N-chloro-succinimide / N,N-dimethyl-formamide; dichloromethane / 20 - 22 °C 1.2: 0 - 22 °C 2.1: fac-tris(2-phenylpyridinato-N,C2')iridium(III) / 20 - 22 °C / Sealed tube; Irradiation; Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium carbonate; In dimethyl sulfoxide; at 150℃; for 12h;Inert atmosphere; | <strong>[96606-37-0]2,4,6-trifluorobenzonitrile</strong> (0.25g, 1.6mmol), potassium carbonate (0.99g, 7.2mmol), 2-phenylbenzimidazole (1.02g, 5.2mmol), DMSO 8ml , 150 heated to reflux 12h.Cooling to room temperature the precipitated solid was poured into 200ml of water was stirred 0.5h, filtered off with suction to give a white solid, purified by column chromatography to give a white solid 0.95g, 88% yield |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With sodium hydride; In N,N-dimethyl-formamide; at 20℃; | General procedure: To a solution of TBZ (1.0 equiv) (for TBZ-10, 11, 12, 13, 18) or 2-phenyl-1H-benzo[d]imidazole (1.0 equiv) (for TBZ-20) with sodium hydride (1.2 equiv) in DMF for 15 min, then corresponding iodomethane, benzyl bromide, 4-methoxybenzylchloride, 3-nitrobenzyl bromide, 5-(chloromethyl)-1,2,3-trimethoxybenzene(1.0 equiv) was added slowly at room temperature. On completion of the reaction monitored by TLC, the solvent was evaporated and the residue was purified by silica gel chromatography by DCM/MeOH system to afford the final product. |
87% | With sodium hydroxide; In water; at 20℃; for 0.333333h;Micellar solution; | General procedure: To the reaction vessel containing benzimidazole or imidazole (1mmol), alkyl halide (1mmol), 50percent NaOH (0.5mL) and anionic surfactant sodium dodecyl sulfate (5molpercent) was added and the reaction mixture was vigorously stirred at room temperature or 60°C. After the completion of reaction (TLC) followed by standard workup using ethyl acetate as extracting solvent the crude product was purified over silica-gel (60?120 mesh) using ethyl acetate?hexane (3:7) as eluent to afford pure products. Identities of the products were judged by the comparison of melting point, IR data, 1H NMR, 13C NMR and HRMS analyses. |
41% | With sodium hydroxide; In dimethyl sulfoxide; at 40℃; for 3h;Inert atmosphere; | 1-Benzyl-<strong>[716-79-0]2-phenylbenzimidazole</strong> (L) was prepared by adding benzyl bromide (0.288 g, 1.6 mmol) to a suspension of 1-H-<strong>[716-79-0]2-phenylbenzimidazole</strong> (0.294 g, 1.5 mmol) and NaOH (0.120 g, 3 mmol) in DMSO (1 mL) followed by stirring the mixture in an argon atmosphere at 40°C. After 1.5 h, DMSO (0.5 mL) was added, because the mixture became very viscous and did not allow to be mixed. The mixture turned yellow 3 h after the reaction; water (10 mL) was added therein, and the precipitate was filtered off. The precipitate was dissolved in ethanol on heating; the obtained solution was evaporated to dryness, and the resulting precipitate was redissolved in CH2Cl2 (1 mL). Under slow evaporation, colorless needle crystals and yellow oil precipitated, the latter was removed with ether. The remaining crystals were dried in vacuum at 50°C for 2 h. Yield, 180 mg (41percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With iron(III) nitrate nonahydrate In acetonitrile at 80℃; for 12h; | Typical Procedure for oxidative synthesis of benzimidazoles General procedure: A mixture of 1.5 mmol o-phenylenediamine, and 1 mmol imine, 5 mol% Fe(NO3)3·9H2O, and 5 ml MeCN were mixed in a 10 ml three-necked flask, one necked is equiped with a condenser, another is equiped with a thermometer with a condenser, and then stirred rapidiy open to air at 80°C for 12 hours. The reaction progress was monitored by TLC. After completion of the reaction, the residue was directly purified by column chromatograph on a silica gel using hexane/ethyl acetate (7:3) as eluent to afford the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium carbonate In water at 130℃; for 20h; Schlenk technique; Sealed tube; | 11 Embodiment 11 In a clean dry 10 ml Schlenk reaction tube, are sequentially added ortho-nitroaniline 35 mg, benzene glycine 113 mg, potassium carbonate 80 mg, in order to 1 ml of water as a solvent, the reaction tube seal, in 130 °C reaction under 20 hours. After the reaction, the reaction mixture directly by rotating the evaporimeter turns on lathe does, then the volume ratio of 3:1 of petroleum ether and ethyl acetate as the eluant, by separating by silica gel column, to obtain 40 mg of pale yellow solid, yield 82%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35%; 35% | With sulfuric acid; dihydrogen peroxide; In water; at 100 - 130℃; | General procedure: A solution of 10.0 mmol of compound 1a-1d in 14 mL of concentrated sulfuric acid was heated to 100-105C, 14 mL (0.26 mol) of 30% aqueous hydrogen peroxide was added dropwise with stirring,and the mixture was stirred for 1 h at 130C. After cooling, the mixture was poured into water and adjusted to pH 4, and the precipitate was filtered off. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With iodine; dimethyl sulfoxide; sodium sulfate at 120℃; for 12h; | |
58% | With iodine; nitrobenzene In 1,4-dioxane at 140℃; for 20h; Sealed tube; chemoselective reaction; | General Procedure for synthesis of 3 General procedure: Acetophenone 1 (1mmol), 2-amino aniline 2 (1mmol), I2 (13mg, 5mol%), PhNO2 (123mg, 1mmol) and 1,4-dioxane (3 mL) were added to a reaction tube. The reaction mixture was stirred in a sealed tube at 140 °C for 20 h. The reaction was monitored by TLC. Once the reaction was completed, the reaction mixture was treated with H2O (15.0 mL) and EtOAc (8.0 mL). The organic phase was then separated, and the aqueous phase was extracted with EtOAc (3 x 8 mL). The combined organic phase was dried over Na2SO4, then the solvent was removed under a reduced pressure and the remaining residue was purified by column chromatography. |
70 mg | With iodine; sodium sulfate In dimethyl sulfoxide at 120℃; for 14h; Sealed tube; |
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In 2-methoxy-ethanol at 150℃; for 14h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 40% 2: 48% | With iodine; dimethyl sulfoxide; sodium sulfate at 120℃; for 12h; | |
With nitric acid In dimethyl sulfoxide at 100℃; for 12h; Sealed tube; | 2 Example 2 Put 0.1mmol oxidized lignin model substrate 1 in a 10mL pressure tube, add 0.01mmol HNO3, 1mL DMSO and 0.2mmol o-phenylenediamine 2,After tightening the cap, heat the resulting reaction solution (the concentration of oxidized lignin in the reaction solution is 0.1 mmol/mL) in an oil bath at 100°C for 12 hours,The decomposition reaction is carried out. After the reaction is completed, the obtained product is taken out and the solvent is drained and separated by a column to obtain two nitrogen-containing heterocyclic products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; acetic acid In 1,2-dichloro-ethane at 120℃; for 24h; Schlenk technique; Sealed tube; | |
49% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; silver bis(trifluoromethylsulfonyl)imide In 1,2-dichloro-ethane at 120℃; for 13h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With sulfuric acid; dihydrogen peroxide In water at 100 - 120℃; for 0.5h; | Synthesis of 2-alkylimidazole-4,5-dicarboxylic acids 2a-2i (general procedure). General procedure: To a stirred solution of 10.0 mmol of compound 1a-1i in 10 mL of conc. H2SO4 we added dropwise 10 mL (0.11 mmol) of 33% aqueous hydrogen peroxide at 100-105°C. The mixture was stirred for 0.5 h at 120°C, let to cool down, and poured in water. The pH of the solution was adjusted to ~2 with sodium carbonate, and the precipitate of 2-alkylimidazole-4,5-dicarboxylic acid 2a-2i was filtered off and recrystallized from water. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With potassium carbonate; In dimethyl sulfoxide; at 150℃; for 12h; | <strong>[3512-17-2]<strong>[3512-17-2]2,4,6-Trifluoropyridin</strong>e</strong> (0.5 g, 3.76 mmol), potassium carbonate (5.19 g, 37.6 mmol), 2-phenylbenzimidazole (2.41 g, 12.4 mmol), DMSO 8 ml, heated at 150 C for 12 h. .After cooling to room temperature, a large amount of solid was poured out in 200 ml of water and stirred for 0.5 h, and filtered to give a white solid. After purification by column chromatography, ethanol was recrystallized to give white solid 1.92 g, yield 78%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With Imidazole hydrochloride In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 8h; | 19 4.3. General procedure for the synthesis of benzimidazole derivatives (3f-3j) General procedure: A mixture of 1a (0.54 g, 5 mmol), imidazolium chloride (0.09 g, 0.5 mmol) and N, N-dimethylbenzamide (0.55 g, 7.5 mmol) in 5mL xylene was heated to 140 °C and stirred at this temperature for 8 h. When the reaction was completed, 50mL water was added and the resulting mixture was extracted with 50 mL ethyl acetate twice. The combined organic layer was successively washed with H2O (50 mL) and then brine (50 mL), then dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using petroleum ether and ethyl acetate as the eluent or recrystallized from petroleum ether/EA to give the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | at 250℃; for 3h; Autoclave; Inert atmosphere; | 1-2; 2; 4 Example 1-1 General procedure: o-phenylenediamine (3 mmol, 324 mg)And phthalic acid (3 mmol, 498 mg),It was placed in an autoclave container made of SUS316 and having a volume of about 10 mL.After making the inside of this autoclave container nitrogen gas atmosphere,Deaerated pure water was introduced.Put this autoclave container in the heating furnace,The furnace temperature was raised to 200 ° C.At this time,The pressure was maintained at 25 MPa.3 hours laterThe temperature in the heating furnace was quickly lowered.Also,The pressure inside the autoclave vessel was reduced to atmospheric pressure.Next,Recover solid reaction products from inside the autoclave vessel,Dry under vacuum for 24 hours.As a result of analysis by NMR spectroscopy,The yield of 2- (2-carboxyphenyl) benzimidazole was 98%.Send feedbackHistorySaved |
Multi-step reaction with 2 steps 1: 3 h / 200 °C / 187519 Torr / Autoclave; Inert atmosphere 2: water / 3 h / 375 °C / 187519 Torr / Autoclave; Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium phosphate; copper diacetate In N,N-dimethyl-formamide at 130℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 41% 2: 28% | In acetonitrile for 0.166667h; Irradiation; chemoselective reaction; | 3.3. Synthesis of 2-substituted benzimidazoles and benzothiazoles (3&5) General procedure: A mixture of 1,2-Diaminobenzene 1 or 2-Mercaptoaniline 4(1 mmol), benzyl bromides (1 mmol) 2 and 4 % Cu:ZnS NPs (10 mol %)in 10 ml of CH3CN were irradiated in visible light (100W OSRAMTungsten Lamp, EFP 64627 HLX) with continuous stirring for the appropriatetime. Catalyst was separated by centrifugation after thecompletion of reaction. Evaporation of the above solution gave thecrude product which was purified using crystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 78% 2: 19% | With [bis(acetoxy)iodo]benzene; iodine; palladium diacetate In acetonitrile at 80℃; for 3h; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: potassium hydroxide / acetone / 12 h / 50 °C / Heating 2: ethyl acetate / 12 h / 80 °C / Reflux 3: sodium tetrahydroborate / methanol / 0.5 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.7% | With sulfuric acid at 40 - 85℃; | 2-1; 2-2; 2-3; 2-4; 2-1; 2-2 Example 2-4 Add 40 g (0.206 mol) of 2-phenylbenzimidazole to 150 g (1.53 mol) of concentrated sulfuric acid in five batches at a controlled temperature of 40 to 50 °C. After the materials are added to the mixture, the next batch of 2-Phenyl benzimidazole. After the addition was completed, the reaction mixture was heated to 85 °C and the reaction was continued until the content of 2-phenylbenzimidazole was less than 1% to complete the reaction. Then, the sulfonated solution was added to 300 g of water, and then heated to 80 °C and stirred for 1 h, and filtered to obtain 180.5 g of a filter cake. The filter cake was washed with 200 g of water, stirred at 