1-(4-METHOXYPHENYL)-1H-PYRROLE

General procedure: A mixture of pyrrole (3 ml), Cs2CO3 (1.96 g, 6 mmol), Cu0/4A or Cu2+/4A (0.3 g) and the appropriate aryl halide (3 mmol) were stirred at 135 C (bath temperature) for 4-36 h. Before adding to the mixture, Cu2+/4A was preheated at ca. 150 C for 1 h. The mixture was filtered, the solid was washed with dichloromethane. The filtrate was extracted with deionised water (2 x 40 ml). The organic phase was dried over Na2SO4 and concentrated in vacuum. The residue was distilled and clarified. Certain products (3c, 3f) were purified by recrystallization from MeOH.General procedure: To a solution of N-heterocycle (1 equiv), bromobenzene (1.02 equiv) and tBuOK (2 equiv) in dry DMF, CuFe2O4 (10 mol %) was added and heated at reflux for 24 h under N2 atmosphere. After cooling to room temperature, the mixture was diluted with ethyl acetate and the catalyst was separated by a magnetic separator. The catalyst was washed with ethyl acetate. The combined ethyl acetate layer was washed with water (twice), dried over anhydrous Na2SO4, and concentrated to yield the crude product, which was further purified by silica gel column chromatography using petroleum ether/ethyl acetate to yield N-arylated product.General procedure: A mixture of N-unsubstituted compound 2 (1.0 mmol), aryl halide 1 (1.2 mmol), and t-BuONa (1.2 mmol) was stirred in DMF (0.3 mL) inthe presence of Cu(OAc)2·H2O (1 mol%) and 2-phenyl-2-(4-phenyl-1H-1, 2, 3-triazol-1-yl)ethanol (1 mol%) at 120 C for the time given inTable 2. The mixture was washed with EtOAc; after removal of thesolvent, the residue was purified by column chromatography (silicagel, petroleum ether-EtOAc).General procedure: A flame-dried Schlenk test tube with a magnetic stirring bar was charged with CuI (0.038 mg, 0.0002 mol), Cs2CO3 (0.65 g, 0.002 mol), heterocycle (0.0014mol), 1-bromo-4-methoxybenzene (0.185 g, 0.001 mol) and DMF (10 mL) under N2. A rubber septum was replaced with a glass stopper, and the system was then evacuated twice and back filled with N2. After being stirred at 120 C for 24 h, the reaction mixture was diluted with 2-3 mL of ethyl acetate, filtered through a plug of silica gel, and washed with 30-50 mL of ethyl acetate. The filtrate was concentrated and the resulting residue was purified by column chromatography on silica gel to provide the desired product. A solution of BBr3 (0.23 mL, 0.0025mol) in CH2Cl2 (5 mL) was added dropwise to the solution of 1-(4-methoxyphenyl)-1H-heterocycle (0.001 mol) in CH2Cl2 (10 mL) cooled to 0 C. The resulting solution was stirred for 4 h at room temperature. And the solution was washed by NaHCO3, NH4Cl, NaCl solution in sequence. The CH2Cl2 was dried over anhydrous sodium sulfate, removed under vacuum, and the residue was purified by chromatography on silica gel to yield the 4-(1H-heterocycle -1-yl)phenol.4-(1H-heterocycle -1-yl)phenol (0.001 mol), N, N?-dicyclohexyl carbodiimide (DCC) (0.0012 mol), 4-dimethylaminopyridine (DMAP) (0.0002 mol) in 10 mL chloroform were placed in a Pyrex glass tube, sealed and heated at 80 C for 12 h. After cooling to room temperature, the white solid was filtrated off, and the solvent was removed under vacuum. The crude product was purified by chromatography on silica gel with to gain the desired products.General procedure: In a 50mL RB, N-H heterocycles (1.0mmol), aryl halide (1mmol), Cu(II)Pc (0.01mmol), NaOH (1.5mmol) and DMSO (2mL) was added. This reaction mixture was stirred to a preheated oil bath at 100C for 8-12h. After completion of the reaction, it was cooled to room temperature and 20mL ethyl acetate was added. It was filtered; solid catalyst was separated and washed with 2×5mL ethyl acetate. The washing and filtrate were combined and washed with water. Ethyl acetate was removed under reduced pressure and product was purified with column chromatography.General procedure: To a solution of Cu(OAc)2·H2O (0.01 mmol) in DMF (2 mL) were added aryl iodide (1.2 mmol), nitrogen-containing heterocycle (1.0 mmol), and Cs2CO3 (2 mmol) under nitrogen atmosphere. The mixture was stirred at 110 C for 24 h. After cooling to ambient temperature, the mixture was partitioned between water and ethyl acetate. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel.General procedure: A 25 mL Schlenk tube was charged with Cu2O (0.05 mmol), ArX (0.5 mmol), NHR1R2 (0.75 mmol), NaOH (1 mmol), TBAB (0.1 mmol), L2 (0.1 mmol) and H2O/EtOH (1 mL, 1/1, v/v). The mixture was stirred at 120 C for 12 h. The reaction mixture was extracted with ethyl acetate (3 10 mL), washed with water and brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatograph on silica gel(ethyl acetate/petroleum ether as the eluent) to provide the target products 3a-3w and 6.General procedure: CuSO4·5H2O (12.50 mg, 0.05 mmol), the aryl iodide or bromide(1.0 mmol), pyrrole (1.5 mmol), NaOH (80 mg, 2 mmol), and DMSO(2 mL) were placed in a 10 mL sealed tube. The mixture was heatedat 110 C in a preheated oil bath for 12 h. It was then cooled to roomtemperature, diluted with 20 mL H2O, and the mixture was extractedwith ethyl acetate (3 × 20 mL). The combined organic phases waswashed with water and brine, dried over anhydrous Na2SO4, andconcentrated