Concurrent primary and secondary deuterium kinetic isotope effects in anilinolysis of O-aryl methyl phosphonochloridothioates

Abstract

The nucleophilic substitution reactions of Y-O-aryl methyl phosphonochloridothioates with substituted anilines (XC₆H₄NH₂) and deuterated anilines (XC₆H₄ND₂) are investigated kinetically in acetonitrile at 55.0 °C. The Hammett and Brønsted plots for substituent (X) variations in the nucleophiles are biphasic concave downwards with a break region between X = H and 4-Cl. The deuterium kinetic isotope effects (DKIEs) are primary normal (k_H/k_D = 1.03–1.30) for stronger nucleophiles (X = 4-MeO, 4-Me and H), and extremely large secondary inverse (k_H/k_D = 0.367–0.567) for weaker nucleophiles (X = 4-Cl, 3-Cl and 3-NO₂). The cross-interaction constants are negative (ρ_XY(H) = −0.95 and ρ_XY(D) = −1.11) for stronger nucleophiles, while positive (ρ_XY(H) = +0.77 and ρ_XY(D) = +0.21) for weaker nucleophiles. These kinetic results indicate that the mechanism changes from a concerted process involving frontside nucleophilic attack for stronger nucleophiles to a stepwise process with a rate-limiting leaving group expulsion from the intermediate involving backside attack for weaker nucleophiles. A hydrogen-bonded, four-center-type transition state (TS) is suggested for a frontside attack, while a trigonal bipyramidal pentacoordinate TS is suggested for a backside attack. The unusually small DKIEs, as small as or equal to 0.4, for weaker nucleophiles seem to be ascribed to severe steric congestion in the TS.