26644-00-8Relevant articles and documents
(E)-(Hydroxyimino)(hydroxymethoxyphosphinyl)acetic Acid: Synthesis and pH-Dependent Fragmentation
Kashemirov, Boris A.,Fujimoto, Mari,McKenna, Charles E.
, p. 9437 - 9440 (1995)
In contrast to both its parent "troika" acid (E-1, a phosphorylating agent at pH 7 and 25 deg C) and its C-methyl isomer (E-2, which is stable at both acidic and neutral pH), (E)-(hydroxyimino)(hydroxymethoxyphosphinyl)acetic acid E-3 was unreactive at pH 7 and 25 deg C but at pH 1.5 fragmented to methyl phosphate 10 (15percent) and methyl phosphorocyanidate 11 (85percent).The minor product is consistent with solvent phosphorylation, the reaction exclusively observed with E-1.The non-phosphorylating fragmentation pathway is proposed to involve a preliminary E -> Z isomerization of 3 prior to Cα-Cβ cleavage.Dual fragmentation pathways were also detected (31P NMR) when the DCHA+ salt of E-3 (E-9) was heated in acetonitrile or EtOH; in addition to phosphorylation products (16-19percent), 11 was formed (81-84percent).Reaction of E-9 in refluxing EtOH:t-BuOH (1:1) showed low stereoselectivity in product formation (ca. 3:1 ethyl methyl phosphate : t-butyl methyl phosphate), supporting a dissociative phosphorylation process.
Decomposition of N-Phosphorylated Nitrogen Mustards: A Mechanistic Investigation
Roux, Charlotte le,Modro, Agnes M.,Modro, Tomasz A.
, p. 3832 - 3839 (2007/10/02)
Lithium methyl N-(2-chloroethyl)phosphoramidate (2b) and lithium methyl N,N-bis(2-chloroethyl)phosphoramidate (2c) were prepared as models of N-phosphorylated mustards used in cancer chemotherapy.The decomposition of those substrates in D2O and in D2O-pyridine-d5 was studied to elucidate the mechanism of their alkylating reactivity.The products of the decomposition and the variation of the proportions of the products with time were determined, and the results led to the following conclusions.Decomposition of substrates of the type 2 can follow three independent pathways: (i) 1,5-cyclization to a 1,3,2-oxazaphospholidine derivative, followed by fast ring opening via the pH-dependent P-O or P-N bond cleavage; (ii) 1,3-cyclization to a N-phosphorylated aziridinium derivative, followed by the nucleophilic opening of the aziridine ring; (iii) fragmentation to metaphosphate and aziridine species, followed by rapid reactions of those intermediates with nucleophiles.The first pathway deactivates the substrate with respect to the alkylating reactivity.Relative contributions of individual pathways to the decomposition are highly sensitive to the detailed structure of the substrate and to the nucleophilic composition of the reaction medium.
