* 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.
Stage #1: With sulfuric acid; sodium nitrite In water at 12℃; Stage #2: With hydrogen bromide; copper(I) bromide In water at 40 - 65℃;
adding 1020 g of 2-bromo-5-aminoanisole to the reaction vessel,Add about 30percent sulfuric acid 8380 g and stir.Then, a solution of 455 g of sodium nitrite and 1000 g of water was added dropwise, and the process temperature was controlled at about 12 °C.After the addition is completed, the mixture is stirred for a while to prepare a diazonium salt for use. Add 520 g of cuprous bromide and HBr 1350 g to another reaction flask.The above diazonium salt is added under stirring, and the temperature rises when decomposed, and the controlled temperature is 40 to 65 °C.After the addition, continue to stir, keep the reaction for a period of time, stir, cool, filter,The brown solid 2,5-dibromoanisole was obtained in an amount of 1086 g, and the content was more than 97percent, and the yield was 81percent.
Reference：
[1] Patent: CN109320403, 2019, A, . Location in patent: Paragraph 0011; 0013; 0014; 0016; 0018; 0019
EXAMPLE 19 4-Bromo-3-methoxyanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide To a suspension of <strong>[846023-24-3]2-cyano-N-(2,4-dichloro-5-methoxyphenyl)acetamide</strong> (6.1 g, 23.5 mmol) in 500 mL of isopropanol was added 5-amino-2-bromoanisole (5.0 g, 24.8 mmol). This mixture was heated to reflux to give a clear yellow solution. To this solution, triethylorthoformate (10.6 mL, 63.5 mmol) was added dropwise and the reaction mixture was heated at reflux for 5 hours. An additional 10.6 mL of triethylorthoformate was added and the mixture was heated at reflux overnight. The mixture was allowed to cool to room temperature. The solid was collected by filtration, washed with isopropanol and ethyl acetate, and then dried overnight at ~40 C. under reduced pressure to give 8.1 g (73%) of 4-bromo-3-methoxyanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide as a yellow solid, mp >250 C.; MS (ES) m/z470.0, 472.0 (M+H)+ Analysis for C18H14BrCl2N3O3; Calcd: C, 45.89; H, 3.00; N, 8.92.
To a solution of 4-bromo-3-methoxyaniline (1k) (2.00 g, 9.9 mmol) in water (50 mL) was added hydrochloric acid (4 mL) and sodium nitrite , NaNO2) (0.75 g, 10.9 mmol) is slowly added at 0°C. The mixture was stirred at 0 °C for 30 minutes and then potassium carbonate (1.67 g, 11.9 mmol), copper cyanide (CuCN) (1.06 g, 11.9 mmol) and potassium cyanide (KCN) Mmol) dissolved in water (50 mL). The mixture is stirred at 70°C , cooled, and extracted with toluene. Magnesium sulfate is added to the extracted organic layer to remove water and concentrated under reduced pressure. The concentrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane: ether = 6: 1) , 4-bromo-3-methoxybenzonitrile can be obtained in the form of yellow powder.
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