10.1021/ic102220m.s001 David R. Edwards David R. Edwards Alexei A. Neverov Alexei A. Neverov R. Stan Brown R. Stan Brown Study on the Transesterification of Methyl Aryl Phosphorothioates in Methanol Promoted by Cd(II), Mn(II), and a Synthetic Pd(II) Complex American Chemical Society 2011 Methyl Aryl Phosphorothioates sspH rate constants 3O group aryl substitutions methanolytic cleavage 2 b displays 3OD binding LG 2011-03-07 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Study_on_the_Transesterification_of_Methyl_Aryl_Phosphorothioates_in_Methanol_Promoted_by_Cd_II_Mn_II_and_a_Synthetic_Pd_II_Complex/2686162 Methanol solutions containing Cd(II), Mn(II), and a palladacycle, (dimethanol <i>bis</i>(<i>N,N</i>-dimethylbenzylamine-2C,N)palladium(II) (<b>3</b>), are shown to promote the methanolytic transesterification of <i>O</i>-methyl <i>O</i>-4-nitrophenyl phosphorothioate (<b>2b</b>) at 25 °C with impressive rate accelerations of 10<sup>6</sup>−10<sup>11</sup> over the background methoxide promoted reaction. A detailed mechanistic investigation of the methanolytic cleavage of <b>2a</b>−<b>d</b> having various leaving group aryl substitutions, and particularly the 4-nitrophenyl derivative (<b>2b</b>), catalyzed by Pd-complex <b>3</b> is presented. Plots of <i>k</i><sub>obs</sub> versus palladacycle [<b>3</b>] demonstrate strong saturation binding to form <b>2b</b>:<b>3</b>. Numerical fits of the kinetic data to a universal binding equation provide binding constants, <i>K</i><sub>b</sub>, and first order catalytic rate constants for the methanolysis reaction of the <b>2b</b>:<b>3</b> complex (<i>k</i><sub>cat</sub>) which, when corrected for buffer effects, give corrected (<i>k</i><sub>cat</sub><sup>corr</sup>) rate constants. A sigmoidal shaped plot of log(<i>k</i><sub>cat</sub><sup>corr</sup>) versus <sub>s</sub><sup>s</sup>pH (in methanol) for the cleavage of <b>2b</b> displays a broad <sub>s</sub><sup>s</sup>pH independent region from 5.6 ≤ <sub>s</sub><sup>s</sup>pH ≤ ∼10 with a <i>k</i><sup>minimum</sup> = (1.45 ± 0.24) × 10<sup>−2</sup> s<sup>−1</sup> and a [lyoxide] dependent wing plateauing above a kinetically determined <sub>s</sub><sup>s</sup>p<i>K</i><sub>a</sub> of 12.71 ± 0.17 to give a <i>k</i><sup>maximum</sup> = 7.1 ± 1.7 s<sup>−1</sup>. Brønsted plots were constructed for reaction of <b>2a</b>−<b>d</b> at <sub>s</sub><sup>s</sup>pH 8.7 and 14.1, corresponding to reaction in the midpoints of the low and high <sub>s</sub><sup>s</sup>pH plateaus. The Brønsted coefficients (β<sup>LG</sup>) are computed as −0.01 ± 0.03 and −0.86 ± 0.004 at low and high <sub>s</sub><sup>s</sup>pH, respectively. In the low <sub>s</sub><sup>s</sup>pH plateau, and under conditions of saturating <b>3</b>, a solvent deuterium kinetic isotope effect of <i>k</i><sup>H</sup>/<i>k</i><sup>D</sup> = 1.17 ± 0.08 is observed; activation parameters (Δ<i>H</i><sub>Pd</sub><sup>⧧</sup> = 14.0 ± 0.6 kcal/mol and Δ<i>S</i><sub>Pd</sub><sup>⧧</sup>= −20 ± 2 cal/mol·K) were obtained for the <b>3</b>-catalyzed cleavage reaction of <b>2b</b>. Possible mechanisms are discussed for the reactions catalyzed by <b>3</b> at low and high <sub>s</sub><sup>s</sup>pH. This catalytic system is shown to promote the methanolytic cleavage of <i>O,O-</i>dimethyl phosphorothioate in CD<sub>3</sub>OD, producing (CD<sub>3</sub>O)<sub>2</sub>PO(S<sup>−</sup>) with a half time for reaction of 34 min.