* 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 hydrogenchloride; potassium iodide; sodium nitrite In water at 0 - 20℃; for 3 h;
To a solution of 5-fluoro-2-nitroaniline (70.0 g, 448 mmol) in HCl (350 mL, 37percent in water) at 0° C. was added sodium nitrite (32.2 g, 469 mmol, in 100 mL water) dropwise. The mixture was stirred for 1 h at which time, potassium iodide (82.0 g, 490 mmol, in 100 mL H2O) was added dropwise. The mixture was stirred at rt for 2 h and then extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4) and purified by flash chromatography to provide the title compound (98.6 g, 368 mmol, 83percent). 1H NMR (400 MHz, CDCl3) δ ppm 7.15-7.23 (m, 1H), 7.75 (dd, J=3.50Hz, J=7.60Hz, 1H), 7.97 (dd, J=1.6 Hz, J=8.8 Hz, 1H).
With copper(l) iodide; 1,10-Phenanthroline; oxygen; sodium iodide In dimethyl sulfoxide at 160℃; for 24 h; Schlenk technique
Silak reaction tube equipped with a magnetic stirrer was added11.4 mg of copper iodide,5.9 mg of 1,10-phenanthroline, 37 mg of 2-nitro-5-fluorobenzoic acid,36 mg of sodium iodide and 4 mL of dimethylsulfoxide.The reaction was heated at 160 ° C for 24 hours in the presence of oxygen.After the reaction was completed, distilled water was added to quench the reaction,Extraction with ethyl acetate 3 times, each time 10mL,The combined organic phases are concentrated,31.5 mg of 2-nitro-5-fluoroiodobenzene was obtained,The yield is 59percent.
Reference:
[1] Journal of Organic Chemistry, 2016, vol. 81, # 7, p. 2794 - 2803
[2] Patent: CN107325002, 2017, A, . Location in patent: Paragraph 0079
5-fluoro-4'-methylsulfinyl-2-nitrobiphenylamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; In N-methyl-acetamide; benzene;
A. 5-Fluoro-4'-Methylsulfinyl-2-Nitrobiphenylarmine 2-Iodo-4-fluoronitrobenzene (0.2 mole) and 4-methylsulfinylaniline (0.2 mole) are refluxed in dry dimethylformamide (300 ml.) containing copper powder (5 g) and some powdered potassium carbonate (20 g) under nitrogen for 18 hours. The suspension is filtered, and the organics are washed with water (6 times 100 ml.) in benzene (600 ml.). The benzene layer is extracted with 2.5 N HCl (7*200 ml.), and the acid layer is poured onto powdered sodium bicarbonate. The basic solution is extracted with benzene (6 times 200 ml.), the benzene layer is washed with water (3 times 100 ml.), is separated, dried (MgSO4) and filtered. Evaporation of the solvent followed by chromatography on a 2 in.*24 in. column of silica-gel (Baker), eluted with various proportions of benzene-hexane mixtures, gives pure 5-fluoro-4'-methylsulfinyl-2-nitrobiphenylamine.
With potassium carbonate; In N-methyl-acetamide; benzene;
A. 5-fluoro-4'-methylsulfinyl-2-nitrobiphenylamine 2-Iodo-4-fluoronitrobenzene (0.2 mole) and p-methylsulfinylaniline (0.2 mole) are refluxed in dry dimethylformamide (300 ml.) containing copper powder (5 gm.) and some powdered potassium carbonate (20 gm.) under nitrogen for 18 hours. The solution is filtered and the organics washed with water (6 * 100 ml.) in benzene (600 ml.). The benzene layer is extracted with 2.5 N HCl (7 * 200 ml.) and the acid layer poured onto powdered sodium bicarbonate. The basic solution is extracted with benzene (6 * 200 ml.), the benzene layer washed with water (3 * 100 ml.), separated, dried (MgSO4) and filtered. Evaporation of the solvent followed by chromatography on a 2 in. * 24 in. column of silica-gel (Baker) eluted with various proportions of benzene-hexane mixtures gives pure 5-fluoro-4'-methylsulfinyl-2-nitrobiphenylamine.
5-fluoro-4'-methylsulfinyl-2-nitrobiphenyl sulfide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In tetrahydrofuran; N-methyl-acetamide; mineral oil;
A. 5-Fluoro-4'-Methylsulfinyl-2-Nitrobiphenyl sulfide 4-Methylsulfinylthiophenol (0.2 mole) is dissolved in dry tetrahydrofuran (100 ml.) and sodium hydride (50% dispersion in mineral oil, 0.2 mole) is added over 30 minutes. The solution is evaporated to dryness and the residue is rinsed well with n-hexane. The powdered salt is stirred under N2 at reflux with 4-fluoro-2-iodonitrobenzene (0.2 mole) in dry dimethylformamide for 16 hours, evaporated to dryness and extracted into chloroform (3 times 200 ml.). The organics are washed with water (2*100 ml.), separated and dried (MgSO4). The solution is filtered, evaporated to dryness and put on a column of silica-gel (Baker 2 in. times 2 ft.) and various fractions are eluted with portions of benzene-n-hexane. In this way, pure 5-fluoro-4'-methylsulfinyl-2-nitrobiphenyl sulfide is obtained.
