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

The design, synthesis, characterization, and genotoxicity of 4,4' diaminobi phenyl (benzidine) analogs with substituents in the 3,3' and/or 2,2' positi ons are reported. Analogs containing bulky substituents in the 3,3' positio ns significantly reduce or eliminate mutagenic activity, while substituents in the 2,2'-positions increase the dihedral angle across the biphenyl link age-a property that can be utilized in the design of novel nonmutagenic col orants. 2,2'-Dimethylbenzidine was found to be mutagenic in both the standa rd Salmonella mammalian mutagenicity assay (Ames test) with metabolic aciti vation and the preincubation assay protocol. 2,2'-Dichloro-5,5'-dipropoxybe nzidine, 2,2'-dimethoxy-5.5'-dipropoxybenzidine and 2,2'-dimethyl-5,5'-dipr opoxybenzidine were nonmutagenic in both assays. The corresponding bis-acet oacetamido derivatives of the latter two compounds were also nonmutagenic. Good yields with minimal purification were obtained for certain diamines, p roviding potentially useful nongenotoxic intermediates in the synthesis of bisazo and bisazomethine dyes and pigments. (C) 2000 Elsevier Science Ltd. All rights reserved.