Dimethylmandelic Acid

Two recent reviews of the reactions and uses of diazomethane have appeared.8 9 

Submitted by J. L. Riebsomer and James Irvine. Checked by H. R. Snvder and R. L. Rowland. 

Ethyl 2,5-dimethylphenylkydroxymalonate. One hundred and seventy-four grams (1 mole) of ethyl oxomalonate (Note 1) and 265 g. (2.5 moles) of J -xylene are mixed in a 1-1. threenecked flask equipped with a good stirrer, a dropping funnel, and a calcium chloride drying tube. Suitable precautions are taken to exclude moisture from the reaction mixture. While the mixture is cooled in an ice-water bath and stirred vigorously, 325 g. 

5-Dimethylmandelic acid. A mixture prepared from 140 g. (0.5 mole) of 2,5-dimethylphenylhydroxymalonic ester and a cold solution of 140 g. of potassium hydroxide in 560 ml. of water in a 1-1. round-bottomed flask is warmed on a steam bath for 5 hours. The alkaline solution is cooled and extracted with one 100-ml. portion of ether to remove any material not soluble in alkali. The alkaline solution is acidified with 300 ml. of concentrated hydrochloric acid and then warmed on a steam bath and stirred for 2 hours (or until there is no further evidence that carbon dioxide is escaping). The mixture is cooled, the oily layer is extracted with ether, the ethereal solution is dried with anhydrous sodium sulfate, and the ether is distilled under partial vacuum (Note 3). The oily residue is crystallized from benzene. The yield of 2,5-dimethyImandelic acid melting at 116.5-117° is 55-63 g. (63-70%) (Note 4). 

The ethyl oxomalonate must be of good quality. It has been found possible to use nitrogen peroxide (now available in cylinders from the du Pont Company) in the preparation of this reagent. The general conditions are the same as in the previous method in Organic Syntheses 1 except that the generating flask 

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Dimethylmandelic acid has been prepared by the procedure described above 2 and by the reaction between 2,5-dimethylphenylmagnesium bromide and chloral, followed by alkaline hydrolysis.3... 

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