Showing papers on "Triazene published in 1987"

Triazene drug metabolites. Part 4. Kinetics and mechanism of the decomposition of 1-aryl-3-benzoyloxymethyl-3-methyltriazenes in mixed aqueous–organic solvents

Abstract: 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 pH8, specific acid catalysis is observed. No nucleophilic catalysis is detected at any pH. The observed first-order rate constant, kobs, vary with the substituent in both the 1-aryl and benzoyl rings. Hammett σ values of 1.28 and 1.41 are obtained for substituents in the benzoyl group in 50% MeCN–H2O and 60% dioxane–H2O respectively. A Hammett ρ value of –1.84 is obtained in 50% 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 logkobs 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‡ca. 80 kJ mol–1 and ΔS‡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 XII. Methanolysis of 3-alkyl-3,4-dihydro-1,2,3-benzotriazin-4-ols: evidence for ring-chain tautomerism with the cytotoxic monoalkyltriazenes

Abstract: A series of 4-hydroxy-3,4-dihydro-1,2,3-benzotriazines ("triazinols"), potential pro-drugs for the cytotoxic monoalkyltriazenes, have been investigated for anti-tumor activity and have been found to have marginal activity against the TLX5 tumor. The in vivo anti-tumor activity correlates with previously observed in vitro cytotoxicity of the compounds. The chemical behaviour of the triazinols is consistent with carbinolamine triazene ring-chain tautomerism in solution. The triazinols undergo methanolysis to give a series of new 4-methoxytriazines; the rate of methanolysis is primarily dependent on the substituent at C-4 of the triazinol. Those triazinols that undergo methanolysis rapidly are also more active biologically, suggesting that cytotoxicity and anti-tumor activity derive from the insitu generation of the open chain triazene.

Triazene metabolism. VI. 3-Azidomethyl-3-alkyl-1-aryltriazenes, a new class of anti-tumour triazene with potential pro-drug applications.

Abstract: The synthesis of a new series of 3-azidomethyl-3-methyl-1-aryltriazenes is described. 3-Acetoxymethyl-3-methyl-1-aryltriazenes react with a large molar excess of sodium azide in aqueous acetone to afford the 3-azidomethyltriazenes in high yield. The rate of formation of the azidomethyltriazene increasing azide concentration, suggesting either an SN2 mechanism or a significant ionic strength effect on an SN1 reaction. In the absence of azide ion, the acetoxymethyltriazene undergoes a slow hydrolysis to give a bis-anilinomethane, which presumably arises via hydrolysis of the triazene to the aniline followed by condensation with formaldehyde released during the hydrolysis. The azidomethyltriazenes undergo facile hydrolysis in aqueous buffer solution with identical kinetic parameters to those of the hydrolysis of hydroxymethyltriazenes, suggesting that the azides may be good pro-drugs for the cytotoxic monomethyltriazene, the hydrolysis product derived from the hydroxymethyltriazene. Indeed, the azidomethyltriazenes have comparable anti-tumour activity against the P388 and PC6 tumours to other triazenes in this series. Furthermore, the azidomethyltriazenes display selective toxicity towards a human tumour cell line (the BE cell line) which is deficient in the repair of O6-methylguanine lesions, suggesting that these triazenes are capable of generating the monomethyltriazene without the need for metabolic activation.

Reactions of Substituted Arenediazonium Chlorides with Methylamine- Formaldehyde Premix Revisited: Reactivity and Transformations of Methylolamine Intermediates and Their Biological Significance

Abstract: 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.

Triazene derivative, production thereof and agricultural and horticultural fungicide containing said derivative as active component

Abstract: NEW MATERIAL:A triazene derivative of formula I (X is halogen; Y is lower alkyl, lower alkoxyl or OH; R is lower alkynyl) EXAMPLE:1,1-Dimethyl-3-(3-chloro-4,5-dipropargyloxyphenyl)triazene USE:An agricultural and horticultural fungicide It exhibits strong selective fungicidal effect against phytopathogenic fungus and other mold resistant to cyclic imide fungicides PREPARATION:The compound of formula I can be produced by diazotizing the aniline derivative of formula II and reacting the obtained diazonium salt with the secondary amine of formula III

Triazene drug metabolites. Part 6. The interaction of N-hydroxymethyl-triazenes with lanthanide-induced shift reagents

Abstract: Paramagnetic induced chemical shifts were obtained for a series of 1-aryl-3-hydroxymethyl-3-methyltriazenes and related compounds by the addition of Pr(thd)3 or Eu(fod)3. Induced shifts were shown to be pseudo-contact in origin. Qualitative work using Pr(thd)3 inducated that the N–CH2–O proton resonances are shifted the most, followed by the N–Me resonances. Neither 1-aryl-3-methyl-nor 1-aryl-3,3-dimethyl-triazenes exhibit induced shifts of the N–Me resonances, which indicates that binding of the hydroxymethyltriazenes to the lanthanide ion occurs through the hydroxyl function. Quantitative work using Eu(fod)3 allowed values of ΔB, the paramagnetic shift of the bound hydroxymethyltriazene, and KB, the equilibrium binding constant, to be calculated. The data are consistent with 1 : 1 complex formation and values of KB, which lie between 10–60 l mol–1, are little affected by the aromatic substituent. Correlation of the pseudo-contact induced shifts, ΔB, with r3(where r is the distance between the resonating nucleus and the Eu3+ ion) occurs when the hydroxymethyltriazene is assumed to bind to Eu3+ through the hydroxyl oxygen atom. In contrast, 3-hydroxymethyl-3-methyl-1-(3′-pyridyl)triazene binds to both Pr3+ and Eu3+ through the pyridyl nitrogen atom.

Mechanism of the Reaction of 1,3-Diaryltriazenes with Tetracyanoethylene in the Presence of Acetic Acid.

Abstract: The mechanism for the reaction of 1,3-diaryltriazenes with tetracyanoethylene (TCNE) in the presence of acetic acid, giving Schiff's bases and arylhydrazonomalononitriles, has been investigated. The intermediacy of arylazomalononitriles was confirmed by crossover experiments using an arylamine different from the component of the triazene. The route to the azo compounds via TCNE–triazene adducts had already been established by a tracer experiment using an 15N-labelled triazene. However, the crossover experiments, as well as the result of the reaction of a triazene with the TCNE–2,6-dimethylaniline adduct, revealed an alternative route via TCNE–ArNH2 adducts in the presence of acetic acid.

Complexes with Triazenes

Abstract: Triazene = diazoamine compounds forming complexes with manganese belong to the acid type Ar-N=N-N(OH)-R or its N-oxide tautomer Ar-N(H)-N=N(+)(R)-O(-), both derived from N-substituted hydroxylamines. Only that ligand tautomer is depicted in this section that is most relevant to the manganese complexes. Chelation occurs by metal substitution of the proton and formation of further coordinate bonds.

Nitrations of 4′,5′-Dihydropsoralens: A Route to Radiopharmaceutical Precursors.

Abstract: Unlike the nitration of the fully-aromatic furocoumarin, methoxsalen, which yields a single nitration product, the nitration of the 4′,5′-dihydro compound generates a condition-variant mixture of three nitro products. Reduction, diazotization, and pyrrolidine-trapping of one of these, the 4′,5′-dihydro-5-nitro-8- methoxypsoralen, provides a pyrrolidine triazene precursor for radioiodination of the dihydropsoralen system.