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 kobs=k′/[1 +Kw/(Ka. OH)]; Ka/Kw 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 SN2(P) attack of water on the anion of (I) and SN2(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′Ka/Kw) 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.