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Multiparameter kinetic analysis of alkaline hydrolysis of a series of aryl diphenylphosphinothioates: models for P=S neurotoxins
Author(s) -
Um IkHwan,
Han JeongYoon,
Shin YoungHee,
Dust Julian M.
Publication year - 2017
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.3657
Subject(s) - chemistry , substituent , thio , leaving group , hammett equation , concerted reaction , aryl , stereochemistry , hydrolysis , reaction rate constant , reaction mechanism , medicinal chemistry , kinetic energy , computational chemistry , kinetics , catalysis , organic chemistry , alkyl , physics , quantum mechanics
Alkaline hydrolysis of a series of X‐substituted‐phenyl diphenylphosphinothioates ( 2a‐i ) in 80 mol%/20 mol% DMSO at 25.0 ± 0.1°C has been studied kinetically and assessed through a multiparameter approach. Substrates 2a to 2i are approximately 12 to 22 times less reactive than their P=O analogues 1a to 1i (ie, the thio effect). The Brønsted‐type plot for the reactions of 2a to 2i is linear with β lg = −0.43, consistent with a concerted mechanism. Hammett plots correlated with σ o and σ − constants also support a concerted mechanism; the Yukawa‐Tsuno plot results in an excellent linear correlation with ρ X = 1.26 and r = 0.30, indicating that expulsion of the leaving group occurs in the rate‐determining step (RDS). The Δ H ‡ value increases from 10.5 to 11.7 and 13.9 kcal/mol as substituent X in the leaving group changes from 3,4‐(NO 2 ) 2 to 4‐NO 2 and H, in turn, while T Δ S ‡ remains constant at −6.0 kcal/mol. The strong dependence of Δ H ‡ on the electronic nature of substituent X also indicates that the leaving group departs in the RDS. The reaction mechanism and origin of the thio effect are discussed by comparison of the current kinetic results with those reported for the reactions of 1a to 1i . The results suggest that for useful OP neurotoxins the mechanism of abiotic hydrolysis is concerted (with varying degrees of asynchronicity) when the substrate bears good leaving groups.