Open-chain nitrogen compounds. Part VI. The formation of bis(1-aryl-3- methyltriazen-3-ylmethyl) methylamines in the reaction of diazonium ions with mixtures of formaldehyde and methylamine

The synthesis of a series of N,N-bis(1-aryl-3-methyltriazen-3-ylmethyl) methylamines from coupling diazonium salts with mixtures of methylamine and formaldehyde is described. These novel bis-triazenes, or heptazanonadienes, have significant anti-tumour activity against the TLX5 lymphoma in mouse. The mechanism of formation of these triazenes is discussed with reference to the implication to the presumed equilibria taking place in the methylamine/formaldehyde solution. The formation of the bis-triazene is usually accompanied by the formation of a 3-hydroxymethyitriazene, and it has been shown that the hydroxymethyltriazene can be transformed into the bis-triazene. The proportions of the two products are strongly influenced by the relative amounts of methylamine and formaldehyde. Coupling the p-bromobenzenediazonium salt to a 1:1 methylamine/formaldehyde mixture affords mainly the bis-triazene, whereas a 1:50 mixture gives almost totally the hydroxymethyl triazene. These results suggest that the two triazenes arise from diazonium coupling to different species in the amine/formaldehyde mixture; this hypothesis is supported by the formation of identical product mixtures from coupling the diazonium ion with (a) a 1:1 MeNH2/CH2O mixture, and (b) the cyclic trimer of the carbinolamine MeNHCH2OH, and by the identification of a minor product from the reaction of p-chlorobenzenediazonium fluoroborate with MeNH2/CH2O as bis(1-p-chlorophenyl-3-methyltriazen-3-yl) methane.