In tetrahydrofuran; N-methyl-acetamide; mineral oil;
A. 5-fluoro-4'-methylsulfinyl-2-nitrobiphenyl sulfide p-Methylsulfinylthiophenol 0.2 mole) is dissolved in dry tetrahydrofuran (100 ml.) and sodium hydride (50% dispersion in mineral oil, 0.2 mole) is added over 30 minutes. The solution is evaporated to dryness and the residue rinsed well with n-hexane. The powdered salt is stirred under N2 at reflux with 4-fluoro-2-iodonitrobenzene (0.2 mole) in dry dimethylformamide for 16 hours, evaporated to dryness and extracted into chloroform (3 * 200 ml.). The organics are washed with water (2 * 100 ml.), separated and dried (MgSO4). The solution is filtered, evaporated to dryness and put on a column of silica-gel (Baker 2 in. * 2 ft.) and various fractions eluted with portions of benzene-n-hexane. In this way, pure 5-fluoro-4'-methylsulfinyl-2-nitrobiphenyl sulfide is obtained.
With hydrogenchloride; potassium iodide; sodium nitrite; In water; at 0 - 20℃; for 3h;
To a solution of 5-fluoro-2-nitroaniline (70.0 g, 448 mmol) in HCl (350 mL, 37% in water) at 0 C. was added sodium nitrite (32.2 g, 469 mmol, in 100 mL water) dropwise. The mixture was stirred for 1 h at which time, potassium iodide (82.0 g, 490 mmol, in 100 mL H2O) was added dropwise. The mixture was stirred at rt for 2 h and then extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4) and purified by flash chromatography to provide the title compound (98.6 g, 368 mmol, 83%). 1H NMR (400 MHz, CDCl3) delta ppm 7.15-7.23 (m, 1H), 7.75 (dd, J=3.50Hz, J=7.60Hz, 1H), 7.97 (dd, J=1.6 Hz, J=8.8 Hz, 1H).
To <strong>[41860-64-4]4-fluoro-2-iodo-1-nitrobenzene</strong> (40.0 g, 150 mmol) in THF (200 mL) at -40 C. was added phenylmagnesium chloride (80.0 mL, 2M in THF, 161 mmol) dropwise. The reaction was stirred for 30 min followed by dropwise addition of CuCN.2LiCl (26.0 g, 150 mmol) in THF. The mixture was stirred an additional 30 min at which time allyl bromide (20.0 g, 161 mmol) was added. The reaction was stirred at -40 C. for 2 h followed by rt overnight. The reaction was quenched with saturated ammonium chloride and extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4) and concentrated. Purification by flash chromatography provided the title compound of step B (11.0 g, 60.7 mmol, 42%). 1H NMR (400 MHz, CDCl3) delta ppm 3.70 (d, J=6.4 Hz, 2H), 5.08-5.71 (m, 2H), 6.87-6.02 (m, 1H), 7.01-7.11 (m, 2H), 7.95-8.05 (m, 1H).
With tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; toluene; for 0.5h;Reflux;
[450] To a solution of <strong>[41860-64-4]4-fluoro-2-iodo-1-nitrobenzene</strong> (2.37 g, 8.9 mmol) in dioxane (10 mL) was added diethylzinc in toluene (13.3 mL, 13.3 mmol) and tetrakis(triphenyl- phosphine)palladium(0) (0.5 g, 0.43 mmol). The mixture was heated to reflux for 30 mm. Upon cooling, the reaction mixture was concentrated in vacuo and the resulting residue was purified by flash column chromatography on silica gel (heptane/EtOAc) to give 2-ethyl-4-fluoro-1-nitrobenzene (A6) as a red oil.
With copper(l) iodide; 1,10-Phenanthroline; oxygen; sodium iodide; In dimethyl sulfoxide; at 160℃; for 24h;Schlenk technique;
Silak reaction tube equipped with a magnetic stirrer was added11.4 mg of copper iodide,5.9 mg of 1,10-phenanthroline, 37 mg of 2-nitro-5-fluorobenzoic acid,36 mg of sodium iodide and 4 mL of dimethylsulfoxide.The reaction was heated at 160 C for 24 hours in the presence of oxygen.After the reaction was completed, distilled water was added to quench the reaction,Extraction with ethyl acetate 3 times, each time 10mL,The combined organic phases are concentrated,31.5 mg of 2-nitro-5-fluoroiodobenzene was obtained,The yield is 59%.