The Racemization of Amino Acids in Aqueous Solution by Acetic Anhydride

In a previous investigation du Vigneaud and Sealock (1) have reported that the sodium salt of acetyl-l-tryptophane in aqueous solution at 35-40” is completely racemized by acetic anhydride within a few hours. The ease of racemization and particularly the mild conditions under which the reaction occurred seemed to us to offer an excellent method for racemizing amino acids if the reaction should prove to be a general one. The present investigation was therefore undertaken to extend the study to other representative amino acids and further to study in greater detail the conditions under which the reaction will take place. The amino acids selected for the work were methionine and cystine, the sulfur-containing amino acids, glutamic acid represent,ing the dibasic acids, arginine as an example of the basic amino acids, tyrosine and phenylalanine as representatipes of the monoamino acids, and finally proline which contains a secondary amino or imino group. The sodium salts of the acetyl derivatives of all these amino acids with the exception of proline were racemized in aqueous solution by acetic anhydride. In the case of proline no racemization occurred. With cystine some decomposition resulted with the separation of free sulfur, although the reaction was carried out at only 36”. When free acetyl-l-cystine in aqueous solution without any NaOH was treat.ed with acetic anhydride, no racemization occurred, nor was there any decomposition. Furthermore, the acetyl-l-cystine was not racemized or decomposed by the alkali alone under the above conditions. The lack of racemization of the proline and the splitting out of sulfur from cystine during its racemization we regard as being very