Triazene drug metabolites. Part 10. Metal-ion catalysed decomposition of monoalkyltriazenes in ethanol solutions

Abstract

The metal ions Fe²⁺, Zn²⁺ and Cu²⁺ bring about the rapid decomposition of 1-aryl-3-alkyltriazenes to the corresponding anilines. For Fe²⁺, a linear dependence of the pseudo-first-order rate constant, k₀ on [Fe²⁺] was observed, while for Zn²⁺ and Cu²⁺ plots of k₀versus[metal ion] were curved and indicative of complex formation. For Fe²⁺, second-order rate constants k₂^Fe2+ for substituted 1-aryl-3-methyltriazenes follow a Hammett relationship giving rise to a ρ value of –3.0. For Zn²⁺ and Cu²⁺, the data were analysed in terms of an equilibrium constant, K^M2+, for the dissociation of a metal-ion-triazene complex and the first-order rate constant for the collapse of this complex to products, k₂^M2+. Hammett ρ values of 1.0 for both K^Zn2+ and K^Cu2+ are found, and the corresponding ρ values for k₂^Zn2+ and K₂^Cu2+ are –1.3 and –1.9. There is reasonable correlation between the Taft E_s parameter for the alkyl group and K^Cu2+, giving a δ value of –1.6. The dependence of k₂^Cu2+ on the alkyl group is not simple: k₂^Cu2+ decreases in the order Pr > Et ≠ PhCH₂ca. 4-MeOC₆H₄CH₂ > CD₃ca. Me. The reactions catalysed by Cu²⁺ are inhibited by added nucleophilies e.g. Br^– and N-methylimidazole.

A mechanism is proposed in which the triazene complexes to the metal ion via the N(1) nitrogen atom of the E–cis conformer, then undergoes a fast proton transfer to form a complex involving the unconjugated tautomer which subsequently decomposes via unimolecular scission of the N(2)–N(3) bond to form an alkyldiazonium ion and an aniline–metal complex. The observed products then arise from rapid solvolysis of the metal–aniline complex and the alkyl diazomum ion.