Synthesis and evaluation of organic pigments and intermediates. 1. Nonmutagenic benzidine analogs David Hinks a, *, Harold S. Freeman a , Monthon Nakpathom a , Jolanta Sokolowska b a Department of Textile Engineering, Chemistry and Science, North Carolina State University, Raleigh, N.C. 27695-8301, USA b Technical University of Lodz, Lodz, Poland Received 20 July 1999; accepted 17 August 1999 Abstract The design, synthesis, characterization, and genotoxicity of 4,4 0 diaminobiphenyl (benzidine) analogs with sub- stituents in the 3,3 0 and/or 2,2 0 positions are reported. Analogs containing bulky substituents in the 3,3 0 positions sig- ni®cantly reduce or eliminate mutagenic activity, while substituents in the 2,2 0 -positions increase the dihedral angle across the biphenyl linkage±±a property that can be utilized in the design of novel nonmutagenic colorants. 2,2 0 - Dimethylbenzidine was found to be mutagenic in both the standard Salmonella mammalian mutagenicity assay (Ames test) with metabolic acitivation and the preincubation assay protocol. 2,2 0 -Dichloro-5,5 0 -dipropoxybenzidine, 2,2 0 - dimethoxy-5,5 0 -dipropoxybenzidine and 2,2 0 -dimethyl-5,5 0 -dipropoxybenzidine were nonmutagenic in both assays. The corresponding bis-acetoacetamido derivatives of the latter two compounds were also nonmutagenic. Good yields with minimal puri®cation were obtained for certain diamines, providing potentially useful nongenotoxic intermediates in the synthesis of bisazo and bisazomethine dyes and pigments. # 2000 Elsevier Science Ltd. All rights reserved. Keywords: Nonmutagenic; Benzidine intermediates; Dihedral angle 1. Introduction Benzidine I is one of the few known human car- cinogens [1,2]. Also, certain homologs of benzidine are mutagenic and suspected human carcinogens. In fact, some of the most common benzidine homologs still used in colorant synthesis, such as 3,3 0 -dimethylbenzidine II, 3,3 0 -dimethoxybenzidine III, and 3,3 0 -dichlorobenzidine IV may reasonably be expected to be carcinogenic [3]. Colorants prepared from genotoxic intermediates can be either direct acting mutagens or promutagens [4]. By genotoxic is meant interactions between DNA and substances that produce heritable changes in a cell or organism. A promutagen is a compound exhibiting mutagenic activity following metabolic 0143-7208/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved. PII: S0143-7208(99)00078-9 Dyes and Pigments 44 (2000) 199±207 * Corresponding author. Tel.: (919) 515 6554; fax: (919) 515 6532. E-mail address: david_hinks@ncsv.edu (D. Hinks).