5-Bromo-2-chlorobenzoic acid

white to light yellow crystal powder

First, sodium periodate solution was configured: 5.5 g (25.56 mmol) of sodium periodate was dissolved in 38 ml of water and 23 ml of acetic acid.Next, add 10 g (63.9 mmol) of 2-chlorobenzoic acid, 6.6 g (63.9 mmol) of sodium bromide and sodium periodate solution to the reaction flask and heat to 30°C.At this temperature, 5.6 ml of concentrated sulfuric acid was slowly added dropwise. After completion of the dropwise addition of concentrated sulfuric acid, the temperature was raised to 50-65°C and reacted at this temperature for 2-3 hours.Thin layer chromatography (TLC) detection reaction is completed, cooled, poured into ice water, solid precipitated, filtered, The filter cake was washed with water several times to obtain the product 2-chloro-5-bromobenzoic acid 13.2 g, yield 87.8percent.This example is the preparation of 2-chloro-5-bromo-benzoic acid, and the specific method is as follows:2.14 g of molybdenum hexacarbonyl (0.01 mol) was added to a 1 L autoclave.217.0 g of 2-hydroxy-5-bromobenzoic acid (1.0 mol), 185.0 g of carbon tetrachloride (1.2 mol) and 250 mL of dimethyl sulfoxide, Heat to 150 ° C, The reaction was stirred for 6 h.After the end of the controlled reaction in HPLC, Evaporate the solvent under reduced pressure.Then add 250 mL of acetonitrile, Warm up to 70 ° C and stir to dissolve.Then add neutral alumina for hot filtration.The filtrate was cooled to room temperature.A pale yellow solid precipitated.Then, 564 mL of an ethanol/water mixed solvent (volume ratio 1:3) was added.After heating and dissolving, Slowly cool to 60 ° C first, After a small amount of crystals are precipitated, Cooled to 50 ° C for 1 h, Finally, it was slowly cooled to 28 ° C and stirred for 3 h.filter, Collecting white solids, Washed twice in cold water and dried.217.0 g of white solid 2-chloro-5-bromo-benzoic acid were obtained.The yield was 92.1percent and the purity was 99.9percent (HPLC).into a 250ml reaction flask added the 46g O-chlorobenzotrichloride (0.2mol, 1eq) and 0.2g Fe powder. Stirring at room temperature, and added the drops of 35g Br2, after that maintain the reaction temperature at 35-40 ° C for 6 h. Ventilation with nitrogen will blow out excess Br2, and absorbed with alkali. Cooled at 10 ° C, and added the drops of 60 g of concentrated sulfuric acid (exothermic, dripping speed control to prevent the flow), after that heated at 100 ° C for 5 h; temperature get down at 60 ° C below, then slowly added the drops of 150mL water(intense heat, gas overflow, strictly control the drop speed to prevent the flow), and maintain 60-80 ° C stirring for 1h, than after gradually cooling to 15 ° C, the mixture has been filtered and washed with 100 mL of water, after that obtained the white crude, the purity of the crude product is 91percent and yield is 99percent. The crude product has been recrystallized with 60percent aqueous acetic acid, then obtained white solid 42.0g (yield 90percent, HPLC purity is 98.8percent).60.00 g (0.26 mol) of 5_bromo-2-chlorobenzoic acid (1) was added to 200 mL of dry dichloromethane. 1.5 mL (5.2 mol) of DMF was added dropwise, and 32 mL (0.39 mmol) of oxalyl chloride was slowly dropped into the reaction solution four times under ice-cold bath conditions, and the temperature of the reaction solution was required to be between 0 and 5 ° C. The solution was slowly warmed to room temperature for 12 h. The reaction was monitored by thin layer chromatography TLC until the reaction of the starting material was completed, and solvent and oxalyl chloride were evaporated under reduced pressure. The oxalyl chloride was distilled off three times with dichloromethane, and cooled to give a white solid (2) 53.5 g. Yield 89.1percent

Molecular Weight:235.46
XLogP3:2.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:233.90832
Monoisotopic Mass:233.90832
Topological Polar Surface Area:37.3
Heavy Atom Count:11
Complexity:163
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes