2-Chloro-4-(methylsulfonyl)benzoic acid

WHITE TO LIGHT YELLOW OR LIGHT PINK POWDER

Acetonitrile (4 ml) and compound 5 (100 mg, 0.46 mmol) were added to a 10 ml three-necked flask and stirred until dissolved.After cooling to 0°C, add NaClO2 (124 mg, 1.38 mmol) of an aqueous solution of 1 ml and HCl (117 μL) was stirred for 0.5 h and then warmed to 80° C. and stirring was continued for 0.5 h.After the reaction was monitored by TLC, the mixture was cooled to room temperature, and the mixture was dried on acetonitrile, adjusted to pH 2 with 1N HCl aqueous solution, and extracted with ethyl acetate/water.The organic phase was obtained, and the organic phase was dried over anhydrous Na 2 SO 4 , and the organic solvent was removed by rotary drying to obtain a crude product. The crude product was purified by column chromatography and petroleum ether:ethyl acetate (glacial acetic acid)=1:1 (5 Torr) was eluted to give Compound 32. White solid 50 mg, 46.6percent yield.117 g of 2-chloro-4-methylsulfonyltoluene obtained in step 1) and 75 g of 40percent phosphoric acid were added to a 500 ml four-necked flask;After stirring to raise the temperature to 160 ° C, dilute nitric acid with a concentration of 68percent (ie 15.2 mol / L) was slowly added dropwise;During the dropwise addition, the temperature was kept at 160 ° C;Reaction to the end, stop adding dilute nitric acid;After the reaction was completed, the water was slowly added to the reaction mixture, stirred and cooled for about 30 minutes at room temperature, filtered, The filter cake was washed, the washed material was added to a 1000ml four-necked flask equipped with 400g of water, Then add dichloroethane refined filter (dichloroethane added amount of 2-chloro-4-methylsulphenyl toluene quality of 1.8 times)124g of white crystals of 2-chloro-4-methylsulphonylbenzoic acid dried in an amount of 99.0percent or more, The final molar yield of 2-chloro-4-methylsulfonylbenzoic acid was found to be 94.3percent.Table 1 2-Chloro-4-(methylsulfonyl)toluene (0.100 mol, 20.50 g), CuI (0.001 mol, 0.19 g) and 25 wtpercent HNO3 (12.60 g) were added in sequence to a 100 mL high pressure reaction kettle equipped with stirrer and a temperature measuring device. Oxygen gas filled the kettle until the pressure was 1.5 MPa. The reaction solution was heated to 160 C slowly (approximately 0.7 h). The autoclave pressure was raised to 2.5 MPa. The reaction was continued for 4 h with stirring at keeping 160 C (thermostated). At the conclusion of the reaction the pressure declined to 0.8 MPa and was stable (9 molpercentNO2 and 5 molpercent NO, gaseous species concentration determined by the concentration of NO2- and NO3- after passing the gas through NaOH solution). Thin layer chromatography (TLC) was used to determine reaction conversions in some instances. After the reaction was finished, a 25 wtpercent NaOH solution (0.200 mol NaOH) was added into the reaction solution and stirring was continued. After reduced pressure filtering, 36 wtpercent hydrochloric acid was used to adjust the pH of the filtrate to pH 2. The resulting precipitate was collected by filtration. This precipitate was added to MeOH (110 mL) containing 3.00 g of activated carbon. The mixture was heated gently to reflux temperature (60 C). The precipitate dissolved completely. Stirring was continued for 1 h. The mixture was filtered, and allowed to cool at 10 C. After 8 h at -5 C the reaction was filtered. The solid precipitate was dried at 80 C for 5 h to give 19.70 g (0.084 mol) of the product as white crystals. The yield was 84.2percent and the product purity was 99.7percent.EXAMPLE 3 The procedure of was repeated using dichloroethane as solvent in place of ethyl acetate. The yield of 2-chloro-4-methylsulphonylbenzoic acid was 88.6percent.EXAMPLE II This example teaches the preparation of the n-propyl ester of EXAMPLE 7 STR22 Water (350 g) and aqueous sodium hydroxide solution (43.4 g, 0.51 Mol) were added to a stirred solution of the product of Example 6 in toluene (285 ml, ca 0.175 Mol). The reaction was heated to reflux and the toluene azeotropically distilled off, while returning water to the reaction. The reaction was maintained at reflux for 16 hours. The reaction was cooled to 10° C. and sulphuric acid (25.0 g, 0.26 Mol) added dropwise while maintaining the temperature at 10° C. The precipitate was filtered off, washed with a little cold water and dried under vacuum at 80° C. for 12 hours to yield 2-chloro-4-methylsulphonylbenzoic acid (34.3 g).Aqueous phases were combined and acidified to pH 0-1 with 18percent hydrochloric acid and the resulting solids filtered off to yield 3.93 g of product with a melting point of 187-192°C. HPLC determined the sulfone to be 94.9 weight percent of the benzoic acid with a technical yield of 91.4percent.

Molecular Weight:234.66
XLogP3:1.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:233.9753576
Monoisotopic Mass:233.9753576
Topological Polar Surface Area:79.8
Heavy Atom Count:14
Complexity:319
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes