* 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.
With copper(I) sulfide; N,N,N,N,-tetramethylethylenediamine In methanol at 20℃; for 24 h;
General procedure: A 10mL round bottom flask was charged with a magnetic stirring bar, benzimidazole 1 (59mg, 0.5mmol), boronic acid 2 (1.0mmol), Cu2S (4mg, 0.025mmol), and MeOH (2mL), followed with the addition of TMEDA (0.075mL, 0.5mmol). The flask was sealed with a septum, through which was inserted 18-gauche needle. This setup allowed air to go into the reaction and avoid contamination of a mixture. The reaction mixture was stirred from 400 to 600rpm for appropriate time and extracted with EtOAc (2×15mL). Combined organic layers were washed with saturated aqueous solution of ethylenediaminetetraacetic acid disodium salt (15mL), and then dried over anhydrous Na2SO4. Volatiles were removed under reduced pressure and the residue was purified by column chromatography (silica gel, hexanes – EtOAc) to yield the title product, which was characterized by 1H NMR, 13C NMR, HRMS, and melting point (if solid).
81%
With triethylamine In methanol at 20℃; for 5 h;
General procedure: In a typical reaction, arylboronic acid (1 mmol), amino-compound (1 mmol), catalyst (5 wtpercent), Et3N (2 mmol) were mixed in methanol ( 5mL) in a 25mL round bottomed flask. The reaction mixture was subjected under continuous stirring at room temperature for 5 h. Reaction was monitored from time to time using TLC. After completion of the reaction, catalyst was separated with the aid of an external magnet and reaction mixture was taken in ethyl acetate. The organiclayer was washed using brine solution, dried over sodium sulfate. After evaporating the solvent, the crude product was puried by column chromatography using 230–400 silica mesh. The recovered catalyst was washed with methanol and ethyl acetate, dried in oven and kept in desiccator for further use.
74%
With [2,2]bipyridinyl; oxygen; copper diacetate In water at 20℃; for 24 h;
General procedure: Under an O2 atmosphere, a mixture of 4-methoxyphenylboroic acid (1a, 60.8 mg, 0.40 mmol), imidazole (2a, 13.6 mg, 0.20 mmol), Cu(OAc)2 (3.6 mg, 0.020 mmol), ligand I (3.7 mg, 0.020 mmol), and Brij 30 (21.8 mg, 0.060 mmol) in H2O (4 mL) was stirred at room temperature for 24 h. The mixture was diluted with brine and extracted with AcOEt (30 mL.x.3). The organic layer was washed with H2O (10 mL.x.3) and dried over MgSO4. The solvent was removed under the reduced pressure and the residue was purified by SiO2 column chromatography using AcOEt to give N-(4-methoxyphenyl)imidazole (3aa) (23.7 mg, 68percent).
Reference：
[1] Synthesis, 2008, # 5, p. 795 - 799
[2] Tetrahedron, 2018, vol. 74, # 5, p. 606 - 617
[3] Green Chemistry, 2018, vol. 20, # 21, p. 4891 - 4900
[4] Catalysis Communications, 2018, vol. 109, p. 38 - 42
[5] Tetrahedron, 2012, vol. 68, # 38, p. 7794 - 7798
2
[ 288-32-4 ]
[ 106-37-6 ]
[ 10040-96-7 ]
Yield
Reaction Conditions
Operation in experiment
90%
With copper(l) iodide; caesium carbonate; dimethylbiguanide In N,N-dimethyl-formamide at 20 - 110℃; for 15.1667 h;
General procedure: A 25 mL flask with a magnetic stirring bar was charged with CuI(9.6 mg, 0.05 mmol), metformin (0.1 mmol), Cs2CO3 (652 mg,2.0 mmol), imidazole (1.0 mmol), an aryl halide (1.1 mmol), andDMF (5 mL). The mixture was stirred for 10 min at room temperature,and then heated to 110∘C for the appropriate amount of time(see Table 2). The progress of the reaction was monitored by TLC.After completion of the reaction, the mixture was extracted with EtOAc (5 1 mL) and the organic phase separated and evaporated. Further purification by column chromatography gave the desired coupled product.
85%
With caesium carbonate In N,N-dimethyl-formamide at 100℃; for 12 h;
General procedure: A mixture of aryl halide (2.4 mmol) and Cs2CO3(4.0 mmol,0.650 g), nitrogen-containing heterocycle (2.0 mmol), dry DMF(3 mL) solvent and catalyst was stirred at 100C in an oil bath under air. After cooling to room temperature, catalyst was first separated out by centrifugation and the liquid part was extracted with water and diethylether (2 × 15 mL). The organic layers thus collected were combined and washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified bycolumn chromatography on silica gel (mesh 60–120) using an n-hexane/ethylacetate mixture as the eluent to collect the desiredproduct. The product was analyzed by 1H and13C NMR and mass spectroscopy.
81%
With C40H34CuIN6O6; sodium hydroxide In dimethyl sulfoxide at 100℃; for 4 h; Sealed tube
General procedure: For the catalysis reaction, the catalyst C1 (12 mg,0.01 mmol), imidazole (1.0 mmol), aryl halide(1.0 mmol), NaOH (80 mg, 2.0 mmol), and dimethylsulfoxide (DMSO, 5 mL) were taken in a sealed tube. The reaction mixture was stirred at 100 °C for 4 h and then cooled to room temperature. After adding 5 mL of H2O, the solution was extracted with ethyl acetate. The organic layer was then dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure.The N-arylated product was finally obtained by columnchromatography on silica gel.
Reference：
[1] Synlett, 2012, vol. 23, # 8, p. 1240 - 1244
[2] Tetrahedron Letters, 2013, vol. 54, # 52, p. 7095 - 7099
[3] Journal of Organic Chemistry, 2007, vol. 72, # 8, p. 2737 - 2743
[4] Applied Catalysis A: General, 2016, vol. 513, p. 53 - 66
[5] Indian Journal of Chemistry - Section A Inorganic, Physical, Theoretical and Analytical Chemistry, 2018, vol. 57A, # 2, p. 181 - 185
[6] Applied Organometallic Chemistry, 2017, vol. 31, # 11,
[7] Tetrahedron, 2017, vol. 73, # 16, p. 2191 - 2195
[8] Synlett, 2008, # 19, p. 3068 - 3072
3
[ 288-32-4 ]
[ 589-87-7 ]
[ 10040-96-7 ]
Yield
Reaction Conditions
Operation in experiment
94%
With C40H34CuIN6O6; sodium hydroxide In dimethyl sulfoxide at 100℃; for 4 h; Sealed tube
General procedure: For the catalysis reaction, the catalyst C1 (12 mg,0.01 mmol), imidazole (1.0 mmol), aryl halide(1.0 mmol), NaOH (80 mg, 2.0 mmol), and dimethylsulfoxide (DMSO, 5 mL) were taken in a sealed tube. The reaction mixture was stirred at 100 °C for 4 h and then cooled to room temperature. After adding 5 mL of H2O, the solution was extracted with ethyl acetate. The organic layer was then dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure.The N-arylated product was finally obtained by columnchromatography on silica gel.
92%
With copper(l) chloride; sodium hydroxide; 3-(diphenylphosphino)propionic acid In dimethyl sulfoxide at 120℃; for 14 h; Inert atmosphere; Sealed tube
General procedure: NH-containing heterocycle (1.4 mmol) and DMF (2.0 mL) were added to a mixture of CuCl (15.0 molpercent) and ligand 1 (20.0 molpercent) in DMF (2.0 mL), aryl iodide (1.0 mmol), NaOH (2.0 mmol). The mixture was vigorously stirred at 120 °C for 14 h under a dry nitrogen atmosphere. After completion of the reaction (as monitored by TLC), H2O was added and the organic layer was extracted with EtOAc, washed with brine and dried over MgSO4. The solution was filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography. The purity of the compounds was checked by 1H NMR and yields are based on aryl iodide. All the products are known and the spectroscopic data (FT‑IR and NMR) and melting points were consistent with those reported in the literature.
82%
With Cu/Al2O3; potassium hydroxide In N,N-dimethyl-formamide at 80℃; Green chemistry
General procedure: To equimolar amounts (0.1mmol) of the halide and the nitrogenated nucleophile in DMF were added KOH and the 3D heterogeneous Cu/Al2O3 catalytic system. The reaction mixture was heated at 80°C under orbital stirring in a Kimble vial (7mL) for 2–4h. Once the reaction had finished (TLC control), the solvent was separated from the catalyst and this was successively washed with methanol and dichloromethane (5mL). The organic solvents were removed under vacuum and the residue was purified by column chromatography to afford the desired compound (2–4).
82%
With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 1 h;
General procedure: The reaction flask, containing 0.02 g Cu(II) nanocatalyst(contains 0.4 molpercent of Cu(II)), imidazole (2.0 mmol),K2CO3 (1.0 mmol), and corresponding aryl halide(1.0 mmol) in 2.5 cm3 DMF, was immersed in a preheated oil bath and the reaction mixture was stirred under air atmosphere at 120 C until no further conversion of the starting aryl halide was observed by thin-layer chromatography(TLC). After completion of the reaction, the resulting mixture was allowed to cool to room temperature,and then the catalyst was separated out by an external permanent magnet, washed with ethyl acetate (EtOAc) anddried. The residue mixture was diluted by H2O and extracted with EtOAc (3 9 10 cm3). The extracted organic phases were dried over anhydrous Na2SO4, filtrated, concentrated and, finally, purified by silica gel chromatography using petroleum ether/ethyl acetate to afford the corresponding pure N-arylimidazole.
70%
With potassium carbonate In toluene at 110℃; for 14 h;
To a solution of N–H heterocycle (1 mmol) and aryl halide (2 mmol) in toluene were added catalyst (0.07 g, 0.016 mmol) and K2CO3 (276 g, 2 mmol) and the mixture stirred at 110 °C for the specified time. The progress of the reaction was monitored by TLC. The reaction mixture allowed cooling to room temperature and ethyl acetate (25 mL) was added and the mixture stirred for 15 min to ensure product removal from catalyst. Then the catalyst was filtered, washed with ethyl acetate (2 9 25 mL). The organic layer was evaporated under vacuum on a rotary evaporator and the crude product was obtained. Further purification was achieved by column chromatography using ethyl acetate/n-hexane gradient. Structural assignments of the products are based on their 1H NMR and melting point.
