Issue 6, 1987

Chemistry of nitrogen mustard [2-chloro-N-(2-chloroethyl)-N-methylethanamine] studied by nuclear magnetic resonance spectroscopy

Abstract

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 characterised 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.

Article information

Article type
Paper

J. Chem. Soc., Perkin Trans. 2, 1987, 705-713

Chemistry of nitrogen mustard [2-chloro-N-(2-chloroethyl)-N-methylethanamine] studied by nuclear magnetic resonance spectroscopy

B. T. Golding, M. J. Kebbell and I. M. Lockhart, J. Chem. Soc., Perkin Trans. 2, 1987, 705 DOI: 10.1039/P29870000705

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