Unambiguous synthesis of asymmetrically substituted chlorinated benzidines, and a study of their mutagenicity in the Ames test: potent activity of 3,5,3'-trichlorobenzidine.
3,5-Dichlorobenzidine and 3,5,3'-trichlorobenzidine were prepared by the reaction of 2,6-dichloronitrosobenzene with aniline and 2-chloroaniline, respectively, to give the appropriate substituted azobenzene; reduction and rearrangement gave the desired benzidine derivatives. The products were purified and characterized by mass spectrometry and [1H] nuclear magnetic resonance spectroscopy. The mutagenic activities of the chlorinated benzidines were determined, using the Ames tester strain TA98. 3,5,3'-Trichlorobenzidine is the most potent benzidine derivative yet reported. The activities of five chlorinated benzidines are compared, and rules for the effect of substitution on activity are discussed.
Josephy
P D
PD
Department of Chemistry and Biochemistry, University of Guelph, Ontario, Canada.
Williams
L L
LL
D000818:Animals; D001560:Benzidines / Q000138:chemical synthesis* / Q000494:pharmacology; D001711:Biotransformation; D002712:Chlorides; D006224:Cricetinae; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000138:chemical synthesis*; D009154:Mutation; D012486:Salmonella typhimurium / Q000187:drug effects
D001560:Benzidines; D002712:Chlorides; D007202:Indicators and Reagents; D009153:Mutagens