142273-07-2Relevant academic research and scientific papers
Open-chain nitrogen compounds. Part XIV. Synthesis of 1-aryl-3-aryloxymethyl-3-methyltriazenes and 1-aryl-3-(hydroxyaryl)methyl-3-methyltriazenes
Merrin, M. P.,Hooper, D. L.,LaFrance, R. J.,Snooks, R.,Vaughan, K.
, p. 144 - 150 (2007/10/02)
The synthesis of a new series of 1-aryl-3-aryloxymethyl-3-methyltriazenes (2) has been achieved by the reaction of the acetoxymethyltriazene (Ar-N=N-NMe-CH2OAc) with the appropriate phenol in dry chloroform solution.Triazenes of type 2 are also formed by the reaction of the acetoxymethyltriazene with the sodium phenolate, generated by the reaction of the phenol with sodium hydride in dry chloroform, but under these conditions a second product is formed, which has been identified as an isomer of 2.The structure of the second product has been elucidated by spectroscopic analysis to be the 1-aryl-3-(hydroxyaryl)methyl-3-methyltriazene (3).The formation of these two isomeric products is accounted for by the ambident nature of the nucleophilic phenolate ion in the displacement of the acetoxy leaving group.The mass spectra of all the triazenes of type 2 exhibit a fairly intense peak at M - 102, which is suggested to arise from a novel intramolecular rearrangement.Two examples of the triazenes of type 2 have been tested for antitumour activity on the NCI tumour panel and have shown statistically significant differential sensitivity in several cell lines.Preliminary investigation of the stability of these triazenes in physiological-pH buffer suggests that they may have the appropriate chemical stability for pro-drug application in therapy. Key words: triazene, synthesis, antitumour, phenol, spectroscopy, aryloxymethyltriazene, prodrugs.