Reference：
[1] Journal of Organic Chemistry, 2009, vol. 74, # 20, p. 7951 - 7954
[2] Tetrahedron Letters, 2007, vol. 48, # 24, p. 4207 - 4210
[3] Journal of the Chinese Chemical Society, 2013, vol. 60, # 8, p. 1007 - 1013
[4] Indian Journal of Chemistry - Section A Inorganic, Physical, Theoretical and Analytical Chemistry, 2018, vol. 57A, # 2, p. 181 - 185
[5] Journal of Chemical Research, 2014, vol. 38, # 2, p. 128 - 129
[6] European Journal of Inorganic Chemistry, 2017, vol. 2017, # 40, p. 4803 - 4807
[7] Synthesis, 2010, # 9, p. 1505 - 1511
[8] Organic Letters, 2009, vol. 11, # 15, p. 3294 - 3297
[9] Chemistry - A European Journal, 2004, vol. 10, # 22, p. 5607 - 5622
[10] Chemistry - A European Journal, 2006, vol. 12, # 13, p. 3636 - 3646
[11] European Journal of Organic Chemistry, 2011, # 18, p. 3353 - 3360
[12] Journal of Organic Chemistry, 2009, vol. 74, # 5, p. 2200 - 2202
[13] Chemistry - A European Journal, 2009, vol. 15, # 36, p. 8971 - 8974
[14] ChemSusChem, 2017, vol. 10, # 24, p. 4855 - 4863
[15] Advanced Synthesis and Catalysis, 2006, vol. 348, # 15, p. 2197 - 2202
[16] Synlett, 2009, # 16, p. 2663 - 2668
[17] Journal of Catalysis, 2016, vol. 334, p. 110 - 115
[18] Monatshefte fur Chemie, 2018, vol. 149, # 6, p. 1101 - 1109
[19] Letters in Organic Chemistry, 2011, vol. 8, # 5, p. 325 - 331
[20] Organic Letters, 2006, vol. 8, # 13, p. 2779 - 2782
[21] Synlett, 2008, # 19, p. 3068 - 3072
[22] Journal of Medicinal Chemistry, 2015, vol. 58, # 24, p. 9680 - 9696
[23] Catalysis Letters, 2016, vol. 146, # 1, p. 193 - 203
[24] Asian Journal of Chemistry, 2013, vol. 25, # 11, p. 6240 - 6242
4
[ 288-32-4 ]
[ 589-87-7 ]
[ 132464-89-2 ]
[ 10040-96-7 ]
Reference：
[1] Journal of Organic Chemistry, 2007, vol. 72, # 16, p. 6190 - 6199
5
[ 50-00-0 ]
[ 131543-46-9 ]
[ 106-40-1 ]
[ 10040-96-7 ]
Reference：
[1] European Journal of Inorganic Chemistry, 2006, # 6, p. 1268 - 1274
[2] Dalton Transactions, 2012, vol. 41, # 17, p. 5377 - 5390
[3] Organometallics, 2014, vol. 33, # 4, p. 898 - 908
[4] Organic Letters, 2018, vol. 20, # 19, p. 6215 - 6219
6
[ 288-32-4 ]
[ 460-00-4 ]
[ 10040-96-7 ]
Reference：
[1] Angewandte Chemie - International Edition, 2012, vol. 51, # 32, p. 8012 - 8016
7
[ 288-32-4 ]
[ 10040-96-7 ]
Reference：
[1] Journal of Chemical Research - Part S, 2000, # 8, p. 367 - 369
8
[ 106-37-6 ]
[ 10040-96-7 ]
Reference：
[1] Chemistry - A European Journal, 2006, vol. 12, # 13, p. 3636 - 3646
9
[ 106-40-1 ]
[ 10040-96-7 ]
Reference：
[1] Chemistry - An Asian Journal, 2011, vol. 6, # 3, p. 863 - 867
[2] Asian Journal of Chemistry, 2012, vol. 24, # 3, p. 1325 - 1327
10
[ 18156-74-6 ]
[ 460-00-4 ]
[ 420-56-4 ]
[ 10040-96-7 ]
Reference：
[1] Journal of Organic Chemistry, 2011, vol. 76, # 4, p. 1151 - 1154
11
[ 50-00-0 ]
[ 10040-96-7 ]
Reference：
[1] Chemistry - An Asian Journal, 2011, vol. 6, # 3, p. 863 - 867
[2] Asian Journal of Chemistry, 2012, vol. 24, # 3, p. 1325 - 1327
With caesium carbonate;copper(I) oxide; trans-N,N'-bis(pyridin-2-ylmethylene)cyclohexane-1,2-diamine; at 82℃; for 48h;
Example 1.8 [0553] Preparation of 1-(4-imidazol-1-yl-phenyl)-1H-pyrazole [0554] Operating protocol B (82 C., 48 hours) was followed using 117 mg of Chxn-Py-Al (0.4 mmoles), 535 mg of 1-(4?-bromophenyl)-1H-imidazole (2.4 mmoles), 136 mg of pyrazole (2 mmoles) and 1.2 ml of acetonitrile. [0555] The residue obtained was purified by silica gel chromatography (eluent: dichloromethane/methanol, 100/0 to 98/2). [0556] 387 mg of a colourless solid was obtained, corresponding to a yield of 92% by weight. [0557] The compound obtained had the following formula: [CHEMMOL-00047]
With C40H34CuIN6O6; sodium hydroxide; In dimethyl sulfoxide; at 100℃; for 4h;Sealed tube;
General procedure: For the catalysis reaction, the catalyst C1 (12 mg,0.01 mmol), imidazole (1.0 mmol), aryl halide(1.0 mmol), NaOH (80 mg, 2.0 mmol), and dimethylsulfoxide (DMSO, 5 mL) were taken in a sealed tube. The reaction mixture was stirred at 100 C for 4 h and then cooled to room temperature. After adding 5 mL of H2O, the solution was extracted with ethyl acetate. The organic layer was then dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure.The N-arylated product was finally obtained by columnchromatography on silica gel.
