4-broMo-N,N-bis(4-Methoxyphenyl)aniline

Synthesis of 4-bromo-N, N-bis(4-methoxyphenyl)aniline. 2. N, N-bis(4- methoxyphenyl)aniline 1 (9.0 g, 29.5 mmol) was dissolved in 100 mL dimethylformamide in a 250 mL round bottom flask. N-bromosuccinimide (5.25 g, 29.5 mmol) was dissolved in 30 mL dimethylformamide and added dropwise to the reaction mixture. The reaction was allowed to stir at room temperature while being monitored by thin layer chromatography (TLC) (Reaction Time = 23 h). The reaction mixture was quenched using 600 mL water and extracted with 4 x 150 mL dichloromethane. The organic layers were combined and washed with 4 x 150 mL saturated sodium thiosulfate solution and dried over sodium sulfate. The solvent was removed under reduced pressure. The product was purified along with materials prepared previously using flash chromatography on silica gel eluting with 5:1 hexanes:ethylacetate (12.1 g, 100percent). N, N-bis(4-methoxyphenyl)aniline 1 (9.0 g, 29.5 mmol) was dissolved in 100 mL dimethylformamide in a 250 mL round bottom flask. N-bromosuccinimide (5.25 g, 29.5 mmol) was dissolved in 30 mL dimethylformamide and added dropwise to the reaction mixture. The reaction was allowed to stir at room temperature while being monitored by thin layer chromatography (TLC) (Reaction Time=23 h). The reaction mixture was quenched using 600 mL water and extracted with 4×150 mL dichloromethane. The organic layers were combined and washed with 4×150 mL saturated sodium thiosulfate solution and dried over sodium sulfate. The solvent was removed under reduced pressure. The product was purified along with materials prepared previously using flash chromatography on silica gel eluting with 5:1 hexanes:ethylacetate (12.1 g, 100percent).The reaction route is as follows:A 1 L three-necked flask was charged with 51.0 g (0.167 mol) of Intermediate 5 (prepared by Example 13)408 g DMF.31.2 g (0.175 mol) of NBS was dissolved in 62.4 g of DMF to form a pale yellow solution.Control the internal temperature 0 ~ 20 , The above solution was slowly added dropwise into a three-necked flask under mechanical stirring, 20 minutes plus finished, And stirred at 0 ~ 20 ° C for 3 hours.Completed the reaction, To the reaction mixture, 200 g of toluene and 300 g of water were added to extract the liquid.The organic phase is washed with water, Dried over anhydrous sodium sulfate, Silica gel column, Decompression solvent was reddish brown viscous liquid.The crude product was recrystallized from ethanol, 58.3g white powder, Yield 90.8percent.To a 100 mL three-necked flask was added p-iodoanisole (1.1 g, 4.8 mmol) in this order, P-bromoaniline (0.34 g, 2.0 mmol), Potassium hydroxide (0.56 g, 10 mmol), 1, 10-phenanthroline (0.03 g, 0.16 mmol) and 60 mL of toluene, Fitted with a reflux condenser, Vacuum, Replace argon protection.Under argon flow, A catalytic amount of cuprous chloride was quickly added, The reaction was heated to reflux for 20 h.After TLC detection of raw materials reaction finished, The reaction was stopped, The solvent was distilled off under reduced pressure, The reaction mixture was dissolved in 100 mL of dichloromethane, And further washed three times with saturated brine (80 mL x 3)The organic phase was dried over anhydrous sodium sulfate overnight.The filtrate was collected by filtration, The solvent was removed under reduced pressure, The crude product was purified by column chromatography on silica gel (200-300 mesh [eluent, V (petroleum ether): V (ethyl acetate) = 8: 1] to give Intermediate 6 (0.60 g) as a pale yellow solid, Yield 78percent.A mixture of 1-iodo-4-methoxybenzene (10.00 g, 42.74 mmol), 4-bromobenzenamine (2.95 g, 17.15 mmol) and 1, 10-phenanthroline anhydrous (0.62 g, 3.42 mmol) in toluene (60 mL) was heated and stirred under nitrogen atmosphere. When the temperature reached to 110 °C, the CuI (0.65 g, 3.42 mmol) and KOH (7.66 g, 136.79 mmol) were added quickly, and then the mixture was stirred at 135 °C for 12 h. After cooled to RT, the mixture was poured into distilled water (50 mL) and extracted with dichloromethane (DCM) (3 * 30 mL). The combined organic layer was dried over MgSOIn a 100 mL three-necked flask, 4-methoxyiodobenzene (10.0 g, 42.74 mmol) and p-bromoaniline (2.9 g, 17.15 mmol), anhydrous 1, 10-phenanthroline (0.6 g, 3.42 mmol) and 60 mL of toluene were added and the temperature was raised to 110 ° C under the protection of nitrogen.Copper iodide (0.7 g, 3.42 mmol) and potassium hydroxide (7.7 g, 136.79 mmol) were added rapidly and the reaction was further allowed to warm to 135 ° C and the reaction was stirred for 12 h. After cooling to room temperature, the reaction mixture was poured into 50 mL of distilled water and extracted with CH 2 Cl 2 (3 × 30 mL). The extract was washed with water, dried over anhydrous MgSO 4 and the solvent was removed under reduced pressure. The crude product was washed with CH 2 Cl 2: PE = 1: 5 V) as eluent, and separated by column chromatography to give 4.63 g of an off-white solid in a yield of 70.4percent.To a stirred solution of 4-iodoanisole (5.85 g, 25 mmol), 4-bromoaniline (1.72 g, 10 mmol), and 1, 10-phenanthroline (0.18 g, 1 mmol) in toluene (100 mL) were added potassium hydroxide (5.61 g, 100 mmol) and copper(I) iodide (0.19 g, 1 mmol). The reaction mixture was heated under reflux for 24 h at 125 °C. The crude product was extracted into dichloromethane, and the organic layer was washed with 1 N HCl solution, brine, and water. The organic layer was dried with anhydrous MgSOAdd 5.00 g of p-bromoaniline, 14.4 g of p-iodoanisole, 0.28 g of CuI, 12.8 g of KOH, and 0.26 g of 1, 10-phenanthroline to a 250 mL two-necked flask. Nitrogen was three times, then 60 mL of anhydrous oxygen-free toluene was added and stirred at 110° C. for 48 hours. After the reaction is completed, it is cooled to room temperature, filtered directly, and the filter residue is washed three times with dichloromethane.The filtrate was then spin-dried under reduced pressure. The resulting crude product was subjected to column chromatography using petroleum ether and dichloromethane in a volume ratio of 3:1 as eluent to obtain 6.02 g of a yellow solid 3 with a yield of 53.8percent.Synthesis steps:To a 250 mL reaction flask was added Compound 1b (4.58 g, 20 mmol) (commercially available), Compound 2b (commercially available) (8.5 g, 30 mmol), Pd2 (dba) 3 (920 mg, 5percent), Tri-tert-butylphosphine (400 mg, 10percent), sodium tert-butoxide (4.58 g, 40 mmol) and toluene (100 mL).Nitrogen was evacuated three times, heated to 110 ° C, maintained at this temperature, reacted for 12 hours, TLC detection of compound 1b reaction completely.After completion of the reaction: the heating was stopped and the temperature was lowered to 20 ° C. The reaction solution was poured into water and extracted with ethyl acetate (10 mL * 2). The combined organic layers were dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The crude product was purified by column chromatography to afford the pale yellow compound 3b(4.3 g, yield 56.4percent).General procedure: C^N chelating ligands were obtained by the classical Suzuki reaction(Scheme 1); the general process is listed as follows: The correspondingbrominated PhCz/TPA (4.0 mmol), 4-phenylpyridine-2-boronic acid(4.8 mmol, 0.96 g), palladium tetraphenylphosphine (0.08 mmol, 0.14 g), anhydrous potassium carbonate (8.0 mmol, 1.11 g), 60 mL oftoluene and 12 mL of deionized water were added to a 100 mL flask under N2 and stirred at 383 K for 12 h. The product was extracted withdichloromethane (30 mL × 3) and distilled under reduced pressure.Then, the product was purified by chromatography on a silica gelcolumn (petroleum ether: ethyl acetate =15:1 as eluent), and the puretarget chelating ligands were obtained. The 1H NMR spectrum, 13CNMR spectrum and ESI-MS of L1-L3 are presented in Figs. S14, S16 andS18. The data were as follows:

Molecular Weight:384.3
XLogP3:5.8
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:5
Exact Mass:383.05209
Monoisotopic Mass:383.05209
Topological Polar Surface Area:21.7
Heavy Atom Count:24
Complexity:333
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes