L. D. Abbott, J. Smith
1949
Citations
0
Influential Citations
3
Citations
Journal
The Journal of biological chemistry
Abstract
Homogentisic acid (2,5-dihydroxyphenylacetic acid), an important intermediate in the metabolism of tyrosine and phenylalanine, is not readily available, nor does a survey of the literature reveal a convenient method for its chemical preparation. The syntheses of Baumann and Frankel (l), Osborne (2), and Neubauer and Flatow (3), although useful as proof of structure, are not suitable as preparative methods. Hahn and Stenner (4) developed a synthesis based on the ozonization of dibenzoylallylhydroquinone which yielded homogentisic acid from hydroquinone in six steps with a 26 per cent yield. In the course of studies on the reactions of ketene diethyl acetal, McElvain and Cohen (5) noted that acid hydrolysis of the reaction product of benzoquinone with ketene acetal yielded homogentisic acid. The procedures involved in these two methods make their use inconvenient as preparative methods in most laboratories. Recent developments in the application of the Willgerodt reaction to the synthesis of arylacetic acids from aryl methyl ketones (6,7) and the commercial availability of the dimethyl ether of hydroquinonel make feasible the synthesis of the dimethyl ether of homogentisic acid (2,8dimethoxyphenylacetic acid) from 2,5-dimethoxyacetophenone. Hydriodic acid, or hydriodic acid and red phosphorus, has been used previously to demethylate the dimethyl ether of homogentisic acid (1, 2). Although this reagent does bring about demethylation of this ether, its use in our hands has been unsatisfactory. We have found 2,5-dimethoxyphenylacetic acid to be easily demethylated with 48 per cent hydrobromic acid, a reagent which has been used to demethylate guaiacol (8). The desired product was thus obtained readily in good yield and in good condition.