92%
With copper(l) chloride; sodium hydroxide; 3-(diphenylphosphino)propionic acid; In dimethyl sulfoxide; at 120℃; for 14h;Inert atmosphere; Sealed tube;
General procedure: NH-containing heterocycle (1.4 mmol) and DMF (2.0 mL) were added to a mixture of CuCl (15.0 mol%) and ligand 1 (20.0 mol%) in DMF (2.0 mL), aryl iodide (1.0 mmol), NaOH (2.0 mmol). The mixture was vigorously stirred at 120 C for 14 h under a dry nitrogen atmosphere. After completion of the reaction (as monitored by TLC), H2O was added and the organic layer was extracted with EtOAc, washed with brine and dried over MgSO4. The solution was filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography. The purity of the compounds was checked by 1H NMR and yields are based on aryl iodide. All the products are known and the spectroscopic data (FT-IR and NMR) and melting points were consistent with those reported in the literature.
82%
With Cu/Al2O3; potassium hydroxide; In N,N-dimethyl-formamide; at 80℃;Green chemistry;
General procedure: To equimolar amounts (0.1mmol) of the halide and the nitrogenated nucleophile in DMF were added KOH and the 3D heterogeneous Cu/Al2O3 catalytic system. The reaction mixture was heated at 80C under orbital stirring in a Kimble vial (7mL) for 2-4h. Once the reaction had finished (TLC control), the solvent was separated from the catalyst and this was successively washed with methanol and dichloromethane (5mL). The organic solvents were removed under vacuum and the residue was purified by column chromatography to afford the desired compound (2-4).
82%
With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 1h;Catalytic behavior;
General procedure: The reaction flask, containing 0.02 g Cu(II) nanocatalyst(contains 0.4 mol% of Cu(II)), imidazole (2.0 mmol),K2CO3 (1.0 mmol), and corresponding aryl halide(1.0 mmol) in 2.5 cm3 DMF, was immersed in a preheated oil bath and the reaction mixture was stirred under air atmosphere at 120 C until no further conversion of the starting aryl halide was observed by thin-layer chromatography(TLC). After completion of the reaction, the resulting mixture was allowed to cool to room temperature,and then the catalyst was separated out by an external permanent magnet, washed with ethyl acetate (EtOAc) anddried. The residue mixture was diluted by H2O and extracted with EtOAc (3 9 10 cm3). The extracted organic phases were dried over anhydrous Na2SO4, filtrated, concentrated and, finally, purified by silica gel chromatography using petroleum ether/ethyl acetate to afford the corresponding pure N-arylimidazole.
70%
With potassium carbonate; In toluene; at 110℃; for 14h;Catalytic behavior;
To a solution of N-H heterocycle (1 mmol) and aryl halide (2 mmol) in toluene were added catalyst (0.07 g, 0.016 mmol) and K2CO3 (276 g, 2 mmol) and the mixture stirred at 110 C for the specified time. The progress of the reaction was monitored by TLC. The reaction mixture allowed cooling to room temperature and ethyl acetate (25 mL) was added and the mixture stirred for 15 min to ensure product removal from catalyst. Then the catalyst was filtered, washed with ethyl acetate (2 9 25 mL). The organic layer was evaporated under vacuum on a rotary evaporator and the crude product was obtained. Further purification was achieved by column chromatography using ethyl acetate/n-hexane gradient. Structural assignments of the products are based on their 1H NMR and melting point.
1-[4-(1H-imidazol-1-yl)phenyl]-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
18%
With potassium carbonate;copper(l) iodide; trans-1,2-cyclohexanediamine; In 1,4-dioxane; at 180℃; for 3h;Microwave;
A mixture of 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1 /-/-indazole (152mg, O.deltammol), potassium carbonate (232mg, 1.68mmol) and copper (I) iodide (1 mg, O.OOdeltammol) was treated with a solution of frans-1 , 2-diaminocyclohexane (9mg, O.Odeltammol) in dioxane followed by a solution of 1-(4-bromophenyl)imidazole (161 mg, 0.72mmol) in dioxane (4ml total volume). This mixture was heated at 18O0C in a microwave reactor for 1 hour. Further copper (I) iodide (1 mg) and frans-1 , 2-diaminocyclohexane (9mg) was added and the reaction heated at 18O0C in a microwave reactor for a further hour. Again further copper (I) iodide (1 mg) and frans-1 , 2-diaminocyclohexane (9mg) was added and the <n="126"/>reaction heated at 18O0C in a microwave reactor for a further hour. The reaction mixture was added to a 5g sep-pack column and eluted with ethyl acetate. The solvent was removed by rotary evaporation and the crude product further purified by MDAP. Further purified using a 5g SCX column, eluting from 1 M ammonia in methanol which was then evaporated off using rotary evaporation to give the title compound (42mg, 18%).LC/Mass Spec (ES): Found 333 (ES+), retention time 2.21 mins. Ci7H15F3N4 requires 332. 1 H-NMR (400MHz, CDCI3): 1.85 (4H, m), 2.73 (4H, m), 7.25 (1 H, m), 7.32 (1 H, m), 7.51 (2H1 m), 7.63 (2H1 m), 7.89 (1 H1 s).
