Acetanilide ions, decomposition

The conductometric results of Meerwein et al. (1957 b) mentioned above demonstrate that, in contrast to other products of the coupling of nucleophiles to arenediazonium ions, the diazosulfones are characterized by a relatively weak and polarized covalent bond between the p-nitrogen and the nucleophilic atom of the nucleophile. This also becomes evident in the ambidentate solvent effects found in the thermal decomposition of methyl benzenediazosulfone by Kice and Gabrielson (1970). In apolar solvents such as benzene or diphenylmethane, they were able to isolate decomposition products arising via a mechanism involving homolytic dissociation of the N — S bond. In a polar, aprotic solvent (acetonitrile), however, the primary product was acetanilide. The latter is thought to arise via an initial hetero-lytic dissociation and reaction of the diazonium ion with the solvent (Scheme 6-11). 

Studies on the acetate of A -hydroxy-AAF indicated that esterification of the hydroxamic acid could be the requisite transformation of an aromatic amine to an ultimate carcinogen. Bioassays indicated that A -acetoxy-AAF resembled direct-acting carcinogens in producing subcutaneous tumors at the site of injection. Unlike /V-hydroxy-AAF, this acetate ester reacted in vitro with various cellular macromolecules (339, 410). The metabolic activation of AAF and decomposition of A -acetoxy-AAF to an electrophile are illustrated in Fig. 1. The possibility that -hydroxy-AAF was esterified in vivo to sulfate or phosphate esters has been examined. Evidence that sulfate esters may be involved in the formation of the ultimate carcinogen of AAF has been supported by several in vivo bioassays. Coadministration of acetanilide, which depletes the intracellular level of sulfate, reduced the carcinogenicity of AAF (487). Coadministration of sulfate ion with AAF enhanced its activity as a liver carcinogen (97). 

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