Oxidation—continued with sodium persulfate

The oxidizing agent is prepared in a 500-ml flask equipped with a magnetic stirrer and cooled in an ice bath as follows In the flask are placed 60 ml of concentrated sulfuric acid and 20 ml of water, and the solution is cooled to 10°. Potassium persulfate (42 g, 0.15 mole) is added slowly to the stirred solution while maintaining the temperature below 10°. The solution is diluted with an additional 65 ml of water maintaining the temperature below 15°. The solution is now cooled to about 7° and 0.08 mole of the ketone is added over 40 minutes. After the addition has been completed, the solution is allowed to come to room temperature and stirring is continued for 20 hours. The solution is diluted carefully with 150 ml of water and extracted twice with 75-ml portions of ether. The ether is washed with sodium bicarbonate solution, followed by water, and the ethereal solution is dried. Removal of the solvent, followed by fractional distillation, affords the product ester. 

Dimethyl-4-nitropyridine-N-oxide-dimethyl sulfate adduct (220 g, 0.75 mole) was dissolved in methanol (1.0 Itr) and the solution heated to reflux. A solution of ammonium persulfate (140 gm) in water (200 ml) was added dropwise over 4 hours after which reflux was continued for 4 hours. Methanol was distilled off under reduced pressure and the residue was basified to pH 10 by addition of caustic lye (105 ml). The mixture was extracted with dichloromethane (2 times 400 ml). The dichloromethane layer was dried over sodium sulfate and filtered. The product was used as its solution in dichloromethane for the next reaction. 

In one purification process (U.S Patent 3,202,481) potassium or sodium permanganate is used to oxidize the impurities Other oxidizing agents also can be used, such as persulfates or chlorates Molybdenum trioxide is used to form a complex with the oxidized phosphorus impurities. The nitric acid is contacted with the oxidizing agent and the molybdenum compound at the boiling point of the acid, and the acid is continuously removed by distillation. The oxidized impurities remain in the residue. As a result, the purified acid will contain less than 0.5 ppb by weight of arsenic and phosphorus. 

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