With copper(l) iodide; caesium carbonate; dimethylbiguanide; In N,N-dimethyl-formamide; at 20 - 110℃; for 15.1667h;
General procedure: A 25 mL flask with a magnetic stirring bar was charged with CuI(9.6 mg, 0.05 mmol), metformin (0.1 mmol), Cs2CO3 (652 mg,2.0 mmol), imidazole (1.0 mmol), an aryl halide (1.1 mmol), andDMF (5 mL). The mixture was stirred for 10 min at room temperature,and then heated to 110?C for the appropriate amount of time(see Table 2). The progress of the reaction was monitored by TLC.After completion of the reaction, the mixture was extracted with EtOAc (5 1 mL) and the organic phase separated and evaporated. Further purification by column chromatography gave the desired coupled product.
85%
With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 12h;Catalytic behavior;
General procedure: A mixture of aryl halide (2.4 mmol) and Cs2CO3(4.0 mmol,0.650 g), nitrogen-containing heterocycle (2.0 mmol), dry DMF(3 mL) solvent and catalyst was stirred at 100C in an oil bath under air. After cooling to room temperature, catalyst was first separated out by centrifugation and the liquid part was extracted with water and diethylether (2 × 15 mL). The organic layers thus collected were combined and washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified bycolumn chromatography on silica gel (mesh 60-120) using an n-hexane/ethylacetate mixture as the eluent to collect the desiredproduct. The product was analyzed by 1H and13C NMR and mass spectroscopy.
81%
With C40H34CuIN6O6; sodium hydroxide; In dimethyl sulfoxide; at 100℃; for 4h;Sealed tube;
General procedure: For the catalysis reaction, the catalyst C1 (12 mg,0.01 mmol), imidazole (1.0 mmol), aryl halide(1.0 mmol), NaOH (80 mg, 2.0 mmol), and dimethylsulfoxide (DMSO, 5 mL) were taken in a sealed tube. The reaction mixture was stirred at 100 C for 4 h and then cooled to room temperature. After adding 5 mL of H2O, the solution was extracted with ethyl acetate. The organic layer was then dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure.The N-arylated product was finally obtained by columnchromatography on silica gel.
With copper(I) sulfide; N,N,N,N,-tetramethylethylenediamine; In methanol; at 20℃; for 24h;
General procedure: A 10mL round bottom flask was charged with a magnetic stirring bar, benzimidazole 1 (59mg, 0.5mmol), boronic acid 2 (1.0mmol), Cu2S (4mg, 0.025mmol), and MeOH (2mL), followed with the addition of TMEDA (0.075mL, 0.5mmol). The flask was sealed with a septum, through which was inserted 18-gauche needle. This setup allowed air to go into the reaction and avoid contamination of a mixture. The reaction mixture was stirred from 400 to 600rpm for appropriate time and extracted with EtOAc (2×15mL). Combined organic layers were washed with saturated aqueous solution of ethylenediaminetetraacetic acid disodium salt (15mL), and then dried over anhydrous Na2SO4. Volatiles were removed under reduced pressure and the residue was purified by column chromatography (silica gel, hexanes - EtOAc) to yield the title product, which was characterized by 1H NMR, 13C NMR, HRMS, and melting point (if solid).
81%
With triethylamine; In methanol; at 20℃; for 5h;
General procedure: In a typical reaction, arylboronic acid (1 mmol), amino-compound (1 mmol), catalyst (5 wt%), Et3N (2 mmol) were mixed in methanol ( 5mL) in a 25mL round bottomed flask. The reaction mixture was subjected under continuous stirring at room temperature for 5 h. Reaction was monitored from time to time using TLC. After completion of the reaction, catalyst was separated with the aid of an external magnet and reaction mixture was taken in ethyl acetate. The organiclayer was washed using brine solution, dried over sodium sulfate. After evaporating the solvent, the crude product was puried by column chromatography using 230-400 silica mesh. The recovered catalyst was washed with methanol and ethyl acetate, dried in oven and kept in desiccator for further use.
74%
With [2,2]bipyridinyl; oxygen; copper diacetate; In water; at 20℃; under 760.051 Torr; for 24h;
General procedure: Under an O2 atmosphere, a mixture of 4-methoxyphenylboroic acid (1a, 60.8 mg, 0.40 mmol), imidazole (2a, 13.6 mg, 0.20 mmol), Cu(OAc)2 (3.6 mg, 0.020 mmol), ligand I (3.7 mg, 0.020 mmol), and Brij 30 (21.8 mg, 0.060 mmol) in H2O (4 mL) was stirred at room temperature for 24 h. The mixture was diluted with brine and extracted with AcOEt (30 mL×3). The organic layer was washed with H2O (10 mL×3) and dried over MgSO4. The solvent was removed under the reduced pressure and the residue was purified by SiO2 column chromatography using AcOEt to give N-(4-methoxyphenyl)imidazole (3aa) (23.7 mg, 68%).
