90476-04-3Relevant academic research and scientific papers
Triazene Drug Metabolites. Part 4. Kinetics and Mechanism of the Decomposition of 1-Aryl-3-benzoyloxymethyl-3-methyltriazenes in Mixed Aqueous-Organic Solvents
Iley, James N.,Moreira, Rui,Rosa, Eduarda
, p. 1503 - 1508 (2007/10/02)
Kinetic studies for the hydrolysis of 1-aryl-3-benzoyloxymethyl-3-methyltriazenes to 1-aryl-3-hydroxymethyl-3-methyltriazenes in mixed aqueous-organic media are reported.Reactions are first-order in the benzoyloxymethyltriazene, and are independent of pH above pH 8.Below pH 8, specific acid catalysis is observed.No nucleophilic catalysis is detected at any pH.The observed first-order rate constants, kobs, vary with the substituent in both the 1-aryl and benzoyl rings.Hammett ? values of 1.28 and 1.41 are obtained for substituents in the benzoyl group in 50percent MeCN-H2O and 60percent dioxane-H2O respectively.A Hammett ρ value of -1.84 is obtained in 50percent MeCN-H2O for substituents in the 1-aryl ring.Observed first-order rate constants also vary with the composition of aqueous dioxane mixtures and a linear correlation between log kobs and the Grunwald-Winstein Y parameter is found to give a slope of 0.99.The solvent deuterium isotope effect, kH2O/kD2O, is 1.26 for the 4-methoxybenzoyl derivative.Values of the activation parameters are ΔH(excit.) ca. 80 kJ mol-1 and ΔS(excit.) ca. -5 J K-1 mol-1.The data are best interpreted in terms of a unimolecular ionisation of the benzoyloxymethyltriazene to form a iminium cation and a benzoate anion.Hydroxymethyltriazene formation results from the capture of the intermediate iminium ion by water.Consistent with this mechanism, a common ion effect of the benzoate anion is observed, and the benzoate ion is ca. 75 times more effective than water at trapping the iminium ion.
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
Manning, Hartford W.,Hemens, Chantal M.,LaFrance, Ronald J.,Tang, York,Vaughan, Keith
, p. 749 - 754 (2007/10/02)
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-hydroxymethyltriazene, 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.
OPEN-CHAIN NITROGEN COMPOUNDS. PART V. HYDROXYMETHYLTRIAZENES: SYNTHESIS OF SOME NEW ALKYL HOMOLOGUES OF THE ANTI-TUMOUR 3-METHYL-3-HYDROXYMETHYLTRIAZENES AND PREPARATION OF THE DERIVED ACETOXYMETHYL-, BENZOYLOXYMETHYL-, AND METHOXYMETHYLTRIAZENES
Hemens, Chantal M.,Manning, Hartford W.,Vaughan, Keith,LaFrance, Ronald,Tang, York
, p. 741 - 748 (2007/10/02)
The synthesis of some new 1-aryl-3-alkyl-3-hydroxymethyltriazenes is described.The method of coupling a diazonium salt with an alkylamine/formaldehyde mixture has been extended to (a) some diazonium ions with para substituents other than -M groups, (b) those with substituents in ortho position, and (c) to homologous alkylamines (e.g. ethylamine, propylamine, etc.).Hydroxymethyltriazenes can also be prepared by the reaction of a 1-aryl-3-methyltriazene with formaldehyde.Several new derivatives of hydroxymethyl function have been prepared.Reaction with acetic anhydride or benzoyl chloride in pyridine affords respectively the acetoxymethyl- and benzoyloxymethyl-triazenes; the acetates and benzoates react readily with methanol to give the novel methoxymethyltriazenes.This is the first report of a series of dialkyltriazenes with an ether linkage in the α position. An ether of this type has also been obtained directly from the diazonium fluoroborate salt by coupling with a mixture of benzylamine and formaldehyde in ethanolic solution.
