REACTIONS OF THE ARSENICALS 609 



is oxidized if the medium is somewhat alkaline (Cohen et al., 1931). These 

 facts emphasize the important role of the pH in determining the direction 

 in which such reactions proceed. Barber (1929) claimed that thiols can 

 reduce pentavalent arsenicals in acid, neutral, or alkaline solutions, and 

 that the resultant trivalent forms combine with excess thiol, as above. 

 He found that the aryl thioarsinites formed with thiolacetate are in general 

 crystalline, are quite soluble, and are not split by acid or alkali; however, 

 they are oxidized in air in alkaline solutions and this is more rapid than 

 for the parent compounds. Cohen et al. (1931) disagree with the mechanism 

 postulated inasmuch as they had found no such reduction in alkaline media. 

 Instead, they assume that around neutrality a 97-arsonate combines with 

 four molecules of a thiol to form an intermediate tetrathioarsonate, which 

 is unstable and splits into two thioalkyl groups (which unite to form a 

 disulfide) and the dithioarsinite. Such a reaction would seem kinetically 

 unlikely and it might be suggested that even in neutral or alkaline solutions 

 the reduction can proceed, since the reduced forms immediately react 

 with SH groups, even though the equilibria under these conditions favor 

 the oxidized form of the arsenical. The dithioarsinites are formed readily 

 in most instances from the monosubstituted arsenicals, and the monothioar- 

 sinites are difficult to obtain; e. g., simply mixing solutions of cysteine and 

 arsenite results in a rapid precipitation of the dithioarsinite (Labes, 1929 b), 

 and the product of the reaction of cysteine with oxophenarsine is the 

 dicysteinyloxophenarsine (Johnson and Voegtlin, 1930). 



Surprisingly little appears to be known about the intimate mechanisms 

 in the reactions of arsenicals with thiols. How should one visualize the 

 fundamental formation of a mercaptide from an arsenoxide, R — As=0? 

 Is it a progressive addition and substitution, which may be written as: 



OH S— R' 



/ / 



R— As=0 -> R— As -^ R— As 



\ \ 



S— R' S— R' 



or is it a simultaneous replacement of the atom (in other words, does 



the monothioarsinite actually occur)? Or is it the arsonous acid form which 



reacts: 



OH S— R' 



/ / 



R — As -> R — As 



\ \ 



OH S— R' 



and, if so, what is the mechanism of the substitution? Eagle (1945) found 

 that over a limited physiological pH range, there is little if any effect of 

 pH on these reactions. It is well known that compounds such as R — AsClg 