With C40H34CuIN6O6; sodium hydroxide; In dimethyl sulfoxide; at 100℃;
General procedure: The optimum reaction conditions were as follows: sodium hydroxide as base (2mmol), dimethyl sulfoxide as solvent (3mL), reaction temperature of 100 , catalyst such as methylene bridged 1,8-naphthyridine copper () The amount of the complex was 0.01 mmol, and the catalytic expansion experiments were carried out with different substituted aryl bromides and iodide substrates. The results are shown in Table 2.The catalyst system is capable of tolerating a C-N coupling reaction of various functionalized aryl halides, including nitrile, nitro, acetyl and ether groups, wherein the catalytic yield of iodide is between 91% and 99 %between.In addition, when the catalytic reaction is highly selective and the substrate is a hydroxyl group or an amino-substituted aryl bromide, the formation of the diaryl ether compound and the diphenylamine compound can be avoided.Reaction conditions: aryl halide (1.0 mmol), imidazole (1.0 mmol), sodium hydroxide (2.0 mmol), complex (0.01 mmol), dimethyl sulfoxide (3 mL), 100 C air atmosphere, B. Isolated yield; c.2-bromopyridine aryl halide.
81%
With C40H34CuIN6O6; sodium hydroxide; In dimethyl sulfoxide; at 100℃;
General procedure: The optimum reaction conditions were as follows: sodium hydroxide as base (2mmol), dimethyl sulfoxide as solvent (3mL), reaction temperature of 100 , catalyst such as methylene bridged 1,8-naphthyridine copper () The amount of the complex was 0.01 mmol, and the catalytic expansion experiments were carried out with different substituted aryl bromides and iodide substrates. The results are shown in Table 2.The catalyst system is capable of tolerating a C-N coupling reaction of various functionalized aryl halides, including nitrile, nitro, acetyl and ether groups, wherein the catalytic yield of iodide is between 91% and 99 %between.In addition, when the catalytic reaction is highly selective and the substrate is a hydroxyl group or an amino-substituted aryl bromide, the formation of the diaryl ether compound and the diphenylamine compound can be avoided.Reaction conditions: aryl halide (1.0 mmol), imidazole (1.0 mmol), sodium hydroxide (2.0 mmol), complex (0.01 mmol), dimethyl sulfoxide (3 mL), 100 C air atmosphere, B. Isolated yield; c.2-bromopyridine aryl halide.
With trans-bis(triphenylphosphine)palladium dichloride; In N,N-dimethyl-formamide; at 90℃; for 1.5h;
1-(Cyclohexylmethyl)-6-(trimethylstannyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (200 mg, 0.506 mmol), <strong>[10040-96-7]1-(4-bromophenyl) imidazole</strong> (94 mg, 0.42 mmol), dichlorobis(triphenylphosphine)palladium(II) (104 mg, 0.10 mmol) in DMF (10 mL) were reacted for 1.5 h at 90 C. The product was purified by reverse-phase semi-preparatory HPLC (30-100% acetonitrile + 0.1% TFA in H2O + 0.1% TFA, over 30 min). The desired fractions were concentrated, the residue was taken up in DMSO (2 mL) and heated at 100 C until completely dissolved. Water was added upon cooling and the desired product precipitated out of solution. The precipitate was collected by vacuum filtration, washed with water and dried under high vacuum to provide the title compound (16 mg, 10% yield) as a tan solid.
With air; heterogeneous copper Schiff-base modified SBA-15 catalyst; In N,N-dimethyl-formamide; at 80℃; for 6h;Catalytic behavior;
At first diphenyliodonium tetrafluoroborate was synthesizedaccording to procedure reported previously [31] and characterizedby1H and13C NMR and mass spectral analysis (see Supplementarycontent). A mixture of N-heteroarene (1.0 mmol), diphenyliodo-nium salt (1.5 mmol), catalyst and DMF (3 mL) was stirred at 80Cfor a desired time in air. After cooled down to room tempera-ture, heterogeneous catalyst was separated out by centrifugation.The liquid part was then subjected to rotary evaporation andthe residue obtained was passed through a silica gel column(dichloromethane/acetone = 5:1-2:1 v/v) to afford the desired ary-lazolium salt. The product was analyzed by1H and13C NMR andmass spectroscopy.
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In tetrahydrofuran; water; at 20℃;Reflux;
Pd(PPh3)4 (112 mg, 96.7 mumol) was added to a mixture of 6 (600 mg, 0.967 mmol) and <strong>[10040-96-7]1-(4-bromophenyl)-1H-imidazole</strong> (863 mg, 3.87 mmol) in aqueous Na2CO3 (2 M, 2.0 mL, 4.0 mmol) and anhydrous THF (18.0 mL), and the solution was stirred at room temperature for 15 min. The resulting two-phase system was refluxed under stirring overnight, and was then allowed to cool to room temperature. To this was added water (50 mL), and the mixture was extracted with CHCl3 (100 mL×3). The organic layer was washed with water (50 mL), dried over anhydrous MgSO4, and filtered. After the solvent was removed by evaporation, the residue was subjected to SEC fractionation to obtain 2 (516 mg, 79%) as a bluish white solid. Mp: 251.8-252.0 C. IR (KBr, cm-1): 1523, 1305, 1273, 1139, 1114, 1055, 989. 1H NMR (500 MHz, CDCl3): delta 7.89 (s, 2H, ArH), 7.65 (d, J=8.6 Hz, 4H, PhH), 7.42 (d, J=8.6 Hz, 4H, PhH), 7.32 (s, 2H, ArH), 7.25 (s, 2H, ArH), 2.01 (s, 6H, CH3). 13C NMR (125 MHz, CDCl3): delta 142.1, 140.9, 136.9, 135.6, 132.7, 130.9, 127.1, 126.2, 123.1, 122.0, 118.2, 14.8. MS (ESI+): m/z=653 [M+H]+. Anal. Calcd for C33H22F6N4S2: C, 60.73; H, 3.40; N, 8.58. Found: C, 60.74; H, 3.48; N, 8.45.
4-(4-imidazol-1-yl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
STEP B: 4-(4-Imidazol-1-yl-phenyl)-piperidine-1-carboxylic acid tert-butyl esterZn dust (5.30 g, 81.3 mmol) was suspended in DMA (35 ml) under nitrogen atmosphere and then treated with 1 ,2-dibromoethane (0.67 ml, 7.8 mmol). The mixture was briefly heated to 60-70C and allowed to cool to room 15 temperature (3 times). Chlorotrimethylsilane (0.66 ml, 5.2 mmol) was then added dropwise and the resulting mixture aged for 30 minutes. A solution of 4- iodo-piperidine-1 -carboxylic acid tert-butyl ester (20.2 g, 65 mmol) in DMA (35 ml) was then added slowly added at a rate to maintain a temperature <65C. The exothermic zinc insertion was allowed to cool to room temperature and20 stirring maintained for 1 hour, to yield a a0.92 M solution of (1-tert-butoxycarbonylpiperidin-4-yl)(iodo)zinc. A freshly prepared solution of <strong>[10040-96-7]1-(4-bromophenyl)-1H-imidazole</strong> (4.0 g, 17.9 mmol), copper(I) iodide (0.204 g, 1.07 mmol) and Pd(dppf)Cl2?CH2Cl2(0.441 g, 0.54 mmol) was then treated with 19 ml of the above solution (17.9 25 mmol) and mixture heated to 80C overnight. The reaction mixture wasallowed to cool to room temperature, diluted with ethyl acetate (100 ml) saturated aqueous NH4Cl, (100 ml), water (50 ml) and stirred for 20 minutes. The mixture was filtered through a pad of CELITE that was further washed with ethyl acetate (2 × 25 ml). The phases were separated, and aqueous layer 30 extracted once more with ethyl acetate (50 ml). The combined organic layer were washed with brine (2 × 100 ml), dried over MgSO4, filtered and concentrated to yield a residue. Purification of the residue over silica gel eluting with a gradient of MeOH in DCM from 0 to 5% yielded 4-(4-imidazol-1 - yl-phenyl)-piperidine-1 -carboxylic acid tert-butyl ester as beige solid.1H NMR (300 MHz, CDCl3) ppm 1.50 (s, 9 H), 1.56 - 1.71 (m, 2 H), 1.81 - 1.91 (m, 2 H), 2.67 - 2.89 (m, 3 H), 4.20 - 4.36 (m, 2 H), 7.31 (d, J=8.7 Hz, 1 H), 7.34 (br s, 4 H), 7.65 (d, J=8.7 Hz, 1 H). MS m/z 328 (M+H)+
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃; for 2h;
A mixture of <strong>[10040-96-7]1-(4-bromophenyl)-1H-imidazole</strong> (450 mg, 2.Ommol), bis(pinacolato)diboron (1.0 g, 4.0 mmol), [1,1?- bis(diphenylphosphino)ferrocene] dichloropalladium(II) (150 mg, 0.2 mmol) and potassium acetate (990 mg, 10 mmol) in dioxane (8 mL) was stirred at 100 C for 2 h.The crude reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-100% EtOAc/DCM to give Compound 579a (490 mg, 89% yield). HPLC RT = 0.73 mm (LCMS Method 0). MS(ES): m/z = 271.2 [M+H]. ?H NMR (400MHz, chloroform-d) oe 8.01 - 7.85 (m, 3H), 7.42 - 7.35 (m, 2H), 7.32 - 7.29 (m, 1H), 7.19 (d, J=0.9 Hz, 1H), 1.35 (s, 12H).
