Reactivity and Mechanism of Hydrolysis of Phosphonamides

Article abstract of DOI:10.1021/ja00397a024

The rates of hydrolysis of three phosphonamides, N,N-dimethylphenylphosphonamide (XII), N-(phenylphosphonyl)pyrrolidine (XIII), and N-(phenylphosphonyl)morpholine (XIV), have been investigated.There is firs-order dependence on acidity in the pH range 4-7 with a pH independent region at low pHs, consistent with saturation due to complete formation of the neutral amide.The specific rate constant (k₂) and the acidity constant (K_a) were obtained from the dependence of pseudo-first-order rate constants on +>; k₂ is 1.27*10^-2 s^-1 and 1.42*10^-3 s^-1 and pK_a is 4.8 and 5.3 for XII and XII, respectively.The small value of the acidity constants is consistent with predominant N-protonation.The activation parameters for XII are ΔH<*> = 11.1 kcal/mol, ΔG<*> = 20.35 kcal/mol, and ΔS<*> 0 -31 eu.Solvent and salt effects on the rate of hydrolysis of XII are insignificant.The solvent isotope effect, k₂(H2O)/K₂(D2O), is 1.2 and K_a(H2O)/K_a(D2O) is 3.2.Fluoride ion catalyzed the rate of reaction of XII.The Broensted β value is about -1, implying rate-determining breakage of the P-N bond.The results appear to be most consistent with an S_N2(P) mechanism.The reactivity of phosphorus amides is discussed in terms of their structure.