80 ° C for 1 h, and filtered to obtain 140 g of filter cake. After vacuum drying, 55.1 g of 2-phenylbenzimidazole-5-sulfonic acid (HS) was obtained, with a content of 93.4%, and the content of 2-phenylbenzimidazole-4-sulfonic acid (isomer) was 6.25%, and the yield was 91.1 % (HS-p-phenylbenzimidazole). The reaction conditions were the same as in Example 2-2, except that the reaction system was added with 5 g of Cu-ZSM-5 catalyst, and the reaction temperature was raised to 60 °C. The ZSM-5 catalyst has a silicon-to-aluminum ratio of 100, and its preparation method is: The ZSM-5 catalyst was immersed in a 5 (weight)% potassium dihydrogen phosphate solution at 20 °C for 4h, and filtered, and the obtained solid was calcined at 500 °C for 1h at a high temperature in a muffle furnace;The ZSM-5 catalyst was further immersed in a 20 (weight)% copper sulfate solution at 20 °C for 3 hours, and filtered, and the obtained solid was dried at 110 °C for 3 hours and calcined at 550 °C for 2 hours. |
88% | With chlorosulfonic acid; sulfuric acid In 1,2-dichloro-ethane at 76℃; for 6h; | 1; 2; 3; 4; 5 Example 2 140g (1.2mol) of chlorosulfonic acid was slowly dropped into 200g of 100% sulfuric acid under stirring, mixed evenly and set aside.Put 194g (1.0mol) of 2-phenylbenzimidazole and 1000g of dichloroethane into a 2L reaction bottle, stir and heat up to 76 ° C, drop the mixed acid prepared above into the reaction bottle for reaction, and the dropping time is 3 hours. After the dropwise addition, the reaction was continued for 3 hours, and the hydrogen chloride gas generated during the reaction was absorbed with the lye.After the reaction, the stirring was stopped and allowed to stand for separation. The light yellow solution in the upper layer was ethylene dichloride, which could be directly applied to the next batch of reaction without adding any losses after distillation.The lower layer of dark liquid was dropped into 2000L of vigorously stirred water, and the hydrolysis temperature was controlled at 10 ° C.After filtration and separation, the obtained white solid was crude 2-phenylbenzimidazole-5-sulfonic acid.Put all the obtained crude product in 2000L of water, add sodium hydroxide solution dropwise with stirring at 25 ° C to adjust the pH to 9, to fully dissolve the solid, then add activated carbon to stir decolorization for 30 minutes, filter out the activated carbon; add 80g dropwise to the filtered clear solution Acetic acid was acidified to PH2.5 and white solid precipitated.After filtration and separation, the solid was dried to obtain 241 g of 2-phenylbenzimidazole-5-sulfonic acid with a molar yield of 88.0% and HPLC purity of 99.4%. |
88% | With chlorosulfonic acid; sulfuric acid In 1,2-dichloro-ethane at 76℃; for 6h; | 1-5 Example 2 Slowly drip 140 g (1.2 mol) of chlorosulfonic acid into the stirring 200 g of 100% sulfuric acid, and mix well for use. Put 194g (1.0mol) 2-phenylbenzimidazole and 1000g dichloroethane into a 2L reaction flask, stir and raise the temperature to 76 °C, drop the mixed acid configured above into the reaction flask for reaction, the dropping time is 3 hours, After the dripping is completed, the reaction is maintained for 3 hours, and the hydrogen chloride gas generated during the reaction is absorbed by the lye.After the reaction, the stirring is stopped and the mixture is allowed to stand for stratification. The upper light yellow solution is dichloroethane, which can be directly applied to the next batch reaction without distilling and adding the loss. The lower dark liquid was dropped into 2000L of vigorously agitated water, and the hydrolysis temperature was controlled at 10°C. It is separated by filtration, and the obtained white solid is the crude 2-phenylbenzimidazole-5-sulfonic acid.Put all the obtained crude product into 2000L water, add dropwise sodium hydroxide solution under stirring at 25 to adjust the pH to 9 to fully dissolve the solid, then add activated carbon and stir for 30 minutes to decolorize, filter out the activated carbon; add 80g dropwise to the filtered clear solution Acetic acid acidified to pH 2.5, and a white solid precipitated. After filtration and separation, the solid was dried to obtain 241 g of 2-phenylbenzimidazole-5-sulfonic acid with a molar yield of 88.0% and an HPLC purity of 99.4% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: 2-phenyl-1H-benzoimidazole; methyl iodide With sodium hydroxide In methanol at 110℃; for 72h; Inert atmosphere; Sealed tube; Stage #2: With methanol; sodium tetrahydroborate for 1h; Inert atmosphere; | |
