Medium effect on the alpha-effect for nucleophilic substitution reactions of p-nitrophenyl acetate with benzohydroxamates and m-chlorophenoxide in DMSO-H2O mixtures as contrasts with MeCN-H2O mixtures: comparing two very different polar aprotic solvent components

Abstract

A kinetic study is reported on nucleophilic substitution reactions of p-nitrophenyl acetate (1a) with three alpha-effect nucleophiles, benzohydroxamate (BHA(-)), p-methylbenzohydroxamate (MBHA(-)), and p-methyl-N-methylbenzohydroxamate (M2BHA(-)), and a reference nucleophile, m-chlorophenoxide (m-ClPhO-), in DMSO-H2O mixtures of varying compositions at 25.0 +/- 0.1 degrees C. Second-order rate constants for the reactions with BHA(-) and MBHA(-) decrease upon addition of DMSO to the reaction medium up to 60 mol % DMSO and then increase thereafter only a little. In contrast, M(2)BHA(-) and m-ClPhO- become much more reactive as the DMSO content in the medium increases. Such contrasting medium effects on reactivity are consistent with the report that hydroxamic acids behave as OH acids in H2O but as NH acids in dipolar aprotic solvents (e.g., DMSO and MeCN). It has been concluded that BHA(-) and MBHA(-) form an equilibrium of a reactive form I with less reactive species II in DMSO-H2O mixtures and the position of the equilibrium is dependent on solvent compositions. BHA(-) and MBHA-exhibit the alpha-effect in H2O but not in in 90 mol % DMSO. In contrast, the alpha-effect yielded by M2BHA-increases steeply up to 70 mol % DMSO and then levels off thereafter.