Anomalous Schmidt reaction products of phenylacetic acid and derivatives

Treatment of carboxylic acids with sodium azide in sulfuric acid normally results in decarboxylation with conversion of the carboxylic acid to an amine (the Schmidt reaction). However, many side reactions have been reported to occur, particularly in the case of α-aryl carboxylic acids, such as sulfonation, direct amination of the phenyl ring, cyclization to a lactam, and elimination of side chains to give aniline. In this study, the reactions of a variety of analogues of phenylacetic acid under given reaction conditions are examined to determine which characteristics are important in the competing side reactions. Some reactions were carried out with TEMPO free radical as a radical scavenger to investigate whether direct amination proceeds by a radical intermediate. Phenylacetic acid is shown to give an ortho-aminated diamine product instead of the para-aminated one expected from direct amination. A mechanism for this side reaction, involving cyclization to a lactam intermediate followed by further cleavage, is proposed; an analogue of the hypothetical intermediate has been isolated for biphenylacetic acids.