Reactions of substituted arenediazonium chlorides with methylamine-formaldehyde premix revisited: reactivity and transformations of methylolamine intermediates and their biological significance.

Modulation of the N-azo coupling between ring-substituted arenediazonium chlorides and premixed methylamine-formaldehyde leads not only to 1-aryl-3-hydroxymethyl-3-methyltriazenes and their dimers, but also to unexpected cyclic and complex products. The syntheses comprise reactions with arenediazonium chlorides bearing both -M and +M substituents at para and ortho/para positions of the phenyl ring. One of the major constituents isolated from a mixture of products is the O-acetate of 3-hydroxymethyl-3-methyl-1-(2,4,6-trichlorophenyl)triazene. This product was obtained from the reaction of 2,4,6-trichlorobenzenediazonium chloride and methylamine-formaldehyde mixture which was then stabilized by acetylation. The structures of the isolated products could be derived from reactive methylolamines and electrophilic intermediates that possible occur in vivo and thereby offer a plausible mechanistic explanation for the carcinogenic and tumour-inhibitory activity associated with the open-chain triazene compounds in the living cell.