57-54-5Relevant academic research and scientific papers
Chemistry of Nitrogen Mustard studied by Nuclear Magnetic Resonance Spectroscopy
Golding, Bernard T.,Kebbell, Michael J.,Lockhart, Ian M.
, p. 705 - 714 (2007/10/02)
Reactions of the nitrogen mustard drug 2-chloro-N-(2-chloroethyl)-N-methylethanamine with nucleophiles in aqueous solution have been studied by 1H and 13C n.m.r. spectroscopy.Conditions have been devised for converting the mustard into the N-2-chloroethyl-N-methylaziridinium ion which has been characterized by 1H n.m.r. spectroscopy.To assist the studies of reactions of the mustard by 13C n.m.r. spectroscopy, it has been prepared labelled at both C-2 atoms by 13C.It is shown that reactions of the mustard with strong nucleophiles (e.g. thiosulphate) proceed to a product of disubstitution, without the aziridinium ion being detected spectroscopically, although its intermediacy is inferred by examining the distribution of 13C in product from 13C-labelled mustard.Less reactive nucleophiles (e.g. thiourea) yield a product of disubstitution via spectroscopically detected intermediates (aziridinium ion and monosubstituted intermediate).Relatively weak nucleophiles (e.g. guanosine) did not give detectable products of substitution; cis- and trans-NN'-2-chloroethyl-NN'-methylpiperazinium dichloride were formed via the aziridinium ion.The reaction of the mustard with excess of ammonia gives a 3 : 2 ratio of 2-amino-N-(2-aminoethyl)-N-methylethanamine and N-methylpiperazine.The distribution of 13C label in these products derived from 13C-labelled drug shows that the triamine is formed via aziridinium intermediates, whilst the piperazine arises via intramolecular cyclisation of the intermediate 2-amino-N-(2-chloroethyl)-N-methylethanamine.