Stage #1: 2-phenyl-1H-benzoimidazole; methyl iodide With sodium hydroxide In methanol at 110℃; for 24h; Inert atmosphere; Sealed tube; Stage #2: With sodium tetrahydroborate In methanol for 1h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | In water for 1h; Microwave irradiation; Heating; Green chemistry; | 4.2. General Methods for Preparation of 2-Substituted Benzimidazoles General procedure: In a typical procedure, a mixture ofo-phenylenediamine (1 equiv.) and acylbenzotriazole (1 equiv.) was subjected to microwave irradiation (20 W, 50 °C) in water (3 mL) for 1 h. After completion of the reaction, aqueous 4N HCl was added and the precipitates were filtered, followed by washing with water. The isolated products were recrystallized in ethanol to get the desired benzimidazoles in pure form. Benzotriazoles could be recovered from the aqueous layer by pH-controlled acidification. 2-Phenyl-1H-benzo[d]imidazole(52). White microcrystals (82%); m.p. 295-296 °C (lit. m.p. 295 °C [75]).1H NMR (500 MHz, DMSO-d6)δ8.32-8.30 (m, 2H), 7.85-7.82 (m, 2H), 7.75-7.70 (m, 3H), 7.54-7.52 (m, 2H);13C NMR (125 MHz, DMSO-d6)δ151.2, 143.8, 134.9, 130.2, 129.5, 128.9, 126.4, 122.5, 121.6, 118.9, 111.3. HRMSm/zcalcd for C13H10N2[M + H]+195.0844, found 195.0856. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tin(II) chloride dihdyrate; choline chloride at 110℃; for 0.75h; | To accomplish this, compound29 was synthesized (Siddiqui et al. 2006) and it was reactedwith p-anisaldehyde; however a complex mixture wasobtained where compounds 14a, 15 and 30 were identifiedand obtained in a ratio of 1:1.3:2.5, respectively, accordingto GCMS analysis (Scheme 6). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; acetic acid In 1,2-dichloro-ethane at 100℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; sodium acetate In chlorobenzene at 120℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With bis[dichlorido(η5-1,2,3,4,5-pentamethyl-cyclopentadienyl)rhodium (III)]; [bis(acetoxy)iodo]benzene at 80℃; for 12h; Schlenk technique; | |
91% | With bis[dichlorido(η5-1,2,3,4,5-pentamethyl-cyclopentadienyl)rhodium (III)]; [bis(acetoxy)iodo]benzene at 80℃; for 12h; Sealed tube; | 25 S1, combine 0.2 mmol 2-phenylbenzimidazole (compound 1), 0.24 mmol 4-isopropyl-1,3-cyclohexanedione (compound 51), 0.3 mmol iodobenzenediacetic acid PhI(OAc)2and 0.005mmol of dichloro(pentamethylcyclopentadienyl) rhodium (III) dimer was added to the pressure-resistant sealed reaction tube, and 1.5 mL of hexafluoroisopropanol (HFIP) was added to the pressure-resistant sealed reaction tube. , the reaction was stirred at 80 °C for 12 h, and the reaction time was tracked and judged by TLC during the reaction;S2, after the reaction finishes, the reaction material obtained in step S1 is taken out from the pressure-resistant sealed reaction tube, steamed to remove the organic solvent, purified by silica gel and rinsed with an eluent (petroleum ether: ethyl acetate=3:1) to obtain the product ( compound 52) in 91% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With bis[dichlorido(η5-1,2,3,4,5-pentamethyl-cyclopentadienyl)rhodium (III)]; silver(I) acetate In 1,2-dichloro-ethane at 100℃; for 5h; Sealed tube; |
Tags: 716-79-0 synthesis path| 716-79-0 SDS| 716-79-0 COA| 716-79-0 purity| 716-79-0 application| 716-79-0 NMR| 716-79-0 COA| 716-79-0 structure
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P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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