Transition from concerted to stepwise processes as a function of leaving group ability: density functional theory and experimental study of lyoxide‐promoted cleavages of phosphorothioate and phosphate triesters in water and methanol

Abstract

The base-promoted solvolysis of a series of O,O-dimethyl O-aryl and O,O-dimethyl O-alkyl phosphorothioates (1) as well as O,O-dimethyl O-aryl and O,O-dimethyl O-alkyl phosphates (2) was studied computationally by density functional theory methods in methanol and water continuum media to determine the transition between concerted and stepwise processes. In addition, an experimental study was undertaken on the solvolysis of these series in basic methanol and water. The computations indicate that the solvolytic mechanism for series 1 involves lyoxide attack anti to the leaving group in a concerted manner with good leaving groups having pK a Lg values < 12.3 in methanol and in a stepwise fashion with the formation of a 5-coordinate thiophosphorane intermediate when the pK a Lg > 12.3. A similar transition from concerted to stepwise mechanism occurs with series 2 in methanol as well as with series 1 and 2 in water, although for the aqueous solvolyses with hydroxide nucleophile, the transitions between concerted and stepwise mechanisms occur with better leaving groups than in the case in methanol. The computational data allow the construction of Brønsted plots of log k 2 ÀOS versus pK a Lg in methanol and water, which are compared with the experimental Brønsted plots determined with these series previously and with new data determined in this work. Both the computational and experimental Brønsted data reveal discontinuities in the plots between substrates bearing O-aryl and O-alkyl leaving groups, with the gradients of the plots being far steeper than, and non-collinear with, the O-aryl leaving groups for solvolysis of the O-alkyl-containing substrates. These discontinuities signify that care should be exercised in interpreting breaks in Brønsted plots in terms of changes in rate-limiting steps that signify the formation of an intermediate during a solvolytic process.

Multiparameter kinetic analysis of alkaline hydrolysis of a series of aryl diphenylphosphinothioates: models for P=S neurotoxins

“…Therefore, the present results are relevant to our understanding of hydrolytic degradation of OP pesticides and to the thio effect that distinguishes between P=O neurotoxins and their P=S analogues. The present findings, combined with previously published results, suggest that other systems, in which the hydrolytic mechanism for OP neurotoxins was presumed to be concerted, likely do proceed via the S N 2(P) route where the leaving groups are good, ie, p K a (LG‐H, the conjugate acid of the leaving group) < 10.…”

“…In terms of the mechanistic continuum, the reactions with hydroxide for both sets of substrates fit the S N 2(P) description. However, the TS for the 2a to 2i set is shifted more from the ideal reaction co‐ordinate in a More O'Ferrall‐Jencks diagram (not shown) toward the penta‐coordinate intermediate corner than is the case for the 1a to 1i series (cf Maxwell et al).…”

“…Through a multiparameter approach to analysis of the kinetics (Hammett, Yukawa‐Tsuno, and Brønsted‐type relationships) and determination of the activation parameters for the alkaline hydrolysis, this study aims to assess the nature and position of the reaction mechanism along the continuum . The relevance of the study to the environmental degradation of P=S OP neurotoxins will also be briefly explored.…”

Linear correlation between effective charge and bond length sensitivity to electronic effects in phosphoryl, sulfonyl, and sulfuryl compounds

“…This value is substantially lower than the β eq of −1.45 recently obtained for the corresponding dimethylphosphorothioate triesters, calculated from β nuc = 0.57 and β lg = −0.88 . A higher β eq of −1.75 has been obtained theoretically from B3LYP/6‐31++G(d,p) computations using integral equation formalism variant polarizable continuum model (IEFPCM) to model an aqueous environment . As noted by Williams, in the reaction of phosphate triesters a β eq value of −1.2 was calculated from β lg and β nuc values for the reaction of substituted aryl diethyl phosphate.…”

“…Indeed, the reaction of phosphate triesters with a nucleophilic attack at the phosphorus atom is likely to happen through a phosphorane intermediate and a stepwise mechanism, in which the fission of the bond to the leaving group is less advanced in phosphate triesters than in their diester and monoester counterparts . On the basis of kinetic and theoretical data for O―P bond cleavage in phosphorothioate triesters, the associative mechanism is proposed. KIE experiments also suggest that the fission of the bond with the leaving group is somewhat less advanced in phosphorothioate triesters than in their phosphate counterparts …”