AMINOPHENOLS AND PHENYLENEDIAMINES 587 



instability may be due to the 1,4 addition of an amino group, which may 

 be followed by reoxidation to the quinonoid form and successive additions 

 leading to polymerization. The pE'a of the amino group of ^-aminophenol 



NH 



+ HgN— < V /) — NH, 



NH 



is 5.8 and of the imino group of j^-quinoneimine is 4.0. The reactions of 

 p-quinoneimine and 2^-quinonediimine with thiols have not been adequately 

 studied, but appear to occur readily. Cysteine prevents enzyme inhibition 

 by p-aminophenol and p-phenylenediamine (Potter, 1942; Kensler et al., 

 1942 a), but this could be due to its ability to keep these substances reduced 

 rather than to reaction with the quinonoid forms. 50-Quinoneimine reacts 

 with cysteine more slowly than does p-benzoquinone or jj-quinonediimine. 

 The free radicals formed during the oxidation of aromatic diamines are 

 usually colored and more stable than the fully oxidized quinonediimines, 

 but under certain conditions (usually in concentrated solutions) can di- 

 merize. This probably seldom occurs in biological systems. One of the most 

 stable free radicals is formed from iV,iV, A"',iV'-tetramethyl-p-phenylene- 

 diamine. If a 10 mM solution of this substance at pH 4.6 is oxidized with 

 a small amount of bromine (around 1/100-1/50 the amount of diamine), 

 the intensely blue radical appears and is indefinitely stable. On the other 

 hand, the fully oxidized quaternary diimonium compound is very unstable 

 in aqueous solution. Thus, for all practical purposes, the oxidation product 

 of the diamine is the free radical. If p-phenylenediamine is treated in the 

 same manner, the result is different; the yellow free radical appears but 

 the solution turns pink within several minutes, this being due to the forma- 

 tion of the diimine and its immediate reaction, the free radical being much 

 less stable than that of the tetramethylated derivative but still more stable 

 than the diimine. Considering the free radical of j3-phenylenediamine as 

 the standard, alkyl groups substituted on the ring do not markedly, in- 

 fluence the stability, whereas substitution on the N atoms increases the 

 stability. Ring substitution of other groups often decreases the stability of 

 the free radical because of a disturbance of the symmetry which is impor- 

 tant in allowing electron motility. It should also be pointed out that even 

 the most stable free radicals are stable only within a certain pH range, 

 usually 3.5 6.0 in aqueous solution, and unfortunately there has been little 

 work on their stabilities at physiological pH. The paper of Michaeiis et al. 

 (1939) is perhaps the best source of information on the properties of these 

 free radical semiquinonediimines. 