89%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃; for 2h;
A mixture of <strong>[10040-96-7]1-(4-bromophenyl)-1H-imidazole</strong> (450 mg, 2.0 mmol), bis(pinacolato)diboron (1.0 g, 4.0 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (150 mg, 0.2 mmol) and potassium acetate (990 mg, 10 mmol) in dioxane (8 mL) was stirred at 100 C. for 2 h. The crude reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-100% EtOAc/DCM to give Compound 579a (490 mg, 89% yield). HPLC RT=0.73 min (LCMS Method O). -MS(ES): m/z=271.2 [M+H]+. -1H NMR (400 MHz, chloroform-d) delta 8.01-7.85 (m, 3H), 7.42-7.35 (m, 2H), 7.32-7.29 (m, 1H), 7.19 (d, J=0.9 Hz, 1H), 1.35 (s, 12H)
2'-O-acetyl-3-O-descladinosyl-3-O-[2-(2'-pyridyl)acetyl]-6-O-methylerythromycin A 9-O-(2-propargyl)oxime-11,12-cyclic carbonate[ No CAS ]
[ 10040-96-7 ]
3-O-descladinosyl-3-O-[2-(2'-pyridyl)acetyl]-6-O-methylerythromycin A 9-O-[3-[(4'-imidazolyl)-1'-phenyl]-2-propargyl]-oxime-11,12-cyclic carbonate[ No CAS ]
2'-O-acetyl-3-O-descladinosyl-3-O-[2-(2'-pyridyl)acetyl]-6-O-methylerythromycin A 9-O-(2-propargyl)oxime-11,12-cyclic carbonate[ No CAS ]
[ 10040-96-7 ]
C52H69N5O13[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
19.9%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In acetonitrile; at 80℃; for 4h;Inert atmosphere; Sealed tube;
General procedure: To a solution of 4 (1.01 g, 1.22 mmol), CuI (23 mg, 0.12 mmol),PdCl2(PPh3)2 (45 mg, 0.064 mmol) and triethylamine (0.26 mL,1.86 mmol) in acetonitrile (10 mL), 2-amino-5-bromopyrimidine(635 mg, 3.65 mmol) were added. The reaction mixture wasrecharged with Ar and stirred at 80 C for 4 h in a sealed tube.The mixture was extracted with ethyl acetate and the organic layerwas washed with water and brine successively. The organic solventwas removed in vacuo. The residue was purified by column chromatography on silica gel (CH2Cl2/C2H5OH/NH3H2O, 10:0.6:0.1) toafford 20-OAc-3f (156 mg, 0.17 mmol, 13.9%).A solution of 20-OAc-3f (156 mg, 0.17 mmol) in MeOH (20 mL)was stirred at 65 C for 3H. The organic solvent was removed invacuo. The residue was purified by preparative TLC (petroleumether/acetone/triethylamine, 5:5:0.2) to yield analytically pureproduct 3f (14 mg, 0.015 mmol, 9.4%).
7(S)-7-deoxy-7-(4-(1H-imidazol-1-yl)phenylthio)lincomycin[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
42%
With tris-(dibenzylideneacetone)dipalladium(0); N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; for 4h;Reflux;
General procedure: To a solution of 1-(4-bromophenyl)-N, N-dimethylmethanamine (23.2 mg,0.108 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos)(10.4 mg, 0.018 mmol) and tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3) (8.3mg, 9.6 mumol) in 1,4-dioxane (1 ml) were added to compound 5(38.2 mg, 0.090 mmol) and N,N-diisopropylethylamine (31.4 mul, 0.180 mmol)and refluxed for 3 h. The mixture was filtrated by either Chromatodisc(0.45 mum) (KURABO INDUSTRIES, Osaka, Japan) or celite. The filtered solidwere washed with MeOH three times and then the assembled solution wasconcentrated under reduced pressure. The resulting residue was purified bypreparative TLC (CHCl3/MeOH/28% aq. NH4OH=10/1/0.1) to obtain thetitle compound as an off-white solid
N-benzyloxycarbonyl-3-[4'-(1''-imidazolyl)-1'-phenyl]-prop-2-ynyl-1-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90.2%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In acetonitrile; at 80℃; for 3h;Inert atmosphere; Sealed tube;
To a solution of 21 (0.212 g, 1.12 mmol), CuI (20 mg, 0.112 mmol), (PPh3)2PdCl2 (40 mg, 0.056 mmol) and triethylamine (0.23 mL, 1.68 mmol) in acetonitrile (10 mL) was added 1-(4-bromophenyl)imidazole (0.5 g, 2.24 mmol). The reaction mixture was recharged with argon and stirred at 80 C for 3 h in a sealed tube. The mixture was extracted with ethyl acetate and the organic layer was washed successively with water and brine. The organic solvent was removed in vacuum. The residue was purified by column chromatography on silica gel (CH2Cl2/PE/NH3?H2O, 8:3:0.1) to afford 22c (0.3354 g, 1.01 mmol, 90.2%).HRMS (ESI) (M+H)+ m/z 332.1389, Calcd for C20H18N3O2 332.1394. 1H NMR (CDCl3, 400 MHz), delta: 7.93 (s, 1 H, H-imidazolyl), 7.55 (d, J = 8.1 Hz, 2 H, H-phenyl), 7.45-7.29 (m, 9 H, H-imidazolyl, H-phenyl), 5.25-5.15(m, 3 H, -NH-, -CH2-O-), 4.28 (s, 2 H, -NH-CH2-).
1-(4-bromophenyl)-3-(7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methyl-1H-imidazol-3-ium iodide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
In N,N-dimethyl-formamide; at 130℃; for 4h;
22.0g of 1- (4-bromophenyl) -1H-imidazole,27.8g of 10-iodocamphor and 50mL of N, N-dimethylformamide were sequentially added to a three-necked flask equipped with a stirrer, a thermometer and a condensing reflux device.The reaction is carried out at 130 C, and the reaction takes about 4 hours to complete the reaction of one of the raw materials.After cooling, 50 mL of ethyl acetate was added to precipitate the product, and the crude product of camphoryl imidazole iodide was filtered to obtain the target compound by recrystallization from ethanol. The product characterization data is as follows: 80% yield,
In N,N-dimethyl-formamide; at 130℃; for 5h;Inert atmosphere;
General procedure: To a solution of 10-iodocamphor (5mmol, 1.39g) in DMF(3ml), substituted phenylimidazoles (5mmol) were added in a pressure tube and N2was used to exclude oxygen. Theresulting reaction mixture was heated at 130C for 5h.After the reaction completed, EtOAc (ca. 6ml) was addedin the mixture. Precipitation was formed and the filtrate wasremoved. The crude product was recrystallized in methanoland dried under vacuum.
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