in vacuo. The residue was purified by flash columnchromatography on silica gel (ethyl acetate/petroleum ether, 1 : 100)to afford the target products. All C-N coupling products reported hereare known products and were characterised by GC-MS and 1H NMR, which were compared with the previously reported dates.General procedure: In 50 mL round bottom flask, aryl halide (1.0 mmol), pyrazole (1.2 mmol), ligand (0.04 mmol), Cu2O (0.10 mmol), cesium carbonate (2.0 mmol), and dry solvent (20 mL) were placed under nitrogen atmosphere. The reaction mixture was heated in oil bath up to specified temperature under constant stirring for 20 h and then allowed to cool to room temperature. The reaction mixture was filtered through a plug of Celite in a fritted filter funnel and washed with ethyl acetate. If DMSO is used as solvent, it is extracted by washing the filtrate with 25 mL water for three times. The organic phase was dried over anhydrous MgSO4 and was removed under reduced pressure to provide the crude product which was purified by column chromatography on silica gel, using hexane and ethyl acetate in 3:1 ratio, respectively, as an eluent.Cu (0.05 mmol), L4 (0.1 mmol), aryl halides(0.5 mmol), imidazoles (0.75 mmol), KOH (1 mmol), TBAB (0.15 mol), and H2O(1 mL) were added to a 10 mL sealed tube. The reaction mixture was reacted at120 C in a pre-heated oil bath for 12 h. The reaction mixture was cooled to room temperature, diluted with 10 mL H2O, and then the mixture was extracted with ethyl acetate (3 20 mL). The combined organic phases were washed withwater and brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatograph on silica gel (ethyl acetate/petroleum ether, 2:1 to pure ethyl acetate) to afford the target products.General procedure: A mixture of pyrrole (3 ml), Cs2CO3 (1.96 g, 6 mmol), Cu0/4A or Cu2+/4A (0.3 g) and the appropriate aryl halide (3 mmol) were stirred at 135 C (bath temperature) for 4-36 h. Before adding to the mixture, Cu2+/4A was preheated at ca. 150 C for 1 h. The mixture was filtered, the solid was washed with dichloromethane. The filtrate was extracted with deionised water (2 x 40 ml). The organic phase was dried over Na2SO4 and concentrated in vacuum. The residue was distilled and clarified. Certain products (3c, 3f) were purified by recrystallization from MeOH.General procedure: An oven-dried Schlenk tube was charged with Cu(OAc)2·H2O (0.1 mmol, 0.01 equiv), Cs2CO3(20 mmol, 2 equiv), and aryl iodide (if solid, 12 mmol, 1.2 equiv). The tube was degassed with argon for three times. Then DMF (20 mL), pyrrole (10 mmol, 1 equiv), and aryl iodide (if liquid, 12 mmol, 1.2 equiv) were added via syringe under room temperature. The mixture was stirred at110 C for 24 h, and then cooled down to room temperature. The reaction mixture was quenched with water (40 mL) and extracted with ethyl ether (20 mL) for three times. The combined organic layers were dried with Na2SO4, filtered and concentrated. The crude products were purified using flash column chromatography on silica gel to afford the desired product.General procedure: To azole (6.0 mmol) and aryl halide (4.0 mmol) in acetonitrile (20 mL) were successively added Cu (50 mg, 0.80 mmol), Cs2CO3 (2.6 g, 8.0 mmol) and, in the case of aryl bromides, KI (99 mg, 6.0 mmol). The mixture was stirred under argon at acetonitrile reflux temperature (the reaction time is given in the product description) before dilution with AcOEt (40 mL) and filtration. Concentration under reduced pressure and purification by chromatography on silica gel (the eluent is given in the product description) led to the expected compounds.General procedure for N-arylation of amines:The N-nucleophile (1.47 mmol), Cu2O (Sigma-Aldrich, 99.99% purity, 0.147 mmol), K3PO4 (2.94 mmol), the aryl halide (1.76 mmol), phase transfer catalyst (0.147 mmol) and water (0.75 mL) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 130 C for 24 h, then the heterogeneous mixture was cooled to RT and diluted with dichloromethane. The resulting solution was directly filtered through a pad of Celite. The combined organic extracts were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of all products was confirmed by 1H and 13C NMR spectroscopic analysis.General procedure: The 128 mu L (1.0mmol) 3-iodo toluene, 208 mu L (1.5mmol) pyrrole, 125 mg calcium base montmorillonite clay, 0.0200g (0.1mmol) copper acetate, 0.2746g (2.0mmol) potassium carbonate by adding 5 ml of dimethyl sulfoxide, 105 °C reaction 7 hours, the reaction is stopped, the centrifugal separation, the separating medium is added to 15 ml distilled water, with 10 ml ethyl acetate extraction three times, combined with the phase, drying with anhydrous magnesium sulfate, the solvent is removed, with petroleum ether with ethyl acetate the volume ratio of 1:50 flow at the mixed liquid chromatographic separation, to obtain yellow oily liquid N-(3-methyl phenyl) pyrrole, its yield is 92percent.

Molecular Weight:173.21
XLogP3:3.1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:2
Exact Mass:173.084063974
Monoisotopic Mass:173.084063974
Topological Polar Surface Area:14.2
Heavy Atom Count:13
Complexity:146
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes