31P Fourier-transform NMR spectroscopy at 40.25 MHz was used to measure the pKB (4.75 ± 0.03) of the cyclohexylammonium salt of phosphoramide mustard (1-CHA) at 20 °C and to study the kinetics and products of the decomposition of 1-CHA at solution pH values between 5.7 and 9.0, at 37 °C, and at pH 7.4 in the presence of either metal ions or nucleophilic trapping agents. The half-life (ry2) of 1 was approximately constant (18 ± 3 min) between pH 9.0 and 7.0 and then increased sharply with lowered pH (~1 00 min at pH 5.7); the rate deceleration caused by metal ions was less pronounced (e.g., ry252 min for 1 M MgCl2, pH 7.4). Hydrolysis of P-N bonds was dominant at pH < 6.5, whereas at pH 7.4-9.0 the individual rate constants for intramolecular nucleophilic displacement of chloride ion to give aziridinium ion 2 (Scheme I) and ring opening of 2 by hydroxide ion were measurable, giving T\j2 (average) a¡ 18 min for 1, and ry2 = 30,18, and 15 min for 2 at pH 7.4, 8.2, and 9.0, respectively. At pH 7.4, 37 °C, aziridinium ions 2 and 4 were intercepted relatively rapidly by an excess of 2-mercaptoethanol and afforded separate 31P NMR signals for the resulting monosubstituted (7) and disubstituted (8) products. The signal intensities for 7 and 8 were fitted to the integrated rate equations for, in effect, two consecutive "first-order" reactions (1 -* 7 -*• 8), thus allowing quantification of the reactivity of intermediate 7, 1/2 =* 16 min. Similar results were obtained for the reaction of 1-CHA with sodium 2-mercaptoethylsulfonate ("mesnum"), whereas thiourea gave no evidence (31P NMR) for the accumulation of S-alkyl trapping products. The decomposition kinetics for nine analogues of 1 (Scheme II: 13, 14, and 25-31) were also studied by 31P NMR, and their relative reactivities were interpreted in terms of resonance and inductive effects, which alter the electron density at the nitrogen position in the PN-(CH2CH2C1)2 moiety. The three N''-alkyl derivatives of 1-CHA (27-29) provided evidence for a considerable amount (30-50%) of intramolecular O-alkylation leading to 2-(alkylamino) -3-(2-chloroethyl)-1,3,2-oxazaphospholidine 2-oxides (e.g., 34, Scheme III). The above data are briefly discussed with regard to the role of 1 as a cytotoxic metabolite 655 (1954).