The Synthesis of Aspartic Acid

No one of the methods proposed for the synthesis of aspartic acid is entirely satisfactory as a practical procedure. The synthesis, described in a recent paper (1) from this laboratory, has been utilized in preparing 50 to 60 gm. lots of recrystallized aspartic acid but even here the beginning reagents are expensive, the over-all yield is only about 30 per cent of the theoretical, and the process is time-consuming because of the number of steps involved. In searching for a convenient and inexpensive method of synthesis it was apparent that reactions with malic, succinic, maleic, or fumaric acid were the most promising. It was expected that ammonia could be made to react satisfactorily with chlorosuccinic or bromosuccinic acid, prepared from any one of the four dibasic acids, or directly with maleic or fumaric acid to give aspartic acid in good yield. Various methods for the preparation of the intermediate bromosuccinic (2-6) and chlorosuccinic acids (7-9) have been reported, whereas Fischer and Raske (10) were able to prepare 2.2 gm. (16 per cent of theory) of crude aspartic acid from bromosuccinic acid and aqueous ammonia. In our experiments with malic and fumaric acids the yields of chlorosuccinic and bromosuccinic acids were poor and only the insoluble ammonium salts resulted when these acids were treated with liquid ammonia or with a saturated solution of the dry gas in alcohol, ether, or pyridine. The formation of ammonium bromosuccinate in ether is in accord with the observations of MeMaster and Magi11 (11). The direct addition of ammonia to maleic and fumaric acids has been investigated by Engel (12) and Stadnikoff (13). When the amination was conducted at 140-150” in aqueous or alcoholic solution, Angel obtained a 30 to 35 per cent yield of aspartic