Chemical System for Oxidation of lAA by Peroxidase 213 



be formed from carboxylic acids and liydrogen peroxide in the pres- 

 ence of strong acids. The last possibility does not seem likely, how- 

 ever, since the reaction of lAA and hydrogen peroxide occurs in 

 acetic acid, where one would expect that the peroxide would be con- 

 sumed in forming peracetic acid. 



Since the spectrum of the indoles used changed little even at pH 

 1, there is probably only a small amount of protonated species present.^ 

 On the other hand a large part of the hydrogen peroxide may be pro- 

 tonated at pH 1 (11, p. 379). At the present time, therefore, we prefer 

 the interpretation that the pH dependency arises from the necessity of 

 protonating hydrogen peroxide to produce a reactive species. 



Assuming that OH+ or an equivalent is the active species facili- 

 tates discussion of the possible points of attack of lAA. For any cationic 

 species the most likely point of attack in an indole is the S-position^ 

 (4). Attack of the side chain in the initial step is unlikely, since a,a- 

 dimethylindole-3-acetic acid undergoes the reaction even more rap- 

 idly than lAA. From a theoretical point of view, the a-hydrogens of 

 lAA would 7iot be active toward an attacking cationic species, since 

 they are already more than normally positive because of electron- 

 withdrawal by the carboxyl group and the ring system. 



Although attack of the 3-position accords well with most of the 

 known oxidations of indoles (15), oxidation at the 2-position might 

 take place either directly (e.g., if lAA were protonated first and hy- 

 drogen peroxide attacked the protonated species^ at the 2-position) 

 or by rearrangement of a group from the 3-position.- 



Oxidation at the 2-position might yield oxindole-3-acetic2 acid 

 as the final product or as an intermediate. This pathway was ruled 



' Protonation of the indole nucleus would certainly cause significant changes 

 in the ultraviolet spectrum because of the formation of indolenine salts: 



H 

 R 



H 



X© 



Contrary to the commonly written form, protonation of an indole probably occurs 

 at the 3-position rather than at the nitrogen, in agreement with the well-estab- 

 lished behavior of a,^-unsaturated amines (6). Protonation at the 3-position also 

 accounts for the dimers obtained from indole (13) and from skatole (unpublished). 

 ^ Chemical precedent for the oxidation of the 2-position has been provided by 

 Witkop (14), who con\erted skatole and tryptophan to the corresponding oxuidoles 

 bv the use of peracetic acid. More recently, Dalgliesh and Kelly (2) have obtained 

 oxindoles from indoles by means of potassium persulfate. There is no reason to 

 assume, however, that the initial oxidation takes place at the 2-position (3). 



