1-(4-BROMO-PHENYL)-1H-PYRROLE

General procedure: Amine (1 mmol), 2, 5-dimethoxytetrahydrofuran (1.1 mmol)and L-(+)-tartaric acid–choline chloride based DES (1.5 g) were added to a 50 mL round bottom flask and the reaction mixturewas stirred at 90 °C. The progress of the reaction was monitoredby TLC. After completion of the reaction, the mixture was cooled to room temperature and the product was extracted with ethyl acetate.After the evaporation of the solvent, the residue was purified by columnchromatography on silica gel to afford the pure product. The DES wasdried under vacuumand reused for the next cycle.General procedure: To a solution of amine (1 mmol) in water (2 ml) was added tetrahydro-2, 5-dimethoxyfuran (1.1 mmol) and γ-FeGeneral procedure: A Schlenk reaction tube was charged with primary aromatic amine (5.0 mmol), 2, 5-dimethoxytetrahydrofuran (6.0 mmol), MgIGeneral 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), CsGeneral 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: 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: 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: Amine (1 mmol), 2, 5-dimethoxytetrahydrofuran (1.1 mmol)and L-(+)-tartaric acid-choline chloride based DES (1.5 g) were added to a 50 mL round bottom flask and the reaction mixturewas stirred at 90 C. The progress of the reaction was monitoredby TLC. After completion of the reaction, the mixture was cooled to room temperature and the product was extracted with ethyl acetate.After the evaporation of the solvent, the residue was purified by columnchromatography on silica gel to afford the pure product. The DES wasdried under vacuumand reused for the next cycle.General procedure: To a solution of amine (1 mmol) in water (2 ml) was added tetrahydro-2, 5-dimethoxyfuran (1.1 mmol) and gamma-Fe2O3(at)SiO2-Sb-IL (0.08 g). The reaction mixture was stirred at 100 C for a certain period of time as required to complete the reaction. During that time, the reaction was monitored constantly by TLC. After completion of the reaction, the catalyst was removed by using a magnet and washed with ethyl acetate. The aqueous solution was extracted by ethyl acetate (3 × 5 ml). The combined organic phase was dehydrated with anhydrous sodium sulfate. After the evaporation of the solvent, the residue was purified by silica gel flash chromatography using petroleum ether/ethyl acetate as the eluent to afford the pure product.General procedure: Oxone (0.09 g, 0.30 mmol) was added to a solution of the aromatic primary amines (2.5 mmol) and 2, 5-dimethoxytetrahydrofuron (3.0 mmol) in a solvent (5 mL) was further added (Scheme1). The reaction mixture was heated under microwave irradiation for 10 min at 110 ± 10 C. The reaction mixture was irradiated until total consumption of the amine was verified by TLC. Water was added and the products were extracted with EtOAc (3x20 mL). The organic phasewas dried over anhydrous MgSO4 and the solvent was removed under reduced pressure. The product was purified on a silica gel column chromatography eluted with mixture of ethylacetate/hexane (1:4) to afford the product.General procedure: A Schlenk reaction tube was charged with primary aromatic amine (5.0 mmol), 2, 5-dimethoxytetrahydrofuran (6.0 mmol), MgI2 etherate (10% mmol), and acetonitrile (10 mL). The reaction mixture was stirred at 80 C for several hours and then concentrated in vacuo. The residue was purified by flash column chromatography on a silica gel to give the desired product.General procedure: 1 mmol of aniline or other aniline derivative were mixed with 1.1 equivalent of acetonylacetone, 0.05 g of CHCl:TASi02 microcapsules (10 mol% L-tartaric acid), and 1 g solvent. The mixture was stirred at a suitable temperature for the required amount of time and monitored by TLC. At the end of the reaction, the capsules were separated by centrifugation, washed twice with acetonitrile, dried under high vacuum for 2 hours, and then used in the next catalytic cycle. The washings were combined with the reaction mixture and the products were separated by evaporation and purified by column chromatography on silica using 10% ethyl acetate in hexane.General procedure: On the benchtop, the electrophile (aryl bromide/triflate, thioester, or acyl chloride, 1.0equiv), organotin (1.1 to 1.3 equiv), Pd(dba)2 (5 mol %), JackiePhos (10 mol % or 15mol %), CuCl (0.5 or 2.0 equiv), and anhydrous KF (for aryl bromide/triflate, 2.0equiv) were added to an oven-dried 8 mL screw-top test tube equipped with a stirbar.The test tube was sealed with a screw-top septum and electrical tape. The reaction vessel was evacuated (ca. 100 mtorr) and backfilled with argon 3 times. If the electrophile were liquid, it was added to the reaction vessel via syringe at this point. Solvent(CH3OH, 1, 4-dioxane, or toluene, 1.0 or 0.5 mL) was then added via syringe. The septum was covered with electrical tape, and the reaction vessel was heated for 12 h(unoptimized reaction time) using a heating block. The cooled reaction mixture was transferred to a separatory funnel, diluted with water, and extracted with diethyl ether(3 x 10 mL). The combined organic layers were washed with brine (10 mL) and dried over Na2SO4. The organic layer was filtered, concentrated under reduced pressure, and purified by column chromatography.General procedure: On the benchtop, the electrophile (aryl bromide/triflate, thioester, or acyl chloride, 1.0equiv), organotin (1.1 to 1.3 equiv), Pd(dba)2 (5 mol %), JackiePhos (10 mol % or 15mol %), CuCl (0.5 or 2.0 equiv), and anhydrous KF (for aryl bromide/triflate, 2.0equiv) were added to an oven-dried 8 mL screw-top test tube equipped with a stirbar.The test tube was sealed with a screw-top septum and electrical tape. The reaction vessel was evacuated (ca. 100 mtorr) and backfilled with argon 3 times. If the electrophile were liquid, it was added to the reaction vessel via syringe at this point. Solvent(CH3OH, 1, 4-dioxane, or toluene, 1.0 or 0.5 mL) was then added via syringe. The septum was covered with electrical tape, and the reaction vessel was heated for 12 h(unoptimized reaction time) using a heating block. The cooled reaction mixture was transferred to a separatory funnel, diluted with water, and extracted with diethyl ether(3 x 10 mL). The combined organic layers were washed with brine (10 mL) and dried over Na2SO4. The organic layer was filtered, concentrated under reduced pressure, and purified by column chromatography.General procedure: To a mixture of aryl halide (0.3 mmol), NiCl2(H2O)1.5 [1] (0.0075 mmol, 2.5 mol %), was charged dry THF (1 mL). The mixture was pumped and refilled with nitrogen for three times. The resulting mixture was stirred at -10 under nitrogen for 30 min. The reaction mixture was quenched through the addition of ice MeOH, then poured into a separatory funnel containing saturated aqueous NH4Cl (ca. 5 mL) and extracted with EtOAc (3 x 5 mL). The combined organic layers were washed with brine and dried over Na2SO4. The crude product was purified by column chromatography. Extent of isomerization can be easily determined via 1H NMR spectroscopy by comparison of the intergral of the singlet from the t-butyl group (1.3-1.4 ppm, 9H) to the integral of the doublet from the benzylic S3 protons of the i-butyl group (2.4-2.5 ppm, 2H). The doublet from the methyls of the i-butyl group could additionally be used (ca. 0.8 ppm, 6H).

Molecular Weight:222.08
XLogP3:3.8
Rotatable Bond Count:1
Exact Mass:220.98401
Monoisotopic Mass:220.98401
Topological Polar Surface Area:4.9
Heavy Atom Count:12
Complexity:135
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes