Synthesis and evaluation of organic pigments and intermediates. 1. Nonmutagenic benzidine analogs

The design, synthesis, characterization, and genotoxicity of 4,4ʹ diaminobiphenyl (benzidine) analogs with substituents in the 3,3ʹ and/or 2,2ʹ positions are reported. Analogs containing bulky substituents in the 3,3ʹ positions significantly reduce or eliminate mutagenic activity, while substituents in the 2,2ʹ-positions increase the dihedral angle across the biphenyl linkage¯¯a property that can be utilized in the design of novel nonmutagenic colorants. 2,2ʹ-Dimethylbenzidine was found to be mutagenic in both the standard Salmonella mammalian mutagenicity assay (Ames test) with metabolic acitivation and the preincubation assay protocol. 2,2ʹ-Dichloro-5,5ʹdipropoxybenzidine, 2,2ʹ-dimethoxy-5,5ʹ-dipropoxybenzidine and 2,2ʹ-dimethyl-5,5ʹdipropoxybenzidine were nonmutagenic in both assays. The corresponding bisacetoacetamido derivatives of the latter two compounds were also nonmutagenic. Good yields with minimal purification were obtained for certain diamines, providing potentially useful nongenotoxic intermediates in the synthesis of bisazo and bisazomethine dyes and pigments.