The geometry of N-hydroxymethyl compounds. Part 4. Studies on ground-state geometry and decomposition of N-(hydroxymethyl)triazenes using MNDO calculations and kinetic studies

Abstract

M N DO calculations of the most favoured conformations of antitumour 3-(hydroxymethyl) -3-methyl-1 -(4-X-pheny1)triazenes (2) indicate N-CH,OH bond lengths of over 1.49 A (lengthened by electronwithdrawing groups), correlated with high lability under physiological conditions (t,lz under 1 s ) .Hydrolysis rates of 20 (X = NO,) in methanol/acetonitrile containing water were determined using high performance liquid chromatography (HPLC) and extrapolated to give a tl/, of 4 3 s at 100% water.Modelling of decomposition pathways of 2d (X = CH,) using M N D O predicts that concerted loss of formaldehyde is not favoured. Loss of [H2COH]+ from nitrogen protonated 2d is also a high energy process, but loss of formaldehyde from deprotonated 2d seems feasible under basic conditions. Under acidic conditions the energetically preferred process is loss of water from protonated 2d to give an iminium ion, even though the required initial 0-protonation is disfavoured over protonation on nitrogen.Paper 2/06822B

Useful yields of organic molecules under dynamic SIMS cluster bombardment

“…Die Synthese von Hydroxymethyltriazen‐Derivaten erfolgte im Zuge von Untersuchungen, die Hydroxymethyltriazene als die direkten Oxidationsprodukte der Dimethyltriazene des Typs 1 auswiesen 2, 17, 19. Nach Reaktion mit Cytochrom‐Enzymen in den Zellen erfolgte in wässrigem Milieu schnelle Abspaltung von Formaldehyd unter Bildung hochreaktiver Monomethyltriazene.…”

Triazenes: A Versatile Tool in Organic Synthesis

“…Derivatives of hydroxymethyltriazenes have been prepared as a result of research indicating hydroxymethyltriazenes as the immediate oxidation products of dimethyltriazenes of the type 1 2, 17, 19. After reaction with cytochrome enzymes in the cell, loss of formaldehyde to generate highly reactive monomethyl triazenes is rapid in aqueous media.…”

Triazene: vielseitige Verbindungen für die organische Synthese

“…[2,17,19] Nach Reaktion mit Cytochrom-Enzymen in den Zellen erfolgte in w‰ssrigem Milieu schnelle Abspaltung von Formaldehyd unter Bildung hochreaktiver Monomethyltriazene. [2,17,19] Nach Reaktion mit Cytochrom-Enzymen in den Zellen erfolgte in w‰ssrigem Milieu schnelle Abspaltung von Formaldehyd unter Bildung hochreaktiver Monomethyltriazene.…”