132434-66-3Relevant academic research and scientific papers
Chemistry of N-phosphorylated nitrogen mustards: The effect of a second nitrogen substituent at phosphorus on the stability of the system
Wan, Huijie,Modro, Tomasz A.
, p. 155 - 168 (1996)
Methyl N,N-diethyl-N′N′-bis(2-chloroethyl)phosphoramidate was prepared as a precursor for the corresponding phosphordiamidate anion, a model for the phosphoramidate mustard, biologically active degradation product of cyclophosphamide drug. Demethylation of the precursor led to a highly unstable ion which underwent spontaneous fragmentation. In the absence of an external nucleophile, the ion decomposed yielding metaphosphoramidate and N-substituted ethyleneimine as primary intermediates. In the presence of pyridine, bis-alkylation of two pyridines took place yielding bis [2-(N-pyridinio)ethyl]amine dication, in addition to some 1,3,2-oxazaphospholidine derivative, formed via the competitive 1,5-cyclization of the demethylated anion. Incubation of the precursor in the presence of thiophenol/triethylamine resulted in two parallel nucleophilic displacements: (i) the O-demethylation followed by bisalkylation of two molecules of thiophenol, together with some 1,5-cyclization; (ii) initial direct displacement of the chlorine at the β-carbon of the precursor, followed by the fragmentation of the system. It is concluded that the electron-rich ionic phosphoramidate substituent, -O(R2N)P(O), highly activates the N-(2-chloroethyl) functional group in alkylation reactions.
