E1cB mechanisms. Part II. Base hydrolysis of substituted phenyl phosphorodiamidates

Abstract

Reaction of hydroxide ion with substituted phenyl NN′-diphenylphosphorodiamidates (I) was measured at 60 °C in 50% ethanol–water (v/v) medium. Rate constants followed the law k_obs=k′/[1 +K_w/(K_a. OH)]; K_a/K_w fitted a good Hammett relationship (ρ= 1·27, r= 0·994) indicating considerable ‘linkage’ through oxygen and phosphorus. The term k′ obeyed a good Hammett σ relationship (ρ= 1·58, r= 0·980); this is interpreted as insignificant P–O cleavage in the transition state of the rate-determining step. Selectivity of 1·58 is argued to arise from a mechanism involving decomposition of the conjugate base of (I). Arguments are presented which eliminate S_N2(P) attack of water on the anion of (I) and S_N2(P) attack of hydroxide ion on the neutral ester as contributors to k′. The ester 4-nitrophenyl phosphorodimorpholidate has a bimolecular rate constant for base hydrolysis some 20,000-fold smaller than the apparent bimolecular rate constant (k₂=k′K_a/K_w) for alkaline hydrolysis of 4-nitrophenyl NN′-diphenylphosphorodiamidate (Ia) in accordance with a different mechanism for the latter. The difference is a reflection of a more favourable enthalpy and entropy of activation.

The absence of racemisation in alkaline hydrolysis of methyl 4-nitrophenyl N-cyclohexylphosphoramidothioate is suggested to be due to more rapid attack of solvent on the planar imidate intermediate (in the E1 cB mechanism) than departure of 4-nitrophenolate anion from the solvent cage.